EJCTS Click here to go to Edwards website
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Gerald D. Buckberg
Manuel Castellá
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Buckberg, G. D.
Right arrow Articles by Saleh, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buckberg, G. D.
Right arrow Articles by Saleh, S.
Related Collections
Right arrow Cardiac - physiology
Right arrow Cardiac - other

Eur J Cardiothorac Surg 2006;29:S98-S106
© 2006 Elsevier Science NL

Active myocyte shortening during the ‘isovolumetric relaxation’ phase of diastole is responsible for ventricular suction; ‘systolic ventricular filling’

Gerald D. Buckberg a , b , c , * , Manuel Castellá b , c , Morteza Gharib a , Saleh Saleh d

a Option on Bioengineering, California Institute of Technology, Pasadena, CA, USA
b Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 62-258 CHS, Los Angeles, CA 90095-1741, USA
c Department of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
d Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Received 17 February 2006; accepted 27 February 2006.

* Corresponding author. Address: Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 62-258 CHS, Los Angeles, CA 90095-1741, USA. Tel.: +1 310 206 1027; fax: +1 310 825 5895. (Email: gbuckberg{at}mednet.ucla.edu).


   Abstract
Top
 Abstract
1. Introduction
 2. Material and methods
 3. Experimental protocol
 4. Crystal orientation
 5. Results
 6. Discussion
 References
 
Objective: To study the ‘isovolumetric relaxation’ phase of rapid ventricular filling by analysis of the shortening of cardiac muscle in the endocardial and epicardial segments of the left ventricle in the dual helical model of the ventricular band, described by Torrent-Guasp. Methods: In 10 pigs (27–82 kg), temporal shortening by sonomicrometer crystals was recorded while recording ECG, and measuring intraventricular pressure and dP/dt with Millar pressure transducers. Results: The following sequence was observed; shortening began in descending or endocardial segment, and 82 ± 23 ms later it was initiated in the epicardial or ascending segment of the band. The descending segment stops shortening during the rapid filling phase of fast descent of ventricular pressure, but the ascending segment shortening continues for 92 ± 33 ms, so that active shortening continues during the period of isovolumetric relaxation. During the rapid filling phase, dopamine decreased the interval between completion of endocardial and termination of epicardial contraction from 92 ± 20 to 33 ± 8 ms. Conversely propranolol delayed the start of epicardial shortening from 82 ± 23 to 121 ± 20 ms, and prolonged the duration of endocardial contraction, causing a closer (21 ± 5 ms vs 92 ± 20 ms) interval between termination of contraction of endocardial and epicardial fibers. The resultant slope of the rapid descent of the left ventricular pressure curve became prolonged. Conclusions: These time sequences show that ongoing unopposed ascending segment shortening occurs during the phase of rapid fall of ventricular pressure. These active shortening phases respond to positive and negative inotropic stimulation, and indicate the classic concept of ‘isovolumetric relaxation’, IVR, must be reconsidered, and the new term ‘isovolumetric contraction’, IVC, or systolic ventricular filing may be used.

Key Words: Isovolumetric relaxation • Isovolumetric contraction • Helical heart • Ventricular myocardial band • Systolic ventricular filling


   1. Introduction
Top
 Abstract
 1. Introduction
2. Material and methods
 3. Experimental protocol
 4. Crystal orientation
 5. Results
 6. Discussion
 References
 
In the classical interpretation of the cardiac cycle, ejection of blood follows myocardial contraction and subsequent ventricular constriction. The resulting decrease in ventricular luminal volume raises intraventricular pressure (isovolumic contraction) which eventually opens the aortic valve. The time interval over which the ventricular pressure increases, from opening of the aortic valve until maximum pressure (about 120 mmHg) is reached, is about 140 ms [1]. Similarly, diastole is comprised of an isovolumetric period characterized by a fast fall in ventricular pressure (from 120 mmHg to near zero after mitral valve opening) followed by a rapid filling phase when atrial blood is sucked into the lower pressure, relaxing ventricle. The time interval over which this pressure drop occurs is approximately 120 ms in the normal human heart.

Remarkably, a convincing mechanism responsible for the precipitous fall in ventricular volume, and its subsequent rapid filling phase, is still missing. The rapidity with which pressure drops to its final value (15–20% of the entire diastolic phase) has perplexed many investigators. The prevailing clinical definition of diastole associates it with the relaxation of the entire myocardium. However, the time scale of the ventricular isovolumetric pressure drop phase is comparable to the time scale of myocardial contraction and left ventricle contraction phase during systole. This time scale gets even shorter as we look at animals with higher heart beat rates. If an active ‘suction-producing’ mechanism does not exist it is difficult to attribute the rapid fall of ventricular pressure to pure isovolumetric relaxation. To address the issue of time scale in the heart beat cycle, some researchers suggest that active diastole is accomplished through the elastic recoil of surrounding connective tissues [2–4]. This hypothesis has served as the impetus for numerous studies investigating the elastic properties of connective tissues, specifically as it pertains to release of energy stored by the preceding systolic phase. One such investigation attributes the rapid recoil to a network of collagen containing elements of elastin [4,5]. To the best of our knowledge, there is no conclusive data that can testify to the existence of these elusive elastic properties of collagen or other connective tissues.

Titin, a recently described protein myofilament, is thought to deform and provide some of the restoring force to the sarcomere [6,7]. Experiments indicate that the elastic response time (the time it takes to produce the relaxed length of sarcomere) of titin is too long to match the 120 ms duration of the isovolumetric period during which the ventricular pressure drops to 85% of its diastolic value. Recent work [8] in rat cardiac myocytes suggests that titin plays a role in determining passive tension. It appears that titin may be an important viscoelastic stiffness element rather than a spring element in the sarcomere.

We will discuss the significance of contraction by a helical fiber band during the isovolumetric phase that follows ventricular ejection, as viable alternative element with spring-like activity on the micro-scale, that can generate the heretofore unexplained ventricular pressure drop. A contractile element in the rapid filling phase during early diastole is suggested since ‘ventricular relaxation’ is an active, energy consuming cellular event with calcium uptake [5,4,9]. However, the existence of such a contracting element is counterintuitive in the sense that its contracting action (like any contracting element) should only result in the shortening of some linear dimension and subsequently in an increase of pressure or decrease of volume bounded by such contracting elements. Because of this misconception, the field of cardiac mechanics has directed their research activities away from searching for such active contractile element.

A central question is whether the contraction of the muscle could decrease the ventricular pressure. The answer to this question can be found in many biological systems such as Nematode worms and Squid mantle where contraction of muscle fiber bands can facilitate locomotion by increasing or decreasing the volume that they bound [10]. It is intriguing to know that if a beating rat heart is placed in a saline bath, the heart continues to beat and it jets rapidly similar to that of squid through the fluid. Fluid is forcefully expelled through the great vessels during systole and is sucked into the ventricle during the diastole [11]. This observation indicates that a negative and positive wall pressure has been exerted on the ventricular volume during systole and diastole, respectively, thus indicating that an active muscle like dynamics is at work both in systole and diastole of mammalian heart. Cowey [10] showed that the trick is in the helical arrangement of muscle fiber bands where by a proper arrangement of fiber bands either volume decrease or increase can be achieved through the contraction of a helically shaped single muscle band that bounds the said volume in a figure-of-eight configuration. It is interesting to note that in an isovolumetric situation the tendency to increase volume will result in an active reduction of pressure in the volume. Brecher showed a suction component in isolated heart experiments [12,13].

Our studies will apply the dual helical model of the ventricular band, described by Torrent-Guasp [14,15], and use sonomicrometer studies to identify and investigate the interface of contraction between the descending (endocardial) and ascending (epicardial) segments of the apical ventricular loop, to extend this structural concept to the physiologic explanation of active diastole in the working helical myocardial band [16–18]. Pharmacologic alterations in contractility between these dual segments of the helix will be tested with the positive and negative inotropic influence of dopamine and propranolol. If valid, this contraction related production of suction will change the concept of ‘isovolumetric relaxation’ into one of ‘isovolumetric contraction’, or systolic ventricular filling [19] and thereby introduce a novel mechanism for the generation of the rapid filling phase after ventricular ejection in normal hearts.


   2. Material and methods
Top
 Abstract
 1. Introduction
 2. Material and methods
3. Experimental protocol
 4. Crystal orientation
 5. Results
 6. Discussion
 References
 
All animals received humane care in compliance with the ‘Principles of Laboratory Animal Care’ formulated by the Institute of Laboratory Animal Resources and the ‘Guide for the Care and Use of Laboratory’ prepared by the National Institutes of Health (NIH Publication no. 86-23, revised 1985).

Ten Yorkshire-Duroc pigs (27–82 kg) were premedicated (ketamine 15 mg/kg, diazepam 0.5 mg/kg intramuscularly) and anesthetized with inhaled isoflurane 1.5% (MAC 1%) throughout the operation. Support with a volume-controlled ventilator (Servo 900C, Siemens-Elema, Sweden) was started after tracheostomy and endotracheal intubation. The femoral artery and vein were cannulated and arterial blood gases measured to keep oxygen tension, carbon dioxide tension, and pH values within the normal range. A balloon-tipped catheter (Model 132F5, Baxter Healthcare Corp., Irvine, CA) was advanced into the pulmonary artery through a jugular vein to measure cardiac output (thermodilution technique) and pulmonary artery pressure.

The pericardium was incised after median sternotomy and a solid-state pressure transducer-tipped catheter (Model MPC-500, Millar Instruments, Inc., Houston, TX) was inserted through the apex to monitor left ventricular pressure (LVP). Regional contractility within the right and left ventricle was measured with pairs of 2 mm ultrasonic microtransducer crystals (Sonometrics, London, Ont., Canada). Each pair of crystals was oriented in order to measure contractility at certain myocardial depth and orientation. The placement position of each crystal was made by using a 1 mm cut of the epicardium and introduction of the crystal to reach the depth selected. In the left ventricle two depths were chosen, endocardial, where the crystals were positioned transmurally to reach the inner surface via the ventricular cavity, or subepicardial, by insertion 1 mm deep into the ventricular muscle. In the left and right ventricle, crystals were positioned in the posterior free wall above the coronary sunus, and laterally by the atrioventricular groove.

Aortic pressure, LVP, dP/dt, and sonomicrometer crystals data were digitally processed by specific hardware and software (Sonometrics, London, Ont., Canada). Velocity of sound through cardiac tissue was fixed to 1590 m/s. Sonomicrometer measurements were recorded with a sampling rate of 95.8 samples/s, a transmitter spacing of 652 ms, transmit inhibit delay of 1.81 ms, and transmit pulse length of 375 ms. Synchronicity between myocardial contractility was compared to left ventricular performance with 1 ms precision, by real time plotting and processing of segment shortening, EKG, LVP and dP/dt. Sequence of contraction of different segments of the heart was then established and compared with ventricular hemodynamics. All cases were performed and analyzed by the same surgeon.


   3. Experimental protocol
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Experimental protocol
4. Crystal orientation
 5. Results
 6. Discussion
 References
 
The insertion of pairs of sonomicrometer crystals in different positions/depth, allowed the extent of segment shortening to be measured in the anterior wall of the left ventricle, recording the dimension angle of contraction and myocardial depth.

Segmental shortening was calculated as follows:


Formula

where EDL and ESL are end diastolic and end systolic length, respectively.

The pattern of orientation is described in the next section. This dimension (angle of highest contractility relative to the long axis of the heart) was registered for both endocardial and subepicardial contraction, and compared with synchronized EKG, LVP and dP/dt. These measurements were compared in real time with different pharmacologic changes of regional contractility, and position sites in the left and right ventricle.


   4. Crystal orientation
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Experimental protocol
 4. Crystal orientation
5. Results
 6. Discussion
 References
 
Torrent-Guasp's model of the helical heart is presented in Fig. 1a and b, that includes the cardiac structures that produce two simple loops that start at the pulmonary artery and end in the aorta. These two components include a horizontal basal loop, comprised of right and left segments that surround the right and left ventricles that changes direction to form an oblique dual apical loop. This change develops through a spiral fold in the ventricular band to cause a dual ventricular helix produced by now obliquely oriented fibers, forming an endocardial or descending and epicardial or ascending segment of the apical loop with an apical vortex.


Figure 1
View larger version (57K):
[in this window]
[in a new window]
  		Fig. 1. (a) Progressive unscrolling of left ventricle in comparison with underlying rope-like model. These figures unfold the horizontal basal loop. Note (A) the intact heart, (B) detachment of the right ventricle free wall or transverse orientation of basal segment. A genu adjacent to the septum separates right and left ventricles, (C) the detached apical loop with segment showing (left side) on right ventricle, and (right side) left ventricle to complete basal loop. (b) Continued unscrolling. These images unfold the oblique apical loop. Note (D) unfolding of the trigone to pull the pulmonary artery laterally and demonstrate the descending segment of apical loop and overlying ascending segment containing the aorta. (E) Unwrapping of the helix formed by the transverse muscle band to show unfolding of the descending segment, with trigone removed and (F) the complete transverse myocardial band, with the central muscle fold to separate the basal and apical loops. The left segment is the transverse basal loop, the right segment is the apical loop. Note that, before this folding, both segments have transverse muscle orientation. The oblique orientation of the descending and ascending segments derive from the architectural folding initiated by the spiral within transverse band, between the basal and apical loops.

 
The sonomicrometer crystals were placed into the intact heart, to test any relationship between sequential temporal and mechanical extent of fiber shortening between couples of crystals to model shape and timing. Their orientation was nested within the principal pathways comprising the suggested rope like arrangement of the helical heart, in concert with the patterns described previously [18,20] that define the external principal direction trajectories of oblique muscle mass thought to comprise the architectural scaffold.


   5. Results
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Experimental protocol
 4. Crystal orientation
 5. Results
6. Discussion
 References
 
5.1 Anterior wall of the left ventricle
The extent of contraction of the anterior wall of the left ventricle results in larger displacement of the crystals, and thus in a steeper slope in the endocardial side of the myocardium than in the epicardial one (Fig. 2 ). The onset of contraction at this anterior wall myocardial depth precedes the systolic rise of LVP and dP/dt, and occurred between the Q and R waves of the EKG (Fig. 3 ). Subendocardial muscle shows two distinct rates as it shortens. First, a short and steep descent followed by a longer and less steep contraction phase. A notch was present on this curve, and divided these phases. In normal hearts, the end of endocardial contraction consistently coincided with the beginning the descent phase of the left ventricular pressure, which is also coincided with the appearance of the negative slope of dP/dt (Fig. 2).


Figure 2
View larger version (66K):
[in this window]
[in a new window]
  		Fig. 2. Different segment shortening tracings of the endocardial and epicardial sites of the anterolateral left ventricle. These sites conform to: (A) The model (upper tracing) and intact ventricle (lower tracing) with position of sonomicrometer crystals. The descending segment is deep, with hatched lines, whereas the ascending segment is superficial (solid line). (B) The simultaneous recording of descending segment and ascending segment contractions, left ventricular pressure and dP/dt from the pressure tracing. Note the delayed start of ascending segment contraction (first dotted line), and its termination after descending segment stopped (second dotted line). The longitudinal lines show the start contraction of descending segment, the start contraction of ascending segment, the stop contraction of descending segment, and the stop contraction of ascending segment.

 

Figure 3
View larger version (46K):
[in this window]
[in a new window]
  		Fig. 3. Comparison of simultaneous recording of tracings from the descending and ascending segments of the apical loop, left ventricular pressure (LVP), the electrocardiogram (EKG) and dP/dt analysis of LVP from recordings from Millar catheters.

 
Subepicardial contraction averaged 12 ± 2% segment shortening, when the angle of cystal placement was oriented at 150 ± 10%, and placed approximately 60° opposite endocardial placement. Subepicardial segment shortening followed contraction of the subendocardial muscle by 82 ± 23 ms, starting at the maximum of height of dP/dt, and finishing 90 ± 20 ms after subendocardial contraction's end, towards the end of the negative wave of dP/dt (Fig. 2).

The force or extent of contraction was more intense towards the apex in both the endocardial and epicardial sides of the left ventricle (Fig. 4 ). This reflected an anisotropic contractile effort as we compared basal and apical segment shortening. For example, basal contraction averaged 35 ± 5% less than apical contraction, and this conical difference was consistent for both the endocardial and the epicardial muscle.


Figure 4
View larger version (56K):
[in this window]
[in a new window]
  		Fig. 4. Sequential shortening of the LV endocardial muscle, showing the anisotropic recording, with more forceful contraction, as the sites of the crystal pairs are moved toward the apex.

 
5.2 Sequence of contraction
Contraction starts initially in the endocardial side of the antero-septal wall of the left ventricle. The initiation of this early contraction corresponded with the Q wave of the EKG and LVP rose, but did not have rapid acceleration, as pressure generation remained below 15 mmHg. The contraction of the anterior wall endocardial segments began before contraction of the rest of the myocardium produced a rapid acceleration or ascent in ventricular pressure recording, rising to exceed aortic diastolic pressure. The early steep slope of segmental shortening of the endocardial regions (Fig. 2) occurred while there was no contraction detected in the subepicardial sites of the segments, located in the subepicardial anterior wall of the left ventricle. Contraction at epicardial segments began 84 ± 10 ms after the initial muscle contraction (the endocardial wall of the left ventricle), and corresponded to the peak of the positive dP/dt wave, the S wave on the QRS complex of the EKG signal (Fig. 2), and most importantly, the steep rise (equivalent to the peak dP/dt) in left ventricular pressure for ejection of blood. For the rest of systole during ejection, contraction was present in all segments of the heart resulting in ‘co-contraction’ of both endocardial and epicardial fibers. The initiation of contraction in the subepicardial fibers, was maximal in a 90° opposite direction from endocardial ones, and coincided with a reduction of the slope of contraction of the subendocardial fibers (Fig. 2).

The termination of active contraction in the LV anterior wall was different in subendocardial and subepicardial segments, thereby producing a disassociation between the absence of contraction in endocardial fibers, during ongoing active contraction in epicardial fibers, as shown in Fig. 2. The first regions to stop shortening were the segments that started first, located in the endocardial side of the antero-septal left ventricle wall. The end of endocardial contraction coincided with the end of the flat peak component values in the left ventricular pressure tracing, corresponding with the start of the negative wave of dP/dt. Simultaneously, contraction persisted in the epicardial component of left anterior wall These segments finished their contraction phase 92 ± 20 ms after that of the RV free wall, posterior LV, and endocardial LV segments.

A linking of velocity of left ventricular pressure descent followed this dissociation between ongoing contraction of subepicardial segment, and stoppage of contraction in the subendocardial segment: this time interval corresponded to the LV tracing recording the previously termed isovolumetric relaxation. During absent contraction of endocardial regions LV pressure deceleration rate was maximal as active shortening of the epicardial fibers persisted as shown in Fig. 2.

Analysis of the pressure recordings, coupled with simultaneous analysis of regional recordings of contraction in endocardial and epicardial, left ventricular segments, shows a linkage between the acceleration and deceleration phases of developed pressure (i.e. the slope velocity of the pressure recording) and regions of contraction. During the initial rapid acceleration, or isovolumetric contraction of left ventricular pressure, all segments shortened simultaneously, whereas, during the later deceleration of LV pressure, only the subepicardial segment was actively shortening. The slope of the rapid fall in ventricular pressure corresponded closely with the dissociation between termination of contraction in the endocardial muscle, and ongoing contraction of the epicardial muscle (Fig. 2). Consequently, a systolic shortening phase persisted throughout the entire LV pressure recording, including during the phases of rapid acceleration and deceleration of ventricular pressure, so that there was no interval of isovolumetric relaxation.

These persistent contractions in the anterior wall epicardial fibers during the cessation of endocardial shortening was associated with a reversal, or upward slope of the endocardial crystal tracing as shown in Fig. 2. This separation or widening between crystals reached the point of maximum fiber stretch (i.e., separation between crystals), only surpassed by the added stretch due to ventricular filling by atrial contraction.

The link between the delay of the contraction between endocardial and epicardial segments was evaluated by intravenous infusions of inotropic drugs or ß-blocker therapy (Fig. 5 ). The delay between the start of contraction in endocardial and epicardial muscle of the anterior wall of the left ventricle decreased to 26 ± 7 ms with dopamine infusion at 10 µg/kg/min. Simultaneously the extent of shortening increased from 25.7 to 29.1% in the endocardial wall, and heart rate rose from 88 to 112 beats per minute to confirm the inotropic and chronotropic catecholamine effect. The time interval between completion of endocardial and termination of epicardial contraction was shortened from 92 ± 20 to 33 ± 8 ms. Conversely, propranolol therapy prolonged the delay between initiation of contraction in endocardial, and epicardial segments to 121 ± 20 ms, reduced the extent of shortening to 19%, and slowed heart rate to 78 beats per minute to define its negative inotropic effect.


Figure 5
View larger version (54K):
[in this window]
[in a new window]
  		Fig. 5. Sequence of contraction of different segments during a study in one subject during basal conditions (left) and with dopamine (middle) or propranolol infusión (right). Black and hatched lines mark the start and end of shortening of endocardial and epicardial muscle, respectively. There is a delay between start of the endocardial and the epicardial myocardium of the anterior wall, that decreases with dopamine from 84 ± 10 to 26 ± 7 ms and increases with propranolol to 121 ± 20 ms. The termination of endocardial shortening is reduced by dopamine, but prolonged with propranolol to (a) narrow the separation during baseline, and (b) flatten the slope of descent of the LV pressure tracing.

 
This propanalol induced pharmacologic prolongation of the duration of separation between the onset of contraction between the endocardial and epicardial segments at the origin of contraction, was also associated with a prolongation of the duration of the endocardial contraction. Thus, the interval or hiatus of separation shortened between the end of endocardial contraction with ongoing epicardial contraction was shortened. Compared to control, termination of contraction of endocardial and epicardial fibers occurred at a closer (21 ± 5 ms vs 92 ± 20 ms) interval. This is in contrast to the prolongation that existed at the time of rapid ascent of the left ventricular pressure curve, while the resultant slope of the rapid descent of the left ventricular pressure curve became prolonged.


   6. Discussion
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Experimental protocol
 4. Crystal orientation
 5. Results
 6. Discussion
References
 
The concept of active diastole remains one of the fundamental challenges of the modern understanding of cardiac function. The early phase of diastole is known to be an energy consuming process accompanied with calcium uptake [9]. This aspect of early cardiac diastole does not fit to the prevailing concept of recoil due to the release of elastic energy by some passive elements of myocine such as titin or connective tissues such as collagen [7,8,11]. These elements are not known to consume energy or have a need for calcium to function. In addition, these passive elements by their nature are incapable of providing the short time scale that is needed to explain the rapid fall of pressure in the early stages of diastole. In this respect, our approach in resolving this dilemma was to shift the emphasis in search for an element that can provide a mechanism for recoil from these passive elements to the cardiac muscles where a global rather than local process could explain the early phases of diastole. However, in order to prove that cardiac muscle may play an active role during diastolic phase, we needed to search and find an element of cardiac muscle that remains activated (contracting) during the so-called ‘relaxation’ phase.

The next challenge was to have a model of cardiac structure that can have a use for this contracting element to correctly predict the nature of the cardiac function during the diastolic phase. Perhaps the most challenging aspect of our experimental approach, in order to avoid blind searches, was to design a model driven intelligent search strategy. In this regard, we adopted the helical fiber band model of Torrent-Guasp as a guide to start our search strategy. This model adheres to previous recognition of helical features of endocardial and epicardial muscle fibers. In addition, it treats these bands as the connected elements of an integrated double helical structure: a feature that was not recognized by the previous investigators in this field. The most important contractile aspect of this model as has been described and documented by Buckberg et al. [16–18] is in its ability to provide a preferential pathway for the maximum shortening of muscle bands along their principle direction. Therefore, a search strategy could be devised in order to find locations and orientation in muscle band that present such maximal contractual displacement.

In our studies, we used sonomicrometer crystals with high temporal and spatial resolution [21] to determine the timing and principle axis of contraction. The maximum extent of shortening between crystal probes was used as a criteria to identify the principal fiber pathway orientation suggested by Torrent-Guasp's helical heart model [14,15]. We explored the relationship of how these two-dimensional devices could identify function in the underlying three-dimensional muscle.

The crystal dimension gauges provide a local view of a global concept, exploring all cardiac regions. These local barometers do not measure either thickening [21–23], twisting [24], torsion [3], cross fiber shearing forces [21,22,25] or inception of the calcium trigger of contraction [5,4]. We recognize these local shortening measurements are influenced by the overlying cross fiber strain and shearing forces of the inner and outer halves of the ventricular wall, thus, in general, they do reflect the deformation influence from neighboring fibers. Consequently, each change in time related regional function is comprised of how three-dimensional spatial architecture alters function within the ventricular wall.

Distinction between each of the varied factors that influence the term ‘contractility’ is not the intent of this manuscript, since no effort was made to measure deformation [26,23], as it influences strain of the cross fiber or transmural shearing forces [22] that may result in a motion that may not be aligned with local myofibers. Therefore, we employed the hypothesis that orientation that renders the maximal contraction are least influenced by the dynamics of neighboring structures. Consequently, despite the limitations of the crystals used for sonomicrometric measurements, these local records take maximal advantage of their temporal and spatial resolution.

Perhaps one of the astonishing aspects of our reported crystal studies is the discovery of a period of the contraction during a time period that previously was termed isovolumetric relaxation. The segment of the heart that showed this unexpected continuous contraction was aligned with what Torrent-Guasp identifies as the epicardial ascending segment. This finding also confirms that the systolic contraction exists both during the phase of ejection, and during the time related period previously termed isovolumetric relaxation. This interval coincides with the rapid drop of ventricular pressure thought previously to reflect elastic recoil related to potential energy stored during the systolic contraction [2,27]. This muscle continues to shorten beyond the end contraction phase of the endocardial muscle forming the descending segment. This finding clearly indicates that the notion of ‘an entire relaxed heart’ during the early diastolic phase is flawed. In addition, one cannot overlook the distinct possibility that the ongoing contraction of the epicardial muscle which forms the ascending segment is the key process in providing an active diastole through reciprocal untwisting of the heart.

It is important to mention that this contraction is most evident when crystal pair orientation were optimized to show the maximum negative displacement. Therefore, it was easy to miss this period if care was not given to optimize the orientation of crystals while searching for the principle orientation of the fiber bands [20]. This fact may explain why so many other investigators missed the opportunity to detect this phenomena.

This active contractile role was also suggested by Shapiro and Rademakers [27] by MRI studies, defining that 50% of filling develops during this time frame, and accentuation of speed and rate untwisting (or reciprocal twisting in a reverse direction) for rapid filling can be made by inotropic drug infusion. Elastic recoil, rather than contraction was thought to be the responsible factor. Brutsaert [5,4,9] further amended the infrastructure for rapid filling by a observing a prolonged contractile phase of systole. Our findings tested this concept with sonomicrometer crystals, and characterized the role of calcium dynamics in this process by infusion with dopamine or propranolol. We did not measure calcium, but rather defined how modulation of calcium flux with either positive or negative inotropic influences by infusión of these agents influenced the linkage of the initiation and completion of contraction of these endocardial and epicardial (or descending and ascending segments) of the dual helical band.

The mechanism of reciprocal twisting for suction relates to the ongoing contraction of the ascending segment, that persists as the only functional component of the apical loop following the cessation of descending segment shortening. This sequence is shown in Fig. 2, which documents (a) co-shortening of the descending and ascending segments during ejection, and (b) prolongation of ascending segment shortening after completion of descending segment shortening. The twisting pattern shown by MRI [27] involves a predominantly counterclockwise twist during ejection and subsequently a clockwise twist during suction [28].

The proposed helical heart contributions to these events include first, a co-shortening of both descending and ascending segments during ejection, with each segment twisting in a different direction. The descending segment is the dominant force to account for the counterclockwise twist and global shortening as seen by echo or MRI during ejection [29]. Second, the ongoing predominantly clockwise twist of the ascending segment (already in action during ejection) now becomes unopposed due to the cessation of descending segment shortening. The resultant cardiac motion from this torsion and reciprocal twisting is the rapid global lengthening observed during the active suction phase by MRI or echocardiogram [29].

The positive inotropic effect of dopamine shortened the interval between initiation and termination of shortening in these segments, raised the extent of shortening, and these sonometric recordings are consistent with the more rapid filling reported by Rademakers on MRI scanning, with an increase from 50 to 60% by MRI recordings [2]. Dobutamine similarly enhances restoring forces, and Bell [30] ascribed this suction to contraction to a smaller volume. Their recent study focuses upon untwisting responsible for elastic recoil, with possible deformation of ‘springs’ that are related to titin as the cause. This concept considers deformation of extracellular matrix with collagen as the suggested mechanism. Our findings of active contraction contradict the prior prevailing opinión of rapid elastic recoil as the responsible element. We have recently also focused upon ‘springs’ [16], but think they relate to deformation of the internal muscle springs conforming to the helical spiral within the descending and ascending segments of the apical loop [16,18] a ‘coil within coil’ formation may exist in the dual helical heart model. Fig. 6 shows the muscular band within the spatial configuration described by Torrent-Guasp.


Figure 6
View larger version (46K):
[in this window]
[in a new window]
  		Fig. 6. This double external spiral arrangement reflects the descending and ascending segments of the apical loop interact for ejection and suction. The ‘springs’ are placed internally, to show the proper fiber orientation of the descending and ascending segments of the helical apical loop. The upper image shows the basal loop with horizontal right and left segments surrounding the apical loop with oblique fibers. This double spiral arrangement is amplified in the lower tracings of the apical loop, colored white, that reflects how the descending and ascending segments of the apical loop interact for ejection and suction. These segments are in repose in diastole in (a). Note that, in (b), during the initiation of ejection, the descending loop becomes dominant and shortens from base to apex, while this motion may stretch the ascending segment. The later contraction of the ascending segment causes ‘co-contraction’ during systole. The descending segment stops shortening before the ascending segment, whose ongoing contraction will lengthen the chamber in (c). However, the non-contracting descending segment stops and retains tension to act as a fulcrum for lengthening.

 
The negative inotropic effect of propranolol, aside from reducing pressure and heart rate, widened the onset of contraction of the epicardium versus the contraction of the endocardium to thereby slow ejection (Fig. 5). Simultaneously, it produced narrowing of the interval for rapid filling, by decreasing the time frame for otherwise unbridled epicardial contraction while the descending segment muscle was not contracting. The result was a delay or prolongation of the downslope of LV pressure and less negative dP/dt. Clearly, further prolongation of the stoppage of the endocardial contraction relative to the ongoing epicardial shortening will increasingly compromise the contractile forces responsible for rapid filling and derail the mechanisms for suction, so that pressure, rather that muscle motion now becomes the principal filling determinant. The consequence is that these tracings introduce a contractile mechanism that both contributes to suction filling in the normal heart, and more importantly implies that when this action becomes disrupted, a contractile cause for diastolic dysfunction may prevail.

Evidence for this prolongation of late systole in hearts with diastolic dysfunction is evident in studies of stunning after ischemia [31], hypertrophy during aortic stenosis [32], post transplant dilatation [33], and tachycardia induced cardiomyopathy [34,7]. Our findings show that this is an active phenomenon, related to loss of the critical gap between completion of shortening in the endocardial region, and ongoing contraction of the epicardial or ascending segment. Such recognition may give rise to using pharmacologic agents that favorably alter calcium flux, either in Na/H exchange inhibitor distribution [35], calcium sensitization without inotropic drugs [36] or other manipulation of systolic factors, since a contractile process now compromises the rapid filling period.

These results imply that the concept of ‘isovolumetric relaxation’ must be discarded, and replaced by the concept of ‘isovolumetric contraction’ or systolic ventricular filling [19] as the basis of rapid filling in the normal heart, and more importantly may introduce a innovative pharmacologic means to deal with diastolic dysfunction that is generated by disruption of this normal contractile element.


   References
Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Experimental protocol
 4. Crystal orientation
 5. Results
 6. Discussion
 References
 

  1. Berne RM, Levy MN. Cardiovascular physiology. 3rd ed.. Saint Louis: Mosby; 1977.
  2. Rademakers FE, Buchalter MB, Rogers WJ, Zerhouni EA, Weisfeldt ML, Weiss JL, Shapiro EP. Dissociation between left ventricular untwisting and filling. Accentuation by catecholamines. Circulation 1992;85(4):1572-1581.[Abstract/Free Full Text]
  3. Ingels NB, Hansen D, Daughters II GT, Stinson EB, Alderman E, Miller DC. Relation between longitudinal, circumferential, and oblique shortening and torsional deformation in the left ventricle of the transplanted human heart. Cir Res 1989;64:915-927.[Abstract/Free Full Text]
  4. Brutsaert DL, Stanislas U, Gillibert TC. Diastolic failure: pathophysiology and therapeutic implications. J Am Coll Cardiol 1993;22:318-325.[Abstract]
  5. Brutsaert DL, Szoka FC. Relaxation and diastole of the heart. Physiol Rev 1989;69:1228-1315.[Abstract/Free Full Text]
  6. Helmes M, Trombitas K, Granzier H. Titin develops restoring force in rat cardiac myocytes. Circ Res 1996;79(3):619-626.[Abstract/Free Full Text]
  7. Bell SP, Nyland L, Tischler MD, McNabb M, Granzier H, LeWinter MM. Alterations in the determinants of diastolic suction during pacing tachycardia. Circ Res 2000;87(3):235-240.[Abstract/Free Full Text]
  8. Yamasaki R, Wu Y, McNabb M, Greaser M, Labeit S, Granzier H. Protein kinase A phosphorylates titin's cardiac-specific N2B domain and reduces passive tension in rat cardiac myocytes. Circ Res 2002;90(11):1181-1188.[Abstract/Free Full Text]
  9. Zile MR, Brutsaert DL. New concepts in diastolic dysfunction and diastolic heart failure. Part II. Causal mechanisms and treatment. Circulation 2002;105(12):1503-1508.[Free Full Text]
  10. Cowey JB. The structure and function of the basement membrane muscle system in amphiporus (Nemertea). Quart J Micro Sc 1952(93):1-15.
  11. Robinson TF, Factor SM, Sonnenblick EH. The heart as a suction pump. Sci Am 1986;254(6):84-91.[Medline]
  12. Brecher GA. Critical review of recent works on ventricular diastolic suction. Circ Res 1958;VI(5):554-566.
  13. Brecher GA. Experimental evidence of ventricular diastolic suction. Circ Res 1956;IV(5):513-518.
  14. Torrent-Guasp F, Ballester M, Buckberg GD, Carreras F, Flotats A, Carrio I, Ferreira A, Samuels LE, Narula J. Spatial orientation of the ventricular muscle band: physiologic contribution and surgical implications. J Thorac Cardiovasc Surg 2001;122(2):389-392.[Free Full Text]
  15. Torrent-Guasp F, Buckberg GD, Clemente C, Cox JL, Coghlan HC, Gharib M. The structure and function of the helical heart and its buttress wrapping. I. The normal macroscopic structure of the heart. Semin Thorac Cardiovasc Surg 2001;13(4):301-319.[Medline]
  16. Buckberg GD, Clemente C, Cox JL, Coghlan HC, Castella M, Torrent-Guasp F, Gharib M. The structure and function of the helical heart and its buttress wrapping. IV. Concepts of dynamic function from the normal macroscopic helical structure. Semin Thorac Cardiovasc Surg 2001;13(4):342-357.[Medline]
  17. Buckberg GD, Coghlan HC, Torrent-Guasp F. The structure and function of the helical heart and its buttress wrapping. V. Anatomic and physiologic considerations in the healthy and failing heart. Semin Thorac Cardiovasc Surg 2001;13(4):358-385.[Medline]
  18. Buckberg GD. Basic science review: the helix and the heart. J Thorac Cardiovasc Surg 2002;124(5):863-883.[Free Full Text]
  19. Torrent-Guasp F, Kocica MJ, Corno A, Komeda M, Cox J, Flotats A, Ballester-Rodes M, Carreras-Costa F. Systolic ventricular filling. Eur J Cardiothorac Surg 2004;25(3):376-386.[Abstract/Free Full Text]
  20. Castella M, Buckberg GD, Saleh S, Gharib M. Structure function interface with sequential shortening of basal and apical components of the myocardial band. Eur J Cardiothorac Surg 2005;27(6):980-987.[Abstract/Free Full Text]
  21. Villarreal FJ, Lew WY, Waldman LK, Covell JW. Transmural myocardial deformation in the ischemic canine left ventricle. Circ Res 1991;68:368-381.[Abstract/Free Full Text]
  22. Waldman LK, Nosan D, Villarreal F, Covell JW. Relation between transmural deformation and local myofiber direction in canine left ventricle. Circ Res 1988;63:550-562.[Abstract/Free Full Text]
  23. Waldman LK, Fung YC, Covell JW. Transmural myocardial deformation in the canine left ventricle: normal in vivo three-dimensional finite strains. Circ Res 1985;57:152-163.[Abstract/Free Full Text]
  24. Beyar R, Sideman S. The dynamic twisting of the left ventricle: a computer study. Ann Biomed Eng 1986;14:547-562.[CrossRef][Medline]
  25. Arts T, Meerbaum S, Reneman RS, Corday E. Torsion of the left ventricle during the ejection phase in the intact dog. Cardiovasc Res 1984;18(3):183-193.[Medline]
  26. LeGrice IJ, Takayama Y, Covell JW. Transverse shear along myocardial cleavage planes provides a mechanism for normal systolic wall thickening. Circ Res 1995;77:182-193.[Abstract/Free Full Text]
  27. Shapiro EP, Rademakers FE. Importance of oblique fiber orientation for left ventricular wall deformation. Technol Health Care 1997;5:21-28.[Medline]
  28. Jung B, Markl M, Foll D, Buckberg GD, Hennig J. Investigating myocardial motion by MRI using tissue phase mapping. Eur J Cardiothorac Surg 2006;29S:S150-S157.[Abstract/Free Full Text]
  29. Buckberg GD, Mahajan A, Jung B, Markl M, Hennig J, Ballester-Rodes M. MRI myocardial motion and fiber tracking; a confirmation of knowledge from different imaging modalities. Eur J Cardiothorac Surg 2006;29S:S165-S177.[Abstract/Free Full Text]
  30. Bell SP, Fabian J, LeWinter MM. Effects of dobutamine on left ventricular restoring forces. Am J Physiol 1998;275(1 Pt 2):H190-H194.[Medline]
  31. Takayama M, Norris RM, Brown MA, Armiger LC, Rivers JT, White HD. Postsystolic shortening of acutely ischemic canine myocardium predicts early and late recovery of function after coronary artery reperfusion. Circulation 1988;78(4):994-1007.[Abstract/Free Full Text]
  32. Stuber M, Scheidegger MB, Fischer SE, Nagel E, Steinemann F, Hess OM. Alterations in the local myocardial motion pattern in patients suffering from pressure overload due to aortic stenosis. Circulation 1999;100:361-368.[Abstract/Free Full Text]
  33. Yun KL, Niczyporuk MA, Daughters GT, Ingels Jr. NB, Stinson EB, Alderman EL, Hansen DE, Miller DC. Alterations in left ventricular diastolic twist mechanics during acute human cardiac allograft rejection. Circulation 1991;83(3):962-973.[Abstract/Free Full Text]
  34. Tibayan FA, Lai DT, Timek TA, Dagum P, Liang D, Daughters GT, Ingels NB, Miller DC. Alterations in left ventricular torsion in tachycardia-induced dilated cardiomyopathy. J Thorac Cardiovasc Surg 2002;124(1):43-49.[Abstract/Free Full Text]
  35. Karmazyn M. Role of sodium–hydrogen exchange in cardiac hypertrophy and heart failure: a novel and promising therapeutic target. Basic Res Cardiol 2001;96(4):325-328.[CrossRef][Medline]
  36. Nijhawan N, Nicolosi AC, Montgomery MW, Aggarwal A, Pagel PS, Warltier DC. Levosimendan enhances cardiac performance after cardiopulmonary bypass: a prospective, randomized placebo-controlled trial. J Cardiovasc Pharmacol 1999;34(2):219-228.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 CirculationHome page
G. Buckberg, J. I.E. Hoffman, A. Mahajan, S. Saleh, and C. Coghlan
Cardiac Mechanics Revisited: The Relationship of Cardiac Architecture to Ventricular Function
Circulation, December 9, 2008; 118(24): 2571 - 2587.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
T. C. Gillebert and N. R. Van de Veire
About left ventricular torsion, sex differences, shear strain, and diastolic heart failure
Eur. Heart J., May 2, 2008; 29(10): 1215 - 1217.
[Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
P. P. Sengupta, J. Korinek, M. Belohlavek, J. Narula, M. A. Vannan, A. Jahangir, and B. K. Khandheria
Left Ventricular Structure and Function: Basic Science for Cardiac Imaging
J. Am. Coll. Cardiol., November 21, 2006; 48(10): 1988 - 2001.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J. E. Stelzer, J. R. Patel, and R. L. Moss
Protein Kinase A-Mediated Acceleration of the Stretch Activation Response in Murine Skinned Myocardium Is Eliminated by Ablation of cMyBP-C
Circ. Res., October 13, 2006; 99(8): 884 - 890.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
J. E. Stelzer and R. L. Moss
Contributions of Stretch Activation to Length-dependent Contraction in Murine Myocardium
J. Gen. Physiol., October 1, 2006; 128(4): 461 - 471.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Gerald D. Buckberg
Manuel Castellá
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Buckberg, G. D.
Right arrow Articles by Saleh, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buckberg, G. D.
Right arrow Articles by Saleh, S.
Related Collections
Right arrow Cardiac - physiology
Right arrow Cardiac - other

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS