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Eur J Cardiothorac Surg 1998;13:78-83
© 1998 Elsevier Science NL

Experimental development of an electrically stimulated biological skeletal muscle ventricle for chronic aortic counterpulsation¹

^a Department of Plastic and Reconstructive Surgery, Medical School, University of Vienna, Vienna, Austria
^b Department of Biomedical Engineering, Medical School, University of Vienna, Vienna, Austria
^c Institute of Anatomy, Department III, Medical School, University of Vienna, Vienna, Austria
^d Department of Cardio-Thoracic Surgery, Medical School, University of Vienna, Vienna, Austria
^e Center for Biomedical Research, Ludwig Boltzmann Institute for Cardiosurgical Research, Medical School, University of Vienna, Vienna, Austria

Received 14 April 1997; received in revised form 20 October 1997; accepted 29 October 1997.

Corresponding author. Present address. Department of Reconstructive and Plastic Surgery, Clinic of Surgery, University of Vienna, Vienna General Hospital, Währinger Gürtel 18–20, A-1090 Vienna, Austria. Tel.: +43 1 404005620; fax: +43 1 404005640.

	Abstract

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Objective: The chronic shortage of donor organs for cardiac transplantation and the high costs for mechanical assist devices demand the development of alternative cardiac assist devices for the treatment of severe heart failure. Cardiac assistance by stimulated skeletal muscles is currently investigated as such a possible alternative. The goal of the presented study was to construct a newly designed biological skeletal muscle ventricle and to evaluate its possible hemodynamic efficacy in an acute sheep model. Methods: A total of 14 adult sheep were used for acute experiments. The entire thoracic aorta including the aortic root was excised from a donor sheep. An aorto-pericardial pouch conduit (APPC) was created by enlarging the aortic circumference in its middle section with two strips of pericardium. This biological conduit was anastomosed in parallel to the descending aorta of a recipient sheep, using the aortic root as an inflow valve to the conduit. Stimulation electrodes were applicated to the thoracodorsal nerve and the latissimus dorsi muscle was detached from the trunk and wrapped around the pouch. ECG-triggered functional electrical stimulation was applied during cardiac diastole to simulate aortic counterpulsation. Stimulation was performed during various hemodynamic conditions. Results: A standardised surgical procedure suitable for long term studies was established during six experiments. An APPC, with 70–80 mm filling volume, was found to be of optimal size. In another eight experiments, hemodynamic measurements were performed. Under stable hemodynamic conditions the stimulation of the biological skeletal muscle ventricle induced a significant increase of mean arterial pressure by 14% and mean diastolic pressure by 26%. During pharmacologically induced periods of cardiac failure, the stimulation of the APPC increased mean arterial pressure by 13% and mean diastolic pressure by 19%. In all eight experiments, the diastolic peak pressure reached supra-systolic values during stimulation. Conclusions: The results demonstrate the hemodynamic efficacy of this newly designed biological skeletal muscle ventricle as an aortic counterpulsation device. Chronic experiments using a preconditioned fatigue-resistant muscle will further help to evaluate its possible clinical significance.

Key Words: Circulatory assist • Aortic counterpulsation • Skeletal muscle ventricle • Functional electrical stimulation • Animal experiment

	Introduction

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Various approaches have been investigated to achieve chronic cardiac assistance using skeletal muscles in the past [1], but only dynamic cardiomyolasty and recently dynamic aortomyoplasty have found their way into clinical practice [2] [3] [4] [5]. These procedures seem to improve the clinical situation of the patients but the hemodynamic efficacy still remains unclear [6]. However, chronic cardiac assistance might be derived from a conditioned LDM, but the optimal design for such a procedure has yet to be found. Therefore, new interest is fueled to electrically stimulated skeletal muscle ventricles [4] [7] [8].

A skeletal muscle ventricle (SMV), consisting of hemocompatible biomaterials only, was designed in order to perform counterpulsation in parallel to the descending aorta. Design and hemodynamic efficacy of this configuration were proofed in a series of acute experiments in sheep.

	Materials and methods

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A total of 14 adult female sheep, weighing 57.5±6.2 kg were used for the acute experiments. The animals were put under general anesthesia and euthanized at the end of the experiments. All animals received human care in accordance with the Austrian federal law for the care and use of laboratory animals.

Prior to the operation, the pericardium and the entire thoracic aorta including the aortic root had been excised from fresh sheep cadavers. These ‘homografts’ were cryopreserved and the pericardium was preserved (2.5% glutaraldehyde solution), both according to approved techniques [9] [10]. At the time of the experiment the homograft was defrosted and both homograft and pericardium were rinsed with 0.9% saline solution. The homograft was longitudinally arteriotomised in its middle part on opposite sides and enlarged by two patches of pericardium to create an aorto-pericardial pouch conduit (APPC), using 4.0 running sutures ( Fig. 2.1) .

The recipient sheep was placed in the right side position to perform a left side lateral flank incision. The left LDM was detached from the thoracic wall, while its insertion to the humeral bone and the supplying neurovascular pedicle were preserved carefully. The LDM was divided longitudinally from its distal end, up to the entry of the neurovascular bundle in order to create two muscle flaps of equal size. A segment of the third rib was removed and the branches of the LDM were placed in the left hemithorax. Then the fifth and sixth rib were resected to provide an optimal access to the descending aorta. The APPC was anastomosed in parallel to the descending aorta of the recipient sheep, using the aortic root as an inflow valve to the conduit. Distal to the commune brachiocephalic trunk, the proximal part of the APPC was anastomosed to the recipient aorta using pledgeted 4.0 single sutures. The distal end of the APPC was cut back to the appropriate length and connected with the descending aorta using 4.0 Prolene running sutures ( Fig. 1 ). The APPC was clamped in its proximal and distal part and emptied mechanically. The two branches of the LDM were wrapped around the neo-ventricle in counterrotating direction. The branches were fixed to the APPC and to each other in order to cover the entire neoventricle and to avoid dislocations of the muscle during stimulation ( Fig. 2). Finally, the clamps were removed and the free ends of the muscular branches were fixed to the remaining parts of the fifth and sixth rib.

View larger version (25K): [in this window] [in a new window]   Fig. 1. Schema of the aorto-pericardial pouch conduit (APPC) in parallel with the descending aorta in sheep. aortic valve (1), commune brachiocephalic trunc (2), descending aorta (3), APPC (4), aortic valve of the APPC (5), Latissimus dorsi muscle (6)

View larger version (149K): [in this window] [in a new window]   Fig. 2. Construction of the biological SMV during operation (1) Aorto-pericardial pouch conduit (APPC) (a) anastomosed with the descending aorta on both ends; inflow (c), outflow (b). (2)Branches of the divided LDM (a+b) wrapped around the APPC; inflow (d) outflow (c).

Rectangular pulses with 0.6 ms duration at a frequency of 28 Hz were used to perform bipolar burst stimulation. The current could be adjusted from 0 to 4 mA and actually was set to achieve maximum tetanic contraction of the LDM. R-wave triggered stimulation at a rate of 1:2 or 1:3 with the native heart rate was applied during the diastole to simulate aortic counterpulsation. The arterial pressure curve derived from the brachiocephalic trunc was selected for the timing of the stimulation. The stimulation was adjusted to increment arterial blood pressure during diastole only and to affect neither the previous nor the following systole.

The animals were instrumented in the following fashion. A flow-directed pulmonary artery catheter was introduced from the left jugular vein. A Millar transducer-tipped aortic catheter was introduced into the left ventricle from the left carotid artery. Saline-filled plastic catheters were placed directly into the brachiocephalic trunk and introduced into the abdominal aorta from the left femoral artery. These hydraulic pressure catheters were connected to Van-den-Burg disposable pressure transducers. All hemodynamic variables were recorded simultaneously by a Hellige computerized registration unit (Hellige), which includes an analog to digital converter and systems for data analysis.

Short periods of stimulation, containing 10–20 muscle contractions only, were applied with respect to the non fatigue-resistant, unconditioned LDM. These sequences of stimulation were performed repetitively with adequate periods of rest for recovery of the muscle. After that, periods of cardiac failure were induced pharmacologically by rapid intravenous infusion of a betablocker (Breviblock®) and the stimulation was repeated after stabilisation of the hemodynamic parameters.

Baseline hemodynamic measurements were taken at the beginning of the operative procedure, after opening the left hemithorax and before stimulation in order to document the general condition of the animals during surgery. A second set of hemodynamic variables was recorded before stimulation with the SMV in an inactivated ‘static’ state and during stimulation. During pharmacologically induced periods of cardiac failure, a third set of hemodynamic measurements was recorded, again with and without stimulation.

Hemodynamic data derived from the left ventricle were analysed for left ventricular peak pressure (LVP-max) and enddiastolic pressure (LVP-min). Data obtained from pressure catheters in the brachiocephalic trunc and the abdominal aorta were calculated separately as p-Truncus (pT) and p-Aorta (pA): maximum and minimum pressure occuring during systole and diastole were evaluated (p-max, p-min); mean arterial pressure (p-mean) and mean diastolic pressure (p-dia) were calculated from the area under the pressure curve.

For statistic analysis, each animal served as its own control. Hemodynamic variables obtained with the SMV in an inactive state (p) were compared with the data obtained during stimulation of the SMV (p-Stim). For purpose of analysis, the heart beat occuring before stimulation of the SMV was used for comparison; only for left ventricular pressure curves the data before the onset of stimulation served as the baseline (LVP) and were compared with the values obtained immediately after stimulation (LVP-Stim). Data used for statistical analysis are presented as mean values, derived from a sequence of three unstimulated and stimulated heart beats. For comparison, the paired t-test was used, with significance interpreted as P<0.05.

	Results

Top Abstract Introduction Materials and methods Results Discussion References

 
During the first experiments (n=6) a standardised surgical procedure, suitable for long term studies could be developed. An APPC with a filling volume of 70–80 ml turned out to be optimal in size with respect to the size of the muscle flaps. The optimal configuration was achieved by enlarging the aortic circumference in its middle section with two 8x4 cm fusiform patches of pericardium and was used during the following experiments (n=8).

Macroscopically, the division of the LDM did not cause marked cyanosis of parts of the muscle or denervation of parts of the LDM in any case (n=14). At the end of each experiment, an investigation of the inner surface of the APPC was performed (n=14). Visual inspection did not reveal aggregates or thrombotic formations.

During the second series of eight experiments, the hemodynamic efficacy of the SMV was evaluated. All hemodynamic data were derived from these experiments (n=8). The hemodynamic condition of the animals was kept relatively stable throughout the experiments. The mean heart rate increased from 90.5±10.1 beats per minute (b/min) at the beginning of the operation to 111±29.5 b/min at the time of stimulation. In the same period, the mean systolic arterial blood pressure (ABP) decreased from 100±24.6 to 75.7±10.8 mmHg. The pharmacologically induced cardiac failure led to a decrease of mean heart rate from 111±29.5 to 102.6±27 b/min and mean systolic ABP from 75.7±10.8 to 40±16.4 mmHg.

Stimulation was performed under stable conditions and did affect left ventricular peak pressure (LVP-max), mean arterial pressure (p-mean) and mean diastolic pressure (p-dia), which increased to supra-systolic values in all experiments. Right ventricular (RVP) and pulmonary artery (PAP) blood pressure did not reveal alterations due to the stimulation.

The time delay between R-wave and the onset of stimulation ranged from 180 to 400 ms with respect to the native heart rate and the burst duration actually ranged from 120 to 300 ms.

Measurements during normal heart function (Table 1, Fig. 3 a)
Stimulation of the SMV caused a significant increase of pT-max by 19% (P<0.04) and pA-max by 27% (P<0.02), while LVP-max decreased, not significantly by 5% (P<0.1). pT-min, pA-min and LVP-min showed a tendency to decrease, but were not altered significantly by FES. pT-mean and pA-mean increased significantly by 14% (P<0.02) and 17% (P<0.02) and pT-dia showed a significant increment of 26% (P<0.01). pA-mean was not applicable because the pressure curve derived from the abdominal aorta did not allow differentiation between diastole and systole.

View larger version (89K): [in this window] [in a new window]   Fig. 3. Sheep 11. Stimulation of the biological SMV in counterpulsation mode during normal heart function (a) and during periods of cardiac failure (b). FES, electrical stimulation; pTruncus, arterial pressure in the brachiocephalic trunc; pAorta, arterial pressure in the abdominal aorta; LVP, left ventricular pressure. Diastolic augmentation marked by arrows.

	Discussion

Top Abstract Introduction Materials and methods Results Discussion References

 
A new type of skeletal muscle ventricle, made of hemocompatible biological materials only and different from already presented configurations [4] [7] [8] was realized in sheep. As a result, a standardised surgical procedure, suitable for long term experiments in sheep, was established.

Activation of the APPC led to reduction of left ventricular peak pressure and induced marked increases of mean arterial and mean diastolic blood pressure. Referring to criterias for aortic counterpulsation [7], the configuration did produce some of the required hemodynamic changes. In fact, counterpulsation-efficacy was not to be expected in this series of acute experiments, in which an unconditioned LDM was used. A total of 10–20 contractions, at a rate of 1:2 or 1:3 with the native heart rate, were far from reaching a steady state, which is necessary to evaluate part of the expected overall influence to the circulation.

Stimulation of the APPC produced diastolic augmentation mainly, but also affected the systole, especially in the abdominal aorta ( Fig. 3). This systolic augmentation is related to the time delay between the onset of the stimulated pulse wave in the abdominal aorta and its onset in the brachiocephalic trunc and does not refer to timing problems. Actually, the anatomical configuration of the APPC seems to require this early onset of the stimulation to achieve optimal diastolic augmentation in the aortic root.

Summarizing our experimental studies, it is too early for direct comparison with Stephenson’s pericardium lined SMV, which worked in circulation up to 589 days [8] or aortomyoplasty, which already has been performed clinically [4]. However, the achieved results encourage us to continue the investigation of our newly designed fully biological SMV. Chronic animal experiments using a conditioned LDM [13] [14] will be performed in order to investigate the long-term behaviour and reliability of the configuration and its overall influence to the circulation.

	Acknowledgments

 
The study was supported by grants of the Austrian Ministry for Health and Sports and the Austrian National Bank.

	Footnotes

 
Poster presentation (P 180) by R. Seitelberger at the 10th Annual Meeting of the European Association for Cardio-thoracic Surgery, Prague, 6–9 October, 1996.

	References

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