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Eur J Cardiothorac Surg 2004;26:S62-S67
© 2004 Elsevier Science NL

Review

Stroke and extra-cardiac perfusion: new vantage points in brain protection

^a Options in Bioengineering, California Institute of Technology, Padasena, CA, USA
^b Department of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1741, USA

^* Address: Department of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, Box 951741, 62-258 CHS, Los Angeles, CA 90095-1741, USA. Tel.: +1 310 2061027; fax: +1 310 8255895. (Email: gbuckberg{at}mednet.ucla.edu).

	Abstract

Top Abstract 1. Introduction 2. Surgical role in... 3. Evolution of approaches 4. Controlled reperfusion 5. Surgical intervention sites 6. Future vantage points Appendix References

 
This report shows a new spectrum of applications of a concept of brain protection for the cardiothoracic surgeon. The underlying treatment deals with an ischemic/reperfusion injury, and novel applications of principles well known in cardiac surgery will be used to provide brain protection. Unique opportunities arise from the uncommon use of circulatory arrest in infants and adults (1–2% of procedures) to the larger areas of sudden death (450,000 pts/year in the US), stroke (700,000 pts/year) and carotid occlusion for peri-operative endarterectomy, and neurologic problems after CPB (30% incidence). Treatment pathways in sudden death will address the brain during CPR, the body to get a cause of arrest with use of peripheral CPB, and a controlled cardiac reperfusate to correct the underlying lesion. Circulatory arrest provides the model to treat, both this uncommon surgical process, with extension as toward treating stroke with controlled reperfusion. Novel models of pretreatment and warm brain reperfusion, that mimic warm heart reperfusion are suggested. Construction of the ultimate brain reperfusate, and its conditions of delivery will follow the valid and tested development phases of a warm cardioplegic solution, but become directed towards the brain. Old tricks that lead to new goals will become our innovative vantage points.

Key Words: Stroke • CPR • Circulatory arrest • Carotid occlusion • Sudden death • Post-CPB brain damage

	1. Introduction

Top Abstract 1. Introduction 2. Surgical role in... 3. Evolution of approaches 4. Controlled reperfusion 5. Surgical intervention sites 6. Future vantage points Appendix References

 
Cerebral damage is the most dreaded complication following a cardiac surgical procedure. Preoccupation with this problem is evident by our prompt checking for awakening after cardiopulmonary bypass, and active limitation of deep hypothermic circulatory arrest (DHCA) intervals, when a dry field is critical in aortic arch or certain congenital heart procedures. Our current focus is directed at limiting brain ischemia intervals to reduce damage after reperfusion. Simultaneously, there is limited recognition that governing the process of controlling cerebral reperfusion may provide a unique remedy to post-operative brain damage.

This presentation will extend today's frequently used surgical cardiac reperfusion strategies toward newly proposed ways to modify reperfusion cerebral damage. The three critical steps needed to confront brain reperfusion injury include: (a) accepting that this process happens, (b) understanding that conventional 1 h cold ischemic intervals are only a precursor towards injury, and (c) following the established cardiac trajectory, by uncovering mechanisms that can be manipulated to avoid or correct brain reoxygenation damage.

	2. Surgical role in brain reperfusion injury

Top Abstract 1. Introduction 2. Surgical role in... 3. Evolution of approaches 4. Controlled reperfusion 5. Surgical intervention sites 6. Future vantage points Appendix References

 
Limitation of surgical focus to circulatory arrest in children and adults imposes a restriction to our learning potential, since only 1–2% of patients fill this category. The treatment gamut widens by addressing peri-operative patients who sustain sudden death and survive CPR, but develop brain damage. Additional arenas include neurologic events after cardiopulmonary bypass, and brain damage after carotid endarterectomy, in CABG patients undergoing cerebral revascularization. Finally, the stroke population becomes a major subset for expansion of our brain protection principles, since it includes the wide spectrum of atherosclerosis patients that develop underlying brain vessel occlusion.

Cardiac surgeons have an advantage in evaluating brain protection studies, since circulatory arrest provides a simple reproducible model for invoking brain injury, allows understanding of signs and events, thereby creating a basis for evolving methods to limit and avoid this devastating complication. Clarity comes from recognizing that replenishment of blood is not the answer, since damage persists despite reperfusion, our central surgical theme. We know that safe ischemic time periods are longer in the heart than brain, since circulatory recovery is expected, while neurologic damage is anticipated.

Brain ischemia and reperfusion after circulatory arrest differs from regional organ ischemia, because unmodified whole body reperfusion causes a global reperfusion injury, that includes the brain as the centerpiece for recognizable damage. Consequently, the door opens for treating the brain and whole body in our efforts to diminish reperfusion damage. Simultaneously, studies can be done to separate treatment of the brain and body, novel perspectives can be gleaned, and most importantly, results can be applied to the broad array of causes of brain damage previously described.

Recognition of these novel treatment possibilities allowed us to do preliminary studies that are summarized in this report, which is also amended to include future management options. Our reperfusion stimulus stems from prior success in cardiac studies [1,2] that provided a launch pad to control the conditions and composition of reperfusion in experimental and clinical studies that produced satisfactory results after prolonged ischemia of the leg [3–5], kidney [6] and lung [7,8].

The control database of the circulatory arrest model has merits beyond its use during deep hypothermia in the surgical setting of prolonged total body ischemia. A fairly reproducible injury is made, since there is no collateral flow to camouflage results from this alternative nutrition source following carotid temporary occlusion in dogs and pigs. The major recovery end point is absence of neurologic dysfunction to correspond to our primary surgical guideline of clinical improvement. This vital end point can then be matched to other measurable goals that include biochemical testing, apoptosis and histochemical damage. These elements of time and pathology are, critical to long-term results, but we must never, however, lose sight of the fact that neurological recovery is the forest, and these measurable elements of damage are the trees that become disrupted by reperfusion injury.

The central themes of dealing with brain damage include the triad of (a) the event, (b) its cause, and (c) support measures while the underlying genesis is sought. Discussion of issues of DHCA and sudden death will be undertaken to focus upon these interweaving factors. Certainly, brain dysfunction after DHCA fills this bill, since surgeons produce this event by turning off the pump, and can determine how to reperfuse the body and brain. Should we modify how we conduct the pump run, restore normal blood supply, or modify the conditions and composition of the reperfusate? I believe that sudden death in the peri-operative interval introduces an even more useful tool to understand this triad, since it makes us focus on how our currently employed cardiac reperfusion interventions can positively modify the secondary neurologic outcome of ventricular fibrillation or asysotole.

	3. Evolution of approaches

Top Abstract 1. Introduction 2. Surgical role in... 3. Evolution of approaches 4. Controlled reperfusion 5. Surgical intervention sites 6. Future vantage points Appendix References

 
The currently accepted mortality of sudden death is 90% from either in or out of hospital events. More importantly, approximately 50% of survivors have severe neurological defects. This reflects a ‘save the heart, lose the brain’ concept, caused by treating only the arrest, but not the cardiac cause of death. A coronary event is responsible in 70% of patients, so that management must treat both reperfusion injury of the heart and brain. Treatment methods that address the heart have limited improvement, unless the cardiac reperfusion injury is directly addressed. Our results in 34 sudden death patients undergoing 72 min of CPR, show 80% survival, with only 6% neurologic complications, a sharp contrast to prior studies [9]. Our prior studies showed complete cardiac functional recovery occurred, confirming that heart reperfusion injury was avoided [10]. The management process (a) maintained brain circulation with keeping monitored blood pressure at 60 mmHg, (b) made the cardiac diagnosis, and (c) performed CABG with controlled reperfusion to the occluded vessel [11].

The implications for this cardiac and brain salvage are large, since 450,000 patients in the US have sudden death, as the interface of (a) aggressive maintenance of brain blood flow, (b) catheterization lab diagnosis (probably using peripheral bypass support) and (c) controlled cardiac reperfusion may change the approach to sudden death with introduction of a new and potentially large surgical interface. Furthermore, this concept of heart salvage by controlled reperfusion can be expanded towards the brain to (a) altering the pump prime to affect other organs that had limited under perfusion during CPR, and (b) applied to vascular surgery, thereby setting the groundwork for applying this regional concept to focal brain ischemia after stroke, or during carotid revascularization in patients needing carotid endarterectomy, either during CABG or as a primary procedure.

	4. Controlled reperfusion

Top Abstract 1. Introduction 2. Surgical role in... 3. Evolution of approaches 4. Controlled reperfusion 5. Surgical intervention sites 6. Future vantage points Appendix References

 
Uncontrolled reperfusion uses normal unmodified blood, while controlled reperfusion alters the conditions (i.e. pressure, temperature, flow dynamics, etc.) and composition (pH, platelets, WBC, complement, ionic components, osmolarity, substrate, drugs, etc.) of reperfusate blood. The spectrum of potential alterations are broad, so that my initial comments will address only the few elements we have altered to define how reperfusate modification positively determines brain recovery. This overview does not define specific treatments, but rather evolves a concept of the value of controlled reperfusion, to open our intellectual portals toward a new scheme of management.

Multi-organ failure from post-operative low output syndrome is recognizably due to poor myocardial protection. I believe that circulatory arrest causes similar multi-organ failure from global reperfusion injury that may develop simultaneously with the impaired neurologic recovery after >60 min of cold global ischemia. We confronted this potential body/brain damage after 90 min of DHCA by showing that modifying the extra-corporeal pump prime allows construction of a global reperfusate. We modified its composition to include WBC filtration, lowering calcium with CPD, adding Mg++, a buffer with THAM, adding a Na+/H+ exchange inhibitor (Cariporide), hyperosmolarity, used low pressure reperfusion and applied alpha stat pH strategy.

Significant modification of reoxygenation damage followed controlling global reperfusion. Compared to untreated studies, early neurologic recovery was markedly improved when measured by a standard score (evaluating central nerve function, respiration, motor and sensory action, consciousness, and behavior). Furthermore oxygen radical and endothelial damage was reduced, cardiac and pulmonary function improved, and less biochemical evidence of global damage was detected. These global findings are relevant to future management of circulatory arrest, and may subsequently be applied towards using temporary bypass to support sudden death patients. Clearly, the prime can be changed to add constituents that modify global reperfusion damage, since the pump becomes the heart, and actively altering the blood components that are delivered may more effectively deal with global reperfusion damage.

Concern about a composite solution rather than a focal mechanism is a standard response. However, reperfusion damage is an event that causes entropy which subsequently alters a spectrum of biochemical and functional components. Consequently, it will be simply impossible to define a single modifiable cause. Instead, we should build upon known factors that can positively modify reperfusion damage, rather than search for a magic bullet that is non-existent. The therapeutic cocktail will grow, rather than shrink as we learn about the disrupted components. The traditional inquiry about the most important component takes me back to the concept of the search for the most important part of the cardioplegic solution. I refer the questioner to the orchestra, asking for a definition the worst instrument. The answer is the instrument that is not playing the right tune, thereby impairing the symphony by creating lack of cohesion. Reperfusion injury causes a chaotic disruption, and treatment must be harmonic and based upon input from many recognized beneficial factors.

This global view does not defeat searching for new individual components, which can subsequently strengthen any existing remedy. The critical investigative steps are to: (a) create a model of damage with normal blood reperfusion, (b) determine if one element can completely overcome this injury, (c) extend ischemic duration to define the limitations of single factors, and (d) then assess if these individual elements can be added to the aforementioned global approach, with the goal of prolonging the ischemic interval by delivering a composite reperfusate that safely limits neurological damage.

	5. Surgical intervention sites

Top Abstract 1. Introduction 2. Surgical role in... 3. Evolution of approaches 4. Controlled reperfusion 5. Surgical intervention sites 6. Future vantage points Appendix References

 
Surgical access allows either pretreatment or direct reperfusate modification. To guide insight into this scheme, I will summarize two individual factors we recently tested in DHCA studies. First, reperfusion damage is closely linked to adverse calcium metabolism, whether the process is global, cardiac or cerebral [12]. Our ongoing studies on pretreatment with Cariporide, a sodium hydrogen exchange (NHE) inhibitor, show that positive brain reperfusion events match our recent cardiac studies [13,14]. NHE inhibition completely avoided neurologic damage after 90 min of DHCA (at 24 h measurement), limited endothelial damage, decreased oxygen radical injury, and minimized global injury by reducing the elution of CK and SGOT [15]. The range of agents that can correct adverse calcium deposition is broad, but these positive findings may generate new studies, especially with testing specific roles in the reperfusion process, as we showed in prior cardiac studies [16].

Second, endothelial damage is one major component of reperfusion damage, with WBC related injury causing oxygen radical production, neutrophil adherence to capillary walls and microvascular obstruction, ultimate focal areas due to ischemia from platelet deposition, and inflammatory reactions. To deal with this component, we studied reperfusate mechanical filtration after 90 min of DHCA by using a special CoBRA filter to deplete WBC's, platelets, and complement complex [17]. Consequently, the brain received a regional reperfusate via perfusion through the carotid vessels prior to global reperfusion by the extra-corporeal circuit. The result was complete neurologic recovery, a finding that completely corresponded to the cardiac response we previously found after NHE inhibition after myocardial ischemia [18]. While isolated reperfusate filtration intervention caused prominent neurological improvement, the positive global changes of changing the pump prime with NHE inhibitors were not achieved. These limitations included more endothelin production, less limitation CK and SGOT release when the circulatory arrest experimental design failed to address the combined body/brain reperfusion damage.

Restriction of studies to only one component will limit straightforward conclusions. For example, the observed positive neurological recovery effects in untreated hearts happened after use of the alpha stat pH strategy, without our defining how pH stat management would influence effects. Prior knowledge that pH stat management causes better oxygenation during arrest induction, luxury brain perfusion, and reduced reperfusion calcium flux [19] was not evaluated. However, the positive brain recovery after alpha stat sets the stage for another study, where the contrast between pH stat and alpha stat is evaluated after DHCA is extended to 2 h. This comparison of singular strategies is simply made to show (a) the benefit of either NHE inhibition or reperfusate blood filtration could potentially be similarly achieved by pH management alone after 90 min of DHCA, (b) each positive result at short ischemic interval sets the stage for prolonging the DHCA period, and (c) once a recovery limitation is encountered, the effects of combining positive effects can then be tested so that (d) a brain reperfusate can be created that uses the interactive beneficial effects of many strategies.

	6. Future vantage points

Top Abstract 1. Introduction 2. Surgical role in... 3. Evolution of approaches 4. Controlled reperfusion 5. Surgical intervention sites 6. Future vantage points Appendix References

 
The stages of our search to limit brain reperfusion damage parallels the developmental process that has been so effective in cardiac studies [20]. The road towards brain recovery is open, and lets cardiac surgeons explore new fields that expand our therapeutic options. I think we will evolve from an initial focus upon isolated components associated with brain damage toward composite strategies. Future investigative and clinical studies that create a new vantage point, a process that extends surgical interventions far beyond the limited realm of our current brain protection interests that are now restricted to circulatory arrest in adults and children.

	Appendix

Top Abstract 1. Introduction 2. Surgical role in... 3. Evolution of approaches 4. Controlled reperfusion 5. Surgical intervention sites 6. Future vantage points Appendix References

 
Conference discussion

Dr M. Turina (Zurich, Switzerland): Gerry (Gerald Buckberg), most of the lesions we encounter clinically, both in strokes and in Type II postoperative lesions, are shown in the CTs to be of ischemic origin, so they are caused by the obstruction of a major vessel, more commonly in the anterior cerebral artery area rather than in the basilar artery region. How do you propose to reperfuse the area where the antegrade blood supply has been blocked?

Dr Buckberg : Our radiologists are developing some very intriguing catheters that can go up in through an area of occlusion, and this will allow the possibility to regionally reperfuse these areas. Until now, there was consideration of only thrombolysis. However, if a regional catheter can be introduced to supply this area, the method of reperfusion can be modified. Instead of simply giving regular blood back, a cerebral reperfusate can be given. This is done by taking blood from the patient's femoral artery, connecting the blood into a system that simulates the way of we currently give a cardioplegic solution. The reperfusate can then be delivered into regional areas in the brain if the occlusion is in the skull. If there is carotid occlusion, this is done more easily with regular angioplasty catheters.

Dr Turina : You will be surprised to hear that this original Gruntzing's idea which we were using in the animal lab, and it was used in the very first patient, was reperfusion through the catheter beyond the lesion, and then it was found that it was not necessary. But it is just a footnote.

Dr Buckberg : A good one.

Dr A. Haverich (Hannover, Germany):): I enjoyed that presentation very much. I have a question regarding the idea of cardiopulmonary resuscitation. I think it is a very interesting concept. Like what we have seen with the defibrillators being distributed all over the country, would you think that every emergency car and maybe every aircraft should be equipped then with a miniaturized extracorporeal bypass machine?

I am asking that question for a good reason, because two weeks ago a venture capital company was visiting me and asking me whether this concept would hold for the future. I said, well, I like the idea, it looks a bit unreal at this point, and I can't imagine how those drivers in an emergency car could actually get the arterial and the venous line into the groin, but from a medical concept I think it's very appealing. My second question, what is the role of the cardiac surgeon in that field?

Dr Buckberg : First of all, it's expansion in scope of how we are looking at things. I believe our data is correct by showing that sudden death patients can be salvaged. This information then opens a new role for the perfusion community, and a new role for the cardiac surgeon to correct the underlying cause of the arrest. This means that treatment involves putting the patient on bypass, decompressing the ventricle and grafting many vessels by using a controlled reperfusate. This sudden death event doesn't usually happen with single vessel disease. Consequently this approach will expand the vista of cardiac surgery by our treating a new arena of sudden death patients.

The potential exists, since conventional treatment results in failure, so that 85 to 95% of these people succumb. Conversely, this novel treatment now salvages 80%, without significant brain injury. This positive result may alter how future emergency rooms are structured and result in building an operating room/cath lab combination region in an emergency room. It is also possible that the paramedical personnel can introduce fem–fem bypass in the field, since this level of technical support will arrive by ambulance, are they are currently well trained to insert fem–fem catheters. Novel treatments may change what a cardiologist does in the cath lab, since pump systems may start to exist in cath labs. The potential exists that instead of bringing patients to the operating room, we may move operating room into the cath lab, and have a novel combined site.

The ultimate consequence is that we are taking a successful strategy surgically, considering ways to modify technology that we use every day, and then applying these methods in a local situation in a hospital where patients develop the sudden death lesion. Simple groin cannulation methods will allow others to initiate the body bypass procedure before the cardiac surgeon begins. In our series, some patients came in by helicopter with CPR. In them, we put them on fem–fem bypass in the cath lab, made a diagnosis by angiography on bypass, then went to the operating room, and the results were okay. This approach then really opens up some very novel doors to what the cardiac surgeon can do. It brings together many things we did before, including coronary bypass, controlled coronary perfusion, a new application in the a sudden death patient, and now we introduce the novel concept of changing the whole pump prime to avoid a body reperfusion injury. So I believe this vision may apply many things we have done in the past to new arenas.

Dr D. Birnbaum (Regensburg, Germany): I would like to amplify on this issue. I enjoyed this conception of cerebral protection very much. We have some experience in this field with a miniaturized heart–lung machine, which we distribute in the hospital such as in the cath laboratory, in the X-ray department and in the emergency room. With this service we have some limited experience: about 50 patients. And just by the way we came to a very interesting observation that whenever the pH at the beginning of the percutaneous application of the heart–lung machine is below 7, the patients will die. If it is above 7, they will survive with this method of extra corporeal circulation. So this is a question of a timely initiation of perfusion. Perfusion is a conception of cardiac surgeons. So this method needs to be in the hands of experienced cardiac surgeons in terms of perfusion.

Now, to our experience, it was very difficult to convince the people in the hospital who are responsible for application for this miniaturized heart–lung machine, which is a life support system, nothing more. It is easy to transport, and easy to apply in the patients by access to the femoral vessels. But to convince the hospital it was at least a two-year job. So how can we go around to advertise our experience as alternative as an effective replacement of conventional resuscitation methods?

Dr Buckberg : Well, I think the way to open this field is to have everyone recognize that your current treatment results in a 90–95% mortality in the sudden death population. When you suddenly show them that a significant series of patients are alive without brain problems, you have then defined a totally different form of therapy. This management salvages patients that are dead. If this novel approach leads a listener, or an editor to ask for a prospective randomized trial, I always tell them my favorite story about creating significant survival that is not possible by standard therapy, where most patients would be dead. I indicate, why doesn't the editor, or the doubter of this data come to the zoo with me, so I can show them why this data is important. When we enter the zoo, we go immediately to the bear cage. I look at the bear and the bear looks at me, and then and I look at the bear and he looks at me again. Then, the bear says, "Good morning, Dr. Buckberg, how are you?" And I say, "That is a talking bear. Do you want him randomized?"

Dr T. Wahlers (Jena, Germany): I would like to support Dr. Birnbaum's comments, however, with regard to my personal practice and patients with myocardial infarction, I can tell you, that my cardiologist has already adopted this aggressive approach.

He has bought his own Medtronic circulatory support system and takes it to the cath lab, and thereafter, if the patients brain is damaged by hypoperfusion, he asks me how can we better perform the perfusion technique and cardiothoracic help.

So we have changed his isolated concept into an integrated approach that we get informed if a patient comes into the hospital with resuscitation, and then we establish the perfusion and see how we proceed together.

And with that strategy, we had an improvement, because the patients he treated alone, many brain damage or malperfused legs or other problems.

Dr L. Bockeria (Moscow, Russia): Can I ask, a patient dies two hours before surgery and he is resuscitated and intubated successfully. Can I take the patient in time for surgery or shall I wait until he wakes up?

Dr Buckberg : This is a very fundamental question, because the the key to this is not the heart, but the brain He has been resuscitated, but arrest can recur unless the cardiac lesion is treated. With continued arrest, two areas are very important. First, we will not move the patient unless we have sustained a peak monitored arterial pressure of 60 mmHg. to insure brain perfusion during CPR. In one patient we had successful heart and brain recovery after CPR for 2 1/2 h at peak arterial pressure of 60 mmHg. More recently, we have started to monitor brain oxygenation by recording jugular venous PO2 with Sonometric monitors in the neck skin. This brain value may very useful, and thus mirror information on PA saturation by Swan-Ganz measurements. More data is needed. Once you are confident that the brain has been preserved during CPR, since you are providing brain blood flow by pressure, the next question is, can the heart come back? Our past experience with controlled cardioplegic reperfusion shows that the heart comes back beautifully and regional function returns. Conversely, if there is sudden occlusion and you use regular blood instead of a controlled reperfusate, an infarct will usually occur, producing regional a akinesia that my go on to later heart failure.

We never wait to see if they wake up, because many develop recurrent fibrillation while you wait to determine consciousness. You must recognize that survival after sudden death by CPR alone, usually means you have only treated the symptom of underlying cardiac disease. The most important decision is to move forward and fix the heart that caused sudden death.

Dr Bockeria : Excuse me, I didn't get an answer. So shall I wait until he is awakened, opened the eyes, or shall I measure his pH?

Dr Buckberg : I would not do that. Our experience would say that what you want to do is that immediately after resuscitation following witnessed arrest, you should get their body supported as quickly as you can on bypass, and then fix cardiac cause of sudden death. We followed this process in several patients that resumed their own circulation after successful CPR, and also had good results with that subset.

I believe the key issue is to realize you must determine the cardiac cause of arrest so this that can be corrected before sudden death recurs. It is critical to find good coronary anatomy to revascularize, and this needs an angiogram before deciding to initiate controlled cardiac reperfusion in the operating room. Conversely, if the patient had multi-vessel disease, with in one two small areas (diagonal of RCA branch only) to resuscitate, I would not proceed with the cardiac part. You must be really sure you can something positive about the heart, as and salvage the brain should be made by immediate effective CPR.

Dr F. Mohr (Leipzig, Germany): I just want to put that into numbers. We have been reviewing and we presented at the AATS a four-year period of about 16,000 patients, and 60 of them had gone through such a situation, and the mortality rate at the very end was 80%, and I am very hesitant in advertising that for the future that this is going to open a new perspective for our field.

For the cardiologist, it is not only the fem–fem bypass, they use a femoral cannula puncturing the septum, venting the left atrium, which makes sense for me. On the other hand, if you look at the real world, patients come to the heart center in myocardial infarction. There is always a time delay of between one and two or three hours. And if we go ahead now and advertise such kind of treatment, I think they will always end up at our ICU, and we will face major, major problems in terms of chronic patients. I agree that, of course, if you institute it early you can preserve some of the brain functions. On the other hand, I am not sure if in the long run we really, really have a real chance to expand our field.

Dr Buckberg : I think results are technique-related. If you reperfuse with regular blood, you will have exactly the mortality you described because this reflects uncontrolled reperfusion. Conversely, I have described a controlled reperfusate that provides the different results that I reported. The method is critical.

Furthermore, You can't really decompress the heart through the left atrium, because this method does not completely empty the left ventricle. The oxygen uptake of the heart is directly related to ventricular decompression. Consequently, left atrial vent is only effective if there is mitral insufficiency. Without this, you must decompress the heart through the left ventricle. So the principles of what we do surgically must be applied surgically. Today, they cannot be applied in the cath lab. Just like the rigidity of a technical procedure, here there must be a discipline of how you protect the heart. The current approach of the cardiologist having a solution and a catheter will not work, for problems happen when people vary a clear precise method. The technique we described was done at four different hospitals, and the results were the same in each center. I think that what you are saying about uncontrolled reperfusion is correct, but deviates from our results with controlled reperfusion.

What we are doing now is based on this novel approach. We are currently setting up a series of five hospitals in the United States that are going to try this aggressive approach with fem–fem bypass and see if they can reproduce these results that I reported today. We are doing this in concert with industry and the NIH. Perhaps in a year or so we will have some more information to see if this can be reproduced by others. Should other centers confirm our findings, this observation may originate a total change in treatment of a large group of patients that are dead by conventional methodology. Clearly, the magnitude of this contribution can only be weighed after this concept is tested by others.

	Footnotes

 
Presented at the EACTS Symposium for the Future of Cardiac Surgery, Frankfurt, Germany, July 1–2, 2004.

	References

Top Abstract 1. Introduction 2. Surgical role in... 3. Evolution of approaches 4. Controlled reperfusion 5. Surgical intervention sites 6. Future vantage points Appendix References

 

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