retrograde warm blood cardioplegia preserves hypertrophied myocardium: a clinical study

Retrograde Warm Blood Cardioplegia Preserves Hypertrophied Myocardium: A Clinical Study Philippe Menasche, MD, PhD, Frangois Tronc, MD, Alix Nguyen, MD, Line Veyssik, MD, Mustapha Demirag, MD, Jacques LariviPre, MD, Olivier Le Dref, MD, Armand H. Piwnica, MD, and Gerard Bloch, MD Department of Cardiovascular Surgery, HBpital LariboisiPre, Paris, France

The ability of retrograde warm blood cardioplegia to preserve hypertrophied myocardium remains controver- sial. This two-part study was undertaken to address this question in patients subjected to aortic valve replacement for calcified aortic valve stenosis complicated with echocardiographically defined left ventricular hypertrophy. Part I was designed to assess the intraoperative patterns of myocardial oxidative metabolism in 20 patients in whom the severity of left ventricular hypertrophy was reflected by a mean (k standard error of the mean) myocardial mass index of 213 2 15 g/m'. After antegrade arrest, warm blood cardioplegia was continu- ously given through the coronary sinus at a flow rate of 200 f 5 mL/min. The use of a low-dilution cardioplegia delivery technique enabled us to keep hematocrit at 25.6% f 0.9% and the core temperature was allowed to drift to 32.7 & 0.2"C. At the end of the arrest period, blood samples were simultaneously taken from inflow (coronary sinus catheter) and outflow (left coronary ostium) cardioplegia and assayed for blood gases, oxygen content and saturation and lactate. Part I1 was designed to compare the clinical outcomes of these 20 warm patients with those of 20 case-matched patients in whom a conventional hypothermic myocardial protection tech-

nadequate preservation of hypertrophied myocardium I remains one of the concerns associated with the use of continuous retrograde warm blood cardioplegia [l]. This concern is based on the expected increase in the metabolic demand of hypertrophied hearts, which leads one to question the ability of retrograde coronary sinus perfusion to supply enough oxygen for avoiding an energy mismatch and the resulting shift of myocardial metabolism toward anaerobiosis. In an attempt to address this question, we assessed the intraoperative patterns of myocardial oxidative metabolism in 20 patients who underwent continuous retrograde warm blood cardioplegia during aortic valve replacement for aortic valve stenosis complicated with echocardiographically defined left ventricular hypertrophy (LVH).

nique was used. The results of part I show that after an average arrest period of 72 * 4 minutes, the residual oxygen demand was still high as reflected by a percent oxygen extraction of 34.8% 4.1%. This demand, however, was adequately met by the supply, as demonstrated by (1) the absence of transmyocardial acid production, (2) a negligible release (outflow minus inflow) of lactate (0.28 k 0.1 mmol/L), and (3) a high residual oxygen saturation (65.7% -+ 3.8%) in outflow cardioplegia. The results of part I1 show that the clinical outcomes of warm patients were overall good and not different from those of the cold group. We conclude that retrograde warm blood cardioplegia can adequately preserve hypertrophied myocardium by keeping its metabolism predomi- nantly aerobic during aortic cross-clamping provided that measures are taken to optimize the determinants of the oxygen demandsupply ratio throughout. These measures include avoidance of left ventricular distention, immediate ablation of any recurring activity during arrest, maintenance of high retrograde flow rates, limita- tion of hemodilution, and uninterrupted mode of cardioplegia delivery.

(Ann Thoruc Surg 1994;57:1429-35)

Material and Methods Operative Technique Cardiopulmonary bypass was established between the ascending aorta and the two venae cavae. The extracor- poreal circuit consisted of a roller pump, a membrane oxygenator, and an in-line arterial filter. After completion of the cannulations, a balloon-ribbed, manually inflatable retrograde cardioplegia catheter (Sarns 3M, Ann Arbor, MI) was inserted blindly into the coronary sinus with the use of a soft malleable stylet. Cardiopulmonary bypass was then initiated at a flow rate of 2.2 L min-' - m-'. The core temperature, as assessed by a nasopharyngeal probe, was allowed to drift and reached an average of 32.7" k 0.2"C during the period of aortic occlusion.

After application of the aortic cross-clamp, delivery of blood cardioplegia was initiated through the aortic root at an infusion rate Of 300 mL/min- As Soon as the heart was arrested, the cardioplegia line was switched to retrograde coronary sinus perfusion, which proceeded thereafter in an uninterrupted fashion throughout the period of aortic

Presented at the Thirtieth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 31-Feb 2, 1994.

Address reprint requests to Dr Menasche, Department of Cardiovascular Surgery, Hdpital LariboisiPre, 2 rue Ambroise Pare, 75010 Paris, France.

0 1994 by The Society of Thoracic Surgeons 0003-4975/94/$7.00

1430 MENASCHG ET AL WARM CARDIOPLEGIA IN HYPERTROPHIED HEARTS

Ann Thorac Surg 1994:57 1429-35

cross-clamping. Perfusion pressures were maintained in the range of 40 mm Hg. An average volume of 3 mL of saline solution usually was required for the inflated balloon to properly seal the coronary sinus. Care was taken that this balloon be positioned as close to the right atrium as possible to avoid mechanical blockade of the distal branches of the sinus and, thereby, to maximize right ventricular preservation.

Our technique of warm blood cardioplegia delivery has been previously described [2]. In brief, it entails the supplementation of pure arterial blood with a minimal volume of highly concentrated crystalloid cardioplegia (15 mEq potassium chloride + 3 mEq magnesium chloride in a 20-mL ampoule). After aortic cross-clamping, the whole content of one ampoule is manually injected into the aortic root circuit blood over a 1-minute period. This results in immediate asystole, which is then maintained by continuous delivery of "minicardioplegia" using an electrically driven syringe whose infusion rate is adjusted on line so as to keep the heart arrested with the minimal dose of potassium. The cardioplegia delivery circuit does not incorporate a heat exchanger so that the temperature of the blood cardioplegia solution is similar to that of the systemic perfusate.

Study Design PART I. This part of the study was designed to assess the patterns of myocardial oxidative metabolism in 20 consec- utive patients who underwent aortic valve replacement for calcified aortic valve stenosis complicated with LVH. Left ventricular hypertrophy was primarily assessed on the echocardiographic measurement of left ventricular mass using the formula of Reicheck and Devereux [3]. The main characteristics of these patients are summarized in Table 1. The severity of their LVH is reflected by a left ventricular mass index, which is approximately twice the normal value. Only one patient had a coronary angiogram performed preoperatively because of clinical symptoms of myocardial ischemia (this patient underwent bypass grafting in addition to his valve replacement).

Immediately before closure of the aortotomy, blood samples were collected simultaneously from the retrograde cardioplegia infusion line (inflow) and the left coronary ostium effluent (outflow). The samples were immediately assayed for blood gases, including measured oxygen content and oxygen saturation using a 2500 co- oximeter (Ciba-Corning, Cergy Pontoise, France). Lactate was simultaneously determined by reflectance spectro- photometry (Eastman Kodak Company, Rochester, NY).

Oxygen extraction was calculated as the difference between the arterial and coronary sinus oxygen contents. The percent extraction was calculated by dividing the extraction by the arterial oxygen content. The myocardial production of acid metabolites was derived from the differential pH and base excess values between outflow cardioplegia (left coronary ostium effluent) and inflow cardioplegia (retrograde cardioplegia infusion catheter), a negative value (that is, a more negative base excess in the outflow relative to the inflow) reflecting intramyocardial

Table 1. Patient Data"

Retrograde Antegrade Warm Cold P

Variable (n = 20) (n = 20) Value

Preoperative demographics Age (Y) Sex (maldfemale) Fractional shortening (%) Left ventricular mass

index (g/m2) Operative variables

Associated proceduresb Cross-clamp time (min) Reperfusion time (min) Cardiopulmonary bypass

Spontaneous return to time (min)

sinus rhythm Postoperative outcome

Hospital mortality Inotropes Intraaortic balloon

Q wave myocardial

Conduction defect of

Creatine kinase (IU/L)

pumping

infarct

new onset

POD 1 POD 2 POD 3

Time to extubation (h)

6 4 2 3 10110

30.5 f 1.8 213 2 15

4 72 f 4 22 t 2

101 f 6

19

1 2 0

0

0

219 f 27 308 f 53 311 f 63 21 5 2

62 f 3 1317

36.1 5 2.7 202 t 11

2 59 ? 2 29 t 3 99 f 6

15

0 1 0

0

1

185 f 21 295 f 33' 279 f 46 25 t 5

NS NS NS NS

NS < 0.01

0.055 NS

NS

NS NS NS

NS

NS

NS NS NS NS

a Where applicable, data are shown as number of patients or mean f standard error of the mean. These procedures consisted of three mitral valve replacements and one coronary artery bypass grafting in the retrograde warm group and of one mitral valve replacement, one coronary artery bypass grafting, and one plication of left ventricular aneurysm in the antegrade cold group. NS = not significant;

p < 0.05 versus POD 1.

POD = postoperative day.

acidosis. Lactate production was similarly determined from the difference between outflow and inflow values.

PART 11. This second arm of the study was designed to compare the 20 patients that make up part I with 20 case-matched patients operated on over the same time frame and who received conventional cold heart protection consisting of single-dose cold (4°C) crystalloid antegrade cardioplegia associated with systemic (28" * 02°C) and topical hypothermia. Comparison between the two groups was primarily based on the assessment of clinical outcomes and included the following end points: number of countershocks required for restoring sinus rhythm, reperfusion time (defined as the interval between removal of the aortic cross-clamp and termination of bypass), death from any cause during the period of hospital stay, Q wave myocardial infarct, requirement for inotropes or intraaortic balloon pumping, atrioventricular conduction defects of new onset, postoperative serum levels of creatine kinase and time to extubation.

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MENASCHI? ET AL 1431 WARM CARDIOPLEGIA IN HYPERTROPHIED HEARTS

Statistics Preoperative variables were compared by unpaired t tests or 2 analysis where appropriate. In part I, comparison of postoperative biochemical data between inflow and outflow cardioplegia was done using two-tailed paired t tests. In part 11, comparison of postoperative events between warm and cold patients was done using 2 or unpaired t tests, except for enzyme data, which were compared by two-way analysis of variance with repeated measurements. Significance was set at the 0.05 level and all values are given as mean f standard error of the mean.

Results Part I The results are summarized in Figures 1 and 2. At the end of an arrest period of 72 f 4 minutes, the high residual oxygen demand of hypertrophied myocardium was reflected by an oxygen extraction of 4.2 +- 0.5 mL/100 mL (which corresponded to a percent extraction of 34.8% f 4.1%).

In face of this demand, supply was primarily determined by two factors: the oxygen content of inflow blood cardioplegia, which averaged 12.2 * 0.4 mL/100 mL (this yielded a mean hematocrit on pump of 25.6% f 0.9%), and the flow rate of retrograde cardioplegia delivery, which averaged 200 * 5 mL/min.

That oxygen supply adequately met oxygen demand was demonstrated by the absence of significant transmyocardial production of acid metabolites, the small (0.28 f 0.1 mmollL), although significant, production of lactate, and the relatively high residual oxygen saturation (65.7% f 3.8%) in the postcapillary blood that exited the left coronary ostium.

Maintenance of high hematocrit values during bypass was made possible by the minicardioplegia delivery technique whereby the average crystalloid cardioplegia load

DEMAND

L ien Extractic

SUPPLY

rnlfmin r - r

ml f100rnl ,O0I 16-

14 -

12 - 10 - 0 -

6-

4 - I 401 A L

Ox en Content Flow Ite of in &%ow Blood Retrograde Cardioplegia Cardioplegia

Delivery

Fig 1 . Determinants of the oxygen demandisupply ratio in 20 patients with hypertrophied myocardium who underwent aortic valve replacement with the use of continuous retrograde warm blood cardioplegia. Inflow refers to blood sampled from the coronary sinus infusion catheter .

Base Excess

-0.4

mmolfL 4 r *pco.001

Lactate

0 Inflow Outflow

sb ** pc0.0001

loo[ n * !

Oxygen Saturation

L mmol/L

Fig 2. Patterns of myocardial oxidative metabolism at the end of the aortic cross-clamping period. Inflow refers to blood sampled from the coronary sinus infusion catheter and outflow to blood sampled from the left coronary ostium efluent.

per patient was approximately 100 mL, which resulted in end-arrest serum potassium levels of 5.6 f 0.3 mEq/L. In addition, 10 patients required one or more bolus injec- tions of procaine to abolish recurrent electromechanical activity during arrest (see Comment), which yielded an average dose of 0.9 mmol/L (range, 0.5 to 1.5 mmoVL).

Part I1 There was no significant difference among the two groups with regard to the major preoperative variables. Likewise, clinical outcomes were not significantly different between patients who received retrograde warm cardioplegia and those of the cold group (see Table 1). The single hospital death, which occurred in the warm group, was in the patient who underwent myocardial revascularization con- comitantly with aortic valve replacement, and was not cardiac-related.

Comment Vulnerability of Hypertrophied Myocardium to Ischemic Arrest It has been recognized for many years that hypertrophied myocardium is more susceptible to ischemia than normal myocardium [4, 51. This increased vulnerability is primarily manifest as an earlier initiation of contracture during ischemia [6, 71 and, consistently, a selective impairment of diastolic function during reperfusion [%lo]. Two distinct, but closely interrelated, mechanisms have been proposed to account for these alterations in postischemic compli- ance: an intrinsically reduced rate of calcium reuptake by the sarcoplasmic reticulum of hypertrophied myocardium, leading to earlier and more severe calcium overload during ischemia [lo-121, and a basally reduced content of high-energy phosphates [ 131, leading to an accelerated

1432 MENASCHC ET AL WARM CARDIOPLEGIA IN HYPERTROPHIED HEARTS

Ann Thorac Surg 1994;57 1429-35

failure of the energy-dependent mechanisms that nor- mally regulate calcium homeostasis. Regardless of the mechanism that is primarily involved, the experimental demonstration of an increased susceptibility of hypertrophied myocardium to global ischemia has been corrobo- rated clinically by the long-standing observation that postoperative ischemic contracture and subendocardial necrosis tend to occur selectively in patients with LVH [14] and by the more recent echocardiography-based finding that excessive LVH is associated with increased morbidity and mortality after aortic valve replacement

Actually, when measurements of the myocardial oxygen consumption of potassium-arrested hearts are ex- pressed by unit mass of myocardium, basal oxygen requirements appear to be similar for hypertrophied (1.3 mL - min-’ - 100 g-’ of left ventricle [16]) and nonhyper- trophied (1.5 mL * min-’ - 100 g-’ of left ventricle [17]) hearts. Nevertheless, the total oxygen demand of the former is expected to be higher because of the greater left ventricular mass.

Until now, clinical evidence that retrograde warm blood cardioplegia allows maintenance of an aerobic state during arrest [18] has been primarily obtained in patients with hearts of normal size. It sounded logical, therefore, to question the ability of retrogradely delivered warm blood cardioplegic solution to supply enough oxygen to match the increased metabolic needs of hypertrophied myocardium. This issue is of real clinical relevance because cold crystalloid [8, 191 and blood [20] cardioplegia has been shown to adequately preserve hypertrophied myocardium so that the use of warm cardioplegia in this setting requires the demonstration of an at least equiva- lent degree of myocardial protection.

Interpretation of Results The major finding of this study is that the presence of LVH does not preclude maintenance of aerobic metabolism during the period of aortic cross-clamping.

Oxygen extraction measured at the end of arrest was 34.8%, which is approximately two times lower than the value corresponding to the working-beating state demonstrated by catheterization studies in patients with aortic valve stenosis [21]. In keeping with the assumption that arrested hypertrophied myocardium has significant residual oxygen requirements due to the increase in left ventricular mass, the percent of oxygen extraction recorded in our patients is approximately twofold [22] to threefold [23] higher than that reported during infusion of cold blood cardioplegia in patients undergoing coronary artery bypass operations and therefore presumed to have nonhy- pertrophied hearts. Conversely, this 35% of oxygen extraction is relatively close to values of oxygen uptake associated with cold blood cardioplegia given to hypertrophied pig (42% [6]) or human (42% [24]) hearts. Addi- tional indirect evidence for the high residual metabolic activity of cardioplegically arrested hypertrophied hearts comes from the observation that high cardioplegia flow rates (up to 250 to 300 mL/min) have been found necessary to correct postcapillary blood acidosis in patients

~ 5 1 .

with LVH [25]. Incidentally, the observation that oxygen extraction during cardioplegic arrest is not very different between patients with hypertrophied myocardium regardless of whether they are given cold (oxygen extraction, 42% [24]) or warm (oxygen extraction, 34.8% [present study]) blood cardioplegia is consistent with the assumption upon which warm blood cardioplegia is based; that is, residual oxygen needs are more dependent on the electromechanical state of the heart than on temperature [26].

In this study, the absence of a demandsupply energy mismatch and, consequently, the maintenance of (pre- dominantly) aerobic metabolic patterns were demonstrated by the following observations: (1) There was no significant myocardial acid production. (2) Although lactate concentration in outflow cardioplegia was significantly higher than in inflow cardioplegia, the magnitude of lactate production was actually small (0.28 ? 0.1 mmol/L), which is likely to be physiologically inconse- quential. It is noteworthy that the myocardial lactate production found in this study is much lower than that reported by Yau and co-workers [27] in patients receiving retrograde warm blood cardioplegia during coronary artery bypass operations. These conflicting results could be explained by the use, in our study, of higher hematocrits, higher retrograde flow rates, the uninterrupted mode of cardioplegia delivery, or a combination of any of the above factors. (3) The oxygen saturation in postcapillary blood (65.7%) was still elevated, which, together with the findings of a high myocardial oxygen uptake and of a small release of anaerobically-produced acid metabolites, does not suggest an impaired ability of myocardial cells to extract oxygen, but rather a potential excess of metabolic supply relative to the demand.

These biochemical findings correlated with overall sat- isfactory clinical outcomes, an observation consistent with the previous experimental [6] and clinical [28] findings that the highest oxygen uptakes during infusion of blood cardioplegia correlate with the best recoveries of left ventricular function, possibly because an ongoing aerobic metabolism allows sustained activity of energy-dependent ionic pumps and the related preservation of cell integrity. This hypothesis tends to be supported by the recent report that warm blood cardioplegia provides superior protection of sarcoplasmic reticulum function [29]. This finding is relevant to the setting of LVH in view of the presumably pivotal role played by the sarcoplasmic reticulum in the genesis of cytosolic calcium overload and subsequent alterations of diastolic function demonstrated by ischemically injured hypertrophied hearts.

In the present study, the postoperative course of nor- mothermically perfused patients was not different from that of patients who received conventional hypothermic protection. Although patients were not randomized but allocated to warm or cold cardioplegia on the sole basis of their respective surgeon’s practice, the case-matching procedure resulted in an equitable distribution of all major preoperative variables. We acknowledge that this cold group is not a real control group because it differed from the warm group with respect to several factors of cardio-

Ann Thorac Surg 1994;57 142935

MENASCHB ET AL 1433 WARM CARDIOPLEGIA IN HYPERTROPHIED HEARTS

plegia delivery. However, it is fairly representative of current hypothermic practices and seemed therefore to represent an acceptable ”standard” for a comparative assessment of the warm technique. To some extent, this comparison is validated by the fact the results yielded by our retrograde warm blood group compare well with those reported in the literature with the use of retrograde cold crystalloid [30] or blood [31] cardioplegia. We con- sider it unlikely that the presumed absence of associated ischemic heart disease in almost all our patients may have biased the results because the presence of critical coronary artery obstructions should rather reinforce the benefits of the retrograde approach. Finally, it is noteworthy that 95% of patients in the warm group spontaneously re- sumed sinus rhythm upon removal of the aortic cross- clamp. This might have further contributed to the avoidance of postischemic myocardial ischemia that may occur when the hypertrophied heart fibrillates because of its inability to increase myocardial blood flow in proportion to the fibrillation-induced increase in oxygen requirements [16].

Practical Implications As previously stated, the residual metabolic activity of the potassium-arrested human hypertrophied myocardium is still high but, unfortunately, it cannot be accurately pre- dicted in the individual patient. For this reason, it is important to optimize the oxygen demandlsupply ratio to avoid any energy mismatch and the related occurrence of myocardial ischemia during the period of aortic occlusion.

The reduction of demand is primarily based on strict maintenance of electromechanical arrest during the cross- clamping period. This implies immediate ablation of any recurring activity either by increasing the potassium load in the blood cardioplegia solution or by giving a bolus of procaine depending on whether the recurring activity features rhythmic contractions or cardiac ondulations, respectively. Oxygen demand also can be reduced by preventing left ventricular distention; to this end, all our patients had direct left ventricular venting through the right superior pulmonary vein.

The increase of oxygen supply requires in turn (1) maintenance of sufficiently high retrograde flow rates, probably in the range of 200 mL1min because higher flows do not seem to further increase the nutritive capillary component of the retrograde pathway [32], and (2) limi- tation of hemodilution, as achieved by the drastic reduction of the crystalloid cardioplegia load that underlies our minicardioplegia delivery technique [2].

Conclusion By virtue of its nonrandomized design, the present study was not intended to assess whether retrograde warm blood cardioplegia provided better protection of hypertrophied myocardium, or not, than conventional cold-based techniques. Our results only provide compelling evidence that retrograde delivery of warm cardioplegic blood can be safely used in the presence of LVH and actually allows one to maintain these hypertrophied hearts in a predom- inantly aerobic state during the period of aortic cross-

clamping provided that the determinants of the oxygen demandkupply ratio remain tightly controlled throughout.

This conclusion is relevant not only to patients undergoing aortic valve replacement but also to those referred for bypass operations and who may have some degree of LVH because of coexisting valvular or hypertensive disease. Our results demonstrate that LVH, by itself, should not lead the surgeon to deny these patients the expected benefits of retrograde warm blood cardioplegia if there is an otherwise sound justification for the use of this technique, as may be the case when acute ischemic symptoms are present at the time of surgical revascularization.

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DISCUSSION

DR JOHN W. HAMMON (Winston Salem, NC): Dr Menaschb, that was a very nice paper. You never actually mentioned the temperature of the cardioplegia, and you said in your abstract that the body temperature is allowed to drift down toward 30°C. Was the cardioplegia temperature the same?

DR MENASCHk Yes. We do not incorporate a heat exchanger in the separate cardioplegia circuit, which means that the temperature of cardioplegia closely parallels that of the systemic perfusate. So the temperature of cardioplegia was actually between 32" and 33°C.

DR HAMMON And you still want to call it warm?

DR MENASCHB: I agree that we had better call it tepid.

DR GEORGE E. CIMOCHOWSKI (Wakes-Barre, PA): I think you have raised the Achilles tendon issue of warm retrograde cardioplegia, and that is in the hypertrophied heart. We had an experience like yours, which was very positive, for the first 20 patients, and then after 61 patients we had accumulated 4 "stone heart" patients. When we looked at those patients we noticed two things. First, the catheter absolutely has to be occlusive, and at the autopsy several of the patients with 10 mL in the balloon did not have occlusion of the large coronary sinus.

Second, in these four deaths with associated coronary bypass grafts, we measured the coronary effluents, and most of the time they were acidotic. When we switched to a new catheter that we developed (with Research Medical, Inc, of Midvale, UT) that had a large-volume occlusive balloon and used continuous cold retrograde preceded and followed by warm cardioplegia, our mortality with the stone heart problem went back to 0.

Would you comment on your conclusion based on only 20 patients that warm cardioplegia protection is safe in large num-

bers of patients? How do you know for sure that cardioplegic solution is not in fact regurgitating via the retrograde catheter? Finally, do you have any data to support the burden of an ischemic problem on top of the hypertrophied myocardium with the warm technique?

DR MENASCHk There are several points in your question. First of all, the study is dealing with 20 patients, but since we have started to use retrograde warm cardioplegia 3 years ago, we have operated on many more patients with aortic valve stenosis or patients with left ventricular hypertrophy, and overall our experience has been rather positive. I do not say that the results have been better than with any other cold-based technique of protection. I am not a blind zealot of this technique. I just say that the results were fairly acceptable from a clinical standpoint and that they are not limited to this cohort of 20 patients.

Now, regarding the point of sinus occlusion by the catheter, I cannot say anything other than I completely support your conclusion. It is critically important in these patients to be sure that you are really delivering cardioplegia in the right direction and not back in the atrium. It turns out that isolated aortic valve replacement does not require you to lift the heart, which makes coronary sinus pressure monitoring much easier. I think that if you are maintaining your flow in the range of 200 mL/min, which usually yields an infusion pressure, let us say, of 30 or 40 mm Hg, you have good evidence that the coronary sinus is properly occluded.

DR LUIS D. BERRIZBEITIA (Browns Mills, NJ): Did you measure systemic lactates in your experiment, and did you notice whether the amount of volume that you have to give to your bypass circuit to maintain adequate flows was higher in the normothermic cardioplegia patients compared with hypothermic?

Ann Thorac Surg 1994;57 1429-35

MENASCHk ET AL 1435 WARM CARDIOPLEGIA IN HYPERTROPHIED HEARTS

DR MENASCHk Yes, we routinely measure lactate in both cold and warm patients, and the lactate concentration in the systemic blood was maintained within a quite fairly acceptable range, usually between 1.5 and 2 mmoVL. Now, if you want me to tell you that these patients tend to be more vasodilated than the cold ones, I will tell you yes, they are. However, it has not resulted in a significant increase in the volume of fluids we give them. We did that initially because we were a little concerned about low peripheral vascular resistance occasionally associated with low systemic arterial pressures, but now that we have become more familiar with the technique, we just try to let them recover and we do not overload them with fluids.

DR SIDNEY LEVITSKY (Boston, MA): This is an excellent paper, Dr Menasche, and you have taught us a great deal. I have one question that may focus our understanding of your outstand- ing clinical results because your technique of retrograde perfusion is quite different from the technique employed by many surgeons in the United States. Most of us insert the retrograde catheter as far distally as we can and either inflate the balloon by hand or allow autoinflation, both of which may result in obstruc- tion of the tributaries of the coronary sinus. However, your catheter placement is in the coronary sinus os, which allows perfusion of all the tributaries.

Do you think that this specific methodologic point is the reason for your excellent results in hypertrophied hearts in that your catheter placement allows for better perfusion of the intercon- necting veins?

DR MENASCHE: Well, it is difficult to answer your question, because many surgeons who put the catheter as far as they can in the sinus report excellent results, and even think that it is not absolutely necessary to try to keep it as close to the atrium as I try.

Now, the major reason for trying to keep it as close to the atrium as possible is actually to maximize, as you know, right ventricular preservation rather than left ventricular preservation. So I really do not know whether it would make a difference in terms of preservation of these hypertrophic hearts to advance it very far into the sinus. Again, it may make a difference in terms of right ventricular preservation, but I am not sure it would make a big difference in terms of left ventricular preservation. I think that the critical determinants, maybe more important than the position of the catheter, are the high arterial oxygen content and the maintenance of a high flow rate.

DR GERARD M. GUIRAUDON (London, Ont, Canada): This is a great paper. If perfusion of the entire coronary sinus system is so important, why not use that old technique that Dr Menasche and I described about 15 years ago: the right atrium is opened, a purse string is stitched around the coronary sinus os, and a Foley catheter is perfectly secured in the coronary sinus. Using a balloon catheter, I am not sure that the mid cardiac vein is initially perfused. The mid cardiac vein can be perfused only when the heart is arrested because, as we have demonstrated, the collateral circulation becomes functional only when the myocardial receives cardioplegia. It probably takes a few minutes of ischemia before the entire heart is perfused through the cardiac vein system. So why don't you just use double venous cannula, open up the right atrium, and catheterize the coronary sinus os, if adequate and immediate myocardial perfusion is critical?

DR MENASCHE: As you probably know, I have opened the right atrium for 10 years, but it seemed that it was old-fashioned to do that, so I felt compelled to switch to the transatrial

approach. But I have nothing to say against what you are describing, and there is no question that if for one reason or another we have problems in getting into the sinus, I do not feel frustrated at all to open the right atrium and to put the catheter under direct vision.

DR WILLARD M. DAGGETT, JR (Boston, MA): Dr Menasche, I am always admiring of the careful way in which you construct your experiments, and I think that this forum is just the place for the presentation of this type of data, which is going to clarify the physiologic effects of different methodologies of myocardial protection. But I think your paper and the discussion afterward illustrate that there are a great many pitfalls to the execution of the technique of warm cardioplegia delivered retrograde.

If you will recall, of the original two papers from Toronto, the first was Dr Lichtenstein's paper, on cardioplegia delivered antegrade with excellent results and a very low intraaortic balloon pump insertion rate; the next paper was on retrograde cardioplegia, and the incidence of intraaortic balloon pumping went right back up again.

So I think that just from a practical standpoint, particularly young cardiac surgeons who are just starting out with methods of myocardial protection want to look at the technique of warm cardioplegia delivered retrograde with a good deal of caution.

DR MENASCHE: Well, there is nothing really special to answer you, Dr Daggett, except that I completely agree with you that this technique is probably, in most cases, a very effective technique, not in all cases unfortunately, as there are still patients who die. But I quite agree with you that it may become a dangerous technique if strict attention is not paid to a lot of technical details.

Once again, the objective was not to convince anyone, this is not my problem, that warm is better than cold. The only limited objective was just to report data so that those who might be interested in using warm cardioplegia will not be deterred from doing that just because of the presence of left ventricular hypertrophy.

DR STEVEN R. GUNDRY (Loma Linda, CA): Doctor Menasch6, once again this is a wonderful paper, and your findings con- firmed our findings that we reported at the American Heart Association last year. I simply want to re-echo two things. Number one, high flows are critically important in this subset of patients, and in fact, we ought to be using high flows on everybody. Number two, it is very clear to most of us now working in the field that a manually inflating balloon is the best way to assure that you are, in fact, occluding the coronary sinus and actually delivering retrograde cardioplegia.

Finally, I want to assure Dr Levitsky, if you will come down to our poster, also presented at this meeting, we have looked at 141 patients with retrograde continuous cardioplegia with aortic valve replacements and coronary artery bypass grafts and have looked at the right ventricular protection as measured by effluent from the right coronary artery or from the acute marginal or posterior descending coronary arteries, and to echo Dr Mena- sche's findings, the right heart in humans shows absolutely normal metabolism and normal extraction of oxygen and no lactate production. So it is a safe technique, even for the right heart.

DR MENASCHB: Well, I do not think that I can do any better conclusion than that of Dr Gundry.

retrograde warm blood cardioplegia preserves hypertrophied myocardium: a clinical study

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