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Ann Thorac Surg 1996;62:957-960
© 1996 The Society of Thoracic Surgeons

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Editorials

Blood Cardioplegia: Do We Still Need to Dilute?

Department of Cardiovascular Surgery, Hôpital Lariboisière, Paris, France

Since the pioneering work of Buckberg [1], it has been a common practice to prepare cold blood cardioplegia by mixing four parts of oxygenated blood to one part of crystalloid solution, and this 4:1 dilution ratio has then been readily applied to the more recent setting of warm heart surgery [2]. However, when my colleagues and I adopted the latter technique 5 years ago, it soon became apparent to us [3] and others [4–6] that an alternative, definitely simpler and equally, if not more, effective means of delivering warm blood cardioplegia was to use pure blood, diverted from the arterial port of the oxygenator and only supplemented with arresting agents (in practice, potassium which, in our formulation, is mixed with magnesium). We coined the term "mini-cardioplegia" because these arresting agents are concentrated in a small volume of saline solution, which is continuously added to the blood cardioplegia circuitry by means of an electrically driven syringe. Initially, the flow rate of the syringe was determined empirically. Subsequently, a nomogram has been developed that, based on the target potassium concentration (20 mmol/L for induction of arrest, 10 mmol/L for its maintenance), the patient's prebypass serum potassium level, and the flow rate of the cardioplegia delivery pump, allows an accurate determination of the flow rate at which the drug pump should be set. This flow is then progressively decreased as long as the heart remains quiescent and is temporarily reincreased whenever there is any resumption of electromechanical activity. The mini-cardioplegia technique allows one to optimize the creation of an aerobic environment through an increase in oxygen supply [7] and to "tailor" the amount of administered potassium to the patient's specific needs while it avoids the detrimental consequences of volume overload and subsequent hemodilution, in particular, peripheral vasodilatation, which is commonly associated with warm systemic perfusion [8]. In addition, the system is extremely easy to handle and has a negligible cost due to the limited number of disposable supplies that it requires (a piece of tubing, a stopcock, and an inexpensive pharmaceutical preparation).

Since the introduction of warm blood cardioplegia, and in spite of the ongoing controversy regarding the optimal cardioplegic temperature, there has been a trend for "cold" surgeons to warm up blood cardioplegic solutions and for "warm" surgeons to cool theirs a little bit. Thus, in the forthcoming years, a "tepid" temperature might emerge as an widely acceptable trade-off. In light of these reasonably predictable changes, it seems timely and appropriate to reassess the way blood cardioplegia is diluted. This, in turn, implies a need to address both rheologic and biochemical issues.

Rheologic Issues

The major reason for diluting blood-based cardioplegic solutions is to avoid the increase in viscosity associated with hypothermia [9] with the subsequently deleterious consequences of red blood cell sludging, that is, occlusion of capillaries (the percentage of perfused capillaries decreases by a factor of three when temperature is lowered from 37°C to 10°C), and tissue underperfusion [10]. This concern is sound as long as blood cardioplegia is cooled to 4°C to 10°C. The question is whether such hypothermic levels are really required. Indeed, recent studies have brought convincing evidence that tepid (29°C) blood cardioplegic solutions provided the best myocardial protection, compared with more hypothermic (9°C) or strictly normothermic (37°C) solutions [11–13]. These data are consistent with the earlier findings that the ultrastructurally determined cardioprotective effects of 27°C blood cardioplegia were not different from those seen at 4°C [14], whereas, in another study, the functional benefits of 20°C blood cardioplegia were actually decreased by further cooling of the solution to 4°C [15].

Thus, if blood cardioplegia is given in the 30°C range (in our practice, we simply allow the core temperature to drift to usually 32°C to 33°C and give cardioplegia at the same temperature, but a heat exchanger can eventually be incorporated in the blood cardioplegia circuitry), increased viscosity is no longer a concern because at 32°C the viscosity/hematocrit relationship is not significantly different from that seen at 37°C, in particular at clinically relevant shear rates [16]. Indeed, it is mainly at temperatures less than 27°C that viscosity sharply increases in response to increasing hematocrit [16] (whereas the thermal transition of erythrocyte deformability [greater rigidity] is around 18°C [17 ]). These assumptions, derived from in vitro studies, are supported by the clinical findings that coronary vascular resistance is not different between patients receiving antegrade warm (37°C) cardioplegia and those in whom the perfusate is cooled to 29°C [12].

From a practical standpoint, reliance on these tepid temperatures for ensuring myocardial protection implies that it may be no longer necessary to lower the hematocrit of the blood cardioplegic solution beyond the value already resulting from the dilutional crystalloid pump prime (which usually averages 25%), at least in the absence of thrombotic diseases such as polycythemia. The safety and efficacy of this minimal dilution technique are now validated by our 5-year experience, which encompasses several hundreds of patients. These results extend those of Bomfim and co-workers [18] who, 15 years ago, reported on the successful use of continuous perfusion of 15°C blood simply enriched with potassium and magnesium (average hematocrit, 22%) in patients undergoing aortic valve replacement. However, for those who wish to move progressively from the standard 4:1 ratio to the use of almost pure blood, new devices are now available that provide great flexibility in the choice of the blood-to-crystalloid mixing ratio. Some degree of dilution can thus be reconciled with avoidance of unnecessary and potentially harmful volume overload [8].

Biochemical Issues

The second major reason for diluting blood cardioplegia is to supply the myocardium with the various purportedly cardioprotective additives included in the crystalloid component of the final mixture. However, the use of a low-dilution delivery technique leads one to question the utility of most of these ingredients.

Arresting Agents
Agents that cause electromechanical arrest are, by definition, those whose inclusion is mandatory. Currently, asystole is ubiquitously achieved by potassium. In the future, however, hyperpolarizing compounds (among which potassium-channel openers are currently raising a great deal of interest) might become effective alternative means of inducing cardioplegia because of the lower energy expenditure of hyperpolarized arrest, as compared with depolarized arrest [19].

One mechanism whereby potassium-based cardioplegia is, paradoxically, energy-consuming is the calcium influx associated with membrane depolarization. For this reason, we have supplemented our concentrated potassium cardioplegic solution with magnesium (the final formulation consists of 16 mmol/L of potassium chloride and 3 mmol/L of magnesium chloride in a 20-mL ampoule of distilled water). Not only does magnesium contribute to electromechanical arrest, but it also antagonizes calcium ions at both the sarcolemmal and intracellular levels, which largely accounts for its well-established cardioprotective effects [20, 21]. An additional advantage of magnesium is its venodilating effect [22], which is clinically relevant if cardioplegic solution is to be directly infused into saphenous vein bypass grafts.

Calcium
Citrate-phosphate-dextrose is commonly added to blood cardioplegic solutions to reduce plasma levels of ionized calcium with the underlying hope that it will contribute to reduce calcium overload and its well-established tissue-damaging effects. This concern, however, is not relevant to the use of continuous warm blood cardioplegia because the maintenance of myocardial aerobic metabolism should result in sufficiently high energy production to drive the pumps responsible for calcium homeostasis. In support of this hypothesis, Liu and co-workers [23] have shown, in isolated rat hearts continuously perfused with oxygenated crystalloid cardioplegia, that solutions at 28°C and 37°C did not cause a significant postischemic intracellular calcium overload (in contrast to colder perfusates). The problem is different if blood cardioplegia is given tepid and in an intermittent fashion because calcium overload can then occur during the ischemic intervals between cardioplegic infusions. However, the crystalloid pump prime already results in a dilutional hypocalcemia with resulting levels of ionized calcium that have been shown not to adversely affect postischemic myocardial recovery or enzyme leakage provided the cardioplegic solution was supplemented with magnesium [24]. Consequently, it is sound to assume that prevention of calcium overload can safely and effectively rely on magnesium rather than on pharmacologic chelators like citrate-phosphate-dextrose in view of the previously mentioned ability of magnesium to act as a powerful antagonist of calcium ions.

Buffers
Buffers, most often tris (hydroxymethyl) aminomethane (THAM), are commonly included in the crystalloid component of blood-based cardioplegic solutions. When cardioplegia is given continuously and at normothermic (or tepid) temperatures, the use of exogenous buffers appears unnecessary because one of the objectives of the resulting aerobic environment is precisely to avoid intracellular acidosis, the prevention of which should be further enhanced by the wash-out effect of continuous blood perfusion. In this setting, the deliberate creation of an extracellular alkalosis can even become deleterious because of the expected stimulation of the sodium/proton exchanger, the resulting increase in intracellular sodium level, and an ultimate calcium overload via the sodium/calcium exchanger.

If blood cardioplegia is given tepid, intermittently, or both, the effectiveness of any added buffer becomes primarily determined by its capacity to counteract tissue acidosis over a wide range of temperatures. In this setting, it remains questionable to try to buffer blood. Under these mildly hypothermic conditions (and the same would hold true for colder temperatures), the "good" buffer will be the one that will change its pK with temperature parallel to the changes in neutrality of water [25]. It is not debatable that the buffer that best meets this criterion is the imidazole residue of histidine present in blood. Thus, it is not fortuitous that the crystalloid cardioplegic solution that has a buffering capacity comparable with that of blood is Bretschneider's solution, which contains a high concentration (195 mmol/L) of histidine [26]. That the addition of THAM does not increase the buffering capacity of blood has been well demonstrated by Neethling and co-workers [27], who failed to show any difference in myocardial pH after 150 minutes of aortic cross-clamping between canine hearts infused with THAM-buffered blood cardioplegia and those receiving unbuffered hyperkalemic blood. Bicarbonate is expected to be still more useless than THAM because of its poor buffering capacity at low temperatures. This is well apparent from the observation that, at the end of a 4-hour cold cardioplegic arrest, subendocardial pH of canine hearts was found to be much more acidotic after the use of bicarbonate-buffered crystalloid cardioplegia (to a pH of 7.80) than after the delivery of blood cardioplegia devoid of any exogenous buffer [28].

Substrates
Among substrates, amino acids, in particular aspartate and glutamate, are those whose supply has been the most strongly advocated, primarily because of their purported ability to anaerobically generate adenosine triphosphate. Whereas this hypothesis is possibly relevant to the use of crystalloid cardioplegia, it becomes more questionable when blood is the cardioplegic vehicle. Under conditions of continuous warm blood perfusion, the heart is likely to fuel its oxidative machinery with its preferred metabolic substrates, which are free fatty acids and glucose, not amino acids. Indeed, a recent study using phosphorus 31 nuclear magnetic resonance spectroscopy in blood-perfused pig hearts has failed to demonstrate any increase in high-energy phosphate levels after glutamate supplementation of the blood cardioplegic solution [29]. In the setting of cold, intermittent blood cardioplegic arrest, there has been experimental evidence that energy-depleted hearts might benefit from aspartate and glutamate supplementation, provided these amino acids were normothermically delivered during cardioplegic induction [30], early reperfusion [31], or both. Reliance on these laboratory findings (in spite of the fact that they are only supported by a limited amount of clinical data [32, 33]) does not preclude the use of the mini-cardioplegia technique because amino acids can easily be concentrated in a small volume of fluid. However, it should be remembered that the whole concept of exogenous fuel supply remains debatable [34, 35] in that postischemic myocardial stunning might be more related to abnormal energy utilization rather than to lack of substrate availability.

Summary

In summary, in the context of warm or tepid blood cardioplegia, the mini-cardioplegia concept has reasonably well-documented advantages over the standard 4:1 dilution ratio, which are of four types: (1) improved oxygen supply because of the combination of a rightward shift of the oxyhemoglobin dissociation curve and a greater number of available red blood cells, (2) improved control of blood volume because of the limitation of fluid overload (which greatly contributes to early postoperative extubation), (3) improved practicality because a simple electrically driven pump can substitute for more complex blood/crystalloid mixing devices, and (4) improved cost-effectiveness because the expenses related to these delivery systems, various biochemical additives, and, eventually, fluid-removing devices like ultrafilters or cell-saving devices are eliminated. Thus, in a period where a positive feature of economic constraints is to force us to reassess our practice patterns, the use of minimally hemodiluted hyperkalemic blood appears as a sound approach for increasing the simplicity and low cost of cardioplegia delivery without compromising the quality of the protection that it currently provides. Furthermore, this concept of concentrated cardioplegia does not exclude the future inclusion, in a still-limited volume of crystalloid vehicle, of additives that would be of clinical benefit, among which agents favorably interfering with neutrophil-endothelial cell interactions appear particularly appealing [36].

Footnotes

Address reprint requests to Dr Menasché, Department of Cardiovascular Surgery, Hôpital Lariboisière, 2, rue Ambroise Paré, 75475 Paris Cédex 10, France.

References

1. Buckberg GD, Dyson CW, Emerson RC. Techniques for administering blood cardioplegia: blood cardioplegia. In: Engelman RM, Levitsky S, eds. Textbook of clinical cardioplegia. Mt. Kisko: Futura, 1982:305–16.
2. Lichstenstein SV, Fremes SE, Abel JG, Christakis GT, Salerno TA. Technical aspects of warm heart surgery. J Cardiac Surg 1991;6:278–85.[Medline]
3. Menasché P, Touchot B, Pradier F, Bloch G, Piwnica A. Simplified method for delivering normothermic blood cardioplegia. Ann Thorac Surg 1993;55:177–8.[Abstract]
4. LeHouerou D, Singh AI, Romano M, Martin V, Lessana A. Minimal hemodilution and optimal potassium use during normothermic aerobic arrest. Ann Thorac Surg 1992;54:809–16.
5. Satyanarayana PV, Rao PSA, Rao KM, Chandra AS, Rao KS, Reddy KV. Continuous normothermic blood cardioplegia: simplified delivery circuit [Letter]. Ann Thorac Surg 1992;54:810.
6. Calafiore AM, Teodori G, Mezzetti A, et al. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg 1995;59:398–402.[Abstract/Free Full Text]
7. Yau TM, Weisel RD, Mickle DAG, et al. Optimal delivery of blood cardioplegia. Circulation 1991;84(Suppl 3):380–8.
8. Menasché P, Fleury JP, Veyssié L, et al. Limitation of vasodilation associated with warm heart operation by a "mini-cardioplegia" delivery technique. Ann Thorac Surg 1993;56:1148–53.[Abstract]
9. O'Neill MJ, Francalancia N, Wolf PD, Parr GVS, Waldhausen JA. Resistance differences between blood and crystalloid cardioplegic solutions with myocardial cooling. J Surg Res 1981;30:354–60.[Medline]
10. Sakai A, Miya J, Sohara Y, Maeta H, Ohshima N, Hori M. Role of red blood cells in the coronary microcirculation during cold blood cardioplegia. Cardiovasc Res 1988;22:62–6.[Medline]
11. Bufkin BL, Mellitt RJ, Gott JP, Huang AS, Pan-Chih, Guyton RA. Aerobic blood cardioplegia for revascularization of acute infarct: effects of delivery temperature. Ann Thorac Surg 1994;58:953–60.[Medline]
12. Hayashida N, Weisel RD, Shirai T, et al. Tepid antegrade and retrograde cardioplegia. Ann Thorac Surg 1995;59:723–9.[Abstract/Free Full Text]
13. Kaukoranta P, Lepojarvi M, Nissinen J, Raatikainen P, Peuhkurinen KJ. Normothermic versus mild hypothermic retrograde blood cardioplegia: a prospective, randomized study. Ann Thorac Surg 1995;60:1087–93.[Abstract/Free Full Text]
14. Axford-Gatley RA, Wilson GJ, Feindel CM. Comparison of blood-based and asanguineous cardioplegic solutions administered at 4°C. An ultrastructural morphometric study in the dog. J Thorac Cardiovasc Surg 1990;100:400–9.[Abstract]
15. Magovern GJ, Flaherty JT, Gott VL, Bulkley BH, Gardner TJ. Failure of blood cardioplegia to protect myocardium at lower temperatures. Circulation 1982;66(Suppl 1):60–7.[Abstract/Free Full Text]
16. Rand PW, Lacombe E, Hunt HE, Austin WH. Viscosity of normal human blood under normothermic and hypothermic conditions. J Appl Physiol 1964;19:117–22.[Abstract/Free Full Text]
17. Hanss M, Koutsouris D. Thermal transitions of red blood cell deformability. Correlation with membrane rheological properties. Biochim Biophys Acta 1984;769:461–70.[Medline]
18. Bomfim V, Kaijser L, Bendz R, Sylven C, Morillo F, Olin C. Myocardial protection during aortic valve replacement. Cardiac metabolism and enzyme release following continuous blood cardioplegia. Scand J Thorac Cardiovasc Surg 1981;15:141–7.[Medline]
19. Cohen NM, Damiano RJ Jr, Wechsler AS. Is there an alternative to potassium arrest? Ann Thorac Surg 1995;60:858–63.[Abstract/Free Full Text]
20. Steenbergen C, Murphy E, Watts JA, London RE. Correlation between cytosolic free calcium, contracture, ATP, and irreversible ischemic injury in perfused rat heart. Circ Res 1990;66:135–46.[Abstract/Free Full Text]
21. Ataka K, Chen DP, Feinberg H, McCully JD, Levitsky S. Prevention of cytosolic calcium accumulation by magnesium cardioplegia in surgically induced ischemia. Surg Forum 1992;43:197–200.
22. Chiavarelli M, Fabi F, Stati T, Chiavarelli R, del Basso P. Effects of cardioplegic solutions and their components on human saphenous vein contractility. Ann Thorac Surg 1992;53:455–9.[Abstract]
23. Liu X, Engelman RM, Rousou JA, Flack JE, Deaton DW, Das DK. Normothermic cardioplegia prevents intracellular calcium accumulation during cardioplegic arrest and reperfusion. Circulation 1994;90(Suppl 2):316–20.
24. Takemoto N, Kuroda H, Hamasaki T, Hara T, Ishiguro S, Mori T. Effect of magnesium and calcium on myocardial protection by cardioplegic solutions. Ann Thorac Surg 1994;57:177–82.[Abstract]
25. Rahn H, Reeves RB, Howell BJ. Hydrogen ion regulation, temperature and evolution. Am Rev Respir Dis 1975;112:165–72.[Medline]
26. Tait GA, Booker PD, Wilson GJ, Coles JG, Steward DJ, McGregor DC. Effect of multidose cardioplegia and cardioplegic solution buffering on myocardial tissue acidosis. J Thorac Cardiovasc Surg 1982;83:824–9.[Abstract]
27. Neethling WML, van den Heever JJ, Cooper S, Meyer JM. Interstitial pH during myocardial preservation: assessment of five methods of myocardial preservation. Ann Thorac Surg 1993;55:420–6.[Abstract]
28. Warner KG, Josa M, Butler MD. Regional changes in myocardial acid production during ischemic arrest: a comparison of sanguineous and asanguineous cardioplegia. Ann Thorac Surg 1988;45:75–81.[Abstract]
29. Ghomeshi HR, Tian G, Ye J, et al. Aspartate/glutamate enriched blood does not improve myocardial energy metabolism during ischemia-reperfusion: a ³¹P MRS study in isolated pig hearts. Presented at the 76th Annual Meeting of The American Association for Thoracic Surgery, San Diego, CA, April 28–May 1, 1996.
30. Rosenkranz ER, Okamoto F, Buckberg GD, Vinten-Johansen J, Robertson JM, Bugyi H. Safety of prolonged aortic clamping with blood cardioplegia. II. Glutamate enrichment in energy-depleted hearts. J Thorac Cardiovasc Surg 1984;88:402–10.[Abstract]
31. Lazar HL, Buckberg GD, Mangarano AM, Becker H. Myocardial energy replenishment and reversal of ischemic damage by substrate enhancement of secondary blood cardioplegia with amino acids during reperfusion. J Thorac Cardiovasc Surg 1980;80:350–9.[Medline]
32. Rosenkranz ER, Buckberg GD, Laks H, Mulder DG. Warm induction of cardioplegia with glutamate-enriched blood in coronary patients with cardiogenic shock who are dependent on inotropic drugs and intra-aortic balloon support. Initial experience and operative strategy. J Thorac Cardiovasc Surg 1983;86:507–18.[Abstract]
33. Beyersdorf F, Kirsh M, Buckberg GD, Allen BS. Warm glutamate/aspartate-enriched blood cardioplegic solution for perioperative sudden death. J Thorac Cardiovasc Surg 1992;104:1141–7.[Abstract]
34. Crooke GA, Harris LJ, Grossi EA, et al. Role of amino acids and enhancement cardioplegia in routine myocardial protection. J Thorac Cardiovasc Surg 1993;106:497–501.[Abstract]
35. Asai T, Grossi EA, LeBoutillier M, et al. Resuscitative retrograde blood cardioplegia. Are amino acids or continuous warm techniques necessary? J Thorac Cardiovasc Surg 1995;109:242–8.[Abstract/Free Full Text]
36. Forbess JM, Hiramatsu T, Nomura F, et al. Anti-CD11b monoclonal antibody improves myocardial function after six hours of hypothermic storage. Ann Thorac Surg 1995;60:1238–44.[Abstract/Free Full Text]

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This Article Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Philippe Menasché Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Menasché, P. Search for Related Content PubMed PubMed Citation Articles by Menasché, P.