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Ann Thorac Surg 1995;59:795-802
© 1995 The Society of Thoracic Surgeons

Functional Recovery After Ischemia: Warm Versus Cold Cardioplegia

Joseph R. Van Camp, MD, Louis A. Brunsting, III, MD, Keith F. Childs, BS, Steven F. Bolling, MD

Section of Thoracic Surgery, University of Michigan Medical School, Ann Arbor, Michigan


   Abstract
Top
 Footnotes
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
Warm continuous retrograde cardioplegia has been introduced for myocardial protection during cardiac operations, particularly in the setting of acute myocardial ischemia because of its theoretical advantage of producing arrest without ischemia. To investigate the ability of warm continuous retrograde cardioplegia to provide myocardial protection after acute global ischemia, versus the more commonly used cold intermittent antegrade cardioplegia, 12 dogs were subjected to 15 minutes of normothermic global myocardial ischemia on cardiopulmonary bypass followed by 75 minutes of protected cardioplegic arrest using either warm continuous retrograde cardioplegia or cold intermittent antegrade cardioplegia. Standard blood cardioplegia at clinically used volumes and flow rates was used. Warm continuous retrograde cardioplegia animals received 30 mL/kg antegrade to induce arrest followed by 1.5 to 1.8 mL • kg-1 • min-1 retrograde at 37°C, whereas cold intermittent antegrade cardioplegia animals received 30 mL/kg antegrade to induce arrest followed by 15 mL/kg antegrade every 15 minutes at 10°C. Load-insensitive left ventricular systolic function, diastolic function, high energy nucleotides, and edema formation were assessed before and after ischemia. Results showed that myocardial preservation using clinically reported flow rates and volumes of warm continuous retrograde cardioplegia was significantly inferior to that provided by clinically used cold intermittent antegrade cardioplegia, as demonstrated by decreased preload recruitable stroke work slope (28 +/- 11 versus 71 +/- 6), increased {alpha} constant of the end diastolic stress-strain relationship (14.2 +/- 3.0 versus 3.6 +/1.0), decreased total nondiffusable nucleotides (40.7 +/- 2.3 versus 57.4 +/- 2.3 µM/g wet weight) and increased water content (82.2% +/- 0.4% versus 80.4% +/- 0.4%). These data demonstrate inadequate myocardial protection with clinically used flow rates of warm continuous retrograde cardioplegia in this model, supporting a cautious approach to the clinical use of warm continuous retrograde cardioplegia in the setting of acute global ischemia.


   Introduction
Top
 Footnotes
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
See also page 802.

See also page 802a.

Clinical cardiac surgery has become safe and effective with current myocardial protection techniques. However, an aging, sicker population requiring difficult, repeat, longer operations will increase the demands on myocardial protection. Recently, a technique of warm continuous retrograde cardioplegia has been introduced maintaining the heart in electromechanical arrest by providing oxygenated warm blood cardioplegia via the coronary sinus [1–3]. Several groups have reported good early clinical results. Theoretically, by producing arrest without ``ischemia'', warm continuous retrograde cardioplegia could provide superior myocardial protection for extended time periods [4–6]. Furthermore, after an ischemic event, warm continuous retrograde cardioplegia potentially can deliver adequate oxygen and nutrients to the stunned, acutely ischemic myocardium, thereby ending ischemia at the time of cardioplegic arrest and providing for early myocardial resuscitation [7]. Therefore in this study, myocardial metabolic and functional recovery after acute global ischemia and reperfusion were examined comparing clinically reported flow rates and volumes of warm continuous retrograde cardioplegia versus a standard technique of cold intermittent antegrade cardioplegia in a surgical model of global ischemia.


   Material and Methods
Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
Twelve adult mongrel dogs weighing 22 to 28 kg were studied in a surgical model of acute global myocardial ischemia followed by cardioplegic protection and reperfusion. All animals were cared for in accordance with the guidelines set forth by the ``Guide for the Care and Use of Laboratory Animals'' published by the National Institutes of Health (NIH publication 85-23, revised 1985). The animals were anesthetized with intravenous pentobarbital (20 mg/kg), and anesthesia was maintained with intermittent dosing as needed. Endotracheal intubation was performed and the animals were placed on a volume-cycled ventilator with a tidal volume of 15 mL/kg and an inspired oxygen fraction of 1.0. Aortic pressure was measured with a fluid-filled line placed in the intrathoracic aorta via the left femoral artery. A pulmonary artery catheter was placed and these lines were connected to a pressure monitor (78204A; Hewlett Packard). A median sternotomy was performed, the azygos vein was ligated, and the aortopulmonary space was dissected for placement of ascending aorta and main pulmonary artery transit-time ultrasonic flow probes (model HT 207; Transonics Systems Inc, Ithaca, NY). Hemispheric piezoelectric, sonomicrometric crystals (3 mHz, 2.5 mm diameter; Channel Industries, Santa Barbara, CA) were sutured to the epicardium of the left ventricle in the major and minor axis orientation. A third pair of flat crystals measured left ventricular free wall thickness. Left ventricular major axis, minor axis, and wall thickness dimensions were measured continuously by sonomicrometry (Triton Technology, San Diego, CA). A high-fidelity pressure transducer catheter (Millar Instruments, Houston, TX) was placed through a puncture site in the apex of the left ventricle for measuring left ventricular pressure. Cardiopulmonary bypass was instituted through a two-stage venous cannula (DLP Inc, Grand Rapids, MI) positioned in the right atrium and arterial cannula placed in the femoral artery. Systemic temperature was maintained at 34° to 36°C while on cardiopulmonary bypass. Thermistor probes were placed in the distribution of the left anterior descending and circumflex arteries to monitor intramyocardial temperature continuously (Yellow Springs Instrument Co, Yellow Springs, OH). Arterial and cardioplegic temperatures were monitored by in line thermistor probes (12100; Sarns, Inc, Ann Arbor, MI).

The experimental protocol is outlined in Figure 1Go and consisted of 15 minutes of normothermic global ischemia obtained by cross-clamping the aorta and opening the aortic root cannula vent. After 15 minutes, according to which group they had been randomized, myocardial arrest was induced with either warm continuous retrograde cardioplegia or cold intermittent antegrade cardioplegia. Standard blood cardioplegia was used throughout the experiments and consisted of blood mixed 4:1 with either high-potassium solution (used for initial arrest) or low-potassium solution (used for subsequent dosing). The final concentrations of the cardioplegic solutions are summarized in Table 1Go.



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  		Fig 1. . Model protocol: 15 minutes of global ischemia followed by 75 minutes of protected arrest and a 30-minute recovery period.

 

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  		Table 1. . Contents of Cardioplegia Solutions Mixed 1:4 With Blood
 
The warm continuous retrograde cardioplegia group (WCR) received initial arresting cardioplegia antegrade at 37°C. If incomplete arrest was achieved after a single dose of cardioplegia, a second dose of high-potassium solution was used. Arrest was achieved in all cases. A coronary sinus catheter (15F; DLP Inc) was placed through a right atriotomy and warm (37°C) continuous retrograde cardioplegia administered at a rate of 1.5 to 1.8 mL • kg-1 • min-1, as reported in the clinical literature. The cardioplegia had a hematocrit of 15% and was 100% saturated, resulting in a calculated O2 content of 8 mL O2/dL. The rate chosen for delivery was based on prior clinical reports from institutions using warm continuous retrograde cardioplegia and was calculated to provide for at least 2.4 mL O2 min per 100 g wet weight of myocardium, which theoretically should more than provide for the reduced metabolic requirements of the warm arrested heart. The pressure at the end of the coronary sinus catheter was measured continuously and was greater than 15 mm Hg at all times (range, 15 to 22 mm Hg). The cold intermittent antegrade group (CIA) received initial arresting cardioplegia (also 30 mL/kg) at 10°C through the aortic root cannula and then repeat antegrade doses (15 mL/kg) every 15 minutes. Saline slush was placed around the heart in the CIA group to emulate clinical conditions and ensure complete cooling. The group characteristics are summarized in Table 2Go.


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  		Table 2. . Summary of Cardioplegia Groups
 
The hearts were maintained in cardioplegic arrest for 75 minutes; therefore, total ischemic time was 90 minutes. After this the aortic cross-clamp was removed and hearts were defibrillated, if necessary. The use and number of defibrillation shocks required was recorded. The coronary sinus catheter was removed and the atriotomy closed. All animals were able to be weaned from cardiopulmonary bypass after 30 minutes of reperfusion. No inotropic agents were administered. Hemodynamic data were collected at a rate of 200 Hz/channel using a personal computer (Macintosh IIci; Apple Computer Inc, Cupertino, CA) with an 8-channel analog to digital converter (MIO-16X, National Instruments Corp, Austin, TX) and in-house software, programmed in LabVIEW 2 (National Instruments Corp). Data were collected over a range of filling conditions of the left ventricle by slowly draining into the venous reservoir. Emptying curves were collected in triplicate, before aortic cross-clamping and after weaning from bypass.

Sonomicrometric data were analyzed to determine the ventricular volume based on a prolate ellipsoid model of the left ventricle using the equation V = (b - 2h)2 (a - 1.1h){pi}/6, where V = internal left ventricular volume, a = major axis dimension (mm), b = minor axis dimension (mm), and h = free wall thickness (mm) [8]. The area of the left ventricle pressure--volume work loops was integrated to yield left ventricular stroke work. Systolic function was evaluated using the preload recruitable stroke work relationship [9].

The diastolic function was evaluated using the end-diastolic wall stress--Lagrangian strain relationship [10]. End-diastolic wall stress ({sigma}) was calculated using the equation {sigma} = pb/2h, where p = end diastolic left ventricular pressure (mm Hg), b = minor axis dimension (mm), and h = wall thickness dimension (mm). The end-diastolic Lagrangian strain ({epsilon}) was calculated using the equation {epsilon} = (V - V0)/V0, where V = left ventricular end-diastolic volume and V0 = left ventricular volume at zero transmural pressure. The end diastolic stress--strain relationships were analyzed using an exponential regression analysis to fit the equation {sigma} = {alpha} (eß{epsilon} - 1).

Full-thickness left ventricle punch biopsy specimens for measurement of high-energy nucleotide and nucleoside analysis were obtained at baseline, at the end of ischemia and at the end of the experiment after reperfusion. Biopsy specimens were obtained from the left anterior descending coronary artery distribution with a liquid nitrogen cooled, suction biopsy gun technique. Tissue was lyophilized for 24 to 48 hours at -40°C and under a 200 mm Hg vacuum to remove water and prevent the degradation of nucleotides and nucleosides. Samples then were homogenized, vortexed and centrifuged to separate the pellet. Supernatant was removed and equal volumes tri-n-octylamine and freon were added. The aqueous phase was pipetted and stored at -70°C for automatic sampling injection using a Waters WISP 712 and column peak separation with a µBondpac C18 column (3.9 x 300 mm). Standard nucleotide and nucleoside curves (Sigma Chemical, St. Louis, MO) were generated from serial dilutions of standards at 10, 25, 50, 100, and 500 µmol/L. Peak areas from standards were integrated and least square curves plotted. A Waters 484 UV absorbance detector was set at 254 nm 1max for nucleotide and nucleoside determinations. Concentrations of total nondiffusable nucleotides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, and inosine monophosphate) and total diffusable nucleosides (adenosine, inosine, hypoxanthine, and xanthine) were calculated and recorded.

Edema formation in the left ventricle was determined at the end of the experiment by calculation of percent water weight of a biopsy specimen taken from the apex of the left ventricle [(wet weight - dry weight) x 100/wet weight)]. Statistical analysis was performed on a personal computer (Macintosh IIci; Apple Computers) using a statistical program (Statview; Abacus Concepts Inc, Berkley, CA). Myocardial water content and defibrillator use were compared using a one-way analysis of variance. All other comparisons were performed by two-way analysis of variance for repeated measures with significance defined as a p value less than 0.05. In the event of a significant measures F value, Scheffé's method was used to localize significant differences. All values are reported as mean +/- standard error of the mean.


   Results
Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Representative digital reconstruction of recorded analog signals are shown in Figure 2Go. The left panel of Figure 3Go shows left ventricular pressure--volume loops generated during gradual emptying of the ventricle, and the right panel shows the corresponding plot of the stroke work--end-diastolic volume or the preload recruitable stroke work. Figure 4Go demonstrates a representative analysis of the end-diastolic stress--Lagrangian strain. The left panel shows the work loops, and the right panel depicts the corresponding exponential regression of this relationship to define the {alpha} and ß coefficients. Table 3Go summarizes the hemodynamic results of both groups before and after ischemia. Table 4Go shows the systolic and diastolic functional analysis results as the average preload recruitable stroke work slope and intercept, and the {alpha} and ß coefficients. Metabolic results of high-energy phosphate--containing compounds are shown in Table 5Go. There were no significant differences between the WCR and CIA groups at baseline before ischemia with regard to any hemodynamic, metabolic, or functional analyses. These data are summarized in Table 3Go.



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  		Fig 2. . Representative analog display of digital recorded data. (Derived LV Volume = calculated volume of the left ventricle from the major, minor, and wall thickness dimensions; LV dP/dT = first derivative of left ventricular pressure; LVP = left ventricular pressure (mm Hg); Major axis crystal = piezoelectric crystal measurement of the left ventricular major axis dimension in millimeters; PAP = pulmonary artery pressure (mm Hg).

 


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  		Fig 3. . Representative analysis of the preload recruitable stroke work. (EDV = end-diastolic volume; LVP = left ventricular pressure; LV volume = calculated volume of the left ventricle; SW = stroke work.)

 


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  		Fig 4. . Representative analysis of the end-diastolic stress to Lagrangian strain relationship for evaluation of diastolic function. (LVP = left ventricular pressure; LV volume = calculated volume of the left ventricle.)

 

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  		Table 3. . Hemodynamic Data After Global Ischemia and Reperfusion Using Either Warm Continuous Retrograde or Cold Intermittent Antegrade Cardioplegia
 

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  		Table 4. . Systolic Functional Analysis Results Shown as Average PRSW Slope and Intercept, and Diastolic Functional Results as {alpha} and ß Coefficients of the End-Diastolic Stress-Strain Relationship
 

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  		Table 5. . Metabolic Recovery Measured as Average Water Weight and Intracellular Nucleotide Levels
 
After ischemia and reperfusion (removal of the aortic cross-clamp), all animals required defibrillation and all animals eventually recovered sinus rhythm. There were no differences in heart rate between groups. The CIA group required 1 +/- 0.2 shocks to convert to a normal rhythm and the WCR group required 1 +/- 0.2 shocks. There was no statistical difference between groups. All the animals were able to be weaned from cardiopulmonary bypass. However, after separation from cardiopulmonary bypass after ischemia, the WCR group required a significantly higher left ventricular end-diastolic pressure (19 +/- 2 versus 9 +/- 0.3 mm Hg; p < 0.05) to maintain a lower mean arterial blood pressure (46 +/- 5 versus 74 +/- 4 mm Hg; p < 0.05) and had a significantly lower left ventricular stroke volume (7 +/- 2 versus 16 +/- 1 mL; p < 0.05) (see Table 3Go). There were no significant differences in the postischemic arterial blood gasses, hematocrits, potassium levels, ionized calcium levels, or cardioplegic hematocrits.

Systolic function, as defined by the slope of the preload recruitable stroke work relationship, was significantly depressed in the WCR group when compared with the CIA group. Similarly, WCR demonstrated increased ventricular stiffness, as the analysis of the {alpha} coefficient from the end-diastolic stress--strain relationship showed worse recovery after ischemia in the WCR group (14.2 +/- 3 versus 3.6 +/- 1).

The metabolic preservation of the ventricle, as assessed by preservation of high-energy nucleotides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, and inosine monophosphate) and their precursor nucleosides (adenosine, inosine, xanthine, and hypoxanthine) also was examined. Although no differences were noted at baseline, the total nondiffusable nucleotide level after ischemia and reperfusion in the WCR group was significantly lower (40.7 +/- 2.3 versus 57.4 +/- 2.3 µM/g wet weight; p < 0.05). In particular the adenosine triphosphate level (25.2 +/- 2.4 versus 45.6 +/- 2.2 µM/g wet weight) was significantly lower in the WCR group when compared with CIA. Myocardial water content after ischemia was higher in the WCR group (82.2% +/- 0.4% versus 80.4% +/- 0.4; p < 0.05) than in the CIA group, indicative of more edema formation in the myocardium.


   Comment
Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
Although current techniques of myocardial protection using cold cardioplegia yield excellent outcome, poor functional recovery occasionally is encountered, as inhomogeneous distribution due to coronary artery disease, injury to contractile proteins from hypothermia, and a finite time the heart can safely remain cold lead to ischemic injury and limit this technique [11]. Avoiding ischemic injury during cardiac operations is dependent on matching and supplying sufficient energy to meet myocardial metabolic demands [12]. Although electromechanical arrest and hypothermia have been shown to reduce myocardial metabolic demand by 95%, the myocardium still requires energy to maintain basic cellular metabolism, ionic equilibrium, and membrane integrity [7]. Unfortunately, anaerobic glycolysis may be inadequate to meet even the much-reduced metabolic demands of the cold arrested heart, as hypothermia impairs glycolysis and energy utilization.

One proposed solution is WCR, which theoretically avoids unequal distribution of cardioplegia, obviates the need for hypothermia, and delivers adequate oxygen and substrate to the myocardium during the operative procedure. Using WCR with 100% O2 saturation and a hematocrit of 20%, the estimated oxygen delivery to the myocardium may be sufficient to avoid any ``ischemia'' whatsoever. In a clinical series warm blood cardioplegia was used in 121 patients undergoing coronary revascularization and was compared retrospectively with 133 patients protected with standard hypothermic cardioplegia [2]. The patients in the warm group had fewer myocardial infarctions, a decreased incidence of low cardiac output syndrome, and less need for balloon counterpulsation. The vast majority of the warm group returned to sinus rhythm spontaneously compared with only 10% receiving cold protection. Warm cardioplegia then was used at the same institution in a higher-risk group including elderly patients and emergent operations with good results [13].

However, these initial clinical studies using warm blood cardioplegia demonstrating good results were retrospective, nonrandomized studies, and results from other groups only demonstrated comparable and not superior results with warm blood cardioplegia. For example, a recent study, of 50 consecutive coronary artery bypass grafting patients protected with either intermittent retrograde cold blood cardioplegia or continuous retrograde warm blood cardioplegia could find no functional or metabolic differences between these two methods of cardioprotection [14]. Finally, in a recent prospective, randomized clinical study of more than 1,000 patients, intermittent cold oxygenated crystalloid cardioplegia was compared with continuous warm blood cardioplegia [15]. There were no significant differences in mortality, Q-wave infarct, or intraaortic balloon use between groups. However, a significantly increased number of neurologic events were seen in warm blood patients (5% versus 1.4%).

Furthermore, there are numerous pitfalls, both theoretical and practical, with warm cardioplegia [16]. The constant infusion of blood cardioplegia yields inadequate visualization of the operative field. Additionally, the safe period for interrupting warm blood cardioplegia to obtain adequate visualization of the operative field is unknown, and such interruption may lead to unprotected warm ischemia. Finally, the optimal flow rates and pressures for warm blood cardioplegia in the presence of severe vessel disease or hypertrophied myocardium are undetermined. One clinical study compared flow rates and hemoglobin concentrations for continuous warm blood cardioplegia and found the best oxygen consumption and adenosine triphosphate levels in high-flow, high-hemoglobin warm group compared with other warm and cold groups [17]. However, no significant difference was found in ventricular performance in this limited study. Continuous retrograde warm blood cardioplegia is technically cumbersome and complications, such as dislodgement of catheters, leading to warm ischemia-induced myocardial dysfunction and death have been reported [18]. Finally, when problems with cardiopulmonary bypass do arise, they can be associated with an increased potential for cerebral injury because the patients are near normothermic.

Unfortunately, laboratory study of warm cardioplegia also has yielded conflicting results. Misare and associates [19] found that intermittent antegrade, cold blood cardioplegia resulted in significantly better recovery of both global and regional systolic function than protection of hearts with continuous antegrade warm blood cardioplegia in left anterior descending coronary artery occlusion and reperfusion model in the pig. In a series of studies from Emory University, continuous retrograde warm blood cardioplegia was compared with cold crystalloid and cold blood cardioplegia in a canine model of acute regional myocardial ischemia [20]. Animals underwent 45 minutes of left anterior descending coronary artery occlusion followed by cardioplegic arrest with cold oxygenated crystalloid cardioplegia, cold blood cardioplegia, or warm blood cardioplegia. Their results showed that ventricular function (preload recruitable stroke work and maximum elastance relationship) were significantly better for warm blood cardioplegia, but that cold blood cardioplegia was nearly as good. Interestingly, diastolic function (stress--strain) revealed decreased diastolic compliance in cold crystalloid hearts, but no significant difference in compliance between warm and cold blood cardioplegia. Left anterior descending coronary artery nucleotide levels and myocardial edema were again only significantly worse with cold crystalloid cardioplegia. In a follow-up study, animals were assigned to cold oxygenated crystalloid cardioplegia, cold blood cardioplegia with modified reperfusate, or continuous aerobic warm blood cardioplegia and subjected to 15 minutes of warm global ischemia followed by a 15-minute occlusion of the left anterior descending coronary artery and then cardioplegic arrest [21]. There were no significant differences in maximum elastance, myocardial oxygen consumption, myocardial edema, or histopathologic evidence of injury between groups. Ventricular function, assessed by the slope of the preload recruitable stroke work relationship and of the diastolic stress-strain relationship, was significantly better for the warm group but intermediate for cold blood. Significantly, the flow rates and volumes of warm continuous retrograde cardioplegia used in these experimental studies far exceed those reported for clinical use.

The infusion rate used in the present study (1.5 to 1.8 mL • kg-1 • min-1) is in the range of that which is published in the clinical literature and used by others and is based on both technical and review articles from leading cardiac surgical institutions that practice retrograde continuous warm blood cardioplegia. Jabar and Panos [22] reported that their flow rate of warm potassium blood cardioplegia was 100 mL/min. If one assumes that the average body weight of a patient undergoing a cardiac operation is between 70 and 80 kg, this flow rate equals 1.2 to 1.3 mL • kg-1 • min-1. This range of clinical dosage of retrograde continuous warm blood cardioplegia also can be noted in other reports. In these clinical articles, Salerno and associates [1] recorded a mean flow of warm cardioplegia of 122 mL/min, Yau and colleagues [23] had a flow of 80 mL/min, and Lichtenstein and co-workers [5] delivered retrograde continuous warm blood cardioplegia at a total rate of 75 to 125 mL/min. Lichtenstein and associates used infusion rates of 50 to 150 mL/min in further clinical reports [2, 4, 13]. Finally, an article by Yau and colleagues [17] demonstrated that normothermic blood cardioplegia was safe in patients when delivered at 80 mL/min. That study was undertaken specifically to determine the clinical effects of differing delivery rates of retrograde continuous warm blood cardioplegia in patients. Furthermore, using the oxygen consumption calculations of Yau and colleagues, our dosage and delivery rate of 1.5 mL • kg-1 • min-1 should deliver adequate oxygen in the fashion proposed by proponents of retrograde continuous warm blood cardioplegia. None of these reports, which come from the institutions clinically using warm cardioplegia, greatly exceeded a delivery rate of 1.5 mL • kg-1 • min-1, and many of the doses were actually less when calculated on a mL • kg-1 • min-1 basis. In constructing a clinically analogous surgical experimental model, the dose of 1.5 mL • kg-1 • min-1 is well within the clinical range commonly used.

Intermittent cold cardioplegia produces myocardial ischemia, which, imposed on any preexisting acute ischemia, may deplete the limited reserve of an impaired ventricle, resulting in poor functional recovery. The proposed beneficial mechanism for warm blood protection in acute ischemia is via reduction of myocardial energy requirements by electromechanical arrest to low levels that can be met by the continuous infusion of warm oxygenated blood cardioplegia. This theoretically prevents ischemia and may allow aerobic resuscitation to begin as soon as an operation starts. However, after acute ischemia, oxygen demand increases in the initial reperfusion-resuscitation phase and functional recovery of the ventricle can be delayed by less than full reperfusion [24]. It is assumed that the delivery of oxygen via the warm retrograde method can provide sufficiently for this initial demand, potentially without the added protection of decreasing the oxygen demand via hypothermia; however, partial, incomplete, or premature resuscitation may be occurring that leads to further damage. In the present study, using this particular clinically derived dosage, hearts rendered globally ischemic and protected with WCR functioned poorly when compared with the hearts protected with hypothermia and cold cardiac arrest. The load-insensitive analyses of systolic and diastolic function were depressed in the WCR group, indicating inferior myocardial protection. Edema formation and a decline in the intracellular high-energy compounds also were seen in the WCR group. Finally, WCR has been touted to have a higher spontaneous return of sinus rhythm, but this was not evident after global ischemia. All of these results could reflect ongoing ischemia after arrest in the WCR group, due to either inadequate cardioplegia distribution, anatomic shunting through thebesian veins, or inadequate oxygen and metabolic supply to meet the increased needs of a globally ischemic heart. The results from our study suggest the latter, that the standard clinically used flows of retrograde blood cardioplegia appeared insufficient to supply the oxygen needed to repay the debt amassed by the entire globally ischemic heart. This may have led to ongoing and persistent injury, in a heart thought to be protected by warm retrograde blood perfusion.

Clear and easily evident benefit of any new myocardial protection strategy is needed before alterations of standard techniques are warranted. Although in certain cases, warm blood cardioplegia may offer theoretical benefit, it is not clear that the potential disadvantages of decreased visibility, neurologic risk, potential ischemic intervals, and technical difficulties justify this technique. For this study, we chose to use a clinically analogous and widely reported flow rate and must caution that this flow rate may not deliver adequate oxygen for the resuscitation of ischemic myocardium, as we found poorer myocardial protection in this model and species using very sensitive methods of detecting alterations in ventricular function. Perhaps much higher ranges of retrograde continuous warm blood cardioplegia flows might be more appropriate for this scenario; however, much higher flow and volumes have more technical difficulties. In summary, this study demonstrated that warm retrograde cardioplegia, delivered at these clinically used rates, was inferior in protecting myocardial function when compared with standard hypothermic blood cardioplegia in this canine model of the globally ischemic heart. These findings dictate cautious use of warm retrograde cardioplegia in the setting of acute ischemia and warrant further investigation.


   Footnotes
Top
 Footnotes
Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
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 Bolling, Section of Thoracic Surgery, Department of Surgery, University of Michigan Hospital, 2120 Taubman Center, Box 0344, Ann Arbor, MI 48109.


   References
Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

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