Preservation of myocardial function and biochemistry after blood and oxygenated crystalloid cardioplegia during cardiac arrest

We compared the ability of blood cardioplegia and oxygenated crystalloid cardioplegic solutions to maintain regional left ventricle contractility and adenosine triphosphate levels after cardiopulmonary bypass. Ten baboons were subjected to 90-minute cardiopulmonary bypass conducted at 28 degrees C. Hemodynamic measurements were made before and after the bypass procedure, and biopsies for high-energy phosphate determinations were performed at different time intervals during and after bypass. The results showed improved maintenance of myocardial contractility (measured with the regional end-systolic pressure-length relationship) with the oxygenated crystalloid solution. Expressed as a percentage of values before bypass, contractility after bypass averaged 81.69% +/- 4.81% and 80.47% +/- 10.05%, respectively, after 10 and 20 minutes using the oxygenated crystalloid cardioplegia. For blood cardioplegia, the corresponding values were 71.9% +/- 8.73% and 64.99% +/- 8.60% (mean +/- standard error of the mean). The 10- and 20-minute postbypass values between the two groups differed significantly (t test, Welch modification: p = 0.0464 and p = 0.0342). Myocardial adenosine triphosphate level was higher immediately after induction of cardiac arrest when blood cardioplegia was used (blood cardioplegia, 6.82 mol.g wet wt-1; crystalloid cardioplegia, 4.95 mol.g wet wt-1; p = 0.0314), but values subsequently equalized.     

Preservation of myocardial energy-rich phosphates by retrograde application of Bretschneider cardioplegia during aortocoronary bypass surgery

The efficacy of myocardial protection obtained by antegrade application of a cardioplegic solution was compared with that obtained by retrograde application via the coronary sinus. Myocardial preservation was assessed using biochemical parameters, i.e. tissue content of lactate, creatine phosphate, nucleotides, nucleosides and hypoxanthine. Nineteen patients undergoing routine aortocoronary bypass surgery were randomly allocated to a study group. During cardiac arrest induced by antegrade Bretschneider cardioplegia, myocardial tissue content of creatine phosphate dropped to 52% of its pre-ischemic value and degradation of nucleotides occurred, characterized mainly by an accumulation of adenosine. Retrograde cardioplegia prevented this catabolism of energy-rich phosphates completely during ischemic cardiac arrest and is therefore considered to be superior to antegrade cardioplegia.     

Preservation of myocardial high-energy phosphates with vagal stimulation and hypothermic cardioplegia

We examined three methods of inducing hypothermic cardioplegic arrest and related each to preservation of high-energy phosphates. Levels of adenosine triphosphate (ATP) and creatine phosphate (CP) in baseline rat hearts were compared with levels found after vagal stimulation combined with cardioplegia containing 15 mEq of potassium chloride (KCl) per liter, cardioplegia with 15 mEq of KCl per liter alone, and cardioplegia with 30 mEq of KCl per liter alone. Vagal stimulation produced complete electromechanical arrest in a shorter time than either 15 or 30 mEq of KCl alone (p less than 0.001 for both cardioplegic solutions compared with vagal stimulation), with fewer ventricular beats after ischemia than cardioplegic solution containing 15 or 30 mEq of KCl (p less than 0.001 and less than 0.01, respectively). Levels of ATP and CP, although less than baseline levels (p less than 0.01 and less than 0.001, respectively), were greater with vagal stimulation than with either 15 or 30 mEq of KCl (p less than 0.001 and less than 0.05, respectively, for ATP and p less than 0.001 for both CP levels). Furthermore, when all groups were combined, ATP and CP levels were found to correlate negatively with arrest time (r = -0.851 and -0.788, respectively; both r values significant at p less than 0.01) and with the number of ventricular beats after ischemia (r = -0.927 and -0.851, respectively; both r values significant at p less than 0.01). We conclude that electromechanical work quantified as time to arrest after aortic cross-clamping and as number of ventricular beats after ischemia correlates negatively with ATP and CP levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraoperative myocardial protection: a comparison of blood and asanguineous cardioplegia

Cardiac arrest was achieved in 84 patients using asanguineous cardioplegia and in 97 patients using cold blood potassium cardioplegia. The patient groups were similar in age, sex ratio, and preoperative risk factors. Other than the cardioplegic solution used, the conduct of each operation was identical. There were no differences in mean total pump time (118 minutes for the asanguineous cardioplegia group versus 117 minutes for the cold blood cardioplegia group) or cross-clamp time (73.5 versus 70 minutes, respectively). However, the blood cardioplegia group had a greater number of distal anastomoses per patient (3.9 versus 3.7; p less than 0.05). Myocardial protection was assessed clinically and by serial electrocardiograms. Cellular integrity was determined by release of the myocardial isoenzyme of serum creatine kinase (CK-MB). Cellular morphology was studied in 6 randomly selected patients in each group by electron microscopic examination of left ventricular myocardial samples obtained before and after bypass. Three patients given blood cardioplegia and 5 given asanguineous cardioplegia required intraaortic balloon counterpulsation at termination of bypass. There were no ultrastructural changes in either group. Electrocardiographic changes (Minnesota code) occurred in 12 of 84 patients receiving asanguineous cardioplegia versus 12 of 97 patients receiving cold blood potassium cardioplegia. To maintain a satisfactory cardiac index (greater than 2.0 L/min/m2), 38 of 84 patients given asanguineous cardioplegia versus 25 of 97 patients given blood cardioplegia required inotropic support up to 24 hours postoperatively (p less than 0.05). Infarct size determined from CK-MB release was significantly greater (p less than 0.05) in patients given asanguineous cardioplegia (36.27 gm-equivalents) than in those given blood cardioplegia (26.7 gm-equivalents).(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental evaluation of myocardial preservation techniques: IV. Potassium cardioplegia.

To investigate whether potassium per se plays a significant role in cold potassium cardioplegia, isolated blood-perfused rabbit papillary muscle preparations were used to determine the recovery of myocardial contractility after normothermic anoxia. Cardioplegia was induced by infusing an isotonic electrolyte solution containing either 5 or 40 mEq/liter of potassium chloride. Anoxic periods of 30 minutes (9 experiments each) 45 minutes (10 experiments each), and 60 minutes (1 experiment each) were compared. Hearts stopped contracting in 45 seconds with infusion of a 40mEq/liter of potassium chloride solution compared to 5 minutes with a 5 mEq/liter solution. After 30 minutes of anoxia, myocardial recovery was 65.39 +/- 24.48 per cent with 5 mEq/liter of potassium chloride and 90.05 +/- 6.40 per cent with 40mEq/liter of potassium chloride. The difference was highly significant (p less than 0.01). After 45 minutes of anoxia the same trend as just described was noted, but the difference was statistically insignificant. After 60 minutes of anoxia, recovery was extremely poor regardless of the potassium concentration of the cardioplegic solution. Our conclusion was that a high potassium solution will arrest the heart rapidly and provide protection against anoxic injury of the myocardium. Its protective effect becomes less significant, however, as the anoxic time is prolonged.     

Regional changes in myocardial acid production during ischemic arrest: a comparison of sanguineous and asanguineous cardioplegia

Regional differences in myocardial acid production have not been characterized during administration of either asanguineous or sanguineous cardioplegia. To investigate this, miniature glass pH electrodes were placed in the right ventricular (RV) myocardium, the left ventricular subendocardial (LV endo) region, and the subepicardial (LV epi) region in a canine model. Multiple doses of either blood cardioplegia (Group 1; N = 11) or crystalloid cardioplegia (Group 2; N = 11) were administered during 4 hours of aortic cross-clamping. The accumulation of hydrogen ions during the cross-clamp period was greater in Group 2 than Group 1 in the LV endo region (629 +/- 79 nm/L versus 66 +/- 31 nm/L; p less than 0.001), the LV epi region (623 +/- 66 nm/L versus 72 +/- 32 nm/L; p less than 0.001), and the RV myocardium (814 +/- 296 nm/L versus 150 +/- 54 nm/L; p less than 0.05). Within each group, the time course of myocardial pH and the accumulation of hydrogen ions did not differ among the LV endo region, LV epi region, and the RV myocardium (p = not significant). These data indicate that transmural and interventricular differences in myocardial pH and hydrogen ion accumulation are not produced in the vented, arrested canine heart. In addition, when compared with asanguineous cardioplegia, blood cardioplegia globally and transmurally reduces acid accumulation during ischemic arrest.     

Preservation of human cardiac contractility during anoxic arrest with glucose-containing cardioplegia

Infusing the aortic root with a hypothermic solution containing glucose, insulin, and potassium (GIK) during aortic cross-clamping and anoxic arrest resulted in a significant preservation of human myocardial contractility indices. Control coronary artery surgery patients had acute postcardiopulmonary bypass dp/dtmax depressed to 79.8 per cent prebypass levels and maintained only 73.0 per cent prebypass Vpm. Patients with aortic root GIK maintained 148.1 per cent prebypass dp/dtmax and 157.2 per cent prebypass Vpm, which were significantly better than control (P less than 0.001). These patients also required significantly less vasopressor (P less than 0.05). Patients who maintained at least 85 per cent prebypass dp/dtmax or Vpm had less need for subsequent vasopressor in the recovery period (P less than 0.05). Peak quantitated subsequent vasopressor need had a negative correlation (P less than 0.05) to percentage prebypass Vpm maintained. GIK root infusion enhanced anaerobic metabolism. Coronary washout of acidotic byproducts and direct cardiac buffer combining with improved glycolytic flux and better global hypothermia appeared to be the mechanisms for contractility preservation. Contractility indices appear to be useful in determining subsequent vasopressor needs.     

Comparison of myocardial temperatures with multidose cardioplegia versus single-dose cardioplegia and myocardial surface cooling during coronary artery bypass grafting

Myocardial hypothermia with multidose cardioplegia has not been compared with single-dose cardioplegia and myocardial surface cooling with a cooling jacket in patients having coronary artery bypass grafting. In this study, 20 patients with three-vessel disease undergoing coronary bypass at 28 degrees C with bicaval cannulation, caval tapes, and pulmonary artery venting (4.9 +/- 0.7 grafts per patient) were prospectively randomized equally into group I (multidose cardioplegia) and group II (single-dose cardioplegia with a cooling jacket). The initial dose of cardioplegic solution was 1000 ml. Group I then received 500 ml of cardioplegic solution every 20 minutes, delivered into the aortic root and available grafts. In group II, after the cardioplegic solution had been administered, a cooling jacket covering the right and left ventricles was applied. In both groups temperatures were recorded every 30 seconds at five ventricular sites: (1) right ventricular epicardium; (2) right ventricular myocardium or cavity, 7 mm; (3) left ventricular epicardium; (4) left ventricular myocardium or cavity, 15 mm; and (5) septum, 20 mm. Group mean temperatures at each site at various times were compared within each group and between the two groups by analysis of variance. Aortic crossclamp time was 60.3 +/- 12.1 minutes in group I and 52.8 +/- 7.3 minutes in group II (p = 0.12); cardiopulmonary bypass time was 103.7 +/- 11.1 minutes in group I versus 87.7 +/- 12.7 minutes in group II (p less than 0.01). One minute after the cardioplegic solution was initially given, temperatures between groups at each site were not statistically different, but left ventricular epicardial temperatures within both groups were significantly higher than in the other four sites. Nineteen minutes after administration of the cardioplegic solution, temperatures in group I at all sites were higher than in group II. Similarly, throughout the entire period of aortic crossclamping, mean temperatures (except left ventricular myocardial site), maximum temperatures, and percentage of time all temperatures were 15 degrees C or higher were greater in group I than in group II. The following conclusions can be reached: 1. Initial myocardial cooling with 1000 ml of cardioplegic solution is not significantly limited by coronary artery disease but is suboptimal (16 degrees or 17 degrees C) in the inferior left ventricular epicardium because of continual warming from the aorta and subdiaphragmatic viscera. 2. Without myocardial surface cooling, excessive external myocardial rewarming to 18 degrees to 22 degrees C occurs within 20 minutes at all sites after delivery of the cardioplegic solution.(ABSTRACT TRUNCATED AT 400 WORDS)     

Metabolic changes and myocardial injury during cardioplegia: a pilot study.

BACKGROUND: The timing, nature, and severity of both increased cardiac troponin I (cTn-I) levels and myocardial injury during ischemic arrest with cardioplegia are unknown. To define them more accurately, we studied myocardial metabolic activity and the release of markers of myocardial cell injury into the coronary sinus before, during, and after cardioplegia. METHODS: We simultaneously measured creatine kinase, creatine kinase-MB, cTn-I, lactate, phosphate, and blood gases in coronary sinus and systemic arterial blood from 12 patients before cardiopulmonary bypass, after removal of the aortic cross-clamp, and after discontinuation of cardiopulmonary bypass. We also measured coronary sinus flow and transmyocardial fluxes of all analytes and calculated myocardial oxygen consumption, myocardial carbon dioxide production, and myocardial energy expenditure. RESULTS: Myocardial lactate release increased 10-fold after removal of the aortic cross-clamp (p = 0.012) and was accompanied by a surge in myocardial phosphate uptake (p = 0.056). These events were associated with only partial cardioplegia-induced suppression of myocardial oxygen consumption (p = 0.0047), myocardial carbon dioxide production (p = 0.0022), and myocardial energy expenditure (p = 0.0029). Simultaneously, coronary sinus cTn-I levels increased from a mean of 0.76 to 2.43 ng/mL after removal of the aortic cross-clamp, and 2.51 ng/mL after cardiopulmonary bypass (p = 0.014), leading to an increase in arterial cTn-I concentration from 0.18 to 0.98 and 3.01 ng/mL (p = 0.0002). Thus, cTn-I release across the myocardium was absent at baseline, became detectable (p = 0.012) after removal of the aortic cross-clamp, and correlated with cross-clamp and pump times. Similar changes occurred with creatine kinase-MB. CONCLUSIONS: Metabolic myocardial stress occurs during ischemic arrest with cardioplegia and is associated with inadequate suppression of metabolism and with a surge in cTn-I and creatine kinase-MB release, which is maximal after removal of the aortic cross-clamp. These changes are likely to represent structural myocardial cell injury.     

Blood cardioplegia: a review and comparison with crystalloid cardioplegia.

The Oxford International Symposium on myocardial preservation provided an appropriate milestone and impetus to survey one aspect of operative myocardial preservation, namely blood cardioplegia, and to contrast it with the more popular crystalloid cardioplegia. This review is by no means complete or exhaustive but represents my best effort to summarize important information that has accumulated in the literature as blood cardioplegia, and our understanding of it, has evolved. It is appropriate to compare blood and crystalloid cardioplegia with respect to biochemical and physiological differences. Clinical comparison has been limited, for the most part, to randomized studies, and a number of differences and details of clinical management of the two techniques have been omitted, either because they seemed unimportant or there was no good information that would allow an objective comparison of their significance. Hopefully, the reader will recognize the intent to focus on meaningful differences and similarities between the two techniques and to present them fairly.     

Preservation of myocardial high-energy phosphates in open-heart surgery with deep general hypothermia and multidose crystalloid cardioplegia

Myocardial energy metabolism during deep general hypothermia (20 degrees C) and multidose crystalloid cardioplegia, and also during subsequent reperfusion, was studied in eight patients undergoing isolated aortic valve replacement. Six serial transmural biopsy samples from the left ventricular apex were analyzed for high-energy phosphates and their degradation products. Reductions in ATP, total adenine nucleotide content and energy charge were insignificant during cardioplegia, as were changes in adenosine and uric acid concentrations. During reperfusion, however, there was slight but significant reduction in total adenine nucleotide content, despite adequate oxygenation as indicated by reversal of lactate accumulation. These observations suggest that the reperfusion phase is accompanied by metabolic aberrations which are not overcome by good oxygenation in relation to the metabolic rate.     

Inconsistent effectiveness of myocardial preservation among cardiac chambers during hypothermic cardioplegia

The purpose of this study was to examine the selective and differential natures of ischemic injuries among three cardiac chambers (right atrium, right ventricle, and left ventricle) from the viewpoint of ultrastructural morphometric study. Twenty consecutive adult patients undergoing cardiac operations were studied. The duration of aortic crossclamp time varied from 36 to 142 minutes (mean 83.4 +/- 36.4 minutes). Two serial specimens (preischemic and ischemic) were obtained from the right atrium, the right ventricle, and the left ventricle, respectively. A total of 120 biopsy specimens was obtained from these 20 patients. The average mitochondrial surface area of the left ventricle was 0.308 +/- 0.062 micron 2 in the preischemic stage and 0.352 +/- 0.083 microns 2 in the ischemic stage. This represented a 14.3% increase in mitochondrial surface area after ischemic injury (p less than 0.01). The mitochondrial surface area of the right ventricle showed an average increase of 43.7%, from 0.252 +/- 0.036 micron 2 in the preischemic stage to 0.362 +/- 0.087 micron 2 in the ischemic stage (p less than 0.0005). With respect to the mitochondrial surface area of the right atrium, there was an increase of 88.0%, from 0.217 +/- 0.044 micron 2 in the preischemic stage to 0.408 +/- 0.084 micron 2 (p less than 0.0005). The difference of mitochondrial swelling among three chambers was statistically significant (right atrium versus right ventricle versus left ventricle, p less than 0.0005). Moreover, the differences of mitochondrial swelling between any two chambers were also highly significant (right atrium versus right ventricle, p less than 0.0005; right ventricle versus left ventricle, p less than 0.01; right atrium versus left ventricle, p less than 0.0005). In conclusion, our findings suggest that from the viewpoint of ultrastructural morphometric study myocardial injury after an average of 83 minutes of ischemic arrest is poorer in the right chambers of the heart than in the left ventricle, with the right atrium having the poorest preservation.     

Prevention of myocardial electrical activity during ischemic arrest with verapamil cardioplegia

The effect of potassium cardioplegia and potassium cardioplegia containing verapamil hydrochloride on myocardial preservation and electrical activity during prolonged aortic occlusion was examined in 40 adult mongrel dogs. Twenty-four animals (Group 1) received potassium cardioplegia, and 16 animals (Group 2) received potassium verapamil cardioplegia. Potassium or potassium verapamil cardioplegia, 10 ml per kilogram of body weight, was administered after application of the aortic cross-clamp and at 30-minute intervals during the 90-minute arrest. Myocardial temperature was maintained within a range of 8 degrees to 10 degrees C with topical ice saline solution, and electrical activity was monitored with specially designed plunge electrodes. Plunge electrode activity was recorded from the myocardium during arrest in 16 of the 24 animals in Group 1; no electrical activity was present in the animals in Group 2 (p less than .001). The addition of verapamil to potassium cardioplegia increased the tolerance of the myocardium to prolonged ischemia and resulted in less depletion of high-energy phosphate stores and better preservation of mitochondrial ultrastructure and left ventricular function. These data suggest that verapamil augments the preservation provided by potassium cardioplegia by initiating and maintaining a more complete electrical arrest.     

Preservation techniques for heart transplantation: comparison of hypothermic storage and hypothermic perfusion

Preservation of the donor heart is an important and controversial subject in heart transplantation. This study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation (n = 14). The donor hearts of group A (n = 7) were placed in simple hypothermic storage for 5 hours. The donor hearts of group B (n = 7) were placed onto a perfusion apparatus for 5 hours, with pressure maintained at 28 cm of H2O and a myocardial temperature of 8 to 10 degrees C. In both groups the hearts were initially protected with isosmolar potassium cardioplegic solution. The perfusate in group B contained moderate sodium, mannitol, glucose, insulin, and oxygen. The ischemic interval within both groups was 6 hours including orthotopic transplantation. Investigation was conducted at three time periods: prepreservation, postpreservation, and immediately after loading. For both groups there was nonsignificant depression of myocardial function (cardiac index, stroke index, stroke work index, ejection fraction, and wall stress) at the postpreservation period. After volume loading, for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than 0.01; stroke index, p less than 0.01) with no significant change in heart rate, systemic vascular resistance, and systolic blood pressure. There was also significant improvement in myocardial performance (p less than 0.05) for the hypothermic perfusion group after volume loading. Ultrastructural changes were minimal for both groups, and there were no major heart transplantation after 6 hours of ischemia; however, hearts retain their contractile capacity better after hypothermic perfusion than after simple hypothermic storage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nicorandil pretreatment and improved myocardial protection during cold blood cardioplegia.

OBJECTIVE: The present study was designed to assess whether pretreatment with nicorandil enhanced myocardial protection provided by cold (15 degrees C) high-potassium (25 mmol/l) blood cardioplegia during open heart surgery. METHODS: Subjects were 40 patients with a variety of acquired heart diseases undergoing cardiac surgery involved cardiopulmonary bypass. They were randomly divided into two groups, 25 pretreated nicorandil (0.3 mg/kg) 30 minutes before aortic cross clamping, 15 not pretreated. After aortic cross clamping, the initial dose of cardioplegic solution (10 ml/kg) was administered through the ascending aorta and supplemental doses of cardioplegia (5 ml/kg) given each 30 minutes thereafter. Preoperative and postoperative cardiac troponin-T, myosin light chain 1 and cardiac enzymes were measured and hemodynamic data recorded. RESULTS: Postoperative serum creatine kinase and myosin light chain 1 were significantly lower in the nicorandil pretreatment group than in controls. Serum glutamic oxalacetic transaminase and troponin-T were lower and cardiac output was higher after surgery in the nicorandil group, although not statistically significant. CONCLUSION: This data suggests that pretreatment with nicorandil enhances the myocardial protection achieved by cold blood cardioplegia.     

Myocardial oxygen tension during surgical revascularization. A clinical comparison between blood cardioplegia and crystalloid cardioplegia.

OBJECTIVE: The aim of this study was to assess the effect of cardioplegic solutions on myocardial oxygenation during surgical revascularization. METHODS: In 30 patients, randomized to receive crystalloid (CC) or blood (BC) cardioplegia, myocardial oxygen tension was measured continuously by polarography. RESULTS: The two groups were comparable in terms of patients' age, sex, pre-operative ejection fraction, coronary disease, perfusion time, and aorta cross-clamping time. However, the BC group required 22% more of cardioplegic solution to stop electrical activity of the heart. Throughout the pre- and post-cardiac arrest periods, oxygen tension between the two groups was similar. At the end of the observation (4th day), myocardial oxygenation increased over 200% in relation to the values before revascularization. During the first infusion of cardioplegia, oxygen tension in the CC group was lower compared to the BC group (0.1 mmHg vs 1.3 mmHg; P<0.05) being the only significant difference between the two groups during cardiac arrest. Throughout the cardiac arrest, myocardial oxygen tension was close to zero regardless of the type of cardioplegia used. Post-operatively, addition of oxygen to the respiratory air increased myocardial oxygenation by over 17% resulting in a positive correlation (r=0.94; P<0.05) between myocardial oxygen tension and peripheral saturation. CONCLUSIONS: In conclusion, the differences in myocardial oxygen tension between the CC and BC groups are trivial. Thus, any potential beneficial effect of blood cardioplegia compared to crystalloid cardioplegia must be due to other circumstances than its oxygen carrying capacity. An important observation is a significant increase in myocardial oxygenation during oxygen supplement to the respiratory air.