Replacing potassium with nicorandil in cold St. Thomas' Hospital cardioplegia improves preservation of energetics and function in pig hearts

BACKGROUND: To determine whether the adenosine triphosphate-sensitive potassium channel opener nicorandil, instead of potassium in cold crystalloid cardioplegia, may enhance cardioprotection, crystalloid cardioplegia with nicorandil, magnesium, and procaine was compared with standard crystalloid cardioplegia in terms of left ventricular performance and efficiency. METHODS: Sixteen pigs were randomly assigned to receive cold hyperkalemic crystalloid cardioplegia (n = 8) or nicorandil in cold saline (n = 8). Cold (4 degrees C) cardioplegic solutions were given antegradely and intermittently, with a cross-clamp time of 60 minutes. The preload recruitable stroke work relationship (PRSW), pressure-volume area (PVA), and myocardial oxygen consumption (MVO(2)) were calculated at baseline and at one and two hours following cross-clamp release, using combined pressure-volume conductance catheters, coronary flow probes, and O(2)-content differences. RESULTS: The left ventricular contractility expressed in PRSW was reduced to 58% (standard deviation [SD]: 20) of baseline in the crystalloid group and to 89% (SD: 20) in the nicorandil group two hours after cross-clamp release (p = 0.044). The slope of the MVO(2)-PVA relationship increased in the crystalloid group from 1.59 (SD: 0.22) before cardioplegia to 2.55 (SD: 0.73) afterwards, significantly more than in the nicorandil group, where the slope changed from 1.69 (SD: 0.30) to 1.95 (SD: 0.47) (p = 0.027). CONCLUSIONS: Nicorandil in a crystalloid cardioplegic solution was easily employed and contractility was significantly better than after standard hyperkalemic cardioplegia. The smaller shift of the slope in the MVO(2)-PVA relationship in the nicorandil group shows improved efficiency in oxygen to mechanical transfer compared with the crystalloid group.     

Adenosine instead of supranormal potassium in cardioplegic solution preserves endothelium-derived hyperpolarization factor-dependent vasodilation.

OBJECTIVE: We have recently shown that adenosine instead of supranormal potassium in cold crystalloid cardioplegia improves cardioprotection. Studies indicate that hyperkalemia has unfavorable effects on vascular endothelial function. Three pathways have been identified as major vasodilatory pathways: the nitric oxide (NO) pathway, the cyclooxygenase (COX) pathway, and the endothelium-derived hyperpolarization (EDHF) pathway, where the EDHF pathway, in particular, seems susceptible to hyperkalemia. We hypothesized that adenosine cardioplegia improves postcardioplegic endothelial function. METHODS: Sixteen pigs were randomized to receive either cold (6 degrees C) hyperkalemic cardioplegia (n=8) or cardioplegia where hyperkalemia was substituted with 1.2 mM adenosine (n=8). After 1h of cold ischemic arrest, coronary blood flow was monitored for the following 2h. The LAD artery was then explanted, and cylindrical rings were mounted for isometric tension recordings in organ chambers. Vessels were preconstricted with U46610 (Thromboxane A(2) analog) and then bradykinin-mediated relaxation was investigated. To differentiate between the vasodilatory pathways the relaxation was assessed in the absence and presence of inhibitors of the COX (indomethacin), NO (L-NAME+carboxy-PTIO), and EDHF (apamin+charybdotoxin) pathways. RESULTS: Invivo: The adenosine group had, as distinct from the hyperkalemic group, a significantly increased coronary blood flow index 1h after cross-clamp release (from (ml/min/100 g, mean+/-SD) 50.9+/-13.9 to 72.8+/-21.9, p=0.010). The difference was, however, not statistically significant between groups. Invitro: Maximal relaxation without blockers was 27.4+/-10.1% of maximal tension in the adenosine group and 22.2+/-7.5% in the hyperkalemic group. To investigate EDHF-dependent vasodilation the vessel rings were simultaneously treated with indomethacin, L-NAME, and carboxy-PTIO. Maximal relaxation in the hyperkalemic group was then reduced to 47.4+/-17.4% of maximal tension, which was a significant reduction compared to the adenosine group with a maximal relaxation of 20.6+/-8.7% (p=0.028). CONCLUSION: Adenosine instead of supranormal potassium in cold crystalloid cardioplegia increases postcardioplegic myocardial blood flow and preserves EDHF-dependent vasodilation.     

Antegrade crystalloid cardioplegia vs antegrade/retrograde cold and tepid blood cardioplegia in CABG.

BACKGROUND: This study evaluated the myocardial protective strategies in isolated coronary bypass surgeries. METHODS: One hundred and twenty-eight patients were prospectively randomized to 3 techniques of myocardial protection; group I (n = 47) antegrade/retrograde tepid blood cardioplegia, group II (n = 40) antegrade/retrograde cold blood cardioplegia with topical cooling, group III (n = 41) antegrade crystalloid cardioplegia with topical cooling. RESULTS: The incidence of spontaneous defibrillation was significantly higher in group I (p < 0.001) while the incidence of low cardiac output was not different between the 3 groups. The incidence of ventricular arrhythmia was higher in group III (p < 0.016 group III vs I). There was no significant statistical difference in hemodynamic recovery between the 3 groups. CK-MB levels were significantly lower in group I versus the other 2 groups, (p = 0.0013, 0.04). Acid release and oxygen extraction were higher in group II than in group I (p = 0.06) during cardioplegia and reperfusion. Lactate release was less in group I at the release of aortic cross-clamp, and reperfusion. There was no significant difference between the 3 groups in ICU stay, ventilation time, or hospital complications. CONCLUSIONS: Tepid blood cardioplegia showed superiority in metabolic and functional recovery, whereas crystalloid cardioplegia had the highest incidence of postoperative arrhythmias. There was no significant statistical difference between the 3 groups in hospital mortality and morbidity.     

Initial experience with low-potassium cold blood cardioplegia: a clinical comparative study.

This study presents the results of bypass grafting in 96 patients operated on for triple-vessel coronary artery disease between May 1988 and September 1990. In the first 54 patients a cold crystalloid solution was employed, and in the 42 more recent patients cold blood low-potassium cardioplegia was employed. There were no differences in postoperative cardiac index or left ventricular stroke work index. Yet, in patients with impaired prebypass left ventricular stroke work index, postbypass left ventricular performance correlated negatively with duration of aortic cross-clamping in the cold crystalloid group (r = -0.441, p = 0.045). In contrast, no correlation was found in the cold blood low-potassium group (r = 0.125, p = 0.587). The incidence of myocardial infarction, need for inotropic support, and need for intraaortic balloon counterpulsation were similar among the groups. Release of the myocardial isoenzyme creatine kinase-MB from 12 to 30 hours after operation was significantly less in the low-potassium blood cardioplegia group. The use of low-potassium blood cardioplegia resulted in a marked reduction in the operative administration of fluids (1,527 +/- 87 versus 3,511 +/- 148 mL; p less than 0.001). In conclusion, low-potassium cold blood cardioplegia is a simple and effective method of myocardial protection. The fact that left ventricular stroke work index recovery was not dependent on the duration of aortic occlusion and that release of the MB isoenzyme of creatine kinase was reduced in the low-potassium blood cardioplegia group implies better myocardial protection.     

Cold blood versus cold crystalloid cardioplegia for repair of ventricular septal defects in pediatric heart surgery: a randomized controlled trial

BACKGROUND: There is little evidence in the literature on the benefits of cold blood cardioplegia in pediatric cardiac surgery. This study investigates the effects of cold crystalloid versus cold blood cardioplegia on myocardial metabolism, reperfusion injury, and clinical outcomes in patients undergoing ventricular septal defect (VSD) repair. METHODS: Patients were randomly assigned to receive antegrade cold (4 to 6 degrees C) St Thomas's I crystalloid (CCC) or blood (CBC) cardioplegia. Changes in myocardial adenine nucleotides and purine levels were monitored in right ventricular biopsies and postoperative serum troponin I (TnI) and lactate release were measured. RESULTS: Forty patients were randomly assigned to CCC (n = 21; age 21.1 +/- 40.8 months) or to CBC (n = 19; age 27.4 +/- 39.3 months). Patient characteristics were similar in the two groups and there was no mortality. After the ischemic period there was a significant drop in adenosine triphosphate levels compared with control values in the CCC (40.4 +/- 9.9 versus 27.5 +/- 12.5 nmol/mg protein, p = 0.01) but not in the CBC group (40.3 +/- 23.2 versus 37.3 +/- 18.9 nmol/mg protein). The fall was more marked in infants compared with children (40% versus 10%, respectively, p = 0.01). Mean total TnI release was 42% lower in the CBC than the CBC group (95% confidence interval 10% to 62%, p = 0.015). Total TnI release was significantly associated with age (p < 0.001) but as levels in infants in the CBC group were the same as for children, the reduction with age was seen almost entirely in the CCC group. There were no differences in the duration of inotropic support, ventilation time, intensive care unit, or hospital stay in the two groups. CONCLUSION: The use of CBC is associated with less metabolic myocardial ischemic stress and reperfusion injury when compared with CCC in pediatric patients undergoing VSD repair.     

A comparison between ischemic preconditioning,intermittent cross-clamp fibrillation and cold crystalloid cardioplegia for myocardial protection during coronary artery bypass graft surgery

The aim of this study was to compare ischemic preconditioning (IPC) with two established methods of myocardial protection, namely cold crystalloid cardioplegia and intermittent cross-clamp fibrillation (ICCF), in coronary artery bypass graft (CABG) surgery. This was a prospective randomised study. Thirty CABG patients were randomised to receive: (a) St Thomas' cardioplegia solution no. 2; (b) ICCF; or (c) IPC (two 3-min periods of ischemia with 2-min of reperfusion). Surgery was performed under standardised conditions by one surgeon (WBP). The primary endpoint was cardiac troponin T release during the first 72 h after surgery. Mean troponin T at 72 h was significantly lower in the IPC group (0.5 microg/l; p=0.05, ANOVA) compared with the cardioplegia and ICCF groups (2.1 and 1.3 microg/l respectively). This suggests that ischemic preconditioning is superior at limiting myocardial necrosis during CABG, but there is no difference between cold crystalloid cardioplegia and intermittent cross-clamp fibrillation.     

Continuous cold blood cardioplegia improves myocardial protection: a prospective randomized study

BACKGROUND: To assess the influence on myocardial protection of the rate of infusion (continuous vs intermittent) of cold blood cardioplegia administered retrogradely during prolonged aortic cross-clamping. The end-points were ventricular performance and biochemical markers of ischemia. METHODS: Seventy patients undergoing myocardial revascularization for three-vessel disease were prospectively randomized to receive intermittent or continuous retrograde cold blood cardioplegia. Hemodynamic measurements were obtained using a rapid-response thermodilution catheter and included right ventricular ejection fraction, cardiac output, left and right ventricular stroke work index, and systemic and pulmonary vascular resistance. Blood samples were obtained from the coronary sinus before cross-clamp application and immediately after cross-clamp removal for determinations of lactate and hypoxanthine. RESULTS: The left ventricular stroke work index trend was significantly superior (p = 0.038) by repeated-measures analysis in continuous cardioplegia. Other hemodynamic measurements revealed a similar trend. The need for postoperative inotropic drugs support was reduced in continuous cardioplegia. The release of lactate in the coronary sinus after unclamping was 2.30 +/- 0.12 mmol/L after intermittent cardioplegia and 1.97 +/- 0.09 mmol/L after continuous cardioplegia (p = 0.036). The release of hypoxanthine was 20.47 +/- 2.74 micromol/L in intermittent cardioplegia and 11.77 +/- 0.69 micromol/L in continuous cardioplegia (p = 0.002). CONCLUSIONS: Continuous cold blood cardioplegia results in improved ventricular performance and reduced myocardial ischemia in comparison with intermittent administration.     

Adenoviral gene transfer to the heart during cardiopulmonary bypass: effect of myocardial protection technique on transgene expression.

OBJECTIVE: Adenoviral gene transfer to the arrested heart during cardiopulmonary bypass (CPB) is a novel method of allowing prolonged vector contact with the myocardium. In this model we investigated the importance of temperature, duration of arrest and cardioplegia on transgene expression. METHODS: First-generation adenoviral vector (1 x 10(12) total viral particles) containing the transgene for the human beta2-adrenoceptor (Adeno-beta(2)AR) or beta-galactosidase (Adeno-beta(gal)) was delivered to neonatal piglets via the proximal aorta, during simulated cardiac surgery, and allowed to dwell for the cross-clamp duration. Four treatment groups received Adeno-beta(2)AR. Groups A (n=4) and B (n=6) underwent cold crystalloid cardioplegia arrest for 10 and 30 min, respectively, Group C (n=5) underwent warm crystalloid cardioplegia arrest for 10 min, and Group D (n=5) underwent warm fibrillatory arrest for 10 min. Group E (n=6) received Adeno-beta(gal) and underwent cold crystalloid cardioplegia arrest (30 min). Animals were weaned off CPB and recovered for 2 days. Receptor density was assessed in membrane fractions using radioligand binding and compared using the Mann-Whitney U-test. RESULTS: Left ventricular transgene overexpression, as evidenced by elevated betaAR density, following Adeno-beta(2)AR treatment was greatest with cold cardioplegia (Group A 588+/-288.8 fmol/mg; P=0.002 and Group B 520+/-250.9 fmol/mg; P=0.01) versus control (Group E 109+/-8.4 fmol/mg). Overexpression also occurred with warm cardioplegia (Group C 274+/-69.5 fmol/mg; P=0.05) and ventricular fibrillation (Group D 215+/-48.4 fmol/mg; P=0.02) versus control. Comparison of the combined cold cardioplegia groups versus those treated with warm conditions showed a trend towards increased expression with cold conditions (P=0.1). Receptor density was also significantly increased in the right ventricle of animals in Group B (165+/-18.1 fmol/mg; P=0.03) and Group D (181+/-23.4 fmol/mg; P=0.02) versus control (Group E 118+/-5.8 fmol/mg). CONCLUSIONS: Cold crystalloid cardioplegia is not detrimental to gene transfer in vivo. In fact, there was a trend towards increased left ventricular transgene expression when the adenoviral vector was delivered following cold versus warm cardioplegia. Shorter periods of contact with the vector may reduce transgene overexpression. Therefore, gene transfer is possible during cardiac surgery with clinically used myocardial protection techniques.     

Superior myocardial protection with nicorandil cardioplegia.

OBJECTIVE: The ATP-sensitive potassium channel (K(ATP)) activator nicorandil used as cardioplegic agent may protect the left ventricle during cardiac arrest. Nicorandil in cold blood was compared with standard hyperkalemic blood and crystalloid cardioplegia. METHODS: Twenty-one pigs were randomly assigned to three groups: (1) cold hyperkalemic crystalloid (n=7); (2) cold hyperkalemic blood (n=7); and (3) nicorandil as cardioplegia in cold blood (n=7). Left ventricular mechanical performance, pressure-volume area (PVA) and myocardial oxygen consumption (MVO(2)) were measured before and at 1 and at 2 h after 60 min of cold global ischemia on cardiopulmonary bypass using intraventricular pressure-volume conductance catheters, coronary flow probes and O(2)-content difference. RESULTS: The slope (M(w)) of the stroke work end-diastolic volume relationship, the preload recriutable stroke work relationship, was unchanged after ischemia in the nicorandil group, but was reduced to averaged 62.5% (standard deviation 14) of baseline values in both hyperkalemic perfusions (P<0.05). The slope of the MVO(2)-PVA relationship was unchanged after nicorandil cardioplegia while the slope after hyperkalemic blood and crystalloid cardioplegia increased with 33% (P<0.02) and 52% (P<0.02) of baseline values, respectively. CONCLUSIONS: Nicorandil as sole cardioplegic agent in cold blood given intermittently preserves left ventricular contractility and myocardial energetics significantly better than traditional forms of cardioplegia after cardiac arrest.     

Is left ventricular regional wall motion after CABG influenced by cardioplegic protection?]

This clinical study was conducted to determine whether different techniques of cardioplegic protection reflected left ventricular regional wall motion after CABG. A total of 43 patients with more than 90% stenosis of the LAD (seg 6 and/or 7) before CABG, who had patent grafts were allocated to two groups: namely, the crystalloid group, comprised of 23 patients given cold crystalloid cardioplegia and topical ice slush, and the blood group, comprised of 20 patients given tepid blood cardioplegia delivered intermittently antegrade. Each group was divided into two subgroups according to whether the left ventricular regional wall motion showed no change or deterioration after CABG. We also examined the relationship between the grading of the collateral artery before CABG and the postoperative ventricular regional wall motion. The number of patients who showed deterioration after CABG was higher in the crystalloid group than in the blood group (p = 0.008). Moreover, patients in the crystalloid group whose collateral artery had been graded as 0 before CABG tended to show deterioration of left ventricular local wall motion after CABG (p = 0.07). Whereas those patients in the blood group did not. In conclusion, the incidence of deterioration after CABG was higher in the crystalloid group than in the blood group.     

Blood warm reperfusion: a necessary adjunct to heart-valve surgery in low-risk patients?

AIM: The aim of this prospective, randomized study was to determine whether blood warm reperfusion improves myocardial protection provided by cold crystalloid cardioplegia in patients undergoing first-time elective heart-valve surgery, using cardiac troponin I release as the criterion for evaluating the adequacy of myocardial protection. METHODS: Seventy patients with a left ventricular ejection fraction greater than 40% were randomly assigned to 1 of 2 myocardial protection strategies: 1) cold crystalloid cardioplegia with no reperfusion or 2) cold crystalloid cardioplegia followed by 2-minute blood warm reperfusion before aortic unclamping. Cardiac troponin I concentrations were measured in serial venous blood samples drawn immediately prior to cardiopulmonary bypass and after aortic unclamping at 6, 9, 12, and 24 h. RESULTS: Randomization produced 2 equivalent groups. The total amount of cardiac troponin I released (7.17+/- 14.8 mg in the crystalloid cardioplegia with no reperfusion group and 5.82+/-4.66 mg in the crystalloid cardioplegia followed by blood warm reperfusion group) was not different (P > 0.2). Cardiac troponin I concentration did not differ for any sample in either of the 2 groups. The total amount of cardiac troponin I released was higher in patients who required inotropic support (9.14 +/-16.2 mg) than those who did not (4.73+/-4.52 mg; P = 0.009). CONCLUSIONS: Our study shows that adding blood warm reperfusion to cold crystalloid cardioplegia provides no additional myocardial protection in low-risk patients undergoing heart-valve surgery.     

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)     

Aspartate and glutamate-enriched cardioplegia in left ventricular dysfunction

BACKGROUND: The effects of exogenous L-aspartate and L-glutamate-enriched cardioplegia on postoperative left ventricular functions after coronary artery bypass surgery in patients with moderate left ventricular dysfunction (left ventricular ejection fraction [LVEF]= 30-40%) were studied. METHODS: In this prospective randomized study, 22 patients with moderate left ventricular dysfunction (mean LVEF = 37.27%+/- 3.43%), who underwent elective coronary artery bypass surgery, were examined. Isothermic substrate-enriched [L-aspartate and L-glutamate (13 mmol/L)] blood cardioplegia was used in 11 patients (Group AG), and cardioplegia including only potassium and sodium bicarbonate was used in 11 patients (Group C). All hemodynamic parameters for left and right heart were studied in both groups. Total perfusion time was 126.63 +/- 44.91 minutes versus 114.81 +/- 43.66 minutes (p = 0.54). The aortic cross-clamp time was 77.09 +/- 28.02 minutes versus 67.81 +/- 22.77 minutes (p = 0.4), respectively. The amount of cardioplegic solutions were 7218.2 +/- 3043.6 mL versus 5454.5 +/- 3048.1 mL (p = 0.167). Mean number of distal anastomosis were 3 +/- 0.89 versus 2.9 +/- 0.7 (p = 0.793). RESULTS: There was no difference between both groups in intra- and postoperative periods. In coronary sinus blood gas measures, myocardial acidosis caused by the aortic cross-clamp was found to be more severe in the Group C, but delta pH (0.12 +/- 0.14 vs. 0.092 +/- 0.058; p = 0.613) and delta lactate (1.39 +/- 1.03 vs. 1.62 +/- 0.85; p = 0.579) were similar in both groups. Free oxygen radical production caused by aortic cross-clamp was significant in the Group C. Not all myocardial enzymes, but Troponin-T levels were found higher in control group than the study group (0.6 +/- 0.36 vs. 0.36 +/- 0.25; p = 0.1). CONCLUSIONS: Although L-aspartate and L-glutamate favor myocardial metabolic functions, they do not have any affect on myocardial functional recovery in patients with moderate left ventricular dysfunction.     

Terminal warm blood cardioplegia improves the recovery of myocardial electrical activity. A retrospective and comparative study.

OBJECTIVE: The effect of terminal warm blood cardioplegia was analyzed in 191 patients undergoing either coronary artery bypass grafting (CABG) or prosthetic heart valve replacement between Jan. 1990 and Dec. 1995. METHODS: Patients were subdivided into 3 historical cohorts based on the method of myocardial protection: Group A (n = 106), multidose cold crystalloid glucose-potassium cardioplegia, alone; Group B (n = 37), cold crystalloid glucose-potassium cardioplegia plus terminal warm blood cardioplegia, Group C (n = 48), cardioplegia induction with cold crystalloid glucose-potassium cardioplegia, maintenance with multidose cold blood cardioplegia, and terminal warm blood cardioplegia. RESULTS: Of patients undergoing CABG, 5.6% of group A, 70.4% of group B, and 86.7% of group C spontaneously resumed sinus rhythm after aortic declamping, as did 9.1% of group A, 60.0% of group B, and 55.6% of group C of patients undergoing prosthetic heart valve replacement. The incidence of spontaneous recovery was significantly better in groups B and C than in group A (p < 0.05). Over 90% of patients without terminal warm blood cardioplegia developed ventricular fibrillation or tachycardia requiring electrical cardioversion (p < 0.05). Postoperatively, patients without terminal warm blood cardioplegia required temporary epicardial pacing more frequently than those with terminal warm blood cardioplegia (p < 0.05). In patients undergoing prosthetic heart valve replacement, groups B and C, the incidence of postoperative atrial fibrillation was significantly lower than in group A. CONCLUSION: Terminal warm blood cardioplegia thus promoted better postoperative electrophysiological cardiac recovery.     

A clinical comparative study between crystalloid and blood-based St Thomas' hospital cardioplegic solution.

OBJECTIVE: Myocardial protection with blood cardioplegia during cardiac surgery is increasingly preferred, but few studies have compared the protective effects of crystalloid cardioplegia to the same solution with blood as the only variable. This clinical study compared the protective effects of crystalloid or blood-based St. Thomas' Hospital cardioplegic solution No. 1. METHODS: Fifty higher risk patients undergoing elective coronary artery bypass surgery, with an ejection fraction less than 40%, were randomly allocated to receive cold (4 degrees C) intermittent crystalloid St. Thomas' No. 1 cardioplegia (n = 25), or a similar blood-based solution (n = 25) with a haematocrit of 10-12%. We determined (1) peri-operative and post-operative arrhythmias, (2) left and right ventricular function (24 h) using the thermodilution technique, (3) left ventricular high-energy phosphate content sampled before ischaemia, the end of ischaemia and the end of bypass. RESULTS: Pre-operative haemodynamic data, aortic cross-clamp and bypass times were similar in both groups of patients; there was no mortality. At the end of ischaemia there were no differences in ATP content between groups but creatine phosphate was maintained at a significantly (P < 0.007) higher level in the blood-based St. Thomas' cardioplegia group than the crystalloid St. Thomas' cardioplegia group (20+/-2 (SE) vs. 13+/-1 micromol/g dry wt, respectively). Return to spontaneous sinus rhythm was significantly (P = 0.002) increased in the blood-based St. Thomas' cardioplegia group (96%) compared to the crystalloid St. Thomas' cardioplegia group (60%). Early post-operative ventricular dysfunction occurred in both groups, but normal LV function (stroke work index) recovered significantly (P = 0.043) more rapidly (by 2 h) in the blood-based St. Thomas' cardioplegia group of patients. CONCLUSIONS: In a higher risk (EF < 40%) group of patients undergoing elective cardiac surgery, addition of blood to an established crystalloid cardioplegic solution significantly enhanced myocardial protection by reducing arrhythmias, improving rate of recovery of function and maintaining myocardial high-energy phosphate content during ischaemia.     

Retrograde versus antegrade cardioplegia: impact on right ventricular function.

Retrograde cardioplegia administered through the coronary sinus has several documented advantages over antegrade cardioplegia but has been thought to provide inadequate right ventricular myocardial protection. We prospectively compared the effects of retrograde and antegrade cardioplegia on right ventricular performance in patients undergoing myocardial revascularization. Two groups of similar age, extent of disease, and preoperative left ventricular ejection fraction received retrograde (n = 16) or antegrade (n = 14) crystalloid cardioplegia. A right ventricular rapid-response thermistor catheter, previously developed and validated in our institution, was used to measure right atrial pressure, pulmonary artery pressure, right ventricular ejection fraction, end-diastolic volume index, and stroke volume index before bypass (baseline) and at several intervals after bypass. There were no differences in cross-clamp time, heart rate, cardiac enzymes, inotrope requirements, or arrhythmias between the two groups. Right ventricular parameters were equivalent in both groups at all time intervals except 30 minutes after bypass, at which time right ventricular end-diastolic volume index was lower (80 +/- 6 versus 93 +/- 6 mL/m2; p less than 0.05) and right ventricular stroke volume index was higher (35 +/- 3 versus 29 +/- 2 mL/m2, p less than 0.05) in the retrograde group compared with the antegrade group, indicating better right ventricular function with retrograde cardioplegia early after bypass. In both groups, right ventricular end-diastolic volume index was higher than baseline (p less than 0.05) during the first 4 hours after bypass. No other important differences were found.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery.

The authors' recent experimental work has demonstrated that myocardial protection using continuous coronary perfusion with warm beta-blocker-enriched blood avoids myocardial ischaemia and minimizes myocardial oedema formation, thus completely preserving left ventricle function. The purpose of this clinical study was to compare this alternative technique in terms of structural and functional myocardial protection with the routinely used crystalloid Bretschneider cardioplegia. Sixty coronary artery surgery patients were randomized to receive either crystalloid cardioplegia or continuous coronary perfusion with warm blood enriched with the ultra-short acting beta-blocker esmolol. Cardiac function was evaluated using transoesophageal echocardiography (fractional area of contraction) and cardiac metabolism using arterial-coronary sinus lactate concentration difference (a - csD(LAC)). From left ventricular biopsies, the authors determined myocardial oedema, heat-shock-protein-70, intercellular-adhesion-molecule and actin pattern. Patients with crystalloid cardioplegia received 3.6 +/- 0.8 grafts during 64 +/- 20 min cross-clamp time (beta-blocker: 3.5 +/- 0.9 grafts during 68 +/- 22 min; NS). Following cross-clamp removal crystalloid cardioplegia hearts released significant lactate amounts (a- csD(LAC)) - 1.0 +/- 0.6 versus - 0.1 +/- 0.2 mmol/litre in beta-blocker hearts; P < 0.05). In crystalloid cardioplegia hearts, myocardial water content increased from 82.1 +/- 2.1% pre-cardiopulmonary bypass to 83.2 +/- 1.7% at the end of cardiopulmonary bypass (P < 0.05); in beta-blocker hearts myocardial water content remained unchanged (pre-cardiopulmonary bypass: 82.3 +/- 1.9%; end of cardiopulmonary bypass: 82.4 +/- 1.7%; NS). At the end of cardiopulmonary bypass, left ventricular biopsies of beta-blocker hearts showed less structural damage as determined by heat shock protein-70, intercellular adhesion molecule-I and deranged actin cross-striation pattern as compared with crystalloid cardioplegia hearts (P < 0.05). The post-cardiopulmonary bypass fractional area of contraction was similar in both groups (beta-blocker: 65 +/- 14%; crystalloid cardioplegia: 62 +/- 16%); however, beta-blocker patients required less inotropic stimulation (dopamine: beta-blocker: 2.9 +/- 2.5 versus crystalloid cardioplegia: 5.0 +/- 2.3 microg/kg per min; P < 0.05). The data suggest that continuous coronary perfusion with warm esmolol-enriched blood results in better myocardial protection compared with crystalloid cardioplegia. It is concluded that the concept of beta-blocker-induced cardiac surgical conditions may be a useful alternative for myocardial protection during coronary artery surgery.     

Release of cardiac troponin I in antegrade crystalloid versus cold blood cardioplegia.

OBJECTIVE: The purpose of this study was to assess the efficacy of myocardial protection, comparing antegrade crystalloid cardioplegia with cold blood cardioplegia, in patients with preserved left ventricular function who were undergoing elective first coronary artery bypass grafting. Release of cardiac troponin I was used as a marker for the effectiveness of myocardial protection. METHODS: A consecutive series of 62 patients were randomly assigned to receive crystalloid or blood cardioplegia. Cardiac troponin I concentrations were determined in venous blood samples before the operation, immediately after unclamping, at 6, 9, 12, and 24 hours, and daily thereafter for 5 days. RESULTS: Rising levels of troponin I were found in all patients. The time course and peak release were similar in the crystalloid cardioplegia and the blood cardioplegia groups. No patients in either group had electrocardiographic evidence of perioperative myocardial infarction. Cardiac troponin I was able to detect small areas of myocardial damage, not revealed by electrocardiography or creatine kinase MB release. Aprotinin administration was associated with lower cardiac troponin I release in both groups. Cardiac troponin I was lower in patients whose conditions did not require electrical defibrillation after aortic unclamping, irrespective of cardioplegia type. The presence of a main stem lesion was associated with higher cardiac troponin I release only in the crystalloid cardioplegia group. CONCLUSIONS: Antegrade cold blood cardioplegia is equally effective as antegrade crystalloid cardioplegia in a randomized group of patients with preserved left ventricular function who were undergoing elective first coronary artery bypass grafting. Aprotinin administration resulted in lower cardiac troponin I release, whereas electrical defibrillation was related to a higher release irrespective of cardioplegia type. The presence of a main stem lesion resulted in higher cardiac troponin I release in the crystalloid cardioplegia group.     

Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation.

OBJECTIVE: Continuous perfusion of the coronary arteries with beta-blocker (esmolol)-enriched normothermic blood during cardiac surgery has been suggested as an alternative technique for myocardial protection. The aim of the present study was to compare the beta-blocker technique to Buckberg's blood cardioplegia during coronary artery bypass grafting (CABG). METHODS: Sixty patients with coronary artery disease were randomly assigned to either the esmolol group (ES, n = 30) or the blood cardioplegia group (BC, n = 30). During aortic crossclamp ES patients received continuous normothermic coronary perfusion with esmolol-enriched blood. Hearts of the BC group were protected by antegrade cold blood cardioplegia according to Buckberg. We measured left ventricular (LV) contractility using TEE (fractional area of contraction, FAC) and hemodynamic parameters prior to cannulation for cardiopulmonary bypass (CPB), after decannulation, and 4 h postoperatively. Myocardial lactate release was measured prior to aortic cross-clamp, during cross-clamp, and after decannulation. LV biopsies for determination of heat-shock protein (HSP-70), actin pattern and intercellular adhesion-molecule (ICAM-I) as indicators for structural changes were collected prior CPB, at the end of the aortic cross-clamp period, and prior to weaning off CPB. RESULTS: There was no significant difference between both groups with respect to grafts and cross-clamp time. ES hearts did not release lactate during cross-clamp. In contrast, BC hearts released significant amounts of lactate. Post CPB FAC and hemodynamics under similar inotropic stimulation showed no difference between groups, whereas at 4 h post CPB measurements showed slightly better values in the ES group: cardiac index: ES: 2.9+/-0.1 (SEM) versus BC: 2.6+/-0.1 L/min per m2 (P < 0.05); FAC: ES: 55+/-3 versus BC: 48+/-3% (P < 0.05). HSP-70 and actin pattern showed no difference between groups; however, ICAM-I showed a significantly higher degree of structural changes in BC hearts: 18+/-2 versus ES: 11+/-1% (P < 0.05). CONCLUSION: Our data demonstrate that application of the beta-blocker technique during routine CABG was associated with slightly better functional recovery and less structural myocardial alteration as compared with intermittent cold blood cardioplegia, however, both techniques provided equivalent myocardial protection in terms of patient outcome. Future studies are required to investigate if myocardial ischemia minimization by use of the beta-blocker technique may be beneficial in compromized hearts.     

Myocardial preservation using lidocaine blood cardioplegia

Prevention of ventricular fibrillation after aortic unclamping using lidocaine hydrochloride as an additive to cold potassium blood cardioplegia was studied prospectively in 46 patients undergoing elective myocardial revascularization. Patients were similar with respect to age, ventricular function, severity of coronary artery disease, cross-clamp time, completeness of revascularization, frequency of internal thoracic artery grafting, systemic temperature at the time of cross-clamp removal, and mean infusate volume and temperature. Patients receiving lidocaine blood cardioplegia (group 1, 23 patients) had a significant reduction in the incidence of ventricular fibrillation (22% versus 74%; p less than 0.0005) and in the mean number of cardioversion attempts required to defibrillate the heart (0.5 +/- 1.3 versus 1.9 +/- 0.97; p less than 0.0005) after cross-clamp removal compared with controls (group 2, 23 patients). There were no differences between the two groups postoperatively with regard to cardiac enzyme release, hemodynamic measurements, or clinical outcome. Patients receiving lidocaine blood cardioplegia tended to have a lower incidence of new postoperative atrial fibrillation (9% versus 26%). Ventricular function was preserved equally in both groups. We conclude that lidocaine is a safe additive to potassium blood cardioplegia and significantly reduces the incidence of ventricular fibrillation after aortic unclamping.