Cardioplegia Group Research Articles

Warm nondepolarizing adenosine and lidocaine cardioplegia: Continuous versus intermittent delivery

Continuous infusion of warm to normothermic cardioplegia may limit the surgeon's visual field, increase coronary vascular resistance, and lead to potassium-exacerbated ischemia-reperfusion damage. Our aim was to examine the versatility of a new normokalemic, nondepolarizing adenosine-lidocaine cardioplegia during continuous or intermittent infusion at 33 degrees C and compare it with lidocaine cardioplegia. Isolated, perfused rat hearts (n = 6 each group) were arrested at 33 degrees C for 40 or 60 minutes with 200 microm of adenosine and 500 microm of lidocaine in Krebs-Henseleit buffer (10 mmol/L glucose, pH 7.6-7.7 at 37 degrees C) or 500 microm of lidocaine in Krebs-Henseleit buffer for 60 minutes delivered at 60 mm Hg. Times to arrest were 7 to 10 seconds for the adenosine-lidocaine groups and 102 seconds for the lidocaine group (P < .05). Total cardioplegia volumes for intermittent (2 minutes every 18 minutes) and continuous deliveries were 122 to 159 mL and 699 to 922 mL for the 40- and 60-minute adenosine-lidocaine arrest protocols, respectively, and 136 mL for the 60-minute intermittent lidocaine group. In the last 2 minutes of the 40- and 60-minute arrest protocols, the coronary vascular resistance was not significantly different for the hearts arrested with adenosine and lidocaine (0.27-0.32 megadyne/sec/cm(-5)). Significantly higher coronary vascular resistance was found in the lidocaine cardioplegia group (0.38 megadyne/sec/cm(-5)). No significant differences were found between the continuous or intermittent adenosine-lidocaine delivery protocols. Hearts arrested with adenosine and lidocaine recovered 88% to 89% of aortic flow and 109% of coronary flow at 60 minutes of reperfusion after 40-minute arrest, and 77% to 86% of aortic flow and 98% to 109% of coronary flow at 60 minutes of reperfusion after 60-minute arrest. Lidocaine cardioplegia led to significantly lower aortic and coronary flows after 60-minute arrest compared with the intermittent adenosine-lidocaine group. We conclude that adenosine-lidocaine cardioplegia can be delivered intermittently or continuously with similar functional recoveries after a 40- or 60-minute arrest at 33 degrees C. Hearts receiving lidocaine cardioplegia took a significantly longer time to arrest, showed higher coronary vascular resistance, and achieved lower functional recovery than the 60-minute adenosine-lidocaine cardioplegia groups. Intermittent or continuous delivery of adenosine-lidocaine cardioplegia may offer an alternative to current surgical hyperkalemic cardioplegia at warm to normothermic temperatures.

Preclinical evaluation of coronary vascular function after cardioplegia with HTK and different antioxidant additives

Due to limited resources, improvement of preservation solutions is still of great importance in cardiac transplant surgery. New additives with antioxidant properties were tested with respect to coronary function of isolated rat hearts. Bretschneider HTK solution containing none or an antioxidant additive (deferoxamine, trolox or LK 616) was used for 8h cold cardioplegia. After reperfusion with Krebs-Henseleit buffer (KHB), we assessed vascular dilator capacity (bradykinin, adenosine triphosphate, reactive hyperemia), myocardial function (left ventricular developed pressure, heart rate, oxygen consumption) and release of biochemical markers (aspartate aminotransferase, creatine kinase, lactate dehydrogenase, troponin, adenosine). Bradykinin- and adenosine triphosphate-induced vasodilations were largely reduced in hearts stored 8h in traditional HTK as compared to unstored controls. Storage in HTK+LK 616 significantly improved bradykinin-induced vasodilation. Vasodilation toward ATP was best preserved in hearts stored in HTK+deferoxamine. Deferoxamine and trolox, both improved reactive hyperaemic response during reperfusion. Left ventricular pressure development was significantly reduced after 8h cardioplegia, but no difference existed between different cardioplegia groups. Release of biochemical markers of tissue injury was similar in all cardioplegia groups. After storage in HTK+LK 616 (100 microM), however, heart marker release was slightly augmented as compared to HTK. Despite similar myocardial function and marker release, coronary vascular function after cardioplegic storage may profit by addition of iron chelators (or antioxidants) to traditional HTK solution.

Release of Brain Natriuretic-Related Peptides (BNP, NT-proBNP) and Cardiac Troponins (cTnT, cTnI) in On-pump and Off-pump Coronary Artery Bypass Surgery

We studied the kinetic release of cardiac troponins (cTnI and cTnT) and B-type natriuretic peptides (BNP and NT-proBNP) in patients undergoing off-pump or on-pump coronary artery bypass surgery. Twenty-five consecutive patients were prospectively enrolled. The patients were divided into three groups: beating heart (I), and cardiopulmonary bypass (CPB) with warm (II) or cold cardioplegia (III). Plasma samples were obtained before anesthesia induction until the sixth day after surgery. The data were analyzed first for off-pump versus the CPB procedures and second for warm versus cold cardioplegia. The plasma troponin releases appeared to be significantly higher in the CPB groups in comparison to the beating heart group (P < 0.001 and P < 0.002 for cTnI and cTnT peak values, respectively). The peak of the B-type natriuretic peptide release appeared to be more delayed in the groups undergoing CPB than in the beating heart group (day 6 versus days 2 and 4 for NT-proBNP and BNP, respectively). Taken together, our results indicated that the new generation of cTnT assays seemed to be more sensitive than the cTnI assays for the diagnosis of myocardium injury. A lower increase in the cTnT values in the warm cardioplegic group indicated less damage of the myocardium than with cold cardioplegia. Our data also confirm better preservation of the myocardium with off-pump cardiac surgery than with CPB.

Evaluation of myocardial metabolism with microdialysis after protection with cold blood- or cold crystalloid cardioplegia. A porcine model

Objectives. There has been a considerable change in the patient population referred for cardiac surgery in the last decade. More complex and marginal patients require optimized myocardial protection. An insufficient cardioplegic procedure results in anaerobic metabolism during cardiac arrest with subsequent lactate accumulation. Increased lactate level is regarded as a predictor for low cardiac output syndrome. In an acute porcine model we examined two standard cardioplegic methods. Myocardial microdialysis was used to investigate the metabolism during cardioplegic arrest and in the reperfusion period. Methods. Twelve domestic pigs were randomly chosen to receive either cold blood-or cold crystalloid cardioplegia. After midline sternotomy two microdialysis probes were implanted in two different regions of the heart. Cardiopulmonary bypass was initiated, aorta was clamped, and antegrade cardioplegia was delivered. These conditions were maintained for 90 min. Subsequent to myocardial reperfusion the animals were observed for 180 min. Microdialysis and plasma markers to characterize myocardial metabolism, and plasma markers for myocardial failure and necrosis were obtained every 30 min. Results. Lactate concentrations were significantly increased in the cold crystalloid cardioplegia group compared to the cold blood cardioplegia group, in tissue dialysate (p < 0.001) as well as in serum (p = 0.018). Pyruvate concentrations in the dialysate were significantly increased in the cold crystalloid cardioplegia group compared to the cold blood cardioplegia group (p = 0.008). There were no significant differences in dialysate concentrations of glycerol. Plasma markers for myocardial failure (Brain Naturetic Peptide) and for myocardial necrosis (Cardiac Troponin T) showed no differences between the groups. Conclusion. The results indicate that cold blood cardioplegia offers superior protection of the heart, in terms of more rapid normalization of myocardial metabolism. The microdialysis technique seems to have a high sensitivity and ability to detect even minor metabolic changes. This enhances the possibility of designing a myocardial protection, which might lower morbidity and mortality risk.

Warm induction cardioplegia and reperfusion dose influence the occurrence of the post CABG TnI level

As a new biochemical marker cardiac troponin-I (CTnI) is a more sensitive and specific marker for detection of differences in myocardium injuries than other chemical enzymes. This study investigates the effect of warm induced and reperfusion blood cardioplegia on the release of troponin-I during the CABG. In our research, 24 three-vessel coronary artery disease (CAD) patients underwent CABG and were divided into two groups randomly: Group of warm induction and reperfusion blood cardioplegia (Group W N=12); Group of simple warm induction and no reperfusion (Group C N=12). The effect of myocardium protection of the two methods of myocardium protection were evaluated by clinical outcome, CTnI. Serial venous blood samples were obtained before and after surgery. In both groups, there were no differences in operative parameters. The level of CTnI increased from postoperative 6 h (P<0.05), reached peak in 24 approximately 72 h and recovered postoperatively on 6th day in both groups. Compared with group C, the plasma concentrations of CTnI in group W were significantly lower at 6 h, 24 h and 72 h (P<0.01). The results suggest that the method of warm induction and reperfusion blood cardioplegia reduces the leakage of CTnI than group of simple warm blood cardioplegia in CABG patients.

Low-Dose Histidine-Tryptophan-Ketoglutarate Solution for Myocardial Protection

The effect of histidine-tryptophan-ketoglutarate (HTK) solution for myocardial protection has been shown in experimental and clinical studies using long ischemic times and high dosages. In our study we compared myocardial protection in isolated coronary bypass with a short period of ischemia using low dosage HTK and cold crystalloid cardioplegia. Each group contained 21 coronary artery disease patients. Cardioplegic solutions were administered antegrade in 10 to 15 mL/kg in one shot. This dosage of HTK was lower than that mentioned in the literature. We measured malondialdehyde, lactate, creatine kinase, creatine kinase-MB, and troponin-I levels. Aortic clamping time in the HTK group 33.9 ± 8.2 minutes, versus 36.2 ± 11.3 minutes in the crystalloid cardioplegia group ( P > .05). Levels of creatine kinase and malondialdehyde were lower in HTK group at 24 hours and 2 minutes, respectively. Lactate levels were lower in the crystalloid cardioplegia group at 2 minutes in the coronary sinus serum sample, but there were no statistically differences among ischemic serum markers in both groups. Only intervals between aortic clamping and cardiac arrest were statistically meaningful (HTK 63.3 ± 14.7 seconds versus crystalloid cardioplegia 53.6 ± 15.6 seconds, P = .044). Our study shows that use of low-dose HTK for short clamping time operations is as successful for myocardial protection as crystalloid cardioplegia. Longer times for fibrillation can be explained with the low levels of potassium in HTK solution, but this length did not cause a biochemical or clinical difference.

Differential myocardial Protein Kinase C (PKC) isoform activity in cardioplegic arrest and hypothermic preservation

Body. Myocardial protection during donor organ procurement remains limited. PKC is thought to be an important mediator of ischemia-reperfusion injury. Our objective was to study isoform-specific PKC activity in a murine model of cardioplegic arrest and hypothermic preservation as utilized in cardiac transplantation. Murine hearts were isolated and perfused on an ex vivo system at normothermic conditions. Baseline hemodynamic measurements were taken after 30 min of perfusion. Hearts were arrested with 3 ml of University of Wisconsin preservation solution delivered via the aortic root ( n = 6) or perfused with 3 ml of saline ( n = 6) and stored for 4 h at 4°C. All hearts were then reperfused at 37°C for 1 h and hemodynamic indices were measured. Activity of PKC isoforms α, ϵ, and δ were measured by protein immunoblotting and compared between groups. All data are expressed as mean ± SEM. Values between groups were compared using Student’s t-test. Postischemic recovery of left ventricular developed pressure (LVDP) was greater in the cardioplegia (CP) versus saline (SA) group: 63 ± 8% versus 26 ± 4%, P < 0.01. Following reperfusion, there was no change in myocardial ϵPKC activity as measured by membrane to cytoplasmic protein ratio between the CP and SA groups: 0.42 ± 0.13 versus 0.56 ± 0.19, P > 0.05. In contrast, αPKC and δPKC isoform activity were inhibited to near baseline levels in the CP versus SA group: 0.72 ± 0.14 versus 1.0 ± 0.10 and 1.2 ± 0.20 versus 2.4 ± 0.29, P < 0.05 between groups. Based on these data, strategies to inhibit myocardial activity of αPKC and δPKC isoforms may be useful in improving cardiac function following prolonged donor heart preservation. In addition, ϵPKC does not appear to play a significant role in this model of cardioplegic arrest and hypothermic preservation.

Cardioprotective effects and the mechanisms of terminal warm blood cardioplegia in pediatric cardiac surgery

Objectives Terminal warm blood cardioplegia has been shown to enhance myocardial protection in adult patients. However, the cardioprotective effects and the mechanisms of terminal warm blood cardioplegia in pediatric heart surgery were still unknown. Methods One hundred three consecutive patients were prospectively randomized to one of two groups. In the control group (n = 52), myocardial protection was achieved with intermittent hyperkalemic cold blood cardioplegia and topical cardiac cooling. In the terminal warm blood cardioplegia group (n = 51), this was supplemented with terminal warm blood cardioplegia before the aorta was declamped. Arterial and coronary sinus blood samples were analyzed to determine myocardial energy metabolism and tissue injury. Results There were no significant differences between the two groups in age (5.5 ± 0.6 years in the control group vs 5.6 ± 0.5 years in the terminal warm blood cardioplegia group), body weight (17.2 ± 1.4 kg in the control group vs 19.8 ± 1.7 kg in the terminal warm blood cardioplegia group), percentage of cyanotic heart diseases (50% in the control group vs 51% in the terminal warm blood cardioplegia group), number of patients who required right ventriculotomy (33% in the control group vs 39% in the terminal warm blood cardioplegia group), cardiopulmonary bypass time (194 ± 12.1 minutes in the control group vs 177 ± 8.6 minutes in the terminal warm blood cardioplegia group), aortic crossclamp time (83.3 ± 5.9 minutes in the control group vs 82.3 ± 5 minutes in the terminal warm blood cardioplegia group), lowest rectal temperature (27.4 ± 0.3°C in the control group vs 28.1 ± 0.3°C in the terminal warm blood cardioplegia group), and myocardial temperature (9.6 ± 0.6°C in the control group vs 9.6 ± 0.7°C in the terminal warm blood cardioplegia group). Spontaneous defibrillation occurred after reperfusion in 80% in the terminal warm blood cardioplegia group, which was significantly ( P < .05) higher than the control group (62%). The lactate extraction rate at 60 minutes of reperfusion was significantly ( P < .05) higher in the terminal warm blood cardioplegia group (9.0 ± 2.8%) than the control group (−3.3 ± 2.4%). The postreperfusion values of cardiac troponin T (7.4 ± 0.6 ng/mL vs 11.2 ± 1.0 ng/mL at 6 hours; 4.6 ± 0.6 ng/mL vs 9.3 ± 1.6 ng/mL at 18 hours) and heart-type fatty acid binding protein (137 ± 28 ng/mL vs 240 ± 30 ng/mL at 2 hours; 88 ± 19 ng/mL vs 162 ± 26 ng/mL at 3 hours) were significantly ( P < .05 vs the control group) lower in the terminal warm blood cardioplegia group. Conclusion Terminal warm blood cardioplegia enhances myocardial protection in pediatric cardiac surgery by an improvement in aerobic energy metabolism and a reduction of myocardial injury or necrosis.

Conduction disturbances in coronary artery bypass surgery

Background: Conduction disturbances are very common after coronary artery bypass grafting (18–45%). Long cross-clamp time, method of cardioplegia, depth of hypothermia, and patient age are some of the risk factors. We planned this study to ascertain the effect of crystalloid or tepid blood cardioplegia (CP) on conduction disturbances. Methods: One hundred patients were randomly divided into two groups. The first group received tepid blood CP and the second received cold crystalloid CP. St. Thomas II CP was used as CCP and the same CP was mixed with blood with a ratio of 4:1 in the tepid CP group. In both groups as an initial bolus, a 10 to 15 ml/kg CP was infused with a pressure of 75 mmHg. Additionally, 400 ml of CP were given every 20 min during the cross clamping period in addition to infusion of 50–100 ml of CP after each distal anastomosis. Blood samples for CK, CK-MB, LDH and Troponin T measurements were obtained at induction, before bypass, after cross clamping, before de-clamping, after de-clamping and after bypass. Postoperative ECGs were analyzed by a cardiologist. Results: There were no deaths in both groups but the mean hospitalization was 8.4±1.7 days in group I, and 14.4±3.1 days in group II ( P=0.004). Although there were significant rises in CK, CK-MB, LDH and Troponin T levels in both groups after CPB or de-clamping, the difference in increment between the two groups was not significant. Twelve patients in group II (24%) developed new fascicular blocks, four of these caused hemodynamic instability and needed inotropic treatment but only one was discharged with LAHB. Four patients in group I (8%) also developed new conduction disturbances within the first hour, but all completely resolved. Incidence of conduction disturbances was significantly increased in the crystalloid CP group ( P=0.019). Conclusion: There were no significant differences in cardiac enzyme measurements between cold crystalloid and tepid blood CP, but crystalloid CP caused more fascicular blocks. We conclude that myocardial protection was equal in both cardioplegia methods whereas conduction disturbances have been assumed to be caused by cold injury to the conduction tissues.

The short-term and long-term effects of warm or tepid cardioplegia

Background: Clinical studies of myocardial protection rarely identify differences in hard clinical outcomes after surgery, either early or late, because most trials lack sufficient statistical power to deal with low-frequency events. Methods: Prospectively collected data concerning all isolated coronary bypass operations from November 1989 to February 2000 were analyzed to determine the effects of cold blood cardioplegia and warm or tepid blood cardioplegia on early and late outcomes after surgery. Warm blood cardioplegia was used in 4532 patients, whereas cold blood cardioplegia was used in 1532. The allocation of patients to receive warm blood cardioplegia and cold blood cardioplegia was random in 749 cases and according to surgeon preference in the remainder. Most patients in the cold blood cardioplegia group had surgery earlier in the time course of the study, and most in the warm blood cardioplegia group underwent surgery later. Results: Perioperative death, myocardial infarction, and death or myocardial infarction were all more common in the cold blood cardioplegia group than in the warm blood cardioplegia group (death 2.5% vs 1.6%, P =.027, adjusted odds ratio 1.45, 95% confidence interval 0.95-2.22, P =.09; myocardial infarction 5.4% vs 2.4%, P <.0001, adjusted odds ratio 1.86, 95% confidence interval 1.36-2.53, P <.0001; death or myocardial infarction 7.3% vs. 3.8%, P <.0001, adjusted odds ratio 1.70, 95% confidence interval 1.30-2.21, P <.0001). Actuarial survival at 60 months was 91.1% ± 1.4% in the warm blood cardioplegia group and 89.9% ± 1.3% in the cold blood cardioplegia group (P =.09), whereas freedom from death or myocardial infarction was 84.7% ± 1.8% and 83.2% ± 1.6%, respectively (P =.16). In multivariate models, cold blood cardioplegia was associated with poorer survival (risk ratio 1.30, 95% confidence interval 0.96-1.75, P =.09) and freedom from any death or late myocardial infarction (risk ratio 1.93, 95% confidence interval 1.56-2.39, P =.0001). Conclusions: In 6064 patients undergoing isolated coronary artery bypass grafting, warm or tepid blood cardioplegia may be associated with better early and late event-free survivals than is cold cardioplegia.J Thorac Cardiovasc Surg 2003;125:711-20

Abstracts

Abstracts

Warm and tepid cardioplegia: Do they provide equal myocardial protection?

Background Cardiac troponin I (CTnI) has been shown to be a marker of myocardial injury. The aim of this prospective, randomized study was to compare intermittent antegrade warm cardioplegia with tepid blood cardioplegia in patients undergoing first elective coronary artery bypass graft, using CTnI release as the criterion for evaluating the adequacy of myocardial protection. Methods Seventy patients were randomly assigned to one of two cardioplegia groups. CTnI concentrations were measured in serial venous blood samples drawn immediately before cardiopulmonary bypass and after aortic unclamping at 6, 9, 12, and 24 hours. Analysis of covariance with repeated measures was performed to test the effect of the type of cardioplegia and time on CTnI concentration. Results The total amount of CTnI released (8.23 ± 20.5 μg in the warm group and 3.19 ± 2.4 μg in the tepid group) was not statistically different ( p = 0.23). The CTnI concentration did not differ for any sample in either of the two groups when adjusted on ejection fraction and the number of preoperative myocardial infarctions ( p = 0.06). No patient in the tepid group versus 4 patients in the warm group showed CTnI evidence of perioperative myocardial infarction ( p = 0.12). Conclusions Our study showed no preference for warm or tepid cardioplegia in terms of myocardial protection, either for clinical or biological data.

Ca2+ channel remodeling in perfused heart: Effects of mechanical work and interventions affecting Ca2+ cycling on sarcolemmal and sarcoplasmic reticulum Ca2+ channels.

We investigated whether changes in cardiac work or in Ca2+ fluxes may affect the expression of sarcolemmal or sarcoplasmic reticulum Ca2+ channels (DHPRs and RyRs, respectively). Isolated rat hearts were perfused at low Ca2+ concentration (0.8 mM instead of 1.5 mM), at low preload (5 cm instead of 20 cm), in the presence of 100 nM nifedipine or with a cardioplegic solution. After 60 min, hypocalcemic perfusion produced significant reduction in [3H]-PN 200-110 and [3H]-ryanodine binding, due to approximately 30% reduction in Bmax (P<0.01), with unchanged Kd. Such modifications were reversible. Similar results were obtained in the nifedipine and cardioplegia groups. Low preload perfusion produced similar contractile effects as hypocalcemic perfusion, but it had no effect on radioligand binding. After hypocalcemic perfusion, DHPR and RyR gene expression, evaluated by RT-PCR, were not modified. Chelerythrine (protein kinase C inhibitor) and lavendustin C (Ca2+/calmodulin-dependent protein kinase II inhibitor), but not H-89 (protein kinase A inhibitor), abolished the effects of hypocalcemic perfusion on [3H]-PN 200-110 and [3H]-ryanodine binding. We conclude that reduced Ca2+ entry and/or intracellular Ca2+ cycling determines DHPR and RyR remodeling through posttranslational protein modifications. Both protein kinase C and Ca2+/calmodulin-dependent protein kinase II appear to play a role in this phenomenon.

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

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. 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. 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). 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.

Retrograde crystalloid cardioplegia preserves left ventricular systolic function better than antegrade cardioplegia in patients with occluded coronary arteries

Objective: To investigate retrograde and antegrade crystalloid cardioplegia in terms of cardiac cooling and postoperative cardiac function. Design: Prospective, randomized, and blinded. Setting: University hospital. Participants: Twenty male patients with triple-vessel disease and proximal occlusion of the circumflex or the left anterior descending coronary artery. Interventions: Left ventricular ejection fraction at rest and during exercise was evaluated by nuclear ventriculography the day before and 3 months after surgery. After induction of anesthesia and hourly for the first 5 postoperative hours, hemodynamic, echocardiographic, and electrocardiographic data were acquired. Myocardial temperature was measured with needle thermistors in 3 myocardial regions. Measurements and Main Results: Demographic and temperature data were analyzed by t-test. Hemodynamic and echocardiographic data were analyzed by analysis of variance. The groups were similar in baseline characteristics. Retrograde cardioplegia cooled the region distal to an occlusion better than antegrade cardioplegia (9.6°C ± 4.8°C v 21.8°C ± 5.9°C; p < 0.01). Hemodynamic, echocardiographic, and electrocardiographic data did not differ between the groups. Three months after surgery, the retrograde cardioplegia group showed a higher left ventricular ejection fraction at rest (58% ± 10% v 47% ± 10%; p < 0.02) and during exercise (58% ± 13% v 47% ± 10%; p ± < 0.05) compared with the antegrade cardioplegia group. Conclusions: Retrograde cardioplegia provides more homogenous myocardial cooling than antegrade cardioplegia in hearts with coronary artery occlusions. The use of retrograde cardioplegia seems to benefit long-term left ventricular function. Copyright © 2000 by W.B. Saunders Company

Cardioplegia and ischemia in the canine heart evaluated by 31P magnetic resonance spectroscopy

Background. Warm continuous blood cardioplegia provides excellent protection, but must be interrupted by ischemic intervals to aid visualization. We hypothesized that (1) as ischemia is prolonged, the reduced metabolic rate offered by cooling gives the advantage to hypothermic cardioplegia; and (2) prior cardioplegia mitigates the deleterious effects of normothermic ischemia. Methods. Isolated cross-perfused canine hearts underwent cardioplegic arrest followed by 45 minutes of global ischemia at 10°C or 37°C, or 45 minutes of normothermic ischemia without prior cardioplegia. Left ventricular function was measured at baseline and during 2 hours of recovery. Metabolism was continuously evaluated by phosphorus-31 magnetic resonance spectroscopy. Results. Adenosine triphosphate was 71% ± 4%, 71% ± 7%, and 38% ± 5% of baseline at 30 minutes, and 71% ± 4%, 48% ± 5%, and 39% ± 6% at 42 minutes of ischemia in the cold ischemia, warm ischemia, and normothermic ischemia without prior cardioplegia groups, respectively. Left ventricular systolic function, left ventricular relaxation, and high-energy phosphate levels recovered fully after cold cardioplegia and ischemia. Prior cardioplegia delayed the decline in intracellular pH during normothermic ischemia initially by 9 minutes, and better preserved left ventricular relaxation during recovery, but did not ameliorate the severe postischemic impairment of left ventricular systolic function, marked adenosine triphosphate depletion, and creatine phosphate increase. Left ventricular distensibility decreased in all groups. Conclusions. When cardioplegia is followed by prolonged ischemia, better protection is provided by hypothermia than by normothermia. Prior cardioplegia confers little advantage on recovery after prolonged normothermic ischemia but delays initial ischemic metabolic deterioration, which would contribute to the safety of brief interruptions of warm cardioplegia.

Insulin cardioplegia for elective coronary bypass surgery

Background: Improved methods of myocardial preservation are required to reduce the morbidity and mortality of coronary bypass surgery for high-risk subgroups. Metabolic stimulation with insulin, glucose solutions, or both has been proposed as a method to preserve the ischemic myocardium. We performed a prospective, double-blind, randomized trial to evaluate the effects of insulin and glucose as cardioplegic additives when used as part of a tepid continuous blood cardioplegic strategy. Methods: We randomized 56 male patients undergoing elective isolated coronary bypass surgery to 1 of 4 cardioplegic groups containing either 42 or 84 mmol/L glucose with or without 10 IU/L of insulin. Perioperative assessments of myocardial metabolism and left ventricular function were performed. Results: Insulin-enhanced cardioplegia was associated with beneficial effects on both myocardial metabolic and functional recovery after cardioplegic arrest. Insulin’s effect was independent of the ambient glucose concentration. Conclusions: Cardioplegic formulations containing a 42 mmol/L concentration of glucose and a 10 IU/L concentration of insulin provide significant benefit to patients undergoing isolated coronary bypass surgery. The clinical effect of these formulations will need to be assessed in high-risk subgroups of patients, such as those with unstable angina, recent myocardial infarction, or poor left ventricular function. (J Thorac Cardiovasc Surg 2000;119:1176-84)

Mechanisms of myocardial protection by adenosine-supplemented cardioplegic solution: Myofilament and metabolic responses

Objective: Adenosine supplementation of cardioplegic solutions in cardiac operations improves postarrest myocardial recovery after cardioplegic arrest and reperfusion; however, the mechanism of the action of adenosine remains unknown. We tested the hypotheses that adenosine-supplemented cardioplegic solution improves myofibrillar protein cooperative interaction and increases myocardial anaerobic glycolysis. Methods: The hearts of male Sprague-Dawley rats were randomized to undergo 120 minutes of cardioplegic arrest with 1 of 3 cardioplegic solutions: (1) St Thomas’ Hospital No. 2 cardioplegic solution (St Thomas group), (2) St Thomas’ Hospital No. 2 cardioplegic solution plus adenosine (100 μmol/L) (adenosine group), and (3) St Thomas’ Hospital No. 2 cardioplegic solution plus adenosine (100 μmol/L) plus the nonspecific adenosine receptor antagonist 8-p -sulfophenyltheophylline (50 μmol/L) (sulfophenyltheophylline group). A fourth group of hearts underwent no cardioplegic arrest. Results: Systolic and diastolic functional recovery was improved in the adenosine group compared with that in the other two groups, independent of coronary flow. Adenosine supplementation of cardioplegic solution prevented the decrease in myofibrillar protein cooperative interaction seen after cardioplegic arrest and reperfusion (St Thomas and sulfophenyltheophylline groups). Adenosine-supplemented cardioplegic solution also caused significantly increased anaerobic glycolysis during cardioplegic arrest. These responses were blocked in the sulfophenyltheophylline group. Conclusions: The changes in myocardial glycolytic activity and myofilament cooperativity coincided with functional recovery in the three cardioplegia groups and may represent mechanisms underlying protection with adenosine-supplemented cardioplegic solution. (J Thorac Cardiovasc Surg 2000;119:601-9)

Intermittent antegrade warm blood cardioplegia for CABG: extended interval of cardioplegia

Background. Intermittent delivery of warm cardioplegia provides a bloodless surgical field, but it is clinically important to evaluate the periods of normothermic ischemia. The aims of this study are to compare intermittent antegrade warm blood cardioplegia (IAWBC) with intermittent antegrade cold blood cardioplegia (IACBC) groups in terms of myocardial protection, and also to evaluate whether the length of ischemic time in the IAWBC group has an effect on myocardial dysfunction.Methods. This study is based on a retrospective review of patients who underwent elective coronary artery bypass surgery: 162 consecutive patients with IAWBC and 107 consecutive patients with IACBC.Results. The creatinine kinase peak was smaller in the IAWBC group compared with the IACBC group (p < 0.0001). The cardiac index after cardiopulmonary bypass was higher in the IAWBC group (p < 0.02), and the amount of inotropic support required to wean from cardiopulmonary bypass was less in the IAWBC group compared with the IACBC group (p < 0.0001).Conclusions. IAWBC with 30 minutes of ischemia provides to be clinically acceptable myocardial protection for coronary bypass 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. (J Thorac Cardiovasc Surg 1999; 118:452-9)