Background: Most of the studies conducted have investigated the beneficial effects of ischemic preconditioning on normothermic myocardial ischemia. However, the effect of preconditioning could be attenuated through the use of multidose cold cardioplegia as practiced in contemporary clinical heart surgical procedures. The purpose of this study was to investigate whether preconditioning improves postischemic cardiac function in a model of $25^{\circ}C$ moderate hypothermic ischemic heart induced by cold cardioplegia in isolated rat hearts. Material and Method: The isolated Sprague-Dawley rat hearts were randomly assigned to four groups All hearts were perfused at 37$^{\circ}C$ for 20 minutes with Krebs-Henseleit solution before the baseline hemodynamic data were obtained, Group 1 consisted of preconditioned hearts that received 3 minutes of global ischemic preconditioning at 37$^{\circ}C$, followed by 5 minutes of reperfusion before 120 minutes of cardioplegic arrest (n=6). Cold (4$^{\circ}C$) St. Thomas Hospital cardioplegia solution was infused to induce cardioplegic arrest. Maintaining the heart at $25^{\circ}C$, infusion of the cardioplegia solution was repeated every 20 minutes throughout the 120 minutes of ischemic period. Group 2 consisted of control hearts that underwent no manipulations between the periods of equilibrium and 120 minutes of cardioplegic arrest (n=6). After 2 hours of cardioplegic arrest, Krebs solution was infused and hemodynamic data were obtained for 30 minuts (group 1, 2: cold cardioplegia group). Group 3 received two episodes of ischemic preconditioning before 30 min of 37$^{\circ}C$ normothermic ischemia and 30 minutes of reperfusion (n=6) Group 4 soloed as ischemic controls for group 3 (group 3, 4: warm ischemia group). Result: Preconditioning did not influence parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP) and left ventricular dp/dt (LV dp/dt) in the cold cardioplegia group. (p=NS) However, preconditioning before warm ischemia attenuated the ischemia induced cardiac dysfunction, Improving the LVSP, LVEDP, RPP, and LV dp/dt. Less leakage of CPK and LDH were observed in the ischemic preconditioning group compared to the control group (p<0.05). Conclusion: Ischemic preconditioning improved postischemic cardiac function after warm ischemia, but did not protect cold cardioplegic hearts.
Hypothermia is widely acknowledged as fundamental component of myocardial protection during cardiac operations. Although it prolongs the period of ischemic arrest by reducing oxygen demands, hypothermia is associated with a number of major disadvantages, including its detrimental effects on enzymatic function, energy generation, and cellular integrity. The ideal way to rotect the heart is to electromechanically arrest it and perfus it with blood that is aerobic arrest. However alternative technique has been developed, based on the principles of electromechanical arrest and normothermic aerobic perfusion using continuous warm blood cardioplegia. To determine if continuous warm blood cardioplegia was beneficial in clinical practice during valvular surgery, we studied two groups of patients matched by numbers and clinical characteristics. Group included is 31 patients undergoing valvular surgery who received intermittent cold crystalloid cardioplegia. Group II included 30 patients undergoing valvular surgery who received continuous warm blood cardioplegia. Our results suggest that the heartbeat in 100% of patients treated with continuous warm blood cardioplegia converted to normal sinus rhythm spontaneously after the removal of the aortic cross-clamp, compared to only 31% of the cold cardioplegia group. After operation, pericardial closure rate was 90% area in the warm group, compared to 35% area in the cold group. 12 hours after the operation, the total amount of urine output in the warm group was greater than that in the cold group(2863${\pm}$127 ml versus 2257${\pm}$127 ml; p<0.05). After the operation, left diaphragmatic elevation developed in 55% of the cold group but in 0% of the warm group. CK-MB level in the warm group was significantly lower than cold group(2.28${\pm}$0.62 versus 9.96${\pm}$2.12; p<0.01) 1 hour after operation and CK-MB level in the warm group was significantly lower than cold group(1.80${\pm}$1.01 versus 6.00${\pm}$1.74; p<0.05) 12hours after operation. Continuous warm blood cardioplegia is at least as safe and effective as hypothermic technique in patients undergoing cardiac valvular surgery. Conceptually, this represents a new approach to the problem of maintaining myocardial preservation during cardiac operations.
We have investigated whether the supplement of magnesium to cold blood cardioplegia improves myocardial protection. Sixty patients scheduled for elective valvular heart surgery were randomly assigned to a control group (n=30) which received conventional cold blood cardioplegia and an Mg group (n=30) which received cold blood cardioplegia supplemented with 2 g of magnesium sulfate. Electrolytes levels including $Mg^{++}$, hematological and biochemical variables, cytokines, myocardial marker levels, and postoperative outcomes were compared between two groups before, during or idler operation. $Mg^{++}\;and\;Ca^{++}$ levels in the Mg group were higher than those of the control group after surgery. The total WBC counts, CK-MB, troponin-I and Interleukin-6 levels in the Mg group were lower than those of the control group after surgery. Postoperative incidence of atrial fibrillation was lower in the Mg group compared with the control group. These results showed that $Mg^{++}$ attenuated inflammatory reaction, myocardial damage, and hypomagnesemia during valvular surgery and reduced postoperative arrhythmia incidence without side effects.
Fructose-l, 6-diphosphate as an additive to cold crystalloid cardioplegia [St. Thomas sol.] was studied prospectively in 60 patients undergoing open heart surgery from January 1, 1991, to June 30, 1991. Thirty patients received cardioplegia with FDP[group I ] and 30 patients received cardioplegia without FDP [group II ]. There were no differences between two groups pre-operatively with regard to age, heart disease, cross-clamp time, cardiac enzymes, or hemodynamic measurements [p>0.05]. Cardiopulmonary bypass was established using ascending aorta and vena cava cannulation employing moderate systemic hypothermia [30oC nasopharyngeal temperature] and hemodilution All patients received cardioplegia through the aortic root at aortic root pressure of 80mm Hg. The composition of the cardioplegic solution and its delivery were identical in both groups except for the addition of FDP[1.5 mg/mL] in group I. The cardioplegic infusate consisted of St. Thomas Hospital solution. The initial dose was infused through the aortic root. Topical myocardial cooling with saline slush was employed in all patients. Recorded operative data were cardiopulmonary bypass and cross-clamp times, amount of cardioplegic infusate. Blood samples for assessment of lactate dehydrogenase [LDH], creatine kinase [CK] and transaminases [GOT, GPT] were obtained before and at 1,2,3,7th postoperative period. Better myocardial protection effect was noted in group I than group II with respect to the % change of cardiac enzymes, although the differences were not significant. We conclude that FDP is a safe additive to crystalloid cardioplegia and may be beneficial in open heart surgery patients.
Hypothermic cardioplegia is a well established method to optimize myocardial preservation during ischemic arrest, and it has been demonstrated that oxygenation of crystalloid cardioplegic solutions markedly enhances myocardial protection, The addition of a small amount of red blood cells to a crystalloid cardioplegic solutions improves capillary perfusion. Considering these results, we changed our cardioplegic solution from cold oxygenated crystalloid[Group 2] to cold oxygenated diluted blood[Group 1]. In this investigation, we examined the effects of two hypothermic potassium cardioplegic solutions on myocardial preservation in 50 patients[30 of Group 1 and 20 of Group 2] of child age group. Factors considered preoperatively included age, sex, body weight, preoperative diagnosis, and they showed no statistical differences, Intraoperative factors considered included duration of cardiopulmonary bypass, duration of aortic occlusion, operative mortality, which also revealed no statistically significant differences, We measured the serum levels of GOT[glutamate oxaloacetate transaminase] and CPK [creatine phosphokinase] during the first two days postoperatively, which, in both groups, showed significantly higher values until postoperative 1 day, and decreasing tendancy thereafter, however we failed to find any significant difference between two groups regarding the serum levels of those enzymes each day. Time for extubation and use of inotropics also revealed no significant differences. Defibrillation was needed less in Group 1 than in Group 2[p<0.05], and one case of supraventricular tachyarrhythmia occured in Group l. We conclude that cold oxygenated diluted blood cardioplegia provides no less preservation than does an oxygenated crystalloid cardioplegic solution in child age group.
Using an isolated rat heart preparation under both aerobic and ischemic condition, we observed the myocardial protective effect of verapamil cardioplegia. Isolated working hearts were subjected to global ischemia at 25oC. Before ischemic arrest, rat hearts were treated with cold potassium cardioplegic solution [K=30 mEq/L] in control group and cold potassium cardioplegic solution added with verapamil [1 mg/L] in other group. After 30 min. of ischemia, hemodynamic parameters and creatine kinase leakage in coronary effluent were observed. Verapamil group exhibited greater percent of recovery in aortic pressure [p<0.01], aortic flow [p<0.01], and stroke volume [p<0.05]. Although there were no significant difference in creatine kinase leakage and the percent recovery of cardiac output between verapamil and control group, verapamil group showed better myocardial function. But the time to recover regular sinus rhythm was significantly [p<0.001] prolonged in verapamil group.
Background: The aim of this study is to define the cardioprotective effects (hemodynamic, cytochemical and ultrastructural of the newly developed Histidine-Tryptophan-Ketoglutarate (HTK) cardioplegia compared to DelNido cardioplegia. Material and Method: Seventy-nine isolated rat hearts were divided into three groups on the basis of techniques of cardioplegia infusion. Twenty-eight hearts (Group 1) were flushed with cold DelNido cardioplegia with every 40 minutes for 2 hours. Twenty-seven hearts (Group 2) were flushed with cold HTK cardioplegia for once during the 2 hours. Twenty-four hearts (Group 3) were flushed with cold HTK cardioplegia with every 40 minutes for 2 hours. Heart rate, left ventricular developed pressure (LVDP), changes of + dp/dt max, coronary flow, and rate-pressure product value were measured at pre-ischemic, post-reperfusion 15 minutes, 30 minutes, and 45 minutes for hemodynamic study. Aspartate aminotransferase (AST), lactate dehydrogenase (LD), creatine kinase (CK), CK-MB, troponin-I, myoglobin, and lactate were measured at pre-ischemic and post-reperfusion 45 minutes for cytochemical parameters. Mitochondrial scores were counted in 3 cases from each group for ultrastructural assessment. Result: In hemodynamic study, there were no significant differences among group 1, group 2, and group 3. However, the decrease values of heart rate in group 2 and 3 exhibited significantly lower values than in group 1. In cytochemical study, there were no significant differences among group 1, group 2, and group 3. However, the increase values of lactate in group 2 and 3 exhibited significantly lower values than in group 1. In ultrastructural assessment, the mean myocardial mitochondria scores in group 1, group 2, and group 3 were 2.14$\pm$0.10, 1.52$\pm$0.57, and 2.10$\pm$0.16. Conclusion: HTK solution provides adequate myocardial protection with some advantages over DelNido solution in isolated rat hearts.
Background: It has been reported that the recently developed intermittent antegrade warm blood cardioplegia (IAWBC) has better myocardial protective effects during coronary artery bypass surgery than cold blood cardioplegia or continuos retrograde cold blood cardioplegia. The aim of this study is to evaluate the safety and usefulness of IAWBC by comparing it retrospectively with intermittent retrograde cold blood cardioplegia (lRCBC). Material and Method: From April 2001 to Feb. 2003, fifty seven patients who underwent isolated coronary surgery were divided into two groups (IAWBC vs. IRCBC). The two group had similar demographic and angiographic characteristics. There were no statistical differences in age, sex, Canadian Cardiovascular Society Functional Classification for angina, ejection fraction, and number of grafts. Result: Aortic cross clamping time and total pump time in IAWBC (99$\pm$23 and vs. 126$\pm$32 min) were shorter than those of IRCBC (118$\pm$32 min. and 185$\pm$48 min.)(p<0.05). The reperfusion time (13$\pm$7 min) in IAWBC was shorter than that of IRCBC (62$\pm$109 min.)(p<0.05). CKMB at 12 hours and 24 hours (16$\pm$15 and 9$\pm$13) in IAWBC was lower than that of IRCBC (33$\pm$47 and 17$\pm$26)(p<0.05). The awakening time in IAWBC (2$\pm$1 hour) was shorter than that of IRCBC (4$\pm$3)(p<0.05). The number of spontaneous heart beat recovery in IAWBC (85%) was more than that of IRCBC (35%)(p<0.05). The cardiac index after discontinuing cardio-pulmonary bypass was significantly elevated in the IAWBC group. The prevalence of perioperative myocardial infarction in IAWBC (4%) was lower than that of IRCBC group (20%)(p<0.05). Conclusion: Intermittent antegrade warm blood cardioplegia is a safe, reliable, and effective technique for myocardial protection. It can also provide simpler and economic way than the retrograde cold cardioplegia by shortening of cardiopulmonary bypass time and avoiding retrograde cannulation for coronary sinus.
Background: In cardiac surgery, hypothermia is associated with a number of major disadvantage, including its detrimental effects on enzymatic function, energy generation and cellular integrity. Warm cardioplegia with normothermic cardiopulmonary bypass cause three times more incidence of permanent neurologic deficits than the cold crystalloid cardioplegia with hypothermic cardiopulmonary bypass. Interruptions or inadequate distribution of warm cardioplegia may induce anaerobic metabolism and warm ischemic injury. To avoid these problems, tepid blood cardioplegia was recently introduced. Material and Method: To evaluate whether continuous tepid blood cardioplegia is beneficial in clinical practice during valvular surgery, we studied two groups of patients matched by numbers and clinical characteristics. Warm group(37$^{\circ}C$) consisted of 18 patients who underwent valvular surgery with continuous warm blood cardioplegia. Tepid group(32$^{\circ}C$) consisted of 17 patients who underwent valvular surgery with continuous tepid blood cardioplegia. Result: Heartbeat in 100% of the patients receiving continuous warm blood cardioplegia and 88.2% of the patients receiving continuous tepid blood cardioplegia converted to normal sinus rhythm spontaneously after removal of the aortic cross clamp. There were no differences between these two groups in CPB time, ACC time, the amount of crystalloid cardioplegia used and peak level of potassium. During the operation, the total amount of urine output was more in the warm group than the tepid group(2372${\pm}$243 ml versus 1535${\pm}$130 ml, p<0.01). There were no differences between the two groups in troponin T level measured 1hr and 12hrs after the operation. Conclusion: Continuous tepid blood cardioplegia is as safe and effective as continuous warm blood cardioplegia undergoing cardiac valve surgery in myocardial protection.
The clinical experience with the activated clotting time[A.C.T.] for the control of heparin and protamine therapy during cardiopulmonary bypass in 40 patients between April, 1987 and September, 1987 is reviewed retrospectively. All of patients used with cold blood potassium cardioplegia for myocardial protection under standard cardiopulmonary bypass, priming and perfusate techniques respectively. This study was divided into 2 groups of patients followed by cardiopulmonary bypass time. Twenty patients, within 60 minutes of cardiopulmonary bypass time[group A] were compared with twenty patients, from 60 to 120 minutes of cardiopulmonary bypass time[group B]. Using blood cardioplegia for myocardial protection, Author observed wide variation of A.C.T. in individual response to initial heparinization[2mg /kg] and no requirement of additional heparin during cardiopulmonary bypass until 120 minutes. Total heparin amount during cardiopulmonary bypass was not related to body weight and body surface area in the both groups. After cardiopulmonary bypass, amounts of protamine for neutralization of heparin were more required in group B.
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