Cardioprotective effects of lidoflazine in extensive aorta-coronary bypass grafting

The cardioprotective effects of lidoflazine, a calcium entry blocker, were tested in patients undergoing multiple aorta-coronary bypass grafting (at least four grafts). Intermittent aortic cross-clamping at 25 degrees to 28 degrees C was used. Mean cross-clamp time was 11 minutes for one distal anastomosis. Patients were randomized into three groups: a control group (I), a group (II) pretreated with 0.5 mg . kg-1 lidoflazine intravenously before cardiopulmonary bypass (CPB), and a group (III) pretreated with 1 mg . kg-1 lidoflazine intravenously. The following markers of ischemia are used: (1) adenosine triphosphate (ATP), creatine phosphate (CP) and glycogen determined in transmural left ventricular biopsy specimens taken at the beginning and end of CPB; (2) ultrastructure in a similar pair of specimens; and (3) hemodynamic recovery 15 minutes after cessation of CPB. At the end of the intervention, ATP decreased to 73% in Group I but remained unchanged in Groups II (98%) and III (88%). CP decreased to 82% in Group I and remained unaltered in Groups II (100%) and III (110%). Glycogen decreased in Group I (to 44%) and in Group II (78%) but remained unchanged in Group II (138%). Ultrastructural study showed better preservation of the glycocalyx and sarcolemma in Group III than in Group I. Left ventricular stroke work index remained unaltered after CPB in Group III but decreased in Groups I and II to about 60% of its initial value. Thus lidoflazine pretreatment protects the myocardium in a dose-dependent manner against deterioration of myocardial function and structure.     

Nifedipine as an adjunct to St. Thomas' Hospital cardioplegia. A double-blind, placebo-controlled, randomized clinical trial

The cardioprotective effect of the addition of the slow calcium-channel blocker nifedipine to cardioplegic solution was tested in two double-blind placebo controlled randomized studies. The first study included 24 patients undergoing aortic-coronary bypass grafting, and the second included 24 patients undergoing aortic valve replacement. Nifedipine at a dose of 200 micrograms/L or placebo was added to St. Thomas' Hospital cardioplegic solution. The following markers of ischemia were used: adenosine triphosphate and its catabolites, creatine phosphate and inorganic phosphate, determined in transmural left ventricular biopsy specimens taken before, at the end of, and after aortic cross-clamping; hemodynamic recovery 15 minutes after cessation of cardiopulmonary bypass; clinical outcome in terms of the incidence of arrhythmias, low cardiac output, positive inotropic support immediately after operation, and follow-up at 15 months. The main difference between the two studies was that myocardial temperature during cross-clamping remained constant at 14 degrees C in coronary bypass grafting but increased to 25 degrees C in valve operations despite the application of the same amounts of cardioplegic solutions. This lower temperature resulted in better preservation of high-energy phosphates in coronary bypass operations as compared to the placebo group having valve replacement operations. According to analysis of variance, a drug effect could be demonstrated only in the aortic valve replacement study: Accumulation of breakdown products of the adenine nucleotide pool was less in the nifedipine group than in the placebo group (p less than 0.05). Adenosine triphosphate decreased only to 84% in the nifedipine group and to 72% in the placebo group. Despite this adenosine triphosphate-sparing effect, weaning from cardiopulmonary bypass was more difficult in the nifedipine group. Left ventricular stroke work index 15 minutes after bypass was decreased to 72% of the prebypass value in the nifedipine group (t test, p less than 0.01) and only to 86% in the placebo group (p = NS). In contrast, after the patients were admitted to the intensive care unit, the incidence of low cardiac output tended to be lower in the nifedipine group than in the placebo group: 33% versus 58% (p = NS). In conclusion, ischemia-induced degradation of nucleotides as it occurs when myocardial cooling is inadequate can be prevented by the addition of nifedipine to the St. Thomas' Hospital cardioplegic solution. This effect, however, is not associated with an improved clinical outcome.     

体外循环旁路洗入七氟醚对冠状动脉旁路移植术患者心肌损伤的影响

目的 评价体外循环(CPB)旁路洗入七氟醚对冠状动脉旁路移植术(CABG)患者心肌损伤的影响.方法 择期CPB下行CABG的患者40例,年龄50 ～ 64岁,体重53～90 kg,ASA分级Ⅱ或Ⅲ级,采用随机数字表法,将患者随机分为2组(n=20):对照组(C组)和七氟醚组(S组).S组于CPB开始即刻通过体外循环机洗入1.0％ ～2.0％七氟醚,持续到CPB结束,C组不给予七氟醚.于麻醉诱导后5 min(T0)、术后6 h(T1)、12 h(T2)及24 h(T3)时采集血样,测定血浆心肌肌钙蛋白I(cTnI)浓度和磷酸肌酸激酶同工酶(CK-MB)活性.于主动脉阻断前和CPB结束时取右心耳组织,电镜下观察心肌超微结构,并行心肌细胞线粒体损伤评分.结果 与C组比较,S组T2和T3时血浆cTnI浓度,CPB结束时心肌细胞线粒体损伤评分降低(P＜0.05),血浆CK-MB活性差异无统计学意义(P＞0.05).S组心肌病理学损伤较C组减轻.结论 CPB旁路洗入七氟醚可减轻CABG术患者的心肌损伤.     

Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonary bypass

Inotropes are often used to treat myocardial dysfunction shortly after cardiopulmonary bypass (CPB). beta-Adrenergic agonists improve contractility, in part by increasing cyclic adenosine monophosphate (cAMP) production, whereas phosphodiesterase type III inhibitors prevent its breakdown. CPB is associated with abnormalities at the beta-receptor level and diminished adenyl cyclase activity, both of which tend to decrease cAMP. These effects may be increased in the presence of preexisting myocardial dysfunction. We tested the hypothesis that inhibition of phosphodiesterase type III before global myocardial ischemia and pharmacologic arrest results in the preservation of intramyocardial cAMP concentration during CPB. Twenty adult patients undergoing coronary artery bypass grafting with CPB were studied. After CPB was instituted, a myocardial biopsy was obtained from the apex of the left ventricle. Patients were randomized to receive either placebo or milrinone (50 micro/kg) through the bypass pump 10 min before aortic cross-clamping. Another myocardial biopsy was performed adjacent to the left ventricular apex just before weaning from CPB. Myocardial cAMP concentration was determined by radioimmunoassay. Myocyte protein content was determined by the Bradford method by using a commercial kit. There were no significant demographic differences between the groups; however, patients in the Milrinone group had a lower left ventricular ejection fraction than placebo (41% +/- 13% vs 53% +/- 7%; P < 0.05). Patients who received milrinone had larger cAMP concentrations at the end of CPB compared with placebo (21 +/- 12.5 pmol/mg protein versus 12.8 +/- 2.2 pmol/mg protein; P < 0.05). The administration of milrinone before aortic cross-clamping is associated with increased intramyocardial cAMP concentration at the end of CPB. IMPLICATIONS: The administration of a single dose of milrinone before aortic cross-clamping resulted in significantly larger intramyocardial cyclic adenosine monophosphate concentration in myocardial biopsy specimens compared with controls.     

Relationship between hemodynamics and cardiac metabolism in the reperfusion period following hypothermic global ischemia

Ten mongrel dogs were subjected to hypothermic ischemic cardioplegia for two hours followed by 30 minutes of reperfusion to characterize the relationship between hemodynamic parameters during reperfusion and the recovery of high energy store of the post-ischemic left ventricular myocardium. Dogs were anesthetized with intravenous pentobarbital 30 mg/kg, and standard cardiopulmonary bypass was instituted with the flow rate of 80 ml/min/kg and perfusion pressure around 80 mmHg. Ischemic cardioplegia was obtained by cross-clamping of the aorta for 2 hours under 20°C of myocardial temperature. After termination of cardioplegia, the heart was rewarmed by the support of cardiopulmonary bypass with the flow rate of 80 ml/min/kg until the myocardial temperature reached 36 °C. Hemodynamic parameters were measured throughout the experiment and myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) were measured at the end of experiment. Correlation was significant between myocardial ATP and coronary blood flow and myocardial oxygen consumption. However, myocardial creatine phosphate correlated poorly to coronary blood flow, myocardial oxygen consumption and other hemodynamic parameters. These results indicate that the recovery of myocardial high energy store is partly related to coronary blood flow and myocardial oxygen consumption, but other parameters are probably involved in the process of early recovery of the myocardium from ischemic cardioplegia. This study was supported in part by a Grant from the Japan Heart Foundation for 1979.     

Changes in myocardial high-energy phosphate stores and carbohydrate metabolism during intermittent aortic crossclamping in dogs on cardiopulmonary bypass at 34 degrees and 25 degrees C

The effect of cooling to 25 degrees C on myocardial metabolism was studied during four periods of global ischemia (10 minutes each) followed by 15 minutes of reperfusion in dogs on cardiopulmonary bypass. Systemic and heart temperature at normothermia (group N, 34 degrees C; n = 15) was compared with general hypothermia (group H, 25 degrees C; n = 16). Before and at the end of each aortic crossclamp period in small myocardial biopsy specimens the adenosine triphosphate, creatine phosphate, inorganic phosphate, glycogen, and lactate content was analyzed. Also, lactate and inorganic phosphate were measured in the coronary effluents during the repetitive periods of reperfusion. Hemodynamic function was not different at 60 minutes after cardiopulmonary bypass compared with pre-cardiopulmonary bypass values, and was not different between the groups N and H. The tissue content of adenosine triphosphate and glycogen decreased progressively during the experimental period, resulting in slightly depressed values in both groups at the end of cardiopulmonary bypass. Pronounced effects of ischemia and reperfusion on tissue content of creatine phosphate, inorganic phosphate, and lactate were observed after each period of ischemia. The net decrease in tissue creatine phosphate content was not different between groups N and H (41 +/- 4 versus 38 +/- 4 mumol.gm-1 dry weight; mean +/- standard error of the mean) after 10 minutes of ischemia. However, during ischemia the net inorganic phosphate increase in myocardial tissue was significantly higher in group H (70 +/- 7 mumol.gm-1) than in group N (44 +/- 3 mumol.gm-1). These findings do not support the notion that myocardial protection is improved during hypothermia. Moreover, quantitatively the release of inorganic phosphate and lactate did not correlate with the amount accumulated in the myocardial tissue during the preceding periods of ischemia. The release appeared to be temperature dependent, that is, significantly reduced at 25 degrees C. The present data demonstrate why clinical outcome is satisfactory in both surgical procedures, when in general the periods of aortic crossclamping do not exceed 10 minutes each and the reperfusion periods in between the ischemic episodes last about 15 minutes. Besides, the findings indicate that hypothermia is not strictly necessary under these circumstances.     

Comparison of catecholamine effects on canine myocardial metabolism and regional blood flow during and after cardiopulmonary bypass

The acute metabolic and hemodynamic effects of dopamine, dobutamine (both at 10 micrograms . kg-1 . min), and isoproterenol (at 0.05 or 0.1 micrograms . kg-1. min) were determined in dogs following 20 minutes of normothermic global myocardial ischemia. The catecholamines were started 10 minutes before cardiopulmonary bypass (CPB) was discontinued and were continued for 1 hour after bypass. Regional myocardial and systemic blood flow distribution was measured by means of the radioactive microsphere technique. On bypass all catecholamines sharply increased heart rate, myocardial oxygen consumption, and left ventricular blood flow (p less than 0.01). Because the hearts were unloaded, these data suggest that velocity of contraction is an important component of myocardial oxygen consumption. Although these drugs did not lower myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels, the significant rise in oxygen consumption suggested that inotropic treatment on bypass may not be beneficial. Furthermore, renal blood flow was diminished in dobutamine-treated dogs (p less than 0.01) and tended to decrease with isoproterenol infusion. No change was seen with dopamine infusion. After bypass, dobutamine treatment increased cardiac output (p less than 0.01) and stroke volume (p = 0.017) with no change in heart rate, myocardial oxygen consumption, high-energy phosphate levels, and total or transmural distribution of left ventricular blood flow. Dopamine infusion did not change cardiac output but did increase oxygen consumption (p less than 0.01). Isoproterenol showed a slight inotropic effect, but frequent ventricular arrhythmias were present during weaning from bypass. In all treatment groups, blood flow in the other systemic beds (cerebral, gastrointestinal, and renal) was similar to that in control dogs. These data suggest that dobutamine is the most efficient of the drugs tested for support of the heart following global myocardial ischemia but, when given during bypass, it appears to decrease renal blood flow.     

Does isoflurane optimize myocardial protection during cardiopulmonary bypass?

OBJECTIVE: To investigate the possible myocardial protective effect of isoflurane during aortic cross-clamp and cardioplegic cardiac arrest in patients undergoing conventional coronary artery bypass graft surgery. DESIGN: Prospective, randomized. SETTING: University medical center. PARTICIPANTS: Forty-nine patients undergoing elective coronary artery bypass graft surgery divided into 2 groups: control group (n = 21) and isoflurane group (n = 28). INTERVENTION: Isoflurane was administered in the pre-cardiopulmonary bypass (CPB) period to the isoflurane group. MEASUREMENTS AND MAIN RESULTS: Hemodynamics and ST- segment variations were monitored in the pre-CPB period and after weaning from CPB in both groups. Incidence of reperfusion arrhythmias after release of aortic cross-clamp was compared. In the isoflurane group, the mean cardiac index after CPB was significantly higher than the pre-CPB value, whereas no difference between the 2 values was found in the control group. The higher cardiac index in the isoflurane group was associated with a lesser degree of ST- segment changes than in the control group. There was no significant difference between the 2 groups in the incidence of reperfusion arrhythmias after release of aortic cross-clamp. CONCLUSION: The present report suggests that administration of isoflurane before aortic cross-clamping in patients undergoing coronary artery bypass graft surgery may optimize the myocardial protective effect of cardioplegia. Isoflurane may be particularly advantageous whenever prolonged periods of aortic cross-clamping or inadequate delivery of cardioplegia is expected.     

Heparin-coated circuits reduce myocardial injury in heart or heart-lung transplantation: a prospective, randomized study.

BACKGROUND: The effects of heparin-coated (HC) circuits have been primarily investigated in routine cardiac operations with limited duration of cardiopulmonary bypass (CPB) and ischemia. Their benefits have not been conclusively proven but could be more significant when CPB and ischemic times are longer, such as during heart transplantation (HTx) or heart-lung transplantation (HLTx). METHODS: In a 22-month period, 29 patients undergoing HTx and HLTx were randomly divided into two groups using HC (Duraflo II, n = 14, 10 HTx and 4 HLTx) or uncoated but identical circuits (NHC group, n = 15, 10 HTx and 5 HLTx). All patients received full systemic heparinization (3 mg/kg) during CPB. Plasma endotoxin, interleukin (IL)-6, IL-8, IL-10, IL-12, and cardiac troponin-I were measured before heparin administration, immediately after aortic cross-clamping, 5, 30, 60, 90, 120 minutes, and 12 and 24 hours after aortic declamping. The intensive care unit (ICU) staff and the laboratory technologists were blinded as to the use of HC circuits. RESULTS: No statistically significant differences between groups were found with respect to all baseline values, duration of CPB and aortic cross-clamping, graft ischemic time, doses of heparin, postoperative blood loss and transfusion, peak lactate and creatine kinase-MB isoenzyme values, duration of mechanical ventilation, or length of ICU stay. One patient in each group died during the hospital stay. Patients in the HC group needed more protamine sulfate after CPB. Although endotoxin levels were similar in the two groups, significantly lower IL-6, IL-8, and IL-10 levels were observed 1 hour after aortic declamping in the HC group. The release of cardiac troponin-I was also significantly reduced in the HC group 12 and 24 hours after reperfusion. CONCLUSIONS: The use of HC circuit limits both pro- and anti-inflammatory responses to CPB. It may also reduce myocardial injury after prolonged duration of CPB and ischemia.     

Role of protease inhibition in myocardial preservation in prolonged hypothermic cardioplegia followed by reperfusion. Effect of aprotinin in an experimental model

The effects of aprotinin on canine myocardium subjected to cardioplegia and global ischemia for 4 hours and then reperfused for 1 hour were investigated. Lysosomal and mitochondrial enzymes and cyclic nucleotides (adenosine cyclic monophosphate and guanosine cyclic monophosphate) were measured in coronary sinus blood. Aprotinin was given intravenously before cardiopulmonary bypass at total doses of 10 X 10(3) kallikrein units per kilogram (group A, six dogs) and 20 X 10(3) KU/kg (group B, six dogs). In group A, three dogs survived but with poor cardiac function; all dogs in group B survived and had better cardiac function. Lysosomal (N-acetyl-beta-D-glucosaminidase) and mitochondrial (aspartate aminotransferase) enzymes in coronary sinus blood at 60 minutes of reperfusion were significantly (p less than 0.05) lower in group B than in group A. In both groups, guanosine cyclic monophosphate was significantly (p less than 0.01) lower during reperfusion than before cardiopulmonary bypass; however, the values were significantly (p less than 0.05) higher in group B than in group A. Serum adenosine cyclic monophosphate was lower during reperfusion than before bypass in both groups, but it recovered during reperfusion in group B. Myocardial adenosine triphosphate was well preserved in both groups but creatine phosphate was decreased (p less than 0.01) in group A. These results suggest that aprotinin at a dose of 20 X 10(3) KU/kg may be effective in preserving myocardial viability and function after prolonged cardioplegia.     

Ischemic preconditioning in myocardial revascularization with intermittent aortic cross-clamping

BACKGROUND: This study tests the hypothesis that initial brief periods of ischemia can increase the protection obtained by intermittent aortic cross-clamping. METHODS: In the control group (n = 18), the procedure was performed under intermittent aortic cross-clamping at 32 degrees C. Patients in the preconditioned gorup (n = 17) received a stimulus of two 3-minute periods of cross-clamping followed by 2 minutes of reperfusion prior to standard operation. CKMB, troponin 1, adenosine, and lactate were obtained from the great cardiac vein at the onset of cardiopulmonary bypass (CPB), at the end of the first anastomosis, and at the end of CPB. RESULTS: CKMB and troponin I were slightly higher at the end of CPB in the control group, while there was no difference between adenosine and lactate levels. [table: see text]. CONCLUSION: There was no difference between groups in terms of myocardial protection.     

Protection of the Myocardium with High-Energy Solutions

An approach to intraoperative protection of the myocardium is described that attempts to increase glucose utilization by infusion of high-energy solutions during aortic cross-clamping. Infusion of hypertonic glucose or glucose plus insulin prior to aortic cross-clamping has enhanced contractility and increased high-energy phosphate moieties in animals with induced ischemia. Recent pilot experiments in our laboratory suggest that infusions of creatine may result in increased production of creatine phosphate, which in turn induces phosphorylation of adenosine diphosphate to adenosine triphosphate, possibly enhancing myocardial contractility. The intraoperative clinical benefits of these infusions remain to be proved, however.     

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

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

Superior result of ketone body ratio in normothermic cardiopulmonary bypass

Nineteen patients undergoing aortocoronary bypass surgery were divided into two groups according to the perfusion temperature, either normothermia (36 degrees C) or hypothermia (30 degrees C). The hepatic blood flow was measured at three points before, during and after cardiopulmonary bypass. Arterial and hepatic venous ketone body ratios (AKBR, HKBR) and hepatic venous saturation (ShvO2) were measured throughout the surgery. RESULTS: Hepatic blood flow in both groups was identical before, during, and after the CPB. The significantly lower ShvO2 levels were observed during the CPB in the normothermic group. The both AKBR and HKBR in the hypothermic group decreased severely after the initiation of CPB (p < 0.01). However, the reduction in AKBR and HKBR was less severe in the normothermic group. CONCLUSIONS: Normothermic CPB provides adequate liver perfusion and results in a better hepatic metabolism than hypothermic cardiopulmonary bypass.     

大剂量抑肽酶对体外循环心内直视手术病人心肌的保护作用

目的：观察体外循环（ＣＰＢ）心内直视手术中使用大剂量抑肽酶对心肌保护的影响。方法：１２０例心脏瓣膜置换手术病人,随机分成两组：Ａ组（抑肽酶组,ｎ＝６０）,Ｂ组（对照组,ｎ＝６０）,ＡＢ两组均在主动脉阻断后行冷晶体停跳,至开放关作末次温血灌注。     

Preconditioning the human heart.

The phenomenon of ischaemic preconditioning protects the myocardium by limiting infarct size in animal models of ischaemia and reperfusion. Ischaemic preconditioning may be induced by short periods of ischaemia and reperfusion. We investigated whether the human heart can be ischaemically preconditioned during coronary artery bypass grafting (CABG). Patients were enrolled into two separate studies. In the first study myocardial adenosine triphosphate (ATP) was used as the measured endpoint, assayed from myocardial biopsies taken at onset of cardiopulmonary bypass (CPB), at the end of the preconditioning stimulus, and at the end of a 10 min sustained ischaemic insult. In the second study the release of myocardial troponin T was used as the endpoint; taken at pre-CPB, and at 1, 6, 24, and 72 h after CPB. In both studies, patients were randomised into either the preconditioning group or the control group. Preconditioning was induced, after the onset of CPB, with two 3 min periods of crossclamping and an intervening 2 min of reperfusion, followed by 10 min sustained ischaemia. The control group only received 10 min of sustained ischaemia. Ischaemic preconditioning resulted in a slower rate of ATP (mumol/g dry weight) depletion in the preconditioned hearts at the end of the 10 min of sustained ischaemia (preconditioned: 11.5 +/- 0.8 vs control: 7.2 +/- 0.3; P < 0.005). Also, preconditioning resulted in a slower rate of troponin T release which was significantly different at 72 h after CPB in the preconditioned group (0.3 milligram) when compared with the control group (1.4 milligrams; P < 0.05). In addition, more patients in the preconditioned group had troponin T levels lower than 0.5 milligram at 72 h than in the control group (10 vs 3 patients). Both groups of patients received the same number of grafts, and underwent the same length of ischaemia during the procedure. We conclude that in patients undergoing CABG surgery, ischaemic preconditioning may reduce myocardial injury as shown by the favourable changes in myocardial ATP, and serum troponin T levels.     

The effects of milrinone on hemodynamics in patients undergoing cardiac surgery

The phosphodiesterase inhibitor, milrinone is used to treat low cardiac output syndrome, especially after cardiac surgery. But there were few reports about the precise hemodynamic effects at separation from cardiopulmonary bypass (CPB). We examined the hemodynamic effects of milrinone in 24 patients undergoing elective coronary artery bypass graft (CABG). Patients were assigned to the milrinone group (n = 12) and the control group (n = 12). Before separation from CPB, milrinone was administered as a loading dose of 50 micrograms.kg-1 into the reservoir of CPB at rectal temperature 33.5 degrees C and simultaneously a continuous infusion of 0.5 microgram.kg-1.min-1 was started. In addition, dopamine and nitroglycerine were administered in both groups. Hemodynamic measurements were performed before CPB, just after the weaning from CPB, 15, 30, 60 minutes after the weaning from CPB. Cardiac index increased significantly (P < 0.01) in the milrinone group as compared with the control group. Systemic vascular resistance index and mean arterial pressure decreased significantly (P < 0.0001, P < 0.05, respectively) in the milrinone group as compared with the control group. There were no significant differences in heart rate, mean pulmonary arterial pressure, pulmonary artery occlusion pressure, mean right atrial pressure, stroke volume index, and pulmonary vascular resistance index between the two groups. These hemodynamic effects showed that milrinone supported cardiac performance after CPB for CABG.     

地氟烷在二尖瓣置换手术中对缺血再灌注心肌的保护作用

在心脏外科手术中心肌缺血再灌注(ischemia-reperfusion,I-R)损伤的防治是急需解决的问题。缺血预处理(ischemic preconditioning,IPC)具有心肌保护作用[1,2]。研究显示挥发性麻醉药也具有类似IPC的麻醉药预处理(anesthetic-induced preconditioning,APC)作用[3,4],能减轻I-R后     

七氟醚后处理对体外循环下冠状动脉旁路移植术病人心肌缺血再灌注损伤的影响

目的 探讨七氟醚后处理对体外循环(CPB)下冠状动脉旁路移植术病人心肌缺血再灌注损伤的影响.方法 择期行冠状动脉旁路移植术病人40例,性别不限,年龄55～64岁,BMI＜30 kg/m2,NYHA心功能分级Ⅰ～Ⅲ级,随机分为2组(n=20):对照组(C组)和七氟醚后处理组(S组).S组于主动脉开放即刻通过体外循环机吸入2%七氟醚,持续15 min,C组不给予任何处理.分别于麻醉诱导后、CPB转流前、停机后10 min、术毕、术后6和24 h时,记录MAP、HR、CVP、平均肺动脉压、肺动脉楔压、CO和S(v)O2,计算CI、SVI、体循环血管阻力指数和肺循环血管阻力指数.分别于主动脉阻断前、复灌6 h和术后24 h时,中心静脉取血样,测定血浆肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)的活性以及肌钙蛋白I(TnI)浓度.分别于主动脉阻断前和CPB停机时,取右心耳心肌组织,观察心肌细胞超微结构,并对心肌细胞损伤程度进行评分.结果 两组间各时点血液动力学和心功能指标比较差异无统计学意义(P＞0.05).与C组比较,S组复灌6 h时血浆CK-MB和LDH活性降低,术后24 h时血浆CK活性和TnI浓度降低,CPB停机后心肌细胞损伤程度评分降低(P＜0.05).结论 七氟醚后处理可减轻CPB下冠状动脉旁路移植术病人心肌缺血再灌注损伤.     

Pretreatment with aminophylline reduces release of Troponin I and neutrophil activation in the myocardium of patients undergoing cardioplegic arrest.

OBJECTIVE: Cardioplegic arrest and subsequent reperfusion results in myocardial injury partly related to local inflammation in the heart. It has been proven that aminophylline has numerous anti-inflammatory effects. This study has been designed to evaluate the effects of aminophylline used as a cardioprotective agent for patients undergoing cardiopulmonary bypass (CPB) for valve replacement. METHODS: Thirty patients undergoing elective valve replacement were randomized to receive either aminophylline (n=15), or normal saline (control n=15). Administration of aminophylline (5mg/kg) was injected intravenously after induction of anesthesia. The cardiac Troponin I (cTnI), myocardial myeloperoxidase (MPO) activity, atrial cyclic AMP, and a coronary sinus neutrophil count were measured before and after cardioplegic arrest. RESULTS: There were no differences between the two groups with regard to clinical variables. The cTnI concentration increased significantly after aortic declamping in both groups. However, it was significantly lower, 8h after aortic declamping, in aminophylline group (1.00+/-0.41 vs 2.37+/-1.35 ng/ml p=0.038). The atrial cAMP was significantly higher before aortic cross-clamping in aminophylline group (42.5+/-6.7 pmol/g tissue vs 30.6+/-12.4 pmol/g tissue p=0.04). In addition, we found that the aminophylline group had a significantly lower MPO after reperfusion (1.50+/-0.58 U/g tissue vs 0.86+/-0.24 U/g tissue p=0.003), and a significantly lower neutrophil count 30 min after aortic declamping (0.68+/-0.11x10(3) cell/ml vs 0.32+/-0.16x10(3) cell/ml, p=0.023). CONCLUSIONS: Pretreatment with intravenous aminophylline reduces the subclinical myocardial injury and neutrophil activation in patients undergoing CPB for valve replacement.