Impact of pexelizumab, an anti-C5 complement antibody, on total mortality and adverse cardiovascular outcomes in cardiac surgical patients undergoing cardiopulmonary bypass

Background

During cardiac surgery requiring cardiopulmonary bypass, pro-inflammatory complement pathways are activated by exposure of blood to bio-incompatible surfaces of the extracorporeal circuit and reperfusion of ischemic organs. Complement activation promotes the generation of additional inflammatory mediators thereby exacerbating tissue injury. We examined the safety and efficacy of a C5 complement inhibitor for attenuating inflammation-mediated cardiovascular dysfunction in cardiac surgical patients undergoing cardiopulmonary bypass.

Methods

Pexelizumab (Alexion Pharmaceuticals, Inc, Cheshire, CT), a recombinant, single-chain, anti-C5 monoclonal antibody, was evaluated in a randomized, double-blinded, placebo-controlled, multicenter trial that involved 914 patients undergoing coronary artery bypass grafting with or without valve surgery requiring cardiopulmonary bypass.

Results

Pexelizumab was administered intravenously as a bolus (2.0 mg/kg) or bolus plus infusion (2.0 mg/kg plus 0.05 mg/kg/h for 24 hours), and inhibited complement activation. There were no statistically significant differences between placebo-treated and pexelizumab-treated patients in the primary endpoint (composite of death, or new Q-wave, or non-Q-wave [myocardial-specific isoform of creatine kinase > 60 ng/mL] myocardial infarction, or left ventricular dysfunction, or new central nervous system deficit). However, post hoc analysis revealed a reduction in the composite of death or myocardial infarction (myocardial-specific isoform of creatine kinase ≥ 100 ng/mL) for the isolated coronary artery bypass grafting, bolus plus infusion subgroup on POD 4 (p = 0.007) and on POD 30 (p = 0.004).

Conclusions

Pexelizumab had no statistically significant effect on the primary endpoint. However, the reduction in death or myocardial infarction (myocardial-specific isoform of creatine kinase ≥ 100 ng/mL) as revealed in the post hoc analysis in the isolated coronary artery bypass grafting bolus plus infusion subpopulation, suggests that further investigation of anti-C5 therapy for ameliorating complement-mediated inflammation and myocardial injury is warranted.     

Myosin: a highly sensitive indicator of myocardial necrosis after cardiac operations

Plasma levels of ventricular myosin fragments, determined with monoclonal antibodies to myosin heavy chains, were studied in 27 patients after cardiac operations (17 aorta-coronary bypass grafts and 10 valve replacements) to assess their possible role as a marker of perioperative myocardial necrosis. Five patients had perioperative myocardial necrosis after aorta-coronary bypass grafts as indicated by changes in the electrocardiogram and elevated levels of the MB isoenzyme of creatine kinase. Six more patients were also studied after thoracic operations performed by the same sternotomy approach. After cardiac operations, myosin levels increased from postoperative day 3 and reached peak values on day 7. Peak myosin values in patients with perioperative myocardial necrosis after aorta-coronary bypass grafting were significantly higher than in patients after an identical operation but without perioperative myocardial infarction (3793 +/- 592 versus 369 +/- 47 ng/ml; p less than 0.001). These results suggest that plasma myosin is a sensitive marker of myocardial necrosis. Furthermore, peak plasma levels of ventricular myosin after coronary bypass grafting without myocardial infarction (mean value 369 +/- 47 ng/ml) were not significantly different from peak levels after thoracic operations (mean value 253 +/- 52 ng/ml), whereas they were significantly higher after valve replacement (mean value 794 +/- 149 ng/ml; p less than 0.01). These results indicate that a certain degree of myocardial necrosis occurs during value replacement that is undetectable by the usual diagnostic criteria for perioperative myocardial infarction. We conclude that the plasma level of ventricular myosin fragments is a more specific and accurate marker of perioperative myocardial necrosis than changes in the electrocardiogram or elevated creatine kinase MB levels. Therefore the detection of myosin fragments, which appear in the serum on the third day after cardiac operations, may be useful for precise comparisons of different techniques of myocardial protection.     

Reperfusion ventricular fibrillation during coronary artery bypass operations and its association with postoperative enzyme release

Elevated creatine kinase MB level is the most common marker of myocardial infarction in patients who have had a recent coronary bypass operation. This study was performed to determine whether there is any relationship between reperfusion rhythms, their treatment, and postoperative creatine kinase MB concentrations. Twenty patients were monitored during coronary bypass operations. Four patients had no reperfusion ventricular fibrillation and no elevation of creatine kinase MB postoperatively. Of the 16 remaining patients, all had ventricular fibrillation and 12 had an elevation of postoperative creatine kinase MB (p less than 0.015). There was also a 75% correlation between the time in ventricular fibrillation and postoperative creatine kinase MB level. There was no correlation between other measured parameters, such as cross-clamp time, bypass time, or the number of defibrillations. It is concluded that reperfusion ventricular fibrillation is associated with release of creatine kinase MB, and the time in ventricular fibrillation is correlated with the postoperative creatine kinase MB level.     

Changes in serum creatine kinase and lactate dehydrogenase caused by acute perioperative myocardial infarction and by transatrial cardiac surgical procedures

A prospective clinical study was conducted to ascertain if a patient's postoperative elevation in serum creatine kinase MB isoenzyme coupled with determination of the lactate dehydrogenase1/lactate dehydrogenase2 ratio could differentiate whether atrial or ventricular myocardium was the source of these changes. Animal studies have shown that atrial myocardium is as rich a source of creatine kinase MB as is ventricular myocardium. Atrial myocardium has a lactate dehydrogenase1/lactate dehydrogenase2 ratio less than 1.00, whereas in ventricular myocardium the ratio is greater than 1.00. Sixty-four patients were assigned to six groups on the basis of serial electrocardiograms and vectorcardiograms by a cardiologist who was unaware of their clinical courses. The control group (Group 1) consisted of 16 patients admitted to the coronary care unit who had no electrocardiographic changes. Three surgical groups without electrocardiographic or vectorcardiographic evidence of perioperative myocardial infarction were studied: 10 patients undergoing routine coronary artery bypass procedures (Group 2), six adults undergoing repair of secundum atrial septal defect (Group 3), and 13 patients having mitral valve replacement (Group 4). Two groups of surgical patients who had acute perioperative transmural myocardial infarctions confirmed by serial electrocardiograms and vectorcardiograms were studied: 15 patients (Group 5) who had elective coronary artery bypass procedures and four (Group 6) who had mitral valve replacement. This study suggests that serum creatine kinase MB levels in excess of 50 IU/L on the postoperative day 1 and day 2 samples coupled with serum lactate dehydrogenase1/lactate dehydrogenase2 ratios greater than 1.00 on the postoperative day 2 and day 3 samples support the diagnosis of acute myocardial infarction. Patient groups undergoing procedures necessitating atriotomies had average elevations in serum creatine kinase MB and in the lactate dehydrogenase1/lactate dehydrogenase2 ratio, but these were significantly less than those seen when acute perioperative myocardial infarction had occurred.     

Reinfusion of shed blood after coronary operation causes elevation of cardiac enzyme levels.

We studied the effect of reinfusing mediastinal and chest tube drainage (autotransfusion) after coronary artery bypass grafting on circulating levels of creatine kinase, lactate dehydrogenase, and serum glutamic-oxaloacetic transaminase in 20 patients. Reinfusion of 469 +/- 171 mL (mean +/- standard deviation) of drainage caused enzyme levels to rise to 372% (creatine kinase), 159% (serum glutamic-oxaloacetic transaminase), and 143% (lactate dehydrogenase) of their levels before autotransfusion. The MB fraction of the circulating creatine kinase was not elevated. Enzyme changes caused by autotransfusion can potentially mimic or mask the presence of perioperative myocardial infarction. Enzyme determinations after coronary artery bypass grafting must be carefully interpreted when reinfusion of shed blood is used as a blood salvage technique. Routine measurement of these enzymes after operation may not be warranted.     

Levels of Troponin I and Cardiac Enzymes After Reinfusion of Shed Blood in Coronary Operations

Background. Reinfusion of shed blood after coronary artery bypass grafting might increase the levels of cardiac enzymes with consequent difficulties in the diagnosis of perioperative myocardial infarction.

Methods. Thirty consecutive patients undergoing coronary artery bypass grafting who bled at least 400 mL within the first 4 hours after operation underwent reinfusion of shed blood. Thirty consecutive patients who were not autotransfused served as control. All patients underwent enzyme determination (total creatine kinase, MB fraction, lactate dehydrogenase, and troponin I) in the shed blood and in circulating blood preoperatively, at arrival in the intensive care unit, and 6, 24, and 48 hours after operation.

Results. The shed blood contained significantly higher concentration of cardiac enzymes than the circulating blood at all time intervals (p = 0.0001). The levels of creatine kinase, its MB fraction, and lactate dehydrogenase in circulating blood were significantly elevated in patients receiving autotransfusion up to 24 hours after autotransfusion. The blood levels of troponin I were not significantly different between the two group of patients at all time points. The percent fraction of MB did not increase after autotransfusion.

Conclusions. The measurement of cardiac troponin I is a useful marker for the diagnosis of perioperative myocardial infarction in patients undergoing transfusion of shed blood after coronary operation.     

Infusion of nifedipine after coronary artery bypass grafting decreases the incidence of early postoperative myocardial ischemia

We performed a randomized study on patients undergoing elective coronary bypass grafting to examine whether postoperative infusion of nifedipine (n = 25) could reduce the incidence of isolated transient myocardial ischemia, myocardial infarction, or both. The control group (n = 25) received nitroglycerin. Hemodynamic and Holter monitoring and serial assessment of enzymatic and electrocardiographic changes were performed for all patients. Both groups showed comparable preoperative and operative data. The incidence of myocardial infarction was significantly lower in the nifedipine group (n = 1) as compared with the control group (n = 4), whereas the number of patients with isolated transient myocardial ischemia was similar in both groups (nifedipine, 3; control, 4). At the time of peak activity, levels of creatine kinase (350 +/- 129 versus 511 +/- 287 IU/mL), creatine kinase-MB (8.4 +/- 5.4 versus 17.1 +/- 11.0 IU/mL), and glutamate-oxaloacetate-transaminase (30.4 +/- 4.4 versus 41.0 +/- 7.9 IU/mL) were markedly lower in the nifedipine group (p less than 0.05). We conclude that infusion of nifedipine after elective coronary artery bypass grafting effectively decreases the incidence of myocardial infarction and the extent of myocardial necrosis during the early postoperative period.     

Pericardial cardiac troponin I release after coronary artery bypass grafting.

Pericardial fluid can reflect the composition of cardiac interstitium in myocardial ischemia. This study investigated the hypothesis that pericardial cardiac troponin I (CTnI) measurements could be a more accurate marker of perioperative myocardial infarction (MI) than serum CTnI after coronary artery bypass grafting (CABG). Postoperative arterial and pericardial blood samples were taken in 102 subjects undergoing elective CABG allocated to one of three groups according to the 12-lead electrocardiogram (ECG) abnormalities observed during the first postoperative 24 h: Group 1 = normal ECG; Group 2 = nonspecific ECG abnormalities; and Group 3 = perioperative Q-wave MI. Peak pericardial CTnI concentrations were much higher than peak serum concentrations in all subjects and significantly greater in Group 3 than in Groups 1 and 2 (1,318 +/- 1,810 ng/mL vs 367 +/- 339 ng/mL and 558 +/- 608 ng/mL, respectively; P < 0.01). However, no significant difference between groups occurred at any time for pericardial/serum CTnI ratios, indicating that time courses of CTnI were not different in pericardial fluid and serum. A significant correlation was found between serum and pericardial CTnI concentrations (R = 0.70, P < 0.001). Pericardial CTnI was not more accurate than serum CTnI in predicting Q-wave MI as shown by the low value of the area under the receiver-operator characteristic curve (= 0.71). Peak and early pericardial CTnI were also not accurate in predicting an increase of serum CTnI greater than a cutoff value of 19 ng/mL. Thus, pericardial CTnI measurements were less useful than serum CTnI measurements in the diagnosis of perioperative MI after CABG. IMPLICATIONS: Although cardiac troponin I concentrations were much higher in pericardial fluid than in serum and significantly increased in subjects who experienced perioperative Q-wave myocardial infarction, pericardial cardiac troponin I measurements were of less value than serum cardiac troponin I measurements for the diagnosis of perioperative myocardial infarction after coronary artery bypass grafting and cannot be recommended in routine clinical practice.     

Biochemical assessment of myocardial injury after cardiac surgery: effects of a platelet activating factor antagonist, bilateral internal thoracic artery grafts, and coronary endarterectomy

OBJECTIVE: Platelet activating factor antagonists reduce ischemia-reperfusion injury in experiments, but there is no supportive clinical evidence. METHODS: A single-center, double-blind, minimized, placebo-controlled, randomized trial of low-dose (10 mg) or high-dose (100 mg) platelet activating factor antagonist was conducted in 150 patients undergoing coronary artery bypass grafting. Myocardial injury was determined by serial measurements of the MB isoenzyme of creatine kinase and cardiac troponin T. The effects of single or bilateral internal thoracic artery grafting and coronary endarterectomy on myocardial injury were also assessed. RESULTS: The placebo and platelet activating factor antagonist groups were similar with respect to preoperative, intraoperative, and postoperative factors. Four patients (2.7%) died before discharge, 3 from cardiac events. Thirteen patients (9%) had biochemical evidence of myocardial infarction, of whom 3 died. Stepwise multiple regression analysis demonstrated that duration of cardiopulmonary bypass was the most important determinant of elevations in creatine kinase MB isoenzyme and cardiac troponin T up to 6 hours after the operation and that the use of a platelet activating factor antagonist and the number of internal thoracic artery grafts did not influence myocardial injury at any time. Endarterectomy was performed in 11 patients (7%), of whom 6 (55%) had biochemically defined myocardial infarction and of whom 1 died (9%). Endarterectomy was the most important determinant of elevated levels of creatine kinase MB isoenzyme and cardiac troponin T 24 and 48 hours after the operation. CONCLUSION: Platelet activating factor antagonists do not reduce perioperative myocardial injury. Bilateral and single internal thoracic artery grafting results in similar levels of myocardial injury, whereas endarterectomy is frequently associated with biochemical evidence of myocardial injury.     

The association of elevated creatine kinase-myocardial band on mortality after coronary artery bypass grafting surgery is time and magnitude limited.

OBJECTIVE: The joint European Society of Cardiology and American College of Cardiology consensus statement on myocardial necrosis after revascularization stated that any amount of myocardial necrosis as detected by cardiac enzymes should be labeled a myocardial infarct. However, it also stated that more data collection is necessary to better interpret the elevation of cardiac enzymes after coronary artery bypass grafting. We sought to determine if a single postoperative value of creatine kinase-myocardial band could be used as a risk factor to help predict mortality after coronary artery bypass surgery. METHODS: A retrospective analysis of prospectively collected data on 1161 patients undergoing first-time, isolated coronary artery bypass surgery utilizing normothermic cardiopulmonary bypass was conducted. Creatine kinase-myocardial band was measured the morning after surgery. Binary logistic regression, Cox proportional hazard models, and overlapping quintiles were used to illuminate the association between creatine kinase-myocardial band elevation and mortality after coronary artery bypass surgery. RESULTS: We found a threshold value of creatine kinase-myocardial band, 40 ng/mL, above which elevations were associated with increased death rates. This association held after adjustment for other factors known to contribute to postoperative mortality. However, after 1 year, there was no longer a statistically significant higher mortality associated with elevated creatinine kinase-myocardial band > 40 ng/mL. CONCLUSION: Elevation of creatine kinase-myocardial band the morning after surgery above a threshold 40 ng/mL is associated with an increased risk of mortality.     

冠状动脉旁路移植术后血清肌钙蛋白T的动态变化

目的研究冠状动脉旁路移植术(CABG)后血清肌钙蛋白T(TnT)的动态变化及临床意义。方法采用双抗体夹心酶联免疫吸附测定法(ELISA),测定37例患者CABG后血清TnT的浓度变化,并与肌酸激酶(CK)和肌酸激酶同工酶(CK-MB)进行比较。结果TnT在CABG后4～12小时达到峰值,术后6～8天恢复正常。CK-MB于术后4～16小时升至峰值,术后48小时即恢复正常。CABG后TnT峰值与主动脉阻断时间呈正相关(r=0.55,P＜0.05)。结论TnT在CABG后对于诊断微小心肌损伤、判断预后具有高特异性、高敏感性。     

Myocardial function in early hours after coronary artery bypass grafting in patients with left ventricular dysfunction: comparison of blood and crystalloid cardioplegia

AIM: This study was done to evaluate a myocardial function in the early hours after coronary artery bypass grafting (CABG) in patients with left ventricular dysfunction and to compare blood and crystalloid cardioplegia. METHODS: One hundred consecutive patients with left ventricular ejection fraction <35% scheduled for CABG were randomly divided into 2 groups. In the 1st group we used cold blood cardioplegia, in the 2nd group cold crystalloid cardioplegia. We measured hemodynamic data in the early hours after operation, enzyme release and we collected relevant clinical data. RESULTS: The mortality rate in the crystalloid and blood cardioplegia group was 2% and 0%, respectively. We didn't find any significant difference in the incidence of perioperative myocardial infarction, arrhythmia and use of intraaortic balloon pumping between groups. Differences between groups were found in the enzymatic response. Average creatine kinase and MB isoenzyme of creatine kinase (CK-MB), was lower in the blood cardioplegia group lower during the whole examined period. We also found some significant differences in hemodynamic data in the postoperative period. In the crystalloid cardioplegia group there was a decrease in left ventricular stroke work index immediately after operation. The preoperative value was reached in about 2 hours after operation. On the other hand, we didn't find this decrease in the blood cardioplegia group. This difference between groups was statistically significant. Other hemodynamic data didn't show any significant difference. CONCLUSION: Blood cardioplegia shows earlier improvement of myocardial function after the operation. It could be beneficial in patients with severe left ventricular dysfunction.     

Markers of myocardial ischemia after minimally invasive and conventional coronary operation

Background. The purpose of this study was to evaluate the course of serum markers of myocardial tissue damage after two different types of minimally invasive coronary surgical procedures (MICS) as compared with conventional coronary artery bypass grafting (CABG).

Methods. We enrolled 87 patients with one- or two- vessel disease scheduled for one of the three procedures: minimally invasive direct coronary artery bypass grafting (MIDCABG) by lateral thoracotomy (n = 29), the OCTOPUS method by median sternotomy (n = 27), and CABG (n = 31). Creatine kinase activity (CK), creatine kinase MB activity (CK-MB act), creatine kinase MB mass concentration (CK-MB mass), myoglobin concentration (MG), and cardiac troponin I concentration (cTnI) were measured perioperatively until the second postoperative day.

Results. Creatine kinase-MB, CK-MB mass, and cTnI were significantly higher after CABG and were nearly maintained within the normal range in MICS. Creatine kinase and MG were significantly lower in the OCTOPUS group than in the MIDCABG or CABG groups.

Conclusions. Minimally invasive coronary surgical procedures cause less myocardial injury than CABG as indicated by specific serum markers. However, higher CK and MG reflect more substantial skeletal muscle trauma during MIDCABG operation compared with Octopus procedures.     

CK-MB release following coronary artery bypass grafting in the absence of myocardial infarction

Elevation of levels of the myocardial-specific isoenzyme of creatine kinase (CK-MB) in the immediate postoperative period in patients undergoing coronary artery bypass grafting is usually associated with myocardial necrosis. However, mean isoenzyme elevations of 18 +/- 2 IU/L (standard error of the mean) were recently observed in 6 patients in the absence of electrocardiographic or scintigraphic (technetium 99m stannous pyrophosphate) evidence of perioperative myocardial infarction. To test the hypothesis that surgical trauma of the atrium and aorta during cannulation for cardiopulmonary bypass might contribute to elevated CK-MB levels, biopsy of the right atrial appendage and aorta of 7 patients was done at operation, the tissue samples were assayed for total creatine kinase (CK) activity using the Rosalki technique, and for CK-MB using column chromatography. The results indicate that the human atrium is a rich source of CK, with the proportion of CK-MB similar to that present in the ventricle (20%). In addition, technical considerations inherent in the performance of coronary bypass surgery may result in release of CK-MB, causing elevated serum enzyme levels in the post-coronary artery bypass patient in the absence of myocardial infarction.     

The effect of leukocyte-depleted blood cardioplegia in patients with severe left ventricular dysfunction: a randomized, double-blind study

BACKGROUND: The propensity for leukocytes to cause reperfusion injury in patients undergoing heart surgery is widely accepted. Reperfusion injury may result in myocardial damage and unfavorable operative outcome, especially in patients with severely reduced ejection fractions. This study was performed to evaluate the impact of leukocyte filtration on the postoperative course of patients undergoing coronary bypass surgery. METHODS: Thirty-two patients with coronary artery disease and left ventricular ejection fraction less than 35% were included in this double-blind, randomized study. Two serial leukocyte removal filters (Pall BC1B filter [Pall Biomedical, Portsmouth, England], group F, 15 patients) or two dummy filters (group C, 17 patients) were connected to the blood cardioplegia line. Leukocyte count, hemodynamic measurement, and transesophageal echocardiography were performed before and after cardiopulmonary bypass. Cardiac-specific enzymes were analyzed from arterial blood during the first 72 hours and from coronary sinus blood 30 and 60 minutes after aortic unclamping. RESULTS: Patient characteristics were similar in the two groups (ejection fraction 20.9% +/- 4.3% in group C and 21.1% +/- 4.8% in group F; P =.773). No early death or perioperative myocardial infarction occurred. Leukocyte count, hemodynamic parameters, cardiac troponin T, cardiac troponin I, and creatine kinase MB mass levels in arterial blood were similar in the two groups. Group F showed lower release of cardiac troponin T from the coronary sinus 30 minutes after unclamping of the aorta (group F, 0.263 +/- 0.12 ng/mL; group C, 0.6 +/- 0.32 ng/mL; P =.005). Lower doses of dopamine were necessary after cardiopulmonary bypass (group F, 0.36 +/- 0.11 mg x kg(-1) x min(-1); group C, 0.49 +/- 0.14 mg x kg(-1) x min(-1); P =.003). A moderate increase in ejection fraction was observed at 30 minutes in both groups (group F, 30.3% +/- 6.2%; group C, 28.0% +/- 6.3%; P =.239) and a significant increase at 60 minutes in group F (group F, 32.5% +/- 6.0%; group C, 27.4% +/- 7.5%; P =.012). CONCLUSIONS: These results indicate that serial leukocyte filters connected to the blood cardioplegia line decrease myocardial cell injury and may therefore help to improve outcome of patients with severely depressed ejection fractions undergoing coronary artery bypass grafting.     

Operative myocardial protection: does an elevated level of creatine phosphokinase-MB isoenzyme always indicate myocardial necrosis?

Creatine phosphokinase-MB isoenzyme appears in the serum of virtually all patients who have undergone cardiac operations, but whether it represents myocardial cellular necrosis remains controversial. In 17 adult patients who underwent coronary artery bypass grafting or valve replacement, serial determinations of the serum levels of creatine phosphokinase-MB isoenzyme, ultrastructural studies of left ventricular myocardium before aortic cross-clamping and 10 minutes after reperfusion and postoperative electrocardiographic recordings were undertaken. The isoenzyme was detected in all patients; those having valve replacement had higher peak values than those who underwent coronary artery bypass grafting. No correlation was found between the duration of aortic cross-clamping and the peak level of isoenzyme after reperfusion. In spite of appreciable isoenzyme release from the myocardium, all the specimens obtained from this series of patients after reperfusion showed myocardial ultrastructural changes indicative of mild to moderate ischemic damage, considered to be reversible according to the criteria described by Jennings and Schaper. Except for one new Q wave, electrocardiographic changes in this series were nonspecific and transient. It is postulated that when sufficient myocardial mass is involved, such as in global ischemia during cardiac surgery, the MB isoenzyme of creatine phosphokinase leaked from reversibly damaged myocytes may become detectable and elevated in the serum. Thus, although the isoenzyme remains a sensitive indicator of myocardial protection, its presence does not necessarily indicate irreversible damage and myocardial necrosis.     

Emergency aortocoronary bypass after failed angioplasty

One thousand two hundred fourteen percutaneous transluminal coronary angioplasties were performed over a 38-month period. Sixty patients required immediate emergency coronary artery bypass grafting after angioplasty failure; 7 of these had evidence of acute myocardial infarction before angioplasty and were excluded from the study. Of the 53 patients remaining, 27 (51%) had electrocardiographic and enzyme evidence of postoperative myocardial infarction. Two patients died (4%), and 10 had postoperative complications (19%). No statistical significance was noted comparing age, sex, incidence of prior myocardial infarction or myocardial dysfunction, time for revascularization, or average number of grafts completed in those with single-vessel (n = 21) versus multiple-vessel (n = 32) coronary artery disease. Postoperatively, those with multiple-vessel disease required intraaortic balloon pump support (p = 0.06) and antiarrhythmic medications more frequently than single-vessel patients (p less than 0.01) and had a higher complication rate (p less than 0.05). Although not reaching statistical significance, the data also suggest a higher death and postoperative myocardial infarction rate in patients with multiple-vessel disease. Emergency coronary artery bypass grafting after failed percutaneous transluminal coronary angioplasty carries a higher morbidity and mortality than elective coronary artery bypass grafting, particularly for patients with multiple-vessel coronary artery disease.     

Cardiac protection by volatile anaesthetics: a multicentre randomized controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass

BACKGROUND AND OBJECTIVES: To evaluate the effects of total intravenous anaesthesia vs. volatile anaesthesia on cardiac troponin release in coronary artery bypass grafting with cardiopulmonary bypass, we performed a multicentre randomized controlled study to compare postoperative cardiac troponin release in patients receiving two different anaesthesia plans. METHODS: We randomly assigned 75 patients to propofol (intravenous anaesthetic) and 75 patients to desflurane (volatile anaesthetic) in addition to an opiate-based anaesthesia for coronary artery bypass grafting. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. RESULTS: There was a significant (P < 0.001) difference in the postoperative median (25th-75th percentiles) peak of troponin I in patients receiving propofol 5,5 (2,3-9,5) ng dL(-1) when compared to patients receiving desflurane 2,5 (1,1-5,3) ng dL(-1). The median (interquartile) troponin I area under the curve analysis confirmed the results: 68 (30.5-104.8) vs. 36.3 (17.9-86.6) h ng dL(-1) (P = 0.002). Patients receiving volatile anaesthetics had reduced need for postoperative inotropic support (24/75, 32.0% vs. 31/75, 41.3%, P = 0.04), and tends toward a reduction in number of Q-wave myocardial infarction, time on mechanical ventilation, intensive care unit and overall hospital stay. CONCLUSIONS: Myocardial damage measured by cardiac troponin release could be reduced by volatile anaesthetics in coronary artery bypass surgery.     

Reversible cardiac sympathectomy by high thoracic epidural anesthesia improves regional left ventricular function in patients undergoing coronary artery bypass grafting: a randomized trial

HYPOTHESIS: To evaluate the effects of high thoracic epidural anesthesia (TEA) on global and regional myocardial function and on perioperative coronary risk in patients undergoing coronary artery bypass grafting. DESIGN, SETTING, AND PATIENTS: Prospective and randomized clinical trial blinded for the primary outcome measure of 73 patients scheduled for coronary artery bypass grafting who had a left ventricular ejection fraction of 50% or more conducted from February 1, 2000, through August 31, 2000, at University Hospital, Münster, Germany. INTERVENTIONS: Of 73 randomized patients, 37 were control subjects (who received general anesthesia only) and 36 were in the group who received general anesthesia and high TEA. MAIN OUTCOME MEASURES: The primary outcome measure was regional left ventricular function after myocardial revascularization, assessed by transesophageal echocardiography. We further determined the plasma concentrations of cardiac troponin I and atrial and brain natriuretic peptides. Secondary outcome measures were postoperative complications recorded to 14 days and mortality recorded to 720 days. RESULTS: High TEA was effective in all patients of this group, the somatosensory block extended from T1 through T7 vertebrae. Regional left ventricular function was significantly improved (mean [SD] global wall motion index, 0.74 [0.18] vs 0.38 [0.16]; P<.05), and cardiac troponin I concentrations were reduced by 72% (mean [SD], 5.7 [1.5] vs 1.6 [0.7] ng/mL, P<.05) in patients with high TEA. Natriuretic peptide concentrations peaked during reperfusion (atrial natriuretic peptide) and 24 hours after reperfusion (brain natriuretic peptide). High TEA reduced the mean (SD) peak concentrations of atrial natriuretic peptide by 54% (211 [63] vs 98 [33] ng/mL, P =.03) and brain natriuretic peptide by 43% (189 [39] vs 108 [21] ng/mL, P =.01). One of 36 patients who received high TEA and 3 of 37 controls died. CONCLUSIONS: Reversible cardiac sympathectomy by high TEA improves regional left ventricular function and reduces postoperative ischemia after coronary artery bypass grafting. These effects of high TEA may improve the long-term outcome after myocardial revascularization.     

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.