Rephael Mohr

Tumor necrosis factor-alpha is released from the isolated heart undergoing ischemia and reperfusion

OBJECTIVES The purpose of this study was to examine whether tumor necrosis factor-alpha (TNF-alpha) is released directly from the ischemic myocardium undergoing reperfusion. BACKGROUND Tumor necrosis factor-alpha is a protein hormone produced by systemic leukocytes (primarily by activated macrophages). It has been implicated as a systemic mediator in the development of septic shock and other pathologic conditions. Serum TNF-alpha has also been detected in a variety of cardiac disease states and after myocardial ischemia-reperfusion injury. METHODS Nine isolated rat hearts undergoing 30 min of perfusion, followed by warm cardioplegic arrest, 1 h of global ischemia and 30 min of reperfusion, were investigated using the modified Langendorff model. RESULTS Significant amounts of TNF-alpha (752 +/- 212 pmol/ml) were detected in the effluent during the first minute of reperfusion. Tumor necrosis factor-alpha levels correlated with postischemic deterioration in peak systolic pressures (r = 0.7882, p = 0.012), dP/dt max (r = 0.6795, p = 0.044), time-pressure integral (r = 0.7661, p = 0.0016) and postischemic creatine kinase levels (r = 0.8367, p = 0.005). The deterioration in coronary flow, however, was inversely correlated with TNF-alpha levels (r = -0.7581, p = 0.018). CONCLUSIONS To our knowledge, this study is the first to suggest that the isolated rat myocardium synthesizes and releases TNF-alpha in response to ischemia and reperfusion, which directly correlates with the postischemic deterioration in myocardial mechanical performance and the amount of cellular necrosis.

Anti–Tumor Necrosis Factor-Alpha Improves Myocardial Recovery After Ischemia and Reperfusion ☆

OBJECTIVES This study sought to assess the importance of locally released or paracrine myocardial tumor necrosis factor-alpha (TNF-alpha) in the evolution of postischemic myocardial dysfunction and to use immunohistochemical studies to localize TNF-alpha within the myocardium. BACKGROUND TNF-alpha is implicated as a systemic mediator in the development of myocardial ischemia-reperfusion injury by promoting leukocyte myocardial infiltration, and it has been shown to originate from noncardiac peripheral mononuclear cells. We have recently documented in a blood-free environment the release of TNF-alpha from the ischemic-reperfused myocardium. METHODS Isolated rat hearts undergoing 1 h of global cardioplegia-induced ischemia and 30 min of reperfusion were investigated with use of the modified Langendorff model. Hearts were randomly divided into three subgroups: group A, control group; and groups B and C, isolated hearts receiving cardioplegic solution containing monoclonal hamster antimurine TNF-alpha antibodies (group B) or hamster IgG (group C). RESULTS Significant amounts of TNF-alpha were detected in group A and group C effluent on 1 min of reperfusion (752 +/- 212 and 958 +/- 409 pmol/ml, respectively). However, in group B, TNF-alpha was below detectable levels. In this group, postischemic left ventricular peak systolic pressures, first derivative of the rise in left ventricular pressure (dP/dtmax), pressure-time integral, coronary flow and O2 consumption improved (analysis of variance [ANOVA] p < 0.0001 for all variables) compared with values in groups A and C; creatine kinase levels decreased (p < 0.005); and myocardial structure was preserved. Immunohistochemical staining localized TNF-alpha to cardiac myocytes and to endothelial cells. CONCLUSIONS Anti-TNF-alpha neutralizes local TNF-alpha release from cardiac myocytes after ischemia and improves myocardial recovery during reperfusion, indicating that postischemic paracrine TNF-alpha release plays an active role in myocardial dysfunction.

Coronary artery bypass without cardiopulmonary bypass: Analysis of short-term and mid-term outcome in 220 patients

Two hundred twenty patients, preferentially those with high-risk conditions, underwent coronary artery bypass grafting without cardiopulmonary bypass. Early unfavorable outcome events included operative mortality (7 patients, 3.2%), nonfatal perioperative myocardial infarction (6 patients, 2.7%), cerebrovascular accident (1 patient, 0.4%), and sternal infection (3 patients, 1.4%). There were two deaths (13%) among 15 patients with calcified aorta and four (12%) in 33 patients who underwent emergency operation. Multivariate analysis revealed these two risk factors to be the only predictors of early mortality (odds ratios, 8.0 and 9.8, respectively). Preoperative risk factors such as left ventricular dysfunction (ejection fraction < or = 35%) (40 patients, 18%), congestive heart failure (46 patients, 21%), acute myocardial infarction (59 patients, 27%), cardiogenic shock (7 patients, 3%), age 70 years or older (59 patients, 27%), renal failure (19 patients, 9%), and cerebrovascular accident and carotid disease (11 patients, 5%) were not found to be major predictors of early mortality or unfavorable outcome. During 12 months of follow-up (range 1 to 21 months), there were four cardiac and three noncardiac deaths (1-year actuarial survival 93%) and 17 cases (7.7%) of early return of angina. Calcified aorta, nonuse of the internal mammary artery, reoperation, and diabetes mellitus were independent predictors of unfavorable events. We conclude that coronary artery bypass grafting without cardiopulmonary bypass can be done with relatively low operative mortality, although there seems to be an increased risk for early return of angina. This procedure should therefore be considered for patients with appropriate coronary anatomy, in whom cardiopulmonary bypass poses a high risk. This procedure is still hazardous with calcified aorta or emergency operation.

Low-molecular-weight heparin for prosthetic heart valves: treatment failure

There is no adequate substitute therapy for patients with prosthetic heart valves, in whom anticoagulation with warfarin or unfractionated heparin must be withheld. In the literature there are several reports describing successful treatment with low-molecular-weight heparin in patients with prosthetic heart valves. We report two cases of low-molecular-weight heparin treatment failure resulting in thrombosed prosthetic heart valves with stormy clinical presentations, who underwent successful valve replacements.

Platelet protection by low-dose aprotinin in cardiopulmonary bypass: Electron microscopic study

To evaluate the effect of low-dose aprotinin during cardiopulmonary bypass on platelet function and clinical hemostasis, 30 patients undergoing various cardiopulmonary bypass procedures employing bubble oxygenators were randomized to receive either low-dose aprotinin (2 x 10(6) KIU in the cardiopulmonary bypass priming solution, 15 patients [group A]) or placebo (15 patients [group B]). Blood samples were collected before and after cardiopulmonary bypass to assess platelet count and aggregation on extracellular matrix, which was studied by a scanning electron microscope. On a scale of 1 to 4 preoperative mean platelet aggregation grades were similar in both groups (3.8 +/- 0.5 and 3.5 +/- 0.5 for groups A and B, respectively). Postoperatively, platelet aggregation on extracellular matrix decreased slightly in group A (2.8 +/- 1.3; p < 0.01) and significantly in group B (1.3 +/- 0.5; p < 0.001). Eleven of the 15 patients in group A remained in aggregation grade 3 or 4 compared with none of the group B patients. Platelet count was similar in both groups preoperatively and postoperatively. Total 24-hour postoperative bleeding and blood requirement were lower in the aprotinin group (487 +/- 121 mL and 2.3 +/- 1.0 units) than in the placebo group (752 +/- 404 mL and 6.8 +/- 5.1 units; p < 0.01). These results show that the use of low-dose aprotinin during cardiopulmonary bypass provides improved postoperative hemostasis, which might be related to the protection of the platelet aggregating capacity.

Sternal wound infections in patients after coronary artery bypass grafting using bilateral skeletonized internal mammary arteries.

OBJECTIVES This study evaluated the risks of sternal wound infections in patients undergoing myocardial revascularization using bilateral skeletonized internal mammary arteries (IMAs). BACKGROUND The skeletonized IMA is longer than the pedicled one, thus providing the cardiac surgeon with increased versatility for arterial myocardial revascularization without the use of vein grafts. It is isolated from the chest wall gently with scissors and silver clips, and no cauterization is employed. Preservation of collateral blood supply to the sternum and avoidance of thermal injury enable more rapid healing and decrease the risk of sternal wound infection. METHODS From April 1996 to August 1997, 545 patients underwent arterial myocardial revascularization using bilateral skeletonized IMAs. The right gastroepiploic artery was used in 100 patients (18%). The average age of the patients was 65 years; 431 (79%) were men and 114 (21%) were women; 179 (33%) were older than 70 years of age; 166 (30%) were diabetics. The average number of grafts was 3.2 per patient. RESULTS The 30-day operative mortality rate was 2% (n = 11). There were six perioperative infarcts (1.1%) and six strokes (1.1%); 9 patients had sternal infection (1.7%) and 15 (2.8%) had superficial infection. Risk factors for sternal infection were chronic obstructive pulmonary disease and emergency operation. Superficial sternal wound infections were more common in women and in patients with chronic obstructive pulmonary disease, renal failure, or peripheral vascular disease. The 1-year actuarial survival rate was 97%. Two of the six late deaths were not cardiac-related. Late dehiscence occurred in three patients (0.6%). The death rate (early and late) of patients with any sternal complication was higher than that of patients without those complications (33% vs. 2.7%). CONCLUSIONS Routine arterial myocardial revascularization using bilateral skeletonized IMAs is safe, and postoperative morbidity and mortality rates are low, even in elderly patients and those with diabetes. Chronic obstructive pulmonary disease and emergency operations were found to be associated with an increased risk of sternal infections, and the authors recommend avoiding the use of bilateral skeletonized IMAs in patients with these preoperative risk factors.

Bilateral internal thoracic artery grafting : midterm results of composite versus in situ crossover graft

BACKGROUND Two common techniques of bilateral internal thoracic artery grafting are the composite T graft and in situ crossover graft. The superiority of one method over the other has not yet been established. METHODS From April 1996 to July 1999, bilateral skeletonized internal thoracic arteries were used as T grafts (composite group, n = 649) and in situ grafts (cross group, n = 351) in 1,000 consecutive patients. In the cross group, in situ right internal thoracic artery was routed anterior to the aorta across the midline for grafting to the left anterior descending artery, and the left internal thoracic artery was used for the circumflex branches. RESULTS The two groups had comparable preoperative risk profiles. Bypass time and aortic cross-clamping time were longer in the composite group (80 +/- 38 and 67 +/- 29 minutes versus 66 +/- 43 and 55 +/- 34 minutes, respectively). Number of anastomoses per patient was similar (3.1 versus 3.2). However, more sequential anastomoses were performed in the composite group (62% versus 53%), and the gastroepiploic artery was used more often in the cross group (30% versus 19%). Thirty-day mortality was 3.9% in the composite and 2.3% in the cross group (not significant). Occurrence of postoperative complications (sternal infection, myocardial infarction, cerebrovascular accident, and bleeding) was similar. Late follow-up (2 to 56 months) showed increased return of angina (6% versus 3.1%; p = 0.046) and decreased 4-year survival (Kaplan-Meier; 86% +/- 2.7% versus 92.4% +/- 1.5%; p = 0.07) in composite patients. CONCLUSIONS Early results of bilateral internal thoracic artery grafting with composite T graft are comparable with those of in situ grafts. However, increased angina return and decreased midterm survival led us to recommend in situ grafting whenever technically possible.

Influence of bilateral skeletonized harvesting on occurrence of deep sternal wound infection in 1,000 consecutive patients undergoing bilateral internal thoracic artery grafting.

ObjectiveTo evaluate the risk of deep sternal infection in a large patient cohort following bilateral internal thoracic artery (BITA) grafting using skeletonized BITA dissection. Summary Background DataComplete myocardial revascularization using BITAs improves long-term survival and lowers the rate of repeat operations. Harvesting of ITAs as skeletonized vessels preserves sternal collateral blood supply, thus enabling rapid sternal healing with less risk of deep sternal infection. MethodsOne thousand consecutive patients (763 men, 340 patients >70 years old, 304 diabetics) underwent skeletonized BITA grafting from April 1996 to July 1999. ResultsThe 30-day mortality rate was 3.4%. There were 10 perioperative infarcts, 16 strokes, and 22 deep sternal infections. There was an increased risk of deep sternal infection in repeat coronary artery bypass grafting (CABG) operations (15%), chronic obstructive pulmonary disease (COPD) (6.2%), congestive heart failure (4.7%), left ventricular dysfunction (ejection fraction < 35%, 4.5%), and longer aortic cross-clamping time. After adjustment for other demographic, clinical, and surgical predictors, the only independent predictors of deep sternal infection were repeat operations, COPD, and duration of aortic cross-clamping. No patients in the reoperation subgroup died, but three of six COPD patients with deep sternal infection died, and COPD was an independent predictor of overall (early + late) mortality. ConclusionsSkeletonized BITA grafting carries an acceptable risk of deep sternal infection but is not recommended for repeat CABG or for patients with COPD.

Coronary artery bypass without cardiopulmonary bypass for patients with acute myocardial infarction.

OBJECTIVE Between January 1992 and December 1994, 57 patients having an acute myocardial infarction with coronary anatomy suitable for coronary artery bypass grafting without cardiopulmonary bypass underwent this procedure within 1 week of the infarction. We describe the surgical results of these high-risk patients. METHODS The study population included 43 male patients (75%) and 14 female patients (25%) whose mean age was 58.5 +/- 10.4 years. Thirty-two patients (56%) underwent emergency bypass grafting within 48 hours of an acute myocardial infarction, 4 of them (12.5%) as a bailout procedure after complicated percutaneous transluminal coronary angioplasty. Of these 32 patients, 7 patients (22%) were in cardiogenic shock, and 10 patients (31%) required preoperative intra-aortic balloon pump. Twenty-five patients (44%) underwent coronary bypass grafting 2 to 7 days after an acute myocardial infarction. The mean number of grafts per patient was 1.8 (range, 1-4), and the internal thoracic artery was used in 47 patients (82%). Only 7 patients (12%) received grafts to a circumflex marginal branch. RESULTS Operative mortality was 1.7% (1 patient), and the mean postoperative hospital stay was 6.8 +/- 3 days. One- and 5-year actuarial survivals were 94.7% and 82.3%, respectively. Angina returned in 7 patients (12%), 1 of whom underwent reoperation. Multivariate analysis revealed renal failure and preoperative cardiogenic shock to be independent predictors of overall mortality. Old myocardial infarction and operation within the first 48 hours were independent predictors of overall unfavorable outcome events. CONCLUSIONS These results suggest that coronary artery bypass grafting without cardiopulmonary bypass is a relatively low-risk procedure for patients having an infarction with coronary anatomy suitable for this technique.

Technical aspects of double-skeletonized internal mammary artery grafting

BACKGROUND Bilateral internal mammary artery (IMA) grafting is performed to provide complete arterial myocardial revascularization with the intention of decreasing postoperative return of angina and the need for reoperation. We present here technical views of double-skeletonized IMA grafting, and evaluate its clinical outcome. METHODS Skeletonized IMA is harvested gently with scissors and silver clips, without use of cauterization, and embedded in a small syringe filled with papaverine. Three strategies for arterial revascularization were employed in 762 consecutive patients: (1) the cross arrangement (242 patients, 32%), where the in situ right internal mammary artery (RIMA) is used for the left anterior descending artery (LAD), in situ left internal mammary artery (LIMA) to circumflex marginal branches and the gastroepiploic artery for the right coronary artery (RCA); (2) the composite arrangement (476 patients, 62%), where free IMA is attached end-to-side to the other in situ IMA; and (3) the natural arrangement (44 patients, 6%), where the in situ RIMA is connected to the RCA and in situ LIMA to LAD. Mean age was 66 years (range 30 to 92). Two hundred ninety-two patients (38%) were older than 70, and 229 (30%) were diabetic. RESULTS Operative mortality was 2.5% (n = 19). The mortality of urgent and elective cases was 1.2% (8 of 663), and that of emergency operation was 11% (11 of 99). There were 9 (1.2%) perioperative myocardial infarctions, and 10 patients (1.3%) sustained strokes. Sternal wound infection occurred in 14 (1.8%). CONCLUSIONS The three strategies described here provide the surgeon with the versatility required for arterial revascularization with bilateral IMAs in most patients referred for coronary artery bypass grafting.