Arterial myocardial revascularization with in situ crossover right internal thoracic artery to left anterior descending artery.

BACKGROUND: The extra length obtained by skeletonizing the internal thoracic arteries (ITAs) enables versatile use of in situ bilateral ITAs for coronary artery bypass grafting, as the longer skeletonized right ITA more easily reaches the anastomotic site on the left anterior descending coronary artery. METHODS: Between April 1996 and November 1999, 365 consecutive patients underwent revascularization with bilateral in situ ITAs (29% of 1,250 grafting procedures performed with both ITAs in our department during this period). The right ITA was routed anterior to the aorta to graft the left anterior descending coronary artery, and the in situ left ITA was used to graft circumflex branches. Right coronary artery branches were grafted with right gastroepiploic artery or saphenous vein graft. The right ITA crossed the midline above the aorta at the most cranial point to avoid damage in case of a repeat sternotomy in the future. RESULTS: The operative mortality rate was 2.2% (8 patients). Postoperative morbidity included seven strokes (1.9%), eight sternal wound infections (2.2%), and four perioperative myocardial infarctions (1.1%). Follow-up (6 to 49 months) of 97% of hospital survivors showed a return of angina in 3%. Postoperative coronary angiography (22 patients) revealed a 95% patency rate of both ITAs. One-year and 4-year survival rates (Kaplan-Meier) were 95% and 92.4%, respectively. Important predictors of an early unfavorable event were chronic obstructive pulmonary disease, old age (> or = 70 years), emergency operation, and diabetes. Chronic obstructive pulmonary disease was the only independent predictor of sternal wound infection (odds ratio, 15; 95% confidence interval, 2.8 to 80). It also predicted decreased late survival (hazard ratio, 8.3; 95% confidence interval, 3 to 21.5). CONCLUSIONS: With skeletonized dissection of ITAs, the right ITA easily reaches the left anterior descending coronary artery for left-sided arterial revascularization with in situ bilateral ITAs. This procedure is safe, but we recommend avoiding its use in patients with chronic obstructive pulmonary disease.

Composite arterial grafting with double skeletonized internal thoracic arteries.

OBJECTIVES: Composite arterial grafting is a surgical technique for arterial myocardial revascularization, in which free arterial conduits are proximally anastomosed end-to-side to an intact internal thoracic artery (ITA). This report describes technical aspects and results of composite grafting using bilateral skeletonized ITAs. METHODS: From April 1996 to February 1999, 1057 patients underwent coronary artery bypass grafting (CABG) using bilateral skeletonized internal thoracic arteries. In 600 of them (57%), composite arterial grafting was performed. There were 452 men and 148 women. The mean age was 69 +/- 7 years. Two-hundred and six patients (34%) were diabetics, 84 (14%) had severe left ventricular dysfunction (ejection fraction of < 35%), and 26 (4.3%) underwent emergency operations. In 574 patients, the right ITA was used as a free graft connected to the in-situ left ITA. In 26, the free left ITA was attached to the in-situ right ITA, and in 38, mini-composite grafts (free distal left ITA on the left ITA, or free distal right ITA on the right ITA) were constructed. The average number of grafts was 3.0/patient (range, 2--6). RESULTS: The operative mortality was 2.8% (n = 17), and there were ten (1.7%), deep sternal wound infections. The mean follow-up was 25 months (range, 14--36 months). The 3-year survival was 92.5%. Ninety-seven percent of the surviving patients were angina-free. CONCLUSIONS: We currently perform this surgery routinely in most patients referred for CABG, and regard bilateral skeletonized internal thoracic arteries as the most appropriate arterial conduits for the composite technique.

Effect of age on outcome of bilateral skeletonized internal thoracic artery grafting.

BACKGROUND: Elderly patients are considered to be at higher risk for coronary artery bypass grafting. Surgical techniques of arterial myocardial revascularization without vein grafts were primarily reserved for the young. This report evaluates the impact of age on the outcome of 634 consecutive patients who underwent double skeletonized internal thoracic artery grafting between April 1996 and December 1997. METHODS: Patients were stratified into five age groups: One hundred ninety-six were less than 60 years of age, 98 between 60 and 65 years, 132 between 65 and 70 years, 116 between 70 and 75 years, and 92 were older than 75 years. The groups did not differ with regard to preoperative risk factors. RESULTS: Hospital mortality was 2.5% (n = 16). Mortality of urgent and elective operations was 1.6%, and that of emergency operations was 9.7% (p < 0.001). There were 7 (1.1%) myocardial infarctions, 9 strokes (1.4%), and 10 deep sternal wound infections (1.6%). Using the Mantel-Haenszel test, there was no relation between age and hospital mortality, myocardial infarctions, strokes, or sternal infections. A correlation was found between advanced age and early unfavorable events (6.7%, 7.2%, 12.9%, 15.5%, and 15.2% in corresponding age groups, p < 0.003), and late mortality (0.6%, 1%, 1.5%, 4.3%, and 9.8%, respectively, p < 0.01). However, early return of angina was lower (2.6%, 1%, 0.8%, 0.9%, and 0%, p < 0.06). CONCLUSIONS: This retrospective, nonrandomized study suggests that older age is not a risk factor for operative mortality in patients undergoing coronary artery bypass grafting with double skeletonized internal thoracic arteries. Apart from avoiding morbidity associated with leg incisions, older patients showed an interesting trend toward lower rates of angina return. Older patients, however, sustained increased perioperative morbidity and late mortality rates.

Bilateral skeletonized internal thoracic artery grafts in patients with diabetes mellitus.

OBJECTIVE: Increased risk of deep sternal infections has prohibited routine bilateral internal thoracic artery grafting in diabetic patients. The technique for harvesting the skeletonized internal thoracic artery provides the potential to minimize this risk. The purpose of this study was to compare the outcome of bypass grafting with bilateral skeletonized internal thoracic arteries in diabetic and nondiabetic patients. METHODS: From May 1996 to April 1998, 231 consecutive diabetic and 534 nondiabetic patients underwent bilateral skeletonized internal thoracic artery grafting. Mean age was 66 years. Compared with the nondiabetic group, the diabetic group comprised more women (29% vs 18%, P =.001), had a greater prevalence of hypertension (53% vs 44%, P =.019) and congestive heart failure (20% vs 14%, P =.016), but a lower prevalence of preoperative acute myocardial infarction (26% vs 34%, P =.027). RESULTS: Operative mortality of diabetic patients was comparable with that of nondiabetic patients (3% vs 2.6%). The two groups also had similar occurrences of deep sternal infection (2.6% vs 1.7%, respectively, P =.40). Deep sternal infection was significantly more prevalent in obese, diabetic women (3/20 = 15%) than in diabetic patients without this combination of risk factors (3/211 = 1.4%, P <.0001) (odds ratio 11.1, confidence interval 2.1-59.4). Diabetic patients also had a higher incidence of stroke (3.5% vs 0.9%, P =.014). Three-year actuarial survival of diabetic patients was lower (91.3% vs 94.7%, P =.083). CONCLUSIONS: Bilateral skeletonized internal thoracic artery grafting is a good surgical revascularization option in diabetic patients. Operative mortality and prevalence of sternal infection are comparable with those of nondiabetic patients. However, the risk of sternal infection in obese diabetic women is high, and for them we advocate the use of a single artery instead of bilateral internal thoracic arteries.

Interaction between paracrine tumor necrosis factor-alpha and paracrine angiotensin II during myocardial ischemia.

OBJECTIVES: The purpose of this study was to explore interactions between paracrine angiotensin II (Ang-II) and tumor necrosis factor-alpha (TNF-alpha) during myocardial ischemia. BACKGROUND: Ischemic myocardium releases significant amounts of TNF-alpha. This paracrine release correlated with postischemic myocardial injury. Other studies showed myocardial protection obtained by the use of angiotensin-converting enzyme inhibitors (i.e., captopril) and the Ang-II type 1 receptor antagonist losartan after ischemia. The possibility that these agents decrease TNF-alpha synthesis has not yet been investigated. METHODS: Using the modified Langendorff model, isolated rat hearts underwent either 90 min of nonischemic perfusion (control group) or 1 h of global cardioplegic ischemia. In both groups, either captopril (360 micromol/liter) or losartan (182.2 micromol/liter) was added before ischemia. The hearts were assayed for messenger ribonucleic acid (mRNA) expression and effluent TNF-alpha levels. In addition, cardiac myocytes were incubated in cell culture with Ang-II. RESULTS: After ischemia, TNF-alpha mRNA expression intensified from 0.63 +/- 0.06 (control group) to 0.92 +/- 0.12 (p < 0.03), and effluent TNF-alpha levels were 711 +/- 154 pg/ml. The TNF-alpha mRNA expression declined to 0.46 +/- 0.07 (p < 0.01) and 0.65 +/- 0.08 (p < 0.02) in captopril- and losartan-treated hearts, respectively. Effluent TNF-alpha was below detectable levels. Concentrations of TNF-alpha in supernatants of incubated cardiac myocytes treated with 10 and 50 nmol/liter of Ang-II were 206.0 +/- 47.0 pg/ml and 810 +/- 130 pg/ml, respectively (p < 0.004). When pretreated with 700 micromol/liter of losartan, TNF-alpha was below detectable levels. CONCLUSIONS: This study presents an original explanation for previously reported myocardial protection after ischemia, obtained by the use of captopril and losartan. These drugs reduce TNF-alpha synthesis, providing strong evidence of active interactions between paracrine TNF-alpha and Ang-II in the evolution of the ischemic cascade.

Emergency myocardial revascularization for acute myocardial infarction: survival benefits of avoiding cardiopulmonary bypass.

OBJECTIVE: Emergency coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI) is associated with increased operative mortality. It has been suggested that this mortality might be reduced by performing the operation without cardiopulmonary bypass (CPB). METHODS: Between January 1992 and April 1998, 77 patients underwent emergency CABG within 48 h of AMI. Thirty seven were operated on with CPB, and 40 without CPB. The two groups were similar regarding age, gender, left-ventricular ejection fraction (EF) and preoperative use of intra-aortic balloon pump (IABP; 50%). The mean number of grafts/patient was 3 in the CPB group, and 1.9 in the No-CPB group (P<0.0001). RESULTS: Operative mortality in the CPB group was 24% (nine of 37) compared to 5% (two of 40) without CPB (P=0.015). Follow-up ranged between 6 and 66 months. There were no late deaths in the CPB group compared to nine (22%) in the No-CPB group (P<0.0066). Patients operated on with CPB had lower rates of recurrent angina (0 versus 15%; P=0.04) and re-interventions (0 versus 15%; P=0.04). CONCLUSIONS: Our experience suggests that CABG without CPB is the preferred method of myocardial revascularization, due to the fact that it carries lower mortality than CABG with CPB. The trade-off includes increased rates of recurrent angina, re-interventions and late mortality.

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.

Routine use of bilateral skeletonized internal mammary arteries for myocardial revascularization.

BACKGROUND: Complete arterial myocardial revascularization without the use of saphenous veins grafts was primarily performed on selected patient populations such as the young and nondiabetic. In a recently developed surgical technique, the internal mammary artery is dissected gently as a longer skeletonized artery, providing greater versatility for complete arterial revascularization, without saphenous veins grafts. METHODS: We prospectively evaluated the impact of the routine use of double skeletonized internal mammary artery in 472 patients who underwent coronary artery bypass grafting between April 1996 and June 1997. Their average age was 65 years (30 to 87 years), 383 (83%) were men, and 89 (17%) women. One hundred sixty-nine (36%) of the patients were older than 70 years, and 145 (31%) were diabetic. The average number of grafts was 3.2 per patient (two to six grafts). RESULTS: Operative mortality was 1.7% (n = 8). The mortality of urgent and elective patients was 0.7% (3 of 410 patients), and that of emergency operations was 8.1% (5 of 62 patients; p < 0.01). There were three (0.6%) perioperative infarcts, and 6 patients (1.3%) sustained strokes. Sternal wound infection occurred in 8 patients (1.7%). Postoperative follow-up (1 to 25 months) was available in 462 patients (99%). Two-year actuarial survival was 96.8%, and 92% of the surviving patients are well and free of angina. Neither diabetes mellitus nor old age (>70 years) were significant independent predictors of any early or late untoward events. None of the 70 diabetic patients more than 65 years of age developed sternal wound infection. Chronic lung disease was found to be the only independent predictor for sternal infections. CONCLUSIONS: Routine use of bilateral skeletonized internal mammary artery is a safe replacement for the current myocardial revascularization technique even in the old and diabetic patients.

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.

Effects of an angiotensin II antagonist on ischemic and nonischemic isolated rat hearts.

BACKGROUND: Increasing evidence suggests that a locally integrated or intramyocardial renin-angiotensin system plays a significant role in ischemia-reperfusion injury. We evaluated the effects of losartan, an angiotensin II type 1 receptor blocking agent, on ischemic and nonischemic isolated rat hearts. METHODS: Using the modified Langendorff model, hearts were perfused with either low or high doses of losartan (18.2 mmol/L or 182.2 mmol/L, respectively) or with saline added to Krebs-Henseleit solution during phase I of the study. During phase II, hearts were exposed to a 60-minute period of global ischemia. Ischemic arrest was induced with warm cardioplegic solution (KCl, 16 mEq/L) containing either high-dose losartan (182.2 mmol/L) or Krebs-Henseleit solution only. RESULTS: During phase I of the study, no statistically significant differences were observed between the low-dose losartan group and the control group. However, hearts treated with high-dose losartan demonstrated an increase in peak systolic pressure, maximum first derivative of pressure, pressure-time integral, coronary flow, and oxygen consumption (p < 0.0001). During phase II, hearts treated with losartan showed a significantly better recovery on reperfusion, as reflected by better contractility (p < 0.001), higher oxygen consumption (p < 0.001), higher coronary flow (p < 0.0001), and lower creatine phosphokinase levels (41.1 +/- 1.7 versus 73.3 +/- 5.6 U/L; p < 0.001). CONCLUSIONS: High doses of losartan have a positive inotropic effect on normally perfused hearts. Given in cardioplegic solution, the drug has a significant protective effect on ischemic isolated rat hearts.

[Routine use of of two internal mammary arteries for coronary bypass grafting--one year experience at the Tel Aviv Medical Center].

The skeletonized internal mammary artery (IMA) is longer, and its immediate spontaneous blood flow is greater than that of the pedicled IMA, thus providing increased versatility for complete, arterial myocardial revascularization without the use of saphenous vein grafts. From April 1996 to May 1997, 583 patients underwent coronary artery bypass grafting here and in 415 (71%) complete arterial revascularization was achieved using bilateral skeletonized IMA. The right gastroepiploic artery was used in 57 (13%); there were 329 males (79%) and 86 women (21%); average age was 64 (30-87) and 175 (36%) were older than 70; 131 (32%) were diabetics. Average number of grafts was 3.2 (range 2-6 grafts). At 30 days, 5 (1.2%) had died and there had been 6 perioperative infarcts (1.4%), 5 CVA's (1.2%), and 6 had sternal wound infections (1.4%). Up to 1-12 months of follow-up was achieved in 409 (99%). Late mortality was 1.4% (of which 3 were noncardiac). 394 (97%) were angina-free at latest follow-up. We conclude that arterial revascularization using bilateral skeletonized IMA is safe, as postoperative morbidity and mortality are low, even in old and diabetic patients.

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.

Captopril in cardioplegia and reperfusion: protective effects on the ischemic heart.

BACKGROUND: Previous studies have shown that long-term treatment with the angiotensin-converting enzyme inhibitor captopril attenuates left ventricular dilatation and improves survival after extensive myocardial infarction. However, there is only sparse evidence of the immediate effects of the drug on hearts undergoing global ischemia and reperfusion. The purpose of this study was to investigate the direct effect of captopril, given in cardioplegia or after ischemia, on the functional recovery of the reperfused myocardium. METHODS: Isolated rat hearts undergoing warm cardioplegic arrest followed by 1 hour of global ischemia and 30 minutes of reperfusion were studied using the modified Langendorff model. RESULTS: After ischemia, hearts receiving captopril (360 mumol/L) either in the cardioplegic solution (n = 9) or during reperfusion (n = 9) developed higher pressure (p < 0.001), greater first derivative of the rise in left ventricular pressure (p < 0.01 and p < 0.001, respectively), greater first derivative of the fall in left ventricular pressure (p < 0.001 and p < 0.002), higher pressure-time integral (p < 0.001), greater coronary flow (p < 0.001), and higher oxygen consumption values (p < 0.001 and p < 0.003) compared with the control group (n = 9). Hearts receiving captopril both in the cardioplegia and during reperfusion (n = 9) had the best recovery of all three groups and lower levels of creatine kinase (47.8 +/- 5.9 U/L versus 73.3 +/- 5.6 U/L; p < 0.01) compared with the control group. CONCLUSIONS: Captopril given in cardioplegia and in reperfusion has a favorable, protective, and additive effect on the recovery of isolated rat hearts undergoing global ischemia and reperfusion; hemodynamic performance improves, coronary flow and oxygen consumption increase, and myocardial damage decreases.

High-dose isosorbide dinitrate for myocardial revascularization with composite arterial grafts.

BACKGROUND: Composite arterial grafting for myocardial revascularization is a surgical technique in which free arterial conduits are proximally attached to an in situ internal mammary artery. METHODS: Composite arterial grafting was performed in 78 patients with internal mammary artery (n = 24), inferior epigastric artery (n = 21), or radial artery (n = 33) connected to the internal mammary artery. Overall, 254 distal anastomoses were performed (average number, 3.3 per patient), 225 of which were arterial. All patients were treated postoperatively with high-dose isosorbide dinitrate (4 to 20 mg/h for 24 hours). RESULTS: The in-hospital mortality rate was 2.6% (2 patients). Early recatheterization studies performed 3 weeks (range, 1 to 20 weeks) after operation in 30 patients demonstrated patency rates of 100%, 93%, and 100% for the composite internal mammary artery, inferior epigastric artery, and radial artery groups, respectively. In addition, two inferior epigastric artery conduits had major intraluminal constriction. At a mean follow-up of 20 months (range, 1 to 42 months) all patients are alive, and all but 2 in the inferior epigastric group (97%) are angina free. CONCLUSIONS: This surgical technique can be safely used. On the basis of our experience, the right internal mammary artery and the radial artery are the most suitable conduits for this procedure. High-dose nitrates given perioperatively prevent spasm and ensure early patency rates.

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.

Long-range correlation properties of coding and noncoding DNA sequences: GenBank analysis.

An open question in computational molecular biology is whether long-range correlations are present in both coding and noncoding DNA or only in the latter. To answer this question, we consider all 33301 coding and all 29453 noncoding eukaryotic sequences--each of length larger than 512 base pairs (bp)--in the present release of the GenBank to dtermine whether there is any statistically significant distinction in their long-range correlation properties. Standard fast Fourier transform (FFT) analysis indicates that coding sequences have practically no correlations in the range from 10 bp to 100 bp (spectral exponent beta=0.00 +/- 0.04, where the uncertainty is two standard deviations). In contrast, for noncoding sequences, the average value of the spectral exponent beta is positive (0.16 +/- 0.05) which unambiguously shows the presence of long-range correlations. We also separately analyze the 874 coding and the 1157 noncoding sequences that have more than 4096 bp and find a larger region of power-law behavior. We calculate the probability that these two data sets (coding and noncoding) were drawn from the same distribution and we find that it is less than 10(-10). We obtain independent confirmation of these findings using the method of detrended fluctuation analysis (DFA), which is designed to treat sequences with statistical heterogeneity, such as DNA's known mosaic structure ("patchiness") arising from the nonstationarity of nucleotide concentration. The near-perfect agreement between the two independent analysis methods, FFT and DFA, increases the confidence in the reliability of our conclusion.

Role of protease inhibition in myocardial preservation following ischemia and reperfusion.

Aprotinin, a naturally occurring protease inhibitor, in concentrations of 10(6) KIU/L was found to have no effect on myocardial performance in normally perfused isolated rat hearts, before ischemia. Given during the preischemic period, the drug had a significant protective effect on the reperfused hearts, following cardioplegic ischemia: better contractility upon reperfusion (p < 0.011), faster decline of the ischemic contracture, higher coronary flow (p < 0.025), lower AV-difference (p < 0.05), and lower CPK levels (p < 0.01).

Transvenous implantable cardiovascular defibrillator lead system: experience in 28 patients.

Morbidity and mortality following Automatic Implantable Cardioverter Defibrillation (AICD) is mostly related to thoracotomy performed during placement of epicardial leads. From July 1991 to January 1994, a transvenous lead system (TLS) (Endotak C; CPI) was implanted in 28 patients (24 males, 4 females, age 15-76 years) who suffered from life threatening ventricular tachyarrhythmias. Twenty four patients had a previous MI, mean LVEF was 26% (14-65%), two had mitral valve prolapse (one with prolonged QT), one had hypertrophic and another had dilated cardiomyopathy. The implantation procedure was performed in the operating room (n = 26) or in the Cath lab. (n = 2). Nineteen (out of the 28) patients were treated with Amiodarome before implantation (5 out of 7 had LVEF < 30%). A satisfactory defibrillation threshold (DFT) was achieved using Endotak lead alone in 22 (79%) patients. These patients had LVEF between 10% to 65% (less than 30% in three patients). In six patients the DFT was measured as lower than 20 J, and a subcutaneous patch was added (LVEF 12-38%, 4 patients with Amiodarome therapy). The implanted devices were all from CPI: 1600 (n = 5), PRX (n = 7), P2 (n = 15), PRX II (n = 1). During a 1-32 months of follow-up one patient died from severe CHF. The implanted device operated in 9/28 patients. The only complication related to implantation was infection at the pocket site (n = 2), which responded to antibiotic therapy in one patient, but required device explantation in another patient. The device was reimplanted in that patient three month later, with no further complications.(ABSTRACT TRUNCATED AT 250 WORDS)