Effect of tumor necrosis factor-alpha on endothelial and inducible nitric oxide synthase messenger ribonucleic acid expression and nitric oxide synthesis in ischemic and nonischemic isolated rat heart.

OBJECTIVES: The present study aimed to investigate the influence of endogenous tumor necrosis factor-alpha (TNF-alpha) that was synthesized during ischemia and exogenous TNF-alpha on endothelial and inducible nitric oxide synthase (eNOS and iNOS) messenger ribonucleic acid (mRNA) expression and nitric oxide (NO) production in the isolated rat heart. BACKGROUND: Tumor necrosis factor-alpha is recognized as being a proinflammatory cytokine with a significant cardiodepressant effect. One of the proposed mechanisms for TNF-alpha-induced cardiac contractile dysfunction is increased NO production via iNOS mRNA upregulation, but the role of NO in TNF-alpha-induced myocardial dysfunction is highly controversial. METHODS: Isolated rat hearts studied by a modified Langendorff model were randomly divided into subgroups to investigate the effect of 1-h global cardioplegic ischemia or the effect of 1-h perfusion with exogenous TNF-alpha on the expression of eNOS mRNA and iNOS mRNA and on NO production. RESULTS: After 1 h of ischemia, there were significant increases in TNF levels in the effluent (from hearts), and eNOS mRNA expression had declined (from 0.91 +/- 0.08 to 0.68 +/- 0.19, p < 0.001); but there were no changes in iNOS mRNA expression, and NO was below detectable levels. Perfusion of isolated hearts with TNF-alpha had a cardiodepressant effect and decreased eNOS mRNA expression to 0.67 +/- 0.04 (p < 0.002). Inducible nitric oxide synthase mRNA was unchanged, and NO was below detectable levels. CONCLUSIONS: We believe this is the first study to directly show that TNF-alpha does not increase NO synthesis and release but does downregulate eNOS mRNA in the ischemic and nonischemic isolated rat heart.

Drug-eluting stents compared with bilateral internal thoracic artery grafts for diabetic patients.

BACKGROUND: Diabetic patients with multivessel coronary artery disease who undergo coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI) are at greater risk of late morbidity and mortality than nondiabetic patients. We questioned earlier comparisons of these two approaches that showed no differences in survival rates. This study compares drug-eluting stents (DES) and bilateral internal thoracic artery (BITA) grafting in diabetic patients with multivessel coronary artery disease. METHODS: All diabetic patients who underwent left-sided arterial revascularization with BITA grafting between January 2002 and May 2006 were evaluated. Their outcomes were compared with those of diabetic patients who underwent PCI with DES (Cypher). The Cox proportional hazards model defined predictors of outcome events after forcing propensity score with patients' characteristics into the model. RESULTS: The outcomes of 226 BITA patients were compared with those of 271 DES patients (mean follow-up 62 months). The 5-year reintervention-free survival (Kaplan-Meier 86% versus 65%, log rank p = 0.000) and major adverse cardiovascular events-free survival (81% versus 54%, p = 0.001) were significantly better in the BITA group. Assignment to the PCI group was associated with decreased adjusted survival (hazard ratio 3.01, 95% confidence interval: 1.59 to 5.73, p = 0.000) and increased risk of target vessel reinterventions (hazard ratio 7.00, 95% confidence interval: 3.1 to 15.70). The adjusted risk of major adverse cardiovascular events increased with the number of DES-treated vessels. CONCLUSIONS: This is the first demonstration of significantly better long-term adjusted survival and outcomes of diabetic patients who underwent CABG with BITA grafting compared with diabetic patients who underwent PCI with DES.

A new thermoregulation system for maintaining perioperative normothermia and attenuating myocardial injury in off-pump coronary artery bypass surgery.

BACKGROUND: Most patients undergoing coronary artery bypass surgery demonstrate perioperative mild-to-moderate hypothermia (<36 degrees C). Patients undergoing off-pump coronary artery bypass (OPCAB) grafting may become even more severely hypothermic for want of cardiopulmonary bypass rewarming. One consequence is increased circulating catecholamine levels that induce an elevated systemic vascular resistance (SVR), which causes a subsequent deterioration in cardiac output. MATERIALS AND METHODS: We assessed the ability of the Allon thermoregulatory (AT) system to maintain normothermia and its impact on hemodynamics and myocardial function in patients undergoing OPCAB surgery. In this study, the first 60 of 120 suitable patients were assigned to AT (n = 40) or routine thermal care (RTC) (n = 20). Core body temperature, cardiac index (CI), SVR, and cardiac-specific troponin I (cTnI) were analyzed perioperatively for patients in both groups. RESULTS: Core body temperature was significantly higher in the AT group (from 36.1 degrees C +/- 0.5 degrees C at induction of anesthesia to 37 degrees C +/- 0.5 degrees C during surgery) than in the RTC group (from 35.8 degrees C +/- 0.4 degrees C to 35.2 degrees C +/- 0.8 degrees C, respectively; P <.01). SVR was significantly lower, and CI was greater (at comparable time points), whereas cTnI levels in the AT group were lower than in the RTC group from the end of surgery until 24 hours postoperatively (7.4 +/- 17.7 g/L versus 31.9 +/- 47.4 g/L; P =.03). These findings indicate the possibility for less ischemic damage sustained intraoperatively in the AT group. CONCLUSIONS: Maintenance of perioperative normothermia (36.5 degrees C-37.5 degrees C) during OPCAB procedures can be efficiently achieved with the Allon thermoregulation system. The system was found to be superior to other routinely used methods of temperature maintenance. Benefits may include lowering afterload (as expressed by reduced SVR), an improved CI, and attenuation of myocardial injury (as assessed by cTnI levels).