Effects of different degrees of sympathetic antagonism on cytokine network in patients with ischemic dilated cardiomyopathy.

BACKGROUND: The proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Recent studies have shown that beta-adrenergic blockade can modulate cytokine production. This study investigates the different impact of different degrees of sympathetic antagonism on circulating levels of cytokines in patients with heart failure resulting from ischemic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Thirty-five patients with IDC were randomly assigned to receive metoprolol or carvedilol in an open-label study. Echocardiographic measurements and circulating levels of tumor necrosis (TNF)-alpha and interleukin (IL)-1beta and IL-6 were obtained at baseline and after 3 months of treatment. The 2 beta-blockers significantly improved the left ventricular ejection fraction and reduced end-diastolic and end-systolic volume. The magnitude of these changes was greater with carvedilol than with metoprolol (respectively P < .001, P < .05, and P < .05). Both treatments induced a significant decrease in the levels of cytokines (for all P < .01), but the decrease in TNF-alpha and IL-1beta was more consistent in the carvedilol group ( P < .01). CONCLUSION: Our results support the hypothesis that a more complete block of sympathetic activity by carvedilol induces a greater decrease in the circulating levels of proinflammatory cytokines that could explain, at least in part, the better improvement in the left ventricular remodelling and systolic function in patients with IDC.

Exercise training improves diastolic perfusion time in patients with coronary artery disease.

Exercise training elicits an improvement in work capacity and in left-ventricular function in patients with coronary artery disease. An improvement in myocardial oxygen supply accounts for these effects. The aim of this study was to test the hypothesis that exercise training could favorably influence diastolic perfusion time, a major determinant of subendocardial perfusion. Twenty-two male patients with coronary artery disease were randomized to a training or control group. At the study entry and after one year, all patients underwent an exercise stress test. After one year, rest heart rate was lower and diastolic perfusion time was higher in the training group but not in the control group. At peak of exercise, diastolic perfusion time increased and ST-segment depression decreased significantly in the training group but not in the control group. A significant relation was found between the R-R interval and the diastolic perfusion time either before or after training, with a difference in the intercepts of two regressions. Training shifted updown-line regression, effecting a higher value of diastolic perfusion time for a given value of heart rate. Thus, training increases diastolic perfusion time, independently from the effect on heart rate. This mechanism may contribute to the improvement of myocardial perfusion.