Mean platelet volume in predicting short- and long-term morbidity and mortality in patients with or without ST-segment elevation myocardial infarction.

Mean platelet volume (MPV) is a marker of platelet activation. An increased MPV is associated with acute myocardial infarction (AMI) and long-term mortality. The aim of this study was to compare MPV in patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). Also, we investigated the value of MPV on in-hospital mortality and long-term prognosis of patients with STEMI and NSTEMI. We studied 429 patients with AMI (70.4% male, 61.9 ± 12.4 years; 279 patients with STEMI, 150 patients with NSTEMI). MPV and platelet count were similar in both groups. Elevated MPV increased the risk of death by 3.1-fold (p < 0.001) in STEMI group during the hospitalization. However, increased MPV was not associated with in-hospital mortality in NSTEMI group. The area under the receiver operating characteristic curve of MPV was 0.868 (95% CI, 0.830-0.907) for predicting two-year mortality. A cut-off point of 11.1 fL showed a sensitivity of 81% and a specifity of 77% for prediction of two-year mortality. Kaplan-Meier survival curve showed two-year mortality rate of 12.5% in patients with MPV >11.1 fL versus 9.9% in patients with MPV <11.1 fL (p < 0.001). Cox regression analysis showed MPV to be an independent predictor of two-year mortality (Hazard ratio 1.7; 95% CI 1.5-1.9; p < 0.001). An increased MPV is an independent predictor of in-hospital mortality in patients with STEMI. However, elevated levels of MPV did not predict in hospital mortality in NSTEMI group. The increase in MPV values was independently correlated with two-year mortality in all study patients.

Effects of chronic trimetazidine treatment on myocardial preconditioning in anesthetized rats.

Trimetazidine is a widely used anti-ischemic agent, but effects of its chronic treatment on myocardial preconditioning in anesthetized animals have not been investigated. The aim of this study was to examine the effects of 15-day treatment of trimetazidine on ischemic preconditioning and carbachol-induced preconditioning in anesthetized rats. Ischemic preconditioning, induced by 5 min of coronary artery occlusion and 5 min of reperfusion, significantly decreased the total number of ventricular ectopic beats, the incidence of ventricular tachycardia and abolished the occurrence of ventricular fibrillation (VF) during 30 min of ischemia. Trimetazidine (10 mg/kg/day, i.p. for 15 days and 10 mg/kg, i.v.) itself attenuated these arrhythmia parameters with no marked effect on hemodynamic effects. In the presence of trimetazidine, anti-arrhythmic effects of ischemic preconditioning were present. Carbachol infusion induced preconditioning with a marked depression of mean arterial blood pressure, heart rate and the total number of ventricular ectopic beats. No VF was observed in carbachol-induced preconditioning. The marked reductions in arrhythmia parameters that induced carbachol-induced preconditioning were also preserved in the presence of trimetazidine. Arrhythmia scores and myocardial infarct size were reduced significantly with ischemic preconditioning or carbachol-induced preconditioning and were not modified by trimetazidine. Lactate and malondialdehyde levels were suppressed significantly with preconditioning or trimetazidine + preconditioning groups. These results show that chronic treatment of trimetazidine protects the heart against ischemia-induced arrhythmias, reduces myocardial infarct size, plasma lactate and malondialdehyde levels, and preserves the effects of ischemic and pharmacological preconditioning in anesthetized rats.

Effects of fasudil, a Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats.

The aim of this study was to examine the effects of fasudil, a Rho-kinase inhibitor, on ischemic preconditioning and carbachol preconditioning in anesthetized rats. The total number of ventricular ectopic beats was markedly augmented with fasudil at 0.3 mg/kg and depressed with fasudil at 10 mg/kg. Fasudil at 10 mg/kg also markedly decreased the ventricular tachycardia incidence. Ischemic preconditioning, induced by 5 min coronary artery occlusion and 5 min reperfusion, decreased the incidence of ventricular tachycardia and abolished the occurrence of ventricular fibrillation. The incidences of ventricular tachycardia and ventricular fibrillation in the fasudil (10 mg/kg) + ischemic preconditioning group were found to be similar to the ischemic preconditioning group. However, low doses of fasudil (0.3 and 1 mg/kg) appeared to prevent the antiarrhythmic effects of ischemic preconditioning. Carbachol (4 microg/kg/min for 5 min) induced marked reductions in mean arterial blood pressure, heart rate and abolished ventricular tachycardia. Marked reductions in ventricular ectopic beats and ventricular tachycardia were noted in the fasudil (10 mg/kg) + carbachol preconditioning group. Lactate levels were markedly reduced in the ischemic preconditioning group and this reduction was prominently inhibited with fasudil at 1 mg/kg. Ischemic preconditioning caused a marked decrease in plasma malondialdehyde levels. Fasudil (10 mg/kg), ischemic preconditioning and carbachol preconditioning each generated marked reductions in ischemic myocardial malondialdehyde levels. Decreases in infarct size were observed with fasudil (10 mg/kg) treatment, ischemic preconditioning and carbachol preconditioning when compared to control. These results suggest that low doses of fasudil (0.3 and 1 mg/kg) appeared to prevents the effects of ischemic preconditioning and carbachol preconditioning, but a high dose of fasudil (10 mg/kg) was able to produce cardioprotective effects on myocardium against arrhythmias, infarct size or biochemical parameters and mimic the effects of ischemic preconditioning in anesthetized rats.

Effects of Y-27632, a selective Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats.

The objective of this study was to examine the effects of Y-27632, a selective Rho-kinase inhibitor, on ischemic preconditioning (IP) and carbachol preconditioning (CP) in anesthetized rats. Administration of Y-27632 (0.1 mg/kg) produced slight, but not significant, reduction in mean arterial blood pressure and suppressed the total number of ventricular ectopic beats (VEBs). IP, induced by 5 min coronary artery occlusion and 5 min reperfusion, decreased the incidence of ventricular tachycardia (VT) from 100 (n=30) to 25% (n=24) and abolished the occurrence of ventricular fibrillation (VF) (40% in control group) during 30 min of ischemia. The incidences of VT and VF in Y-27632+IP group were found to be similar to IP group. Carbachol (4 microg/kg/min for 5 min) induced marked depressions in mean arterial blood pressure, heart rate and attenuated the total number of VEBs, but significant reductions in VT and VF incidences were noted in Y-27632+CP group. Y-27632 infusion for 5 min abolished VF occurrence. Marked reductions in plasma lactate levels were observed in all treatment and preconditioning groups. IP led to marked decrease in malondialdehyde levels. Decreases in infarct size were also observed with all groups when compared to control. These results suggest that infusion of Y-27632 was able to produce cardioprotective effects on myocardium against arrhythmias, infarct size or biochemical parameters and mimic the effects of ischemic preconditioning in anesthetized rats. Therefore, it is likely that inhibition of Rho-kinase is involved in the signaling cascade of myocardial preconditioning.

Effects of trimetazidine on myocardial preconditioning in anesthetized rats.

Trimetazidine is a widely used anti-ischemic agent, but its effect on myocardial preconditioning in anesthetized animals has not been investigated. The aim of this study was to examine the effects of trimetazidine on ischemic preconditioning and carbachol preconditioning in anesthetized rats. Ischemic preconditioning, induced by 5-min coronary artery occlusion and 5-min reperfusion, decreased the incidence of ventricular tachycardia and abolished the occurrence of ventricular fibrillation during 30-min ischemia. Trimetazidine (10 mg/kg, i.v.) alone attenuated these parameters of arrhythmia. Carbachol infusion induced preconditioning with a marked depression of mean arterial blood pressure, heart rate and ventricular tachycardia. The marked reductions in parameters of arrhythmia induced by ischemic preconditioning and carbachol preconditioning were preserved in the presence of trimetazidine. Arrhythmia scores and myocardial infarct size were significantly reduced with ischemic preconditioning or carbachol preconditioning and were not inhibited by trimetazidine. These results show that trimetazidine protects the heart against ischemia-induced arrhythmias, reduces myocardial infarct size, preserves the effects of ischemic preconditioning and pharmacological preconditioning, and is able to mimic ischemic preconditioning in anesthetized rats.