Taxol, a microtubule stabilizer, improves cardiac contractile function during ischemia in vitro

Abstract

Ischemic heart disease is one of the leading causes of heart failure, and microtubule disruption has been implicated in the response to ischemia in cardiac myocytes. The present study was designed to explore the effects of taxol, a microtubule stabilizer, on cardiac contractile function during ischemia. Heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure, maximal time derivatives of pressure and work index were analyzed in isolated rat or rabbit hearts during ischemia. In addition, intracellular calcium concentrations ([Ca(2+)](i)) and Ca(2+) transients were examined by Fura-2-AM and Fluo-3-AM, respectively. Reactive oxygen species (ROS) and oxidative enzyme activities were measured with fluorometric or spectrophotometric techniques. It was found that taxol could improve the cardiac contractile function during ischemia. This effect was identified based on a blunting of the decrease in heart rate, left ventricular developed pressure, maximal time derivatives of pressure and work index during ischemia, which might be related to the preservation of calcium homeostasis and ROS levels. The preservation of calcium homeostasis included a decrease in the rise of [Ca(2+)](i) and maintenance of the amplitude and decay time of Ca(2+) transients. The reduction in ROS levels was associated with increased activity of mitochondrial electron transport chain complex I and complex III. In conclusion, taxol could effectively improve the cardiac contractile function during ischemia by preserving calcium homeostasis and ROS levels. This study presents evidence that taxol could represent a novel approach to drug development for heart failure.