Lujan HL, DiCarlo SE. Sex differences to myocardial ischemia and -adrenergic receptor blockade in conscious rats. Am J Physiol Heart Circ Physiol 294: H1523-H1529, 2008. First published February 8, 2008 doi:10.1152/ajpheart.01241.2007.-We recently documented sex differences in the susceptibility to reperfusion-induced sustained ventricular tachycardia and -adrenergic receptor blockade in conscious rats. However, the effect of sex on ischemia-induced ventricular arrhythmias and -adrenergic receptor blockade is underinvestigated. Therefore, we tested the hypothesis that gonadal hormones influence the ventricular arrhythmia threshold (VAT) induced by coronary artery occlusion as well as the response to -adrenergic receptor blockade. The VAT was defined as the time from coronary occlusion to sustained ventricular tachycardia resulting in a reduction in arterial pressure. Male and female intact and gonadectomized (GnX) rats were instrumented with a radiotelemetry device for recording arterial pressure, temperature, and ECG, as well as a Doppler ultrasonic flow probe to measure cardiac output and a snare around the left main coronary artery. The VAT was determined in conscious rats by pulling on the snare. The VAT was significantly longer in intact females (5.56 Ϯ 0.19) vs. intact males (4.31 Ϯ 0.14 min). This sex difference was abolished by GnX. Specifically, GnX decreased the VAT in females (4.55 Ϯ 0.22) and increased the VAT in males (5.14 Ϯ 0.30 min). Thus male sex hormones increase and female sex hormones decrease the susceptibility to ischemia-induced sustained ventricular tachycardia. -Adrenergic receptor blockade increased the VAT in intact males and GnX females only. Thus gonadal hormones influence the response to -adrenergic receptor blockade. Uncovering major differences between males and females in the pathophysiology of the cardiovascular system may result in sex-specific optimization of patient treatments. cardiovascular risks; arrhythmia ISCHEMIA-INDUCED TACHYARRHYTHMIAS that culminate in ventricular fibrillation (19) are the leading cause of death in industrially developed countries (36). Despite the clinical relevance of ischemia-induced arrhythmias, very little experimental data are available regarding sex-specific responses. Specifically, Humphreys and colleagues (20), in the pentobarbital sodium-anesthetized rat as well as isolated rat heart, reported that females experienced fewer arrhythmias than males during myocardial ischemia.Other investigators using different mechanisms to induce arrhythmias also reported a sex difference. For example, Du and colleagues (14), in the in situ perfused rat heart model with chronic infarction and failure, documented that ventricular arrhythmias, triggered by sympathetic activation, were less frequent in female than in male rats. Similarly, Teplitz and colleagues (46), in the pentobarbital sodium-anesthetized rat, reported that male rat hearts are more susceptible than female hearts to epinephrine-induced arrhythmias and more than twice as many male rats di...