Calcium channel blocking agents function as negative inotropic agents when they are administered in vitro directly to the myocardium. In patients with coronary artery disease, however, such direct effects are attenuated by a number of other factors, including decreased afterload and resultant reflex sympathetic stimulation, increased coronary blood flow with improved myocardial perfusion, and protection of mitochondria. Nifedipine has not been observed to cause significant left ventricular depression in patients with angina pectoris; this is primarily due to peripheral arteriolar vasodilatation, which reduces impedance of left ventricular ejection. In addition, the relief of myocardial ischemia by nifedipine plays a major role in improving systolic and diastolic function. The clinical response to calcium channel blockers may differ in patients with idiopathic dilated cardiomyopathy, for whom the factor of fluctuating ischemia is less important.