Effects of nicardipine on myocardial metabolism and coronary haemodynamics

摘要

>1 Nicardipine is a dilator of the coronary vasculature and has a membrane-stabilising effect in ischaemia. In animal models of infarction, it preserved ventricular pump function, and infarct size, wall thinning and left ventricular dilatation were lessened. Pre-treatment before coronary ligation in baboons reduced infarct size.>2 Nicardipine protected myocytes from irreversible contracture when exposed to veratrine and calcium, unlike diltiazem and nifedipine.>3 Intravenous nicardipine increases resting heart rate and mean arterial pressure, and reduces coronary vascular resistance. The coronary vasodilator effects are not affected by β-adrenoceptor blockade.>4 During a cold-pressor test at constant heart rate, arterio-coronary sinus difference in oxygen and the myocardial lactate uptake were improved, along with better indices of left ventricular function. In pacing-stress tests, lactate extraction fraction reduction was improved.>5 An atrial pacing study using MUGA scanning showed improvement or normalisation of ventricular wall motion.>6 In pacing-induced angina, nicardipine reduced lactate production, glucose extraction and glutamate uptake from control levels, reflecting a faster recovery of aerobic metabolism.>7 After PTCA, lactate production was less after intracoronary injection of nicardipine and lactate extraction returned earlier than in controls, indicating a protective effect on the ischaemic myocardium.>8 In a long-term angina study, nicardipine increased exercise duration and reduced ST segment depression at peak exercise. Lactate uptake was increased, the extent being related to plasma levels of nicardipine. Alanine and glutamine production fell, transcardiac release of thromboxane B2 was reduced, and that of 6-keto-PGF1α increased.>9 Nicardipine improves myocardial metabolism in ischaemia, by increasing oxygen delivery in such areas. No negative inotropic effects were noted, rather, left ventricular function improved at rest and during exercise. Afterload reduction is also seen, favouring blood flow redistribution to underperfused areas. Nicardipine may also help maintain the integrity of myocyte membrane in ischaemia.