Intracoronary nifedipine in human beings: magnitude and time course of changes in left ventricular contraction/relaxation and coronary sinus blood flow

Eight patients, all men, having at least 75% stenosis of the proximal, middle or both segments of the left anterior descending coronary artery, underwent intracoronary drug studies at the time of cardiac catheterization after saphenous vein bypass grafting. Nifedipine, 0.1 mg dissolved in saline solution, was infused into a left anterior descending graft that was the primary blood supply to each patient's anterior left ventricular wall and septum. High fidelity left ventricular pressure and its first derivative, dP/dt, and aortic pressure were sampled synchronously with coronary sinus blood flow by the thermodilution technique. The time constant of isovolumic pressure decay (T) was derived. In five patients, percent systolic shortening and mean shortening velocity were determined from myocardial markers implanted into the midwall of the myocardium at the time of cardiac surgery. In response to nifedipine, left ventricular systolic pressure decreased and end-diastolic pressure increased up to 60 seconds. Both positive and negative dP/dt also decreased up to 60 seconds, whereas coronary sinus blood flow increased up to 5 minutes. T was increased at 1 minute but returned to baseline by 3 minutes. Percent systolic shortening and mean shortening velocity were decreased at 1 minute but returned to control level by 3 minutes. Thus, although both left ventricular systolic and diastolic function were depressed by intracoronary administration of nifedipine, coronary sinus blood flow was augmented and remained increased long after changes in left ventricular contraction and relaxation had subsided. These temporal differences are consistent with animal studies showing a differential depressant effect of nifedipine on calcium uptake in smooth muscle and cardiac muscle.