Effects of nifedipine on myocardial blood flow and systolic function in humans with ischemic heart disease

Objective To test the hypothesis that, in humans with ischemic heart diseas e, nifedipine is a primary dilator of the coronary circulation and in gener al exerts a net positive effect on the balance of myocardial oxygen supply and demand. Methods Positron-emission tomography with [N-13]-ammonia was used to measur e myocardial blood flow in patients at rest, and during infusion of adenosi ne and ingestion of nifedipine (10 mg capsule, a bite-and-chew technique). Myocardial segments were defined physiologically on the basis of blood flow to adenosine as being normal or having mild, moderate, or severe impairmen t of dilator reserve. Myocardial systolic function was assessed under compa rable physiologic conditions using gated single-photon-emission computed to mography radionuclide ventriculography. Results Our study population consisted of 13 male patients and one female p atient. Ingestion of nifedipine increased heart rate (from 63 +/- 1 1 to 80 +/- 16 beats/min, P<0.001) and, as intended, lowered systolic arterial pre ssure (from 148 +/- 20 to 123 +/- 14 mmHg, P < 0.001) but had no effect on heart rate-pressure product (which changed from 9283 +/- 1576 to 9942 +/- 2 162 mmHg/min). Myocardial blood flow in patients at rest in segments with m ild, moderate, and severe reductions of dilator capacity (0.63 +/- 0.20, 0. 67 +/- 0.25, and 0.58 +/- 0.27 ml/min per g, respectively) was less (P<0.01 ) than normal (0.91 +/- 0.29 ml/min per g). Nevertheless, flow of blood was increased versus that at rest (P< 0.01) by infusion of adenosine (to 1.78 +/- 0.13, 1.29 +/- 0.16, and 0.75 +/- 0.22 ml/min per g) and ingestion of n ifedipine (to 1.17 +/-0.51, 1.06 +/- 0.36, 0.85 +/- 0.42 ml/min per g) in s egments with mild, moderate, and severe reductions of dilator capacity as w ell as in normal segments (to 3.18 +/- 0.85 ml/min per g with adenosine and 1.68 +/- 0.65 ml/min per g with nifedipine). Global left ventricular systo lic function remained unchanged versus baseline (ejection fraction 0.74 +/- 0.09) with nifedipine (0.78 +/- 0.10). Regional contraction expressed in n ormalized amplitude units also remained unchanged versus baseline in respon se to nifedipine. Conclusion Nifedipine increases myocardial blood flow in humans with ischem ic heart disease in normal segments as well as in segments with mild, moder ate, and severe reductions of dilator capacity, albeit to a lesser extent w ith increasing impairment of dilator capacity. Both global and regional lef t ventricular contractile function also are not adversely affected by nifed ipine. These improvements in myocardial blood flow in face of no change or a decrease in myocardial demand for oxygen reflect an overall favorable eff ect on the balance between the supply of and demand for myocardial oxygen. Coronary Artery Dis 10:185-194 (C) 1999 Lippincott Williams & Wilkins.