Energy conservation in ischemic rat heart by nifedipine plus propranolol

Abstract

Both nifedipine the calcium channel blocker and propranolol the β-blocker have been proposed for the treatment of ischemic heart disease and hypertension. The combination of nifedipine and propranolol has recently been tested in patients, in general with favourable results. In a few case reports, however, potential dangers with this therapy have been described. Few studies have been conducted to test the effect of nifedipine on high-energy phosphate metabolism in the ischemic heart, although it is generally assumed that the drug prevents breakdown of adenosine 5′-triphosphate (ATP). In addition, it is surprising that the action of nifedipine plus propranolol on ischemic heart has not been studied in animals. We induced ischemia in isolated perfused rat hearts (60 or 75% reduction in coronary flow in the absence of drugs). With a novel high performance liquid chromatographic assay we were able to measure the effect of nifedipine and propranolol on purine release, a sensitive index for myocardial ATP breakdown. The calcium antagonist prevented, in a dose dependent manner, the release of purine nucleosides and oxypurines from the ischemic heart, indicating decreased ATP breakdown. Nifedipine (100 μg/l) reduced, for instance, adenosine release by 93% ( P <0·02). This reduction did not seem to be due to a negative inotropic action of the drug. DL-Propranolol (30–150 μg/l) was ineffective. However, the addition of propranolol (150 μg/l) to the perfusion medium containing nifedipine (15 μg/l) could further reduced the release of adenosine, inosine, (hypo)xanthine and urate. Total purine release was unchanged with propranolol, decreased with nifedipine by 33% ( P < 0·005), and with both drugs by 47% ( P < 0·001 vs. nifedipine). We conclude that nifedipine (plus propranolol) conserves energy in the ischemic heart.