The effect of verapamil on myocardial exchange of free fatty acids, citrate, lactate and glucose in coronary artery disease.

Abstract

Twelve patients with coronary artery stenosis (greater than 50% diameter reduction) underwent two identical periods of atrial pacing before and after i.v. verapamil (0.1 mg/kg). Myocardial exchanges of free fatty acids (FFA), citrate, lactate and glucose were evaluated from measurements of arterio-coronary sinus differences (n = 12) and coronary sinus blood flow (CSBF) (n = 9). Before verapamil 11 patients developed angina. Verapamil abolished pain in seven and improved pacing time to angina in four patients. After verapamil, aortic pressure decreased (P less than 0.05), while the rate pressure product remained unchanged during rest and pacing. Verapamil decreased CSBF by 20% (P less than 0.05) during pacing, and increased oxygen extraction both during pacing and recovery. During pacing verapamil increase net FFA extraction (P less than 0.01) and uptake (1 to 8 mumol/min P less than 0.05), and decreased glucose extraction (P less than 0.05) and uptake (22 to 11 mumol/min P less than 0.02. Verapamil increased myocardial citrate release during pacing (P less than 0.05), suggesting a citrate inhibition of glycolysis as a possible mechanism of the inhibited glucose uptake. During pacing, verapamil reduced lactate release in seven patients (P less than 0.05) and decreased lactate extraction in five patients (P less than 0.05). The results suggest that verapamil mediates its beneficial effect on pacing-induced angina, in part by changing substrate utilization of the ischaemic myocardium in man towards that of normal heart.