Publications

The effects of oral propranolol and digoxin and digoxin alone and in combination on angina frequency, heart size, systolic time intervals and treadmill exercise tolerance, were assessed in 20 patients with coronary heart disease. Oral propranolol alone reduced the average frequency of angina pectoris from 16 to 7 attacks per week (P less than 0.02). However, the mean duration of exercise was not significantly improved because 8 patients with abnormal left ventricular function exhibited a decrease in exercise tolerance. Combined propranolol and digoxin improved exercise tolerance in these patients, and, consequently, mean exercise duration in all patients increased significantly from the control value of 390 +/- 42 to 458 +/- 46 s (P less than 0.01). Propranolol alone also resulted in a significant increase in left heart size from 46.5 +/- 1.3 to 47.7 +/- 1.5 mm/m2 (P less than 0.001), which was reversed by the addition of digoxin. Therefore, oral propranolol combined with digoxin is advantageous in patients with angina pectoris who have abnormal ventricular function or large hearts.

Peptic and chymotryptic peptides were isolated form the NADP-specific glutamate dehydrogenase of Neurospora crassa and substantially sequenced. Out of 452 residues in the polypeptide chain, 265 were recovered in the peptic and 427 in the chymotryptic peptides. Together with the tryptic peptides [Wootton, J. C., Taylor, J. G., Jackson, A. A., Chambers, G. K. & Fincham, J. R. S. (1975) Biochem. J. 149, 749-755], these establish the complete sequence of the chain, including the acid and amide assignments, except for seven places where overlaps are inadequate. These remaining alignments are deduced from information on the CNBr fragments obtained in another laboratory [Blumenthal, K. M., Moon, K. & Smith, E. L. (1975), J. Biol. Chem. 250, 3644-3654]. Further information has been deposited as Supplementary Publication SUP 50054 (17 pages) with the British Library (Lending Division), Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies may be obtained under the terms given in Biochem. J. (1975) 145, 5.

Coronary vascular and myocardial responses to selective hypoxic and/or hypercapnic carotid chemoreceptor stimulation were investigated in constantly ventilated, pentobarbital or urethan-chloralose anesthetized dogs. Bilaterally isolated carotid chemoreceptors were perfused with autologous blood of varying O2 and CO2 tensions via an extracorporeal lung circuit. Systemic gas tensions were unchanged. Effects of carotid chemoreceptor stimulation on coronary vascular resistance, left ventricular dP/dt, and strain-gauge arch output were studied at natural coronary blood flow with the chest closed and during constant-flow perfusion of the left common coronary artery with the chest open. Carotid chemoreceptor stimulation slightly increased left ventricular dP/dt and slightly decreased the strain-gauge arch output, while markedly increasing systemic pressure. Coronary blood flow increased; however, coronary vascular resistance wa.as not affected. These studies show that local carotid body stimulation increases coronary blood flow but has little effect on the myocardium. The increase in coronary blood flow results mainly from an increase in systemic arterial pressure. Thus these data provide little evidence for increased sympathetic activity of the heart during local stimulation of the carotid chemoreceptors with hypoxic and hypercapnic blood.