Summary
In the isolated canine heart-lung preparation modified to measure coronary outflow and myocardial oxygen consumption, an infusion of carbochromen of 1 mg/min produced an increase in coronary outflow of 120.0% and a decrease in myocardial oxygen consumption of 11.0% at a cumulative dose of 28.0±3.8 mg, resulting in an increase in efficiency of 22.4%. At a total dose of 40 mg, the corresponding figures were +181.0%, −15.0% and +38.0% respectively. No change in heart rate was observed. An infusion of propranolol of 1 mg/min, on the other hand, was characterized by decreases in myocardial contractility and heart rate starting with cumulative doses of 20 mg and 40 mg respectively. At a cumulative dose of 62.9±3.0 mg a marked degree of myocardial failure occurred (peak failure) characterized by a decrease in cardiac output (−53.3%), dp/dt (−50.8%), heart rate (−18.5%) and myocardial oxygen consumption (−25.5%). In a separate series exposed to the same infusion of propranolol but in which the decrease in heart rate was prevented by pacing, identical changes were observed except that myocardial oxygen consumption decreased only by 7.7%. It may be concluded from this study that carbochromen, in confirmation of reports by other investigators, increases coronary out-flow markedly. Carbochromen decreases myocardial oxygen consumption by a direct effect on myocardial metabolism as is evident from the fact that this decrease is not accompanied by changes in any of the parameters which are known to influence myocardial oxygen consumption such as heart rate. Propranolol has no effect on myocardial oxygen consumption unless it is given in a dose which produces myocardial failure and a decrease in heart rate. The decrease in heart rate following propranolol bears a close relationship to the decrease in myocardial oxygen consumption.
Similar content being viewed by others
References
Becker LC, Fortuin NJ, Pitt B (1971) Effect of ischemia and antianginal drugs on the distribution of radioactive microspheres in the canine left ventricle. Cir Res 3:353–361
Bing RJ, Bender SR, Dunn MI, Fry GA, Fuller WM, Liu SCK, Miller HS, Moses JW, Ritzmann LW, Segal JP, Shugoll GI, Tillmanns H, Wallace A (1974) Antianginal effects of chromonar. Clin Pharmacol Ther 16:4–13
Bounhoure JP, Salvador M, Lesbre JPh (1967) Etude de l'action du carbochromene dans le traitement de la douleur angineuse. Rev Med Toulouse 3:353–360
Fawaz G, Simaan J (1971) Is pressure work of the isolated canine heart dependent on release of catecholamines. Naunyn-Schmiedeberg's Arch Pharmacol 270:136–145
Fawaz G, Simaan J (1971) The cardiodynamic and metabolic effects of verapamil on the isolated dog heart. Naunyn-Schmiedeberg's Arch Pharmacol 310:139–145
Fawaz G, Tutunji B (1959) Ouabain-induced ventricular tachycardia and its effect on the performance and metabolism of the dog heart. Br J Pharmacol 14:355–357
Fortuin NJ, Kaihara S, Becker LC, Pitt B (1971) Regional myocardial blood flow in the dog studied with radioactive microspheres. Cardiovasc Res 5:331–336
Freise G, Eisenbarth D (1968) Die Behandlung der schweren Koronarisuffizienz mit Intensain. Med Welt 36:1896–1904
Grayson J, Irvine M, Parratt R (1971) Effects of carbochromen and dipyridamole on blood flow and heat production in the normal and ischaemic canine myocardium. Cardiovasc Res 5:41–47
Gross GJ, Winbury MM (1973) Beta-adrenergic blockade on intramyocardial distribution of coronary blood flow. J Pharmacol Exp Ther 187:451–464
Kipsidze NN, Capidze GJe (1970) Zur Frage der Therapie der Coronarinsuffizienz mit Carbochromen. Arzneim Forsch 20:456–459
Murray JF, Escobar E, Jones NL, Rapaport E (1966) Hemodynamic effects of two beta-adrenergic blocking drugs in anesthetized intact dogs. Am Heart J 72:39–49
Ostrowski JU (1977) Action of carbochromen on heart mitochondria. J Mol Cell Cardiol 9:(Suppl) 37
Parratt JR, Ledingham IMCA, Mcardle CS (1973) Effect of a coronary vasodilator drug (carbochromen) on blood flow and oxygen extraction in acute myocardial infarction. Cardiovasc Res 7:401–407
Rowe GG, Terry W, Stenlund RR, Thomsen JH, Querimit AS (1969) Systemic and coronary hemodynamic effects of 3-(β-diethylaminoethyl)-4-methyl-7-carbethoxy-methoxy-2-oxo-(1,2-chromene)-hydrochloride (Intensain, A-27053). Arch Int Pharmacodyn 178:99–103
Rudolph W, Meixner L, Künzig HJ (1967) Pharmacodynamic action on coronary flow and cardiac metabolism in man. A study of 3-3-(β-diethylamino-ethyl)-4-methyl-7-carbethoxy-methoxy-2-oxo-(1,2-chromene) hydrochloride. Klin. Wochenschr 45:333–353
Schraven E (1976) Regulation of lipid and carbohydrate metabolism of the heart by carbochromen. Arzneim Forsch (Drug Res) 26:197–200
Simaan J, Fawaz G (1968) Effects of dipyridamole on the dog heart-lung preparation. Cardiovasc Res 2:68–72
Simaan J, Fawaz G (1968) The mechanical efficiency of the Starting heart-lung preparation. Pflügers Arch 302:123–132
Simaan J, Fawaz G (1971) The effect of endogenous catecholamines and noradrenaline administration on the performance of the isolated canine heart. Naunyn-Schmiedeberg's Arch Pharmacol 268:17–26
Simaan J, Fawaz G, Jarawan S (1971) The effect of ouabain-induced contractility on myocardial oxygen consumption. Naunyn-Schmiedeberg's Arch Pharmacol 271:249–261
Simaan J, Fawaz G (1973a) The metabolic effect of noradrenaline on the isolated canine heart after blockade of the chronotrophic action by veratramine. Naunyn-Schmiedeberg's Arch Pharmacol 277:199–209
Simaan J, Fawaz G (1973b) The effect of theophylline alone and in combination with ouabain on the isolated dog heart. Naunyn-Schmiedeberg's Arch Pharmacol 278:45–54
Simaan J, Fawaz G (1976) The cardiodynamic and metabolic effects of glucagon. Naunyn-Schmiedeberg's Arch Pharmacol 294:277–383
Somani P, Laddu AR, Hardman HF (1970) Nutritional circulation in the heart. III. Effect of isoproterenol and beta-adrenergic blockade on myocardial hemodynamics and rubidium-86 extraction in the isolated supported heart preparation. J Pharmacol Exp Ther 175:577–592
Stein PD, Brooks HL, Matson JL, Hyland JW (1968) Effect of beta-adrenergic blockade on coronary blood flow. Cardiovasc Res 2:63–67
Warltier DC, Gross GJ, Harden HF (1976) Effect of propranolol on regional myocardial blood flow and oxygen consumption. J Pharmacol Exp Ther 198:435–443
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Simaan, J., Fawaz, G. The cardiodynamic and metabolic effects of carbochromen and propranolol on the isolated dog heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 314, 171–175 (1980). https://doi.org/10.1007/BF00504534
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00504534