Nifedipine Effects in Severe Myocardial Ischaemia in the Dog Due to Left Anterior Descending Coronary Occlusion with Left Circumflex Coronary Artery Constriction

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1987 May 1

PMID 3594071

Authors

L Szekeres

E Udvary

A Vegh

Affiliations

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Abstract

The effects of nifedipine were studied in a model of local myocardial ischaemia, comprising anaesthetized thoracotomized dogs in which a critical constriction of the left circumflex coronary artery (LCX) was combined with sudden occlusion of the left anterior descending coronary artery (LAD). Since more than one coronary artery is involved in ischaemic heart disease, the model seems to reflect the clinical situation very closely. In this model, infusion of 1 microgram kg-1 min-1 nifedipine increased myocardial blood flow within the stenosed area served by the LCX as well as in the myocardial region supplied by the LAD, mainly in the subepicardium. Accordingly, the drug reduced ischaemic ST-segment elevation only in the epicardium. It is suggested that nifedipine directed flow to the sub-epicardium of the ischaemic area by improving the collateral circulation. This redistribution of flow resulted in a decrease in the endo/epicardial flow ratio. Nifedipine did not change the inhomogeneity of electrical activation indicating that it has no effect on the ischaemia-induced conduction delay. At the same time nifedipine was not able to reduce either the number of extrasystoles appearing in the early postocclusion and reperfusion phase or the incidence of ventricular fibrillation occurring mainly during reperfusion.

References

WINBURY M, Howe B, Hefner M . Effect of nitrates and other coronary dilators on large and small coronary vessels: an hypothesis for the mechanism of action of nitrates. J Pharmacol Exp Ther. 1969; 168(1):70-95. View

Szekeres L, Udvary E, Vegh A . Importance of myocardial blood flow changes in the protective action of diltiazem in a new model of myocardial ischaemia. Br J Pharmacol. 1985; 86(2):341-50. PMC: 1916689. DOI: 10.1111/j.1476-5381.1985.tb08902.x. View

WILLIAMS D, Scherlag B, Hope R, El-Sherif N, LAZZARA R . The pathophysiology of malignant ventricular arrhythmias during acute myocardial ischemia. Circulation. 1974; 50(6):1163-72. DOI: 10.1161/01.cir.50.6.1163. View

FLECKENSTEIN A . Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977; 17:149-66. DOI: 10.1146/annurev.pa.17.040177.001053. View

Henry P, Shuchleib R, Borda L, Roberts R, Williamson J, Sobel B . Effects of nifedipine on myocardial perfusion and ischemic injury in dogs. Circ Res. 1978; 43(3):372-80. DOI: 10.1161/01.res.43.3.372. View

Selwyn A, Welman E, Fox K, Horlock P, Pratt T, Klein M . The effects of nifedipine on acute experimental myocardial ischemia and infarction in dogs. Circ Res. 1979; 44(1):16-23. DOI: 10.1161/01.res.44.1.16. View

EKELUND L . Ca-blockers and peripheral circulation--physiological viewpoints. Acta Pharmacol Toxicol (Copenh). 1978; 43 Suppl 1:33-43. DOI: 10.1111/j.1600-0773.1978.tb03566.x. View

NAYLER W, Ferrari R, Williams A . Protective effect of pretreatment with verapamil, nifedipine and propranolol on mitochondrial function in the ischemic and reperfused myocardium. Am J Cardiol. 1980; 46(2):242-8. DOI: 10.1016/0002-9149(80)90064-8. View

Ellrodt G, Chew C, Singh B . Therapeutic implications of slow-channel blockade in cardiocirculatory disorders. Circulation. 1980; 62(4):669-79. DOI: 10.1161/01.cir.62.4.669. View

10.

Henry P . Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol. 1980; 46(6):1047-58. DOI: 10.1016/0002-9149(80)90366-5. View

11.

Jolly S, HARDMAN H, Gross G . Comparison of two dihydropyridine calcium antagonists on coronary collateral blood flow in acute myocardial ischemia. J Pharmacol Exp Ther. 1981; 217(1):20-5. View

12.

Weintraub W, Hattori S, Agarwal J, Bodenheimer M, Banka V, Helfant R . Variable effect of nifedipine on myocardial blood flow at three grades of coronary occlusion in the dog. Circ Res. 1981; 48(6 Pt 1):937-42. DOI: 10.1161/01.res.48.6.937. View

13.

Ribeiro L, Brandon T, DeBauche T, Maroko P, Miller R . Antiarrhythmic and hemodynamic effects of calcium channel blocking agents during coronary arterial reperfusion. Comparative effects of verapamil and nifedipine. Am J Cardiol. 1981; 48(1):69-74. DOI: 10.1016/0002-9149(81)90573-7. View

14.

Millard R, Lathrop D, GRUPP G, Ashraf M, GRUPP I, Schwartz A . Differential cardiovascular effects of calcium channel blocking agents: potential mechanisms. Am J Cardiol. 1982; 49(3):499-506. DOI: 10.1016/s0002-9149(82)80002-7. View

15.

Sheehan F, Epstein S . Effects of calcium channel blocking agents on reperfusion arrhythmias. Am Heart J. 1982; 103(6):973-7. DOI: 10.1016/0002-8703(82)90559-2. View

16.

Perez J, Borda L, Schuchleib R, Henry P . Inotropic and chronotropic effects of vasodilators. J Pharmacol Exp Ther. 1982; 221(3):609-13. View

17.

Zyvoloski M, Brooks H, Gross G, Warltier D . Myocardial perfusion distal to an acute or chronic coronary artery occlusion: effects of diltiazem and nifedipine. J Pharmacol Exp Ther. 1982; 222(2):494-500. View

18.

Weintraub W, Akizuki S, Agarwal J, Bodenheimer M, Banka V, Helfant R . Comparative effects of nitroglycerin and nifedipine on myocardial blood flow and contraction during flow-limiting coronary stenosis in the dog. Am J Cardiol. 1982; 50(2):281-8. DOI: 10.1016/0002-9149(82)90178-3. View

19.

Nakaya H, Schwartz A, Millard R . Reflex chronotropic and inotropic effects of calcium channel-blocking agents in conscious dogs. Diltiazem, verapamil, and nifedipine compared. Circ Res. 1983; 52(3):302-11. DOI: 10.1161/01.res.52.3.302. View

20.

Melin J, Becker L, Hutchins G . Protective effect of early and late treatment with nifedipine during myocardial infarction in the conscious dog. Circulation. 1984; 69(1):131-41. DOI: 10.1161/01.cir.69.1.131. View