The Action of Aminophylline on the Acutely Transplanted Dog Heart: Effect of Alpha- and Beta-adrenoceptor Blockade

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1975 Feb 1

PMID 238696

Authors

H J Paoloni

D E Wilcken

Affiliations

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Abstract

1 Aminophylline inhibits the coronary vasodilator actions of adenosine. Our previous studies suggested that low dose infusions of aminophylline reduce coronary blood flow in the isolated heart. In the present study we investigated the actions of aminophylline on coronary blood flow and myocardial contractility in a transplanted heart model. Drugs were given by close coronary arterial infusion. 2 Aminophylline in low doses (200 mug/min) reduced coronary blood flow by 21 plus or minus 2% (mean plus or minus s.e. mean) but did not alter myocardial contractility or heart rate. Higher doses (500 and 1000 mug/min) increased coronary blood flow and myocardial contractility without changing heart rate. 3 Alpha-adrenoceptor blockade with phenoxybenzamine did not affect the response to a low dose of aminophylline (200 mug/min). 4 Propranolol in doses of 10 and 30mug/min blocked beta-adrenoceptors but did not change coronary blood flow. The higher dose reduced myocardial contractility. 5 The effects of a high dose of aminophylline (1000 mug/min) on coronary blood flow were not changed by either alpha- or beta-adrenoceptor blockade, although propranolol (30 mug/min) reduced the augmentation in myocardial contractility. 6 The results show that when given in doses which do not alter myocardial contractility, aminophylline reduces coronary blood flow in the isolated heart and that this is not mediated through an alpha-adrenoceptor mechanism. They also show that the increases in coronary blood flow and positive inotropic effects obtained with higher doses of aminophylline are not mediated through catecholamines and suggest that higher doses of aminophylline have a small direct coronary vasodilator action. The low dose vasoconstrictor response may be produced by inhibition of the coronary vasodilator action of locally produced adenosine.

References

STARR I, Gamble C, Margolies A, Donal J, Joseph N, EAGLE E . A CLINICAL STUDY OF THE ACTION OF 10 COMMONLY USED DRUGS ON CARDIAC OUTPUT, WORK AND SIZE; ON RESPIRATION, ON METABOLIC RATE AND ON THE ELECTROCARDIOGRAM. J Clin Invest. 1937; 16(5):799-823. PMC: 424919. DOI: 10.1172/JCI100906. View

Wolf M, BERNE R . Coronary vasodilator properties of purine and pyrimidine derivatives. Circ Res. 1956; 4(3):343-8. DOI: 10.1161/01.res.4.3.343. View

MELVILLE K, Lu F . Effect of epinephrine, aminophylline, nitroglycerine and papaverine on coronary inflow and on heart contraction, as recorded concurrently. J Pharmacol Exp Ther. 1950; 99(3):286-303. View

Siegel J, SONNENBLICK E, JUDGE R, Wilson W . THE QUANTIFICATION OF MYOCARDIAL CONTRACTILITY IN DOG AND MAN. Cardiologia (Basel). 1964; 45:189-221. DOI: 10.1159/000168110. View

Siegel J, SONNENBLICK E . Isometric time-tension relationships as an index of myocardial contractility. Circ Res. 1963; 12:597-610. DOI: 10.1161/01.res.12.6.597. View

RALL T, WEST T . The potentiation of cardiac inotropic responses to norepinephrine by theophylline. J Pharmacol Exp Ther. 1963; 139:269-74. View

BERNE R . Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow. Am J Physiol. 1963; 204:317-22. DOI: 10.1152/ajplegacy.1963.204.2.317. View

NAYLER W . Effect of caffeine on cardiac contractile activity and radiocalcium movement. Am J Physiol. 1963; 204:969-74. DOI: 10.1152/ajplegacy.1963.204.6.969. View

Butcher R, SUTHERLAND E . Adenosine 3',5'-phosphate in biological materials. I. Purification and properties of cyclic 3',5'-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3',5'-phosphate in human urine. J Biol Chem. 1962; 237:1244-50. View

10.

BARTELSTONE H, NASMYTH P, TELFORD J . The significance of adenosine cyclic 3',5'-monophosphate for the contraction of smooth muscle. J Physiol. 1967; 188(2):159-76. PMC: 1396005. DOI: 10.1113/jphysiol.1967.sp008131. View

11.

Epstein S, LEVEY G, Skelton C . Adenyl cyclase and cyclic AMP. Biochemical links in the regulation of myocardial contractility. Circulation. 1971; 43(3):437-50. DOI: 10.1161/01.cir.43.3.437. View

12.

Siegel J . The myocardial contractile state and its role in the response to anesthesia and surgery. Anesthesiology. 1969; 30(5):519-64. DOI: 10.1097/00000542-196905000-00012. View

13.

Parratt J, Grayson J . Myocardial vascular reactivity after beta-adrenergic blockade. Lancet. 1966; 1(7433):338-40. DOI: 10.1016/s0140-6736(66)91321-3. View

14.

BOAKE W, Folts J . The effect of beta-adrenergic blockade on coronary blood flow in the homografted canine heart. Arch Int Pharmacodyn Ther. 1971; 192(1):96-104. View

15.

BLINKS J, OLSON C, JEWELL B, BRAVENY P . Influence of caffeine and other methylxanthines on mechanical properties of isolated mammalian heart muscle. Evidence for a dual mechanism of action. Circ Res. 1972; 30(4):367-92. DOI: 10.1161/01.res.30.4.367. View

16.

Davis W, Macdonald D, Mason D . The effects of pronethalol and propranolol on the coronary circulation of the dog. Br J Pharmacol. 1969; 37(2):338-56. PMC: 1703682. DOI: 10.1111/j.1476-5381.1969.tb10571.x. View

17.

Marcus M, Skelton C, Grauer L, Epstein S . Effects of theophylline on myocardial mechanics. Am J Physiol. 1972; 222(6):1361-5. DOI: 10.1152/ajplegacy.1972.222.6.1361. View

18.

Massingham R, NASMYTH P . The nature of the positive inotropic response of the isolated frog heart to theophylline and to iminazole. Br J Pharmacol. 1972; 45(2):229-39. PMC: 1666134. DOI: 10.1111/j.1476-5381.1972.tb08078.x. View

19.

McNeill J, Nassar M, BRODY T . The effect of theophylline on amine-induced cardiac phosphorylase activation and cardiac contractility. J Pharmacol Exp Ther. 1969; 165(2):234-41. View

20.

Paoloni H, Wilcken D . The effects of 2,6-bis(diethanolamino)-4-piperidino-pyrimido(5,4-D)pyrimidine (RA233) on the coronary circulation of the acutely transplanted dog heart: comparison with dipyridamole and adenosine. J Pharmacol Exp Ther. 1972; 183(1):137-45. View