The ACTION OF AMINOPHYLLINE ON THE ACUTELY TRANSPLANTED DOG HEART: EFFECT OF Α‐ AND Β‐ADRENOCEPTOR BLOCKADE

Paoloni, H. J.; Wilcken, D. E. L.

doi:10.1111/j.1476-5381.1975.tb07346.x

Cited by 7 publications

(2 citation statements)

References 32 publications

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“…The positive inotropic effects of the drug have been clearly demonstrated in isolated atrial2" 22 and papillary muscle23-25 and also in the isolated heart26' 27 and in anesthetized dog preparations.' 28 Aminophylline reduces the left ventricular filling pressure in patients with and without heart disease, '20, 23, 29-3 findings compatible with those in the present study in which LV end-diastolic diameter fell.…”

Section: Discussionsupporting

confidence: 83%

Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs.

Rutherford¹,

Vatner²,

Braunwald³

1981

Circulation

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SUMMARY The effects of aminophylline, 1 mg/kg/min infused intravenously for 10 minutes, were examined on left ventricular (LV) diameter, pressure, and indexes of myocardial contractility, as well as systemic, coronary and regional hemodynamics in conscious dogs. Aminophylline increased mean arterial pressure 12 i 2%, LV systolic pressure 8 ± 1%, LV dP/dt 20 ± 2%, velocity of myocardial fiber shortening 13 ± 2% and heart rate 5 ± 2%, and reduced LV end-diastolic diameter 2 ± 0.5%. Vascular resistance rose in the systemic bed 13 ± 5%, the coronary bed 26 ± 3%, the mesenteric bed 26 ± 5% and the iliac bed 36 ± 4%, but did not rise in the renal bed. Both 0-adrenergic receptor blockade with propranolol and chronic treatment with reserpine attentuated but did not abolish the positive inotropic response induced by aminophylline. Alphaadrenergic receptor blockade with phentolamine prevented aminophylline-induced vasoconstriction in the systemic, coronary, mesenteric and iliac beds. In contrast to the vasoconstriction with i.v. aminophylline, when the drug was infused directly into the iliac artery, it elicited marked iliac vasodilation. Thus, in the intact conscious dog, i.v. aminophylline, in a dose that had little effect on heart rate, increased LV contractility and reduced preload. The increase in contractility was dependent in part on intact f-adrenergic nervous activity and endogenous catecholamine stores. The increases in systemic, coronary, iliac and mesenteric resistances involved a-adrenergic mechanisms. These actions appear to involve autonomic mechanisms, because the only direct effect of aminophylline on the iliac artery was marked vasodilation.THEOPHYLLINE ethylenediamine (aminophylline) is widely used in the treatment of cardiovascular and respiratory disease. In part, the therapeutic rationale is based on the concept that aminophylline is a potent peripheral vasodilator. It has been shown to decrease total systemic," 2 renal3'5 and, in particular, coronary', 6-11 vascular resistances in anesthetized animal preparations. Ritchie12 noted that experimentally, it can be demonstrated that the xanthines dilate coronary arteries and increase coronary blood flow, and this finding has led to their use in treating coronary artery disease. The most widely used methylated xanthine derivative is aminophylline, which is a combination of theophylline and ethylenediamine. The latter substance, believed to be therapeutically inert, increases the solubility of theophylline. 12 Because aminophylline is widely used clinically and because of the observation that the effects of many interventions differ substantially in anesthetized and conscious animals,'3 we studied this drug in intact, conscious dogs.A primary goal of this study was to determine the effects of aminophylline on regional blood flow distribution using techniques designed to yield continuous direct measurements in healthy, conscious animals in which the effects of anesthesia and surgical trauma on circulatory and reflex control were absent.To understand the act...

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Section: Discussionsupporting

confidence: 83%

Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs.

Rutherford¹,

Vatner²,

Braunwald³

1981

Circulation

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“…The frequency response of the left ventricular recording system was flat ± 5% to 35 Hz using a sine wave pressure generator. 10 Recordings were made at fast paper speed (200 mm/sec) for accurate analysis.…”

Section: Experimental Modelmentioning

confidence: 99%

Histamine receptors in the coronary circulation of the dog. Effects of mepyramine and metiamide on responses to histamine infusions.

Giles¹,

Heise²,

Wilcken³

1977

Circulation Research

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SUMMARY The effect of histamine on coronary blood flow (CBF) was studied in anaesthetized greyhounds. CBF and systemic blood pressure were measured using electromagnetic flow transducers and catheters in the aorta during infusions of drugs into the left circumflex coronary artery. Histamine infusions (5, 10, and 20 figjmin) produced dose-related increases in CBF without changing heart rate or blood pressure. Metiamide (100 /ig/min) given simultaneously produced a parallel displacement of the histamine dose-response curve to the right (P < 0.05) with a dose ratio of 2. Mepyramine (100 /ig/min) produced a larger parallel displacement of the dose-response curve (dose ratio = 4). Together, metiamide and mepyramine greatly reduced the histamine response (dose ratio = 16), showing that the metiamide blockade is augmented in the presence of mepyramine. Similarly, mepyramine blockade is augmented in the presence of metiamide. The increase in CBF produced by histamine infusion (20 pig/ min) was similar to the peak flow response of reactive hyperemia following 8-second occlusions. However, mepyramine and metiamide together had no effect on the peak flow response, duration, or total repayment of flow debt in reactive hyperemia. These results show that histamine-induced coronary vasodilation is mediated by both H, and H, receptors. However, the vasodilation of reactive hyperemia after brief coronary artery occlusions does not appear to involve histamine.HISTAMINE acts through at least two specific receptors.'• 2 The development of H, receptor antagonists 3 and more recently of specific H 2 antagonists 2 has made it possible to identify the presence in tissues of these two receptors. Histamine is taken up actively by the heart 4 and its release may be quantified.5 " But the role of histamine in the regulation of the coronary circulation and the nature of coronary histamine receptors are unknown.In the present investigation we have studied the action of histamine in the coronary circulation, using low dose close coronary arterial infusions of histamine and specific H, and H 2 receptor antagonists. By giving drugs in this way we avoided systemic effects. The results show that there are H, and H, receptors in the coronary vasculature with vasodilator effects similar in magnitude to that found during reactive hyperemia following brief coronary artery occlusions. We extended the study to examine the effects on myocardial reactive hyperemia of blocking histamine responses with both H, and H, receptor antagonists. Methods EXPERIMENTAL MODELExperiments were performed on anesthetised. healthy, young grayhounds weighing 19-30 kg. Anesthesia was induced with thiopentone (20 mg/kg. iv) and maintained by ventilation with a Harvard respirator using a 2:1 nitrous oxide-oxygen mixture and sodium pentobarbital. Sodium pentobarbital (20 mg/kg. iv) was given as an initial bolus and further doses were administered as necessary to suppress respiration. The nitrous oxide-oxygen gas mixture was passed through a humidifier to maintain body temperat...

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The Cardiovascular Effects of Methylxanthines

2010

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In the concentration range that is normally achieved in humans, e.g., after the drinking of coffee or in patients treated with theophylline, the cardiovascular effects of methylxanthines are primarily due to antagonism of adenosine A(1) and A(2) receptors. Inhibition of phosphodiesterases or mobilization of intracellular calcium requires much higher concentrations. In conscious humans, acute exposure to caffeine results in an increase in blood pressure by an increased total peripheral resistance, and a slight decrease in heart rate. This overall hemodynamic response is composed of direct effects of caffeine on vascular tone, on myocardial contractility and conduction, and on the sympathetic nervous system. Caffeine is the most widely consumed methylxanthine, mainly derived from coffee intake. Regular coffee consumption can affect various traditional cardiovascular risk factors, including a slight increase in blood pressure, an increase in plasma cholesterol and homocysteine levels, and a reduced incidence of type 2 diabetes mellitus. Although most prospective studies have not reported an association between coffee consumption and coronary heart disease, these findings do not exclude that the acute hemodynamic and neurohumoral effects of coffee consumption could have an adverse effect in selected patient groups who are more vulnerable for these effects, based on their genetic profile or medication use.

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The ACTION OF AMINOPHYLLINE ON THE ACUTELY TRANSPLANTED DOG HEART: EFFECT OF Α‐ AND Β‐ADRENOCEPTOR BLOCKADE

Cited by 7 publications

References 32 publications

Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs.

Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs.

Histamine receptors in the coronary circulation of the dog. Effects of mepyramine and metiamide on responses to histamine infusions.

The Cardiovascular Effects of Methylxanthines

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