Effects of Propranolol and Its Stereoisomers upon Coronary Vascular Resistance

Whitsitt, Leighton S.; Lucchesi, Benedict R.

doi:10.1161/01.res.21.3.305

Cited by 52 publications

(13 citation statements)

References 21 publications

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“…Presumably the 3-adrenoceptor mediated vasodilator stimulus was removed by denervation at the time of transplantation. In the present studies, the larger dose of propranolol (30,ug/min) produced a small negative inotropic effect due either to the inhibition of 1-receptor stimulation by circulating catecholamines (Davis, MacDonald & Mason, 1969) or to a direct depressant effect on the transplanted heart or to both (Whitsitt & Lucchesi, 1967 both Cohen et al (1970) in the rat heart and Massingham & Nasmyth (1972) in the frog heart, who found that the positive inotropic effects of aminophylline were not influenced by 13-receptor blockade with propranolol. However, Marcus et al (1972) produced ,-adrenoceptor blockade in the cat isolated papillary muscle with non-depressant doses of propranolol and reported that this reduced the maximum positive inotropic action of theophylline by 40%.…”

Section: Aminophylline and 3-adrenoceptor Blockadesupporting

confidence: 43%

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

Paoloni

Wilcken

1975

British J Pharmacology

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I 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 pg/min) reduced coronary blood flow by 21 ± 2% (mean ± s.e. mean) but did not alter myocardial contractility or heart rate. Higher doses (500 and 1000,ug/min) increased coronary blood flow and myocardial contractility without changing heart rate. 3 a-Adrenoceptor blockade with phenoxybenzamine did not affect the response to a low dose of aminophylline (200 pg/min). 4 Propranolol in doses of 10 and 30,ug/min blocked ,B-adrenoceptors but did not change coronary blood flow. The higher dose reduced myocardial contractility. 5The effects of a high dose of aminophylline (1000,g/min) on coronary blood flow were not changed by either a-or ,B-adrenoceptor blockade, although propranolol (30,ug/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 a-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.

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Section: Aminophylline and 3-adrenoceptor Blockadesupporting

confidence: 43%

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

Paoloni

Wilcken

1975

British J Pharmacology

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“…In this connection, in animals at rest, propranolol can produce an increase in subendocardial flow in an ischemic zone (Becker et al, 1971;Vatner et al, 1977), and at rest when heart rate slows after propranolol, both regional function and total coronary flow improve (Tomoike et al, 1978b). Finally, in normal regions of the heart, a major decrease in coronary blood flow occurs after propranolol primarily because of decreased myocardial oxygen consumption, although propranolol may directly increase coronary vascular resistance (Whitsitt and Lucchesi, 1967). Thus, coronary "steal" during exercise may be diminished by reduction of the workload in normal regions produced by propranolol (Guyton et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Reduction of exercise-induced regional myocardial dysfunction by propranolol. Studies in a canine model of chronic coronary artery stenosis.

Kumada¹,

Gallagher²,

Shirato³

et al. 1980

Circulation Research

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SUMMARY In 10 dogs, we placed a Doppler flow probe, an ameroid constrictor, and a hydraulic cuff occluder around the left circumflex coronary artery (CA). Ultrasonic dimension gauges were implanted in control segments (CS) and ischemic segments (IS) of the left ventricle (LV). A microtransducer was used to measure LV pressure (LVP). Sixteen to 35 days later, when CA occlusion was nearly complete and collaterals had developed, the dogs were studied by telemetry during exercise, while running behind a van (8-11 mph for 3.5 minutes). Control exercise and exercise after propranolol (P) (average dose 0.5 mg/kg, iv) were conducted on the same day 2 hours apart. During control exercise, significant increases occurred in heart rate (HR) (116-249 beats/min), LVP (124-163 mm Hg), end-diastolic pressure (EDP) (8.1-25.9 mm Hg), peak (+)dP/dt (3618-7348 mm Hg/sec), and percent shortening (%AL) of CS (19.7-28.8) (all P < 0.01), but percent systolic wall thickening (%AW) and %AL of IS decreased greatly [22.2 ± 3.8 to 5.1 ± 1.3% (P< 0.01) and 12.6 ± 2.1 to 7.1 ± 2.4% (P< 0.01), respectively]. During matched exercise periods after P, significantly less marked increases occurred in HR (101-182 beats /min), LVP (123-139 mm Hg), EDP (9.4-20.9 mm Hg), peak (+)dP/dt (2801-4312 mm Hg/sec), and %AL of CS (17.1-22.4%) (all P < 0.01). However, %AW and %AL of IS did not deteriorate [19.0 ± 3.6 to 14.3 ± 3.2% (NS) and 11.3 ± 3.1 to 11.5 ± 3.9% (NS)]; both were significantly different from control exercise (P < 0.01). It is concluded that amelioration by propranolol of an exercise-induced myocardial oxygen demand-supply imbalance in a collateral-dependent zone can markedly reduce regional ischemia and dysfunction at the same exercise level.

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“…Propranolol at the dose employed (3 mg/kg) decreases ventricular contractility both by eliminating sympathetic stimulation of the heart and also by a direct depressing action on the myocardium (17,18). Propranolol has also been shown to interfere directly with a mechanism facilitating transfer of calcium ion into the myocardial cell (43) and this agent may by this mechanism also lower intracellular calcium stores.…”

Section: Discussionmentioning

confidence: 99%

“…Seven of the eight dogs were studied also in the conscious state after administration of a large dose of propranolol, 3.0 mg/kg. This dose of propranolol is considerably in excess of that required to produce blockade of beta adrenergic receptors and exerts a direct depressant effect on the myocardium (17,18). In both of these latter circumstances, end diastolic diameter was maintained constant by saline infusion as heart rate was increased.…”

Section: Introductionmentioning

confidence: 99%

Extent of Regulation of the Heart's Contractile State in the Conscious Dog by Alteration in the Frequency of Contraction

Higgins¹,

Vatner²,

Franklin³

et al. 1973

J. Clin. Invest.

130

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A B S T R A C T The effects of alterations in the frequency of contraction over the range from 94 to 220/ min on left ventricular pressure, diameter, and dP/dt were studied in 10 dogs instrumented with ultrasonic diameter gauges and miniature pressure gauges. The same dogs were studied on separate days in the conscious state, after general anesthesia with pentobarbital Na, 30 mg/kg, and in the conscious state after pretreatment with propranolol, 3 mg/kg. End diastolic diameter was maintained constant during alterations in frequency by infusing saline intravenously. The maximum increases in peak dP/dt and dP/dt/P in the conscious state were 14 and 10%, respectively. After anesthesia, raising the frequency of contraction from 122 to 220/min caused maximum increases in peak dP/dt and dP/dt/P of 36 and 30%, respectively. In the conscious state after cardiac depression by propranolol, the maximum increases in peak dP/dt and dP/dt/P were 23 and 23%, respectively. Thus, increasing the frequency of contraction of the normal heart of the conscious dog causes only a slight inotropic effect, but this effect is significantly greater in the presence of myocardial depression produced by anesthesia with pentobarbital Na or in the conscious animal after a myocardial-depressing dose of propranolol.

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Effects of Propranolol and Its Stereoisomers upon Coronary Vascular Resistance

Cited by 52 publications

References 21 publications

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

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

Reduction of exercise-induced regional myocardial dysfunction by propranolol. Studies in a canine model of chronic coronary artery stenosis.

Extent of Regulation of the Heart's Contractile State in the Conscious Dog by Alteration in the Frequency of Contraction

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