Beneficial Actions of Bevantolol on Subendocardial Blood Flow and Contractile Function in Ischemic Myocardium

Gross, G. J.; Buck, J.; Warltier, David C.; Hardman, Harold F.

doi:10.1097/00005344-197901000-00013

Cited by 23 publications

(6 citation statements)

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“…Pacing also abolished the improvement induced by beta blockade in myocardial contraction in dogs with left ventricular (LV) dysfunction due to chronic mitral regurgitation [16]. Experiments in animal models of infarction have shown that prolonged administration of atenolol led to left ventricular remodelling and improved function [17], while acute administration of beta-blockers increased the contractile force in ischaemic canine myocardium [18,19]. With regard to possible effects of beta-block on coronary vasculature, Grover et al [20] found a higher proportion of perfused capillaries and greater volume fraction of capillaries and arterioles after acute use of practolol in normal rabbit hearts.…”

Section: Bradycardia and The Coronary Circulationmentioning

confidence: 99%

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

2005

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Angiogenesis and improved left ventricular function as a consequence of long-term bradycardia were first demonstrated in normal hearts, either electrically paced (rabbits, pigs) or treated with a selective sinus blocking drug alinidine (rats). Here we review the evidence that chronic heart rate reduction can have similar effects in the heart with compromised vascular supply, due to either hypertensive or haemodynamic overload hypertrophy (rats, rabbits) or ischaemic damage (rats, rabbits, pigs). Bradycardia induced over several weeks increased capillarity in all hypertrophied hearts, and in border and remote left ventricular myocardium of infarcted hearts. In some, but not all cases, coronary blood flow was improved by heart rate reduction, suggesting enlargement of the resistance vasculature in some circumstances. Cardiac or left ventricular function indices, which were depressed by hypertrophy or ischaemic damage, were preserved or even enhanced by chronic heart rate reduction. The expansion of the capillary bed in the vascularly compromised heart induced by bradycardia may be stimulated by mechanical stretch of the endothelium and/or VEGF activated by chamber dilation and myocyte stretch. The increased number of capillaries and more homogeneous distribution of capillary perfusion would support the better pump function, even in the absence of higher coronary flow. The beneficial impact of chronic heart rate reduction on myocardial angiogenesis and function in cardiac hypertrophy and infarction may be major factor in the success of beta-blockers in treatment of human heart failure.

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Section: Bradycardia and The Coronary Circulationmentioning

confidence: 99%

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

2005

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“…The present study demonstrated that bisoprolol improves perfusion of the ischaemic myocardium in anaesthetized open-chest pigs. This is, however, not surprising since a large number of other fladrenoceptor antagonists also possess this property (Vatner et al, 1977;Tomoike et al, 1978;Berdeaux et al, 1979;Buck et al, 1979;Gross et al, 1979;Saxena, 1983;. On the other hand, negative results have also been obtained in earlier studies (Becker et al, 1975;Kloner et al, 1976;Berdeaux et al, 1977).…”

Section: Systemic Haemodynamicsmentioning

confidence: 93%

“…It is interesting that bisoprolol increases blood flow to the ischaemic myocardial segment, in particular to the subendocardium, even at doses which only moderately inhibit isoprenaline-induced increases in heart rate and contractility present results). Using other fi-adrenoceptor antagonists or specific bradycardiac drugs, several investigators have shown that the endocardium, especially, benefits from a prolongation of the duration of diastole (Berdeaux et al, 1979;Gross et al, 1979;Buck et al, 1981;Schamhardt et al, 1981b;Saxena, 1983;Daemmgen et al, 1985;Guth et al, 1987).…”

Section: Systemic Haemodynamicsmentioning

confidence: 99%

“…Since, in animals with an intact coronary circulation, doses lower than lOOOpgkg-1 did not affect systolic wall thickening, it is unlikely that the drug-induced negative inotropic effect prevented an improvement in regional function. Moreover, a number of fiadrenoceptor antagonists have been shown to improve the regional contractile function of ischaemic myocardium despite their negative inotropic action on the normal myocardium (Tomoike et al, 1978;Gross et al, 1979, Buck et al, 1981. A third reason may be the duration of ischaemia preceding the administration of bisoprolol: numerous studies in dogs and pigs have shown that even after complete restoration of blood flow subsequent to partial or complete occlusion of a coronary artery lasting up to 20min, recovery of contractile function takes place only after a considerable delay (Heyndrickx et al, 1975;Ramanathan et al, 1978;van der Giessen et al, 1986).…”

Section: Systemic Haemodynamicsmentioning

confidence: 99%

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Bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs

Sassen

Boer

Rensen

et al. 1988

British J Pharmacology

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1 The ability of the cardioselective f-adrenoceptor antagonist bisoprolol ((f-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropyl-amino-2-propanol hemifumarate, EMD 33512) to suppress isoprenaline-induced increases in heart rate and maximal rate of rise in left ventricular pressure (LVdP/dt,,j was studied in 6 anaesthetized pigs given 4 cumulative doses (16, 64, 256 and 1024pgkg-1). Bisoprolol was about 2 times more effective in suppressing isoprenaline-induced increases in LVdP/dt,, than those in heart rate.2 In 8 animals which had a partial stenosis of the left anterior descending coronary artery (LADCA), the effects of 3 consecutive doses (50, 200 and 750 pg kg-1) of bisoprolol were studied on systemic haemodynamics, regional myocardial perfusion and function. The effects of the drug were compared with those obtained in a group of 9 animals with LADCA stenosis which did not receive any treatment.3 The lowest dose of bisoprolol (50ugkg-1) increased perfusion of the ischaemic myocardium (which had been reduced from 123 + 20m1min-100g-1 to 42+ llmlmin1 100g-1) by 21 + 10mlmin1 100g-1 (P < 0.05). In particular the subendocardial layers, which were most severely affected by the stenosis (a decrease from 128 + 19mlmin' 100g-1 to 20 + 6mlmin-100g-1) benefited from the administration of the drug (an increase of 30 + 10mlmin-1 100g-1). Perfusion of the subepicardium was not significantly affected. With the higher dose only a minor additional improvement in perfusion of the ischaemic myocardium was observed. 4 The negative chronotropic response is the most likely factor leading to the improvement in perfusion. 5 Myocardial wall thickening, which decreased from 41+2% to 9 +4% (P <0.05) due to the hypoperfusion, did not improve after administration of the drug. This lack of improvement may possibly be due to the duration of ischaemia before and the magnitude of the flow deficit after bisoprolol administration.6 Between 15 and 60min of ischaemia, 5 of the 9 untreated animals had an episode of ventricular fibrillation compared with only 1 of the 8 animals treated with bisoprolol, in spite of an initially larger flow reduction in the treated animals. The more homogeneous flow distribution after bisoprolol might account for the lower incidence of arrhythmias in this group. 7 It was demonstrated that bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs even at doses (50.pgkg-1) that only moderately antagonize isoprenaline-induced cardiostimulatory effects.

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“…No experiments in pithed animals devoid of vascular reflexes have been reported, but in anaesthetized dogs, Gross et al (1979) observed that 1 mg kg-' of bevantolol i.v. reduced the tachycardic responses to 0.3 igkg-' of isoprenaline by 70-80% with little effect on the hypotensive responses, but the effects of other agonist and antagonist doses were not studied and cardiac output and peripheral resistance were not measured.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular effects of bevantolol, a selective β₁‐adrenoceptor antagonist with a novel pharmacological profile

Dukes

Williams

1985

British J Pharmacology

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1Bevantolol was more potent in blocking the chronotropic than the hypotensive effects of isoprenaline in pithed rats. 2 Bevantolol itself induced bradycardia, so that it was not possible to estimate the pA2 from nonparallel dose-response curves relating isoprenaline concentration to tachycardia. 3 Bevantolol caused hypertension in pithed rats, an effect attenuated by phentolamine, implying that bevantolol may be an a-adrenoceptor agonist. 4 Bevantolol potentiated the pressor effects of noradrenaline, the maximum potentiation equalling that produced by prior chemical sympathectomy with guanethidine, implying that bevantolol may block noradrenaline uptake. 5 In isolated atria bevantolol-induced bradycardia was associated with a positive shift in take-off potential, a reduction in the maximum rate of depolarization (Vmax), and a lengthening of action potential duration (APD). No change in the slope of the slow diastolic depolarization occurred except at the highest concentration (18 ymol I -'). 6 In atrial and ventricular muscle bevantolol reduced V and overshoot potential, implying reduction of fast inward sodium current (Class I antiarrhythmic action). 7 In pithed rats bevantolol lengthened the P-R interval in the ECG, and produced atrioventricular (A-V) block, and bundle-branch block. In isolated A-V nodal preparations, intranodal conduction time was greatly increased, implying restriction of inward current through calcium channels responsible for nodal depolarization. 8 Bevantolol had no negative inotropic effect in pithed rats, or in isolated atria, and did not alter the positive inotropic effect of raised extracellular calcium concentration, implying absence of restriction of current through calcium channels controlling contraction of the myocardium.

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Beneficial Actions of Bevantolol on Subendocardial Blood Flow and Contractile Function in Ischemic Myocardium

Cited by 23 publications

References 0 publications

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

Bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs

Cardiovascular effects of bevantolol, a selective β₁‐adrenoceptor antagonist with a novel pharmacological profile

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Beneficial Actions of Bevantolol on Subendocardial Blood Flow and Contractile Function in Ischemic Myocardium

Cited by 23 publications

References 0 publications

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

Bisoprolol improves perfusion of ischaemic myocardium in anaesthetized pigs

Cardiovascular effects of bevantolol, a selective β1‐adrenoceptor antagonist with a novel pharmacological profile

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Cardiovascular effects of bevantolol, a selective β₁‐adrenoceptor antagonist with a novel pharmacological profile