Effects of Atenolol on Regional Myocardial Blood Flow and St Segment Elevation in the Canine Myocardium

Abstract

I The effects of atenolol on regional myocardial blood flow (RMBF) and on ST segment elevation were studied both in normal and ischaemic regions of the myocardium in dogs. Some of the experiments were performed with cardiac pacing or after bilateral stellectomy.2 In the absence of cardiac pacing, atenolol (1 mg/kg, i.v.) induced a marked reduction in heart rate and contractile force and a decrease in RMBF, which was of the same magnitude in normal and ischaemic areas. There was no modification in the endo/epi flow ratio. ST segment elevation in ischaemic areas was significantly reduced. 3 Bilateral steliectomy induced similar effects to those of atenolol. Atenolol after bilateral stellectomy exhibited no additional effects. 4 In dogs submitted to cardiac pacing, atenolol no longer decreased RMBF and ST segment elevation. 5 These results demonstrate that with atenolol, there is no correlation between bradycardia and the endo/epi flow ratio while there is one between bradycardia and reduction in ST segment elevation.

Intrinsic sympathomimetic activity and coronary blood flow.

“…Cardioselective P-adrenoceptor blocking drugs would leave vascular P2-adrenoceptors (mediating vasodilation) unaffected, and this would balance any activation of vascular a-adrenoceptors. However, our results are not in agreement with this theory, since pindolol, which is non-cardioselective (Giudicelli et al, 1969) maintained ischaemic flow, whereas atenolol, which is cardioselective, decreased it (Berdeaux et al, 1977). Thus, like in non-ischaemic areas, it appears that ISA is essential in maintaining flow in ischaemic areas, since propranolol and atenolol which are devoid of ISA reduce this flow while pindolol and practolol which exhibit ISA do not affect its value.…”

“…Regarding the distribution of coronary blood flow within the myocardium, it is now well established that some P-adrenoceptor blocking agents are able to produce a beneficial redistribution of flow from the epicardium towards the endocardium of the ischaemic as well as of the non-ischaemic canine heart (Becker etal., 1971;Gross & Winbury, 1973;Becker et al, 1975;Warltier et al, 1976;Berdeaux et al, 1978). The pharmacological analysis of this phenomenon reveals that it can only develop when Pl-adrenoceptor blockade inducing bradycardia and coronary vascular P2-adrenoceptor blockade, leading to an unmasking of a-adrenoceptors which predominate in the epicardium (Zuberbuhler & Bohr, 1965), are simultaneously achieved (Berdeaux et al, 1977(Berdeaux et al, , 1978Giudicelli & Berdeaux, 1981). Thus, only non-cardioselective P-adrenoceptor blocking agents, e.g.…”

“…The pharmacological analysis of this phenomenon reveals that it can only develop when Pl-adrenoceptor blockade inducing bradycardia and coronary vascular P2-adrenoceptor blockade, leading to an unmasking of a-adrenoceptors which predominate in the epicardium (Zuberbuhler & Bohr, 1965), are simultaneously achieved (Berdeaux et al, 1977(Berdeaux et al, , 1978Giudicelli & Berdeaux, 1981). Thus, only non-cardioselective P-adrenoceptor blocking agents, e.g.…”

Reduction of heart rate by chronic β1-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart

“…Such a decrease in myocyte O 2 consumption might inhibit capillary growth, because tissue PO 2 is a strong determinant for induction and/or maintenance of capillary growth (9,31). A second possible explanation is that because AT administration reduces myocardial blood flow (3,13), it follows that shear stress and wall tension, the two vital mechanical stimuli needed for the activation of endothelial cells and angiogenesis (6), would also be diminished within a capillary network during an entire period of ␤-blocker treatment. One additional explanation for the lack of capillary growth may be the use of 1-yr-old rats.…”

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

“…Aside from the protective effects of beta-blockade against catecholamine damage or beta-receptor downregulation in the myocardium, the associated bradycardia has been considered to be a major factor in its ability to preserve cardiac function. For example, ST segment elevation after gradual occlusion of the coronary artery was eliminated by atenolol, but cardiac pacing that returned heart rate to its original level prevented this effect [15]. 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].…”