Contribution of ?-adrenoceptors to the contractility of the human myocardium in chronic coronary heart disease

Abstract

Sympathetic regulation of the myocardium is mediated by a population of β -and α -adrenoceptors. Even the myocardium isolated from patients with chronic coronary insufficiency retains some basal adrenoceptor activity. A blockade of these receptors causes a negative inotropic effect [1]. Under the conditions of an α -adrenoceptor blockade, the effect of norepinephrine on the isolated myocardium of patients with chronic coronary heart disease (CHD) is augmented by a factor of 1.5 [1]. This finding is in good agreement with the fact that simultaneous stimulation of adrenoceptors is accompanied by mutual attenuation of their inotropic effects [2]. Conversely, a blockade of receptors of one type is equilibrated by an increased activity of receptors of the other type.Inotropic effects of the α -adrenoceptors are related to phosphoinositide metabolism, the products of which play the role of intracellular messengers. Therefore, α -adrenoceptor stimulation is one of the possible mechanisms of endogenous cardioprotection [3]. It is in this connection that Academician E.I. Chazov remarked, "Disturbance in the adrenergic regulation of the myocardium in chronic cardiac insufficiency is a topical problem" [4].The present study aims to investigate the capability of the α 1 -adrenoceptors for maintaining the contractile function of the myocardium in chronic coronary insufficiency.The study was performed on perfused myocardial strips isolated from biopsy material of the right atrial auricle. The excision of the right atrial auricle is obligatory during surgery conducted under the conditions of extracorporeal circulation. We investigated the myocardium in two groups of male patients. The test group included six patients with chronic CHD and angina of effort (functional classes III-IV according to the NYHA). These patients (mean age 50 ± 3 years) underwent aortocoronary bypass grafting. The control group included four patients with WPW syndrome (mean age 43 ± 2.4 years).Muscle strips were no less than 5 mm in length and no more than 1 mm 2 in section, had parallel fibers, and lacked a connective tissue membrane. The strips were perfused with Krebs-Henseleit solution saturated with carbogen (95% O 2 and 5% CO 2 ) in a thermally stabilized chamber (1 ml) at 36° C [1, 5].The frequency of muscle contractions was determined by rectangular-shaped electrical pulses with a 5-ms duration and an amplitude exceeding the excitation threshold by 20-30%. The pulses were transmitted through two massive silver electrodes located in the chamber. By means of a micromanipulator, the muscles were stretched out to achieve the maximum possible inotropic effect. The muscle tension was monitored throughout the adaptation period (60 min). After the end of adaptation, the final muscle tension was produced and contractive activity was recorded.The muscle contractive activity was assessed in the isometric mode by changes in the curves of tension and its first derivative [1,5]. A 6MKh1S mechanotron converter was used as an isometric sensor. The following param...