Alpha-adrenoceptor control of norepinephrine release from acutely ischaemic myocardium: effects of blood flow, arrhythmias, and regional conduction delay.
We studied the effects of yohimbine, and alpha-adrenoceptor blocker with selectivity for the alpha 2-subtype, on myocardial norepinephrine (NE) overflow, regional myocardial blood flow (RMBF), and patterns of epicardial conduction abnormalities during occlusion of the proximal left anterior coronary artery in an open-chest anaesthetised dog model. With a 12-min period of coronary occlusion (n = 9), spontaneous overflow of NE into ischaemic venous effluent was not observed either before or after yohimbine (1 mg/kg i.v.), but the drug significantly potentiated the enhanced NE overflow during supramaximal stimulation of the left stellate ganglion at low (1 Hz) and high (10 Hz) frequency [peak NE 4.3 +/- 0.4 pmol/ml control; 11.8 +/- 5.4 pmol/ml yohimbine (p less than 0.005)] with a delayed return towards prestimulation levels. Myocardial NE overflow on coronary reperfusion was also enhanced. Yohimbine increased arterial epinephrine two- to threefold but did not substantially alter myocardial lactate overflow during coronary occlusion. RMBF was reduced 24 and 36% to ischaemic endocardium and epicardium, respectively (p less than 0.01, compared with control occlusion). This contrasted with a 9 and 6% decrease in flow to the respective nonischaemic areas (p = NS, compared with control occlusion. Spontaneous ventricular fibrillation and the area and magnitude of epicardial conduction abnormalities in the ischaemic myocardium were both increased compared with the control occlusion. Thus, alpha-blockers with selectivity for the alpha 2-adrenoceptor may be detrimental to acutely ischaemic myocardium, presumably through increased local catecholamine release at the nerve terminal.
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003326:Coronary Circulation; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D006439:Hemodynamics; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D002395:Catecholamines; D007773:Lactates; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D009638:Norepinephrine