Electrophysiological effects of alpha-adrenoceptor stimulation in perfused and superfused myocardium.
To investigate possible mechanisms for the differing electrophysiological actions of alpha-adrenoceptor stimulation in superfused myocardium and isolated, perfused hearts, we compared the cellular electrophysiological responses to methoxamine (10(-7), 10(-6) and 10(-5)M) in isolated, buffer-perfused guinea-pig hearts and superfused right ventricular tissue at 32 degrees C and 37 degrees C. During superfusion at 32 degrees C with 10(-7)M methoxamine, action potential duration increased. Similar increases in action potential duration and refractory period were seen with 10(-6) M methoxamine while with 10(-5)M methoxamine action potential duration increased but refractory period was unchanged. At 37 degrees C, no changes occurred with 10(-7)M and 10(-6)M methoxamine, but with 10(-5)M, action potential duration increased. Perfusion of isolated hearts with 10(-7)M and 10(-6)M methoxamine had no effect on action potential duration and refractory period at 32 degrees C, but with 10(-5)M methoxamine, refractory period increased. No changes occurred in the hearts at 37 degrees C. Methoxamine had no effect on maximum upstroke velocity of the action potential, conduction time, QRS width and pacing threshold in the perfused hearts or the superfused ventricular strips. Methoxamine (10(-6)M) also reduced action potential duration and refractory period in hearts made globally ischaemic, confirming previous results. Thus, methoxamine increases action potential duration and refractory period in superfused ventricular tissue (32 degrees C greater than 37 degrees C), has no effect in normally perfused hearts, but during myocardial ischaemia reduces action potential duration and refractory period.
Academic Cardiology Unit, St. Mary's Hospital Medical School, London, UK.
N A
NA
Flores
D J
DJ
Sheridan
D000200:Action Potentials / Q000187:drug effects*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology; D006168:Guinea Pigs; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D015425:Myocardial Reperfusion; D011312:Pressure; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D013696:Temperature; D044005:Tetrahydroisoquinolines
D000317:Adrenergic alpha-Antagonists; D000634:Aminoquinolines; D011942:Receptors, Adrenergic, alpha; D044005:Tetrahydroisoquinolines; C058534:abanoquil; D008729:Methoxamine