Temporal relationship of contractility and myocardial potassium balance following beta-adrenergic stimulation of the in situ pig heart.
Lower intracellular Na+ during beta-adrenergic stimulation provides an increased driving force for Na-Ca exchange, which might attenuate the inotropic response. Since (1) Na+ reduction is coupled to K+ uptake, and (2) K+ uptake lags behind the positive inotropic response to isoproterenol, we could examine the effect of Na-Ca exchange by comparing cardiac contractility and K+ balance following intracoronary isoproterenol infusion (0.6-0.8 microgram min-1). In 8 open-chest pigs, potassium concentrations were continuously measured by PVC-valinomycin mini-electrodes in arterial blood (a), and in myocardial venous blood in a shunt from the coronary sinus (cs) to the right atrium. Shunt flow, aortic flow, a left ventricular segment length and left ventricular pressure (LVP) were also continuously recorded. 64 (41-85)% (median and 95% confidence interval) of the LV dP/dt increase occurred within 1 min; thereafter contractility rose slowly. During the first minute of isoproterenol infusion, there was a small net myocardial K+ release, which then reversed to K+ accumulation. A maximum a-cs K+ concentration difference of 0.20 (0.09-0.39) mM occurred at 3.0 (2.0-4.25) min, falling to 0.05 (0.01-0.10) mM after 6.5 (3.75-8.75) min, at which point accumulated myocardial K+ uptake was 135 (27-219) mumol 100 g-1. Heart rate remained unchanged and intramural ECG indicated no sign of ischemia during the first 1.5 min of isoproterenol infusion. At 6.25 (5.0-8.0) min after stop of isoproterenol, LV dP/dt was 12 (9-24)% lower than before infusion (P less than 0.02) whereas myocardial K+ content remained higher than control. Thus, the monovalent cation shift succeeding the positive inotropic response was not associated with reduced contractility, but could explain the undershoot of LV dP/dt after stopping isoproterenol.
Ellingsen
O
O
Institute for Experimental Medical Research, University of Oslo, Norway.
Vengen
O A
OA
Sejersted
O M
OM
Ilebekk
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004562:Electrocardiography; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D013552:Swine
D000318:Adrenergic beta-Agonists; D007545:Isoproterenol; D011188:Potassium