Effect of verapamil on restoration of cardiac performance in raised [K+]o by adrenergic stimulation in the rabbit.
Modulation of the L-type calcium channel by catecholamines improves action potential parameters in single ventricular myocytes depolarized by high [K+]o Tyrode. Whether this modulation is important in offsetting the negative effects of hyperkalaemia in the whole heart is not known. We tested the effects of the calcium channel antagonist, verapamil, on restoration of cardiac performance by adrenergic stimulation in high [K+]o in anaesthetized rabbits and isolated perfused working rabbit hearts. Raised [K+]o decreased SBP, LVP and LVdP/dtmax in vivo ([K+]a 8.6 +/- 0.2 mM; n = 10) and aortic flow (AF) in the isolated heart (8 mM [K+]o Tyrode; n = 25). However, the negative effects of raised [K+]a were offset by isoprenaline (Iso, 1 microgram kg-1 min-1 i.v.) in vivo and by noradrenaline (NA, 80 nM) in the isolated heart. Verapamil (0.15 mg kg-1 i.v.; 15 nM isolated heart) markedly potentiated the negative inotropic effects of raised [K+]o in both preparations. Verapamil attenuated the effect of isoprenaline in vivo but in the isolated heart, the protective effect of NA in 8 mM [K+] Tyrode (AF 97 +/- 10 mL min-1 in 8 mM [K+]o compared with AF 141 +/- 8.5 mL min-1 in 8 mM [K+]o + NA) was offset by the drug (90 +/- 8 mL min-1 in 8 mM [K+]o + NA + V). Furthermore, verapamil abolished aortic flow in 8 mM [K+]o alone. These findings suggest that the heart may be critically dependent on modulation of intracellular calcium in order to tolerate concentrations of K+ similar to those seen during a short burst of intensive exercise ([K+]a 8.6 mM).
O'Neill
M
M
University Laboratory of Physiology, Oxford, UK.
Ryan
D M
DM
Paterson
D J
DJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001784:Blood Gas Analysis; D002316:Cardiotonic Agents / Q000494:pharmacology; D005260:Female; D006863:Hydrogen-Ion Concentration; D006947:Hyperkalemia / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology*; D011817:Rabbits; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D002316:Cardiotonic Agents; D014700:Verapamil; D007545:Isoproterenol; D011188:Potassium