Effect of hyperkalemia on myocardial depression by verapamil in isolated hearts.
Verapamil can produce depression of left ventricular function, delayed atrioventricular conduction, and hypotension, which can be potentiated by hyperkalemia. We sought to investigate a direct cardiac interaction between verapamil and hyperkalemia. Studies utilized isolated guinea pig hearts (Langendorff) paced at 250 beats/min. Hearts were randomly assigned to perfusion (Krebs-Henseleit buffer) with potassium concentrations ([K]+) of 1.5, 3, 6 and 9 mmol/l. Infusion of verapamil at rates of 0.2 to 60 micrograms/min (approximately 3 x 10(-8) to 10(-5) mol/l) produced concentration-dependent reduction of isovolumic left ventricular developed pressure. As [K]+ increased, concentration response curves showed parallel shifts to the left. The ED50 for reduction of left ventricular developed pressure significantly decreased: 8.2 +/- 3.7, 2.9 +/- 1.4, 1.2 +/- 0.7, 0.6 +/- 0.2 micrograms/min (mean +/- SD), respectively. Nifedipine and diltiazem were also studied in hearts perfused with 3 and 9 nmol/l [K]+. Infusion of nifedipine 0.003-1 microgram/min (approximately 10(-9) to 3 x 10(-7) mol/l) produced concentration-dependent reduction of left ventricular developed pressure but the ED50 was not affected by [K]+: 0.06 +/- 0.03 and 0.05 +/- 0.04 microgram/min, respectively. Nifedipine vehicle was without effect at the infusion rates tested. Infusion of diltiazem 2-200 micrograms/min (approximately 3 x 10(-7) to 3 x 10(-5) mol/l) also produced concentration-dependent reduction of left ventricular developed pressure. The ED50 for diltiazem-induced reduction of left ventricular developed pressure was significantly reduced by elevated [K]+: 20.1 +/- 6.7 and 3.5 +/- 0.9 micrograms/min with 3 and 9 mmol/l [K]+, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Jolly
S R
SR
Cardiology Section/Department of Medicine, East Carolina University School of Medicine, Greenville, NC 27858-4354.
Wilson
V P
VP
Movahed
A
A
Mehta
P
P
Boyd
S G
SG
Reeves
W C
WC
D000818:Animals; D003864:Depression, Chemical; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006947:Hyperkalemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine