title: Effect of hyperkalemia on myocardial depression by verapamil in isolated hearts.
abstract: 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)
authors.affiliation: Cardiology Section/Department of Medicine, East Carolina University School of Medicine, Greenville, NC 27858-4354.
authors.forename: S R
authors.initials: SR
authors.lastname: Jolly
authors.forename: V P
authors.initials: VP
authors.lastname: Wilson
authors.forename: A
authors.initials: A
authors.lastname: Movahed
authors.forename: P
authors.initials: P
authors.lastname: Mehta
authors.forename: S G
authors.initials: SG
authors.lastname: Boyd
authors.forename: W C
authors.initials: WC
authors.lastname: Reeves
mesh_terms: 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*
chemical_list: D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine