title: Comparative effects of diltiazem with enflurane or desflurane on myocardial contractility and heart rate in the isolated rat hearts.
abstract: BACKGROUND
  The volatile anesthetics may reduce cardiac contractility by limiting both membrane Ca2+ entry and altering intracellular Ca2+ release. Additional pharmacological effects of calcium channel blockers could potentially enhance anesthetic-induced depression. The aim of this study was to compare the direct cardiac effects of enflurane and a new volatile anesthetic, desflurane, in combination with diltiazem on the isolated Sprague-Dawley rat heart.
  
  
  METHODS
  After stabilization period isolated rat hearts (n = 40) were perfused with an oxygenated modified Krebs' solution at 55 mmHg equilibrated with 1, 2 and 3 MAC of enflurane (1.7, 3.4 and 5.1 vol% respectively) or desflurane (6, 12 and 18 vol% respectively) in combination with 100 ng/mL diltiazem at 36 degrees C. Isovolumetric left ventricular pressure (LVP), rate of change of ventricular pressure (dp/dt), spontaneous heart rate and coronary flow were measured. To examine the indirect metabolic effect due to autoregulation of coronary flow, O2 delivery (DO2), myocardial O2 consumption (MVO2) and percent O2 extraction (POE) were also monitored.
  
  
  RESULTS
  Diltiazem plus enflurane or desflurane depressed LVP and dp/dt dose-dependently. Enflurane plus diltiazem significantly decreased heart rate more than desflurane plus diltiazem in a dose-dependent manner. Desflurane plus diltiazem significantly increased coronary flow more than enflurane plus diltiazem and oxygen delivery increased proportionally with coronary flow. But there were statistically insignificant dose-dependent increases in both groups. Myocardial oxygen consumption and percentage of oxygen extraction were also decreased dose-dependently in both groups. Bradydysrhythmia that accompanied atrioventricular dissociation occurred with diltiazem plus high enflurane or desflurane concentration at an incidence of 46% and 40% respectively.
  
  
  CONCLUSIONS
  These in vitro results demonstrate that diltiazem plus enflurane or desflurane depresses left ventricular contractile function and diltiazem plus enflurane causes higher incidence of bradydysrhythmia more than equivalent levels of diltiazem plus desflurane.
authors.affiliation: Department of Anesthesia, College of Medicine, Korea University, Seoul, Korea.
authors.forename: M K
authors.initials: MK
authors.lastname: Lee
authors.forename: I O
authors.initials: IO
authors.lastname: Lee
authors.forename: M H
authors.initials: MH
authors.lastname: Kong
authors.forename: N S
authors.initials: NS
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Choi
authors.forename: S H
authors.initials: SH
authors.lastname: Lim
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000077335:Desflurane; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004737:Enflurane / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D004737:Enflurane; D000077335:Desflurane; D007530:Isoflurane; D004110:Diltiazem