Hypothermia modifies anesthetic effect on contractile force and Ca2+ transients in cardiac Purkinje fibers.
Mild hypothermia enhances cardiac contractility, and volatile anesthetics depress contractility. Contractile force (tension) and Ca2+ transients were measured in canine Purkinje fibers at 35 and 25 degrees C with and without halothane and isoflurane to examine how anesthetics attenuate the positive inotropic effect of mild hypothermia. Isometric tension and light emitted from the photoprotein aequorin were used to assess contractility and intracellular Ca2+ transients in fibers stimulated at 40-60 pulses/min. At 35 degrees C, each anesthetic depressed peak tension and peak Ca2+ transients and decreased contractile force duration but, for halothane, increased Ca2+ transient duration. Decreases in tension by both anesthetics at 35 degrees C were converted to marked increases in tension at 25 degrees C, whereas Ca2+ transients were little changed. Removal of anesthetics at 25 degrees C greatly increased tension with a small increase in Ca2+ transients that was much lower than that at 35 degrees C. The curve relating peak contractile force as a function of Ca2+ transients at 25 degrees C during stepwise increases in extracellular CaCl2 was shifted steeper and leftward of the curve at 35 degrees C. These studies suggest that the positive inotropic effect of mild hypothermia is due primarily to increased myofibrillar Ca2+ sensitivity and that anesthetics decrease tension during hypothermia by decreasing myofibrillar Ca2+ sensitivity. Reduced influx of transsarcolemmal or sarcoplasmic reticular Ca2+ may also play a role during mild hypothermia.
Sprung
J
J
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee.
Stowe
D F
DF
Kampine
J P
JP
Bosnjak
Z J
ZJ
D000331:Aequorin; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004285:Dogs; D004594:Electrophysiology; D006221:Halothane / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007036:Hypothermia, Induced; D007530:Isoflurane / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009994:Osmolar Concentration; D011690:Purkinje Fibers / Q000502:physiology*; D013696:Temperature
D000777:Anesthetics; D000331:Aequorin; D007530:Isoflurane; D002118:Calcium; D006221:Halothane