Effects of moderate and deep hypothermia on Ca2+ signaling in rat ventricular myocytes.
OBJECTIVE
We investigated whether the degree of hypothermia determines the impairment in cardiac muscle function upon rewarming and whether the sarcoplasmic reticulum Ca2+ release channel, RyR(2), contributes to hypothermia-induced changes in myoplasmic [Ca2+].


METHODS
Tension measurements using rat papillary muscle and calcium transients (Fluorescent Ca2+ indicator Fura 2-AM) in rat ventricular myocytes were compared during deep (10 degrees C-16 degrees C) and moderate hypothermic (28 degrees C) myocardial temperatures. In a second experiment, myocytes were pretreated with dantrolene, an RyR(2) antagonist; calcium transients were determined at control temperatures (32 degrees C), 16 degrees C, and upon rewarming (32 degrees C).


RESULTS
Papillary muscle contractility and myocyte calcium transients were significantly reduced during and after rewarming from 16 degrees C. At 28 degrees C, papillary muscle isometric tension was potentiated and calcium transients were unaffected. After rewarming from 28 degrees C, excitation-contraction coupling was maintained as isometric tension returned to 90% of control values. After rewarming from 16 degrees C, myocytes pretreated with dantrolene had return of calcium transients to 89% of control values while myocytes not treated with dantrolene recovered to only 50% of their control values.


CONCLUSIONS
We conclude that deep hypothermia, as opposed to moderate hypothermia of the myocardium, disrupts excitation-contraction coupling at cellular and tissue levels. Our finding of preserved calcium transients in dantrolene-pretreated myocytes exposed to deep hypothermia suggests a potential role for the RyR(2) channel in post-hypothermia reductions in cardiac function.
Groban
Leanne
L
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1009, USA. lgroban@wfubmc.edu
Zapata-Sudo
Gisele
G
Lin
Marina
M
Nelson
Thomas E
TE
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D003080:Cold Temperature; D003620:Dantrolene / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D003620:Dantrolene; D002118:Calcium