Isoflurane and halothane inhibit tetanic contractions in rabbit myocardium in vitro.
Rabbit right ventricular papillary muscles were tetanized by rapid stimulation in the presence of 1 microM ryanodine, an inhibitor of sarcoplasmic reticular function. Tetanic contractions elicited in this manner increased in strength as extracellular calcium concentration [Ca+2]ext was raised from 0.5 to 5 mM, exhibited saturation behavior above [Ca+2]ext = 5 mM, and were blocked by nifedipine. Accompanying membrane potentials depolarized to +10 mV and repolarized to -60 mV between stimuli. These data suggest that rabbit myocardial tetany is supported in large part by extracellular calcium influx via slow (L-type) calcium channels, consistent with similar recent findings in the ferret. At [Ca+2]ext = 2.5 mM, isoflurane (0.6-2.3%, gas phase) and halothane (0.4-1.5%) inhibited the strength of tetanic contractions in dose-dependent fashion. At [Ca+2]ext = 20 mM neither isoflurane (1.2%) nor halothane (0.8%) inhibited tetanic contraction strength. These data demonstrate that isoflurane and halothane inhibit contractile activity that is dependent on transsarcolemmal calcium influx via pathways independent of the ryanodine-sensitive sarcoplasmic reticulum. The exact sites of inhibition (e.g., slow channel vs. intracellular transit vs. myofibrillar binding) are not identified, but inhibition by either anesthetic may be competitively reversed by high extracellular calcium concentrations.
DeTraglia
M C
MC
Department of Anesthesiology, Rochester General Hospital, New York 14621.
Komai
H
H
Redon
D
D
Rusy
B F
BF
D000818:Animals; D002118:Calcium / Q000502:physiology; D003864:Depression, Chemical; D004558:Electric Stimulation; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology
D012433:Ryanodine; D007530:Isoflurane; D009543:Nifedipine; D002118:Calcium; D006221:Halothane