Depression of myocardial force and stiffness without change in crossbridge kinetics: effects of volatile anesthetics reproduced by nifedipine.
The authors examined the effects of nifedipine, a sarcolemmal slow Ca2+ channel blocker, on dynamic stiffness and force of rabbit right ventricular trabeculum and papillary muscle in Ba2+ contracture, in an attempt to reproduce the effects of halothane, enflurane, and isoflurane on a similar preparation as reported by Shibata et al. Once barium contracture force was established, muscle length was perturbed with small amplitude sinusoidal oscillations in the frequency range of 0.1-100 Hz. Nifedipine 1 microM was then added to the superfusate and dynamic stiffness was again measured. Additional barium was used to determine restoration of contracture force to and beyond control levels. Nifedipine produced a significant decrease in contracture force and high-frequency stiffness with no effect on the frequency (fmin) at which stiffness amplitude exhibited a minimum (P less than 0.005). Contracture force and stiffness could be restored by adding additional barium to the nifedipine-treated muscles. These results are similar to those reported by Shibata et al. using volatile anesthetics. Since nifedipine, which acts specifically at the sarcolemmal slow Ca2+ channel, affects contracture force and dynamic stiffness in this preparation in a manner similar to the volatile anesthetics, the authors suggest that the anesthetics studied by Shibata et al. may well exert a significant component of their negative inotropic activity via their action on the sarcolemmal slow Ca2+ channel.
Chung
O Y
OY
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Blanck
T J
TJ
Berman
M R
MR
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D003864:Depression, Chemical; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D011817:Rabbits; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D014835:Volatilization
D000777:Anesthetics; D015220:Calcium Channels; D009543:Nifedipine