Comparison of volatile anesthetic effects on actin-myosin cross-bridge cycling in neonatal versus adult cardiac muscle

Background The neonatal myocardium is more sensitive to volatile anesthetics compared with adults. The greater myocardial sensitivity of neonates may be attributable to greater anesthetic effect on force regulation at the level of the cross-bridge. In the current study, the authors compared the effects of 1 and 2 minimum alveolar concentration (MAC) halothane and sevoflurane on cardiac muscle from 0- to 3-day-old (neonate) and Sd-day-old (adult) rats. Methods: Triton X-100-skinned muscle strips were maximally activated at pCa (negative logarithm of the Ca2+ concentration) of 4.0, and the following were measured in the presence or absence of anesthetic: Rate of force redevelopment after rapid shortening and restretching (k(tr)) and isometric stiffness at maximal activation and in rigor. The fraction of attached cross-bridges (alpha(fs)) and apparent rate constants for cross-bridge attachment (f(app)) and detachment (g(app)) were calculated assuming a two-state model for cross-bridge cycling. Anesthetic-induced changes in the mean stiffness per cross-bridge were also estimated from values in rigor versus maximum activation in the presence or absence of anesthetic. Results: Neonatal cardiac muscle displayed significantly smaller alpha(fs), slower k(tr), and slower f(app) compared with adult cardiac muscle; however, g(app) was not significantly different, Halothane, and sevoflurane to a significantly lesser extent, decreased alpha(fs), f(app), and the mean force per cross-bridge and increased g(app) to a greater extent in neonates, Conclusions: These data indicate that weaker force production in neonatal cardiac muscle involves, at least in Dart, less efficient cross-bridge cycling kinetics. The authors conclude that the greater myocardial sensitivity of neonates to volatile anesthetics reflects, at least in Dart, a direct inhibition of crossbridge cycling, especially the rates of cross-bridge attachment and detachment.