Dose-related depression of left ventricular function or cardiac output has been reported in humans and in vivo animal studies with sevoflurane (SEVO) anesthesia and myocardial depressant effect of SEVO appeared to be comparable to that produced
by
isoflurane (ISO). This study was designed to determine the mechanical and electrophysiologic mechanism of the direct negative inotropic effects of SEVO. The offects of SEVO were comprared to those produced by equipotent concentration of ISO in
the
same
isolated myocardial preparations. Isometric force of isolated guinea pig ventricular papillary muscle was studied in normal and 26 mM K+ Tyrode's solution. Rat papillary muscle was also used to evaluate the effect on Ca2+ release from the
sarcoplasmic
reticulum (SR) at low stimulation rates. Muscles were bathed at 36-37℃ in normal K= Tyrode's solution bubbled with 95% O2/5% CO2 (pH 7.4) and were electrically stimulated following rest and at rates up to 3 Hz. Normal and slow action potentials
were
evaluated by using conventional microelectrodes. Muscles were also subjected to rapid cooling (from 37℃ to 2℃) in order to elicit a transient rapid cooling contracture (RCC) known to be activated by Ca2+ content released from the SR. RCCs were
elicited after 2 Hz stimulation, which produced an RCC tension similar to that of the preceding contraction in control. SEVO and ISO were administered by dial setting in each vaporizer at 1.7 (1 MAC) and 3.4% (2 MAC), and 1.15 (1 MAC) and 2.3% (2
MAC),
respectively. ~20% and 40% depression of contractility was shown at 1.7 and 3.4% concentration of SEVO and the extent of depression was similar to equipotent concentration of ISO from rested state up to 3Hz stimulation rates. 1 and 2 MAC
concentrations
of SEVO (1.7 and 3.4%) or ISO 91.15% and 2.3%) in normal K+ Tyrode's solution caused dose-related depression of peak force at low stimulation rates (RS, 0.1, and 0.5 Hz). Although the normal action potential (AP) amplitude or Vmax were not
changed,
APD50 and APD90 were prolonged characteristically at 2 MAC of both anesthetics. Whereas no contractile depression was shown at RS and 0.1 Hz stimulation rates in rat papillary muscles, significant depression ws noted from 0.5 to 3 Hz in 3.4% SEVO
or
2.3% ISO. In the partially depolarized (26 mM K+ Tyrode's solution) (-adrenergically stimulated myocardium, 2 MAC concentration of both anesthetics caused selective depression of late peak in the biphasic contraction without changing early peak.
In
slow
AP, 3.4% SEVO or 2.3% ISO did not cause any change in AP amplitude and Vmax whereas APD50 and APD90 were prolonged as in Normal Aps. Rapid cooling preceded by 15 min rest showed little contractile force and marked prologation of the time to peak
contracture with almost complete absence of contracture after 2Hz stimulation rates following 3.4% SEVO or 2.3% ISO. Although complete recovery of peak force could be observed, little restoration of RCC was shown after washout for 15 minutes at 2
MAC
concentration of both anesthetics characteristically. The effect of SEVO on isolated myocardial contraction was similar to that of ISO. While neither anesthetic depressed the rapid initial Ca+ release from the SR, the depression of RCC and late
tension
suggest an alteration in some SR pathway. The direct myocardial depressant effects of SEVO and ISO are likely to be related to depressed Ca2+ influx through the cardiac memebrane, while AP prolongation may be due to actions on K+ currents.
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