[Mechanism of QT interval prolongation induced by sevoflurane in guinea-pig ventricular myocyte].

BACKGROUND: Sevoflurane causes QT interval prolongation clinically, but its precise mechanism has not been clarified. We examined the mechanism of QT interval prolongation induced by sevoflurane by means of electrophysiological technique in guinea-pig ventricular myocyte. METHODS: Electrocardiogram was recorded in guinea-pig and effect of sevoflurane (1, 2, 4%) was examined. Action potential (AP), delayed rectified potassium current (IKr), and L-type calcium channel current (ICa) were monitored as whole-cell current and by voltage clamp techniques in guinea-pig single ventricular myocytes. Sevoflurane was applied by bubbling into the bathing solution. RESULTS: Sevoflurane (1, 2, 4%) increased QTc value. Sevoflurane prolonged the duration of AP at 2%, but shortened it at 6%. IKr was reduced to 35% of control in the presence of 2% sevoflurane, but a higher concentration (6%) did not show further inhibition. ICa was reduced only to 87% of control in the presence of 2% sevoflurane and the reduction was dose-dependent (4, 6%). CONCLUSIONS: Sevoflurane 2% inhibited IKr, but it showed only slight inhibition on ICa. Because the duration of AP is regulated by ICa (plateau phase) and IKr (repolarization), greater inhibition of IKr than ICa could result in prolongation of AP. It is suggested that this mechanism may play a role in QT interval prolongation under sevoflurane anesthesia.

The effects of propofol on neural and endothelial control of in situ rat mesenteric vascular smooth muscle transmembrane potentials.

UNLABELLED: We indirectly assessed the in vivo effect of propofol on sympathetic neural and endothelial control of vascular smooth muscle (VSM) tone in Sprague-Dawley rats by measurement of in situ responses of VSM transmembrane potential (E(m)) in intact, small mesenteric arteries and veins superfused with physiologic salt solution. Measurements were made before, during, and after propofol infusion (10 and 30 mg x kg(-1) x h(-1)) in sympathetically innervated and locally denervated vessels. Propofol's effect on E(m) response to superfusion with acetylcholine (ACh), in physiologic salt solution also containing NG-nitro-L-arginine-methyl-ester and indomethacin, was determined in innervated vessels. At 30 mg x kg(-1) x h(-1), propofol caused greater arterial VSM hyperpolarization in innervated compared with denervated vessels (4.8 +/- 2.0 mV versus 2.8 +/- 1.5 mV, respectively). ACh hyperpolarized arterial, but not venous, VSM (e.g., 11.7 +/- 2.4 mV at 10(-4) M). ACh-induced hyperpolarization was eliminated by 30 mg x kg(-1) x h(-1) propofol. Assuming a close inverse correlation between magnitude of VSM E(m) and contractile force, these results suggest that propofol attenuates both sympathetic neural and nonneural regulation of VSM tone. They also suggest that propofol and ACh may act competitively in the second messenger cascade regulating VSM K+ channel activity in mesenteric resistance arteries. IMPLICATIONS: Vascular smooth muscle (VSM) contractile force responses to the IV anesthetic, propofol, were indirectly assessed by VSM membrane potential changes to clarify the mechanisms underlying attenuation of peripheral vascular control of arterial blood pressure. Results indicate that propofol-induced VSM membrane hyperpolarization and coupled reduction of VSM contractile force underlie such attenuation.

Effects of ropivacaine on membrane potential and voltage-dependent calcium channel current in single guinea-pig ventricular myocytes.

PURPOSE: This study was undertaken to assess the effects of ropivacaine on the membrane action potential and the voltage-dependent L-type calcium channel current ( I(Ca)) in guinea-pig single ventricular myocytes. METHODS: Single ventricular myocytes were prepared by enzymatic dispersion. Whole-cell current and voltage-clamp techniques were used to monitor membrane potentials and I(Ca). RESULTS: Ropivacaine (10(-5) and 10(-4) M) reduced the overshoot and shortened the duration of the action potential. Hyperpolarization of the resting membrane potential was observed in the presence of ropivacaine (10(-4) M). Ropivacaine (10(-5)-10(-3) M) reduced I(Ca) dose-dependently and reversibly, and the 50% inhibitory concentration (IC(50)) of ropivacaine was estimated as 4.3 x 10(-4) M. Furthermore, the inhibition of I(Ca) was not a use-dependent block. CONCLUSION: Ropivacaine has an inhibitory effect on I(Ca) in the guinea-pig single ventricular myocyte. It is concluded that the mild negative inotropic effect induced by ropivacaine can be attributed in part to shortening of the duration of the action potential, which is caused by inhibition of I(Ca).