The Direct Myocardial Depressant Effect of Methylmethacrylate Monomer in vitro: Mechanical and Electrophysiological Actions / 대한마취과학회지

BACKGROUND: Methylmethacrylate monomer (MMA) bone cement has been associated with sudden systemic hypotension. The present study was aimed to explore the mechanism of direct myocardial depressant actions of MMA. METHODS: The isometric contraction of isolated guinea pig's right ventricular papillary muscle was measured. Normal and slow action potentials were evaluated by a conventional micro-electrode technique. The effects of MMA on sarcoplasmic reticulum (SR) function were evaluated by its effect on: rapid cooling contractures, rested state contraction of rat papillary muscle in normal Tyrode's solution and of guinea pig's papillary muscle in low Na+ Tyrode's solution. To measure the inward calcium currents (ICa), whole cell patch clamp techniques were applied. RESULTS: MMA caused a dose-dependent depression of the peak force (PF) and maximal rate of peak force (dF/dt-max). About a 30% depression of PF was shown at rested state (RS) contraction in rat myocardium and under low Na+ Tyrode's solution in guinea pig myocardium, respectively. In the 26 mM K+ Tyrode's solution, MMA caused dose-dependent depression of late force development without alteration in early force development. MMA depressed rapid cooling contracture accompanied by prolongation of time to peak contracture. MMA did not alter the amplitude or maximum depolarization rate of normal and slow action potentials. Action potential durations were significantly reduced. In patch clamp studies, MMA reduced ICa in a dose-dependent manner. CONCLUSIONS: MMA depressed cardiac contractility in a dose-dependent manner and may be partly related to the depression of Ca2+ influx through the cardiac membrane. SR Ca2+ release seems to be mildly inhibited by MMA. Based on common clinical concentrations, the direct myocardial depressant effect of MMA may not be a main cause of hypotension during an operation.

notropic and Electrophysiologic Effect of Azumolene in Intact Myocardium In Vitro / 대한마취과학회지

BACKGROUND: The effects of various concentrations (10, 25 micrometer) of azumolene, an analogue of dantrolene, were studied in isolated guinea pig ventricular papillary muscles by measuring the effects on myocardial contractility and electrophysiologic parameters. METHODS: Isometric forces were studied in normal and 26 mM K Tyrode's solution. Rapid cooling contracture, an index of SR Ca2 content, was performed. Normal and slow action potentials (APs) were evaluated by using conventional microelectrode technique. RESULTS: Ten and 25 micrometer azumolene depressed peak force and maximum rate of force development ( 30 40%). Dose-dependent depression was shown at 2 and 3 Hz stimulation rate. Rapid cooling contractures following 10 and 25 micrometer azumolene was not altered compared to control while peak force at 2 Hz stimulation rate just prior to cooling was depressed similarly to normal Tyrode's solution. In 26 mM K Tyrode's solution, 10 and 25 micrometer azumolene caused depression of early (10 micrometer: 20%) and late (10 micrometer: 50%) force development. In slow APs, shortening of AP duration at 20, 50, and 90% of the repolarization phase, as well as a small but significant reduction of dV/dt-max ( 20%) were shown at 0.25 Hz stimulation rate. There was no alteration in AP parameters in normal APs. CONCLUSIONS: The direct myocardial depressant action of azumolene seems to be at least in part caused by inhibition of Ca2 influx via the Ca2 channel in sarcolemma. It seems likely that azumolene does not alter the sarcoplasmic reticulum function such as Ca2 uptake and release in cardiac muscle.

The Effects of Flumazenil and Verapamil on the Relaxation of Midazolam in Isolated Guinea-pig Tracheal Smooth Muscle / 대한마취과학회지

BACKGROUND: Midazolam relaxes airway smooth muscle. The aim of this study is to evaluate the influence of flumazenil or verapamil on the relaxation effects of midazolam in tracheal smooth muscle of guinea pig. METHODS: After isolating guinea-pig tracheal preparations, the maximal tracheal tones were induced by 2 10(-7) M carbachol. When tracheal tones stabilized, midazolam was added cumulatively (10(-6), 3 10(-6), 10(-5), 3 10(-5), 10(-4) M, n=14) with or without flumazenil (10(-6) M, n=15) and verapamil (10(-5) M, n=13) to obtain the concentration-relaxation curves, and then the ED50 and ED95 calculated. RESULTS: Midazolam decreased maximal tracheal smooth muscle tones in concentration-dependent manners. Pretreatment with flumazenil had no effect on the midazolam-induced relaxation. Verapamil enhanced the relaxation effect of midazolam. CONCLUSIONS: Midazolam relaxes airway smooth muscle and has synergistic effect with calcium channel blocker, verapamil.

Effects of Ketamine on Intracellular Ca2+ Pooling in Guinea Pig Trachea / 대한마취과학회지

BACKGROUND: The potent bronchodilatory effects of ketamine on airway smooth muscle tone are important in the management of patients with asthma, but its mode of action is unclear. In the present study we evaluated that effects on isolated guinea pig tracheal smooth muscle. METHODS: Changes of isometric contraction of strip were measured. (1) Serial stimulation with acetylcholine(ACh) in Krebs solution or with A23187, nifedipine, ketamine were evaluated. After that, ACh stimulation was induced in Ca2+ free solution. (2) In Ca2+ free solution, ACh contraction was obtained(L1) and emptied by repetitive ACh stimulation. Internal stores were refilled by Ca2+ with ACh stimulation. During the incubation period, A23187, nifedipine, ketamine, cyclopiazonic acid + ketamine was added and tested for their ability to inhibit refilling. Refilling was evaluated by ACh produced contraction (L2) with ratio (L2/L1). (3) Effects of ketamine on the contraction induced by caffeine were also checked. RESULTS: Ketamine inhibited amplitude dose-dependently by successive application of ACh in modified Krebs solution and Ca2+ free solution. Ca2+ influx through voltage gated channels were inhibited with nifedipine but not with A23187. ACh sensitive internal store were different when A23187, nifedipine and ketamine were applied in Ca2+ free solution. Refilling of internal store were potentiated by A23187, but decreased by nifedipine and ketamine. Caffeine produced contractions in the presence of ketamine were not significantly different from control. CONCLUSION: We concluded that the inhibitory effects of ketamine in guinea pig trachea were by acting through voltage and receptor gated channels in dose-depedent manner and these effects may be interferences of intracellular second messengers system.