Pierre-Yves Gueugniaud

Effects of Desflurane in Rat Myocardium: Comparison with Isoflurane and Halothane

Background The cardiovascular effects of desflurane have been investigated in several in vivo animal and human studies. To determine the possible contributions of myocardial depression, the effects of desflurane on various contractile parameters in isolated cardiac papillary muscles were compared with those of isoflurane and halothane. Methods The effects of desflurane, isoflurane, and halothane (0.5-2.5 minimum alveolar concentration [MAC]) were studied in rat left ventricular papillary muscles (29 [degree sign] Celsius; pH 7.40; stimulation frequency, 12 pulses/min). The inotropic effects were compared under low (isotony) and high (isometry) loads, using the maximum unloaded shortening velocity (Vmax) and maximum isometric active force (AF). The lusitropic effects were compared in isotonic and isometric conditions. Results Desflurane has no significant inotropic effect (AF at 2.5 MAC: 95 +/- 11% of control values; NS) in contrast with halothane and isoflurane (AF at 2.5 MAC: 37 +/- 14 vs. 65 +/- 10%, respectively; P <0.05). After alpha- and beta-adrenoceptor blockade or pretreatment with reserpine, desflurane induced a negative inotropic effect (AF at 2.5 MAC: 83 +/- 11 vs. 89 +/- 8%, respectively) that was not significantly different from that of isoflurane (AF at 2.5 MAC: 80 +/- 12%). Halothane induced a negative lusitropic effect under low load, which was significantly greater than those of isoflurane and desflurane. In contrast to halothane, isoflurane and desflurane induced no significant lusitropic effect under high load and did not modify postrest potentiation. These results suggest that desflurane did not impair sarcoplasmic reticulum function. Conclusions When compared with isoflurane, desflurane induced a moderate positive inotropic effect related to intramyocardial catecholamine release. After adrenoceptor blockade, desflurane induced a negative inotropic effect comparable with that induced by isoflurane.

Myocardial effects of halothane and isoflurane in hamsters with hypertrophic cardiomyopathy.

Background: The effects of halothane and isoflurane on myocardial contraction and relaxation in diseased myocardium are not completely understood. Methods: The effects of equianesthetic concentrations of halothane and isoflurane on inotropy and lusitropy in left ventricular papillary muscles of healthy hamsters and those with genetically induced cardiomyopathy (strain BIO 14.6) were investigated in vitro (29 [degree sign] Celsius; pH 7.40; Ca2+ 2.5 mM; stimulation frequency, 3/min) in isotonic and isometric conditions. Results: Halothane induced a negative inotropic effect that was greater in cardiomyopathic than in healthy hamsters (1.5 vol%, active isometric force (AF): 19 +/‐ 8% vs. 28 +/‐ 11% of control values; P <0.05). Isoflurane induced a negative inotropic effect that was greater in cardiomyopathic than in healthy hamsters (2.0 vol%, AF: 64 +/‐ 13% vs. 75 +/‐ 11% of control values; P < 0.01). However, the negative inotropic effects of halothane and isoflurane were not different for cardiomyopathic or healthy hamsters when their concentrations were corrected for minimum alveolar concentration (MAC) values in each strain. Halothane induced a negative lusitropic effect under low load, which was more important in cardiomyopathic hamsters, suggesting a greater impairment in calcium uptake by the sarcoplasmic reticulum. In contrast, isoflurane induced a moderate positive lusitropic effect under low load in healthy but not in cardiomyopathic hamsters. Halothane and isoflurane induced no significant lusitropic effect under high load. Conclusions: Halothane and isoflurane had greater negative inotropic effects in cardiomyopathic than in healthy hamsters. Nevertheless, no significant differences in their inotropic effects were noted when concentrations were correlated as a multiple of MAC in each strain.

interaction of Isoflurane and Sevoflurane with α- and β-adrenoceptor Stimulations in Rat Myocardium

BACKGROUND: Halothane potentiates the positive inotropic effects of alpha- and beta-adrenoceptor stimulations but impairs the positive lusitropic effect of beta-adrenoceptor stimulations. However, the interactions of isoflurane and sevoflurane with alpha- and beta-adrenoceptor stimulation have not been entirely defined. METHODS: The effects of 1 minimum alveolar concentration isoflurane and sevoflurane on the inotropic responses induced by phenylephrine (10(-8) to 10(-4) M) or isoproterenol (10(-8 to 10(-4) M) were studied in rat left ventricular papillary muscles in vitro (Krebs-Henseleit solution, 29 degrees C; pH, 7.4; 0.5 mM calcium; stimulation frequency, 12 pulses/min). The positive lusitropic effects of alpha- and beta-adrenoceptor stimulations were studied under isotonic and isometric conditions. Data are mean percentages of baseline +/- SEM. RESULTS: In control groups, phenylephrine (134 +/- 8%; P < 0.05) and isoproterenol (171 +/- 7%; P < 0.05) induced a positive inotropic effect. Isoflurane enhanced the positive inotropic effects of phenylephrine (185 +/- 10%; P < 0.05) and of isoproterenol (203 +/- 11%; P < 0.05). Sevoflurane enhanced the positive inotropic effects of phenylephrine (187 +/- 10%; P < 0.05) and of isoproterenol (228 +/- 11%; P < 0.05). These potentiations were similar to those previously reported with halothane. Isoflurane and sevoflurane did not modify the positive lusitropic effects under low and high loads of isoproterenol. CONCLUSION: Although isoflurane and sevoflurane have moderate negative inotropic effects, they potentiated the positive inotropic effects of alpha- and beta-adrenoceptor stimulations but did not modify the positive lusitropic effects of beta-adrenoceptor stimulation.

Interaction of Halogenated Anesthetics with Dobutamine in Rat Myocardium

BACKGROUNDnHalogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations, but their interactions with dobutamine remain unknown.nnnMETHODSnThe effects of halothane, isoflurane, sevoflurane, and desflurane (1 and 2 minimum alveolar concentration) on the inotropic responses induced by dobutamine (10(-8)-10(-4) M) were studied in rat left ventricular papillary muscles in vitro. Inotropic effects were studied under low (isotony) and high (isometry) loads. The authors also studied the lusitropic effects in isotonic (R1) and isometric (R2) conditions. Data are the mean percentage of baseline +/- SD.nnnRESULTSnDobutamine induced a positive inotropic effect (active isometric force: 185+/-36%, P < 0.001) and a positive lusitropic effect under low load (R1: 78+/-9%, P < 0.001), but not under high load (R2: 95+/-21%, not significant). Halothane, isoflurane, and sevoflurane did not modify the positive inotropic effect of dobutamine. Even in the presence of alpha-adrenoceptor blockade, isoflurane did not potentiate the positive inotropic effect of dobutamine. Desflurane significantly enhanced the positive inotropic effect of dobutamine (active isometric force: 239+/-35%, P < 0.001), but this potentiation was abolished by pretreatment with reserpine. In contrast to halothane, isoflurane, sevoflurane, and desflurane did not significantly modify the lusitropic effects of dobutamine.nnnCONCLUSIONSnHalogenated anesthetics, except desflurane, did not modify the positive inotropic effects of dobutamine. Desflurane enhanced the positive inotropic effect of dobutamine, but this effect was related to the desflurane-induced release in intramyocardial catecholamine stores.

Myocardial effects of Desflurane in hamsters with hypertrophic cardiomyopathy

Background The effects of desflurane on myocardial contraction and relaxation in diseased myocardium have not been completely understood. Methods The effects of desflurane (1.8 to 9.4 vol%) in left ventricular papillary muscles of healthy hamsters and those with genetically induced cardiomyopathy (strain BIO 14.6) were investigated in vitro (29 [degree sign]C, pH 7.40, Ca2+ 2.5 mM; stimulation frequency, 3/min) under low (isotony) and high (isometry) load. Data are mean percentages of baseline +/− SD. Results Desflurane induced no significant inotropic effect in healthy muscles (maximum unloaded shortening velocity and isometric active force at 9.4 vol%: 97 +/− 9% and 92 +/− 20%, respectively). In contrast, in cardiomyopathic muscles, desflurane induced a moderate negative inotropic effect (maximum unloaded shortening velocity and active force at 9.4 vol%: 84 +/− 19% and 75 +/− 25%, respectively). The negative inotropic effect was more pronounced than that in healthy muscles under low (P < 0.05) but not high load, and even when concentrations were corrected for minimum alveolar concentrations in each strain. Adrenoceptor blockade or pretreatment with reserpine did not modify the inotropic effect of desflurane, suggesting the absence of intramyocardial catecholamine release. However, tyramine also did not induce any significant catecholamine release in hamster myocardium. In both strains, desflurane induced no significant lusitropic effect under low or high load. Conclusions Desflurane had no inotropic effect in healthy muscles and a moderate negative inotropic effect in cardiomyopathic muscles. The absence of desflurane‐induced intramyocardial catecholamine release was related to hamster myocardium characteristics.

Improving Access to Thrombolysis and Inhospital Management Times in Ischemic Stroke: A Stepped-Wedge Randomized Trial

Background and Purpose— A suboptimal number of ischemic stroke patients eligible for thrombolysis actually receive it, partly because of extended inhospital delays. We developed a comprehensive program designed for emergency unit staff and evaluated its effectiveness for reducing intrahospital times and improving access to thrombolysis. Methods— We conducted a randomized stepped-wedge controlled trial in 18 emergency unit. The sequentially implemented training intervention, targeting emergency physicians and nurses, was based on specifically designed videos and interactive simulation workshops on intrahospital management optimization. The effectiveness was assessed on intrahospital times and thrombolysis proportion. During the study period, all consecutive patients with confirmed ischemic stroke and no contraindications to thrombolysis were included. Results— A total of 328 patients were enrolled in the control group and 363 in the intervention group. Mean age was 73.6 years. Overall thrombolysis proportion was 34.2% in the intervention group versus 25.6% in the control group (adjusted odds ratio, 1.42; 95% confidence interval, 1.01–2.01), thrombolysis proportion within 4 hours 30 minutes almost doubled (adjusted odds ratio, 1.9; 95% confidence interval, 1.32–2.73). Although imaging-to-stroke unit time was significantly decreased in the intervention group (39 versus 53 minutes; P=0.03), median door-to-imaging and door-to-needle times were not different between groups (P=0.70 and P=0.40, respectively). Conclusions— An interactive and multifaceted training program targeting emergency professionals was significantly associated with an increased access to thrombolysis, especially within 4 hours and 30 minutes. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT02814760.