Anesthesia and analgesia
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Anesthesia and analgesia · Jan 2000
Sevoflurane and isoflurane do not enhance the pre- and postischemic eicosanoid production in guinea pig hearts.
Eicosanoids and volatile anesthetics can influence cardiac reperfusion injury. Accordingly, we analyzed the effects of sevoflurane and isoflurane applied in clinically relevant concentrations on the myocardial production of prostacyclin and thromboxane A2 (TxA2) and on heart function. Isolated guinea pig hearts, perfused with crystalloid buffer, performed pressure-volume work. Between two working phases, hearts were subjected to 15 min of global ischemia followed by reperfusion. The hearts received no anesthetic, 1 minimum alveolar anesthetic concentration (MAC) isoflurane (1.2 vol%), or 0.5 and 1 MAC sevoflurane (1 vol% and 2 vol%), either only preischemically or pre- and postischemically. In additional groups, cyclooxygenase function was examined by an infusion of 1 microM arachidonic acid (AA) in the absence and presence of sevoflurane. The variables measured included the myocardial production of prostacyclin, TxA2 and lactate, consumption of pyruvate, coronary perfusion pressure, and the tissue level of isoprostane 8-iso-PGF2alpha. External heart work, determined pre- and postischemically, served to assess recovery of heart function. Volatile anesthetics had no impact on postischemic recovery of myocardial function (50%-60% recovery), perfusion pressure, lactate production, or isoprostane content. Release of prostacyclin and TxA2 was increased in the early reperfusion phase 5-8- and 2-4-fold, respectively, indicating enhanced AA liberation. Isoflurane and sevoflurane did not augment the eicosanoid release. Only 2 vol% sevoflurane applied during reperfusion prevented the increased eicosanoid formation in this phase. Infusion of AA increased prostacyclin production approximately 200-fold under all conditions, decreased pyruvate consumption irreversibly, and markedly attenuated postischemic heart work (25% recovery). None of these effects were mitigated by 2 vol% sevoflurane. In conclusion, only sevoflurane at 2 vol% attenuated the increased liberation of AA during reperfusion. Decreased eicosanoid formation had no effect on myocardial recovery in our experimental setting while excess AA was deleterious. Because eicosanoids influence intravascular platelet and leukocyte adhesion and activation, sevoflurane may have effects in reperfused tissues beyond those of isoflurane. ⋯ In an isolated guinea pig heart model, myocardial eicosanoid release was not increased by isoflurane or sevoflurane, either before or after ischemia. Sevoflurane (2 vol%) but not isoflurane attenuated the increased release of eicosanoids during reperfusion.
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Anesthesia and analgesia · Jan 2000
Biography Historical ArticleErnst Trier Mørch: inventor, medical pioneer, heroic freedom fighter.
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Anesthesia and analgesia · Jan 2000
Perinatal cocaine exposure impairs myocardial beta-adrenoceptor signaling in the neonatal rat.
Cardiac dysfunction occurs in infants with prenatal cocaine exposure, and gestational cocaine exposure induces presynaptic and postsynaptic changes in the central monoaminergic receptor pathways. The hypothesis of this study is that prenatal cocaine exposure adversely affects the peripheral adrenergic receptor (betaAR) signaling pathway in the neonatal rat heart. Timed pregnant rats received daily intragastric treatment with saline or cocaine 20 mg/kg or 60 mg/kg from Gestational Day 2 until parturition. After birth, nursing mothers either continued to receive the same treatment or received no treatment. Adenylyl cyclase activity, betaAR density, and the amount of immunoreactive G proteins were measured in myocardial membranes obtained from the offspring on Postnatal Day 1 or 7. On Postnatal Day 1, prenatal cocaine exposure increased the betaAR number but did not affect isoproterenol-stimulated adenylyl cyclase activity. On Postnatal Day 7, perinatal cocaine exposure significantly attenuated isoproterenol-stimulated adenylyl cyclase activity in the absence of betaAR up-regulation. Prenatal cocaine exposure also significantly increased Gi protein and reduced GTP-stimulated adenylyl cyclase activity in Postnatal Day 1 cocaine (20 mg/kg) pups compared with saline (P < 0.05). Therefore, perinatal cocaine exposure impaired the myocardial betaAR-cAMP signaling pathway during the first week of postnatal life in the rat. ⋯ This study shows that maternal cocaine use during pregnancy impairs the beta-adrenoceptor signaling pathway in the rat during the first week of life. Abnormal cardiac function in the cocaine-exposed neonate may be related to a defect in beta-adrenoceptors, because they regulate cardiac function.