Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to having anti-ischaemic effects, halothane can protect isolated rat hearts and isolated cardiomyocytes against reperfusion injury of the "oxygen paradox" type. The aim of this study was to investigate if halothane can also protect against myocardial reperfusion injury in vivo. Twenty-two rabbits anaesthetized with alpha-chloralose underwent 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Seven animals received 1 MAC of halothane for the first 15 min of reperfusion (halothane group), and eight animals served as untreated controls (controls group). In seven additional animals, the haemodynamic effects of halothane were antagonized by an i.v. infusion of noradrenaline (halothane-noradrenaline group). We measured cardiac output (CO) by an ultrasonic flow probe around the ascending aorta, left ventricular pressure (LVP) by a tip manometer and infarct size by triphenyltetrazolium staining. Baseline LVP was mean 92 (SEM 4) mm Hg and CO was 289 (16) ml min-1. During coronary occlusion, LVP was reduced to 86 (4)% of baseline and CO to 84 (4)% (similar in all groups). During halothane administration at reperfusion, LVP declined further to 55 (6)% of baseline and CO to 66 (9)% (P < 0.05 halothane group vs control group). Noradrenaline prevented the reduction in LVP (halothane-noradrenaline group 87 (5)% of baseline, control group 84 (6)% and reduction in CO (halothane-noradrenaline group 89 (5)%, control group 83 (6)%. Infarct size was 49 (6)% of the area at risk in controls and was reduced markedly by administration of halothane to 32 (3)% in the halothane group (P < 0.05) and to 30 (3)% in the halothane-noradrenaline group (P < 0.05). Treatment with halothane during the early reperfusion period after myocardial ischaemia protected the myocardium against infarction in vivo, independent of the haemodynamic effect of halothane.
 ...
PMID:Halothane reduces reperfusion injury after regional ischaemia in the rabbit heart in vivo. 930 95

We have investigated in rat brain slices the effects of the volatile anaesthetics enflurane, isoflurane and halothane on spontaneous discharge patterns and mean firing rates of cerebellar Purkinje cells. In the absence of these anaesthetics, Purkinje cells fired bursts of action potentials separated by quiescent periods lasting less than 2 s. Mean discharge rates were 10.8 (SEM 0.4) Hz at 23 +/- 1 degrees C and 25.6 (1.2) Hz at 35 +/- 1 degrees C. The agents exhibited qualitatively different effects when applied at concentrations corresponding to 1-3 MAC. Enflurane markedly lengthened burst and inter-burst durations. Isoflurane acted in a similar manner, but effects were less pronounced. In contrast with isoflurane and enflurane, halothane shortened burst durations. At concentrations corresponding to 1-1.5 MAC, halothane, isoflurane and enflurane significantly depressed action potential firing by 15-30% (P < 0.05). Enflurane 1.2 mmol litre-1 (2.0 MAC), isoflurane 0.9 mmol litre-1 (2.8 MAC) and halothane 0.9 mmol litre-1 (3.8 MAC) depressed spontaneous spike rates by 50%. The changes in discharge patterns and the concentration-dependent decrease in the firing rates were similar at 23 +/- 1 degrees C and 35 +/- 1 degrees C. In summary, we observed that neither the anaesthetic-induced alterations in spontaneous discharge patterns nor the EC50 values of the concentration-dependent depression of the mean firing rates were in accordance with the Meyer-Overton rule. However, at clinically relevant concentrations, depression of average spike rates did not differ significantly between the anaesthetics and thus followed the rule. Our results suggest that anaesthetic actions, which are in accordance with the rule, are frequently masked by several side effects.
 ...
PMID:Effects of volatile anaesthetics on spontaneous action potential firing of cerebellar Purkinje cells in vitro do not follow the Meyer-Overton rule. 942 2

In an attempt to determine if there is any overlap in local and general anaesthetic binding sites, we have examined the effects of thiopental, phenobarbital, pentobarbital, propofol, ketamine (racemic and R(+)/S(-)), alfaxalone, etomidate and halothane on [3H]tetracaine binding to rat cerebrocortical membranes. Membranes were prepared in Tris HCI 50 mmol litre-1, pH 7.4, by homogenization and centrifugation. Binding assays were performed in 1-ml volumes of Tris HCI buffer at room temperature or 37 degrees C for halothane. Binding of [3H]tetracaine was displaced dose-dependently by unlabelled tetracaine with a mean pIC50 value of 6.91 (SEM 0.07) (123 nmol litre-1). With the exception of propofol (at high concentrations), all i.v. anaesthetic agents failed to displace the binding of [3H]tetracaine. In contrast, halothane produced a dose-dependent and statistically significant reduction in total [3H]tetracaine binding at clinically achievable concentrations (0.289, 0.885 and 1.484 mmol litre-1 equivalent to 1.0, 3.1 and 5.1 rat MAC) without markedly affecting the pIC50. Collectively these data may suggest some overlap in the binding sites for [3H]tetracaine and volatile but not i.v. general anaesthetic agents.
 ...
PMID:Effects of i.v. anaesthetic agents and halothane on [3H]tetracaine binding to rat cerebrocortical membranes. 950 82

We have examined the short-term effects of three volatile anaesthetics, halothane, isoflurane and desflurane, on mucociliary activity in the rabbit maxillary sinus in vivo. Mucociliary activity was recorded photoelectrically and the signal processed by fast Fourier transformation. Administration of 1.0 MAC of halothane, isoflurane or desflurane caused a temporary increase in mucociliary activity, with mean peak responses of 47.8 (SEM 13.0)%, 44.0 (9.6)% and 45.1 (23.7)% (n = 6), respectively. The response to all three compounds was biphasic; an initial peak was observed within 2 min and a second peak at 3-8 min. The second response was not significant for halothane. In contrast, desflurane produced a significant second peak while the first was small and failed to reach significance. Halothane displayed an initial peak within 2 min which was blocked by atropine but not by the neurokinin 1 (NK1) receptor antagonist CP-99. The second peak at 3-5 min was less pronounced for halothane than for isoflurane or desflurane. The second peak was not affected by atropine pretreatment, but was blocked by pretreatment with CP-99. A combination of atropine and CP-99 pretreatment abolished the mucociliary response to halothane. Atropine pretreatment did not affect, whereas CP-99 significantly reduced, the response to desflurane. We conclude that the NK1-mediated response was most pronounced for desflurane which is considered the most airway irritating compound of the three. It is likely that the size of the NK1-mediated response reflects the airway-irritating properties of the volatile anaesthetic used.
 ...
PMID:Changes in mucociliary activity may be used to investigate the airway-irritating potency of volatile anaesthetics. 964 Jan 54

It is known that volatile anaesthetics protect myocardial tissue against ischaemic and reperfusion injury in vitro. In this investigation, we have determined the effects of the inhalation anaesthetics, enflurane, isoflurane, sevoflurane and desflurane, administered only during early reperfusion, on myocardial reperfusion injury in vivo. Fifty chloralose-anaesthetized rabbits were subjected to 30 min of occlusion of a major coronary artery followed by 120 min of reperfusion. Left ventricular pressure (LVP, tip-manometer), cardiac output (CO, ultrasonic flow probe) and infarct size (triphenyltetrazolium staining) were determined. During the first 15 min of reperfusion, five groups of 10 rabbits each received 1 MAC of enflurane (enflurane group), isoflurane (isoflurane group), sevoflurane (sevoflurane group) or desflurane (desflurane group), and 10 rabbits served as untreated controls (control group). Haemodynamic baseline values were similar between groups (mean LVP 106 (SEM 2) mm Hg; CO 281(7) ml min-1). During coronary occlusion, LVP and CO were reduced to the same extent in all groups (LVP 89% of baseline; CO 89%). Administration of inhalation anaesthetics during early reperfusion further reduced both variables, but they recovered after discontinuation of the anaesthetics to values not different from control animals. Infarct size was reduced from 49 (5)% of the area at risk in the control group to 32 (3)% in the desflurane group (P = 0.021), and to 36 (2)% in the sevoflurane group (P = 0.097). In the enflurane group, infarct size was 39 (5)% (P = 0.272). Isoflurane had no effect on infarct size (48 (5)%, P = 1.000). The results show that desflurane and sevoflurane markedly reduced infarct size and therefore can protect myocardium against reperfusion injury in vivo. Enflurane had only a marginal effect and isoflurane offered no protection against reperfusion injury in vivo. These different effects suggest different protective mechanisms at the cellular level.
 ...
PMID:Effects of enflurane, isoflurane, sevoflurane and desflurane on reperfusion injury after regional myocardial ischaemia in the rabbit heart in vivo. 1021 Oct 18

A specific action against myocardial reperfusion injury of the oxygen paradox type was recently characterized for halothane after anoxic perfusion in isolated rat hearts and isolated cardiomyocytes. In this study, we have characterized the protective effects of the clinically available inhalation anaesthetics during reperfusion after ischaemia. In isolated, isovolumically beating rat hearts perfused at a constant flow (10 ml min-1, PO2 80 kPa) and paced at 350 beat min-1, we determined left ventricular developed pressure (LVDP) and release of creatine kinase (CKR) as indices of myocardial performance and cellular injury, respectively. Seven control hearts underwent 30 min of no-flow ischaemia and 1 h of reperfusion. In the treatment groups, halothane, enflurane, isoflurane, sevoflurane or desflurane (each group n = 6) was added to the perfusion medium for the first 30 min of reperfusion at a concentration corresponding to 1.5 MAC in the rat. In the control group, cellular injury occurred at early reperfusion (peak CKR 283 (SEM 57) iu litre-1 at 10 min of reperfusion). Peak CKR to the coronary venous effluent was attenuated by all anaesthetics (halothane group 156 (45), enflurane group 134 (20), sevoflurane group 132 (20), desflurane group 159 (25) iu litre-1; each P < 0.05). Isoflurane did not differ from controls (303 (53) iu litre-1; P = 0.5). In the sevoflurane group, there was a delayed peak CKR after discontinuation of the anaesthetic at 30 min of reperfusion (260 (34) iu litre-1). Functional recovery was improved by all anaesthetics, but was seen much earlier with desflurane (LVDP 28 (3)% of baseline at 5 min reperfusion compared with halothane (6 (1)%), enflurane (11 (3)%), isoflurane (9 (6)%), sevoflurane (10 (2)%) and controls (3 (1)% of baseline)). At 30 min of reperfusion, recovery of LVDP was improved to a similar extent by all anaesthetics (halothane 30 (9)%, enflurane 36 (9)%, isoflurane 33 (5)%, sevoflurane 30 (5)%, desflurane 36 (4)% of baseline values) compared with controls (13 (5)%; each P < 0.05). All inhalation anaesthetics protected against myocardial reperfusion injury, but showed differences in attenuation of cellular injury and functional recovery. These differences may suggest different protective mechanisms.
 ...
PMID:Effects of halothane, enflurane, isoflurane, sevoflurane and desflurane on myocardial reperfusion injury in the isolated rat heart. 1021 Oct 19

The effects of halothane, isoflurane, sevoflurane (0.5, 1 and 2 MAC) and pentobarbital (10(-5) M, 10(-4) M and 3 x 10(-4) M) on hypocapnia- and bicarbonate-induced constriction of isolated dog middle cerebral arteries were investigated in vitro. The isometric tension of isolated cerebral arterial rings was measured in an organ bath containing Krebs bicarbonate solution, aerated with 5% CO2 and 95% O2. Hypocapnia, induced by replacing the bathing solution with one that had been equilibrated with 2.5% CO2 and 97.5% O2, produced a sustained vasoconstriction (268 +/- 36 mg, mean +/- SEM). Exposure of arterial rings to a bathing solution that contained double the concentration of NaHCO3 (50 mM) elicited a phasic constriction followed by a gradual decrease in tension (309 +/- 34 mg). Although halothane, isoflurane, and sevoflurane attenuated both hypocapnia- and bicarbonate-induced constrictions in a dose-dependent manner, the inhibition of these constrictions was greater in rings treated with halothane than in those treated with isoflurane or sevoflurane when compared at equipotent concentrations. These alkaline-induced constrictions were attenuated by pentobarbital only at the highest concentration of 3 x 10(-4) M. Halothane (1 and 2 MAC) attenuated the constriction induced by hypocapnia to a greater extent than that induced by 15 mM KCl, whereas pentobarbital (10(-4) M and 3 x 10(-4) M) attenuated hypocapnia-induced constriction less than KCl-induced constriction. These results indicate that alkaline-induced constriction is more vulnerable to halothane than other volatile anesthetics and pentobarbital. The mechanisms of the inhibitory effects of halothane and pentobarbital on alkaline-induced cerebral vasoconstriction seem to differ; the inhibitory effect of pentobarbital, but not of halothane may be, in part, ascribed to its inhibitory effect on the Ca++ influx.
 ...
PMID:Inhibitory effects of halothane, isoflurane, sevoflurane, and pentobarbital on the constriction induced by hypocapnia and bicarbonate in isolated canine cerebral arteries. 1077 3

Protein kinase C (PKC) is an important enzyme involved in the regulation of neurotransmission and might also be important in the mediation of ischemic neuronal death. PKC has been implicated as a target of volatile anesthetics as well as in anesthetic protection against ischemia. The present study tested the effect of isoflurane and sevoflurane, both used in neuroanesthetic practice, on presynaptic free cytosolic Ca2+ ([Ca2+](i)) and PKC activity. To measure [Ca2+](i) and PKC activation simultaneously, rat synaptosomes, mostly containing presynaptic terminals, were loaded with the fluorescent probes fura-2 and fim-1, respectively. The synaptosomes were exposed to either isoflurane or sevoflurane in concentrations corresponding to 1 and 2 MAC values in rats, both in Ca2+-containing and Ca2+-free medium. After 8 minutes of anesthetic exposure, 1 mM 4-aminopyridine was added to induce membrane depolarization. Isoflurane 1 and 2 MAC increased the basal PKC activity after 8 minutes in Ca2+-containing medium by 15.1% (3.6%) and 30.5% (5.5%) compared with control, respectively [mean (SEM); n = 9, both values P < 0.05]. Sevoflurane 2 MAC transiently decreased but thereafter increased the PKC activity (P < 0.05). In Ca2+ -free medium sevoflurane attenuated the PKC activity (P < 0.05). The anesthetics did not alter the depolarization-evoked enzyme activation. Furthermore, 2 MAC of both isoflurane and sevoflurane increased the basal- and attenuated the depolarization-evoked increase in [Ca2+](i) (P < 0.05). The present study supports the hypotheses that volatile anesthetics affect presynaptic PKC activity and that the anesthetic effect on enzyme activation seems to be related to an increase in [Ca2+](i).
 ...
PMID:The effect of isoflurane and sevoflurane on cerebrocortical presynaptic Ca2+ and protein kinase C activity. 1282 68

Nitric oxide (NO) is the mediator of ischemic preconditioning against myocardial infarction. Desflurane produces anesthetic preconditioning to protect the myocardium against infarction. In the model of myocardial ischemia-reperfusion injury in rabbits, we evaluated desflurane-induced ischemic preconditioning and studied its mechanism of NO synthesis. Thirty-two male adult New Zealand white rabbits were anesthetized with intravenous (IV) 30 mg/kg pentobarbital followed by 5 mg/kg/hr infusion. All rabbits were subjected to 30 minutes (min) long lasting left anterior descending coronary artery (LAD) occlusion and three hours (hr) of subsequent reperfusion. Before LAD occlusion, the rabbits were randomly allocated into four groups for preconditioning treatment (eight for each group). The control group did not receive any preconditioning treatment. The desflurane group received inhaled desflurane 1.0 MAC (minimal end-tidal alveolar concentration) for 30 min that was followed by a 15 min washout period. The L-NAME-desflurane group received L-NAME (NG-nitro-L-arginine methyl ester; non-selective Nitric Oxide Synthetase (NOS) inhibitor) 1 mg/kg IV 15 min before 1.0 MAC inhaled desflurane for 30 min. The L-NAME group received L-NAME 1 mg/kg IV. Infarct volume, ventricular arrhythmia, plasma lactate dehydrogenase (LDH), creatine kinase (CK) activity and myocardial perfusion were recorded simultaneously. We have found that hemodynamic values of the coronary blood flow before, during, and after LAD occlusion were not significantly different among these four groups. For the myocardial ischemia-reperfusion injury animals, the infarction size (mean +/- SEM) in the desflurane group was significantly reduced to 18 +/- 3% in the area at risk as compared with 42 +/- 7% in the control group, 35 +/- 6 in the L-NAME group, and 34 +/- 4% in the L-NAME-desflurane group. The plasma LDH, CK levels, and duration of ventricular arrhythmia were also significantly decreased in the desflurane group during ischemia-reperfusion injury. Our results indicate that desflurane is an anesthetic preconditioning agent, which could protect the myocardium against the ischemia-reperfusion injury. This beneficial effect of desflurane on the ischemic preconditioning is probably through NO release since L-NAME abrogates the desflurane preconditioning effect.
 ...
PMID:Effect of desflurane-induced preconditioning following ischemia-reperfusion on nitric oxide release in rabbits. 1556 90

The present study assessed the impact of time (6 h) on cerebral blood flow (CBF) during isoflurane anesthesia with and without vasopressor administration. All animals were prepared for measurement of CBF by the radiolabeled microsphere method under 1.4% end-tidal (1.0 MAC) isoflurane anesthesia. Surgery required 45 min and was followed by a 15 min stabilization period. In group 1 (n = 6), isoflurane 1.4% was administered for 6 h. CBF after 1 h of isoflurane was 92 +/- 9 ml/min/100 g (mean +/- SEM) and declined to 61 +/- 5 ml/min/100 g at 2 h and further declined to 37 +/- 5 ml/min/100 g at 6 hr. In group 2 (n = 6), isoflurane 1.4% was administered during the first hour. Thereafter, isoflurane 1.4% was continued, angiotensin II (0.3 mug/kg/min) was administered intravenously, and blood was withdrawn to maintain CPP constant for an additional 5 h, with hourly CBF determination. In this group, control CBF was 95 +/- 16 ml/min/100 g and flow was maintained at the control level through 4 h and then declined to 50 +/- 5 ml/min/100 g at 5 and 6 h. In group 3 (n = 6), 1.4% isoflurane was administered and phenylephrine (2.0 mug/kg/min) infusion was combined with hemorrhage to maintain control CPP in an identical sequence to group 2. In group 3, control CBF was 88 +/- 14 ml/min/100 g. As in group 1, CBF decreased significantly at 2 h (p < 0.05) to 68 +/- 13 ml/min/100 g and further declined to 49 +/- 7 ml/min/100 g at 6 h. In all three groups, CMRO2 remained at control levels and there were no changes in arterial carbon dioxide or CPP for the duration of the study. These data demonstrate that the hyperemia caused by isoflurane resolves over time during stable 1 MAC isoflurane anesthesia. The unanticipated interaction of angiotensin II and isoflurane producing a sustained cerebral hyperemia suggests that previous studies that used angiotensin II to support MABP during isoflurane may have reported the effects of angiotensin II in addition to or rather than the effects of isoflurane.
 ...
PMID:Changes in cerebral blood flow over time during isoflurane anesthesia in dogs. 1581 31


<< Previous 1 2 3 4 5 6 7 Next >>