Catabolism and excretion of crosslinked hemoglobin.
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Animals↗
Biomedical subjects
L Triner
Publications and source records attributed to L Triner.
Risk of myocardial ischaemia during anaesthesia in treated and untreated hypertensive patients.
Hypertensive patients were monitored for myocardial ischaemia during anaesthesia and surgery with the V5 lead of a standard electrocardiograph. Myocardial ischaemia was detected in 11 of 39 untreated hypertensive patients and in four of seven receiving therapy with a diuretic, but in none of 44 receiving atenolol. Fourteen of the atenolol-treated patients were receiving the drug on a long-term basis and the remaining 30 were treated acutely only on the morning of surgery. When myocardial ischaemia was observed, it was always associated with noxious stimulation and tachycardia, but a conspicuous increase in arterial pressure was not usually present. We conclude that myocardial ischaemia is prevalent during anaesthesia in untreated hypertensive patients, and that pretreatment with atenolol, but not diuretics, provides prophylaxis.
Anesthesia↗
Myocardial ischemia in untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic blocking agent.
In a non-double-blind, prospective, randomized study, the intra-operative electrocardiograms of 128 mildly hypertensive surgical patients were examined in order to determine the incidence of myocardial ischemia during anesthesia. No patient had been receiving chronic antihypertensive therapy prior to the study, but a single small oral dose of a beta-adrenergic blocking agent (labetalol, atenolol, or oxprenolol) was given to 89 of them along with premedication. Forty-four per cent of the untreated control patients and 61% of the patients pretreated with a beta-adrenergic blocking agent had normal preoperative electrocardiograms and no risk factors for coronary artery disease other than hypertension (this difference between groups was not statistically significant). During tracheal intubation and/or emergence from anesthesia, a brief, self-limited episode of myocardial ischemia was detected in 11 of 39 untreated control patients, and in two of 89 patients pretreated with a beta-adrenergic blocking agent (P less than 0.001). Tachycardia always accompanied the ischemic events, but a conspicuous increase in blood pressure did not. The authors conclude that mild hypertension, when untreated prior to the induction of anesthesia, is associated with a high incidence of myocardial ischemia; and that a single small oral dose of a beta-adrenergic blocking agent, given with pre-medication, can significantly reduce that risk.
Administration, Oral↗
Effect of halothane on myocardial cyclic AMP and cyclic GMP content of mice.
Halothane, in anesthetic concentrations (0.6-1.8 volumes/100 ml), produced a dose-dependent decrease in myocardial cyclic AMP (cAMP) content and an increase in cyclic GMP (cGMP) content in mice exposed to a continuous flow of the anesthetic carried in air for 15 min. Atropine (up to 20 mg/kg i.p.) did not alter significantly the myocardial cyclic nucleotides content or the effect of halothane on cAMP and cGMP content. Prazosin and yohimbine had no significant effect on cAMP or cGMP content in the absence of halothane. Both alpha adrenergic antagonists inhibited the halothane-induced increase in cGMP content (ID50, 0.24 and 0.54 mumol/kg i.p. for prazosin and yohimbine, respectively). In contrast, the decrease in cAMP content induced by halothane was not altered by alpha adrenergic antagonists. Propranolol (2 mg/kg i.p.) diminished myocardial cAMP level and prevented the halothane effect on myocardial cAMP content. Pretreatment with 6-hydroxydopamine did not change the cGMP response to halothane. Thus, the action of halothane on myocardial cyclic nucleotides content appears to be predominantly a peripheral effect, not related to cellular mechanisms mediated by muscarinic receptors. The results suggest that the increase in cGMP content induced by halothane does not require intact adrenergic nerve endings and that cellular processes associated with the alpha adrenoceptor system may be involved; the decrease in cAMP content may be due to an inhibition of the beta stimulatory action of catecholamines on adenylate cyclase.
Adrenergic alpha-Antagonists↗
Effect of halothane on rat liver adenylate cyclase: role of cytosol components.
Halothane, in a number of tissues, alters the activity of adenylate cyclase, the enzyme that catalyzes the formation of cyclic 3',5'-adenosine monophosphate, an important intracellular regulator. The present studies demonstrate that in rat liver whole homogenates, basal and glucagon-stimulated adenylate cyclase activity is increased by halothane. In isolated rat liver membranes, halothane does not increase basal activity and it decreases activity stimulated by glucagon. Suspension of membranes in the cytosol fraction restores the halothane-induced increase of basal and glucagon-stimulated activity. When cytosol denatured by trypsin or heat was used, the halothane-induced increase in glucagon-stimulated activity was lost, but the increase of basal activity was still observed. Suspension of membranes in albumin solution restored the effect of halothane on basal activity only. These results suggest that presence of heat-labile proteins in the cytosol fraction that modulate the halothane interaction with rat liver adenylate cyclase.
Adenylyl Cyclase Inhibitors↗
Enhanced oxygen unloading by an interdimerically crosslinked hemoglobin in an isolated perfused rabbit heart.
Coronary perfusion has shown that an intramolecularly crosslinked hemoglobin (Hb) with a very low affinity for O2 (Hb crosslinked covalently between the beta chains with 2-nor-2-formylpyridoxal 5'-phosphate, HbXL) has several advantages over ordinary Hb. As predicted from in vitro oxygenation curves, much more O2 was unloaded to the heart at three different heart rates, at two perfusion rates, and when the perfusate was equilibrated with 25% as well as 95% O2. In all cases, the improved O2 unloading occurred at higher tissue O2 pressures than with normal Hb. The greater O2 consumption with HbXL was accompanied by better mechanical performance because, after 90 min of perfusion, the HbXL-perfused hearts maintained two-thirds of their original contractility (dp/dt), while that of the Hb-perfused hearts had declined to one-fifth. A special advantage of HbXL is its ability to unload significant amounts of O2 even at low temperature (10 degrees C), in contrast to whole blood. This should make it useful for supporting aerobic metabolism during low-temperature cardioplegia in cardiac surgery and for organ preservation.
Animals↗
Effect of volatile anaesthetics and nitrous oxide-fentanyl anaesthesia on bleeding time.
Fifty-one patients were divided randomly into four groups: halothane in oxygen; fentanyl plus nitrous oxide in oxygen; enflurane in oxygen; or isoflurane in oxygen. Standardized bleeding time was measured using a Simplate II bleeding device before and at least 40 min after the induction of anaesthesia. Arterial pressure was maintained at +/- 20% of control values and temperature was kept at 35-37 degrees C. The bleeding time was prolonged by 33% in the halothane group (P less than 0.01) and by 20% in the nitrous oxide-fentanyl group (n.s.). There was essentially no change in bleeding time in the groups receiving enflurane or isoflurane, although there was considerable variability within each group, which did not seem to be related to differences in sex, age, type of surgery, concentration of agent used or surgical procedure.
Adult↗
Developmental changes in adenylate cyclase activity in canine myocardium.
Basal and epinephrine-induced adenylate cyclase activity in homogenates of dog myocardium increased significantly from birth to adulthood, without further change with advancing age. The stimulatory effect of epinephrine (i.e. the net increase over basal activity), however, increased (p less than 0.05) during the first week after birth only and then remained constant. While fluoride-stimulated activity increased, 5'-guanylyl imidodiphosphate [Gpp(NH)p]-stimulated activity declined gradually during development (p less than 0.05). In the presence of Gpp(NH)p and epinephrine at concentrations producing a maximal effect, the enzyme activities in all dogs, except in the 1-day-old, were not significantly different and were comparable to that of fluoride-stimulated activity in adult dogs. The results suggest that age-related alterations in the characteristics of the guanine nucleotide regulatory protein may account, at least in part, for the changes in adenylate cyclase activity occurring during development.
Adenylyl Cyclases↗
Deuterated halothane--anesthetic potency, anticonvulsant activity, and effect on cerebellar cyclic guanosine 3',5'-monophosphate.
The effect of substituting deuterium for hydrogen in the halothane molecule on anesthetic potency, motor activity, and cerebellar cyclic guanosine 3',5'-monophosphate (cGMP) content was studied in mice. The concentration of halothane required to abolish the righting reflex in 50% of the mice (ED50RR) was chosen as index of anesthetic potency; cerebellar control of motor activity was evaluated by the incidence of isoniazid-induced convulsions. The ED50RR for deuterated (D)-halothane was similar to that of halothane (0.87 +/- 0.04 and 0.88 +/- 0.03 vol%, respectively). Both D-halothane and halothane (0.15-0.90 vol%) protected the mice against isoniazid-induced convulsions and decreased cerebellar cGMP content in a dose-dependent manner. D-halothane and halothane were equipotent on both parameters. Thus deuteration did not alter the anesthetic potency, the anticonvulsant activity, or the effect on cerebellar cGMP content of the anesthetic. Furthermore, the reactivity of the C-H bond is probably not critical for these actions of halothane.
Animals↗
Effect of enflurane on cerebellar cGMP and on motor activity in the mouse.
The effect of enflurane on the cerebellar content of the intracellular mediator cyclic 3', 5'-guanosine monophosphate (cGMP) and on motor activity was studied in mice. Seizures, as an index of increased motor activity, associated with an increase in cerebellar cGMP content were induced with isoniazide or picrotoxin. Enflurane 0.28-1.68 vol% produced a dose-dependent, reversible decrease in cerebellar cGMP (by about 50% at 0.28 vol%) and delayed or prevented both the increase in cerebellar cGMP and the convulsions induced by isoniazide. Enflurane also protected against picrotoxin-induced convulsions, but not against strychnine-induced convulsions which presumably do not involve cerebellar mechanisms. These results indicate that enflurane affects the cerebellar mechanisms controlling motor activity and it is postulated that this action contributes to the decrease in muscle tone induced by enflurane.
Animals↗
Use of metyrosine in the anaesthetic management of patients with catecholamine-secreting tumours. A case report.
Metyrosine 1.5 g daily for days decreased 24-h urine metanephrine concentration by about 60% in a patient with multiple catecholamine-secreting paragangliomas. Despite the considerable inhibition of catecholamine synthesis, this patient exhibited stress-induced sympathetic overactivity, indicated by increases in arterial pressure and serum catecholamine and urine metanephrine concentrations. It is concluded that metyrosine should be introduced early to the preoperative regimen. In this way, optimal inhibitory effect on catecholamine synthesis can be obtained and maintained for a sufficient time to allow catecholamine stores to become as close to normal as possible. Attainment of the optimal therapeutic effect is not clearly defined, but would seem to be best gauged by a combination of clinical tests of sympathetic responses and of suppression of urinary excretion of metanephrines or VMA.
Anesthesia, Epidural↗
Effect of a prostaglandin antagonist, N-0164, on cAMP generation and hydrolysis in the rat uterus.
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Adenylyl Cyclases↗
Halothane effect on cGMP and control of motor activity in mouse cerebellum.
The effect of halothane on cerebellar control of motor activity and on cerebellar cyclic 3',5'-guanosine monophosphate (cGMP) content was studied in mice. Isoniazide and picrotoxin were used to increase motor activity and induce seizures associated with an increase in cerebellar cGMP content. Halothane markedly decreased the cerebellar cGMP content (by 60 per cent at 0.61 per cent, the concentration at which 50 per cent of mice lost righting reflex) and prevented the isoniazide-induced increase in cGMP content. Halothane, 0.61 per cent, significantly reduced both isoniazide- and picrotoxin-induced motor activity; the ED50 convulsive dose of isoniazide (137.7 +/- 7.04) and of picrotoxin (1.9 +/- 0.2 mg x kg-1, sc) was about three times higher (402.2 +/- 17.9 and 5.8 +/- 0.6 mg x kg-1, sc, respectively) in mice exposed to halothane. In contrast, halothane did not alter the ED50 convulsive dose of strychnine, which has a different site and mechanism of action, blockade of glycine receptors, a mechanism not involving the cerebellar system. These results indicate that halothane has a significant effect on the cerebellar control of motor activity and that cGMP plays an important role in the alteration of cerebellar function by halothane.
Animals↗
Halothane effect on beta-adrenergic receptors in canine myocardium.
Halothane depresses the inotropic state of the heart, possibly by decreasing the rate of formation of cyclic 3',5'-adenosine monophosphate (cAMP) through depression of the activity of adenylate cyclase, the cAMP-generating enzyme. As catecholamines regulate the inotropic state and adenylate cyclase activity by binding to myocardial beta-adrenergic receptors, the effect of halothane on binding to these receptors was studied to determine whether this was a site of halothane effect. Beta-adrenergic binding was measured at binding equilibrium in vitro in a canine myocardial membrane preparation in the absence and presence of halothane, 3 to 5 vol%, using as the radioligand 3H-dihydroalprenolol (3H-DHA), a beta-adrenergic antagonist with high affinity and radioactivity. In addition, the effect of halothane on the binding of l-isoproterenol, a beta-adrenergic agonist, was measured by displacement of 3H-DHA. The results indicate that halothane has no effect on either the affinity of canine myocardial beta-adrenergic receptors for 3H-DHA or l-isoproterenol, nor does it alter the number of available receptors at binding equilibrium.
Adenylyl Cyclases↗
Halothane effect on cAMP generation and hydrolysis in rat brain.
The volatile anesthetic halothane increased the rate of cAMP generation and decreased the rate of cAMP hydrolysis in rat cerebral cortex and cerebellum. The effect of halothane on the enzymes was reflected in a two-fold rise in cAMP content of cerebral cortical tissue exposed to the anesthetic at 3 vol% for 15 and 30 min. The action of halothane on adenylate cyclase is calcium-independent and different from the action of guanine nucleotides, sodium fluoride and specific transmitters. The Vmax of the enzyme is higher in the presence of the anesthetic. It is suggested that halothane, through conformational changes of the enzyme, renders more catalytic sites operative.
3',5'-Cyclic-AMP Phosphodiesterases↗
Effect of benzothiadiazine derivatives on cyclic nucleotide phosphodiesterase and on the tension of the aortic strip.
Diazoxide and chlorothiazide (0.1--1.5 mM) had a dose-dependent inhibitory effect on the rate of cAMP and cGMP hydrolysis determined in a 500-g supernatant of rat aorta homogenates; both compounds were weaker inhibitors of cAMP and cGMP hydrolysis than theophylline. cAMP and cGMP content of the aorta did not change in the presence of diazoxide or chlorothiazide; diazoxide, however, further increased the isoproterenol-induced rise in cAMP, while chlorothiazide did not. Both benzothiadiazines decreased the maximum tension of the aortic strip induced by serotonin, phenylephrine or potassium. Diazoxide was a stronger and chlorothiazide a weaker inhibitor of the contractile response than theophylline. Comparison of the biochemical and functional effects of diazoxide and chlorothiazide indicates that the inhibitory effect of these compounds on cyclic nucleotide phosphodiesterase does not by itself explain their vasodilating effect.
2',3'-Cyclic-Nucleotide Phosphodiesterases↗
Effects of halothane on the cyclic 3',5'-adenosine monophosphate enzyme system in human platelets.
A study of the effects of halothane on the cyclic 3',5'-adenosine monophosphate (cAMP) system in human platelets was undertaken since cAMP has been implicated in the regulation of the process of platelet aggregation and this anesthetic has been reported to decrease platelet aggregation and, in other tissues, to increase adenylate cyclase activity. When exposed to halothane 0.5 to 10 vol%, adenylate cyclase activity was increased in the platelet preparation in a dose-dependent manner, reaching a maximum at 5 vol% (93% increase above basal activity). Platelet aggregation was also inhibited by halothane in a dose-dependent manner, with a maximum effect at about 5 vol% halothane (a decrease of 70%). Kinetic analysis of platelet cAMP-phosphodiesterase suggested two forms of activity, neither of which was altered by halothone. The results that the impairment of platelet aggregation observed with halothane may be brought about by the halothane-induced activation of platelet adenylate cyclase, which may result in a higher cAMP level, inhibiting platelet aggregation.
3',5'-Cyclic-AMP Phosphodiesterases↗
Dopamine-sensitive adenylate cyclase activity in the rat caudate nucleus during exposure to halothane and enflurane.
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Adenylyl Cyclases↗