ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID

摘要:

The disposition of morphine in serum and that in the cerebral cortex during normocarbia and hypercarbia were determined in dogs. Normocarbia (pHa‘7.41; PaCO236 torr) was maintained by controlled ventilation. Hypercarbia (pHa’7.41; PaCO269 torr) was induced by inhalation of 10 per cent CO2, balance O2. After achievement of a steady acid–base status, morphine sulfate, 2 mg/kg, was injected intravenously. Thereafter, serial samples of serum and cerebral cortex were taken at intervals for as long as four hours and analyzed for morphine concentration using radioimmunoassay. Serum morphine concentrations 2 and 5 minutes following intravenous injection were higher in dogs with hypercarbia, although the serum half-life during the elimination phase remained unchanged, 65–67 minutes. The initial volume of distribution, V1was smaller during hypercarbia. Also, during hypercarbia morphine concentrations in the cerebral cortex were significantly higher at 15, 60, 120, and 240 minutes than those found during normocarbia. The half-lives of morphine in the cerebral cortex were 4.1 hours during normocarbia and 6.9 hours during hypercarbia. These results suggest that the initial higher drug concentrations in the serum and the increased cerebral blood flow during hypercarbia facilitated the penetrance of morphine into the brain. Once in the brain, a greater proportion of morphine was probably present in the protonated form and thus less able to pass through lipid barriers back into the circulation.

ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID

摘要:

Malignant hyperthermia (MH) is characterized in part by sympathetic hyperactivity associated with increased levels of circulating catecholamines. Controversy exists as to whether the sympathetic nervous system is in some way abnormal and primarily contributing to MH, or whether the sympathetic response is secondary to the stress of MH originating from skeletal muscle. Total spinal anesthesia with resulting sympathetic denervation was used in genetically susceptible Poland China swine to investigate this question. isobaric tetracaine, 1.2–2.2 mg/kg, was injected via the sacral hiatus into the cerebrospinal fluid to produce total spinal anesthesia (paralysis of all four limbs). Total spinal anesthesia failed to prevent the occurrence or attenuate the course of MH in swine given halothane, 1 per cent (five pigs) or halothane and succinylcholine, 3 mg/kg (one pig). Total spinal anesthesia did prevent the expected increases in norepinephrine and epinephrine during MH in all six swine. Since dantrolene is specifically therapeutic in MH, its effect on the sympathetic response to stress was measured in two other susceptible swine. Treatment with dantrolene, 10 mg/kg, intravenously, did not prevent increases in catecholamines due to stress caused by either respiratory and metabolic acidosis (Paco2110 torr, base excess −20) combined or hemorrhagic hypotension (mean pressure 40 torr). The authors conclude that the sympathetic nervous system is involved in porcine MH only as a secondary response to stress; that conduction anesthesia will not protect pigs from MH; and that the efficacy of dantrolene in porcine MH is due to its effects on skeletal muscle rather than to depression of the sympathetic nervous system.

ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID

摘要:

The effect of hypocapnic alkalosis induced by hyperventilation on whole-body and hind-limb oxygen uptake (&OV0312;o2) was studied in dogs anesthetized with pentobarbital. In the intact dog with a self-perfused hind limb, increasingpHa from 7.41 to 7.58 increased whole-body &OV0312;o28 per cent and decreased hind-limb &OV0312;o26 per cent. Isolated hind limbs perfused with heparinized whole blood had similar decreases in &OV0312;o2with increases in arterial blood pH (pHa). However, isolated hind limbs perfused with whole blood containing citrate, phosphate, and dextrose (CPD) showed muscle twitches, had larger &OV0312;o2, values at identicalpHa's, and had an increase in &OV0312;o2with increase inpHa. These changes with a CPD perfusate were associated with low levels of ionized calcium (< 0.5 mEq/l), disappeared when calcium ion spontaneously increased to 1.0 mEq/l, and could be prevented or abolished by the addition of calcium chloride, dantrolene,d-tubocurarine, or succinylcholine. These results are in accord with the findings of others regarding an increase in whole-body &OV0312;o2with hypocapnic alkalosis, but do not support a contributory role of skeletal muscle to the overall increase

ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID

摘要:

In an effort to determine whether halothane alters cyclic nucleotide levels in the nervous system, mice were exposed to air (control) or halothane 0.7, 1.4, 2.4, 3.0, or 4.4 per cent in air, for 15 minutes. After quick-freezing in liquid nitrogen, levels of 3,5‘-cyclic guanosine monophosphate (cGMP) and 3’,5‘-cyclic adenosine monophosphate (cAMP) in the cerebral cortex, cerebellum, and spinal cord were determined. Lactate and pyruvate were measured in the cerebral cortex and cerebellum as an index of brain oxygenation, and blood-gas andpH values were measured in replicate experiments. Three groups of studies were made: 1) control, 2) low halothane concentrations (0.7–2.4 per cent) without hypoxia and acidosis, and 3) high halothane concentrations (3.0 and 4.4 per cent) accompanied by hypoxia and acidosis. Low halothane concentrations increased cGMP in the cerebral cortex, depressed it in the cerebellum, and had no effect on levels in the spinal cord. Similar alterations were seen after exposure to high halothane concentrations that included a hypoxic component, except that cGMP in the spinal cord was depressed. Since anoxia decreases cGMP in the cerebral cortex and cerebellum, the increase in cGMP in the cortex suggests that the effect of halothane cannot be attributed to hypoxia. The only effect of halothane on cAMP was to depress the levels of the nucleotide in the cortex at halothane concentrations of 2.4 per cent or more. The authors conclude that halothane has a greater effect on cGMP than on cAMP, and that the biochemical responses to the anesthetic vary among regions of the nervous system.

ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID

摘要:

Potassium chloride (KCI) given subcutaneously in high concentrations causes necrosis of skin, possibly from vasoconstriction around the injection site. The authors studied guinea pigs given subcutaneous injections of various volumes and concentrations of KCI and observed the severity of the cutaneous lesions. In further experiments, therapeutic agents were injected subcutaneously 10 minutes after KCI infiltration. The severity of cutaneous lesions was not affected by various volumes of KCI of the same concentration, but was correlated positively with increasing concentrations of the salt when concentration was varied. Dextrose, 5 per cent, and sodium bicarbonate, 1 M, had no effect on the cutaneous lesions caused by KCl, while hyaluronidase, 150 U/ml, lessened them. Lidocaine, 1 per cent, a vasodilator, eliminated cutaneous lesions caused by KCl. KCl-induced lesions may be due to vasoconstriction, which can be relieved by lidocaine.

ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID

摘要:

Recent studies have suggested that local anesthetics administered as an aerosol may have clinical use as bronchodilators. To assess direct actions on airway smooth muscle the authors studied the effects of five local anesthetics on intrinsic and agonist-induced tone of guinea pig tracheal chains. Drug effects were recorded with an isotonic transducer against a tension of cither 300 mg or 4 g and were expressed as percentages of the maximal relaxation produced by isoproterenol (10-6M) or the maximal contracture produced by acetylcholine (10-3M). Bath solution was usually maintained atpH 7.5, but the effects of lidocainc were also studied atpH 7.0 andpH 8.0, produced by changing the concentrations of carbon dioxide and bicarbonate ion. In lightly weighted tracheal chains, tricaine produced purely relaxant effects, whereas lidocaine, bupivacaine, procaine, and tetracaine produced contracture at low concentrations and relaxation at higher concentrations. The transition from contracture to relaxation occurred at a breakpoint concentration characteristic for each anesthetic. Lidocainc produced dose-related contracture from 3 × 10-5to 10-3M, with greater effect (P< .05) atpH 7.0 than atpH 8.0; correlation coefficients for contracture as an exponential function of lidocaine concentration were significantly greater (P< .01) for ionized drug (r = 0.96) or total drug (r = 0.92) than for nonionized drug (r = 0.71). All local anesthetics produced predominantly relaxant effects when tested in heavily weighted chains that were partially contracted with carbamylcholine (3 × 10-7M) or histamine (3 × 10-5M). At low concentrations, 3 × 10-5to 10-4M, procaine (P< .001), tetracaine (P< .05) and bupivacaine (P< .05) were more effective against carbamylcholine than histamine; the low-dose anticholinergic effects of procaine and tetracaine were greater (P< .01) than those of other local anesthetics and at 10-3M produced relaxation equivalent to 47 ± 3 (±SE) and 40 ± 7 per cent, respectively, of the maximal effect of isoproterenol. At high concentration, 10-3M, tricaine, bupivacaine, and tetracaine produced nearly complete relaxation of both carbamylcholine- and histamine-enhanced tone, but the relaxant effects of lidocaine and procaine were significantly less (P< .01). Our results show that there are marked differences in the direct effects of local anesthetics on airway smooth muscle that could affect their clinical use as bronchodilators. These differences include extent of contracture, anticholinergic effects at low concentrations, and nonspecific relaxant effects at high concentration. The poor correlation of contracture with concentration of nonionized drug suggests a superficial site of action for the contractor effect.

ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID

摘要:

The effects of various plasma concentrations of lidocaine on nitrous oxide anesthesia in man and halothane requirements in the dog were studied. The response to incision of the skin was observed in 20 patients who were anesthetized with nitrous oxide, 70 per cent inspired, and oxygen, 30 per cent, plus various plasma levels of lidocaine. In addition, changes in the MAC of halothane in dogs were observed at various levels of lidocaine. In both circumstances lidocaine concentrations of 3 to 6 Mg/ml decreased anesthetic requirements approximately 10 to 28 per cent. At clinically common concentrations of lidocaine, significant decreases in anesthetic requirements should be anticipated

ISSN:0003-3022    

出版商:OVID    

年代:1977

数据来源: OVID