Interaction between halothane and morphine on isolated heart muscle.

The present study describes the effects of halothane on morphine activity in the isolated left atria of the rat. Concentration-response curves were obtained for the negative inotropic effects of morphine on electrically stimulated left atria. Morphine significantly decreased the contractile force, with an inhibitory concentration 16 (IC16) of 3.130.698 +/- 22.5 X 10(-9) M. The opiate agonist was more potent in reserpinized rats, causing a consistent negative inotropic action over a wide range (10(-8)-10(-4) M) or morphine concentrations. The IC16 of morphine was significantly (P less than 0.001) decreased in the presence of 1.5% v/v halothane. The administration of L-naloxone (3 X 10(-7)-10(-6) M) but not D-naloxone (10(-6) M) antagonized the inhibitory effects of morphine in the presence of halothane. These results demonstrate that halothane increases the potency of morphine on the isolated left atria and suggest that this effect is mediated by opioid receptors.

High doses of L-naloxone but neither D-naloxone nor beta-funaltrexamine prevent hyperthermia-induced seizures in rat pups.

The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist beta-funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degrees C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and beta-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L-naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures.

Halothane, isoflurane and enflurane potentiate the effect of noradrenaline on ventricular automaticity in the rat heart: evidence of the involvement of both alpha- and beta-adrenoceptors.

Direct evidence has been sought as to what extent the sensitization of heart to the arrhythmogenic action of sympathomimetic drugs in the presence of the inhalatory anaesthetics, halothane, isoflurane and enflurane, is mediated by either alpha- or beta-adrenoceptors. For this purpose, the effects of isoprenaline, noradrenaline and phenylephrine on ventricular automaticity induced by local injury have been studied in the isolated right ventricle of the rat. Isoprenaline was more potent in increasing ventricular automaticity than either phenylephrine or noradrenaline. The anaesthetic potentiated the effects of noradrenaline, as well as that of higher concentrations of phenylephrine, but not those of isoprenaline. These results support the contention that increases in ventricular automaticity induced by sympathomimetic drugs are mainly mediated by adrenoceptors of the beta-type. However, the simultaneous activation of both alpha- and beta-adrenoceptors seems to be necessary for the effect of the anaesthetics in sensitizing the heart to sympathomimetic drugs.

Cerebrospinal fluid leucine-enkephalin-like levels in febrile convulsions.

Enkephalin levels were measured in the cerebrospinal fluid (CSF) of 17 patients with febrile convulsions and 11 control patients without a history of pain or convulsive disorders. Enkephalins were extracted from CSF by adsorption with synthetic resin XAD-2 eluted with methanol, and assayed using the radioreceptor assay (RRA). Results were expressed as Leucine-Enkephalin (Leu-E) equivalents. Enkephalin levels in CSF were 2.27 +/- 0.42 pmol/ml (mean +/- SE) in the convulsion group and the 4.8 +/- 0.8 pmol/ml (mean +/- SE) in the control group. Statistical comparison in both groups shows significant differences (p less than 0.001). These results suggest a correlation between convulsions and enkephalin levels in CSF.

[Acute ischemia of lower limb and long-term treatment with epidural bupivacaine]. / Isquemia aguda de miembro inferior y tratamiento con bupivacaína epidural a largo plazo.

We report the treatment of an ischemic lower limb (arterial obstruction shown by angiography at popliteal level, proximal to common tibioperoneal artery) with 0.125% and 0.20% epidural bupivacaine, which was continuously administered by pump during 30 days. Simultaneously, 8 mg morphine chloride was administered every 24 hours by epidural route, anticoagulation with heparin was started, and transcutaneous electrical stimulation was used. The favorable outcome, with sufficient peripheral revascularization, permitted to preserve the limb. During therapy no sign of cardiac toxicity attributable to bupivacaine was detected.

[Postoperative analgesia and dexamethasone]. / Analgesia postoperatoria y dexametasona.

A randomized, double-blind, prospective study was carried out in 100 patients who had undergone some type of surgical treatment in order to evaluate the degree of pain and relief of pain, the degree of achieved analgesia according to the opinion of the observer and consumption of analgesic agents. The evaluation was carried out on seven occasions during the first 12 hours of the postoperative period. Patients received dexamethasone (4 mg before or after the operation or 8 mg after the operation), 6-methylprednisolone (16 mg at the end of the operation) or nothing (control group). Regardless of type, dose or timing of administration of the drugs, all patients receiving corticosteroids presented less pain, more relief of pain (expressed by themselves or in opinion of the observer) and needed lower doses of analgesics during the studied time.

[Administration of lysine acetylsalicylate and meperidine in acute postoperative pain]. / Administración de acetilsalicilato de lisina y meperidina en el dolor agudo postoperatorio.

INTRODUCTION: Postoperative analgesia is insufficiently done due, among others, to the undesirable effects of analgesic agents. OBJECTIVE: The aim of this study was to analyze the effects of the simultaneous administration of opiates (meperidine) and AINES (lysine acetylsalicylate, ASL). MATERIAL AND METHODS: We studied 160 patients during the immediate postoperative phase. All of them underwent programmed surgery with the same general anesthetic technique. Patients were allocated into 8 groups of treatment: A) ASL 900 mg and 1.800 mg/8 h, B) ASL 900 mg and 3.600 mg/8 h, C) ASL 900 mg and meperidine 100 mg/8 h, D) ASL 900 mg and 1.800 mg/8 h together with meperidine 100 mg/8 h, E) meperidine 50 mg and ASL 1.800 mg/8 h, F) meperidine 50 mg and ASL 3.600 mg/8 h, G) meperidine 50 mg and 100 mg/8 h, and H) meperidine 50 mg and 100 mg/8 h together with ASL 1.800 mg/8 h. The effects of analgesic agents were evaluated on the basis of patient's appreciation of the degree of pain and relief and on the basis of an observer who did not know the therapeutic regime administered. Results were compared according to the analysis of variance in a graded factorial design. A p value less than 0.05 was considered significant. RESULTS: The degree of pain was significantly lower in groups C, D, G and H (specially in G and H) than in the remaining groups, but there were no significant differences between them. The lowest pain relief was observed in groups A, B, E and F. The highest attenuation of pain was achieved in groups G and H. The highest attenuation of pain was achieved in groups G and H. The observer considered that the two latter groups were those with the highest pain relief, followed by groups C and D. The remaining patients failed to show appreciable improvement. Nausea and vomiting only occurred in some patients after administration of a bolus of meperidine. There were no other secondary effects. CONCLUSIONS: The best degree of postoperative analgesia is achieved after administration of continuous infusion of meperidine 100 mg/8 h. Simultaneous infusion of ASL 1.800 mg/8 h did not improve the analgesia obtained with a bolus of 900 mg of ASL nor with a bolus of 50 mg of meperidine. Secondary effects were only nausea and vomiting and coincided with the administration of a bolus of meperidine.

Interaction between inhalational anaesthetics and enoximone on isolated heart muscle.

1. The present study describes the effects of halothane or isoflurane on enoximone activity in the isolated left atria of the rat. 2. Concentration-response curves were obtained for the positive inotropic effects of enoximone on electrically stimulated left atria. 3. Enoximone significantly (P < 0.01) increased the contractile force (56% maximum) with all the concentrations tested (10(-9) -10(-3) M). 4. When halothane (1.5% v/v) was present in the organ bath, the maximum effect obtained with enoximone (9%) was significantly lower than that obtained with enoximone alone. 5. Similar results were obtained with enoximone in the presence of halothane plus diltiazem. Isoflurane (1.5% v/v) did not significantly modify the maximum effect obtained with enoximone alone. 6. The administration of diltiazem antagonized the positive inotropic effects of enoximone in the presence of isoflurane or halothane. 7. These results shows that halothane, but not isoflurane, decreased the potency of enoximone on the isolated left atria and suggests that this effect may be mediated by the blocking of the influx of extracellular calcium through voltage-dependent calcium channels inhibited by diltiazem.

Naloxone modifies the inotropic decrease induced by halothane on isolated left atria.

1. The present study evaluates the interaction between naloxone and halothane on the left atria. 2. Halothane produced significant decrease in auricular inotropism at concentrations ranging from 0.3 to 2.5 v/v%. 3. Naloxone modified the concentration response curve to halothane. The antagonism between both drugs is consistent with a competitive antagonism since the curve obtained had a slope which did not differ significantly from -1. 4. These results suggest that the negative inotropic effects induced by halothane could be mediated by opioid receptors.

Endorphin levels in cerebrospinal fluid of patients with postoperative and chronic pain.

The authors measured endorphin levels in the cerebrospinal fluid (CSF) of 12 patients with chronic pain due to lumbar disc syndrome and eight patients with acute postoperative pain. These were compared with CSF endorphin levels in 20 control patients with no history of pain. Endorphins were extracted by adsorption to a synthetic resin (Amberlite XAD-2), eluted with methanol, and assayed using the electrically stimulated mouse vas deferens. Results were expressed as methionine-enkephalin (Met-E) equivalents, which was the standard in the bioassay. The CSF endorphin level was 0.42 +/- 0.07 pmol/ml (mean +/- SE) in the postoperative group, 1.44 +/- 0.2 pmol/ml in the chronic pain group, and 4.36 +/- 0.89 pmol/ml in the control group. CSF endorphin levels in the two pain groups differed significantly from both the control group and each other. These results suggest a correlation between pain levels and endorphin concentration in the CSF; however, in the acute postoperative pain group the influence of other factors such as anesthesia or surgical stress cannot be evaluated.

Interactions between diltiazem and inhalation anaesthetics in the isolated heart.

It has been postulated that inhalation anaesthetics may interfere with calcium movement across cell membranes. We have evaluated the interaction between diltiazem and the inhalation anaesthetics halothane and isoflurane on sinus automaticity in the isolated right atrium (SAIRA). Isoflurane significantly reduced atrial rate at all concentrations tested. However, halothane produced only a small but significant decrease at the higher concentrations used (1-2 v/v%). Diltiazem modified the maximal negative chronotropic response to inhalation anaesthetics. Maximum depression of SAIRA was significantly greater in the presence of two different doses of diltiazem compared with exposure to halothane and isoflurane alone. These results suggest that inhalation anaesthetics may block the influx of extracellular calcium through voltage-dependent calcium channels inhibited by diltiazem.

Effects of diltiazem on hyperthermia induced seizures in the rat pup.

1. We studied the effects of a calcium antagonist diltiazem, as well as diazepam and phenytoin on hyperthermia induced seizures in unrestrained 15 day-old rats. 2. Saline injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degree C at 50 min. 3. At this time all rats pups had generalized seizures. 4. Similar results were obtained when the animals were pretreated with phenytoin (100% showed seizures). 5. Animals receiving diltiazem had a temperature of 41.5 +/- 0.1 degree C at 90 min of exposure to 40 degrees C environment. 6. However, diltiazem completely prevented seizures. 7. The rats treated with diazepam showed lower temperature than in saline, diltiazem and phenytoin groups and no seizures were observed in this experimental group.

Temperature-dependent effects of halothane and isoflurane on the isolated left atrium.

The aim of the present study was to examine whether changes in temperature alter the effects of halothane and isoflurane on isolated left atria. Concentration-response curves for inotropic effects at different temperatures (30 degrees C, 37 degrees C, 40 degrees C) on electrically stimulated left atria of the rat were obtained. The change of temperature modified the maximal negative inotropic response to halothane. The maximal decrease induced by halothane was 12 +/- 2.3 per cent at 37 degrees C and 18 +/- 2.5 per cent at 30 degrees C. When the temperature increased up to 40 degrees C the maximal decrease of atrial inotropism was 46 +/- 2.1 per cent--significantly higher than obtained at 37 degrees C. However, the maximal effect obtained by isoflurane was not significantly affected by temperature (30 degrees C = 7 +/- 1.6 per cent; 37 degrees C = 8 +/- 1.8 per cent; 40 degrees C = 2 +/- 0.8 per cent). Furthermore the potency of halothane (expressed as the concentration which produced 50 per cent inhibition - IC 50 per cent), decreased significantly at 30 degrees C (IC 50 = 1.34 +/- 0.18) and increased at 40 degrees C (IC 50 = 0.44 +/- 0.17) when compared with its potency at 37 degrees C (IC 50 = 0.96 +/- 0.08). On the other hand changes in temperature did not significantly modify the IC 50 for isoflurane obtained at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of halothane, isoflurane and enflurane on isolated rat heart muscle.

Since the effects in the intact organism are complicated by central as well as peripheral effects, we compared the direct cardiac effects of three commonly used inhalational anaesthetics--halothane, isoflurane and enflurane--on isolated heart muscle. Concentration-response curves for inotropic, chronotropic and ventricular automaticity effects of halothane, isoflurane and enflurane (0.1-2% v/v) on electrically stimulated left atria, right atria and right ventricles of the rat were obtained. All three inhalational anaesthetics significantly decreased contractile force; the inhibitory concentration 50 (IC50) of enflurane was 0.55 +/- 0.06% v/v, significantly lower than halothane (0.96 +/- 0.08% v/v) and isoflurane (0.67 +/- 0.05% v/v). Similar results were obtained on atrial nomotopic rate. Halothane, isoflurane and enflurane produced negative chronotropic effects in this preparation. On the other hand, halothane and isoflurane significantly reduced the ventricular ectopic automaticity. However enflurane (0.3, 0.5, 1% v/v) increased ventricular rate. There were statistically significant differences between the IC50 values of atrial and ventricular rate for halothane and isoflurane. These results indicate: (a) direct negative inotropic and chronotropic effects for the three inhalational anaesthetics tested; (b) anti-dysrhythmic actions for halothane and isoflurane; and (c) dysrhythmogenic effects of enflurane.

Postoperative analgesia induced by subarachnoid lidocaine plus calcitonin.

A randomized double-blind study tested the analgesic effects of subarachnoid administration of salmon calcitonin (sCT) in acute postoperative pain. Sixty patients were grouped according to type of surgery (intraabdominal, extraabdominal, and lower extremities), subdivided into those given subarachnoid lidocaine 1 mg/kg plus sCT (100 IU) or lidocaine plus saline. Pain was evaluated by a descriptive scale 3, 6, 12, 24, 48, and 72 hr after surgery, as well as by the frequency of the patients' requests for postoperative analgesics. In all instances, the sCT-treated patients had significantly less postoperative pain. Similarly, the requests for analgesics was significantly lower or absent in the sCT-treated group. Minor side effects such as nausea and vomiting, abdominal pain, and "nervousness" were observed in a small number of sCT-treated patients. In our series of 30 patients, subarachnoid administration of sCT was an effective analgesic with minimal side effects. Its safety remains to be proved by further studies.