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Biomedical subjects

M M Puig

Publications and source records attributed to M M Puig.

At least 55 records · Page 3Linked to original sources
PubMed1992

On the mechanism of the interaction of ketamine and halothane in vitro.

1. Electrically induced contraction of guinea pig ileum myenteric plexus-longitudinal muscle was inhibited by ketamine and halothane with IC50s of 2.1 x 10(-4) M and 1.8 v/v% respectively. 2. The inhibitory action of ketamine was partially antagonized by naloxone and the selective kappa antagonist nor-binaltorphimine. 3. The actions of ketamine and halothane were synergistic at high levels of response (above 30% inhibition). 4. The actions of ketamine and halothane became antagonistic after treatment with pertussis toxin. 5. The interaction of ketamine and halothane was similar to the interaction of morphine and halothane.

Animals↗
PubMed1992

Bretylium tosylate and electrically induced cardiac arrhythmias during hypothermia in dogs.

The effect of bretylium tosylate on plasma catecholamines and on electrically induced arrhythmias was evaluated in anesthetized hypothermic dogs. Bretylium at a dose of 7.5 mg/kg was administered prior to cooling from 37 degrees C to 27 degrees C. During cooling, the ventricular arrhythmia threshold (VAT) in control animals decreased from 10.1 +/- 1.9 to 4.4 +/- 1.3 impulses, while the VAT in bretylium-treated animals increased from 9.8 +/- 2.9 to 23.2 +/- 2.7 impulses. Catecholamine levels increased during cooling in all animals. In control animals, the epinephrine/norepinephrine ratio was unchanged, but in animals treated with bretylium tosylate, the ratio increased more than 10-fold (from 0.48 +/- 0.1 to 5.49 +/- 0.32 at 29.9 degrees C). The demonstrated increase in catecholamine levels during hypothermia suggests that the protection offered by bretylium tosylate against cardiac arrhythmias is not explained by modification of catecholamine levels, and is more likely due to an alteration of the electrophysiologic properties of cardiac tissues.

Animals↗
PubMed1991

Kappa-opioid receptor-mediated thermonociceptive mechanisms in streptozotocin diabetes.

The effects of the benzomorphan kappa-opiate antagonist MR 2266 and its dextro enantiomer MR 2267 were assessed on thermonociception in male Swiss Webster mice. Experimental diabetes was induced by injecting streptozotocin (200 mg/kg IP, 7-8 days before). Animals with dextrose treatment (5 g/kg, IP, at the time of opiate injection) were used as acute hyperglycemic controls. Nociception was assessed by supraspinal nociceptive reflex (licking and jumping in hot plate test) indicative of higher cognitive process as well as a predominantly lower spinal monosynaptic reflex (tail immersion test). In normoglycemic, acute hyperglycemic and diabetic mice, MR 2266 decreased, while MR 2267 increased, the reaction latencies. The results indicate tonic stereospecific kappa-opiate receptor-mediated spinal and supraspinal thermonociceptive reactions are not modulated by experimental diabetes and thus are distinct from those of naloxone-sensitive mu-opiate receptor sites.

Animals↗
PubMed1991

Morphine-ethanol interaction on body temperature.

1. The interaction between ethanol and morphine on core temperature was investigated in Swiss Webster mice. 2. Morphine (2.5-30 mg/kg) and ethanol (0.5-3.0 mg/g) administered individually resulted in a dose dependent decrease in body temperature. 3. When both drugs were injected simultaneously, body temperature decreased less than it would be expected to if the effects were additive. 4. Naloxone antagonized the hypothermic effect of morphine, but the hypothermic effect of ethanol and that of the combination of morphine plus ethanol was only reversed with high doses of naloxone (10 mg/kg). 5. Individual morphine and ethanol plasma levels were not significantly altered by their concomitant administration. 6. Binding of tritiated naloxone to opiate receptors in mouse brain membrane preparations was unchanged by pretreatment with ethanol (0.5 and 2 mg/g). 7. The interaction between morphine and ethanol was found to be less than additive and not related to pharmacokinetic changes of either drug.

Animals↗
PubMed1991

Kappa-opiate agonist-induced inhibition of gastrointestinal transit in different strains of mice.

The effects of kappa-opiate agonists on gastrointestinal motility was assessed in Swiss Webster, C57BL/6, BALB/c and DBA/2 strains of mice. The kappa-agonists, PD 117302, U-69593 and U-50488H (3 mg kg-1), were injected subcutaneously and the distance travelled by a charcoal meal in the gastrointestinal tract was measured. All kappa-agonists induced significant inhibition of charcoal meal transit; however, there were significant strain differences in the antitransit effect. It is concluded that kappa-receptors are involved in the inhibition of gastrointestinal transit and that the negative data reported in the literature may be due to a genotype-dependent effect of kappa-agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Prevention of hyperthermia-induced convulsions in immature rat by MR-2266, a kappa antagonist.

The opioid receptor subtypes involved in hyperthermia-induced convulsions were studied by testing different opioid receptor-selective antagonists in unrestrained 15-day-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 40.4 +/- 0.2 degrees C at 60 min. At this time all rat pups had convulsions and died. Similar results were obtained when the animals were pretreated with beta-funaltrexamine or 1 mg/kg ICI-154129. However, the injection of 10 mg/kg ICI-154129 prevented hyperthermia-induced convulsions (only 20% of the rats showed generalized convulsions at 90 min). Rats treated with the kappa antagonist MR-2266 also showed an increase in rectal temperature. However, none of the animals had convulsions or died. These results suggest that the kappa-opioid receptors are involved in convulsions induced by hyperthermia.

Animals↗
PubMed1990

Effects of the benzomorphan kappa-opiate, MR 2266 and its (+) enantiomer MR 2267, on thermonociceptive reactions in different strains of mice.

The effects of the benzomorphan kappa opiate MR 2266 and its dextro enantiomer MR 2267 were assessed on thermonociception in Swiss Webster, C57BL/6, BALB/c and DBA/2 strains of mice. In the hot plate (60 +/- 0.5 degrees C, cut-off time 120 s and tail immersion tests, MR 2266 (10 mg/kg, s.c., 15 min before) decreased, while MR 2267 (10 mg/kg s.c., 15 min before) increased the reaction latencies. In the hot plate test, the sensitivities for the effects of MR 2266 and MR 2267 on jump latency in different strains of mice were as follows: MR 2266; BALB greater than Swiss greater than C57BL greater than DBA and MR 2267; DBA greater than BALB = Swiss greater than C57BL. In the immersion test, for the hyperalgesic response of MR 2266, the rank order of strains was; BALB greater than C57BL and DBA greater than or equal to Swiss while the rank order for the analgesic effect of MR 2267 was; Swiss greater than DBA and BALB. The results indicate the presence of tonic kappa-receptor-mediated regulation of the spinal and supra-spinal thermonociceptive reactions which is stereospecific and strain dependent.

Animals↗
PubMed1990

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.

Animals↗
PubMed1990

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)

Animals↗
PubMed1990

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.

Animals↗
PubMed1990

Synergistic interaction of morphine and halothane in the guinea pig ileum: effects of pertussis toxin.

The effects of pertussis toxin on the actions of morphine and halothane in the guinea pig ileum are described. Both morphine and halothane produce a dose-related inhibition of electrically induced muscle contraction. The IC50 of morphine was unchanged by the toxin (2.1 and 2.2 X 10(-7) M in control and toxin-pretreated animals). However, the IC50 of halothane was increased from 2.1 to an extrapolated value of 9.1 vol/vol% by pertussis toxin. At high levels of inhibition the interaction between morphine and halothane was synergistic and was converted to additive in the presence of the toxin. These results demonstrate that in the myenteric longitudinal muscle preparation the effects of halothane, but not those of morphine, are mediated by the substrate for pertussis toxin, possibly a Gi membrane protein. The present study provides significant evidence that the effects of halothane on neuronal tissue are dependent upon an interaction with a specific membrane protein.

Animals↗
PubMed1990

Effects of azepexole on opioid receptors and endogenous opioid release in the guinea pig ileum.

The interactions of the opioid and adrenergic systems were investigated in the guinea pig myenteric plexus longitudinal muscle preparation. Morphine and azepexole (a highly selective alpha 2-adrenergic agonist) inhibit the electrically induced contractions with ED50 of 1.9 X 10(-7) M and 3.1 X 10(-6) M, respectively. The effect of morphine but not that of azepexole was competitively antagonized by naloxone. Stimulation of the preparation at 10 Hz was used to induce endogenous opioid release that was unaffected by azepexole. The authors' findings indicate that the effects of morphine and azepexole are additive, but that there is no direct interaction between the opioid and adrenergic receptors in the ileum. These observations provide some additional insight into the ability of alpha 2-agonists to enhance the effects of opioids and inhalation anesthetics.

Adrenergic alpha-Agonists↗
PubMed1990

Streptozotocin-diabetes attenuates alpha 2-adrenoceptor agonist-induced delay in small intestinal transit in mice.

1. The effect of alpha 2-adrenoceptor agonists on gastrointestinal motility was assessed in normoglycaemic and streptozotocin-diabetic mice. 2. The alpha 2-adrenoceptor agonists used were: clonidine (0.1, 0.3 and 1 mg kg-1, azepexole (10, 20 and 40 mg kg-1), tizanidine (1, 3 and 10 mg kg-1) and ST-91 (10, 20 and 30 mg kg-1). 3. Acute hyperglycaemia was induced by D-(+)-glucose (5 g kg-1) and chronic hyperglycaemia by streptozotocin (200 mg kg-1) injection. 4. The gut motility was quantitated using the charcoal meal test. 5. The results indicate that in normoglycaemic and acutely hyperglycaemic mice, all of the alpha 2-adrenoceptor agonists used produced significant inhibition of meal transit. 6. However, in streptozotocin-diabetic mice, the anti-transit effect of alpha 2-adrenoceptor agonists was attenuated. 7. Since streptozotocin-induced diabetes but not acute hyperglycaemia was associated with the attenuation of anti-transit effect, elevated blood sugar is not the mechanism for the observed effect. 8. As with groups treated with clonidine, azepexole or tizanidine, the anti-transit effect of a peripherally acting alpha 2-adrenoceptor agonist, ST-91, was attenuated in streptozotocin-diabetic mice. This suggests the involvement of peripheral mechanism(s) in attenuating the anti-transit effect of alpha 2-adrenoceptor agonists. 9. These results identify the need for critical evaluation of the role and efficacy of alpha 2-adrenoceptor agonists in the therapeutic management of diabetic diarrhoea.

Adrenergic alpha-Agonists↗
PubMed1990

Effects of kappa- and mu-selective opiate agonists on colonic temperature in normoglycaemic and streptozotocin-treated hyperglycaemic mice.

The thermic responses of highly selective k-(U-69593 and U-50488H) and mu-(sufentanil and fentanyl) agonists were assessed in normoglycaemic and hyperglycaemic mice. Hyperglycaemia was induced by streptozotocin injection. The opiates were injected subcutaneously and colonic temperatures monitored for 90 min. after injection. In normoglycaemic animals the k-agonists induced a significant hypothermic response and hyperglycaemia did not modify this effect. In normoglycaemic mice, low doses of mu-selective agonists predominantly produced hypothermia, while in high doses resulted in hyperthermia. In chronic hyperglycaemic mice, hyperthermia was the predominant effect of mu-opiates. The present results characterize the time course and dose response of some of the currently available highly selective kappa- and mu-opiate agonists for the first time in mice and suggest that hyperglycaemia differentially affects the opiate receptor subtypes that mediate thermoregulatory events.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1990

Effect of pertussis toxin on the interaction of azepexole and halothane.

The effect of pertussis toxin on the interaction of azepexole and halothane was determined on the guinea pig ileum. Both azepexole and halothane inhibited electrically induced contractions with IC50 values of 3.3 X 10(-6) M and 1.5 V/V%, respectively. The two drugs interacted synergistically at concentrations producing inhibition greater than 50%. Pretreatment with pertussis toxin reduced the potency of each agent individually and abolished the synergistic interaction. The results demonstrate that the effects of halothane and azepexole involve a pertussis-sensitive G protein, thus suggesting that the effects of volatile anesthetics are mediated in part by this group of membrane associated proteins.

Adrenergic alpha-Agonists↗
PubMed1990

Anesthesia for angioembolization of brain arteriovenous malformations: a retrospective assessment.

We reviewed the anesthetic management of 55 patients under 18 years of age during angioembolization of arteriovenous malformations. Patients were grouped according to age: less than 1 month (A), 1-11 months (B), 1-5 years (C) and 7-13 years (D). All had general endotracheal anesthesia. In groups A and B, approximately 43% received pure narcotic and 43% balanced while only 14% had pure inhalational anesthesia. In groups C and D, 41 and 52% received pure inhalation and balanced anesthesia, respectively, while only 7% had pure narcotics. Hypotension was induced in 50% (C and D) and in 20% (A and B) of the patients. Intraoperative lasix or phlebotomy was used in 28, 16, 13 and 0% of groups A, B, C and D, respectively. Two arrests occurred immediately after the injection of the embolizing material. From our review, no single type of anesthesia can be advocated over all others. The use of invasive monitoring (arterial and central venous lines), precise fluid management and the avoidance of nitrous oxide will help to decrease the incidence of intraoperative complications during anesthesia.

Anesthesia, General↗