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A Jayaram

Publications and source records attributed to A Jayaram.

13 recordsLinked to original sources
PubMed1997

RB 101, a purported pro drug inhibitor of enkephalin metabolism, is antinociceptive in pregnant mice.

In an earlier study, we demonstrated the enhancement of pregnancy-induced analgesia with an inhibitor of endogenous enkephalin metabolism. The purpose of the present study was to evaluate the antinociceptive effect of another inhibitor of enkephalin metabolism, RB 101, on pregnant mice. Further, since other studies have shown RB 101 to be free of opioid side effects, we examined its effect on respiratory rate. Analgesia was assessed using the hot plate test, and respiratory rate was measured by recording the output from an end-tidal carbon dioxide detector. In pregnant mice, experiments were conducted on Day 17 or Day 18 of pregnancy; mice usually deliver on Day 19. For the hot plate test, animals were tested in the following groups: Group 1, RB 101 150 mg/kg (n = 15); Group 2, RB 101 50 mg/kg (n = 15); Group 3, RB 101 vehicle (n = 15); Group 4, morphine 5 mg/kg (n = 14); and Group 5, RB 101 150 mg/kg + naloxone 5 mg/kg (n = 10). The test was repeated on the second day after delivery in animals in Groups 1 and 3 (given RB 101 150 mg/kg and RB 101 vehicle, respectively). RB 101 150 mg/kg and morphine 5 mg/kg were significantly different (mean percentage of maximum possible effect 30.0 and 37.7, respectively, at 30 min and 41.6 and 32.6, respectively, at 60 min) in their antinociceptive effect in pregnant animals from all other groups. Naloxone, when coadministered with RB 101, prevented the development of antinociception. RB 101 150 mg/kg was not antinociceptive after delivery. Depression of respiratory rate was tested in a separate set of animals in the following groups: Group 1, RB 101 150 mg/kg (n = 16); Group 2, morphine 5 mg/kg (n = 16); Group 3, RB 101 vehicle (n = 15). Morphine 5 mg/kg produced significant depression of respiratory rate at 30 min postinjection when compared with RB 101 150 mg/kg and RB 101 vehicle (mean percent change in respiratory rate was 78.5% compared with 87.7% and 92.4%, respectively, where 100% = no change). These results suggest that drugs such as RB 101 may produce antinociception with minimal effects on respiration.

Analgesics↗
PubMed1997

Ultrasound examination of the stomach contents of women in the postpartum period.

This study used ultrasound imaging to compare stomach contents and gastric emptying of women in the postpartum period with those of nonpregnant women. In the first part of the study, the presence or absence of solid food particles was compared between patients presenting for postpartum tubal ligation (n = 28) and those presenting for gynecological surgery (n = 24). In the second part of the study, gastric emptying of solid food in a group of women in the postpartum period (n = 20) was compared with that of a group of nonpregnant volunteers (n = 21). After a standardized meal, the subjects were not allowed any food for 4 h, and the stomach contents were examined by ultrasound. Results of the first part of the study showed that 11 of the 28 patients presenting for postpartum tubal ligation compared with none of the gynecologic patients had solid food particles in the stomach prior to surgery. In the second part of the study, 19 of 20 women in the postpartum group still had food particles in the stomach 4 h after the meal as compared with only 4 of 21 in the non-pregnant group. Both differences were statistically significant. Our results indicate that gastric contents of women in the postpartum period may include food particles and that there is delayed gastric emptying of solid food in the postpartum period.

Adult↗
PubMed1995

SCH 32615, an enkephalinase inhibitor, enhances pregnancy-induced analgesia in mice.

Increased tolerance to noxious stimuli during pregnancy has been demonstrated. The purpose of this study was to examine the effect of SCH 32615, an inhibitor of one of the enzymes (enkephalinase) responsible for the degradation of endogenous enkephalins, on pregnancy-induced analgesia in mice. Analgesia was tested using the hot-plate and tail-flick tests. For the hot-plate test, animals were tested in late pregnancy (Day 17 or Day 18 of pregnancy; mice deliver on Day 19) and in the postpartum period (Days 2 and 8 after delivery) in the following groups: i) no treatment (n = 15); ii) vehicle only (n = 15); iii) SCH 32615 250 mg/kg (n = 20), 150 mg/kg (n = 15), 50 mg/kg (n = 14); iv) naloxone 5 mg/kg (n = 15); v) naloxone 5 mg/kg+SCH 32615 150 mg/kg (n = 10); vi) nonpregnant control given SCH 32615 150 mg/kg (n = 14). All drugs were given subcutaneously. Hot-plate latency (HPL) was significantly higher in pregnant mice (mean hot-plate latency 17.5 s) than postpartum mice (mean hot-plate latency 11 s on Day 2 and 8.5 s on Day 8). SCH 32615 250 mg/kg and 150 mg/kg significantly enhanced this analgesia in pregnant mice (mean percent of maximum possible effect 24.2 and 29.9, respectively) but not SCH 32615 50 mg/kg or the vehicle alone (mean percent of maximum possible effect 12.4 and 0.5, respectively). Naloxone significantly lowered HPL in pregnant mice (19.8 s-16.2 s) and antagonized the effect of SCH 32615.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1995

An enkephalinase inhibitor, SCH 32615, augments analgesia induced by surgery in mice.

BACKGROUND: Stress-induced analgesia is a well recognized phenomenon in animals and humans in which endogenous opioids have been implicated. However, analgesia induced by surgical stress has not been reported. The purpose of this study was to determine whether surgery evokes analgesia and to examine the effect of SCH 32615, an inhibitor of one of the enzymes (enkephalinase) responsible for the degradation of enkephalins, on this analgesia, in mice. METHODS: Analgesia was tested using the hot-plate test. Animals were tested before any procedure was done and then at hourly intervals thereafter. Under halothane anesthesia, the anterior abdominal wall was incised, and the abdominal aorta was compressed against the vertebral column for 1 s. This was repeated for a total of three times at 5-s intervals. At the end of the procedure, the following drug(s) were administered subcutaneously to different groups of animals: (1) no drugs, only surgery (n = 15); (2) 5 mg/kg naloxone (n = 15); (3) 150 mg/kg SCH 32615 (n = 14); (4) 150 mg/kg SCH 32615 plus 5 mg/kg naloxone (n = 15); and (5) SCH 32615 vehicle (0.9% methylcellulose; n = 13). Two more groups of animals were included as controls and were anesthetized, but no surgical procedure was performed. One control group (n = 13) received 0.9% methylcellulose and the other 150 mg/kg SCH 32615 (n = 12). RESULTS: Hot-plate latency was significantly longer after surgery (hot-plate latency at 4 h after surgery 29.3 +/- 3.2 (SE) s and at 5 h 30.7 +/- 5 s versus baseline 15.8 +/- 7 s; P < 0.05). Naloxone (5 mg/kg) inhibited this analgesic effect of surgery. SCH 32615 significantly enhanced this analgesia (percentage of maximal possible effect (%MPE) at 4 h 33.7 +/- 8.7%, at 5 h 27.5 +/- 4.7%, and at 6 h 23.2 +/- 4.7%; P < 0.05 compared to all other groups), and naloxone antagonized its effect. Anesthesia without surgery did not evoke subsequent analgesia, and SCH 32615 was not analgesic in the absence of antecedent surgery. CONCLUSIONS: Surgery activated endogenous analgesia, the development of which was prevented by naloxone. SCH 32615, an enkephalinase inhibitor, significantly enhanced this analgesia.

Analgesia↗
PubMed1994

Endogenous vasopressin and renin-angiotensin systems support blood pressure after epidural block in humans.

BACKGROUND: Studies in experimental animals show that endogenous Arg-vasopressin (AVP) and the renin-angiotensin system support blood pressure when the sympathetic system is impaired pharmacologically or after epidural anesthesia. However, extrapolation to humans is uncertain. Therefore, we administered an AVP type V1 receptor antagonist and an angiotensin-converting enzyme inhibitor to volunteers and measured the effect on blood pressure after epidural anesthesia. METHODS: Healthy volunteers in whom epidural catheters were placed were randomly assigned to receive 1.25 mg intravenous enalapril or saline placebo followed by 0.5 mg AVP type V1 antagonist beta-mercapto-beta, beta-cyclopentamethylene-propionyl-o-Met-Tyr-Arg-vasopressin (AVPA) or saline placebo. Finally, 2% lidocaine was injected to obtain a T2 level. Controls received intramuscular lidocaine. RESULTS: Blood pressure did not significantly change after T-2 epidural anesthesia in subjects treated with saline placebo, AVPA or enalapril alone (n = 10, for each treatment). In contrast, combined treatment with enalapril and AVPA resulted in a 36 +/- 11% decrease in blood pressure after epidural dosing (n = 6). Controls given intramuscular lidocaine, in place of the epidural did not develop hypotension after AVPA and enalapril treatment (n = 10). CONCLUSIONS: Endogenous AVP and the renin-angiotensin system play important roles in maintaining blood pressure after epidural anesthesia in healthy subjects.

Adult↗
PubMed1994

Intrathecal cholinergic agonists lessen bupivacaine spinal-block-induced hypotension in rats.

Hypotension is an important side effect of spinal anesthesia. Intrathecal (IT) cholinergic agonists, including neostigmine (NEO), increase arterial blood pressure by stimulating spinal sympathetic neurons. Therefore, we tested the ability of IT cholinergic agonists to prevent the hypotensive effect of IT bupivacaine (BUP) (430 nmol) in rats instrumented with IT and arterial catheters. The mean arterial pressure (MAP) decreased 35 +/- 4 mm Hg (n = 10) after IT-BUP alone. In contrast, MAP did not significantly change after IT-BUP + IT-NEO (12.5 and 25 nmol; n = 5 for each dose). Intramuscular (IM) NEO was not effective, and MAP decreased 38 +/- 4 mm Hg after IT-BUP + IM-NEO (25 nmol; n = 5). Three additional cholinesterase inhibitors, physostigmine, edrophonium, and ambenonium, as well as the direct-acting cholinergic agonists carbachol, oxotremorine, and arecoline, each lessened the hypotension seen after IT-BUP. Furthermore, the nonselective muscarinic antagonist, atropine, as well as the M2 receptor selective antagonist, methoctramine, prevented the vasopressor effect of IT-NEO in our model. Finally, the nicotinic antagonist, mecamylamine, and the M1 selective antagonist, pirenzepine, did not affect the pressor effects of NEO in our model. In conclusion, IT cholinergic agonists lessen BUP spinal-block-induced hypotension in rats by a muscarinic dependent pathway.

Anesthesia, Spinal↗
PubMed1993

Progesterone-mediated potentiation of spinal sufentanil in rats.

Pregnancy is associated with an increased sensitivity to both general and local anesthetics. The exact reason is uncertain, but increased concentrations of progesterone and endogenous opiates have been implicated. Therefore, we tested the ability of intrathecally administered progesterone to produce analgesia and to potentiate the effects of spinal sufentanil. Female rats had intrathecal catheters implanted for drug administration, and analgesia was measured using the tail flick assay or hemostat clamp test. Animals were pretreated first with 10 micrograms, 20 micrograms, or 40 micrograms of intrathecal progesterone (n = 5, for each dose) and then given a minimally analgesic dose of sufentanil. Pretreatment with progesterone potentiated sufentanil's effect and resulted in almost complete analgesia. In contrast, in animals not pretreated with progesterone, the same dose of sufentanil resulted in minimal analgesia (n = 15). Intrathecal progesterone alone had no analgesic effects. No behavioral or motor effects were noted after progesterone treatment. Cerebral spinal fluid progesterone levels were within physiologic range. Furthermore, 100 micrograms of progesterone administered intramuscularly did not potentiate sufentanil analgesia. A major progesterone metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, 5 micrograms, 10 micrograms, or 20 micrograms (n = 5, for each dose), also potentiated sufentanil analgesia when administered intrathecally. In contrast, a stereoisomer, 5 beta-pregnane-3 beta-ol-20-one failed to show potentiation. Finally, two drugs that block gamma-aminobutyric acid-mediated increases in chloride ion conductance, picrotoxin and bicuculline, each blocked progesterone-mediated potentiation of sufentanil analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1992

Ultrasound examination of the stomach contents of parturients.

A noninvasive method to determine the actual stomach contents of parturients may help to identify factors responsible for delayed gastric emptying as well as define the risk of aspiration of gastric contents in individual patients. Therefore, we tested the ability of ultrasound imaging to identify noninvasively the stomach contents of laboring and nonlaboring pregnant volunteers. A preliminary study demonstrated that the stomach contents could be identified by ultrasound in 20 healthy volunteers and in 34 parturients, not yet in active labor, scanned after consuming liquids or solid food. Next, 39 parturients in active labor were scanned at varying postprandial times. Sixteen parturients in active labor who had not eaten for 8-24 h still had food detected in the stomach. In fact, nearly two-thirds of the patients in active labor who were scanned had solid food present in the stomach independent of the interval between last oral intake and the ultrasound scan. The present study demonstrates that high-resolution ultrasonography is capable of noninvasively identifying the stomach contents of parturients. These results confirm the clinical impression that emptying of the stomach is delayed for many hours after the onset of labor.

Adult↗