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C W Loomis

Publications and source records attributed to C W Loomis.

At least 19 recordsLinked to original sources
PubMed1998

Inhibition of strychnine-allodynia is mediated by spinal adenosine A1- but not A2-receptors in the rat.

Intrathecal (i.t.) strychnine produces localized allodynia in the rat without peripheral or central nerve injury. Intrathecal CPA (A1-selective agonist) and CGS-21680 (A2-selective agonist) dose-dependently inhibited strychnine-allodynia but with a 50-fold difference in potency (0.02-0.07 vs. 2.7-3.1 microgram, respectively). The anti-allodynic effect of CPA and CGS was completely blocked by pretreatment with the A1-selective antagonist, DPCPX (10 microgram i.t. ), but unaffected by the A2-selective antagonist, CSC (2 microgram i.t. ). The results indicate that spinal A1-, but not A2-, receptors modulate abnormal somatosensory input in the strychnine model, and suggest a difference in spinal purinergic modulation in injury vs. non-injury models of allodynia.

Adenosine↗
PubMed1997

Comparable dose-dependent inhibition of AP-7 sensitive strychnine-induced allodynia and paw pinch-induced nociception by mexiletine in the rat.

The blockade of spinal glycine receptors with intrathecal (i.t.) strychnine produces segmentally-localized allodynia in the rat; a reversible and highly reproducible effect that is attained without peripheral or central nerve injury. We investigated the effect of i.v. mexiletine, an orally active congener of lidocaine, on strychnine allodynia and compared the dose-response relationship of mexiletine in normal (noxious paw pinch) versus abnormal (i.t. strychnine) nociceptive conditions. In addition, we determined the dose-response effect of i.t. AP-7 (an NMDA antagonist) on strychnine allodynia. Male, Sprague-Dawley rats, fitted with chronic i.t. catheters, were lightly anesthetized with urethane. Stimulus evoked changes in blood pressure and heart rate were recorded from the left carotid artery and cortical electroence-phalographic (EEG) activity was continuously monitored using subdermal needle electrodes. After i.t. strychnine (40 micrograms), repetitive brushing of the hair (hair deflection) evoked a progressive increase in mean arterial pressure and heart rate, an abrupt motor withdrawal response, and desynchronization of the EEG, equivalent to those elicited by the chemical nociceptive agent, mustard oil (without strychnine). Pretreatment with mexiletine (5-30 mg/kg i.v. 5 min before i.t. strychnine) dose-dependently inhibited the responses evoked by noxious hind paw pinch (no strychnine) and hair deflection (after i.t. strychnine) with equal potency (ED50's = 9.1-17 mg/kg). Below 30 mg/kg, this effect was achieved without a change in EEG synchrony (cortical activity reflecting the level of anesthesia) and without affecting motor efferent pathways. Strychnine allodynia was also significantly blocked by i.t. AP-7. The ED50's and 95% confidence intervals were 1.1 micrograms (0.7-1.8) for mean arterial pressure, 1.7 micrograms (0.5-6.0) for heart rate, and 0.4 microgram (0.07-2.0) for withdrawal duration. Cortical EEG synchrony was unchanged after i.t. AP-7 consistent with a spinal site of action. The data indicate that: (i) robust allodynia can be selectively induced with i.t. strychnine in animals whose somatosensory systems are otherwise normal; (ii) sub-anesthetic doses of i.v. mexiletine inhibit the abnormal responses to low-threshold (A-fiber) afferent input in the strychnine model of allodynia (i.e., in the absence of peripheral or central nerve injury) at doses which affect normal nociception; and (iii) in the presence of i.t. strychnine, low-threshold afferent input activates a spinal NMDA-receptor mediated process normally restricted to noxious afferent input. Systemic mexiletine may have an important spinal site of action in abnormal pain states.

2-Amino-5-phosphonovalerate↗
PubMed1997

Characterization of an esophagocardiovascular reflex in the rat.

A cardiovascular reflex evoked by esophageal distension (ECR) in urethan-anesthetized male Sprague-Dawley rats was studied to 1) determine whether the relevant sensory input from the esophagus is conveyed by vagal and/or spinal afferents and 2) evaluate the effects and sites of action of antinociceptive agents. Esophageal distension evoked a rise in arterial blood pressure and heart rate that increased linearly with the log of inflation pressure (25-150 mmHg). Distension (100 mmHg for 20 s) of the lower esophagus was a more effective stimulus than distension of the upper esophagus. The ECR was attenuated by unilateral and abolished by bilateral cervical vagotomy and dose dependently inhibited by morphine (1.0-4.0 mg/kg iv) or by intrathecal (T4-T5) administration of dexmedetomidine (DX, 0.05-0.5 microgram), but not by intrathecal (T4-T5) morphine (4-16 micrograms) or intrathecal (L1-L2) or intravenous DX (0.05-0.5 microgram). The ECR was also inhibited by capsaicin and by the topical administration of DX or morphine to the solitary complex. The pressor response persisted after intravenous pancuronium, scopolamine, and methscopolamine. The ECR circuit appears to consist of vagal afferents, efferent sympathetic preganglionic pathways originating in the thoracic spinal cord, and bulbospinal neurons yet to be identified. This reflex fulfills some criteria of a nociceptive event, but this interpretation requires further investigation.

Adrenergic alpha-Agonists↗
PubMed1996

Strychnine-sensitive modulation is selective for non-noxious somatosensory input in the spinal cord of the rat.

Touch-evoked allodynia, an important symptom of clinical neural injury pain, can be modelled acutely and reversibly in the urethane-anesthetized rat using intrathecal (i.t.) strychnine (STR). Allodynia, after i.t. STR (40 micrograms), is manifest as a significant enhancement of cardiovascular and motor responses evoked by normally innocuous brushing of the hair (hair deflection), as compared to responses evoked by either hair deflection after i.t. saline (SAL), or to i.t. STR (40 micrograms) with no tactile stimulus. The present study investigated: (1) the pharmacology of afferent neural inputs involved in STR-dependent allodynia using neonatal capsaicin and the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX); and (2) the effect of i.t. STR on responses evoked by peripheral noxious stimulation. Neonatal capsaicin (25 mg/kg, s.c., post-natal day (PND) 1, and 50 mg/kg, s.c., PND 2, 3, 4, 11, 25, 55 and 85) significantly attenuated the responses evoked by noxious mechanical, thermal or chemical stimuli, but had no effect on STR-dependent allodynia. All hair deflection-evoked, STR-dependent responses were dose-dependently inhibited by i.t. NBQX. The ED50 values and 95% confidence intervals were 10.4 micrograms (5.5-19.6) for the motor withdrawal response, 14.4 micrograms (8.6-24.0) for changes in MAP and 12.2 micrograms (6.8-21.8) for changes in HR. Cortical EEG synchrony was unchanged by i.t. NBQX confirming its spinal locus of action. Intrathecal STR neither reduced nor enhanced the responses elicited by noxious stimuli in capsaicin- or vehicle-pretreated rats. These results indicate that STR-dependent allodynia is initiated by primary afferents not normally involved in nociception (possibly A beta-fibers), and that STR-sensitive modulation in the spinal cord is selective for non-noxious sensory input. The sensitivity of STR-dependent allodynia to non-NMDA receptor antagonists, and the failure of i.t. STR to produce hyperalgesia to mechanical, thermal or chemical noxious stimuli, confirm the independence of nociceptive pathways and STR-sensitive afferent inputs in this model.

Anesthesia, General↗
PubMed1995

Strychnine-dependent allodynia in the urethane-anesthetized rat is segmentally distributed and prevented by intrathecal glycine and betaine.

The blockade of spinal glycine receptors with intrathecal strychnine produces a reversible allodynia-like state in the rat. Thus, hair deflection, in the presence of intrathecal strychnine, induces cardiovascular and motor withdrawal responses comparable with those evoked by noxious thermal, mechanical, or chemical stimulation in the absence of strychnine. In the present study, we mapped the cutaneous sites of abnormal sensitivity to hair deflection throughout the strychnine time course to investigate the segmental distribution of strychnine-induced allodynia. The ability of intrathecal glycine and the glycine derivative betaine to reverse strychnine-induced allodynia was also determined using dose-response analysis. Following intrathecal strychnine (40 micrograms), stroking the legs, flanks, lower back, and tail with a cotton-tipped applicator evoked a pronounced increase in mean arterial pressure, tachycardia, and an abrupt motor withdrawal response in urethane-anesthetized rats. These abnormal responses were only evoked by hair deflection at discrete sites, corresponding to the cutaneous dermatomes innervated by spinal segments near the site of strychnine injection. In rats with intrathecal catheters lying laterally in the subarachnoid space, allodynic sites were observed unilaterally on the ipsilateral side of intrathecal strychnine injection. Recovery from strychnine was complete by 30 min in all affected dermatomes. The cardiovascular and motor withdrawal responses to hair deflection were dose dependently inhibited by intrathecal glycine and intrathecal betaine. The ED50 (95% confidence interval) for intrathecal glycine was 609 (429-865) micrograms for the heart rate response, 694 (548-878) micrograms for the pressor response, and 549 (458-658) micrograms for the motor withdrawal response. The corresponding values for intrathecal betaine were 981 (509-1889), 1045 (740-1476), and 1083 (843-1391) micrograms, respectively. There was no difference in the effect of betaine on sensory-evoked cardiovascular and motor responses. Cortical electroencephalographic activity was not affected by intrathecal glycine or betaine, consistent with a spinal locus of action in reversing strychnine-induced allodynia. These results support the hypothesis that removal of spinal glycinergic modulation from low threshold afferent input with intrathecal strychnine results in segmentally localized, tactile-evoked allodynia.

Anesthetics, Intravenous↗
PubMed1992

Intrathecal oxymetazoline does not produce neurotoxicity in the spinal cord of the rat.

To determine if intrathecal (i.t.) oxymetazoline (OXY) induces histological evidence of spinal neurotoxicity, male, Sprague-Dawley rats (300-450 g; implanted with an i.t. catheter) were treated with i.t. saline or 100 nmol OXY twice daily for 3 days, or 200 or 300 nmol OXY once daily for 3 days. Spantide (D-Arg1, D-Try7,9, Leu11-substance P; 0.067 nmol = 0.1 microgram, 0.167 nmol = 0.25 microgram or 0.334 nmol = 0.5 microgram) or capsaicin (0.164 mumol = 50 micrograms), given as a single i.t. injection, were used as positive controls. Animals were killed 12 h after the last injection of saline or OXY, and 72 h after spantide or capsaicin. Spinal cord sections (L1 and adjacent segments) were examined by light microscopy for changes in gross morphology, substance P-like immunoreactivity (SP-IR) and calcitonin gene related peptide-like immunoreactivity (CGRP-IR). All doses of i.t. OXY produced antinociception (tail-flick ED50 = 53.7 nmol, paw pressure withdrawal ED50 = 93.3 nmol). Rectal temperature decreased by 1.5-2.4 degrees C up to 12 h after 100 nmol of i.t. OXY. There were no signs of inflammation or necrosis, and no detectable loss or damage to either spinal afferents or motor neurons as judged by SP-IR and CGRP-IR structures in spinal cords of OXY-treated animals (all doses) as compared to i.t. saline controls. Spantide (0.1 microgram) had no antinociceptive or neurotoxic effect; 0.25 microgram induced irreversible loss of the TF reflex and transient hind limb paralysis; 0.5 microgram induced irreversible loss of TF and PP responses, permanent hind limb paralysis, bladder and bowel dysfunction. The spinal cords from these animals showed signs of extensive necrosis, cavitation, and haemorrhage in the ventral horn accompanied by a loss of CGRP-IR motor neurons. Capsaicin-treated rats exhibited a permanent loss of the TF but not the PP response and a marked reduction of SP-IR spinal afferents in the dorsal horn. It is concluded that i.t. OXY produces antinociception in the rat with no detectable spinal neurotoxicity as assessed by parameters which are sensitive to the neurotoxins, spantide and capsaicin.

Analgesics↗
PubMed1992

In vivo catechol activity in the rat locus coeruleus following different nociceptive stimuli and naloxone.

The nucleus locus coeruleus (LC) has been implicated in the processing of spinal reflexes following noxious stimuli. It has been demonstrated that noxious stimuli activate LC neuronal firing, but little is known about the neurochemical changes that might occur following such activation. To determine the effects of different noxious stimuli on LC neuronal activity, anaesthetized rats were exposed to mechanical (tail pinch), thermal (55 degrees C water), and chemical (5% Formalin injected in the hind paw) stimuli; the catechol oxidation current (CA.OC), an index of noradrenergic neuronal activity, in the locus coeruleus was monitored using differential normal pulse voltammetry. In addition, the effect of the opioid antagonist naloxone on the CA.OC in the LC was examined. Exposure to both mechanical and chemical stimuli significantly increased CA.OC indicating an increase in LC noradrenergic neuronal activity, while the thermal stimulus had no effect. Treatment with naloxone (1 mg/kg i.v.) had no effect on CA.OC in the LC. The results show a differential responsiveness of LC noradrenergic neurons to different modes of noxious stimuli and fail to demonstrate a tonic opioid regulation of these neurons in the anaesthetized rat.

Animals↗
PubMed1992

Intrathecal St-587: effects on nociceptive reflexes and blood pressure in the rat.

The purpose of this study was to determine the effect of i.t. St 587 (lumbar injection) on tail-flick (TF) latency and paw pressure (PP) withdrawal threshold in conscious rats, and the effect of i.t. (midthoracic injection) and i.v. St 587 on blood pressure in urethane-anesthetized rats. Unlike i.t. methoxamine (alpha 1 agonist), which produced antinociception, i.t. St 587 (0.5-30 micrograms) decreased TF latency and PP threshold below base line. Hyperalgesia was also produced by i.t. Wy 27127 (alpha 2-selective antagonist). At i.t. doses of St 587 > 3 micrograms, there was an apparent but incomplete return of TF latency and PP threshold toward base line. Pretreatment with i.t. prazosin (2.5 micrograms) enhanced the hyperalgesic effect of 30 micrograms, but not 1 microgram of St 587. Intrathecal St 587 and Wy 27127 each antagonized the antinociceptive effect of i.t. guanfacine (alpha 2 agonist) in the TF and PP tests. Intravenous St 587 produced a dose-dependent pressor effect that was antagonized by pretreatment with i.v. prazosin (0.14 mg/kg; 52-fold increase in the ED50), but weakly antagonized by Wy 27127 (0.5 mg/kg; 1.5-fold increase in the ED50). ST-587 also produced a dose-dependent pressor response after i.t. injection which was antagonized by i.t. prazosin (10 micrograms) or i.v. hexamethonium (10 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A study of the analgesic interaction between intrathecal morphine and subcutaneous nalbuphine in the rat.

Nalbuphine reverses opioid-induced respiratory depression, but the effect on analgesia is unclear. The analgesic interaction between subcutaneous (sc) nalbuphine and intrathecal morphine in conscious, male, Sprague-Dawley rats implanted with chronic intrathecal catheters was investigated. Nalbuphine (10 mg/kg) injected 30 min after intrathecal morphine (4 micrograms) significantly antagonized the effect of morphine in the tail flick test. The antagonism was rapid in onset and persisted beyond the experimental period of 240 min. The magnitude and the duration of the effect were comparable to that observed with sc naloxone (1 mg/kg). In contrast to the results in the tail flick test, nalbuphine enhanced the effect of intrathecal morphine in the noninflamed paw pressure test. Nalbuphine (10 mg/kg) alone had no effect on the time course of tail flick latency but significantly increased paw pressure threshold during the 15-90 min interval after sc injection. Nalbuphine (0.5 mg/kg, sc) alone had no antinociceptive effect in either pain test and did not antagonize the antinociceptive effect of intrathecal morphine (4 micrograms) in the tail flick test. However, sc nalbuphine (0.5 mg/kg), injected 30 min after intrathecal morphine (1.5 micrograms), significantly enhanced the effect of morphine in the paw pressure test compared with intrathecal morphine + sc saline-treated rats. The results indicate a complex analgesic interaction between intrathecal morphine and sc nalbuphine. The net analgesic effect during the interaction was determined by the following: 1) the doses of morphine and nalbuphine; 2) the time after nalbuphine administration; and 3) the nature of the nociceptive stimulus. At lower doses, sc nalbuphine appeared to potentiate the effect of intrathecal morphine in the noninflamed paw pressure test.

Analgesics↗
PubMed1988

Intrathecal oxymetazoline produces analgesia via spinal alpha-adrenoceptors and potentiates spinal morphine.

The intrathecal (i.t.) injection of 100 nmol of oxymetazoline to male, Sprague-Dawley rats significantly increased tail flick latency and paw pressure threshold for 10 h as compared to i.t. saline-treated rats. Oxymetazoline-induced antinociception was accompanied by a 2 degree C decrease in rectal temperature and a delayed but mild sedative effect. Intrathecal phentolamine (50 micrograms), injected 8 h after i.t. oxymetazoline, completely reversed the analgesic and hypothermic effects but did not affect sedation. The intravenous injection of oxymetazoline (100 nmol) had no effect in the paw pressure test and virtually no effect in the tail flick test. Co-injection of i.t. morphine and i.t. oxymetazoline in a molar ratio of 1:28 resulted in significant potentiation of their antinociceptive effects as determined by isobolographic analysis. For i.t. morphine alone, the ED50 and 95% confidence interval (95% CI) was 3.8 nmol (2.8-5.6) in the tail flick test and 7.7 nmol (5.4-12.8) in the paw pressure test. In the combination, the ED50 (95% CI) of i.t. morphine was 0.7 nmol (0.6-0.8) in the tail flick test and 1.2 nmol (1.1-1.4) in the paw pressure test, corresponding to an approximate 6-fold increase in potency. The data indicate that: (1) the antinociceptive and hypothermic effects of i.t. oxymetazoline at 8 h are mediated by spinal alpha-adrenoceptors; (2) peripheral sites, and probably supraspinal sites, do not contribute to i.t. oxymetazoline-induced antinociception [corrected]; and (3) oxymetazoline potentiates the analgesic effects of morphine in the spinal cord of the naive rat.

Analgesics↗
PubMed1988

A study of the interaction between clonidine and morphine on analgesia and blood pressure during continuous intrathecal infusion in the rat.

In the rat, the continuous intrathecal (i.t.) infusion of clonidine (0.4 microgram/hr) significantly increased the tail-flick latency (TF) and the threshold for paw pressure (PP) withdrawal for 5 days and decreased the systolic blood pressure (up to 24 mm Hg) for 7 days. The antinociceptive effect of continuous intrathecal infusion of clonidine (0.4 microgram/hr) in the tail flick and paw pressure tests was not attenuated in rats that were tolerant to morphine. The acute intrathecal administration of clonidine (2.7 micrograms) and morphine (1.0 microgram) resulted in a synergistic interaction in the tail-flick and paw pressure tests. A synergistic interaction was also observed during the continuous intrathecal infusion of morphine (1.25 micrograms/hr) and clonidine (0.2 microgram/hr) in the tail-flick and paw pressure tests. Individually, these doses of morphine and clonidine had no antinociceptive effect. However, intrathecal infusion together yielded peak tail-flick and paw pressure responses comparable to that of 0.4 microgram/hr clonidine alone, without affecting systolic blood pressure. No delay in the onset of tolerance to the analgesic effect was observed with the combination as compared with clonidine (0.4 microgram/hr) alone. The data indicate that clonidine-induced spinal analgesia is independent of endogenous opioid systems linked to mu-receptors in the spinal cord, and that optimization of spinal analgesia (e.g. synergism) can be achieved during continuous intrathecal infusion without affecting cardiovascular activity.

Analgesics↗
PubMed1988

Tolerance to intrathecal oxymetazoline-induced analgesia, with paradigm-dependent cross-tolerance to intrathecal morphine.

Male, Sprague-Dawley rats, implanted with intrathecal (i.t.) catheters, were given repeated i.t. injections of morphine (40 nmol), oxymetazoline (100 nmol) or saline (10 microliter) at 12-h intervals for 3 days. Antinociception was determined 1 or 1.5 hr after each injection using the tail-flick and paw-pressure tests. Complete tolerance to i.t. morphine and oxymetazoline developed within 72 and 24 hr, respectively. Antinociception after i.t. oxymetazoline (100 nmol) in morphine-tolerant rats, and after i.t. morphine (20 nmol) in oxymetazoline-tolerant rats, was not significantly different from their respective effects in saline-pretreated rats. These data suggest an absence of cross-tolerance between morphine and oxymetazoline in the rat spinal cord. In a separate group of rats, the continuous i.t. infusion of morphine (26 nmol/hr) produced significant antinociception; tolerance to morphine developed within 36 hr. The antinociceptive effect of i.t. oxymetazoline (100 nmol) was significantly attenuated in rats pretreated with continuous i.t. morphine as compared to saline-pretreated rats. In rats pretreated with continuous i.t. oxymetazoline, cross-tolerance to morphine could not be determined due to severe adverse effects during oxymetazoline infusion. The results of this study suggest that functional cross-tolerance between morphine and alpha adrenoceptor agonists in the spinal cord cannot be excluded on the basis of repeated i.t. injection experiments alone.

Analgesia↗
PubMed1987

Monoamine and opioid interactions in spinal analgesia and tolerance.

Noradrenergic and serotonergic neurons, originating in the brainstem and terminating in the dorsal horn, modulate the spinal processing of nociception. The inhibitory effects of norepinephrine (NE) and serotonin (5-HT) on elements of nociceptive transmission may be direct, or secondary to the release of neuromodulators such as opioid peptides. Two major criteria have been used in pharmacological studies of spinal opioid and monoamine interactions: the ability of opioid antagonists to attenuate the antinociceptive effects evoked by stimulating the release of endogenous NE and 5-HT in the lumbar spinal cord, or by the intrathecal injection of exogenous NE and 5-HT; and the development of cross tolerance between opioids and each of NE and 5-HT. Evidence regarding the spinal interaction between opioids and monoamines in mediating behavioural analgesia is reviewed. Recent results from this laboratory indicate that IT (-)naloxone but not (+)naloxone produces dose-dependent antagonism of IT NE-induced antinociception in the rat. This effect was not due to hyperalgesia. In rats made tolerant to spinal morphine using continuous IT infusion, the antinociceptive effect of continuous IT NE was significantly attenuated. However, no cross tolerance was observed between morphine and 5-HT. Observations from a variety of studies support the hypothesis of a spinal opioid link which contributes, in part, to NE-induced antinociception. However, this interaction remains to be conclusively established.

Analgesia↗
PubMed1987

Determination of cross tolerance in rat spinal cord using intrathecal infusion via sequential mini-osmotic pumps.

Continuous intrathecal (IT) infusion via ALZET mini-osmotic pumps was used to induced spinal tolerance to morphine in the rat. Naloxone (1 mg/kg IP), injected on day 3 of continuous IT morphine (10 micrograms/hr), produced mild withdrawal symptoms in all morphine-treated animals. In rats pretreated with continuous IT morphine (10 micrograms/hr) or saline, systemic morphine (2, 4, 8, 10 and 15 mg/kg IP) produced equivalent, dose-dependent antinociception using the tail-flick and paw pressure tests. The rostral and caudal distribution of methylene blue dye in rat spinal cord was determined on days 1-7 of continuous IT infusion. The dye remained localized near the catheter tip throughout infusion; maximum distribution was 1.5 cm rostrally and 1.0 cm caudally. The data indicate that morphine, infused at the rate of 10 micrograms/hr, does not undergo extensive redistribution in the spinal cord. A sequential, double mini-osmotic pump technique for cross tolerance studies in rat spinal cord is described. In rats pretreated with continuous IT norepinephrine for 4 days, the antinociceptive actions of continuous IT morphine were reduced but not significantly different from saline-pretreated animals. These data suggest that morphine, injected into the spinal cord, does not produce behavioural analgesia by activation of local adrenergic systems.

Analgesics↗
PubMed1986

Arterial isoflurane concentration and EEG burst suppression during cardiopulmonary bypass.

Isoflurane (1.5 to 3.0 vol% in oxygen) was used to control intraoperative hypertension in 10 patients undergoing hypothermic cardiopulmonary bypass surgery. Isoflurane was administered through the membrane oxygenator of the bypass pump and yielded plateau concentrations in arterial blood ranging from 36.6 to 84.4 micrograms/ml (0.5 and 1.16 vol%, respectively). Isoflurane dosing resulted in prolonged periods (21 to 63 minutes) of EEG burst suppression and isoelectric activity in nine patients. Burst suppression was not a result of hypothermia. There was a close temporal relationship between isoflurane concentration and the onset of burst suppression (mean onset time: 27.3 +/- 4.56 minutes after isoflurane begun). The mean arterial isoflurane concentration at the onset of burst suppression was 46.5 +/- 10.7 micrograms/ml; the nasopharyngeal temperature was 26.0 degrees +/- 0.61 degrees C. Isoflurane was eliminated rapidly from blood with a mean apparent t1/2 of 18.8 +/- 5.46 minutes.

Adult↗
PubMed1985

A comparative study of the inhibition of hepatic aldehyde dehydrogenases in the rat by methyltetrazolethiol, calcium carbimide, and disulfiram.

Methyltetrazolethiol (1-methyl-5-mercapto-1,2,3,4-tetrazole, MTT) is a heterocyclic substituent of the cephalosporin antibiotics, cefamandole, cefoperazone, and moxalactam. Pretreatment of rats with MTT has been reported to increase blood acetaldehyde concentration after ethanol administration. The time course of MTT-induced inhibition of hepatic aldehyde dehydrogenases (ALDH) was determined in adult, male Sprague-Dawley rats in comparison with the hepatic ALDH inhibition induced by calcium carbimide (calcium cyanamide, CC) and disulfiram (D). The apparent onset of maximal inhibition of hepatic low Km ALDH occurred at 2 h for 50 mg/kg MTT (subcutaneous, s.c.) and 7 mg/kg CC (oral) and at 24 h for 300 mg/kg D (oral). The relative magnitude of maximal inhibition of low Km ALDH was CC greater than D greater than MTT. The relative duration of enzyme inhibition was D greater than MTT greater than CC. High Km ALDH was only inhibited by CC. Hepatic low Km ALDH was selectively inhibited by s.c. and oral administration of 125 mg/kg MTT. For s.c. administration of 125 mg/kg MTT, the magnitude of maximal enzyme inhibition and the duration of inhibition were greater than for the 50 mg/kg dose. Oral administration of 125 mg/kg MTT produced similar inhibition of hepatic low Km ALDH compared with s.c. administration of the same dose. The time course of blood ethanol and acetaldehyde concentrations was determined for the intravenous infusion of two 0.3-g/kg doses of ethanol to rats that were pretreated orally with saline (1 h), MTT (125 mg/kg, 2 h), or CC (7 mg/kg, 1 h). The relative increase in blood acetaldehyde concentration compared with saline pretreatment was CC greater than MTT. The elimination of ethanol from blood was slower in the MTT- and CC-pretreated animals, and this effect was more pronounced for CC pretreatment. Overall, the data demonstrate that the characteristics of hepatic ALDH inhibition for MTT are different from those of the known ALDH inhibitors, CC and D.

Acetaldehyde↗
PubMed1985

Analgesia and autonomic function following intrathecal administration of morphine and norepinephrine to the rat.

The acute intrathecal (i.t.) administration of 10, 25, 50, and 100 microgram morphine and 7.5, 10, 15, and 30 microgram (-)norepinephrine (NE) to the rat produced dose-dependent, long-lasting analgesia as assessed by the tail-flick and hot-plate tests. For i.t. morphine, maximum analgesia was observed 30-60 min after drug administration. The duration of analgesia in the tail-flick test ranged from 30 to 150 min; the duration of analgesia in the hot-plate test ranged from 60 to 120 min. For i.t. NE, maximum analgesia was observed 15-60 min after drug infusion. The duration of NE-induced analgesia in the hot-plate test ranged from 45 to 120 min and was 120 min in the tail-flick test. The effects of acute i.t. and intravenous (i.v.) infusions of morphine (10 microgram) and NE (15 microgram) on heart rate, blood pressure, arterial pH, partial pressure of oxygen (Po2), partial pressure of carbon dioxide (Pco2), and standard bicarbonate were determined over 45 min in rats anesthetized with alpha-chloralose (70 mg/kg). Morphine significantly decreased Po2 throughout the experiment but did not affect blood pressure, heart rate, pH, Pco2 and standard bicarbonate. A significant increase in blood pressure (137% of control) was observed 2.5 min after i.t. administration of NE. Intravenous NE produced a marked increase in blood pressure (246% of control) followed by a compensatory decrease in heart rate. There were no significant changes in blood gases with i.t. and i.v. NE. The data suggest that i.t. morphine and NE can produce effective analgesia with minimal effects on cardiovascular and respiratory function.

Analgesia↗