Electrocardiographic evidence for cocaine cardiotoxicity in cat

Recent case studies suggest that cocaine overdose may produce life-threatening cardiac arrhythmias. We therefore investigated its effects on the electrocardiogram (leads II and V1) and arterial blood pressure in cats anesthetized with pentobarbital. Cocaine was administered by intravenous infusion over a 2-min interval at 1 mg/kg in 10 cats. In 5 out of 10 cats an additional infusion of 3 mg/kg cocaine was also administered after hemodynamic and electrocardiographic parameters had returned to control values (i.e., within 10 min). During and following infusion of 1 mg/kg cocaine, no significant change in heart rate or systolic or diastolic blood pressure were found, however the QRS duration increased by 38% (from 46 +/- 5 to 64 +/- 12 ms) (p less than 0.01). Evidence for bundle branch block and (or) premature ventricular beats was observed in 9 out of 10 cats after 1 mg/kg cocaine. Infusion of a further 3 mg/kg cocaine in five cats significantly lowered diastolic blood pressure (from 98 +/- 18 to 64 +/- 28 mmHg; 1 mmHg = 133.3 Pa) (p less than 0.01), and further prolonged QRS to 79 +/- 14 ms, a 75% increase from the mean control value (p less than 0.01). In addition, 1st and 2nd degree atrioventricular block, ventricular extrasystoles, and ectopic rhythms (AV junctional or idioventricular) were observed in four out of five cats given 3 mg/kg cocaine. Mean plasma concentrations of cocaine were 1.37 +/- 0.39 micrograms/mL (4.28 +/- 1.22 microM) (n = 5) at the end of a 1 mg/kg infusion and 2.93 +/- 0.43 micrograms/mL (9.16 +/- 1.34 microM) after a 3 mg/kg infusion (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nitrendipine: an antidote to cardiac and lethal toxicity of cocaine

Nitrendipine, a Ca2+ modulator was tested in the rat as an antagonist to the cardiac toxicity of cocaine and as an antidote to the acute lethal effects of this drug. In a first series of experiments, nitrendipine (1.46 X 10(-3) mg/kg/min) when simultaneously administered intraarterially with cocaine (2 mg/kg/min) suppresses the arrhythmias induced by cocaine and increases survival time from 73 +/- 33 min to 309 +/- 118 min and the lethal dose of cocaine from 146 +/- 66 mg/kg to 618 +/- 236 mg/kg (p less than 0.003). Nitrendipine also protects the heart from the acute morphological lesions induced by cocaine administration and antagonizes some of the central effects of cocaine. In a second series, 5 rats administered 60 mg/kg of cocaine intraperitoneally had a survival time of 8'06 +/- 5'20. Death was attributed to convulsions and respiratory arrest. Animals treated with nitrendipine (129 +/- 23 mg/kg) 4'30" after cocaine administration survived. Nitrendipine appears to have general protective effects against cocaine cardiac toxicity and the acute lethal effects of this alkaloid.     

Field immobilization of bighorn sheep with xylazine hydrochloride and antagonism with idazoxan

Xylazine hydrochloride was used to immobilize 124 Rocky Mountain bighorn sheep (Ovis canadensis canadensis) between 1983 and 1988. Doses of xylazine for free-ranging lambs ranged from 70 to 130 mg with amounts increasing with lamb age. Average doses for 11 free-ranging adult males and 21 adult females darted from the ground were (means +/- SE) 363 +/- 16 and 251 +/- 7 mg, respectively. Adult females captured in "Stevenson's " box traps (n = 7) could be immobilized with significantly (P less than 0.001) less xylazine (93 +/- 9 mg) than free-ranging females but had similar induction times. Long recovery times associated with xylazine immobilization were eliminated with the intravenous administration of idazoxan (RX 781094) at an approximate dosage of 0.1 mg/kg. Eighteen sheep given idazoxan appeared fully recovered within 3 min of injection (means +/- SE = 1.2 +/- 0.2 min). Four mortalities (three lambs, one yearling male) (3% of total) occurred before idazoxan was available for trial.     

Indomethacin does not potentiate renovascular constriction during hypercapnia in unanesthetized rabbits

The role of prostanoids in regulation of the renal circulation during hypercapnia was examined in unanesthetized rabbits. Renal blood flow (RBF) was determined with 15 micron radioactive microspheres during normocapnia (PaCO2 congruent to 30 mmHg) and hypercapnia (PaCO2 congruent to 60 mmHg), before and after intravenous administration of indomethacin (10 mg/kg) or vehicle (n = 6 for each group). Arterial blood pressure was not different among the 4 conditions in each group. RBF was 438 +/- 61 and 326 +/- 69 (P less than 0.05) ml/min per 100 g during normocapnia and hypercapnia, respectively, before indomethacin, and following administration of indomethacin, RBF was 426 +/- 59 ml/min per 100 g during normocapnia and 295 +/- 60 ml/min per 100 g during hypercapnia (P less than 0.05). In the vehicle group, RBF was 409 +/- 74 and 226 +/- 45 (P less than 0.05) ml/min per 100 g during normocapnia and hypercapnia, respectively, before vehicle; and following administration of vehicle, RBF was 371 +/- 46 ml/min per 100 g during normocapnia and 219 +/- 50 (P less than 0.05) ml/min per 100 g during hypercapnia. RBF during normocapnia was not affected by administration of indomethacin or vehicle. The successive responses to hypercapnia were not different within the indomethacin and vehicle groups, and the second responses to hypercapnia were not different between the two groups. These findings suggest that prostanoids do not contribute significantly to regulation of the renal circulation during normocapnia and hypercapnia in unanesthetized rabbits.     

Use of xylazine sedation with yohimbine antagonism in captive gray wolves

Captive gray wolves (Canis lupus) were given 2.2 mg/kg xylazine hydrochloride intramuscularly resulting in profound sedation in 9.1 +/- 0.6 min (mean +/- SE). Heart rate was 42.0 +/- 1.0 beats per minute and respiratory rate was 20.1 +/- 1.6 respirations per minute during sedation. A variety of manipulations could be performed on sedated animals in relative safety. Thirty min after xylazine administration, the animals were given either 0.15 mg/kg yohimbine hydrochloride or 5% dextrose solution intravenously causing recovery in 5.3 +/- 1.0 and 97.1 +/- 14.0 min, respectively (P less than 0.001).     

ACTH-, glucose- and lactate-content of swine plasma during insulin-induced hypoglycemia]

The present investigation was undertaken to determine the content of ACTH, glucose and lactate in plasma of 4 pigs (body weight 82--118 kg) during a circadian period and during an insulin hypoglycemia test using 1 IU/kg in 3 pigs (body weight 96--118 kg) and 4 pigs (body weight 20--30 kg). The plasma ACTH level at rest was 57 +/- 27 pg/ml (Mean +/- SE) for all samples in all animals during a circadian period. Significant diurnal changes were not observed. During insulin-induced hypoglycaemia plasma ACTH rose from a mean (+/- SE) basal level of 35 +/- 15 to a maximum of 673 +/- 100 pg/ml at 60 min in heavier pigs and in lighter pigs to 395 +/- 153 at 30 min and 403 +/- 145 pg/ml at 120 min. Initial ACTH responses were evident 30 min (heavier pigs) and between 0 and 15 min (lighter pigs) after insulin administration. Plasma glucose decreased from a mean (+/- SE) basal level of 80 +/- 10 to a minimum of 6 +/- 1 mg/100 ml at 60 min (heavier pigs) and from 88 +/- 3 to 16 +/- 4 mg/100 ml at 60 min (lighter pigs). After its minimum level the glucose concentration showed a slower increment in the heavier pigs as compared to lighter animals. Plasma lactate rose from a mean (+/- SE) basal level of 19 +/- 10 to a maximum of 76 +/- 42 mg/100 ml at 120 min (heavier pigs) and from 12 +/- 3 to 37 +/- 16 mg/100 ml at 150 min (lighter group). In accordance with the changes in the blood plasma levels of ACTH, glucose and lactate, the clinical symptoms of hypoglycaemia in heavier pigs were more intensive.     

Inhibition of ischemia/reperfusion-induced damage by dexamethasone in isolated working rat hearts: the role of cytochrome c release

We investigated the contribution of dexamethasone treatment on the recovery of postischemic cardiac function and the development of reperfusion-induced arrhythmias in ischemic/reperfused isolated rat hearts. Rats were treated with 2 mg/kg of intraperitoneal injection of dexamethasone, and 24 hours later, hearts were isolated according to the 'working' mode, perfused, and subjected to 30 min global ischemia followed by 120 min reperfusion. Cardiac function including heart rate, coronary flow, aortic flow, and left ventricular developed pressure were recorded. After 60 min and 120 min reperfusion, 2 mg/kg of dexamethasone significantly improved the postischemic recovery of aortic flow and left ventricular developed pressure from their control values of 10.7 +/- 0.3 ml/min and 10.5 +/- 0.3 kPa to 22.2 +/- 0.3 ml/min (p < 0.05) and 14.3 +/- 0.5 kPa (p < 0.05), 19.3 +/- 0.3 ml/min (p < 0.05) and 12.3 +/- 0.5 kPa (p < 0.05), respectively. Heart rate and coronary flow did not show a significant change in postischemic recovery after 60 or 120 min reperfusion. In rats treated with 0.5 mg/kg of actinomycin D injected i.v., one hour before the dexamethasone injection, suppressed the dexamethasone-induced cardiac protection. Electrocardiograms were monitored to determine the incidence of reperfusion-induced ventricular fibrillation. Dexamethasone pretreatment significantly reduces the occurrence of ventricular fibrillation. Cytochrome c release was also observed in the cytoplasm. The results suggest that the inhibition of cytochrome c release is involved in the dexamethasone-induced cardiac protection.     

Chemical immobilization of free-ranging North American bison (Bison bison) in Badlands National Park, South Dakota

Twenty-six free-ranging North American bison (Bison bison) (22 adult bulls, one yearling male and three adult females) were immobilized using a combination of carfentanil and xylazine. For carfentanil the dose range (mean +/- SD) was 1.8-5.0 micrograms/kg (2.4 +/- 0.7 micrograms/kg) and for xylazine 0.004-0.125 mg/kg (0.07 +/- 0.03 mg/kg). Induction time (mean +/- SE) was 14.2 +/- 2.9 min (median 8 min), while the total mean reversal time after administration of a narcotic antagonist was 9.0 +/- 1.4 min (median 8 min). Only one animal that received the highest initial dose of carfentanil (2.5 mg) showed evidence of becoming "re-narcotized." Five animals required two or more doses of carfentanil before becoming immobilized. Overall, small volumes of drug used (mean = 0.62 ml for carfentanil, 0.53 ml for xylazine) enabled the use of 1 to 2 ml darts, increasing both accuracy and impact safety. Darting success approached 100%.     

ACE activity during the hypotension produced by standardized aqueous extract of Cecropia glaziovii Sneth: A comparative study to captopril effects in rats

To evaluate the effect of the standardized aqueous extract (AE) of Cecropia glaziovii Sneth on the plasma angiotensin I converting enzyme (ACE-EC 3.4.15.1) activity, rats were treated with a single dose of AE (1 g/kg, p.o.) or repeatedly (0.5 g/kg/bid, p.o.) for 60 days. Captopril (50 mg/kg, p.o.) was used as positive control on the same animals. The effects on the blood pressure were recorded directly from the femoral artery (single dose), or indirectly by the tail cuff method (repeated doses) in conscious rats. The plasma ACE activity was determined spectrofluorimetrically using Hypuril-Hystidine-Leucine as substrate. The arterial blood pressure, heart rate and plasma ACE activity were not significantly modified within 24 h after a single dose administration of AE. Comparatively, blood pressure in captopril treated rats was reduced by 7-16% and heart rate was increased by 10-20% from 30 min to 24 h after drug administration. ACE activity after captopril presented a dual response: an immediate inhibition peaking at 30 min and a slow reversal to 32% up-regulation after 24 h. To correlate the drug effects upon repeated administration of either compound, normotensive rats were separated in three groups: animals with high ACE (48.8+/-2.6 nmol/min/ml), intermediate ACE (39.4+/-1.4 nmol/min/ml) and low ACE (23.5+/-0.6 nmol/min/ml) activity, significantly different among them. Repeated treatment with AE reduced the mean systolic blood pressure (121.7+/-0.5 mm Hg) by 20 mm Hg after 14 days. The hypotension was reversed upon washout 60 days afterwards. Likely, repeated captopril administration decreased blood pressure by 20 mm Hg throughout treatment in all groups. After 30 days treatment with AE (0.5 g/kg/bid, p.o.) the plasma ACE activity was unchanged in any experimental group. After captopril (50 mg/kg/bid, p.o.) administration the plasma ACE activity was inhibited by 50% within 1 h treatment but it was up-regulated by 120% after 12 h in all groups. It is concluded that the hypotension produced by prolonged treatment with AE of C. glaziovii is unrelated to ACE inhibition.     

Effect of various doses of cocaine on endurance capacity in rats

To determine the effects of a variety of doses of cocaine on endurance capacity, rats were injected intraperitoneally with either 0.1, 0.5, 2.5, 12.5, or 20 mg/kg body wt 20 min before running to exhaustion at 26 m/min up a 10% grade. Animals given saline ran 116 +/- 9 (SE) min. At doses of 12.5 and 20 mg/kg, cocaine reduced endurance time significantly (34 and 74%, respectively). At rest the drug had no effect on liver or fast-twitch muscle glycogen but significantly reduced (20-40%) soleus glycogen at the two highest doses. However, at exhaustion, the quantity of glycogen depleted in the fast-twitch red and white vastus muscles was similar in all groups despite the reduced run times of the animals receiving a higher dose implying a greater rate of glycogenolysis due to cocaine. Blood lactate in the 20 mg/kg group (9.9 +/- 1.2 mM) at exhaustion was nearly twice that of the saline controls at exhaustion (5.1 +/- 0.6). Before exercise plasma norepinephrine (at doses of 2.5, 12.5 and 20 mg/kg) was higher than saline controls and remained higher (20 mg/kg groups) at exhaustion. We conclude that high doses of cocaine cause rapid muscle glycogen depletion and early fatigue. The mechanism by which cocaine causes these effects is not clear.     

Cardiovascular responses to an isosterically modified prostaglandin analog in conscious dogs

The cardiovascular effects of oral and intravenous administration of 0.05 and 0.1 mg/kg of the isosterically modified prostaglandin (PG) analog, (+)- 4-(3-[3-[2-(1-hydroxycyclohexyl)ethyl]-4-oxo-thiazolidinyl] propyl) benzoic acid were ascertained in conscious mongrels. After 0.05 mg/kg p.o., mean arterial pressure (MAP), obtained from indwelling catheters, fell from 105 +/- 1 to 100 +/- 4 mm Hg and total peripheral resistance (TPR) decreased from 0.062 +/- 0.006 to 0.039 +/- 0.002 mm Hg/ml/min. Cardiac output (CO), measured via electromagnetic flow probes, rose from 1.8 +/- 0.2 to 2.6 +/- 0.1 l/min and heart rate from 109 +/- 13 to 128 +/- 8 beats/min. The 0.1 mg/kg p.o. dose produced similar results. Intravenous injection of 0.1 mg/kg immediately dropped MAP from 103 +/- 6 to 58 +/- 3 mm Hg and TPR from 0.049 +/- .006 to .014 +/- .002 mm Hg/ml/min. CO climbed from 2.3 +/- 0.2 to 5.3 +/- 0.5 l/min and HR increased from 126 +/- 9 to 254 +/- 14 beats/min. Stroke volume was not affected by either oral or intravenous administration of the PG analog. Pretreatment with 100 micrograms/kg timolol blunted the CO and HR responses to 0.1 mg/kg iv of the PG analog without affecting the depressor response. Metaraminol infused during injection of 0.1 mg/kg iv of the PG analog diminished all responses. When compared to the cardiovascular effects of hydralazine and nitroprusside, the profile of the PG analog activity closely resembled that produced by the arterial vasodilator, hydralazine; in contrast, nitroprusside (which also dilates veins) reduced stroke volume, but did not significantly affect HR. In conclusion, dilation of the resistance vessels by the PG analog decreased MAP and TPR and reflexly elevated CO and HR in conscious dogs.     

Diuretic, natriuretic and hypotensive effects of synthetic atrial natriuretic factor in conscious newborn calves

The effects of synthetic Atrial Natriuretic Factor (ANF) on urine flow rate, sodium excretion, potassium excretion and arterial blood pressure were studied in 10-12 days-old female calves. In four female calves fitted with a Foley catheter, an intravenous administration of ANF (Ile-ANF 26; 1.6 micrograms/kg body wt during 30 min) induced an increase (P less than 0.01) in urine flow rate (from 1.8 +/- 0.2 to 12.8 +/- 1.1 ml/min), sodium excretion (from 0.15 +/- 0.02 to 0.81 +/- 0.06 mmol/min) and free water clearance (from 0.13 +/- 0.9 to 5.16 +/- 0.5 ml/min). It had no significant effect on potassium excretion. In four calves chronically-instrumented with a carotid catheter, an intravenous administration of synthetic ANF alone (1.6 micrograms/kg body wt during 30 min) induced a gradual decrease (P less than 0.01) in systolic, diastolic and mean arterial blood pressure (from 112 +/- 4 to 72, from 72 +/- 2 to 61 +/- 1 and from 90 +/- 2 to 65 +/- 2 mmHg respectively, at the end of ANF infusion). An intravenous administration of angiotensin II (AII) (0.5 micrograms/kg body wt during 45 min) induced a significant increase in systolic, diastolic and mean arterial blood pressure which was antagonized by an i.v. bolus injection of ANF (0.125 micrograms/kg body wt). However, during a simultaneous administration of AII (0.3 micrograms/kg body wt during 30 min) and ANF (1.6 micrograms/kg body wt. during 30 min), the atrial peptide did not influence the pressure action of AII. These findings indicate that the conscious newborn calf is sensitive to diuretic, natriuretic and hypotensive effects of synthetic ANF.     

Influence of endogenous opioids on the response of selected hormones to exercise in humans

To examine the influence of endogenous opioids on the hormonal response to isotonic exercise, eight males were studied 2 h after oral administration of placebo or 50 mg naltrexone, a long-lasting opioid antagonist. Venous blood samples were obtained before, during, and after 30 min of bicycle exercise at 70% VO2max. Naltrexone had no effect on resting cardiovascular, endocrine, or serum variables. During exercise epinephrine was higher [mean 433 +/- 100 (SE) pg/ml] at 30 min with naltrexone than during placebo (207 +/- 26 pg/ml, P less than 0.05). Plasma norepinephrine showed the same trend but the difference (2,012 +/- 340 pg/ml with naltrexone and 1,562 +/- 241 pg/ml with placebo) was not significant. Plasma glucose was higher at all times with naltrexone. However, the difference was significant only 10 min into recovery from exercise (104.7 +/- 4.7 vs. 94.5 +/- 2.8 mg/dl). Plasma growth hormone and cortisol increased during recovery and these elevations were significantly (P less than 0.05) augmented by naltrexone. Plasma vasopressin and prolactin increased with exercise as did heart rate, blood pressure, lactic acid, and several serum components; these increases were not affected by naltrexone. Psychological tension or anxiety was lower after exercise compared with before and this improved psychological state was not influenced by the naltrexone treatment. These data suggest that exercise-induced activation of the endogenous opioid system may serve to regulate the secretion of several important hormones (i.e., epinephrine) during and after exercise.     

Increased leukotriene C4 in ethchlorvynol-induced acute lung injury in dogs

We investigated whether ethchlorvynol (ECV)-induced acute lung injury (ALI) is associated with an increase in leukotriene C4 (LTC4) production. In six pentobarbital sodium-anesthetized dogs, ECV (15 mg/kg iv) introduced into the pulmonary circulation resulted in a 164 +/- 31% increase in extravascular lung water 120 min after ECV administration. Concomitantly, the mean (+/- SE) concentration of LTC4 in arterial plasma measured by radioimmunoassay following 80% EtOH precipitation, XAD-7 extraction and high-pressure liquid chromatography purification was 5.0 +/- 1.3 pg/ml, unchanged from control (pre-ECV) values. In contrast, in pulmonary edema fluid 120 min post-ECV, the LTC4 concentration was 35.2 +/- 10.8 pg/ml, sevenfold greater than those values found in the arterial plasma (P less than 0.01). In six additional dogs, 120 min after unilateral ALI had been induced with ECV (9 mg/kg iv), LTC4 in the bronchoalveolar lavage (BAL) of the uninjured lung was 12.1 +/- 1.5 pg/ml, unchanged from pre-ECV values, whereas, LTC4 in the BAL of the injured lung increased from a control value of 10.2 +/- 1.6 to 24.2 +/- 3.5 pg/ml (P less than 0.01) 120 min after ECV administration. These results demonstrate that, in ECV-induced acute lung injury, LTC4 concentrations in pulmonary edema fluid are considerably greater than those found in arterial plasma in the case of bilateral acute lung injury and significantly greater in the BAL of the injured lung compared with the uninjured lung in the case of unilateral acute lung injury. The results are a necessary first step in support of the hypothesis that leukotrienes participate in the altered permeability of ECV-induced acute lung injury.     

Persistent changes in arterial blood gases in fetal sheep

Two anaesthetic protocols were compared using pregnant sheep. In both groups of animals, anaesthesia was induced using an intravenous (i.v.) injection of diazepam and ketamine. The ewes were then intubated for positive pressure ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8% halothane. If the ewe showed any signs of awakening, one of two protocols was followed. First, the halothane concentration was increased to 2-3% until the ewe was completely anaesthetized. Second, the halothane concentration was not altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1 mg/kg) until again completely anaesthetized. At the completion of surgery, maternal recovery was rapid and similar between the two groups. However, five days after surgery, the fetal arterial Po(2) and oxygen content of the fetuses receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were statistically significantly depressed when compared with the fetuses receiving additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL). These results led us to conclude that certain anaesthetic protocols, in spite of good maternal recovery, can lead to deleterious effects upon the fetus that persist for at least five days after surgery.     

Relationship of bispectral index values, haemodynamic changes and recovery times during sevoflurane or propofol anaesthesia in rabbits

The aim of this study was to determine and compare the degree of hypnosis achieved during propofol or sevoflurane anaesthesia in rabbits using bispectral index (BIS), and to evaluate its usefulness as a predictor of both haemodynamic changes during anaesthesia and recovery times. Twenty adult male New Zealand White rabbits, average weight 4.4 +/- 0.4 kg, were used for this study. Animals were randomly allocated to one of two groups with 10 rabbits/group. An electroencephalographic recording was obtained from each conscious rabbit prior to drug administration. All animals received buprenorphine as a preanaesthetic medication (0.05 mg/kg, intravenous [i.v.]). Anaesthesia was induced with propofol (8 mg/kg, i.v.) in all animals; 10 rabbits were maintained with sevoflurane via inhalation (1 minimum alveolar concentration--end-tidal sevoflurane concentration of 3.7%--at a fresh gas flow rate of 3 L/min; group I), and 10 were maintained with i.v. propofol (0.6 mg/kg/min; group II). The rabbits were orotracheally intubated and spontaneous ventilation was maintained throughout the study (100% oxygen). After abdominal surgery through a ventral midline laparotomy, rabbits were allowed to recover from anaesthesia. Cardiovascular variables and BIS values were recorded at intervals throughout the procedure, as was the duration of recovery from anaesthesia. In both groups, mean BIS values were significantly decreased immediately after induction, compared with baseline values obtained during consciousness. Anaesthetic depth (evaluated by clinical observation) was similar in both groups; however, group II rabbits had significantly higher (P<0.001) BIS values from 30 s before incision until anaesthesia was discontinued. There was no significant difference in BIS recorded 1 and 5 min after incision as compared with values obtained 30 s before incision in either group. During sevoflurane or propofol administration, correlations were found between BIS values and mean arterial blood pressure (MABP), and between BIS values and heart rate (HR). Mean BIS values at discontinuation of administration of the anaesthetic agent were greater in group II (69.1 +/- 6.0) than in group I (49.3 +/- 2.2). However, recovery from anaesthesia was significantly longer in group II (38.4 +/- 7.2 min) than in group I (11.5 +/- 2.5 min). In conclusion, BIS can be used to differentiate between conscious and unconscious states during anaesthesia in rabbits. BIS values derived from an electroencephalogram at the end of anaesthesia were not useful for predicting the speed of anaesthetic recovery in sevoflurane or propofol-anaesthetized rabbits undergoing abdominal surgery. Despite the correlation found between BIS and haemodynamic parameters, its usefulness as a predictor of clinically important changes in arterial blood pressure and HR in anaesthetized rabbits was limited.     

Failure of naloxone to stimulate luteinizing hormone secretion during pregnancy and steroid treatment of ovariectomized beef cows

The response of serum luteinizing hormone (LH) to naloxone, an opiate antagonist, and gonadotropin-releasing hormone (GnRH) was measured in cows in late pregnancy to assess opioid inhibition of LH. Blood samples were collected at 15-min intervals for 7 h. In a Latin Square arrangement, each cow (n = 6) received naloxone (0, 0.5, and 1.0 mg/kg BW, i.v.; 2 cows each) at Hour 2 on 3 consecutive days (9 +/- 2 days prepartum). GnRH (7 ng/kg body weight, i.v.) was administered at Hour 5 to all cows on each day. Mean serum LH concentrations (x +/- SE) before naloxone injection were similar (0.4 +/- 0.1 ng/ml), with no serum LH pulses observed during the experiment. Mean serum LH concentrations post-naloxone were similar (0.4 +/- 0.1 ng/ml) to concentrations pre-naloxone. Mean serum LH concentrations increased (p less than 0.05) following GnRH administration (7 ng/kg) and did not differ among cows receiving different dosages of naloxone (0 mg/kg, 1.44 +/- 0.20; 0.5 mg/kg, 1.0 +/- 0.1; 1.0 mg/kg, 0.9 +/- 0.1 ng/ml). In Experiment 2, LH response to naloxone and GnRH was measured in 12 ovariectomized cows on Day 19 of estrogen and progesterone treatment (5 micrograms/kg BW estrogen: 0.2 mg/kg BW progesterone) and on Days 7 and 14 after steroid treatment. On Day 19, naloxone failed to increase serum LH concentrations (Pre: 0.4 +/- 0.1; Post: 0.4 +/- 0.1 ng/ml) after 0, 0.5, or 1.0 mg/kg BW.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of medium-chain triglyceride feeding or glucose infusion on glucose kinetics in the newborn rat

Hypoglycaemia which develops in starved newborn rats (0.15 +/- 0.01 mg/ml) is reversed by feeding medium-chain triglycerides (0.66 +/- 0.05 mg/ml). Despite similar glycaemia (0.71 +/- 0.07 mg/ml) starved newborns infused with glucose (10.7 mg/min/kg) show a 30% higher glucose turnover rate than medium-chain triglyceride fed animals (14.1 +/- 0.6 versus 10.6 +/- 0.3 mg/min/kg, p less than 0.01). For a comparable [6-3H]glucose turnover rate (10.5 +/- 0.3 mg/min/kg), glucose-infused (5.25 mg/min/kg) newborns have a 30% lower glycaemia (0.50 +/- 0.03 mg/ml, p less than 0.01) than medium-chain triglyceride-fed newborns. Thus, medium chain triglyceride feeding leads to a 30% decreased capacity of the tissues to utilize glucose. For a similar glucose turnover rate, medium-chain triglyceride-fed newborns have a higher blood lactate concentration than glucose-infused newborns (0.26 +/- 0.03 versus 0.15 +/- 0.02 mg/ml). However, in medium-chain triglyceride-fed newborns, the increase of blood lactate is not only due to the Cori cycle, as glucose recycling is less increased than glucose production. Thus medium-chain triglyceride increases the release of gluconeogenic precursors which are not derived from blood glucose. In presence of a glucose infusion (15.25 mg/min/kg) producing hyperglycaemia (1.35 +/- 0.05 mg/ml), endogenous glucose production is suppressed by only 37%. If 3-mercaptopicolinate, an inhibitor or gluconeogenesis, is given concomitantly, hyperglycaemia is prevented (0.72 +/- 0.08 mg/ml) and endogenous glucose production is suppressed. Glucose infusion in the hypoglycaemic newborn rat might thus lead to a precarious glucose homeostasis.     

Butorphanol/xylazine/ketamine immobilization of free-ranging Baird's tapirs in Costa Rica

Cardiopulmonary effects and the utility of a butorphanol/xylazine/ketamine combination were evaluated during twenty immobilizations of sixteen Baird's tapirs (Tapirus bairdii) between March 1996 and January of 1998 in Corcovado National Park (Costa Rica). The animals were attracted to a bait site and darted from tree platforms. The tapirs were estimated to weigh between 200 to 300 kg. Actual weights of three tapirs taken at later dates fell within the estimated range. A butorphanol, 48+/-1.84 (x +/- SE) mg/animal IM, and xylazine, 101+/-2.72 mg/animal IM, combination was used to immobilize the animals. In some instances, ketamine was used either IM or IV at 187+/-40.86 mg/animal to prolong the immobilization period in addition to the butorphanol/xylazine combination. Naltrexone was used IM to reverse butorphanol at 257+/-16.19 mg/animal. Either yohimbine, 34+/-0.61 or tolazoline at 12+/-10.27 mg/animal, was used to reverse xylazine. The mean time from dart impact to first visible effect was 4.63+/-0.50 min (x +/- SE). Mean time to sternal recumbency was 12.21+/-1.08 min. Mean time the tapirs were immobilized was 45.63+/-3.6 min. Mean time to return to sternal recumbency and standing in animals that received yohimbine and naltrexone was 3.16+/-1.06 and 5.33+/-1.45 min, respectively. Mean time to return to sternal recumbency and standing in animals that received tolazoline and naltrexone was 1.57+/-0.39 and 3.14+/-0.51 min, respectively. Cardiopulmonary parameters including heart rate, respiratory rate, body temperature, electrocardiogram, percent oxygen satoration, and indirect blood pressure were recorded. Arterial blood gas analysis was performed on four animals. A mild degree of hypoxemia was evidenced by low arterial oxygen saturations. Five of 14 (36%) animals measured had oxygen saturations below 90%. Bradycardia (heart rates <45 BPM) was an expected finding in 11 (55%) immobilizations. Induction, recovery and muscle relaxation of each immobilization was graded. Premature arousal, which occurred in six (30%) animals, was the only problem associated with the immobilizations. Butorphanol/xylazine is a recommended protocol for immobilization of calm, free-ranging tapirs lasting less than 30 min. Supplemental intravenous administration of ketamine is recommended for longer procedures. Nasal insufflation of oxygen is recommended.     

Effect of acute or daily cocaine administration on cellular immune response and virus infection in mice

The effects of in vivo cocaine administrations on cellular cytotoxicity were studied. Cocaine induced a dose-related immunosuppression of natural killer cell activity, with maximal depression at 1-5 mg/kg. In addition, the degree of inhibition following a single intraperitoneal (i.p.) or intravenous cocaine dose (acute treatment, 1 mg/kg) was similar to that after repeated administration (subchronic treatment: 1 mg/kg/day i.p. for 7 consecutive days or subcutaneous administration by Alzet 2001 osmotic minipumps). T cells from cocaine-treated mice failed to generate cytotoxic T lymphocytes (CTL) in mixed lymphocyte cultures and acute or subchronic cocaine treatment also inhibited CTL generation in vivo. On the other hand, acute administration induced a very rapid (24-hour) inhibition of natural cytotoxicity, with a return to normal within 72 h after treatment. By contrast, repeated doses led to more protracted immunologic consequences and a delayed recovery (144 h). The effect of cocaine on susceptibility to influenza virus (PR8) infection was also investigated. Both acute and subchronic treatment significantly decreased resistance to PR8 infection. The results clearly indicate that cocaine has a potent suppressive effect on cellular immunity and that abuse can adversely affect the outcome of infectious diseases.