Ciprofloxacin concentrations in serum, bone and bone marrow of rabbits

Ciprofloxacin concentrations were determined in serum, bone and bone marrow of rabbits. Four experimental groups of animals were examined: group A (n = 6) received a dosage of 60 mg/kg/day intramuscularly for 4 weeks, groups B (n = 6), C (n = 15) and D (n = 15) received dosages of 120 mg/kg/day subcutaneously for 2 days, 2 weeks, and 4 weeks, respectively. In the kinetic portion of the study, peak serum concentrations of ciprofloxacin measured at the 15 min sampling time were: 2.61 +/- 0.27 micrograms/ml in the 60 mg/kg/day group (group A) and 3.24 +/- 0.78 micrograms/ml in the 120 mg/kg/day group (group B). At necropsy, rabbits in group A had mean ciprofloxacin concentrations of 3.60 +/- 2.27 micrograms/ml in serum, 2.24 +/- 1.19 micrograms/g in marrow and 1.19 +/- 0.44 micrograms/g in bone. Rabbits in group B achieved mean levels of 4.02 +/- 1.23 micrograms/ml in serum, 2.48 +/- 0.79 micrograms/g in marrow, and 1.35 +/- 0.40 micrograms/g in bone. Rabbits in group C achieved mean levels of 5.65 +/- 2.16 micrograms/ml in serum, 3.74 +/- 1.33 micrograms/g in marrow and 1.92 +/- 0.94 micrograms/g in bone. Rabbits in group D achieved mean levels of 7.24 +/- 2.50 micrograms/ml in serum, 4.48 +/- 1.68 micrograms/g in marrow, and 1.93 +/- 0.54 micrograms/g in bone. Differences between mean values for the four experimental groups were not statistically significant.     

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%.     

Anesthesia of boma-captured Lichtenstein's hartebeest (Sigmoceros lichtensteinii) with a combination of thiafentanil,medetomidine, and ketamine

A dose range was determined for anesthesia of recently boma-captured Lichtenstein's hartebeest (Sigmoceros lichtensteinii) (n = 13) with the synthetic opiate thiafentanil (THIA) (formerly called A3080) combined with medetomidine (MED) and ketamine (KET) in the Kasungu National Park, Malawi on 4 to 5 September 1999. The dose range of 11-29 micrograms/kg THIA (mean +/- SD = 21 +/- 4 micrograms/kg) combined with 5-10 mg/kg MED (8 +/- 1 micrograms/kg) plus 0.7-1.4 mg/kg KET (1.1 +/- 0.2 mg/kg) was found to be safe and effective for the field conditions associated with this study. The anesthesia produced by this drug combination was very predictable and characterized by a short induction time (3:34 +/- 1:20 min:sec), good muscle relaxation, and acceptable physiologic parameters for anesthesia periods ranging from 22:30-35:00 min:sec (31:14 +/- 2:50). Within the range of doses used in this study, times to onset of initial effects and recumbency were not dependent on THAI, MED, or KET doses. Anesthesia was rapidly and completely reversed by intravenous injections of naltrexone at 30 times the THAI dosage (0.69 +/- 0.19 mg/kg) and atipamezole at about four times the MED dosage (38 +/- 14 micrograms/kg). There was no residual effect from ketamine noted following reversal of THIA and MED and no mortality or morbidity was associated with this anesthetic regimen.     

Fentanyl and medetomidine anaesthesia in the rat and its reversal using atipamazole and either nalbuphine or butorphanol.

The intraperitoneal injection of anaesthetic agents is a simple and convenient method of anaesthetizing rats. However, all of the anaesthetic combinations in current use which are administered by intraperitoneal injection produce prolonged sedation, and full recovery of consciousness may take several hours. Fentanyl, a mu agonist opioid, and medetomidine, an alpha 2-adrenoceptor agonist were mixed and administered as a single intraperitoneal injection. Combinations of 300 micrograms/300 micrograms/kg and 300 micrograms/200 micrograms/kg of fentanyl/medetomidine were shown to produce surgical anaesthesia in the rat. This anaesthetic regimen produced significant respiratory depression (P less than 0.01) and animals did not regain their righting reflex until 193 +/- 21 min (mean +/- 1 SD) after injection. Administration by intraperitoneal injection of atipamezole, a specific alpha 2-adrenoceptor antagonist (1 mg/kg) mixed with a mu antagonist/k agonist opioid (nalbuphine, 2 mg/kg or butorphanol 0.4 mg/kg), resulted in a rapid (less than 8 min) reversal of anaesthesia and the associated respiratory depression, and apparent full recovery of consciousness.     

High-density mapping of pulmonary veins and left atrium during ibutilide administration in a canine model of sustained atrial fibrillation

Ibutilide can prolong refractory period and terminate reentry. Whether ibutilide has the same effects on pulmonary vein (PV) focal discharge (FD) is unclear. We induced sustained atrial fibrillation (AF) in seven dogs by rapid left atrial (LA) pacing for 74 +/- 46 days. Ibutilide was repeatedly infused until it terminated AF (0.02 +/- 0.01 mg/kg) or when a cumulative dose was reached (0.04 mg/kg). High-resolution computerized epicardial mapping was performed. We found intermittent FD at the PVs and reentry at the PV-LA junction during AF. Ibutilide increased the cycle length of consecutive reentry from 97 +/- 13 to 112 +/- 18 ms and increased FD from 96 +/- 7 to 113 +/- 9 ms. In four dogs with both FD and reentry at the PVs, the incidence of reentry decreased from 3.5 +/- 1.9/s at baseline to 2.2 +/- 1.8/s after ibutilide administration. However, the incidence of FD remained unchanged. The conducted wave fronts between PV and LA were significantly reduced by ibutilide (10.4 +/- 2.0/s vs. 8.0 +/- 1.6/s). The ibutilide dose needed to terminate AF correlated negatively with the baseline effective refractory period of PV and LA. We conclude that ibutilide reduces reentrant wave fronts but not PV FD in a canine model of pacing-induced sustained AF. These findings suggest that the PV FD during AF is due to nonreentrant mechanisms. High doses of ibutilide may completely terminate all reentrant activity, converting AF to PV tachycardia before the resumption of sinus rhythm.     

Immobilization of gray wolves (Canis lupus) with sufentanil citrate

Gray wolves (Canis lupus) were immobilized with 0.5 mg/kg xylazine plus 7.5 micrograms/kg of either sufentanil (n = 8), etorphine (n = 8), or carfentanil (n = 2). Drug doses used in this study were selected to provide consistency for comparison and are not recommended doses for effective immobilization of wolves. Induction times were similar among groups (11.9 +/- 1.0 min). Thirty min after induction, wolves were given either 0.5 mg/kg naloxone hydrochloride plus 0.15 mg/kg yohimbine hydrochloride or saline only intravenously. Arousal times for wolves given naloxone and yohimbine (1.2 +/- 0.1 min) were shorter than wolves given saline (35.5 +/- 6.4 min). Respiratory rates were similar among the three drug groups (6.9 +/- 1.0 breaths/min). One animal given sufentanil then saline was found dead 108 min after induction. Presumptive diagnosis was renarcotization and hypothermia. Results indicated that sufentanil is an effective opioid immobilizing agent for gray wolves.     

异丙酚复合芬太尼静脉麻醉镇痛对门诊人工流产术的影响

目的:观察异丙酚复合芬太尼静脉麻醉对于人工流产术时及术后的影响。方法:选择2001年3月——2001年9月在本院计划生育门诊就诊、自愿要求无痛人工流产的妇女120例作为无痛人工流产组(简称:无痛组),同期按常规方法行人工流产的妇女120例作为对照组(简称:对照组),进行配对研究。无痛组用异丙酚1.5mg/kg复合芬太尼2μg/kg诱导,术中用异丙酚维持,人工流产术按常规方法施行。结果:无痛组术中异丙酚用量为2.7±0.7mg/kg,芬太尼2μg/kg,术中无知觉,120例妇女均无疼痛主诉。对照组轻度疼痛82例(68.3％),中度疼痛33例(27.5％),重度疼痛3例(4.2％)。无痛组在麻醉诱导及维持期间均出现呼吸频率下降,通过控制呼吸、面罩吸氧,SaO_2可以保持在99％以上,不需气管插管。两组妇女术前及术后宫腔深度无明显差异(P>0.05)。无痛组术中出血量为32.2±23.2ml,对照组为19.8±15.9ml,无痛组较对照组明显增多,有极显著统计学差异(P<0.01)。结论:异丙酚复合芬太尼静脉麻醉对人工流产术的主要影响是手术的出血量略增多,但不影响子宫收缩及术后恶露持续时间,该麻醉是一种有效镇痛方法,适用于门诊人工流产术。     

Immobilization of Himalayan tahr with a xylazine-ketamine mixture and reversal with atipamezole under field conditions

Twenty-nine free-ranging Himalayan tahr (Hemitragus jemlahicus) were darted in the Sagarmatha National Park (Nepal) using different combinations of xylazine and ketamine. Animals in Group 1 (n = 4) received a mean xylazine-ketamine dose of 2.77 +/- 0.99 mg/kg xylazine plus 3.32 +/- 0.19 mg/kg ketamine in males and 2.39 +/- 0.10 mg/kg xylazine plus 4.29 +/- 0.17 mg/kg ketamine in females. Animals in Group 2 (n = 25) received a mean xylazine-ketamine dose of 1.70 +/- 0.41 mg/kg xylazine plus 3.06 +/- 0.74 mg/kg ketamine in males and 1.82 +/- 0.29 mg/kg xylazine plus 3.29 +/- 0.52 mg/kg ketamine in females. No anesthetic-related mortality was recorded. Anesthesia was reversed by a standard dose of 11 mg/animal of atipamezole administered by intramuscular injection. Although all anesthetic dosages immobilized free-ranging tahr successfully, a quick and smooth recovery was obtained (11.1 +/- 5.6 min) only with the dosages of Group 2.     

舒芬太尼复合吗啡硬膜外术后镇痛的最佳剂量配伍

目的：观察腹式子宫全切术后硬膜外镇痛应用舒芬太尼复合吗啡时两种药物不同剂量的镇痛效果和不良反应,以寻找其最佳剂量配伍。方法：选择90例美国麻醉医师协会（ASA）标准Ⅰ-Ⅱ级、年龄20-60岁拟行腹式子宫全切术的病人,均实施腰硬联合麻醉。随机分成3组,每组30例：Ⅰ组：舒芬太尼10μg＋吗啡2 mg＋氟哌利多1 mg＋1%罗哌卡因20 mg;Ⅱ组：舒芬太尼15μg＋吗啡1.5 mg＋氟哌利多1 mg＋1%罗哌卡因20 mg;Ⅲ组：舒芬太尼20μg＋吗啡1 mg＋氟哌利多1 mg＋1%罗哌卡因20mg。术中监测生命体征,记录术后24小时内的镇痛效果、不良反应及辅助镇痛药物的使用情况。镇痛效果评价采用视觉模拟评分（visual analogue scale,VAS）标准。结果：2组各个时间点VAS评分均明显低于1组（P〈0.05）,在术后6 h,8 h,12 h,18 h,24 h与3组有统计学差异（P〈0.05）,3组在2 h,4 h,6 h的VAS评分低于1组（P〈0.05）;2组恶心评分与3组相比明显较低（P〈0.05）,其他不良反应三组间没有统计学差异;各组患者在术后24h内辅助镇痛药物使用情况比较无统计学差异（P〉0.05）。结论：舒芬太尼15μg复合吗啡1.5 mg用于腹式子宫全切术后硬膜外镇痛效果优于其他常用剂量配伍,镇痛效果平稳确切且不良反应少,具有临床应用价值。     

Effect of recombinant human growth hormone on urinary 15N-nitrogen balance in girls with Turner syndrome as compared to children with growth hormone deficiency

15N-nitrogen balances before and on human growth hormone (hGH) were studied in 13 girls with Turner syndrome (TS) aged 4.4-16 (median 13.2) years (45,X0 or equivalent, no X0/XX mosaicism, no estrogen replacement). The results were compared with those reported from 9 patients with growth hormone deficiency (GHD). The TS patients received subcutaneous hGH doses of 2 x 3 (group A, n = 6), 3 x 2 (group B, n = 3), or 2 x 6 (group C, n = 4) IU/m2 on consecutive days. The mean 15N dose given to the patients of groups A and C was higher (13.6 mg/kg) than that given to those of group B (2.7 mg/kg). The lower hGH doses in the first two groups induced small positive mean 15N balance changes (+0.6 +/- 0.6 mg/kg 15N, group A; +0.03 mg/kg, group B). The higher hGH dose in group C caused a more marked mean balance change (+3.0 mg/kg 15N) comparable to that in GHD patients (+3.2 mg/kg). Individual variation of response, however, was larger in patients with TS than in those with GHD. With low and high hGH doses, there were responders and nonresponders. It is concluded from this pilot study in a small number of cases that 15N balance studies might be potentially useful to choose the appropriate hGH dose for long-term treatment in TS patients.     

An outcome study comparing intravenous sedation with midazolam/fentanyl (conscious sedation) versus propofol infusion (deep sedation) for aesthetic surgery

The purpose of this study was to determine the differences in measurable outcomes following aesthetic procedures performed under intravenous sedation with incremental doses of midazolam and fentanyl and those performed under propofol infusion. The authors' hypothesis was that the differences in these outcome parameters are not significant between these intravenous sedation protocols. All intraoperative and perioperative records of 84 consecutive patients having aesthetic surgery under a conscious sedation protocol using incremental doses of intravenous midazolam and fentanyl were retrospectively reviewed and compared with the records of a second group of 85 patients having aesthetic surgery under a deep sedation regimen based primarily on propofol infusion. All procedures were hospital based and performed by two surgeons. Twenty-eight different parameters were examined by chart review. In addition, a patient questionnaire was used to assess patient satisfaction and patient recall of operative and perioperative pain, anxiety, nausea, and vomiting. Multivariate statistical analysis was conducted. The two sedation groups were similar with regard to aesthetic procedures performed and patient demographics. The mean duration of operative time was statistically equivalent (152 minutes and 153 minutes). In both groups, there were minor adverse intraoperative events reported but no significant complications. Transient hypotension was more common in the propofol infusion group (12.9 percent versus 2.4 percent, p = 0.018), but no patient required intervention beyond reducing the sedative agent or increasing intravenous fluids. The amount of supplemental fentanyl given intraoperatively was significantly higher in the group whose primary agent for sedation was propofol infusion than the group who received midazolam/fentanyl (209 mug and 143 mug, respectively). The overall questionnaire response rate was 80 percent for both groups. The midazolam/fentanyl sedation group had more recall of "unpleasant intraoperative events" (17 percent versus 3 percent, p = 0.007). However, both groups had low recall of intraoperative pain, anxiety, and nausea. The propofol infusion group experienced significantly more nausea in the recovery room (p = 0.002), nausea at the time of discharge (p = 0.009), and nausea the evening after the operation (p = 0.013). Greater than 90 percent of the patients in both groups would have the same anesthetic in the future rather than undergo general anesthesia. Patient safety, outcomes, and satisfaction are similar in plastic surgery procedures performed under sedation protocols using either incremental doses of midazolam and fentanyl or propofol infusion. All operative and postoperative outcomes for pain, anxiety, and vomiting were similar in the two groups except for immediate postoperative nausea, which was higher in the propofol infusion group. The overall satisfaction of patients undergoing plastic surgery procedures under these intravenous sedation protocols appears very high.     

Cardiovascular and behavioral responses of gray wolves to ketamine-xylazine immobilization and antagonism by yohimbine

Adult wolves (Canis lupus) were immobilized with 6.6 mg/kg ketamine hydrochloride (KET) and 2.2 mg/kg xylazine hydrochloride (XYL) administered intramuscularly. Induction time was 4.6 +/- 0.3 min (mean +/- SE). Immobilization resulted in significant bradycardia and hypertension (P less than 0.05). Twenty min after induction, the wolves were given 0.05-0.60 mg/kg yohimbine hydrochloride (YOH). Yohimbine given intravenously produced dose-related increases in heart rate (HR) with doses greater than 0.15 mg/kg resulting in extreme tachycardia (greater than 300 bpm). All doses of YOH caused a temporary decrease in mean arterial blood pressure (MABP) with some individual animals manifesting profound hypotension (less than 30 torr) at doses greater than 0.15 mg/kg. Increasing the dose of YOH above 0.15 mg/kg did not significantly decrease either arousal or ambulation times. Administering YOH at 40 or 60 min after induction resulted in decreased arousal and ambulation times. Stimulation by weighing and taking repeated blood samples during anesthesia did not shorten arousal times. We recommend that wolves immobilized with XYL-KET be antagonized with doses of YOH less than 0.15 mg/kg.     

Sedative and cardiovascular effects of midazolam in swine.

The ability to reliably produce sedation in swine is hampered by the paucity of agents available. This project examined the use of a new water soluble benzodiazepine, midazolam, as a sedative in swine. Echocardiographic studies were performed on thirty 23 to 30 kg Yorkshire swine before and 20 minutes after each animal received a single intramuscular dose of 100 micrograms/kg midazolam. Heart rate and respiratory rate decreased significantly compared to nonsedated values (93 +/- 7 versus 117 +/- 2 bpm and 10 +/- 1 versus 20 +/- 1 breaths/min, respectively [p less than 0.05]). However, there was no effect on left ventricular fractional shortening (29.9 greater than 0.05 versus 29.5 +/- 0.05% [p greater than 0.05]). An additional five pigs were instrumented for a dose response study in order to collect hemodynamic data and blood gas values at baseline, and 15 min after the intravenous administration of incremental doses of midazolam (100 to 1,000 micrograms/kg). Despite a significant decrease in heart rate and respiratory rate, cardiac output, blood gases, and pH remained within normal ranges at all dosage levels. Both routes of administration produced sedation for 20 min in all animals. Midazolam is an effective swine sedative that is associated with stable cardiac function.     

Effectiveness of antagonists for tiletamine-zolazepam/xylazine immobilization in female white-tailed deer

A combination of tiletamine-zolazepam/xylazine (TZ/X) is effective in the chemical immobilization of white-tailed deer (Odocoileus virginianus); however, the lengthy duration of immobilization may limit its usefulness. From October to November 2002, 21 captive female deer were assigned randomly to an alpha(2) antagonist treatment to reverse xylazine-induced sedation (seven does per group). All deer were given 220 mg of TZ (4.5+/-0.4 mg/kg) and 110 mg of X (2.2+/-0.2 mg/kg) intramuscularly (IM). Antagonist treatments were either 200 mg of tolazoline (4.0+/-0.4 mg/kg), 11 mg of atipamezole (0.23+/-0.02 mg/kg), or 15 mg of yohimbine (0.30+/-0.02 mg/kg) injected, half intravenously and half subcutaneously, 45 min after the IM TZ/X injection. In addition, 10 other deer (five per group) were immobilized as before and then given tolazoline (200 mg) after 45 min, with either a carrier (dimethyl sulfoxide [DMSO]) or carrier (DMSO) plus flumazenil (5 mg) to reverse the zolazepam portion of TZ. Mean times from antagonist injection until a deer raised its head were different for alpha(2) antagonist treatments (P=0.02). Times were longer for yohimbine (62.3+/-42.7 min) than for either atipamezole (24.3+/-17.1 min) or tolazoline (21.3+/-14.3 min). Mean times from antagonist injection until standing were not different (P=0.15) among yohimbine (112.0+/-56.4 min), atipamezole (89.7+/-62.8 min), or tolazoline (52.6+/-37.2 min). A sedation score based on behavioral criteria was assigned to each deer every 30 min for 5 hr. On the basis of sedation scores, tolazoline resulted in a faster and more complete reversal of immobilization. Flumazenil treatment did not affect recovery.     

Blood pressure and other physiological responses in awake and anesthetized guinea pigs

The effect of combinations of injectable anesthetics on mean arterial blood pressure, blood gases, heart rate and respiration of the guinea pig (NIH Outbred strain) was investigated. After a 30 minute period in which baseline resting cardiorespiratory measurements were obtained, five groups of six pigmented animals having indwelling carotid cannulas were anesthetized with (a) ketamine hydrochloride (30 mg/kg, im)/xylazine (5 mg/kg, im); (b) sodium pentobarbital (15 mg/kg, ip)/fentanyl-droperidol (0.4 mg/kg, im); (c) diazepam (5mg/kg, ip)/fentanyl citrate (0.32 mg/kg, im); (d) diazepam (5 mg/kg, ip)/alphaxalone-alphadolone acetate (45 mg/kg, im); or (e) 1% alpha-chloralose-40% urethane (0.8 ml/100g, ip). Animals were not respirated artificially and no supplemental doses of anesthetic were given. Resting blood pressure in awake animals was measured over time for as long as cannulas remained patent (109 measurements). Mean resting blood pressure, for this strain of guinea pigs, was determined to be 53.1 +/- 4.2 mmHg. There was no indication that mean arterial blood pressure changed with age in animals varying in weight from 215 g to 550 g. Under diazepam/fentanyl, blood pressure rose significantly above resting level to a mean of 71.1 +/- 6.1 mmHg. With the other four combinations, blood pressure stabilized near, but below pre-anesthesia levels (ketamine/xylazine 47.1 +/- 6.8 mmHg; pentobarbital/fentanyl-droperidol, 46.9 +/- 3.2 mmHg; diazepam/alphaxalone-alphadolone, 47.8 +/- 4.8 mmHg; chloralose-urethane, 51.0 +/- 1.2 mmHg). Under diazepam/alphaxalone-alphadolone and chloralose-urethane, respiration was depressed and blood gas levels deviated from normal to the extent that artificial ventilation would be necessary to maintain an adequate physiological state.     

Hypotensive action of prolactin in rats with spontaneous hypertension

Rats (SHR) weighing 240 +/- 10 g with spontaneous hypertension were given intraperitoneally porcine prolactin in doses from 0.2 to 2000 micrograms/kg of body weight. The systolic pressure was measured before hormone administration and 2 hours after it. It was found that prolactin in doses of 200 to 2000 micrograms/kg caused a decrease of the systolic pressure by 22%. The dose of 20 micrograms/kg decreased this pressure by 9% and the dose of 0.2 microgram/kg by 7.9%.     

Isoflurane compared with midazolam for sedation in the intensive care unit.

OBJECTIVE--To compare isoflurane with midazolam for sedation of ventilated patients. DESIGN--Randomised control study. Setting--Intensive care unit in university teaching hospital. PATIENTS--Sixty patients aged 18-76 who required mechanical ventilation. INTERVENTIONS--Sedation with either 0.1-0.6% isoflurane in an air-oxygen mixture (30 patients) or a continuous intravenous infusion of midazolam 0.01-0.20 mg/kg/h (30 patients). Sedation was assessed initially and hourly thereafter on a six point scale. Incremental intravenous doses of morphine 0.05 mg/kg were given for analgesia as required. The trial sedative was stopped when the patient was judged ready for weaning from ventilatory support or at 24 hours (whichever was earlier). END POINT--Achievement of a predetermined level of sedation for as much of the time as possible. MAIN RESULTS--Isoflurane produced satisfactory sedation for a greater proportion of time (86%) than midazolam (64%), and patients sedated with isoflurane recovered more rapidly from sedation. CONCLUSION--Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit.     

Pentobarbital versus medetomidine-ketamine-fentanyl anaesthesia: effects on haemodynamics and the incidence of ischaemia-induced ventricular fibrillation in swine

The present study was performed to compare haemodynamic variables at baseline and the incidence of ventricular fibrillation during the early phase of ischaemia in swine during pentobarbital or medetomidine-ketamine-fentanyl anaesthesia. Twenty-two swine (mean +/- SD: 29+/- 3 kg) were anaesthetized with sodium pentobarbital (induction with 36 mg/kg intraperitoneally, and maintenance with 5-20 mg/kg/h intravenously [i.v.]) and 6 swine (27+/- 3 kg) were anaesthetized with ketamine and fentanyl (premedicated with medetomidine 0.1 mg/kg and ketamine 10 mg/kg intramuscularly, induction with ketamine 20 mg/kg and fentanyl 0.025 mg/kg i.v., and maintenance with ketamine 20 mg/kg/h and fentanyl 0.025 mg/kg/h i.v.). After a stabilization period of 30 min, the left anterior descending coronary artery (LAD) was occluded for 10 min. Haemodynamic data and occurrence of ventricular fibrillation were recorded. The ischaemic area was measured by fluorescing microspheres. Swine anaesthetized with medetomidine-ketamine-fentanyl had significantly lower heart rate, myocardial contractility, peak left ventricular pressure, arterial blood pressure, aortic blood flow, myocardial blood flow and cardiac index at baseline, than swine anaesthetized with pentobarbital. Whereas none of the swine anaesthetized with pentobarbital fibrillated during the LAD occlusion, ventricular fibrillation occurred in 83% of the animals anaesthetized with medetomidine-ketamine-fentanyl (P< 0.001). No significant difference was found in size of ischaemic area between the two groups. Thus, we show a depression in haemodynamic variables at baseline and a higher incidence of ventricular fibrillation during the early phase of ischaemia in swine anaesthetized with medetomidine-ketamine-fentanyl compared to swine anaesthetized with pentobarbital.     

Pyridostigmine enhances even if it does not normalize the growth hormone responses to growth hormone-releasing hormone in patients with Cushing's disease.

Subjects with Cushing's disease have diminished growth hormone (GH) response to growth hormone-releasing hormone (GHRH). The aim of our study was to investigate the underlying mechanism of this diminished GH response in these patients using pyridostigmine (PD), an acetylcholinesterase inhibitor, which is reported to increase GH secretion by reducing somatostatin tone. Eight subjects with untreated Cushing's disease (caused by a pituitary adenoma) and 6 control subjects received GHRH 100 micrograms in 1 ml of saline, as intravenous bolus injection 60 min after (1) placebo (2 tablets, p.o.) or (2) PD (120 mg, p.o.). After GHRH plus placebo, the GH peak (mean +/- SEM) was significantly lower in subjects with Cushing's disease (2.4 +/- 0.5 micrograms/l) compared to control subjects (25.1 +/- 1.8 micrograms/l, p less than 0.05). After GHRH plus PD, the GH peak was significantly enhanced both in subjects with Cushing's disease (7.1 +/- 2.3 micrograms/l, p less than 0.05) and in control subjects (42.3 +/- 4.3 micrograms/l, p less than 0.05). In patients with Cushing's disease, the GH response to GHRH plus PD was lower with respect to the GH response to GHRH alone in normal subjects. We conclude that hypercortisolism may cause a decrease in central cholinergic tone which is in turn hypothesized to be responsible of an enhanced somatostatin release from the hypothalamus. However, other metabolic or central nervous system alterations may act synergistically with hypercortisolism in causing GH inhibition in patients with Cushing's disease.     

Erythrocyte insulin receptor and glucose tolerance test in children treated with prednisolone

Insulin receptors of erythrocytes and oral glucose tolerance test (O-GTT) were investigated in sixteen children treated with prednisolone for various diseases. Ten patients (Group 1) received low doses of prednisolone (0.2-0.5 mg/kg body weight/day) and six patients (Group 2) received higher doses of prednisolone (1.5-2.0 mg/kg body weight/day). Compared to the values for controls, the sums of blood glucose (sigma BS) at O-GTT in both group 1 and group 2 patients were significantly elevated. (422 +/- 75 mg/dl, p less than 0.01 Group 1; 419 +/- 39 mg/dl, p less than 0.01 Group 2; 338 +/- 41 mg/dl controls) Significant differences were not observed in the sums of insulin concentration at O-GTT, fasting blood concentration and basal insulin levels among these two groups and the controls. There was a significant increase in the maximum insulin binding in group 2 (9.13 +/- 0.68% in group 2, 7.97 +/- 1.06% in controls, p less than 0.05), but not in group 1 (8.59 +/- 1.82%). There is no significant difference in binding affinity or the number of receptors between any of these two patients' groups and the controls. When patients in group 1 and group 2 were combined, sigma IRI levels were significantly elevated in the patients (p less than 0.05). These results suggested that prednisolone treatment with a smaller dosage as well as with the higher dosage resulted in a carbohydrate intolerance, the main cause of which is located in a postreceptor step (or steps) of insulin action.