Post-operative analgesia following thoracotomy in the dog: an evaluation of the effects of bupivacaine intercostal nerve block and nalbuphine on respiratory function.

Pain following thoracotomy reduces pulmonary ventilation in man and a similar effect is believed to occur in animals. The effects of two analgesic regimens on arterial blood gas parameters were studied in dogs following thoracotomy. Post-Operative analgesia was provided with intermittent nalbuphine, either alone or in combination with an intercostal nerve block using bupivacaine. Arterial blood gas analysis was carried out at 4, 8 and 16 h post-operatively, both before the administration of nalbuphine and again 30 min later. Animals which received nalbuphine alone had a significant rise in arterial oxygenation following administration of this analgesic. This effect was not observed at 4 and 8 h post-operatively in dogs which had an intercostal block with bupivacaine, but was seen at 16 h post-operatively when it could be anticipated that the effects of bupivacaine would have waned. These results suggest that intercostal block with bupivacaine can provide analgesia for over 8 h, and that the duration of action of nalbuphine in controlling post-operative pain in the dog is probably less than 4 h.     

Reversal of fentanyl/fluanisone neuroleptanalgesia in the rabbit using mixed agonist/antagonist opioids

The reversal of the neuroleptanalgesic combination of fentanyl/fluanisone using mixed agonist/antagonist opioids has been investigated in the rabbit. All of the compounds studied (naloxone, nalbuphine, meptazinol, butorphanol, buprenorphine, pentazocine, doxapram) reversed the respiratory depression and sedation produced by fentanyl/fluanisone. Fentanyl/fluanisone produced profound analgesia for 180 min, which was rapidly and completely antagonized by naloxone. The mixed agonist/antagonist opioids produced a reduction in the degree of analgesia but, in contrast to naloxone, analgesic activity persisted from 120 min (meptazinol) to 420 min (buprenorphine). Administration of buprenorphine to rabbits anaesthetized with fentanyl/fluanisone and midazolam confirmed that the reversal of respiratory depression was accompanied by the return of arterial pH, PCO2 and PCO2 to preanaesthetic values. The use of neuroleptanalgesic anaesthetic regimens, which have been shown to provide effective surgical anaesthesia, combined with reversal using a mixed agonist/antagonist opioid to provide postoperative analgesia, appears to be a valuable refinement of current laboratory animal anaesthetic practice.     

不同剂量地佐辛用于腹腔镜妇科手术超前镇痛的效果观察

目的：观察不同剂量地佐辛用于腹腔镜妇科手术超前镇痛的效果。方法：将90例ASAI．II级、年龄18~60岁拟行腹腔镜妇科手术的患者随机分成3组,每组30例,A组给予地佐辛0．1mg／kg开皮前15rain静脉注射;B组给予地佐辛0．15mg／kg开皮前15min静脉注射;C组给予地佐辛0．2mg／kg开皮前15min静脉注射,采用VAS评分评估术后镇痛效果并观察术后辅助镇痛药物的使用和不良反应的发生情况。结果：B、c组术后2、4、6、8h的VAS评分明显低于A组（P〈0．05）;C组术后2、4h的Ramsay评分明显高于A、B组（P〈0.05）;A组术后辅助镇痛药的使用率明显高于B组和C组（P／0．05）;3组不良反应的发生率比较均无统计学差异（P〉0．05）。结论：开皮前15rain静注地佐辛0．15mg／kg用于腹腔镜妇科手术镇痛效果好,且不增加不良反应的发生率。     

Opioid modulation of ingestive behaviors in the spiny mouse (Acomys cahirinus)

Feeding and drinking behavior were studied in deprived or sated spiny mice (Acomys cahirinus) at various time intervals following peripheral administration of naloxone hydrochloride and butorphanol tartrate. Naloxone attenuated both food and water intake, but not latency to respond, indicating existence of functional opioid-sensitive feeding and drinking systems in this species. Butorphanol tartrate, a mixed opioid agonist/antagonist produced a dose-related enhancement or suppression of feeding, the former naloxone reversible, but had no measureable effect on drinking.     

Pineal N-acetyltransferase, pineal and serum melatonin response to isoproterenol stimulation in underfed male rats

Adult male rats were subjected to 4 weeks of 50% food restriction under lighting regimen of 14 h light and 10 h dark. The pineal response to isoproterenol (ISO) was determined. In the time-course study, animals were injected with 0.5 mg/Kg ISO subcutaneously (SC) and killed at different times up to 180 min post injection. In the dose-response study, various doses of ISO (0.2 mg/Kg to 5.0 mg/Kg) were injected intraperitoneally (IP) and animals were killed 120 min post injection. Body weight, pineal N-acetyltransferase (NATase), pineal and serum melatonin (MT) were determined. After 4 weeks of restricted feeding, body weight was reduced by 40%. In the time-course study, peak pineal NATase occurred 120 min post injection in the ad libitum fed animals. By contrast, the food restricted animals showed a gradual increase of pineal NATase up to 180 min post injection. In the dose-response study, the ad libitum fed animals demonstrated a dose dependent increase of pineal NATase up to 5 mg/kg dose. The food restricted animals, however, achieved their maximal pineal NATase at 1 mg/Kg dose with no further increment at 5 mg/Kg dose. These differences in responsiveness were also reflected in pineal and serum MT levels. These results indicate that underfed animals have abnormal pineal NATase, pineal and serum MT responses to ISO stimulation.     

Mechanisms of effect of adrenocorticotropic hormone on the rat pain sensitivity

The mechanisms of effect of adrenocortricotropic hormone on pain sensitivity were studied in anaesthetized Sprague-Dawley male rats. Systemic ACTH administration increased the pain thresholds (from 3 min up to the 30 min after injection) in rats with normal production of hormones. The initial stage of ACTH analgesic effect was fully eliminated by blockade of opiate receptors, ACTH-induced reaction was observed only from 15 up to 30 min after injection. In rats with deficiency of glucocorticoids production, the duration of ACTH-induced analgesic effect decreased to 15 min. The analgesic effect was completely prevented by combination of blockade of glucocorticoids production and blockade of opiate receptors. Thus the ACTH-induced analgesic effect is provided at least by two mechanisms: 1) appearing during the first minutes after injection (from 3 min up to 15 min) and mediated by opiate receptors rather than glucocorticoids, and 2) appearing from 15 min up to 30 min after injection and mediated by glucocorticoids but not opiate receptors.     

Comparative evaluation of the effects of intravenous administration of cimetidine and ranitidine on several cardiovascular parameters

We have compared the effects of intravenous administration of cimetidine and ranetidine on some cardiovascular parameters. Five healthy volunteers received both cimetidine (3, 5 mg/Kg) and ranetidine (1, 5 mg/Kg). Heart rate, blood pressure and PEP/LVET were recorded at baseline and 5, 10, 30, 45 minutes after administration of both drugs. Intravenous administration of cimetidine and ranetidine did not induce any significant alterations in cardiovascular variables.     

Analgesic activity of substance P following intracerebral administration in rats

Substance P was found to be a potent, long-lasting analgesic in the tail flick test in rats following intracerebral administration, via chronically indwelling cannulae, into the midbrain periaqueductal gray. Substance P was approximately five times as potent as morphine sulfate on a weight basis; however, it was 25 times more potent than morphine on a molar basis. The analgesic activity produced by Substance P was significantly antagonized by pretreatment with naloxone, a narcotic antagonist. The analgesic activity of Substance P exhibited a rapid onset (1 min.), peaked by 3 minutes post infusion and its duration of activity was between 30 and 60 minutes. Thus, Substance P may be yet another endogenous analgesic peptide.     

纳布啡在围手术期镇痛的研究进展

纳布啡是一种新型的菲族镇痛药,属于混合型阿片类受体激动/拮抗剂,可在脊髓水平激动κ受体发挥强效的镇痛效果,其镇痛作用起效迅速、药效持久、疗效确切;同时由于纳布啡独特的部分μ受体拮抗特性,使其与吗啡相比,在发挥镇痛作用的同时呼吸抑制轻、血流动力学平稳以及恶心呕吐、皮肤瘙痒、成瘾性等不良反应发生率更低,因此,纳布啡在围手术期镇痛和临床麻醉等多个领域有着广阔的应用前景。现结合纳布啡独特的药代动力学、药理学特点及作用机制,对纳布啡在围手术期镇痛的研究进展作一综述,以期为临床上合理、有效镇痛提供理论参考和实践依据。     

Comparison of Neurologic Responses to the Use of Medetomidine as a Sole Agent or Preanesthetic in Laboratory Beagles

Different dose regimens of medetomidine (a potent α2-adrenergic agonist), adding up to a combined dose of 80 µg/kg, were administered to laboratory beagles to determine physiologic responses including neurologic. The study was intended to determine EEG responses where sufficient sedative and analgesic effects are reached with medetomidine and in contrast its effects when used with ketamine or halothane. Cardiopulmonary responses were very similar in each dose regimen, showing the characteristic properties of single doses of 80 µg/kg of medetomidine. Effective sedative and analgesic duration seemed to be a function of when the largest dose was administered. Adequate additional sedative and analgesic could be gained from injections at doses of half of the initial one. The potent sedative and analgesic effects of medetomidine confirmed by neurologic evaluation supports its potential use as a premedication to general anesthesia in dogs. In this study, 2 different doses of medetomidine were also tested as premedication to both ketamine HCl and halothane anesthesia. Neorologic responses were determined at the same time cardiopulmonary parameters, anesthetic quality, and dose requirements were recorded. Medetomidine was found to have favorable qualities in conjunction with these anesthetics. Cardiopulmonary parameters remained satisfactory in both groups as preanesthetic medication prior to halothane, but no additional benefits could be seen from doses of 40 µg/kg medetomidine compared to 20 µg/kg, except a significant 30% reduction in halothane requirement. The positive chronotropic and inotropic properties of ketamine restored the medeto-midine-induced bradycardia and produced a short anesthetic period of 15 to 30 min depending on the dose of medetomidine. The quality of anesthesia was better when 40 µg/kg medetomidine was used, but recorvery was quicker with 20 µg/kg medetomidine. Medetomidine significantly reduced cerebral activity as demonstrated by recordings of total amplitude and frequency evaluation of the EEG with compressed spectral analysis. This analytical method was effective in confirming clinical signs of sedation, analgesia, and anesthesia in canine subjects.     

A role of the rostral hypothalamus in the regulation of LHRH release in baboons

In the intact control baboons the plasma level of LH was elevated and reached a peak within 15 minutes after administration of 100 microgram synthetic LHRH. In addition, a second peak in plasma LH appeared within 90 minutes after LHRH injection. Supplementing these results, plasma level of estrogen was elevated within 30 minutes after LHRH injection. Subsequently, frontal deafferentation of the hypothalamus was performed in these baboons. After administration of 100 microgram synthetic LHRH in these frontally deafferented baboons the plasma level of LH was elevated and reached a peak within 15 minutes, as in the intact control baboons. However, there was no second LH peak within 90 minutes after LHRH injection, even though plasma estrogen was elevated within 30 minutes, as in the intact control baboons. It was found that the rostral hypothalamus in baboons is involved in the regulation of LHRH release which promotes to release LH within 90 minutes after LHRH injection.     

Effect of imipramine hydrochloride on the activity of gamma-aminobutyric acid transaminase in regions of the rat brain

The effect of intraperitoneal injection of imipramine hydrochloride on the activity of gamma-aminobutyric acid transaminase was determined in three regions of the rat brain.The cerebral hemispheres did not show a significant change in the activity of gamma-aminobutyric acid transaminase. Cerebellum and brain stem, both, however, showed a very significant decrease in the activity of the enzyme at 15 and 30 minutes after drug administration. At 90 minutes after drug administration, the activity of gamma-aminobutyric acid transaminase had returned to nearly control values.     

Central antalgic activity of resveratrol

A single dose of resveratrol (25 μg/10μl) was injected directly into the right lateral cerebral ventricle (icv) of Wistar rats via an implanted cannula in order to study the analgesic properties of the compound. A control group of rats received 10 μl NaCl 0.9%. The lengthening of the time to reaction to painful stimuli was assessed in the radiant heat tail-flick latency time test. In this study, the response to painful stimuli of the animals treated with resveratrol had a bimodal profile with hypoalgesia or hyperalgesia. In the selected experimental conditions, resveratrol had a definite analgesic effect; the increase in time to reaction ranged from 100-120% (8 rats) to 600-700% (9 rats). In this experiment resveratrol exerts evident central antalgic effects in the majority of rats, which are related to the individual level of excitation and vigilance at baseline. Antinociceptive induced by resveratrol icv injection was maximal at 4-10 min and lasted no longer than 15 min. The effect of resveratrol to produce analgesia after a single icv injection may be interesting for preventing chronic pain.     

Accumulation of labeled gamma-aminobutyric acid into rat brain and brain synaptosomes after i.p. injection

The accumulation of labeled GABA into brain and brain nerve endings was studied in the adult rat after i.p. injection of large doses of neurotransmitter (740 mg/Kg). In the first 5–30 minutes after the injection the exogenous neurotransmitter reaches a stable plasma level of around 5 mM. The accumulation of radioactive GABA into the brain presents a latency of a few minutes from the time of the injection. Thereafter, the accumulation of the neurotransmitter is almost linear with time. Once in the brain tissue labeled GABA is in part broken down. The exogenous neurotransmitter is taken up in GABA-ergic nerve endings with a steep increase between 20 and 30 minutes after the injection. From a quantitative point of view, the data show that the brain accumulation of labeled GABA at 30 minutes post injection is minimal in the respect of the steady state average concentration of the endogenous neurotransmitter (0.014%). However, the amount of radioactive GABA which accumulates in the nerve endings, at the same post injection time, is around 7% of the endogenous neurotransmitter in that comparment. The data thus show a selective enrichment of exogenous systemic GABA in a physiologically important compartment of the brain.     

Delayed onset of single dose tolerance to morphine analgesia

Rats received either 20 mg/Kg of morphine sulfate I.P. or 5 μgm of morphine sulfate microinjected into the periaqueductal gray area of the brain. The analgesic effect of the morphine was determined by comparing pre- and postinjection tailflick latencies. To test for tolerance following a single injection, the procedure was repeated 6, 12 or 24 hours after the first injection and tests. Tolerance was not observed 6 hours after the original injection, tolerance was observed at 12 hours and increased tolerance was present at 24 hours. Single dose tolerance to morphine appears to develop slowly over a period of several hours and during much of this time, the amount of opiate present in the brain was insufficient to produce analgesia. Similarity between central and peripheral administration suggests a central mechanism of single dose tolerance.     

Effects of yohimbine on bradycardia and duration of recumbency in ketamine/xylazine anesthetized ferrets

Eleven adult ferrets (Mustela putorius furo) were anesthetized with ketamine hydrochloride (25 mg/kg, IM) and xylazine hydrochloride (2 mg/kg, IM). Fifteen minutes post-ketamine/xylazine injection, ferrets were treated with yohimbine hydrochloride at a dose of 0.5 mg/kg, or an equal volume of physiologic saline, intramuscularly. Each ferret served as its own control by randomly receiving both treatments with a minimum interval of 2 weeks between treatments on any one ferret. At 15 minutes post-ketamine/xylazine injection, mean heart rate measurements for both treatment groups were 27% less than the mean heart rate measurement reported for unanesthetized ferrets. Intramuscular administration of yohimbine antagonized the ketamine/xylazine induced bradycardia in 10 of the 11 ferrets, (p = 0.0001). In yohimbine treated ferrets, an increase in mean heart rate measurement was noted 5 minutes after the intramuscular administration of yohimbine, and followed, over the next 15 minutes, by a progressive increase in mean heart rate. However, a corresponding decrease in mean heart rate measurement was observed in saline treated controls. Fifteen minutes after the injection of yohimbine, the mean heart rate measurement of yohimbine treated animals had increased to 194 beats per minute. This mean heart rate measurement is nearly 30% greater than the mean heart rate of 150 beats per minute measured at 15 minutes post-saline injection in saline treated controls. Also, yohimbine treatment significantly reduced duration of recumbency in 10 of 11 ferrets (p = 0.0001). Mean duration of recumbency for yohimbine treated ferrets was 41 +/- 9.7 minutes, whereas mean duration of recumbency for saline treated ferrets was determined to be 80 +/- 11.4 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)     

盐酸右美托咪定联合瑞芬太尼在骨科手术中的应用效果及对呼吸功能的影响

本研究考察了盐酸右美托咪定联合瑞芬太尼(观察组,n=68)和丙泊酚联合瑞芬太尼(对照组,n=68)在我院136例骨科手术患者中的应用效果,应用警觉/镇静观察评分(OAA/S)评价患者用药前(T0)、用药10 min后(T1)、用药20 min后(T2)、用药30 min后(T3)和清醒后(T4)的镇静效果,并比较了两组患者在不同时间点的呼吸频率(RR)、血氧饱和度(SpO2)、心率(HR)和平均动脉压(MAP)。研究结果显示,两组患者在T0、T1和T4时间点的OAA/S评分无统计学差异(p>0.05),观察组在T2和T3时间点的OAA/S评分明显小于对照组(p<0.05)。两组患者在T0、T1和T4时间点的RR无统计学差异(p>0.05),观察组在T2和T3时间点时的RR明显大于对照组(p<0.05)。观察组在T2时间点时的SpO2明显大于对照组(p<0.05)。两组患者的SpO2在其他时间段时无明显差异(p>0.05)。两组患者的HR和MAP均未表现出明显差异(p>0.05)。观察组的不良反应发生率为2.94%,明显高于对照组的11.76%(p=0.049)。本研究结论初步表明,与丙泊酚联合瑞芬太尼相比,盐酸右美托咪定联合瑞芬太尼在骨科手术中具有更好的镇静效果,可有效保障患者的呼吸功能,具有良好的血流动力学稳定性和安全性。     

Dose-response of intravenous butorphanol to increase visceral nociceptive threshold in dogs

This study was designed to determine the effective analgesic dose of butorphanol administered intravenously to obtund visceral nociception, as well as to determine duration of this effect. Additionally, cardiovascular changes and sedative effects were defined. Eight healthy dogs were each given five doses of butorphanol (0.025, 0.05, 0.1, 0.2, and 0.4 mg/kg) plus a sterile water placebo intravenously in a randomized blinded format. Antinociception was assessed using an inflatable Silastic balloon inserted into the colon. Blood pressures and pulse rates were measured with a noninvasive monitor. The greatest efficacy and longest duration of antinociception were produced by 0.4 mg/kg of butorphanol, with a duration of 38 +/- 9 min. Arterial blood pressure and pulse rate did not vary at antinociceptive doses. Mild sedation was observed at all doses, which generally lasted longer than the antinociceptive effects. These data suggest that butorphanol can be given alone intravenously to provide visceral antinociception lasting 30-45 min without significant side effects.     

盐酸羟考酮注射液用于腹部全麻患者术后镇痛的有效性和安全性

目的:探讨盐酸羟考酮注射液用于腹部全麻患者术后镇痛的有效性和安全性。方法:选择2016年1月至2016年12月来我院治疗的择期全麻下行腹部手术的患者60例。按照治疗方法,采用随机数字表法将患者平均分为硫酸吗啡注射组(简称吗啡组)和盐酸羟考酮注射组(简称羟考酮组),每组30例。用药3、24、48 h后,采用VAS方法对患者进行疼痛评分。记录术后48 h内患者补救镇痛率以及患者对镇痛的满意度。记录72 h后患者恶心、呕吐等不良事件的发生情况。结果:镇痛48 h内的不同时间点,两组间VAS评分、补救镇痛率与吗啡组相比无显著差异(P0.05)。羟考酮组术后不良事件发生率为16.7%,显著低于吗啡组40.0%(P0.05),羟考酮组患者镇痛满意度显著高与吗啡组(93.3%vs.70.0%),差异具有统计学意义(P0.05)。结论:盐酸羟考酮注射液的镇痛效果与硫酸吗啡相当,且可安全有效地改善患者术后生活质量,提高患者满意度。     

A possible role for cyclic AMP in the initiation of DNA synthesis by isoproterenol-activated parotid gland cells

An intraperitoneal injection of the β-adrenergic agonist dl-isoproterenol hydrochloride (100 mg/Kg body weight) into a rat caused an early, very large (400-fold) cyclic AMP surge (peaking at 10 minutes) in the parotid gland which was followed by a second, much smaller (two-fold) surge 12 to 16 hours later. DNA synthesis began about 16 to 20 hours after the isoproterenol injection and peaked between 24 and 28 hours. The maximum level of DNA-synthetic activity at 24 hours was correlated positively to the magnitude of the small cyclic AMP surge at 12 hours, but not to the size of the much larger cyclic AMP surge at 10 minutes. An intraperitoneal injection of dl-propranolol hydrochloride (59 mg/Kg body weight) at 8 hours after isoproterenol injection abolished the second cyclic AMP surge at 12 hours and markedly (65-75%) reduced the incorporation of [³H]-thymidine into DNA. Injection of dibutyryl cyclic AMP (6.3 mg/Kg body weight) and theophylline (25 mg/Kg body weight) at 8 hours prevented propranolol from inhibiting DNA synthesis. Propranolol appeared specifically to affect the cyclic AMP-dependent pre-DNA-synthetic step because it did not reduce [³H]-thymidine incorporation when injected after the second cyclic AMP surge had passed and DNA synthesis had just begun. Thus, the initial, large cyclic AMP surge following β-adrenergic stimulation may not be necessary for the initiation of prereplicative development, while the much smaller second surge may be needed for the initiation of DNA synthesis.