Porcine malignant hyperthermia: false negatives in the halothane test

Purebred Pietrain pigs presumed (on the basis of pedigree) to be homozygous for malignant hyperthermia (MH) susceptibility were subjected to a 3% halothane challenge test. A few (6%) pigs that should have been MH susceptible on the basis of parental genotype did not develop muscle rigidity in response to repeated halothane tests. Three of these animals were brought into the laboratory, and muscle biopsy specimens were obtained for in vitro analysis. Bundles of intact muscle cells dissected from biopsy specimens were electrically stimulated, and mechanical responses were monitored during exposure to halothane. In all instances, the muscle bundles from the halothane-negative (ie, not sensitive to halothane), but genetically susceptible, pigs gave in vitro responses that were similar of those of halothane-positive MH-susceptible pigs in that tetanic tension was depressed, tetanus relaxation was slowed, and small contractures were produced upon halothane exposure. Thus, the presence of a halothane-sensitive abnormality in the skeletal muscles, in and of itself, is not always sufficient for development of in vivo muscle rigidity during a brief halothane test. Furthermore, when the halothane testing of pigs is conducted by recommended techniques, false negatives still occur in a small percentage of the genetically MH-susceptible animals.     

The effect of halothane anesthesia on the function of the adrenal cortex and some metabolites in the blood plasma of pigs not susceptible to malignant hyperthermia]

The effects were investigated of a 25-minute inhalation of halothane with oxygen on three to four months old pigs of the Large White breed. Symptoms of malignant hyperthermia did not occur. The actual total anesthesia, which causes slight hypoproteinemia, hypoglycemia and hypocholesterolemia without significant changes in the content of non-esterified fatty acids (NEFA) and urea, induced only a slight increase of circulating 11-hydroxycorticosteroids (11-OHCS). The combination of anesthesia with castration of gilts or barrows significantly increased the concentration of 11-OHCS but did not reach the level recorded after the application of ACTH. The higher levels of 11-OHCS were accompanied by higher concentrations of NEFA and glucose. The treatment of the animals lasting half an hour prior to inhalation of halothane at maximum doses or one hour in the control unanesthetized pigs produced an effect, mainly on the 11-OHCS concentration and on the activity of creatine kinase in the plasma. The results indicate that the adrenocortical response to the effect of halothane is not stronger than the response to simple handling connected with excitement and muscular activity of the animals. Therefore there is no reason of considering halothane anesthesia as a factor causing great stress and pigs which in its course do not respond with malignant hyperthermia as animals insensitive to stress. The aptness of denotation of clinical manifestations of genetically defective muscles in pigs is discussed.     

Adrenocortical and metabolic responses to dobutamine infusion during halothane anaesthesia in ponies

The study investigated whether hypotension in halothane-anaesthetised ponies is the stimulus inducing an endocrine stress response by assessing the effect of maintenance of normotension with a dobutamine infusion. Groups of six ponies were studied. After premedication with acepromazine (0.04 mg/kg) anaesthesia was induced with thiopentone (10 mg/kg) and maintained for 120 min with halothane (group AN). Dobutamine was infused to effect (1.1–4.4 μg/kg/min) to maintain arterial pressure at pre anaesthetic levels. The conscious group (CON) were prepared as for AN and then received only dobutamine infusion 1.0 μg/kg/min for 120 min. Arterial blood pressure, pH, oxygen and carbon dioxide tension, pulse rate, haematocrit, and plasma cortisol, glucose and lactate concentrations were measured before, at 20 min intervals during anaesthesia, and 20 and 120 min after anaesthesia ceased. Blood pressure remained close to control in both groups. The AN group became hypercapnic and acidotic, pulse rate and haematocrit increased, cortisol increased more than twofold and plasma glucose and lactate did not change. All values remained at control in the CON group except for small increases in haematocrit and decreases in pulse rate. Maintenance of normotension during halothane anaesthesia did not blunt the adrenocortical response to anaesthesia nor did the same dose of dobutamine alone increase plasma cortisol. Hypotension appears not to be the sole stimulus to equine adrenocortical activity during halothane anaesthesia.     

Gastric Myoelectric Activity after Experimental Gastric Dilatation-Volvulus and Tube Gastrostomy in Dogs

Gastric myoelectric activity was measured after experimental gastric dilatation-volvulus (GDV), GDV and tube gastrostomy, or tube gastrostomy in 12 dogs. Gastric myoelectric activity was recorded for 1 hour before (hour 0) and at hours 5, 24, 48, 72, and 96 after surgically induced GDV in six dogs. Three dogs with induced GDV and tube gastrostomy, and three dogs with tube gastrostomy only were also studied at hours 120, 144, and 168. The only significant change in the slow wave appearance or frequency from hours 0 to 48 was bradygastria at hour 5 in all three groups. A relative increase in the mean percentages of dysrhythmia from hours 72 to 168 in the dogs with a tube gastrostomy was caused by increases in tachygastria and arrhythmias. Dogs with GDV and tube gastrostomy had the greatest mean percentages of dysrhythmia, which were significantly more than those in dogs with GDV alone at hours 48, 72 and 96. The mean percentage of spike activity was less than or equal to 31 and varied widely. In general, there was less spike activity when the frequency of dysrhythmias was high. Thus, gastric myoelectric activity was disrupted from hours 48 to 168 after GDV with tube gastrostomy and after tube gastrostomy alone. Surgically induced GDV alone did not produce any significant or sustained dysrhythmias.     

Endocrine and metabolic responses to halothane and pentobarbitone anaesthesia in sheep

Some metabolic and endocrine responses to anaesthesia in sheep were studied. Adult sheep were anaesthetised with thiopentone and halothane (n=9), acepromazine, thiopentone and halothane (n=8) and pentobarbitone (n=10) on separate occasions. Routine cardiovascular monitoring was carried out and blood samples were taken for assay of cortisol, adrenocorticotrophic hormone (ACTH), arginine vasopressin (AVP), glucose and lactate. Halothane anaesthesia induced hypotension, hypercapnia and respiratory acidosis. Sheep anaesthetised with pentobarbitone were also hypercapnic and acidotic but did not develop hypotension. Plasma cortisol, ACTH and AVP (mean maximum values: cortisol: 83 ng/ml, ACTH 278 ng/ml, AVP 135 pg/ml), increased during halothane anaesthesia but did not change significantly from control values during pentobarbitone anaesthesia (mean maximum values: cortisol: 30 ng/ml, ACTH 71 ng/ml, AVP 7.8 pg/ml). Glucose tended to increase during both halothane and pentobarbitone anaesthesia but lactate decreased. It is not clear what facet of halothane anaesthesia evokes the stress response but it may be associated with cardiovascular depression.     

Ventricular arrhythmogenic dose of epinephrine in dogs and cats anesthetized with tiletamine/zolazepam and halothane

The ventricular arrhythmogenic dose of epinephrine (ADE) was determined in 6 dogs anesthetized with halothane alone or with halothane after injection of tiletamine/zolazepam (TZ). Respiratory rate and tidal volume were controlled and sodium bicarbonate was administered to maintain arterial pH and blood gas values within reference range. Heart rate and arterial blood pressure were recorded during determination of the ADE. The ADE (mean +/- SD) was no different during anesthesia with use of halothane alone (8.9 +/- 4.3) than it was when injections of TZ preceded administration of halothane (6.7 +/- 2.8). Tiletamine/zolazepam was also administered IV immediately after determination of the ADE during halothane-induced anesthesia. The TZ administered in this manner did not alter the ADE. Blood pressure and heart rate were significantly greater during infusion of epinephrine than immediately prior to infusion. The administration of TZ did not alter blood pressure response. The ADE was also determined in 6 cats anesthetized with halothane preceded by administration of TZ. The ADE (mean +/- SD) was 0.7 +/- 0.23 micrograms/kg, a value similar to that reported for cats during anesthesia with halothane alone.     

Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of anesthesia with isoflurane and halothane in horses undergoing arthroscopic surgery

OBJECTIVE: To compare hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of halothane and isoflurane in horses undergoing arthroscopic surgery. ANIMALS: 8 healthy adult horses. PROCEDURE: Anesthesia was maintained with isoflurane or halothane (crossover study). At 6 intervals during anesthesia and surgery, cardiopulmonary variables and related derived values were recorded. Recovery from anesthesia was assessed; gastrointestinal tract motility was subjectively monitored for 72 hours after anesthesia. Horses were administered chromium, and fecal chromium concentration was used to assess intestinal transit time. Venous blood samples were collected for clinicopathologic analyses before and 2, 24, and 48 hours after anesthesia. RESULTS: Compared with halothane-anesthetized horses, cardiac index, oxygen delivery, and heart rate were higher and systemic vascular resistance was lower in isoflurane-anesthetized horses. Mean arterial blood pressure and the dobutamine dose required to maintain blood pressure were similar for both treatments. Duration and quality of recovery from anesthesia did not differ between treatments, although the recovery periods were somewhat shorter with isoflurane. After isoflurane anesthesia, gastrointestinal motility normalized earlier and intestinal transit time of chromium was shorter than that detected after halothane anesthesia. Compared with isoflurane, halothane was associated with increases in serum aspartate transaminase and glutamate dehydrogenase activities, but there were no other important differences in clinicopathologic variables between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with halothane, isoflurane appears to be associated with better hemodynamic stability during anesthesia, less hepatic and muscle damage, and more rapid return of normal intestinal motility after anesthesia in horses undergoing arthroscopic procedures.     

Halothane anesthesia in calves.

Because of the calf's popularity as an experimental animal and its often noted sensitivity to anesthetics and anesthesia, the potency of halothane was studied in eight, young (x = 5.85 weeks), healthy, male Holstein-Friesian calves. The minimal alveolar halothane-O2 concentration (MAC) which just prevented calf movement in response to a tail clamp was 0.76 +/- SEM 0.03 vol% and is less than predictions based on studies in man. The addition of 50% N2O to inspired gases decreased the halothane MAC to 0.59 +/- 0.03%. In the absence of common modifying factors of anesthesia, halothane-O2 caused cardiopulmonary depression in these calves in proportion to anesthetic dose. Only two (total protein and albumin) of 17 selected blood clinical biochemical values were significantly (P less than 0.05) altered from base line within seven days of anesthesia, indicating insults to major organ systems did not occur.     

The effect of a 50% inspired mixture of nitrous oxide on arterial oxygen tension in spontaneously breathing horses anaesthetised with halothane

The effect of nitrous oxide (N₂O) on arterial partial pressure of oxygen (P_aO₂) was evaluated in 20 adult horses anaesthetised with halothane. A fresh gas flow rate of 20ml/kg/min, comprising a 1:1 N₂O/oxygen (O₂) mixture, was supplied via the rotameter flowmeters of an anaesthetic machine to a large animal breathing system. The horses breathed spontaneously from the circuit immediately after endotracheal intubation. Ten horses were subsequently positioned in lateral recumbency and ten in dorsal recumbency. A further twenty adult horses were anaesthetised with halothane and acted as controls; halothane in 20mls/kg/min of O₂ being supplied to the same breathing system. Fifty percent NO caused significant decreases in P_aO₂ for horses in lateral and dorsal recumbency. However when administered to horses in lateral recumbency it did not promote arterial hypoxaemia. There was a higher risk of intraopera- tive arterial hypoxaemia (P_aO₂ < 8.6kPa) associated with its use in spontaneously breathing horses in dorsal recumbency. Arterial hypoxaemia occurred in all horses during the first fifteen minutes of recovery but when N₂O was discontinued, halothane in oxygen supplied to the breathing circuit for five minutes at a flow rate of 20ml/kg/minute was sufficient to ensure that diffusion hypoxia did not occur. The magnitude of the hypoxaemia was not signficantly different between the groups. The time taken to adopt sternal recumbency was significantly shorter in the horses that had received N₂O.     

Comparisons of Sevoflurane, Isoflurane, and Halothane Anesthesia in Spontaneously Breathing Cats

The clinical effects of sevoflurane, isoflurane, and halothane anesthesia with or without nitrous oxide, were compared in healthy, premedicated cats breathing spontaneously during 90 minutes of anesthesia. The effect of nitrous oxide in accelerating the induction of and recovery from anesthesia was more evident for halothane than for sevoflurane or isoflurane. The cats recovered more rapidly from sevoflurane-oxygen than from either halothane- or isoflurane-oxygen. Heart rates did not significantly change during anesthesia with any of the anesthetics. Arterial blood pressures during sevoflurane-oxygen anesthesia were somewhat higher than those with either isoflurane- or halothane-oxygen. There were no significant differences in arterial blood pressures among sevoflurane, isoflurane, and halothane anesthesia when combined with nitrous oxide. The respiration rate during sevoflurane-oxygen was similar to that during halothane-oxygen. There were no significant differences in respiration rate among sevoflurane, isoflurane, and halothane anesthesia when combined with nitrous oxide. The degree of hypercapnia and acidosis during sevoflurane anesthesia was similar to that observed during isoflurane anesthesia and less than during halothane anesthesia. The three anesthetic regimens, with or without nitrous oxide, induced a similar degree of hyperglycemia and hemodilution during anesthesia. Serum biochemical examination did not reveal any hepatic or renal injuries after each anesthesia.     

Minimal Anesthetic Concentration and Cardiopulmonary Dose-Response of Halothane in Ducks

The minimal anesthetic concentration (MAC) for halothane and cardiopulmonary dose-responses at several concentrations of halothane were determined during spontaneous ventilation in nine young adult Pekin ducks. The MAC for halothane was 1.04 +/- 0.11 (mean +/- SD). There were dose-dependent decreases in ventilation, significant reductions in inspiratory and expiratory times, and prolongation of expiratory pause times. The end-tidal halothane concentration at apnea in five ducks was less than 1.53% and anesthetic index was less than 1.51. Heart rate increased significantly as the concentration of halothane was increased, but arterial blood pressure did not change. Cardiac arrhythmias developed in five ducks at end-tidal halothane concentrations as low as 1.15%, and one duck died of cardiac arrest.     

Thiamylal-and halothane-sparing effect of diazepam in dogs

The thiamylal- and halothane-sparing effect of diazepam was studied in two experiments using 32 conditioned dogs. Twenty-four dogs received 0.05, 0.1 or 0.2 ml/kg diazepam or 0.9% saline (placebo) prior to the administration of thiamylal sodium i.v. Eight dogs received 0.1 or 0.2 mg/kg diazepam i.v. or placebo prior to or during halothane anesthesia. All three doses of diazepam significantly decreased the amount of thiamylal required to allow orotracheal intubation. The 0.2 mg/kg i.v. dose of diazepam produced the most significant effects. Premedication of dogs with diazepam did not reduce the concentration of halothane required to maintain anesthesia. The administration of 0.1 and 0.2 mg/kg diazepam i.v. during halothane anesthesia decreased the concentration of halothane required to maintain anesthesia. These studies demonstrate that diazepam reduces the amount of thiamylal required for orotracheal intubation, and when given intra-operatively reduces the concentration of halothane required to maintain anesthesia.     

Halothane testing for malignant hyperthermia in swine: dose-response effects

Purebred Pietrain malignant hyperthermia (MH)-susceptible pigs (n = 102) were subjected to halothane (0%, 1%, 2%, 3%, 4%, and 5%) in oxygen. The number of pigs in each group exhibiting muscle rigidity (MH(+) reaction) and the reaction times were recorded, as were the number of deaths resulting from MH. Mortality was not affected by the halothane concentration. However, halothane concentration did markedly affect the number of MH(+) reactions and the reaction times. False-negative reactions were apparent in the pigs at halothane concentrations less than 3%. Increasing the halothane concentration incrementally to 5% (from 0%) significantly (P less than 0.05) decreased reaction times between treatment groups. The reductions in reaction times which occurred in the pigs given the 3%, 4%, and 5% halothane concentrations (62.1, 56.2, and 50.05)--although significant (P less than 0.05)--would indicate that 3% halothane would generally be sufficient for MH testing.     

Effects of plasma expansion on the pituitary-adrenocortical response to halothane anaesthesia in sheep

The study aimed to investigate the stimulus to adrenocortical activity that is induced by halothane anaesthesia. Groups of 7 sheep were anaesthetised with thiopentone and halothane (TH) or acepromazine, thiopentone and halothane (ATH). During 120 min of anaesthesia hypotension was prevented (mean arterial blood pressure kept at pre-anaesthetic level) by infusion of a modified gelatine plasma replacer given to effect (0.34–1.1 litres with TH and 1.1–3.1 litres with ATH). Pulse rate, arterial blood pressure and gases were measured and sequential samples withdrawn for analysis of plasma cortisol, adrenocorticotrophic hormone (ACTH), arginine vasopressin (AVP), glucose and lactate. Heart rate increased in the ATH but not the TH group. All sheep were well oxygenated but developed hypercapnia and respiratory acidosis. In both groups, cortisol increased more than 2-fold 20 min after the end of anaesthesia but there were no significant changes in ACTH. AVP was measured in the TH group only and increased 3-fold at the end of anaesthesia. Glucose and lactate remained stable except for lactate in the TH group which decreased during anaesthesia. These data indicate that hypotension is a major component of the stimulus inducing adrenocortical activity during halothane anaesthesia. However, maintenance of normotension did not entirely depress the response; halothane itself or decreased perfusion may also contribute.     

Postural Influence on Systemic Blood Pressure in Large Full-term Pregnant Bitches during General Anesthesia

Effects of positioning on systemic blood pressure were evaluated in six full-term pregnant golden retriever bitches during general anesthesia. Two positions (dorsal and left lateral recumbency) were examined. Anesthesia was induced with thiamylal sodium and maintained with halothane in oxygen. Direct arterial blood pressures were recorded from the bitches in each position. Effects of positioning for each bitch during general anesthesia were reexamined after the bitch weaned its pups; thus, each bitch served as its own control. Maternal posture had no significant effect (p greater than 0.05) on systemic blood pressure. Pregnancy had no significant effect (p greater than 0.05) on systemic blood pressure. Supine hypotension did not occur in anesthetized large, full-term pregnant bitches. Dorsal recumbency was an acceptable position for cesarean sections performed with the patient under general anesthesia.     

Cardiovascular effects of butorphanol in halothane-anesthetized dogs

Cardiovascular effects of butorphanol (0.2 mg/kg of body weight, IV) and responses associated with subsequent administration of naloxone (0.04 mg/kg, IV) were studied in halothane (1.2% end-tidal concentration)-anesthetized dogs. Transient, but statistically significant (P less than 0.05), decreases in heart rate, mean and diastolic arterial blood pressures, and rate-pressure product were observed after butorphanol administration. Cardiac index, stroke volume, and systemic vascular resistance did not change significantly. Except for the decrease in heart rate, changes in the values of the cardiovascular variables measured after butorphanol administration did not appear to be clinically relevant. Sixty minutes after butorphanol administration, naloxone was given. Statistically significant (P less than 0.05) increases in heart rate, arterial blood pressures, cardiac index, and rate-pressure product, along with dysrhythmias were observed. Stroke volume and systemic vascular resistance remained unchanged after administration of naloxone. Naloxone administration was associated with changes indicative of increased myocardial oxygen consumption.     

The cardiopulmonary effects of severe blood loss in anesthetized horses

Objective To characterize the acute cardiopulmonary effects of severe hemorrhage in anesthetized horses. Study design Prospective experimental study. Animals Three geldings and six mares, aged 14.4 ± 2.7 years, weighing 486 ± 41 kg (range: 425–550 kg). Methods Horses were anesthetized using xylazine, guaifenesin, ketamine and halothane or isoflurane. Cardiovascular variables, hematocrit, total solids, capillary refill time (CRT) and color of mucous membranes were measured as blood was collected from the carotid artery into sterile plastic bags. Arterial blood gas analysis was also performed. Results The average amount of blood collected from these horses was (mean ± SD) 53 ± 4.8 mL kg^?1 bodyweight (range: 23–32 kg) over 39 ± 4 minutes. Hematocrit decreased from 38 ± 3 to 32 ± 2% after induction of anesthesia and did not change significantly over the period of blood loss. Total solids decreased significantly after induction of anesthesia, and over the period of blood loss. Systolic, mean, diastolic and pulse pressures decreased as blood was lost. Heart rate did not change significantly. Capillary refill time increased from 1.6 ± 0.4 seconds to 4.8 ± 1.3 seconds as blood loss increased. Mucous membrane color deteriorated progressively. Arterial PO₂ decreased significantly over the period of blood loss. Conclusions Hematocrit and heart rate do not change significantly during acute severe hemorrhage in the anesthetized horse. Arterial blood pressure, pulse pressure and PaO₂ decrease as blood loss increases. Changes in mucous membrane color and CRT also occur as blood loss increases. Clinical relevance During severe hemorrhage in the inhalant‐anesthetized horse, both heart rate and hematocrit remain unchanged. Blood pressure decreases and changes in arterial PO₂ correlate most strongly with volume of blood lost.     

苏钟Ⅰ系和Ⅱ系猪的氟烷基因及其对产肉性能的影响

:对 3 0 1头瘦肉型新品系苏钟 系和 系仔猪进行氟烷测验 ,阳性率为 1 .3 3 %。随机抽取氟烷阴性猪 3 4头进行基因型检测 ,有 6头为杂合子 ,由此得知 NN、Nn和 nn3种基因型的频率分别为 81 .2 6%、1 7.4 1 %和 1 .3 3 %,N和 n2种基因的频率分别为 89.97%和 1 0 .0 3 %。对 3种基因型猪的肉质进行评定结果显示 ,4头氟烷阳性猪 ( nn)肉质最差 ,出现 3头严重 PSE肉和 1头轻度 PSE肉 ,而氟烷阴性猪 ( NN或 Nn)未发生 PSE肉。2 0头苏钟 系氟烷阴性猪用阳性公猪测交 ,对产出的 2 0 8头后代进行氟烷测验 ,共检出 4窝中的 2 1头阳性猪。对测交后代进行肥育性能和肉质测定 ,发现阳性猪的日增重和饲料报酬等较低 ,屠宰率、眼肌面积和瘦肉率较高 ,肉质较差     

Malignant hyperthermia in dogs

Malignant hyperthermia (MH) is an anesthetic agent-induced hypermetabolic state. Human beings and several other animal species, including dogs, have been described to be genetically predisposed to development of MH. The halothane-triggered MH syndrome was characterized in genetically predisposed dogs, and in vitro contracture sensitivity of biopsied gracilis muscle exposed to halothane and caffeine was quantitated. Within 1 hour of halothane administration, each MH-susceptible dog developed rapid increases in CO2 production and rectal temperature. Reversal of the hypermetabolic state was achieved when halothane was discontinued and dantrolene sodium was given i.v. Biopsied gracilis muscle from MH-susceptible dogs had abnormal in vitro contracture responses to halothane and caffeine. These findings were consistent with those observed for MH-susceptible human beings and pigs in which a loss in regulation of muscle cell Ca(+)+ is believed to be the primary etiologic event for induction of MH.     

Anesthetic potency and cardiopulmonary effects of sevoflurane in goats: comparison with isoflurane and halothane.

The anesthetic potency and cardiopulmonary effects of sevoflurane were compared with those of isoflurane and halothane in goats. The (mean +/- SD) minimal alveolar concentration (MAC) was 0.96 +/- 0.12% for halothane, 1.29 +/- 0.11% for isoflurane, and 2.33 +/- 0.15% for sevoflurane. Cardiopulmonary effects of sevoflurane, halothane and isoflurane were examined at end-tidal concentrations equivalent to 1, 1.5 and 2 MAC during either spontaneous or controlled ventilation (SV or CV). During SV, there were no significant differences in respiration rate, tidal volume and minute ventilation between anesthetics. Dose-dependent decreases in both tidal volume and minute ventilation induced by halothane were greater than those by either sevoflurane or isoflurane. Hypercapnia and acidosis induced by sevoflurane were not significantly different from those by either isoflurane or halothane at 1 and 1.5 MAC, but were less than those by halothane at 2 MAC. There was no significant difference in heart rate between anesthetics during SV and CV. During SV, all anesthetics induced dose-dependent decreases in arterial pressure, rate pressure product, systemic vascular resistance, left ventricular minute work index and left ventricular stroke work index. Systemic vascular resistance with isoflurane at 2 MAC was lower than that with sevoflurane. During CV, sevoflurane induced dose-dependent circulatory depression (decreases in arterial pressure, cardiac index, rate pressure product, systemic vascular resistance, left ventricular minute work index and right ventricular minute work index), similar to isoflurane. Halothane did not significantly alter systemic vascular resistance from 1 to 2 MAC.