Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 228
Filter
1.
J Equine Vet Sci ; 136: 105052, 2024 May.
Article in English | MEDLINE | ID: mdl-38531516

ABSTRACT

Quarter horses (QH), a prominent athletic breed in Brazil, are affected by muscular genetic disorders such as myosin-heavy chain myopathy (MYHM), polysaccharide storage myopathy (PSSM1), hyperkalemic periodic paralysis (HyPP), and malignant hyperthermia (MH). Bull-catching (vaquejada), primarily involving QH, is a significant equestrian sport in Brazil. Since the allele frequencies (AF) of MYHM, PSSM1, HyPP, and MH in vaquejada QH remain unknown, this study evaluated the AF in 129 QH vaquejada athletes, specifically from the Brazilian Northeast. These variants were exclusively observed in heterozygosity. The MYHM exhibited the highest AF (0.04 ±0.01), followed by PSSM1 (0.01 ±0.01) and the HyPP variant (0.004 ±0.01), while the MH variant was not identified in this study. This study represents the first identification of these variants in vaquejada QH, emphasizing the need to implement measures to prevent the transmission of pathogenic alleles and reduce the occurrence of clinical cases of these genetic diseases.


Subject(s)
Gene Frequency , Horse Diseases , Horses , Muscular Diseases , Muscular Diseases/congenital , Muscular Diseases/genetics , Muscular Diseases/veterinary , Animals , Horses/genetics , Horse Diseases/genetics , Male , Female , Brazil , Paralysis, Hyperkalemic Periodic/genetics , Paralysis, Hyperkalemic Periodic/veterinary , Malignant Hyperthermia/genetics , Malignant Hyperthermia/veterinary , Polysaccharides/metabolism , Genetic Testing
2.
Indian J Pharmacol ; 47(6): 616-9, 2015.
Article in English | MEDLINE | ID: mdl-26729952

ABSTRACT

OBJECTIVES: To investigate if fluoroquinolones (FQs) influence skeletal muscle metabolism of healthy and malignant hyperthermia susceptible (MHS) pigs. MATERIALS AND METHODS: After approval from of the Animal Care Committee, 10 MHS pigs, and 6 MHS pigs were anesthetized with hemodynamic and systemic metabolic monitoring. Microdialysis catheters were placed intramuscularly. After equilibration, levofloxacin and ciprofloxacin were injected as a rapid bolus and continuous infusions. Lactate was measured in the dialysate and statistically analyzed was done (Wilcoxon-test; U-test; P < 0.05). RESULTS: There were no differences in age, weight, and baseline lactate levels between the groups. Both applications of levofloxacin- and ciprofloxacin-induced an increase of local lactate levels in healthy and MHS pigs. No difference between the two groups was observed. CONCLUSION: FQs influence skeletal muscle metabolism. Myotoxic effects of FQs can, therefore, be explained by an influence on the cellular energy balance.


Subject(s)
Anti-Bacterial Agents/pharmacology , Ciprofloxacin/adverse effects , Energy Metabolism/drug effects , Fluoroquinolones/pharmacology , Levofloxacin/adverse effects , Muscle, Skeletal/drug effects , Topoisomerase II Inhibitors/pharmacology , Animals , Animals, Inbred Strains , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Belgium , Ciprofloxacin/administration & dosage , Disease Susceptibility , Drug Resistance , Fluoroquinolones/administration & dosage , Fluoroquinolones/adverse effects , Infusions, Intravenous , Lactic Acid/blood , Levofloxacin/administration & dosage , Malignant Hyperthermia/blood , Malignant Hyperthermia/metabolism , Malignant Hyperthermia/veterinary , Microdialysis , Muscle, Skeletal/metabolism , Sus scrofa , Swine , Swine Diseases/blood , Swine Diseases/metabolism , Topoisomerase II Inhibitors/administration & dosage , Topoisomerase II Inhibitors/adverse effects , Up-Regulation/drug effects
3.
Vet Anaesth Analg ; 41(3): 290-6, 2014 May.
Article in English | MEDLINE | ID: mdl-24224698

ABSTRACT

HISTORY: A four year old male neutered Domestic Short Hair cat presented for general anaesthesia for hind limb orthopaedic surgery. The cat had been anaesthetized four days previously with propofol and isoflurane and made an uneventful recovery. PHYSICAL EXAMINATION AND MANAGEMENT: On pre-anaesthetic examination the cat had a temperature of 38.9 °C and was otherwise healthy. After a premedication of acepromazine and pethidine, anaesthesia was induced with thiopental and maintained with isoflurane in oxygen 50% and nitrous oxide 50%. Increases in heart rate, respiratory rate, end tidal carbon dioxide tension and temperature were observed, occurring sequentially, from 110 to 175 minutes after anaesthetic induction. Despite ceasing all warming measures and attempting to cool the patient, body temperature continued to rapidly rise, reaching 42.5 °C and limb rigidity was observed. Isoflurane administration was stopped and esmolol was administered. Cardiac arrest occurred. Cardio-pulmonary cerebral resuscitation was commenced and a lateral thoracotomy was performed to allow cardiac compressions and internal defibrillation. Atropine, adrenaline, glucose and dopamine were administered and cold saline was instilled into the thoracic cavity. FOLLOW-UP: Resuscitation was unsuccessful and the cat died. CONCLUSIONS: A presumptive diagnosis of malignant hyperthermia was made. Malignant hyperthermia should be considered, even if prior exposure to volatile inhalational anaesthesia was uneventful, and prompt and aggressive therapy instituted.


Subject(s)
Anesthesia, General/veterinary , Cat Diseases/chemically induced , Malignant Hyperthermia/veterinary , Anesthesia, General/adverse effects , Anesthetics, Inhalation/adverse effects , Animals , Cats , Fatal Outcome , Isoflurane/adverse effects , Male , Malignant Hyperthermia/etiology , Malignant Hyperthermia/pathology
4.
J Wildl Dis ; 49(2): 403-7, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23568917

ABSTRACT

Twenty-eight anesthetic events were carried out on 24 free-ranging Scandinavian gray wolves (Canis lupus) by darting from a helicopter with 5 mg medetomidine and 250 mg ketamine during winter in 2002 and 2003. Mean±SD doses were 0.162±0.008 mg medetomidine/kg and 8.1±0.4 mg ketamine/kg in juveniles (7-10 mo old) and 0.110±0.014 mg medetomidine/kg and 5.7±0.5 mg ketamine/kg in adults (>19 mo old). Mean±SD induction time was shorter (P<0.01) in juveniles (2.3±0.8 min) than in adults (4.1±0.6 min). In 26 cases, the animals were completely immobilized after one dart. Muscle relaxation was good, palpebral reflexes were present, and there were no reactions to handling or minor painful stimuli. Mild to severe hyperthermia was detected in 14/28 anesthetic events. Atipamezole (5 mg per mg medetomidine) was injected intramuscularly for reversal 98±28 and 94±40 min after darting in juveniles and adults, respectively. Mean±SD time from administration of atipamezole to coordinated walking was 38±20 min in juveniles and 41±21 min in adults. Recovery was uneventful in 25 anesthetic events, although vomiting was observed in five animals. One adult that did not respond to atipamezole was given intravenous fluids and was fully recovered 8 hr after darting. Two animals died 7-9 hr after capture, despite intensive care. Both mortalities were attributed to shock and circulatory collapse following stress-induced hyperthermia. Although effective, this combination cannot be recommended for darting free-ranging wolves from helicopter at the doses presented here because of the severe hyperthermia seen in several wolves, two deaths, and prolonged recovery in one individual.


Subject(s)
Immobilization/veterinary , Ketamine/administration & dosage , Malignant Hyperthermia/veterinary , Medetomidine/administration & dosage , Wolves/physiology , Anesthesia Recovery Period , Anesthetics, Dissociative/administration & dosage , Anesthetics, Dissociative/adverse effects , Anesthetics, Dissociative/antagonists & inhibitors , Animals , Animals, Newborn , Animals, Wild , Cause of Death , Dose-Response Relationship, Drug , Female , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Hypnotics and Sedatives/antagonists & inhibitors , Imidazoles/pharmacology , Immobilization/methods , Ketamine/adverse effects , Ketamine/antagonists & inhibitors , Male , Malignant Hyperthermia/mortality , Medetomidine/adverse effects , Medetomidine/antagonists & inhibitors
5.
J Anim Sci ; 90(9): 3220-31, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22966081

ABSTRACT

This study aimed at evaluating the effects of trailer design on stress responses and meat quality traits of 3 different pig crosses: 50% Pietrain breeding with halothane (HAL)(Nn) (50Nn); 50% Pietrain breeding with HAL(NN) (50NN); and 25% Pietrain breeding with HAL(NN) genotype (25NN). Over a 6-wk period, pigs (120 pigs/crossbreed) were transported for 7 h in either a pot-belly (PB) or flat-deck (FD) trailer (10 pigs/crossbreed(-1)·trailer(-1)·wk(-1)). Temperature (T) and relative humidity (RH) were monitored in each trailer. Behaviors during loading and unloading, time to load and unload, and latency to rest in lairage were recorded, whereas a sub-population of pigs (4 pigs/crossbreed(-1)·trailer(-1)·wk(-1)) was equipped with gastro-intestinal tract (GIT) temperature monitors. Blood samples were collected at exsanguination for measurement of cortisol, creatine kinase (CK), lactate, haptoglobin, and Pig-MAP concentrations. Meat quality data were collected at 24 h postmortem from the LM and semimembranosus (SM) and adductor (AD) muscles of all 360 pigs. Greater T were recorded in the PB trailer during transportation (P = 0.006) and unloading (P < 0.001). Delta GIT temperature was greater (P = 0.01) in pigs unloaded from the PB. At loading, pigs tended to move backwards more (P = 0.06) when loaded on the FD than the PB trailer. At unloading, an interaction was found between trailer type and crossbreed type, with a greater (P < 0.01) frequency of overlaps in 50NN and 25NN pigs and slips/falls in 50Nn and 50NN pigs from the FD than the PB trailer. Cortisol concentrations at slaughter were greater (P = 0.02) in pigs transported in the PB than FD trailer. Greater lactate concentrations were found in 50Nn and 50NN pigs (P = 0.003) and greater CK concentrations (P < 0.001) in 50Nn pigs. As expected, 50Nn pigs produced leaner (P < 0.001) carcasses, with greater (P = 0.01) dressing percentages, as well as lower (P < 0.001) ultimate pH values and greater (P < 0.001) drip loss percentages in the LM and greater (P = 0.002) drip losses and a paler color (greater L* values, P = 0.02) in the SM than 50NN pigs. When used for long distance transportation under controlled conditions, the PB trailer produced no detrimental effects on animal welfare or pork quality. Pigs with 50% Pietrain crossbreeding appear to be more responsive to transport stress, having the potential to produce acceptable carcass and pork quality, provided pigs are free of the HAL gene.


Subject(s)
Animal Welfare , Meat/standards , Transportation , Animals , Behavior, Animal , Body Composition , Crosses, Genetic , Genotype , Humidity , Male , Malignant Hyperthermia/genetics , Malignant Hyperthermia/veterinary , Swine/genetics , Swine/physiology , Swine Diseases/genetics , Temperature , Time Factors
6.
J Am Vet Med Assoc ; 240(4): 450-3, 2012 Feb 15.
Article in English | MEDLINE | ID: mdl-22309018

ABSTRACT

CASE DESCRIPTION: A 7-month-old male Siberian Husky affected by lower motor neuron tetraparesis was anesthetized for electrodiagnostic testing and collection of muscle and nerve biopsy specimens. CLINICAL FINDINGS: Preanesthetic physical examination revealed a high rectal temperature, and serum biochemical analysis revealed high muscle and liver enzyme activities. The dog was anesthetized twice. The dog was anesthetized with isoflurane and developed moderate hypercarbia and mild hyperthermia. Injectable anesthetic agents were used to anesthetize the dog the second time, during which the dog developed severe malignant hyperthermia. A genetic test performed after anesthesia did not reveal a mutation of the RYR1 gene, the gene that mediates calcium-release channels in skeletal muscle. On the basis of clinical features, and because other neuromuscular disorders were ruled out, a genetic channelopathy involving the skeletal muscle ion channels was suspected. TREATMENT AND OUTCOME: The dog was disconnected from the breathing system, and active cooling of the body was performed with ice packs applied to the body surface and alcohol applied to the foot pads. Cold crystalloid solutions were administered i.v.. Intermittent positive-pressure ventilation with 100% oxygen was performed to decrease end-tidal partial pressure of carbon dioxide. Because dantrolene was not available, acepromazine was administered to facilitate a decrease in body temperature. The dog recovered from malignant hyperthermia and was discharged to the owner after 13 days of hospitalization. CLINICAL RELEVANCE: Dogs affected by genetic muscle disorders should be considered at risk for perianesthetic malignant hyperthermia, even in the absence of an RYR1 gene mutation.


Subject(s)
Anesthesia/veterinary , Dog Diseases/genetics , Malignant Hyperthermia/veterinary , Ryanodine Receptor Calcium Release Channel/genetics , Anesthesia/adverse effects , Animals , Diagnosis, Differential , Dogs , Male , Malignant Hyperthermia/genetics , Mutation
8.
J Vet Intern Med ; 24(5): 1224-8, 2010.
Article in English | MEDLINE | ID: mdl-20584138

ABSTRACT

BACKGROUND: The efficacy of intravenous (IV) administration of azumolene (Az), an analogue 30-fold more soluble than dantrolene, on pigs susceptible to malignant hyperthermia (MH) is incompletely understood. OBJECTIVE: To evaluate efficacy of Az on MH crisis in pigs. ANIMALS: Eight normal (MHN) and 7 susceptible to MH (MHS) pigs (Landrace × Large White × Pietran). METHODS: Prospective, laboratory trial. Hypermetabolic crisis was observed in MHS pigs, but not in MHN pigs, after a combined administration of inhaled halothane (1.5%) and IV injection of succinylcholine (SCh; 2.5 mg/kg). Susceptibility was confirmed using a caffeine and halothane contracture test. Az was administered 15 minutes after administration of SCh. RESULTS: Respiratory acidosis (pH 7.16 ± 0.02; Pco(2) , 46.2 ± 9.1 mmHg, HCO(3) , 22.5 ± 2.3 mmol/L), fever (38.2 ± 1.1°C), cardiac arrhythmias, and muscle contracture were observed in MHS pigs. MHS pigs (n = 5) treated with Az (2 mg/kg IV) survived the crisis with attenuation of signs (pH 7.30 ± 0.10; Pco(2) , 36.3 ± 4.5 mmHg; HCO(3) , 22.9 ± 2.3 mmol/L) and recovery of normal muscle tone and cardiac rhythm. CONCLUSIONS AND CLINICAL IMPORTANCE: Az represents a possible substitute for dantrolene to reverse MH crisis in susceptible pigs.


Subject(s)
Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/therapeutic use , Imidazoles/administration & dosage , Imidazoles/therapeutic use , Malignant Hyperthermia/veterinary , Oxazoles/administration & dosage , Oxazoles/therapeutic use , Swine Diseases/drug therapy , Anesthetics, Inhalation/adverse effects , Animals , Female , Genotype , Halothane/adverse effects , Male , Malignant Hyperthermia/drug therapy , Malignant Hyperthermia/etiology , Malignant Hyperthermia/genetics , Swine , Swine Diseases/genetics
9.
Vet Anaesth Analg ; 37(1): 35-43, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20017817

ABSTRACT

OBJECTIVE: To determine which class of opioid alone or in conjunction with other anesthetic drugs causes post-anesthetic hyperthermia in cats. STUDY DESIGN: Prospective, randomized, crossover study. ANIMALS: Eight adult, healthy, cats (four spayed females and four castrated males weighing 3.8 +/- 0.6 kg). METHODS: Each cat was instrumented with a wireless thermistor in the abdominal cavity. Temperature in all phases was recorded every 5 minutes for 5 hours. Population body temperature (PBT) was recorded for approximately 8 days. Baseline body temperature is the final 24 hours of the PBT. All injectable drugs were given intramuscularly. The cats were administered drugs in four phases: 1) hydromorphone (H) 0.05, 0.1, or 0.2 mg kg(-1); 2) morphine (M) (0.5 mg kg(-1)), buprenorphine (BUP) (0.02 mg kg(-1)), or butorphanol (BUT) (0.2 mg kg(-1)); 3) ketamine (K) (5 mg kg(-1)) or ketamine (5 mg kg(-1)) plus hydromorphone (0.1 mg kg(-1)) (KH); 4) isoflurane in oxygen for 1 hour. Fifteen minutes prior to inhalant anesthetic, cats received either no premed (I), hydromorphone (0.1 mg kg(-1)) (IH), or hydromorphone (0.1 mg kg(-1)) plus ketamine (5 mg kg(-1)) (IHK). RESULTS: Mean PBT for all unmedicated cats was 38.9 +/- 0.6 degrees C (102.0 +/- 1 degrees F). The temperature of cats administered all doses of hydromorphone increased from baseline (p < 0.03) All four opioids (H, M, BUP and BUT) studied increased body temperature compared with baseline (p < 0.005). A significant difference was observed between baseline temperature values and those in treatment KH (p < 0.03). Following recovery from anesthesia, temperature in treatments IH and IHK was different from baseline (p < 0.002). CONCLUSIONS AND CLINICAL RELEVANCE: All of the opioids tested, alone or in combination with ketamine or isoflurane, caused an increase in body temperature. The increase seen was mild to moderate (<40.1 degrees C (104.2 degrees F) and self limiting.


Subject(s)
Analgesics, Opioid/pharmacology , Anesthetics/pharmacology , Body Temperature/drug effects , Cats/physiology , Anesthetics, Combined/pharmacology , Anesthetics, Inhalation/pharmacology , Animals , Buprenorphine/pharmacology , Cross-Over Studies , Female , Hydromorphone/pharmacology , Isoflurane/pharmacology , Ketamine/pharmacology , Male , Malignant Hyperthermia/veterinary , Morphine/pharmacology
10.
J Vet Intern Med ; 23(3): 619-22, 2009.
Article in English | MEDLINE | ID: mdl-19298609

ABSTRACT

BACKGROUND: Anesthetic-induced malignant hyperthermia has been documented in Quarter Horses and is caused by a single-point mutation in the ryanodine receptor 1 gene at nucleotide C7360G generating a R2454G amino acid substitution. An accurate, faster molecular test that is less prone to contamination would facilitate screening for the mutation in horses intended for breeding, in those undergoing surgical procedures, and in those with clinical signs compatible with malignant hyperthermia. OBJECTIVE: To report a rapid and accurate method for the detection of the ryanodine receptor 1 C7360G mutation. ANIMALS: Eleven diseased, 10 healthy, and 225 randomly selected Quarter Horses. METHODS: This study included horses with the ryanodine receptor 1 C7360G mutation as detected by gene sequencing. Available genomic and complementary DNA extracted from whole blood, hair or skeletal muscle was used for genetic analysis. Real-time polymerase chain reaction (RT-PCR) melting curve analysis was performed by equine specific primers and 2 hybridization probes (sensor and anchor probes) that contain the site of the mutation. Results from this method were blinded and compared with nucleic acid sequencing for validation. RESULTS: A rapid genotyping assay with fluorescence resonance energy transfer probes and melting curve analysis was accurate (100% agreement, K= 1) for identification of affected horses. The prevalence of the mutation in a random population of Quarter Horses was 1.3%. CONCLUSIONS AND CLINICAL IMPORTANCE: Malignant hyperthermia in Quarter Horses can be rapidly and accurately detected by RT-PCR melting curve genotyping with hybridization probes.


Subject(s)
Horses/genetics , Ryanodine Receptor Calcium Release Channel/genetics , Animals , Gene Expression Regulation , Genotype , Malignant Hyperthermia/genetics , Malignant Hyperthermia/veterinary , Mutation , Nucleic Acid Denaturation/genetics , Reverse Transcriptase Polymerase Chain Reaction/instrumentation , Reverse Transcriptase Polymerase Chain Reaction/veterinary
11.
J Vet Intern Med ; 23(2): 329-34, 2009.
Article in English | MEDLINE | ID: mdl-19220734

ABSTRACT

BACKGROUND: Anesthetic-induced malignant hyperthermia (MH) has been documented in Quarter Horses with a single point mutation in the ryanodine receptor 1 gene (RyR1) at nucleotide C7360G, generating a R2454G amino acid substitution. However, there have been no reports of nonanesthetic manifestations of MH in horses with the C7360G mutation. OBJECTIVE: To describe clinical manifestations of Quarter Horses with the C7360G mutation. ANIMALS: Eleven Quarter Horses with the RyR1 C7360G mutation. METHODS: This prospective study included horses with suspected MH, undetermined etiology of sudden death, death within hours of onset of rhabdomyolysis, muscle rigidity, stiffness, intermittent sweating, and persistent increases in serum muscle enzyme activities. Whole blood in EDTA and skeletal muscle were processed for genetic and histochemical analysis. Medical records and pedigrees were collected when available. RESULTS: Both anesthetic- and non-anesthetic-associated myopathic manifestations of MH occurred in halter Quarter Horses with mutation of RyR1. The disease is inherited as an autosomal dominant trait. Clinical and laboratory abnormalities were similar in both forms. Rhabdomyolysis was a common finding in both groups of horses. Skeletal muscle histochemical findings were nonspecific and compatible with a noninflammatory myopathic process. CONCLUSIONS AND CLINICAL IMPORTANCE: MH is a potentially fatal disease of Quarter Horses that could be triggered by halogenated anesthetics and other nonanesthetic factors that may include exercise, stress, breeding, illnesses, and concurrent myopathies.


Subject(s)
Horse Diseases/genetics , Malignant Hyperthermia/veterinary , Point Mutation , Ryanodine Receptor Calcium Release Channel/genetics , Animals , DNA/chemistry , DNA/genetics , Female , Histocytochemistry/veterinary , Horses , Male , Malignant Hyperthermia/genetics , Prospective Studies , Sequence Analysis, DNA
12.
J Am Anim Hosp Assoc ; 45(1): 3-13, 2009.
Article in English | MEDLINE | ID: mdl-19122058

ABSTRACT

Clinical and metabolic variables were evaluated in 14 Labrador retrievers with exercise-induced collapse (EIC) before, during, and following completion of a standardized strenuous exercise protocol. Findings were compared with previously reported variables from 14 normal Labrador retrievers that participated in the same protocol. Ten of 14 dogs with EIC developed an abnormal gait during evaluation, and these dogs were significantly more tachycardic and had a more severe respiratory alkalosis after exercise compared to the normal dogs. Muscle biopsy characteristics and sequential lactate and pyruvate concentrations were normal. Genetic testing and linkage analysis excluded malignant hyperthermia as the cause of EIC. Common causes of exercise intolerance were eliminated, but the cause of collapse in EIC was not determined.


Subject(s)
Dog Diseases/physiopathology , Dogs/physiology , Physical Conditioning, Animal/adverse effects , Animals , Biopsy/veterinary , Blood Chemical Analysis , Body Temperature , Carnitine/analysis , Carnitine/blood , Carnitine/urine , Dog Diseases/genetics , Dogs/genetics , Female , Male , Malignant Hyperthermia/veterinary , Quadriceps Muscle/surgery , Rest/physiology , Ryanodine Receptor Calcium Release Channel/genetics
13.
Eur J Anaesthesiol ; 25(1): 48-57, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17686208

ABSTRACT

BACKGROUND: The caffeine/halothane contracture test in North America and the in vitro contracture test in Europe are currently the only validated bioassays for diagnosing malignant hyperthermia susceptibility and phenotyping families. Both tests are invasive requiring surgical muscle biopsy. Here, we report first use of the selective ryanodine receptor type I agonist ryanodine in a percutaneous microdialysis protocol designed to test whether microdialysis-induced local metabolic responses of skeletal muscle due to ryanodine receptor activation can differentiate between malignant hyperthermia-sensitive and normal pigs. METHODS: Six microdialysis catheters were implanted percutaneously into the adductor muscles of the right and left thighs of malignant hyperthermia-susceptible (n = 9) and normal (n = 8) anaesthetized (ketamine/propofol) and mechanically ventilated swine. Systemic blood gases, haemodynamic parameters and creatine kinase levels were measured before, during and after microdialysis perfusion of ryanodine. After a post-implantation equilibration period of 30 min, one catheter perfused (2 micro min-1) with 0.9% NaCl (control) and was compared with the remaining five catheters perfused with increasing concentrations of ryanodine (0.2-100 micromol). Lactate and pyruvate levels were measured enzymatically. RESULTS: Continuous perfusion with ryanodine revealed dose-dependent sigmoidal increases in the dialysate lactate and lactate-pyruvate ratio parameters; these effects were greatly augmented in malignant hyperthermia-susceptible pigs compared to normal pigs (two- to threefold): estimated EC50 greatly decreased (>19-fold) while the maximum effect increased (>twofold) in the malignant hyperthermia-susceptible group. CONCLUSION: The in vivo percutaneous microdialysis protocol for skeletal muscle, using ryanodine as the ryanodine receptor type I agonist and dialysed lactate-pyruvate parameters as metabolic index, can reproducibly differentiate between malignant hyperthermia-susceptible and normal swine.


Subject(s)
Lactates/metabolism , Malignant Hyperthermia/veterinary , Microdialysis/methods , Muscle, Skeletal/metabolism , Pyruvates/metabolism , Ryanodine/pharmacology , Animals , Caffeine/pharmacology , Disease Susceptibility , Halothane/pharmacology , Kinetics , Malignant Hyperthermia/epidemiology , Malignant Hyperthermia/genetics , Microdialysis/veterinary , Muscle, Skeletal/drug effects , Reference Values , Ryanodine Receptor Calcium Release Channel/physiology , Swine , Swine Diseases/epidemiology , Swine Diseases/genetics
16.
Muscle Nerve ; 30(3): 356-65, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15318347

ABSTRACT

Equine malignant hyperthermia MH has been suspected but never genetically confirmed. In this study, we investigated whether mutations in a candidate gene, RyR1, were associated with MH in two clinically affected horses. RyR1 gene sequences revealed polymorphisms in exons 15, 17, and 46 in WTRyR1 and MHRyR1 horses with one derived amino acid change in MHRyR1 exon 46, R2454G. The MHRyR1 horses were genetically heterozygous for this mutation, but presented an MH phenotype with halothane challenge. Skeletal sarcoplasmic reticulum from a R2454G heterozygote collected during a fulminant MH episode showed significantly higher affinity and density of [3H]ryanodine-binding sites compared to WTRyR1, but no differences in Ca2+, Mg2+, and caffeine modulation. In conclusion, an autosomal missense mutation in RyR1 is associated with MH in the horse, providing a screening test for susceptible individuals. [3H]ryanodine-binding analysis suggests that long-lasting changes in RyR1 conformation persists in vitro after the triggering event.


Subject(s)
Horse Diseases/genetics , Malignant Hyperthermia/genetics , Malignant Hyperthermia/veterinary , Mutation , Ryanodine Receptor Calcium Release Channel/genetics , Amino Acid Sequence , Animals , Base Sequence , Histocytochemistry , Horse Diseases/metabolism , Horses , Malignant Hyperthermia/metabolism , Molecular Sequence Data , Muscle, Skeletal/metabolism , Protein Binding , Protein Isoforms/genetics , Protein Isoforms/metabolism , Ryanodine Receptor Calcium Release Channel/metabolism
17.
J Anim Sci ; 80(4): 997-1004, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12002337

ABSTRACT

The objective of this research was to examine the impact of supplementation with creatine monohydrate (CMH) on the quality of various muscles from normal and heterozygous halothane carrier pigs. Twenty-nine crossbred pigs, 16 normal (NN) and 13 halothane carrier (Nn) genotypes, were supplemented with 0 or 25 g x pig(-1) x d(-1) of CMH for 5 d before slaughter. Supplemented pigs gained 2.26 kg more weight (P < 0.05) during 5 d of supplementation. There were trends (P < 0.10) toward higher objective marbling scores and lower cooking loss for supplemented pigs. The 45-min pH was 0.27 units higher (P < 0.05) for supplemented pigs in the semimembranosus; CMH supplementation did not influence (P > 0.05) drip loss or muscle composition. Supplementation with CMH also resulted in lower L* values in two ham muscles, semitendinosus (5.15 units) (P < 0.05) and semimembranosus (1.95 units) (P < 0.10) for Nn carcasses. Genotype had significant effects on most quality indicators, with Nn carcasses producing lower-quality lean as evidenced by less desirable subjective and objective color and higher drip losses. Genotype also affected the composition of several muscles, with the NN carcasses having more fat and less moisture.


Subject(s)
Creatine/administration & dosage , Malignant Hyperthermia/veterinary , Meat/standards , Swine Diseases/genetics , Swine/growth & development , Animal Feed , Animals , Body Temperature , Cooking , Creatine/pharmacology , Dietary Supplements , Female , Genotype , Halothane/adverse effects , Heterozygote , Hydrogen-Ion Concentration , Male , Malignant Hyperthermia/genetics , Malignant Hyperthermia/physiopathology , Muscle, Skeletal/chemistry , Swine/genetics , Swine Diseases/physiopathology , Weight Gain/drug effects
18.
J Anim Sci ; 79(9): 2346-55, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11583421

ABSTRACT

We examined the effects of vitamin and mineral supplementation of the finishing diet on growth and accelerated chilling of carcasses on carcass and muscle traits of halothane gene carrier and noncarrier pigs. Barrows and gilts that were either monomutants (MON, n = 49) or noncarriers (NON, n = 28) of the halothane gene were fed a standard finishing diet until they reached 86 kg. They then were randomly assigned to one of four finishing diets formulated to contain 11 IU/kg vitamin E (0), 311 IU/kg vitamin E plus additional vitamins and minerals (300), 611 IU/kg vitamin E plus additional vitamins and minerals (600), or 911 IU/kg vitamin E plus additional vitamins and minerals (900) until they were slaughtered (118 kg). Alternating carcass sides were assigned either a normal chilling procedure (NC, 4 degrees C for 24 h) or an accelerated chilling procedure (AC, -20 degrees C for 1.5 h and then 4 degrees C for 22.5 h). Supplementing vitamin E in the finishing diet increased (P < 0.05) the concentration of vitamin E in the longissimus muscle. Supplementing vitamin E in the diets of MON pigs did not affect color, firmness, or cooking losses of loins or color and firmness of hams. For the NON genotype, increasing the level of vitamin E in the diet decreased (P < 0.05) the percentage of PSE loins and hams. Color and firmness scores of the gluteus medius and longissimus muscles were improved 0.4 unit (P < 0.005) by AC compared with NC of carcasses. Loin chop juiciness and flavor were improved (P < 0.05) in the MON genotype for AC compared to NC. Accelerated chilling reduced (P < 0.05) the percentage of PSE loins from 38 to 17% and PSE hams from 32 to 10% for the MON genotype, but percentage of PSE was not affected (P > 0.05) by chilling treatment for the NON genotype. No interaction between diet and chill treatments existed for muscle quality traits (P > 0.05). Supplementing finishing diets of NON pigs with at least 600 IU/kg vitamin E, in addition to other vitamins and minerals, or accelerated chilling of MON carcasses can reduce the incidence of PSE pork.


Subject(s)
Food Handling/methods , Meat/standards , Minerals/pharmacology , Swine/genetics , Vitamins/pharmacology , Animals , Cold Temperature , Color , Female , Halothane , Heterozygote , Male , Malignant Hyperthermia/genetics , Malignant Hyperthermia/veterinary , Minerals/administration & dosage , Muscles/chemistry , Random Allocation , Time Factors , Vitamin E/administration & dosage , Vitamin E/pharmacology , Vitamins/administration & dosage , Weight Gain
19.
Anesthesiology ; 95(3): 716-25, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11575546

ABSTRACT

BACKGROUND: Malignant hyperthermia (MH) is an inherited disorder of skeletal muscle characterized by hypercarbia, rhabdomyolysis, generalized skeletal muscle contracture, cardiac dysrhythmia, and renal failure, that develops on exposure to succinylcholine or volatile anesthetic agents. All swine and up to 50% of human MH events are thought to be associated with mutations in the calcium release channel of the sarcoplasmic reticulum, also known as the ryanodine receptor (RYR1). Events resembling MH have been reported in other species, but none have undergone genetic investigation to date. METHODS: To determine the molecular basis of canine MH, a breeding colony was established with a male, mixed-breed, MH-susceptible (MHS) dog that survived an in vivo halothane-succinylcholine challenge. He was mated to three unaffected females to produce four litters and back-crossed to an affected daughter to produce one litter. One of his MHS sons was mated to an unaffected female to produce an additional litter. Forty-seven dogs were phenotyped with an in vitro contracture test and diagnosed as MHS or MH normal based on the North American in vitro contracture test protocol. Nine microsatellite markers in the vicinity of RYR1 on canine chromosome 1 (CFA01) were tested for linkage to the MHS phenotype. Mutational analysis in two MHS and two MH-normal dogs was performed with direct sequencing of polymerase chain reaction products and of cloned fragments that represent frequently mutated human RYR1 regions. A restriction fragment length polymorphism was chosen to detect the candidate mutation in the pedigree at large. RESULTS: Pedigree inspection revealed that MHS in this colony is transmitted as an autosomal dominant trait. FH2294, the marker closest to RYR1, is linked to MHS at a theta = 0.03 with a LOD score of 9.24. A T1640C mutation gives rise to an alanine for valine substitution of amino acid 547 in the RYR1 protein, generating a maximum LOD score of 12.29 at theta = 0.00. All dogs diagnosed as MHS by in vitro contracture test were heterozygous for the mutation, and all MH-normal dogs were homozygous for the T1640 allele. CONCLUSIONS: These results indicate that autosomal dominant canine MH is caused by a mutation in the gene encoding the skeletal muscle calcium release channel and that the MHS trait in this pedigree of mixed-breed dogs is in perfect cosegregation with the RYR1 V547A mutation.


Subject(s)
Dog Diseases/genetics , Malignant Hyperthermia/veterinary , Mutation , Ryanodine Receptor Calcium Release Channel/genetics , Amino Acid Sequence , Animals , Dogs , Female , Genotype , Halothane/pharmacology , In Vitro Techniques , Malignant Hyperthermia/genetics , Molecular Sequence Data , Muscle Contraction/drug effects , Succinylcholine/pharmacology
20.
Rev Esp Anestesiol Reanim ; 48(2): 81-4, 2001 Feb.
Article in Spanish | MEDLINE | ID: mdl-11257956

ABSTRACT

A large-white pig that had not been genetically selected to develop malignant hyperthermia (MH) during anesthesia nevertheless suffered an episode of severe MH after repeated exposure to increasing concentrations of desflurane. MH is a hypermetabolic alteration that may develop in susceptible patients who have inhaled certain drugs or agents that act as triggers. Early identification and appropriate treatment are essential to reduce the likelihood of death associated with this severe alteration. We report a case of late-developing MH triggered by low concentrations of inhaled desflurane.


Subject(s)
Anesthetics, Inhalation/adverse effects , Isoflurane/analogs & derivatives , Isoflurane/administration & dosage , Malignant Hyperthermia/veterinary , Animals , Desflurane , Male , Malignant Hyperthermia/etiology , Swine
SELECTION OF CITATIONS
SEARCH DETAIL
...