A battery-less implantable glucose sensor based on electrical impedance spectroscopy.

The ability to perform accurate continuous glucose monitoring without blood sampling has revolutionised the management of diabetes. Newer methods that can allow measurements during longer periods are necessary to substantially improve patients' quality of life. This paper presents an alternative method for glucose monitoring which is based on electrical impedance spectroscopy. A battery-less implantable bioimpedance spectroscope was designed, built, and used in an in vivo study on pigs. After a recovery period of 14 days post surgery, a total of 236 subcutaneous bioimpedance measurements obtained from intravenous glucose tolerance tests, with glucose concentration ranges between 77.4 and 523.8 mg/dL, were analyzed. The results show that glucose concentrations estimated by subcutaneous bioimpedance measurements correlate very well to the blood glucose reference values. The pigs were clinically healthy throughout the study, and the postmortem examinations revealed no signs of adverse effects related to the sensor. The implantation of the sensor requires minor surgery. The implant, being externally powered, could in principle last indefinitely. These encouraging results demonstrate the potential of the bioimpedance method to be used in future continuous glucose monitoring systems.

Nursing and training of pigs used in renal transplantation studies.

The pig is commonly used in renal transplantation studies since the porcine kidney resembles the human kidney. To meet the requirements of intense caretaking and examination without stress, a 2-week socialisation and training programme was developed. Conventional cross-breed pigs (n = 36) with high health status were trained for 15 min/day in a four-step training programme before kidney transplantation. The systematic training resulted in calm animals, which allowed for ultrasound examination, blood sampling and urine sampling without restraint. When a 2-methacryloyloxyethyl phosphorylcholine polymer-coated jugular catheter introduced via the auricular vein was used for post-operative blood sampling, clotting was avoided. To assess renal function, urinary output was observed and creatinine and cystatin C were measured; the latter was not found to be useful in recently transplanted pigs. The results presented contribute to the 3Rs (refine, reduce, replace).

In Vivo Visualization of ß-Cells by Targeting of GPR44.

GPR44 expression has recently been described as highly ß-cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes. A radiolabeled small-molecule GPR44 antagonist, [11C]AZ12204657, was evaluated for visualization of ß-cells in pigs and nonhuman primates by positron emission tomography as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from subjects without and with diabetes, in combination with insulin staining, was performed to assess ß-cell selectivity of the radiotracer. Proof of principle of in vivo targeting of human islets by [11C]AZ12204657 was shown in the immunodeficient mouse transplantation model. Furthermore, [11C]AZ12204657 bound by a GPR44-mediated mechanism in pancreatic sections from humans and pigs without diabetes, but not those with diabetes. In vivo [11C]AZ12204657 bound specifically to GPR44 in pancreas and spleen and could be competed away dose-dependently in nondiabetic pigs and nonhuman primates. [11C]AZ12204657 is a first-in-class surrogate imaging biomarker for pancreatic ß-cells by targeting the protein GPR44.

A new synthetic granular calcium phosphate compound induces new bone in a sinus lift rabbit model.

OBJECTIVES: The aim of this study was to investigate if a synthetic granular calcium phosphate compound (CPC) and a composite bisphosphonate-linked hyaluronic acid-calcium phosphate hydrogel (HABP·CaP) induced similar or more amount of bone as bovine mineral in a modified sinus lift rabbit model. MATERIAL AND METHODS: Eighteen adult male New Zeeland White rabbits, received randomly one of the two test materials on a random side of the face, and bovine mineral as control on the contralateral side. In a sinus lift, the sinus mucosa was elevated and a titanium mini-implant was placed in the alveolar bone. Augmentation material (CPC, HABP·CaP or bovine bone) was applied in the space around the implant. The rabbits were euthanized three months after surgery and qualitative and histomorphometric evaluation were conducted. Histomorphometric evaluation included three different regions of interest (ROIs) and the bone to implant contact on each installed implant. RESULTS: Qualitative assessment (p = <.05), histomorphometric evaluations (p = < .01), and implant incorporation (p = <.05) showed that CPC and bovine mineral induced similar amount of bone and more than the HABP·CaP hydrogel. CONCLUSION: CPC induced similar amount of bone as bovine mineral and both materials induced more bone than HABP·CaP hydrogel. CLINICAL SIGNIFICANCE: The CPC is suggested as a synthetic alternative for augmentations in the maxillofacial area.

Carprofen neither reduces postoperative facial expression scores in rabbits treated with buprenorphine nor alters long term bone formation after maxillary sinus grafting.

In connection with bilateral maxillary sinus augmentation, the acute effects of the nonsteroidal anti-inflammatory drug carprofen on facial expressions and long-term effects on bone formation were evaluated in 18 male New Zealand White rabbits. A 10×10mm bone window was drilled in the maxilla, the sinus membrane elevated and a titanium mini-implant inserted. One of two test materials was randomly inserted unilaterally and bovine bone chips (control) on the contralateral side in the created space. Rabbits were randomly allocated to receive buprenorphine plus carprofen (n=9) or buprenorphine plus saline (n=9) postoperatively. Buprenorphine was administered subcutaneously every 6h for 3days in a tapered dose (0.05-0.01mg/kg) and carprofen (5mg/kg) or saline administered subcutaneously 1h before, and daily for 4days postoperatively. To assess pain, clinical examination, body weight recording and scoring of facial expressions from photos taken before, and 6-13h after surgery were performed. Twelve weeks after surgery the rabbits were euthanized and sections of maxillary bones and sinuses were analysed with histomorphometry and by qualitative histology. Carprofen had no effect on mean facial expression scores, which increased from 0.0 to 3.6 (carprofen) and 4.3 (saline), of a maximum of 8.0. Neither did carprofen have an effect on bone formation or implant incorporation, whereas the test materials had. In conclusion, treatment with 5mg/kg carprofen once daily for 5days did not reduce facial expression scores after maxillary sinus augmentation in buprenorphine treated rabbits and did not affect long term bone formation.

Cardiovascular side-effects and insulin secretion after intravenous administration of radiolabeled Exendin-4 in pigs.

INTRODUCTION: Radiolabeled Exendin-4, a synthetic glucagon-like peptide-1 (GLP-1) analog, is used as a tracer for diagnostic purposes of ß-cells and in experimental animal research. Exendin-4 can be radiolabeled with (68)Ga, (111)In or (99m)Tc and used for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging to diagnose insulinomas, visualization of pancreatic ß-cell mass and transplanted Islets of Langerhans. In humans, Exendin-4 is widely used as a therapeutic agent for treatment of type 2 diabetes (T2D). The compound, which is administered subcutaneously (SC) may cause nausea, vomiting and a minor increase in the heart rate (HR). However, possible side-effects on cardiovascular functions after intravenous (IV) administration have not been reported. This study describes the Exendin-4 dose at which cardiovascular side-effects occur in pigs and cynomolgus monkeys. The IV effect of the tracer on insulin secretion is also investigated in pigs. METHODS: Seven clinically healthy littermate pigs (40days old) were used; three of them were made diabetic by streptozotocin (STZ). All pigs underwent PET imaging under general anesthesia to examine the glucagon-like peptide-1 receptor (GLP-1R) in ß-cells with radiolabeled Exendin-4. A baseline tracer dose IV [(68)Ga]Exendin-4 (0.025±0.010µg/kg) followed by a competition dose IV [(68)Ga]Exendin-4 (3.98±1.33µg/kg) 60min later were administered. Blood samples were taken and analyzed for insulin secretion by using ELISA. Cardiovascular and respiratory variables were monitored throughout the experiment. RESULTS: Immediately after administration of the high dose [(68)Ga]Exendin-4 the HR rose from 122±14 to 227±40bpm (p<0.01) and from 100±5 to 181±13bpm (p<0.01) in healthy non-diabetic and diabetes-induced pigs, respectively. The tachycardia was observed for >2h and one healthy non-diabetic pig suffered cardiac arrest 3h after the IV [(68)Ga]Exendin-4. Arrhythmia was detected by listening to the heart with a stethoscope up to 4days after the [(68)Ga]Exendin-4 injection. In all animals, no effect on the cardiovascular system was registered after the low dose of IV [(68)Ga]Exendin-4. Insulin secretion increased (p<0.05) when IV [(68)Ga]Exendin-4 was given in dosages ≥0.14µg/kg. CONCLUSIONS: Intravenous administration of ≥2.8µg/kg [(68)Ga]Exendin-4 resulted in severe tachycardia and arrhythmias in healthy non-diabetic and diabetes-induced pigs, and the insulin secretion was stimulated in healthy non-diabetic animals when ≥0.14µg/kg [(68)Ga]Exendin-4 was given.

Intravenous sufentanil-midazolam versus sevoflurane anaesthesia in medetomidine pre-medicated Himalayan rabbits undergoing ovariohysterectomy.

OBJECTIVE: To compare physiological effects of sufentanil-midazolam with sevoflurane for surgical anaesthesia in medetomidine premedicated rabbits. STUDY DESIGN: Prospective, randomized controlled experimental study. ANIMALS: Eighteen female Himalayan rabbits, weight 2.1 ± 0.1 kg. METHODS: Premedication with 0.1 mg kg(-1) medetomidine and 5 mg kg(-1) carprofen subcutaneously, was followed by intravenous anaesthetic induction with sufentanil (2.3 µg mL(-1)) and midazolam (0.45 mg mL(-1)). After endotracheal intubation, anaesthesia was maintained with sufentanil-midazolam (n = 9) or sevoflurane (n = 9). Ovariohysterectomy was performed. Intermittent positive pressure ventilation was performed as required. Physiological variables were studied perioperatively. Group means of physiologic data were generated for different anaesthetic periods. Data were compared for changes from sedation, and between groups by anova. Post-operatively, 0.05 mg kg(-1) buprenorphine was administered once and 5 mg kg(-1) carprofen once daily for 2-3 days. Rabbits were examined and weighed daily until one week after surgery. RESULTS: Smooth induction of anaesthesia was achieved within 5 minutes. Sufentanil and midazolam doses were 0.5 µg kg(-1) and 0.1 mg kg(-1), during induction and 3.9 µg kg(-1) hour(-1) and 0.8 mg kg(-1) hour(-1) during surgery, respectively. End-tidal sevoflurane concentration was 2.1% during surgery. Assisted ventilation was required in nine rabbits receiving sufentanil-midazolam and four receiving sevoflurane. There were no differences between groups in physiologic data other than arterial carbon dioxide. In rabbits receiving sevoflurane, mean arterial pressure decreased pre-surgical intervention, heart rate increased 25% during and after surgery and body weight decreased 4% post-operatively. Post-operative problems sometimes resulted from catheterization of the ear artery. CONCLUSION: Sevoflurane and sufentanil-midazolam provided surgical anaesthesia of similar quality. Arterial blood pressure was sustained during sufentanil-midazolam anaesthesia and rabbits receiving sevoflurane lost body weight following ovariohysterectomy. Mechanical ventilation was required with both anaesthetic regimens. CLINICAL RELEVANCE: Anaesthesia with sufentanil-midazolam in medetomidine premedicated healthy rabbits is useful in the clinical and the research setting, as an alternative to sevoflurane.

Anaesthesia in medetomidine premedicated New Zealand White rabbits: a comparison between intravenous sufentanil-midazolam and isoflurane anaesthesia for orthopaedic surgery.

Eighteen female New Zealand White rabbits (3.9 ± 0.4 kg) were anaesthetized with sufentanil-midazolam by intravenous infusion (SUF-MID, n = 9) or isoflurane (ISO, n = 9) for bilateral creation of an osteochondral defect in the medial femur condyle. Subcutaneous premedication with 0.1 mg/kg medetomidine and anaesthesia induction by intravenous infusion of 1.1 µg/kg sufentanil and 0.2 mg/kg midazolam were identical in both groups. During surgery (60 min), the effects on respiratory and circulatory variables serum lactate, total protein and blood glucose were examined. Intermittent positive pressure ventilation (IPPV) was initiated if apnoea lasted>30 s or if end-tidal CO2 ≥8 kPa. The righting reflex was lost in 3 min. IPPV was necessary during most of the anaesthesia for most of the rabbits. Maintenance doses during surgery were 2.0 µg/kg/h sufentanil and 0.4 mg/kg/h midazolam, and 1.4% isoflurane, respectively. Mean arterial blood pressure (MAP) was higher in group SUF-MID than group ISO during surgery (63 ± 12 vs 50 ± 8 mmHg). In group ISO the heart rate was higher during surgery than before anaesthesia (197 ± 26 vs 158 ± 40 bpm) as was blood glucose (9 ± 2 vs 12 ± 3 mmol/L). Serum lactate levels remained unchanged whereas total protein decreased in both groups. Time to recover from anaesthesia did not differ between groups (20 min). Intravenous sufentanil-midazolam infusion provided surgical anaesthesia with a higher MAP than isoflurane anaesthesia. The protocol can be useful in situations in which gas anaesthesia cannot be used or in animals with limited cardiovascular reserves. However, IPPV is necessary.

Continuous intravenous anaesthesia with sufentanil and midazolam in medetomidine premedicated New Zealand White rabbits.

BACKGROUND: Anaesthesia in rabbits is associated with a high mortality rate, compared to that in cats and dogs. Total intravenous anaesthesia (TIVA) with drugs that provide cardiovascular stability and are rapidly metabolised could be of benefit for use in rabbits. The aim was to evaluate cardiorespiratory effects of TIVA with sufentanil-midazolam in eight New Zealand White rabbits. Subcutaneous premedication with medetomidine (0.1 mg/kg BW) was followed by IV administration of a mixture of 2.5 µg/mL sufentanil and 0.45 mg/mL midazolam at a rate of 0.3 mL/kg BW/h for anaesthetic induction. Additionally, intravenous boluses of 0.1 mL of the mixture were administered every 20 s until the righting reflex was lost. Following endotracheal intubation, anaesthesia was maintained for 60 min with an infusion rate adjusted to supress the pedal withdrawal reflex. Air and oxygen (1:2) were delivered at 3 L/min. Physiological variables were recorded before induction and at predefined time points during and after anaesthesia. RESULTS: Righting and pedal withdrawal reflexes were lost within 3 and 5 min, respectively. Doses of sufentanil and midazolam were 0.48 µg/kg BW and 0.09 mg/kg BW for induction, and 0.72 µg/kg BW/h and 0.13 mg/kg BW/h for maintenance. Apnoea occurred in two rabbits. Induction of anaesthesia caused a significant increase in heart rate, cardiac output and arterial CO2 partial pressure and a decrease in mean arterial pressure, respiratory rate and pH. Mean time from stopping the infusion to endotracheal extubation was 5 min, and to return of the righting reflex 7 min. Anaesthesia was characterized by induction and recovery without excitation, with muscle relaxation, and absence of the pedal withdrawal reflex. CONCLUSIONS: TIVA with sufentanil-midazolam provided smooth induction and recovery of anaesthesia in rabbits but with marked hypotension and respiratory depression, requiring mechanical ventilation. Further evaluation is needed to establish if the protocol is useful for rabbits undergoing surgery.

Muscle glycogen resynthesis, signalling and metabolic responses following acute exercise in exercise-trained pigs carrying the PRKAG3 mutation.

Hampshire pigs carrying the PRKAG3 mutation in the AMP-activated protein kinase (AMPK) γ3 subunit exhibit excessive skeletal muscle glycogen storage and an altered glycogen synthesis signalling response following exercise. AMPK plays an important role as a regulator of carbohydrate and fat metabolism in mammalian cells. Exercise-trained muscles are repeatedly exposed to glycogen degradation and resynthesis, to which the signalling pathways adapt. The aim of this study was to examine the effect of acute exercise on glycogen synthesis signalling pathways, and the levels of insulin and other substrates in blood in exercise-trained pigs with and without the PRKAG3 mutation. After 5 weeks of training, pigs performed two standardized treadmill exercise tests, and skeletal muscle biopsies were obtained immediately after exercise and 3 h postexercise in the first test, and 6 h postexercise in the second test. The PRKAG3 mutation carriers had higher glycogen storage, and resynthesis of glycogen was faster after 3 h but not after 6 h of recovery. Alterations in the concentrations of insulin, glucose, lactate and free fatty acids after exercise did not differ between the genotypes. The carriers showed a lower expression of AMPK and increased phosphorylation of Akt Ser(473) after exercise, compared with non-carriers. Acute exercise stimulated the phosphorylation of AS160 in both genotypes, and the phosphorylation of GSK3α Ser(21) and ACC Ser(79) in the non-carriers. In conclusion, exercise-trained pigs carrying the PRKAG3 mutation show an altered Akt and AMPK signalling response to acute exercise, indicating that glucose metabolism is associated with faster resynthesis of muscle glycogen in this group.

In situ cross-linkable hyaluronan hydrogel enhances chondrogenesis.

The present work describes the feasibility of a cross-linkable injectable hyaluronan hydrogel for cartilage repair. The hydrogel used is a two-component system based on aldehyde-modified hyaluronan and hydrazide-modified polyvinyl alcohol, which are rapidly cross-linked in situ upon mixing. The in vitro study showed that chondrocytes and mesenchymal cells cultured in the gel form cartilage-like tissue, rich in glycosaminoglycans, collagen type II and aggrecan. In a rabbit animal model the injection of the hydrogel improved the healing of a full-thickness cartilage defect created in the knee as compared to non-treated controls. This rabbit study showed that the regenerated cartilage defects stained more intensely for type II collagen upon treatment with the hydrogel. The hyaluronan-based hydrogel may be used as a delivery vehicle for both growth factors and/or cells for cartilage repair. The in vivo study also indicated that the hydrogel alone has a beneficial effect on cartilage regeneration.

Effects of exercise on muscle glycogen synthesis signalling and enzyme activities in pigs carrying the PRKAG3 mutation.

The dominant RN mutation in pigs results in excessive glycogen storage in skeletal muscle. The mutation is situated in the PRKAG3 gene, which encodes a muscle-specific isoform of the AMP-activated protein kinase (AMPK) gamma3 subunit. AMPK is an important regulator of carbohydrate and fat metabolism in mammalian cells. The aim of the present study was to examine the effect of exercise on glycogen synthesis signalling pathways in muscle and to study enzyme activities of importance in carbohydrate metabolism in pigs with or without the PRKAG3 mutation. Glycogen content, metabolic enzyme activities and expression or phosphorylation of signalling proteins were analysed in skeletal muscle specimens obtained at rest, after a single treadmill exercise bout and after 3 h recovery. The PRKAG3 mutation carriers had higher glycogen content, a tendency for lower expression of AMPK (P < 0.07) and higher hexokinase and phosphorylase activities, whereas citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and glycogen synthase activities did not differ between genotypes. Carriers and non-carriers of the RN mutation showed a similar degradation of glycogen after exercise, whereas the rate of resynthesis was faster in the carriers. Acute exercise stimulated Akt phosphorylation on Ser(473) in both genotypes, and the effect was greater in the carriers than in the non-carriers. Acute exercise also stimulated phosphorylation of Akt substrate of 160 kDA and Glycogen synthase kinase 3 in the carriers and GSK3alpha in the non-carriers. In conclusion, the increased rate of glycogen synthesis following exercise in pigs carrying the PRKAG3 mutation correlates with an increased signalling response of Akt and its substrate, AS160, and a higher activity of hexokinase, indicating an increased glucose influx and phosphorylation of glucose, directed towards glycogen synthesis.

Blood concentrations of the cytokines IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma during experimentally induced swine dysentery.

BACKGROUND: Knowledge of the cytokine response at infection with Brachyspira hyodysenteriae can help understanding disease mechanism involved during swine dysentery. Since this knowledge is still limited the aim of the present study was to induce dysentery experimentally in pigs and to monitor the development of important immunoregulatory cytokines in blood collected at various stages of the disease. METHODS: Ten conventional pigs (~23 kg) were orally inoculated with Brachyspira hyodysenteriae B204T. Eight animals developed muco-haemorrhagic diarrhoea with impaired general body condition. Blood was sampled before inoculation and repeatedly during acute dysentery and recovery periods and cytokine levels of IL-1beta, IL-6, Il-10, TNF-alpha and IFN-gamma were measured by ELISA. RESULTS: IL-1beta was increased at the beginning of the dysentery period and coincided with the appearance of Serum amyloid A and clinical signs of disease. TNF-alpha increased in all animals after inoculation, with a peak during dysentery, and IL-6 was found in 3 animals during dysentery and in the 2 animals that did not develop clinical signs of disease. IL-10 was found in all sick animals during the recovery period. IFN-gamma was not detected on any occasion. CONCLUSION: B. hyodysenteriae inoculation induced production of systemic levels of IL-1beta during the dysentery period and increased levels of IL-10 coincided with recovery from dysentery.

Effects of extradural morphine on end-tidal isoflurane concentration and physiological variables in pigs undergoing abdominal surgery: a clinical study.

OBJECTIVE: To evaluate the effects of preoperative extradural morphine on the end-tidal isoflurane (Fe'ISO) concentration and on physiological variables in pigs undergoing abdominal surgery. STUDY DESIGN: Prospective, randomized, blinded study. ANIMALS: Fourteen healthy pigs (20 +/- 4 kg) undergoing intestinal cannulation. MATERIALS AND METHODS: Anaesthesia was induced with a combination of medetomidine (50 microg kg(-1)) and tiletamine-zolazepam (2.5 mg kg(-1)) injected intramuscularly, and was maintained with isoflurane in air and oxygen (FiO(2) = 50% O(2)). In the first group, morphine (0.1 mg kg(-1)) was administered extradurally before surgery. The second group received an equivalent volume of extradural saline as control. During the experiment, heart and respiratory rates, mean arterial blood pressure, tidal volume and minute ventilation were recorded every 10 minutes. The concentration of Fe'ISO was adjusted, according to the depth of anaesthesia, by an experienced animal nurse. Within treatment groups, time-related changes in Fe'ISO and physiological variables were analysed using a repeated measurement anova. Differences in data between treatment groups were analysed at specific time points using a Mann-Whitney U-test. Results are presented as mean +/- SD; p < 0.05 was considered as significant. RESULTS: After the onset of action of the morphine, the Fe'ISO required to maintain anaesthesia was significantly lower in the extradural morphine group compared with control. During the expected maximal effect of the drug, Fe'ISO was significantly lower in the morphine group (0.6 +/- 0.2%) than in the control group (0.9 +/- 0.2%). The decrease in Fe'ISO indicated that the onset of action of morphine was approximately 30 minutes after injection. No significant differences in other clinical variables were found between the groups. CONCLUSION: Pigs that received extradural morphine before abdominal surgery achieved surgical anaesthetic depth at a lower Fe'ISO concentration. CLINICAL RELEVANCE: Extradural morphine allows abdominal surgery to be performed at a lower Fe'ISO concentrations.

Simultaneous detection of porcine proinflammatory cytokines using multiplex flow cytometry by the xMAP technology.

BACKGROUND: Multiplex flow cytometry is in widespread use for detection of cytokines in human samples. However, no report on the measurement of porcine cytokines using this method has previously been published. We report on the detection of the porcine proinflammatory cytokines TNF-alpha, IL-8, and IL-1beta by the xMap-assay for multiplex flow cytometry. METHODS: Commercially available antibodies to porcine cytokines were used as capture antibodies by attaching them to goat anti-mouse IgG coated microspheres with different fluorescent signatures. By the use of biotinylated detection antibodies and SAv-PE the amount of cytokines bound to the spheres were measured. Experiments were performed to determine the limits of detection and the amount of crossreactivity in buffer, serum, and plasma, using spiking with recombinant porcine cytokines. RESULTS: The limit of detection ranged from 0.18 to 12 ng/ml. Generally, the detection limit was higher in serum and plasma, than in buffer. No crossreactivity between reagents was found. CONCLUSIONS: Porcine proinflammatory cytokines can be detected utilizing this method with satisfactory detection limits, and no crossreaction between the reagents involved.

Effect of exercise on proglycogen and macroglycogen content in skeletal muscles of pigs with the Rendement Napole mutation.

OBJECTIVE: To investigate influence of the Rendement Napole (RN-) mutation on proglycogen (PG) and macroglycogen (MG) content in skeletal muscles before and after exercise and evaluate glycogen concentrations within various muscle fiber types. ANIMALS: 5 pigs with the RN- mutation and 3 noncarrier pigs. PROCEDURE: Pigs performed 2 exercise tests on a treadmill. In the first, pigs (mean body weight, 27 kg) ran a distance of approximately 800 m. In the second, pigs (mean body weight, 63 kg) ran until fatigued. Biopsy specimens (biceps femoris muscle) for determination of PG and MG contents were obtained before and after exercise, 24 hours after the first test, and 3 hours after the second test. Histochemical analysis was performed on specimens obtained before and after the second test. RESULTS: Before exercise, PG stores did not differ markedly between groups, but MG stores were twice as high in pigs with the RN- mutation, compared with noncarrier pigs. The MG content decreased to a similar extent in both groups after exercise. Resynthesis of MG was greater in pigs with the RN- mutation than in noncarrier pigs by 3 hours after exercise. A low glycogen content after exercise was observed in many type I and type IIA fibers and in some type lIB fibers. CONCLUSIONS AND CLINICAL RELEVANCE: The RN- mutation was associated with high MG stores in skeletal muscle that did not influence exercise performance. The RN- mutation did not impair glycogenolysis during exercise but may induce faster resynthesis of MG after exercise.