Phospholamban ablation rescues the enhanced propensity to arrhythmias of mice with CaMKII-constitutive phosphorylation of RyR2 at site S2814.

KEY POINTS: Mice with Ca(2+) -calmodulin-dependent protein kinase (CaMKII) constitutive pseudo-phosphorylation of the ryanodine receptor RyR2 at Ser2814 (S2814D(+/+) mice) exhibit a higher open probability of RyR2, higher sarcoplasmic reticulum (SR) Ca(2+) leak in diastole and increased propensity to arrhythmias under stress conditions. We generated phospholamban (PLN)-deficient S2814D(+/+) knock-in mice by crossing two colonies, S2814D(+/+) and PLNKO mice, to test the hypothesis that PLN ablation can prevent the propensity to arrhythmias of S2814D(+/+) mice. PLN ablation partially rescues the altered intracellular Ca(2+) dynamics of S2814D(+/+) hearts and myocytes, but enhances SR Ca(2+) sparks and leak on confocal microscopy. PLN ablation diminishes ventricular arrhythmias promoted by CaMKII phosphorylation of S2814 on RyR2. PLN ablation aborts the arrhythmogenic SR Ca(2+) waves of S2814D(+/+) and transforms them into non-propagating events. A mathematical human myocyte model replicates these results and predicts the increase in SR Ca(2+) uptake required to prevent the arrhythmias induced by a CaMKII-dependent leaky RyR2. ABSTRACT: Mice with constitutive pseudo-phosphorylation at Ser2814-RyR2 (S2814D(+/+) ) have increased propensity to arrhythmias under ß-adrenergic stress conditions. Although abnormal Ca(2+) release from the sarcoplasmic reticulum (SR) has been linked to arrhythmogenesis, the role played by SR Ca(2+) uptake remains controversial. We tested the hypothesis that an increase in SR Ca(2+) uptake is able to rescue the increased arrhythmia propensity of S2814D(+/+) mice. We generated phospholamban (PLN)-deficient/S2814D(+/+) knock-in mice by crossing two colonies, S2814D(+/+) and PLNKO mice (SD(+/+) /KO). SD(+/+) /KO myocytes exhibited both increased SR Ca(2+) uptake seen in PLN knock-out (PLNKO) myocytes and diminished SR Ca(2+) load (relative to PLNKO), a characteristic of S2814D(+/+) myocytes. Ventricular arrhythmias evoked by catecholaminergic challenge (caffeine/adrenaline) in S2814D(+/+) mice in vivo or programmed electric stimulation and high extracellular Ca(2+) in S2814D(+) /(-) hearts ex vivo were significantly diminished by PLN ablation. At the myocyte level, PLN ablation converted the arrhythmogenic Ca(2+) waves evoked by high extracellular Ca(2+) provocation in S2814D(+/+) mice into non-propagated Ca(2+) mini-waves on confocal microscopy. Myocyte Ca(2+) waves, typical of S2814D(+/+) mice, could be evoked in SD(+/+) /KO cells by partially inhibiting SERCA2a. A mathematical human myocyte model replicated these results and allowed for predicting the increase in SR Ca(2+) uptake required to prevent the arrhythmias induced by a Ca(2+) -calmodulin-dependent protein kinase (CaMKII)-dependent leaky RyR2. Our results demonstrate that increasing SR Ca(2+) uptake by PLN ablation can prevent the arrhythmic events triggered by SR Ca(2+) leak due to CaMKII-dependent phosphorylation of the RyR2-S2814 site and underscore the benefits of increasing SERCA2a activity on SR Ca(2+) -triggered arrhythmias.

Metástasis hepáticas de origen no colorrectal ni neuroendocrino: tratamiento en un hospital de segundo nivel / Liver metastases from non-colorectal non-neuroendocrine tumors: treatment in a hospital of second level

Introduction: Surgical treatment of liver metastases is broadly accepted for colorectal and neuroendocrine tumors. However, the approach to liver metastases of other origins is not well established. The objective is the evaluation of factors that might be associated with better or worse perioperative outcomes (morbidity and mortality) and survival of patients with non-colorectal, non-neuroendocrine liver metastases (NCNNLM) treated surgically in a second level hospital. Material and Methods: A prospective study of patients with NCNNLM treated surgically or with radiofrequency was completed in San Cecilio University Hospital of Granada, between March 2003 and June 2013. The statistical analysis was made with IBM-SPSS version 21. Statistical significance was set at p ≤ 0.05. Survival data were analyzed by Kaplan-Meier's method. Results: Twenty-two patients with 26 surgeries were analyzed, 19 liver resections, 6 radiofrequency treatments and 1 combined case with surgery and radiofrequency. Operatory mortality was 0 percent and overage mortality was 23.1 percent. Univariate analysis only showed statistical significance in two of the factors, presence of positive lymphatic nodes during the surgery of the primary tumor and presence of extra-hepatic disease. Accumulated survival was 81 percent, 66 percent and 52 percent at 1, 2 and 3 years respectively. Conclusions: Despite the fact of treating together in the same group several different tumors, the surgical treatment of NCNNLM (with or without radiofrequency) has an acceptable survival rate. Thus, they can be treated with safety when we use a multi-disciplinary approach to these patients.

Introducción: Aunque el tratamiento quirúrgico de las metástasis hepáticas está bien establecido en el cáncer colorrectal y los tumores neuroendocrinos. el enfoque de las metástasis hepáticas de otras localizaciones no está bien definido. El objetivo es valorar aquellos factores que pudieran asociarse a unos mejores o peores resultados perioperatorios (morbimortalidad) y a la supervivencia de los pacientes sometidos a tratamiento quirúrgico de las metástasis hepáticas de tumores no colorrectales ni neuroendocrinos(MHNCNN) en un hospital de segundo nivel. Material y Métodos: Se ha realizado un estudio prospectivo de pacientes con MHNCNN tratadas mediante cirugía y/o radiofrecuencia en el Hospital Universitario San Cecilio de Granada, entre marzo de 2003 y junio de 2013. Para el análisis estadístico se utilizó el programa IBM-SPSS versión 21, considerándose significativo un valor de p ≤ 0,05. El estudio de supervivencia se realizó mediante análisis de Kaplan-Meier. Resultados: Se analizan 22 pacientes, con 26 intervenciones: 19 resecciones quirúrgicas, 6 radiofrecuencias y 1 caso combinando resección y radiofrecuencia. La mortalidad operatoria es de 0 por ciento y la morbilidad del 23 por ciento. El análisis univariante sólo muestra significación estadística en dos factores, presencia de ganglios positivos en la intervención del tumor primario y la existencia de enfermedad extrahepática. La supervivencia acumulada es del 81 por ciento, 66 por ciento y 52 por ciento al año, dos años y tres años. Conclusiones: Aunque con las limitaciones que presenta el agrupar un conjunto heterogéneo de tumores. el tratamiento quirúrgico de las MHNCNN, asociado o no a radiofrecuencia, presenta una tasa de supervivencia aceptable, pudiendo ser estas tratadas con seguridad, siendo fundamental un abordaje multidisciplinario de los pacientes.

Ascitis quilosa asociada a pancreatitis aguda / Chylous ascites associated with acute pancreatitis

Background: Chylous ascites is defined as the presence of thoracic or intestinal lymph in the abdominal cavity. Its association with acute pancreatitis is uncommon. Aim: To report three cases of chilous ascites related with acute pancreatitis. Material and Methods: Review of medical records of three patients with chylous ascites associated with acute pancreatitis. Results: We report three patients with chylous ascites out of 2,188 admissions for acute pancreatitis (0.13 percent). A 39 years old male with a pancreatic pseudocyst. During surgery, chylous ascites was found. He was successfully treated with octreotide and spironolactone. A 71 years male operated for an acute cholecystitis and a perivesicular abscess. Three days after surgery, a chylous fluid appears in the abdominal drainage, which disappears spontaneously. A 73 years old female operated for an acute pancreatitis. During surgery a chylous ascites is found. The patient died four days after surgery. Conclusions: Chylous ascites associated with pancreatitis is uncommon and octreotide may have a therapeutic role for it.

Introducción: La ascitis quilosa (AQ) se define como la presencia de linfa de origen torácico o intestinal en la cavidad abdominal. Asociada a Pancreatitis Aguda (PA), sólo se han documentado 12 casos hasta 2013. El objetivo de este trabajo es presentar tres nuevos casos y realizar una revisión de la presentación, clínica, diagnóstico y tratamiento de esta entidad. Material y Métodos: Se recogen los datos clínicos y evolutivos de tres pacientes con AQ secundaria a pancreatitis aguda (AQPA); esta se ha definido como la presencia de linfa en cavidad abdominal en un paciente con episodio de pancreatitis aguda reciente y sin antecedente traumático, infeccioso, neoplásico o quirúrgico que pudiera ser el responsable de la misma. Se han recogido igualmente todos los casos documentados hasta 2013. Resultados: En los últimos 10 años han sido ingresados 2.188 pacientes por PA entre los cuales, se han diagnosticado 3 casos de AQPA (0,13 por ciento), dos hombres y una mujer, con PA de origen biliar. El diagnóstico ha sido "de visu" intra o postoperatorio. El débito inicial fue de 3.000, 300 y 1.500 cc. El tratamiento ha contado con octeótrido de entrada en todos los casos. En la revisión bibliográfica la AQPA ha sido diagnosticada también "de visu" y los pacientes se han resuelto con tratamiento conservador, tardando una media de 27,7 días si se utiliza octeótrido frente a 46,5 días si no se le ha prescrito. Conclusiones: La AQ asociada a PA sigue siendo infrecuente, su diagnóstico es "de visu" y se resuelve con tratamiento conservador, siendo el octeótrido un fármaco de primera línea.

Aplicación de la ecografía pediátrica en Atención Primaria; interconexión con la atención hospitalaria / The uses of ecography in Pediatric Primay Care; interconnection with hospital care

Introducción: el uso del método ecográfico en Pediatría en Atención Primaria (AP) mejora la calidad asistencial y favorece la eficiencia. Material y métodos: en el presente estudio se realizaron un total de 250 ecografías en un periodo de 12 meses, de mayo de 2009 a mayo de 2010. Resultados: los resultados encontrados por regiones anatomoecográficas fueron en un 45% abdominales, en un 25% craneales, en un 15% de cadera, un 10% parotídeas y tiroideas y un 5% de partes blandas. Dentro de estas, la patología más relevante fue el reflujo gastroesofágico, con un 7,2% de casos del total de las ecografías realizadas. El 1,6% presentó pielectasia renal; el 1,6%, cefalohematoma; el 1,2%, displasia de cadera; el 1,2%, parotiditis aguda; el 1,2%, adenopatía; el 0,4%, atresia de vías biliares; el 0,4%, angioma cervical, y el 0,4%, adenopatía abscesificada. Conclusión: de esto se deriva que la ecografía es una herramienta útil, siendo de especial interés en AP las ecografías abdominal y craneal, seguidas de las de cuello y tiroides y de cadera (AU)

Introduction: The use of ultrasound in pediatric Primary Care improves both the quality and efficiency of care. Material and methods: This study undertook 250 ultrasounds over a 12 month period from May 2009 to April 2010. Results: The results found for each anatomical region were 45% abdominal, 25% cranial, 15% of the hip, 10% of parotid and thyroids and 5% of tender areas. From these, the most relevant pathology was Gastroesophageal Reflux, accounting for 7.2% of all ultrasounds undertaken. Renal pyelectasia accounted for 1.6%, cephalhematoma 1.6%, dysplasia of the hip 1.2%, acute parotitis 1.2%, adenopathy 1.2%, cervical angioma 0.4%, and abscessed adenopathy 0.4%. Conclusions: From this analysis, we conclude that ultrasound is a useful tool for the detection of abdominal and cranial pathologies and secondarily, for thyroid, hip and cervical pathologies (AU)

Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart. Role of Ca2+/calmodulin-dependent protein kinase II.

Returning to normal pH after acidosis, similar to reperfusion after ischemia, is prone to arrhythmias. The type and mechanisms of these arrhythmias have never been explored and were the aim of the present work. Langendorff-perfused rat/mice hearts and rat-isolated myocytes were subjected to respiratory acidosis and then returned to normal pH. Monophasic action potentials and left ventricular developed pressure were recorded. The removal of acidosis provoked ectopic beats that were blunted by 1 muM of the CaMKII inhibitor KN-93, 1 muM thapsigargin, to inhibit sarcoplasmic reticulum (SR) Ca(2+) uptake, and 30 nM ryanodine or 45 muM dantrolene, to inhibit SR Ca(2+) release and were not observed in a transgenic mouse model with inhibition of CaMKII targeted to the SR. Acidosis increased the phosphorylation of Thr(17) site of phospholamban (PT-PLN) and SR Ca(2+) load. Both effects were precluded by KN-93. The return to normal pH was associated with an increase in SR Ca(2+) leak, when compared with that of control or with acidosis at the same SR Ca(2+) content. Ca(2+) leak occurred without changes in the phosphorylation of ryanodine receptors type 2 (RyR2) and was blunted by KN-93. Experiments in planar lipid bilayers confirmed the reversible inhibitory effect of acidosis on RyR2. Ectopic activity was triggered by membrane depolarizations (delayed afterdepolarizations), primarily occurring in epicardium and were prevented by KN-93. The results reveal that arrhythmias after acidosis are dependent on CaMKII activation and are associated with an increase in SR Ca(2+) load, which appears to be mainly due to the increase in PT-PLN.

Uso de la farmacogenética en el diagnóstico diferencial. A propósito de un caso / No disponible

Presentamos el caso clínico de un niño de 8 años con un trastorno por déficit de atencióne hiperactividad que desarrolló un cuadro clínico compatible con psicosis después deluso de metilfenidato en dosis terapéutica. Ante tan grave reacción adversa se le realizó unestudio farmacogenético para intentar dilucidar la causa de dicha reacción. Se estudiaronlos alelos 3*, 4*, 5* y 6* de la enzima CYP2D6 por amplificación en PCR buscando si el pacienteera un metabolizador pobre.Caso clínico: varón de 8 años sin antecedentes de interés que, tras el uso de metilfenidatoen dosis de 5 mg/día durante dos años tiene una buena respuesta clínica y un rendimientoescolar adecuado. Acude a la consulta ambulatoria por presentar un cuadro dehipotonía, bradipsiquia y dificultad en la articulación de la palabra, alternando con verborreay desconexión del medio. Se deriva a urgencias hospitalarias donde, tras la supresiónde la medicación, la sintomatología remitió hasta desaparecer. Todos los estudioscomplementarios fueron normales (hemograma, bioquímica, punción lumbar, electroencefalogramay resonancia magnética nuclear). Cuatro semanas después de este evento elpaciente reinició la medicación reapareciendo el cuadro clínico, que desapareció tras susupresión.La normalidad del estudio genético descarta una alteración farmacocinética relacionadacon la reacción adversa. Este efecto secundario probablemente se deba al uso prolongadode metilfenidato y a los niveles de dopamina mediados por CYP2D6

We present the clinical case of an 8 year old child with attention deficit hyperactivity disorder(ADHD), who developed a psychopathological disorder compatible with acute psychosisafter two years of using therapeutic doses of methylphenidate. We performed a pharmacogeneticstudy in order to find the cause of the serious adverse reaction. Biochemical amplificationby PCR of CYP2D6 and its alleles, 3*, 4*, 5* and 6* was done to find if the reaction was toxic,if the patient had a poor metabolizer genotype. Clinical case: an 8 year old male patient, withoutantecedents, who was being successfully treated for two years with methylphenidate at 5mg/day orally for ADHD, with goodscholastic results as well. The patient went to ambulatoryemergency complaining of hypotonia, bradypsychia and difficulty articulating words with intervalsof verbosity, speech disconnected with reality and having periods of complete verbal absence.The patient was admitted in the pediatric unit. After suspending medication, the clinicalsymptoms improved until they disappeared. Blood profile as well as biochemical complementarytests were normal. A nuclear magnetic resonance (NMR) did not reveal organic alterationwhich could have explained the symptoms. EEG was also normal. After rechallenge, one monthafter the first event, the boy developed the same symptoms. A CYP2D6 genotype analysis wasdone (3*, 4*, 5* y 6* alleles) where we found him to be a normal metabolizer. This discards apharmacokinetic alteration of genetic origin, which could explain an abnormal reaction tomethylphenidate. This adverse reaction could be due to the prolonged use of this drug and theaction of CYP2D6 in the levels of dopamine

Efficiency of eight different AAV serotypes in transducing rat myocardium in vivo.

Recombinant adeno-associated (AAV) viruses have unique properties, which make them ideal vectors for gene transfer targeting the myocardium. Numerous serotypes of AAV have been identified with variable tropisms towards cardiac tissue. In the present study, we investigated the time course of expression of eight different AAV serotypes in rat myocardium and the nature of the immunity against these serotypes. We first assessed whether neutralizing antibodies (NAb) were present for any of the serotype in the rats. We injected 100 microl of each AAV 1-8 serotype (10(12) DNAse resistant particles/ml), encoding LacZ gene, into the apical wall of rat myocardium. At 1, 4, 12 and 24 weeks after gene delivery, the animals were killed and beta-galactosidase (beta-gal) activity was assessed by luminometry. Additionally, LacZ genomic copies and AAV capsids copies were measured through standard polymerase chain reaction analysis and cryo-sections from the area of viral injection were stained for X-gal detection at the same time points. No NAbs were detected against any of AAV serotypes. At all the time points studied, AAV1, 6 and 8 demonstrated the highest efficiency in transducing rat hearts in vivo. Parallel to the results with beta-gal activity, the highest levels LacZ and AAV DNA genomic copies were with AAV1, 6 and 8. The positive X-gal staining depicted by these serotypes confirmed these results. These results indicate that among the various AAV serotypes, AAV1, 6 and 8 have differential tropism for the heart unaffected by pre-existing NAb in the rat. Although AAV 1 and 6 vectors induced rapid and robust expression and reach a plateau at 4 weeks, AAV 8 continued increasing until the end of the study. AAV 2, 5 and 7 vectors were slower to induce expression of the reporter gene, but did reach levels of expression comparable to AAV1 and AAV6 vectors after 3 months.

Nitric oxide induced by ketamine/xylazine anesthesia maintains hepatic blood flow during hypothermia.

Among the anesthetics influencing the nitric oxide (NO) pathway, ketamine is widely reported in the literature. We researched the variations in blood physiological parameters following ketamine/xylazine- or pentobarbital-induced anesthesia, with particular emphasis on plasmatic NO levels and oxidative stress-related factors. The effects of ketamine on hepatic blood flow during deep hypothermia were also examined. Adult male Sprague-Dawley rats were anesthetized intraperitoneally with ketamine/xylazine or with sodium pentobarbital. Animals underwent serial blood extraction to analyze acid-base balance and lactate levels in blood, as well as NO, MDA, SH groups, and AST levels in plasma samples. We demonstrated that ketamine leads to increased plasmatic NO levels, induces metabolic acidosis, and causes oxidative damage, though without reaching hepatic toxicity. When experimental hypothermia was induced, ketamine affected hepatic blood flow. Based on these results, we suggest that studies on physiological processes involving NO should exercise caution if anesthesia is induced by ketamine.

Positive inotropic and negative lusitropic effect of angiotensin II: intracellular mechanisms and second messengers.

In the cat ventricle angiotensin II exerts a positive inotropic effect produced by an increase in intracellular calcium associated with a prolongation of relaxation. The signaling cascades involved in these effects as well as the subcellular mechanisms of the negative lusitropic effect are still not clearly defined. The present study was directed to investigate these issues in cat papillary muscles and isolated myocytes. The functional suppression of the sarcoplasmic reticulum (SR) with either 0.5 microm ryanodine or 0.5 microm ryanodine plus 1 microm thapsigargin or the preincubation of the myocytes with the specific inhibitor of the inositol 1,4,5-triphosphate (IP3) receptors [diphenylborinic acid, ethanolamine ester (2-APB), 5-50 microm] did not prevent the positive inotropic effect and the increment in Ca2+ transient produced by 1 microm angiotensin II. In contrast, protein kinase C (PKC) inhibitors, chelerythrine (20 microm) and calphostin C (1 microm) completely inhibited both, the angiotensin II-induced increase in L-type calcium current and positive inotropic effect. The prolongation of half relaxation time produced by 0.5 microm angiotensin II [207+/-15.4 msec (control) to 235+/-19.98 msec (angiotensin II), P<0.05] was completely blunted by PKC inhibition. This antirelaxant effect, which was independent of intracellular pH changes, was associated with a prolongation of the action potential duration and was preserved after either the inhibition of the SR and the SR Ca2+ ATPase (ryanodine plus thapsigargin) or of the reverse mode of the Na+/Ca2+ exchanger (KB-R7943, 5 microm). We conclude that in feline myocardium the positive inotropic and negative lusitropic effects of angiotensin II are both entirely mediated by PKC without any significant participation of the IP3 limb of the phosphatidylinositol/phospholipase C cascade. The results suggest that the antirelaxant effect of angiotensin II might be determined by the decrease in Ca2+ efflux through the Na+/Ca2+ exchanger produced by the angiotensin II-induced prolongation of the action potential duration.

Metabolic characteristics of the deltoid muscle in patients with chronic obstructive pulmonary disease.

The purpose of this study was to analyse key enzyme activities of the deltoid muscle (DM) in chronic obstructive pulmonary disease (COPD) patients. The activities of one oxidative enzyme (citrate synthase (CS)), two glycolytic enzymes (lacatate dehydrogenase (LD); and phosphofructokinase (PFK)) and one enzyme related to the use of energy stores (creatine kinase (CK)) were determined in the DM of 10 patients with COPD and nine controls. Exercise capacity (cycloergometry) and the handgrip strength were also evaluated. Although exercise capacity was markedly reduced in COPD (57 +/- 20% predicted), their handgrip strength was relatively preserved (77 +/- 19% pred). The activity of LD was higher in the COPD patients (263.9 +/- 68.2 versus 184.4 +/- 46.5 mmol x min(-1) x g(-1), p<0.01), with a similar trend for CS (67.3 +/- 33.3 versus 46.0 +/- 17.4 mmol x min(-1) x g(-1), p = 0.07). Interestingly, the activity of the latter enzyme was significantly higher than controls if only severe COPD patients were considered (81.8 +/- 31.2 mmol x min(-1) x g(-1), p < 0.01). PFK and CK activities were similar for controls and COPD. Chronic obstructive patients show a preserved or even increased (severe disease) oxidative capacity in their deltoid muscle. This coexists with a greater capacity in the anaerobic part of the glycolysis. These findings are different to those previously observed in muscles of the lower limbs.

Subcellular mechanisms of the positive inotropic effect of angiotensin II in cat myocardium.

1. Cat ventricular myocytes loaded with [Ca2+]i- and pHi-sensitive probes were used to examine the subcellular mechanism(s) of the Ang II-induced positive inotropic effect. Ang II (1 microM) produced parallel increases in contraction and Ca2+ transient amplitudes and a slowly developing intracellular alkalisation. Maximal increases in contraction amplitude and Ca2+ transient amplitude were 163 +/- 22 and 43 +/- 8 %, respectively, and occurred between 5 and 7 min after Ang II administration, whereas pHi increase (0.06 +/- 0.03 pH units) became significant only 15 min after the addition of Ang II. Furthermore, the inotropic effect of Ang II was preserved in the presence of Na+-H+ exchanger blockade. These results indicate that the positive inotropic effect of Ang II is independent of changes in pHi. 2. Similar increases in contractility produced by either elevating extracellular [Ca2+] or by Ang II application produced similar increases in peak systolic Ca2+ indicating that an increase in myofilament responsiveness to Ca2+ does not participate in the Ang II-induced positive inotropic effect. 3. Ang II significantly increased the L-type Ca2+ current, as assessed by using the perforated patch-clamp technique (peak current recorded at 0 mV: -1.88 +/- 0.16 pA pF-1 in control vs. -3.03 +/- 0.20 pA pF-1 after 6-8 min of administration of Ang II to the bath solution). 4. The positive inotropic effect of Ang II was not modified in the presence of either KB-R7943, a specific blocker of the Na+-Ca2+ exchanger, or ryanodine plus thapsigargin, used to block the sarcoplasmic reticulum function. 5. The above results allow us to conclude that in the cat ventricle the Ang II-induced positive inotropic effect is due to an increase in the intracellular Ca2+ transient, an enhancement of the L-type Ca2+ current being the dominant mechanism underlying this increase.

Medetomidine/tiletamine/zolazepam and xylazine/tiletamine/zolazepam combinations for immobilization of fallow deer (Cervus dama).

Eleven adult fallow deer (Cervus dama) were anesthetized using a mixture of xylazine/tiletamine/zolazepam, and 10 were anesthetized with a mixture of medetomidine/tiletamine/zolazepam. Anesthesia was adequate for capture in all instances, and minor surgical procedures were possible in seven of the animals treated with xylazine/tiletamine/zolazepam and in all of the animals treated with medetomidine/tiletamine/zolazepam. Blood gas, hematologic, serum biochemical, and cardiorespiratory parameters were measured during all immobilizations. The deer immobilized with xylazine/tiletamine/zolazepam had significantly higher lactate and cortisol values than the deer immobilized with the medetomidine combination. Although both methods were adequate for fallow deer, the medetomidine/tiletamine/zolazepam combination produced superior results.

Basic hematological values in some wild ruminants in captivity.

Analyses of hematological parameters were carried out on eight axis deer (Cervus axis), 12 fallow deer (Cervus dama), 16 red deer (Cervus elaphus hippelaphus), three sambar (Cervus unicolor), nine Père David deer (Elaphurus davidianus), 20 European bison (Bison bonasus), seven nilgai (Boselaphus tragocamelus), eight mouflon (Ovis musimon), four white-bearded gnu (Connochaetes taurinus) and six barbary sheep (Ammotragus lervia). The following parameters were determined: packed cell volume, hemoglobin concentration, red blood cell number, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, leukocyte number and differential leukocyte count. Some degree of interspecific variability was found in the artiodactyls for these hematological parameters. An inverse relationship between mean corpuscular volume and red blood cell number is described, and specific values for these parameters are given for the four subfamilies.

Hematologic and plasma chemistry values in captive psittacine birds.

Reference values for some hematologic parameters in 19 species and plasma chemical values in 11 species of Psittacine birds, including cockatoos, parrots, amazons, macaws, conures, and lories, were established for use in veterinary medicine. The following parameters were studied: hematocrit, hemoglobin concentration, erythrocyte number, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, erythrocyte dimensions, leukocyte number and differential leukocyte count, glucose, urea, uric acid, cholesterol, triglycerides, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine phosphokinase, lactic dehydrogenase, gamma glutamyl transpeptidase, total plasma protein, albumin, globulins, albumin-globulin ratio, sodium, potassium, calcium, magnesium, total phosphorus, chloride, and osmolality. Hematologically, the Psittacine is a very homogeneous avian group, with small differences between species. They are, however, different from other groups of birds.

Capillarity and fibre types in locomotory muscles of wild yellow-legged gulls (Larus cachinnans).

This study analyzes the capillarity and fibre-type distribution of six locomotory muscles of gulls. The morphological basis and the oxygen supply characteristics of the skeletal muscle of a species with a marked pattern of gliding flight are established, thus contributing to a better understanding of the physiology of a kind of flight with low energetic requirements. The four wing muscles studied (scapulotriceps, pectoralis, scapulohumeralis, and extensor metacarpi) exhibited higher percentages of fast oxidative glycolytic fibres (>70%) and lower percentages of slow oxidative fibres (<16%) than the muscles involved in nonflight locomotion (gastrocnemius and iliotibialis). Capillary densities ranged from 816 to 1,233 capillaries mm(-2), having the highest value in the pectoralis. In this muscle, the fast oxidative glycolytic fibres had moderate staining for succinate dehydrogenase and relatively large fibre sizes, as deduced from the low fibre densities (589-665 fibres mm(-2)). All these findings are seen as an adaptive response for gliding, when the wing is held outstretched by isometric contractions. The leg muscles studied included a considerable population of slow oxidative fibres (>14% in many regions), which suggests that they are adapted to postural activities. Regional variations in the relative distributions of fibre types in muscle gastrocnemius may reflect different functional demands placed on this muscle during terrestrial and aquatic locomotion. The predominance of oxidative fibres and capillary densities under 1,000 capillaries mm(-2) in leg muscles is probably a consequence of an adaptation for slow swimming and maintenance of the posture on land rather than for other locomotory capabilities, such as endurance or sprint activities.

Comparative skeletal muscle fibre morphometry among wild birds with different locomotor behaviour.

Six muscles of the mallard duck (Anas platyrhynchos), the common coot (Fulica atra) and the yellow-legged gull (Larus cachinnans) were analysed morphometrically, with special emphasis on their functional implications and physiological needs. Oxidative fibres always had significantly smaller size than anaerobic fibres, although no differences in the number of capillaries per fibre were found. This resulted in greater capillary counts per unit of fibre area and perimeter in oxidative than anaerobic fibres, which indicates that the greater demand for oxygen supply may be achieved by decreasing the size of the muscle fibre rather than by increasing the number of associated capillaries. Fast oxidative fibres of the pectoralis and the triceps of the gull had greater sizes than the fast oxidative fibres of the mallard and the coot, which correlates with the difference in energetic demands between flapping and gliding flight. Greater fibre cross-sectional areas and perimeters seem suited to afford the long-lasting activity with low metabolic demands required during gliding. By contrast, mallards and coots attain a high oxidative metabolism, during sustained flapping flight, by reducing fibre size at the expense of a diminished ability for force generation. Between-species comparisons of the hindlimb muscles only yielded differences for the anaerobic fibres of the gastrocnemius, as an important adaptive response to force generation during burst locomotion. The need to manage sustained swimming abilities effectively may result in similar FOG fibre morphometry of the hindlimb muscles studied, indicating that a compromise between the oxygen flux to the muscle cell and the development of power is highly optimised in oxidative fibres of the bird species studied.

Capillarity and fiber types in locomotory muscles of wild common coots, Fulica atra.

Six locomotory muscles of wild common coots, Fulica atra, were analyzed histochemically. Capillarity and fiber-type distributions were correlated to the functional implications and physiological needs of each muscle. Leg muscles exhibit three unevenly distributed fiber types, a pattern that reflects the great variety of terrestrial and aquatic locomotory performances that coots are able to develop. Aerobic zones are presumably recruited during steady swimming and diving, while regions with anaerobic characteristics may be used for bursts of activity such as sprint swimming or during take off, when coots run along the water's surface. Fiber types and capillarization in wing muscles have a marked oxidative trend. High wing beat frequencies, short and broad wings, and the long distance migrations that these birds perform indicate that the presence of high numbers of oxidative fibers and the well developed capillary supply are needed for enhanced oxygen uptake. The pectoralis muscle, except in its deep part, has exclusively fast oxidative fibers with a very high staining intensity for succinate dehydrogenase assay as compared to the same fiber type of other muscles. Its predominant role in flapping flight justifies these characteristics that are typical of fibers with high aerobic metabolism. The deep part of the pectoralis muscle presents a low proportion of an unusual slow anaerobic fiber type. These fibers could play a role during feeding dives when the bird presses the air out of the feathers by tightening the wings against the body. A linear relationship between capillary and fiber densities in all coot muscles studied reflects an adjustment between fiber diameter and vascularization in order to obtain the oxygen for mitochondrial supply. This strategy seems a suitable way to cope with the rigid aerobic constraints that flying and diving impose upon the coot's physiology. J. Morphol. 237:147-164, 1998. © 1998 Wiley-Liss, Inc.

Hematology and serum chemistry in the white-crowned mangabey (Cercocebus torquatus lunulatus) and in the mandrill (Mandrillus sphinx).

Reference values of some hematologic and plasma chemical parameters were established in two species of clinically normal Cercopithecidae. The following variables were studied in seven mandrills (Mandrillus sphinx) and nine white-crowned mangabeys (Cercocebus torquatus lunulatus): hematocrit, hemoglobin concentration, erythrocyte and leucocyte counts, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, glucose, urea, uric acid, cholesterol, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine phosphokinase, lactic dehydrogenase, gamma glutamyl transpeptidase, total serum proteins, albumin, globulins, albumin-globulin ratio, sodium, potassium, calcium, magnesium, total phosphorus, chloride, and serum osmolality. Few differences were observed when compared with human hematological data and with other species of Cercopithecidae Primates.