Yoshiki Yamaya

β‐Adrenergic or parasympathetic inhibition, heart rate and cardiac output during normoxic and acute hypoxic exercise in humans

Acute hypoxia increases heart rate (HR) and cardiac output (Qt) at a given oxygen consumption (V̇O2) during submaximal exercise. It is widely believed that the underlying mechanism involves increased sympathetic activation and circulating catecholamines acting on cardiac β receptors. Recent evidence indicating a continued role for parasympathetic modulation of HR during moderate exercise suggests that increased parasympathetic withdrawal plays a part in the increase in HR and Qt during hypoxic exercise. To test this, we separately blocked the β‐sympathetic and parasympathetic arms of the autonomic nervous system (ANS) in six healthy subjects (five male, one female; mean ±s.e.m. age = 31.7 ± 1.6 years, normoxic maximal V̇O2 (V̇O2,max) = 3.1 ± 0.3 l min−1) during exercise in conditions of normoxia and acute hypoxia (inspired oxygen fraction = 0.125) to V̇O2,max. Data were collected on different days under the following conditions: (1)control, (2) after 8.0 mg propranolol I.V. and (3) after 0.8 mg glycopyrrolate I.V. Qt was measured using open‐circuit acetylene uptake. Hypoxia increased venous [adrenaline] and [noradrenaline] but not [dopamine] at a given V̇O2 (P < 0.05, P < 0.01 and P= 0.2, respectively). HR/V̇O2 and Qt/V̇O2 increased during hypoxia in all three conditions (P < 0.05). Unexpectedly, the effects of hypoxia on HR and Qt were not significantly different from control with either β‐sympathetic or parasympathetic inhibition. These data suggest that although acute exposure to hypoxia increases circulating [catecholamines], the effects of hypoxia on HR and Qt do not necessarily require intact cardiac muscarinic and β receptors. It may be that cardiac α receptors play a primary role in elevating HR and Qt during hypoxic exercise, or perhaps offer an alternative mechanism when other ANS pathways are blocked.

Role of the giant panda's ‘pseudo-thumb’

The way in which the giant panda, Ailuropoda melanoleuca, uses the radial sesamoid bone — its ‘pseudo-thumb’ — for grasping makes it one of the most extraordinary manipulation systems in mammalian evolution. The bone has been reported to function as an active manipulator, enabling the panda to grasp bamboo stems between the bone and the opposing palm,. We have used computed tomography, magnetic resonance imaging (MRI) and related techniques to analyse a panda hand. The three-dimensional images we obtained indicate that the radial sesamoid bone cannot move independently of its articulated bones, as has been suggested, but rather acts as part of a functional unit of manipulation. The radial sesamoid bone and the accessory carpal bone form a double pincer-like apparatus in the medial and lateral sides of the hand, respectively, enabling the panda to manipulate objects with great dexterity.

CT examination of the manipulation system in the giant panda (Ailuropoda melanoleuca).

The manipulation mechanism of the giant panda (Ailuropida melanoleuca) was examined by means of CT (computed tomography) and 3‐dimensional (3‐D) Volume Rendering techniques. In the 3‐D images of the giant panda hand, not only the bones but also the muscular system was visualised. Sections of the articulated skeleton were obtained. It was demonstrated that the hand of the panda is equipped with separately moulded manipulation units as follows: (1) the radial sesamoid (RS), the radial carpal, and the first metacarpal (R–R–M) complex; and (2) the accessory carpal (AC) and the ulnar (A–U) complex. When the giant panda grasps anything, the R–R–M complex strongly flexes at the wrist joint, the RS becomes parallel with the AC, and the phalanges bend and hold the object. It is shown that the well‐developed opponens pollicis and abductor pollicis brevis muscles envelop and fix the objects between the R–R–M complex and the phalanges during grasping.

Effects of altered FiO2 on maximum V̇O2 in the horse

Although the horse is considered an elite athlete with a specific VO2max some 2-4 times higher than man, maximal O2 transport is compromised both by moderately severe arterial desaturation and by failure to extract all O2 from blood perfusing exercising muscle. This prompted the present study to ascertain whether correction of arterial desaturation would proportionally augment VO2max and, if so, would O2 extraction behave in a manner predicted by diffusional transport limitation. Six two year old thoroughbreds were exercised to VO2max on a treadmill each on three separate occasions breathing gases of FIO2 = 0.15, 0.21 and 0.35, each used once in balanced order. VO2, ventilation, arterial and pulmonary arterial blood gases, pressures and lactate levels were measured both submaximally and maximally at each FIO2 and cardiac output was computed by mass balance for O2. At FIO2 = 0.21, VO2max = 143.9 +/- 4.8 ml kg-1 min-1, arterial saturation (SaO2) was 81.6 +/- 3.3% while venous PO2 (PvO2) was 15.3 +/- 1.4 Torr. At FIO2 = 0.35, VO2max was 172.6 +/- 8.2 ml kg-1 min-1, SaO2 reached 97.4 +/- 0.4% and PvO2 was 23.4 +/- 0.7 Torr. VO2max at FIO2 = 0.15 was 109.8 +/- 4.1 ml kg-1 min-1, SaO2 fell to 68.1 +/- 2.5% and PvO2 was 10.6 +/- 1.0 Torr, all changes being significant, p < 0.01. As FIO2 was varied, VO2max changed proportionally to calculated mean capillary Po2 as well as to total O2 delivery. These data confirm substantial O2 supply dependence of VO2max in the horse, and in such a manner as to be consistent with the hypothesis of combined diffusive and convective transport limitation within muscle.

Effects of Optison on pulmonary gas exchange and hemodynamics.

Optison is a contrast-enhancing agent used in myocardial contrast echocardiography. It consists of small albumin spherules (approximately 4-microm diameter) containing a fluorocarbon gas, octafluoropropane. It is injected IV and, thus, may cause pulmonary manifestations of microembolism. To determine if any such effects do occur, we injected sequential doses of 1, then 3 and then 5 mL Optison IV into 25 kg anesthetized dogs, and measured pulmonary hemodynamic and gas exchange variables frequently for 30 min after each dose. This was done in both 6 healthy and 6 pulmonary hypertensive animals, the latter produced by acute IV injection of 676-microm diameter polystyrene beads, raising pulmonary artery pressure from normal (15 mmHg) to 33 mmHg. Optison-injected animals were compared with albumin-injected controls. Two animals developed severe hypotension in response to albumin and could not be used. Lung compliance and wet/dry weight ratio were unaffected by Optison and no effects on gas exchange were seen at any dose or time in either group of dogs. In the healthy group, there was slight (1 mmHg per mL Optison, transient and delayed pulmonary hypertension without change in cardiac output, suggesting a vasoconstrictor rather than mechanical basis for these small effects. No such changes occurred in the pulmonary hypertensive group. These results imply that usual human doses of Optison (0.5 mL) will produce no significant hemodynamic or gas exchange effects in either healthy or pulmonary hypertensive dogs.

Carpal bone movements in gripping action of the giant panda (Ailuropoda melanoleuca)

The movement of the carpal bones in gripping was clarified in the giant panda (Ailuropoda melanoleuca) by means of macroscopic anatomy, computed tomography (CT) and related 3‐dimensional (3‐D) volume rendering techniques. In the gripping action, 3‐D CT images demonstrated that the radial and 4th carpal bones largely rotate or flex to the radial and ulnar sides respectively. This indicates that these carpal bones on both sides enable the panda to flex the palm from the forearm and to grasp objects by the manipulation mechanism that includes the radial sesamoid. In the macroscopic observations, we found that the smooth articulation surfaces are enlarged between the radial carpal and the radius on the radial side, and between the 4th and ulnar carpals on the ulnar side. The panda skilfully grasps using a double pincer‐like apparatus with the huge radial sesamoid and accessory carpal.

Hypoxic helium breathing does not reduce alveolar-arterial PO2 difference in the horse

In a previous study we evaluated the mechanism of alveolar-arterial PO2 (AaPO2) reduction when nitrogen is replaced with helium in normoxia (FIO2 = 0.21). The reduction in AaPO2 was not due to changes in VA/Q inequality, pulmonary O2 diffusing capacity, or cardiac output, but to more complete diffusion equilibration as a consequence of the higher ventilation and thus PAO2 (which reduced the average slope of the hemoglobin O2 dissociation curve (ODC), and thus enhanced diffusive equilibration). We hypothesized that hypoxic He/O2 breathing in contrast would not reduce the AaPO2 because PAO2 and PaO2, although higher with He than N2, would remain constrained to the linear region of the ODC. Breathing hypoxic gas mixtures did constrain the PAO2 to the linear region of the ODC, even when PAO2 was increased by He/O2 breathing. Thus, the average slope of the ODC did not change when He replaced N2 and this explains the lack of change in AaPO2, as hypothesized.

Plasma thrombin- antithrombin complex concentrations in dogs with malignant tumours

IT has been suggested that coagulation abnormalities such as disseminated intravascular coagulation (DIC) might be caused by the excessive activation of coagulation in dogs with malignant tumours (O’Keefe and Couto 1988). Since excessive activation of coagulation leads to over-generation of thrombin, increased concentrations of thrombin measured in circulating blood would indicate an activation of coagulation. Thrombin-antithrombin complexes (TATs), which are formed rapidly after thrombin production, have been identified as a marker of coagulation activation (Pelzer and others 1988). The plasma TAT concentration has been reported to be useful for evaluating the activation of coagulation in dogs (Ravanat and others 1995), and is available as a marker of the hypercoagulable state in dogs with Cushing’s syndrome (Jacoby and others 2001). However, the plasma TAT concentrations in dogs with malignant tumours have not been reported. This short communication describes the plasma TAT concentrations in dogs with benign or malignant tumours and the incidence of a hypercoagulable state in dogs with malignant tumours. The plasma TAT concentrations of three groups of dogs were examined. Group 1 comprised 16 clinically healthy adult dogs; the dogs were considered clinically normal on the basis of physical examination, routine haematological examination and serum biochemical analysis. Group 2 comprised 11 dogs with benign tumours: five with an adenoma, three with a leiomyoma, two with a haemangioma and one with a lipoma. Group 3 consisted of 62 dogs with malignant tumours, this group was further divided into four subgroups: 27 dogs with epithelial tumours, 17 with mesenchymal tumours except haemangiosarcoma; 10 with haemangiosarcomas and eight with haematopoietic tumours. The dogs in groups 2 and 3 were referred to the Animal Medical Center of Nihon University and their tumours were diagnosed by histopathological examination. None of the dogs received any anticoagulants or blood products before blood sampling. Blood samples were collected into tubes containing 0·13M trisodium citrate (nine parts blood to one part anticoagulant) and centrifuged at 2000 g for 10 minutes, and the citrated plasma was frozen at –30°C until analysis. The plasma TAT concentrations were measured by enzyme immunoassay (TAT Test Kokusai-F; International Reagents Corporation). Mann-Whitney U tests were used to compare plasma TAT concentrations between the groups. For statistical analysis, plasma TAT concentrations undetectable by the assay method used (<0·4 ng/ml) were regarded as 0·4 ng/ml. To detect the incidence of a hypercoagulable state, a reference range of plasma TAT concentration was established as the mean (2sd) concentration obtained from group 1. Dogs with plasma TAT concentrations above the reference range were regarded as displaying a hypercoagulable state. The median (range) plasma TAT concentrations were 0·5 (<0·4 to 0·6) ng/ml in group 1, 0·4 (<0·4 to 6·3) ng/ml in group 2 and 1·3 (0·4 to 49·3) ng/ml in group 3; concentrations were significantly higher in group 3 than in group 1 (P<0·0001). However, there was no significant difference in the plasma TAT concentrations of groups 1 and 2 (P=0·8823) (Fig 1). Within group 3, the TAT concentrations were 0·8 (0·4 to 3·8) ng/ml for the dogs with epithelial tumours, 0·7 (0·4 to 49·3) ng/ml for those with mesenchymal tumours, 17·3 (4·4 to 42·5) ng/ml for those with haemangiosarcomas, and 8·2 (2·1 to 19·0) ng/ml for those with haematopoietic tumours. The plasma TAT concentrations were significantly elevated in all subgroups of group 3 (P<0·001, P<0·01, P<0·0001 and P<0·0001, respectively) compared with group 1 (Fig 2). The mean (2sd) plasma TAT concentration of dogs in group 1 was 0·49 (0·12) ng/ml, and thus dogs with plasma TAT concentrations in excess of 0·61 ng/ml were considered as disVeterinary Record (2005) 156, 839-840

Case report: First confirmed case of canine peritoneal larval cestodiasis caused by Mesocestoides vogae (syn. M. corti) in Japan.

Canine peritoneal larval cestodiasis (CPLC) is an unusual parasitic disease in dogs that is caused by asexual proliferation of larval Mesocestoides. A 12 year-old spayed Shetland sheepdog with abdominal distension was referred to the Animal Medical Center at Nihon University, Japan. The presence of ascites was confirmed by abdominal ultrasonography and X-ray imaging. In addition, a number of parasites were observed in the ascitic fluid collected by abdominal paracentesis. Each of the whitish colored parasites was less than 1mm in size. The parasites were morphologically identified as Mesocestoides sp. tetrathyridia. The parasites had four suckers and calcareous corpuscles, but no hooks or rostellum. Mitochondrial (mt) 12S rDNA and mt cytochrome c oxidase subunit 1 DNA amplified from the tetrathyridia were used for molecular identification to species level. DNA sequence analysis showed that the tetrathyridia shared more than 99% identity with M. vogae (syn. M. corti) for each gene. The patient was treated with a standard dose (5mg/kg) of praziquantel, which was administered subcutaneously twice at an interval of 14 days. This resulted in successful deworming. This is the first case that CPLC was diagnosed in a dog that had never been taken outside of Japan, indicating that M. vogae is distributed in this country.

Trace and Major Elements Status in Bronchoalveolar Lavage Fluid in Dogs with or without Bronchopneumonia

The aim of this study was to investigate the relationships between the bronchopneumonia and mean concentrations of those trace elements in bronchoalveolar lavage fluid (BALF). Twenty-nine dogs were included this study (17 healthy dogs and 12 dogs with respiratory disease). Each BALF sample had been obtained during bronchoscope examination by use of a standardized method. The concentrations of Al, Br, Ca, Cu, Fe, K, Ni, P, Si, Sr and Zn in BALF were measured by the particle-induced X-ray emission method. We found no relationship between the bronchopneumonia and the levels of elements in the BALF, except Ca, P and Zn. The dogs with respiratory disease were found to have a large amount of Ca and Zn, and a high Ca/P and Zn/Cu ratios in BALF compared to those without respiratory disease.