bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Profiles of Ivermectin in Horses following Oral or Intramuscular Administration
Authors: Pérez R. , Godoy C. , Palma C. , Cabezas I. , Muñoz L. , Rubilar L. , Arboix M. , Alvinerie M.
Published: July 2003

A study was undertaken in order to evaluate and compare ivermectin's (IVM) plasma disposition kinetic parameters after oral or intramuscular (IM) administration in horses. Ten clinically healthy adult horses, weighing 380–496 kg body weight (BW), were allocated to two experimental groups of five horses. Group I, was treated with an oral paste formulation of IVM at the manufacturer's recommended dose of 0.2 mg/kg BW. Group II, was treated IM with an injectable 1% formulation of IVM at a dose of 0.2 mg/kg BW. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post‐treatment. After plasma extraction and derivatization, samples were analysed by high‐performance liquid chromatography with fluorescence detection. A computerized kinetic analysis was performed, and data were compared using the Wilcoxon signed rank test. The parent molecule was detected in plasma between 30 min and either 20 (oral) or 40 (IM) days post‐treatment. Significant differences were found for the time corresponding to peak plasma concentrations (tmax) and for absorption half‐life. Peak plasma concentrations (Cmax) of 51.3 ± 16.1 ng/ml (mean ± SD) were obtained after oral administration and of 31.4 ± 6.0 ng/ml for the IM route. The values for area under concentration–time curve were 137.1 ± 35.9 ng day/ml for the group treated orally, and 303.2 ± 4.3 ng day/ml for the IM treated group. The mean plasma residence times were 4.2 ± 0.4 and 8.9 ± 0.7 days for oral and IM‐treated groups, respectively. The results of this study show that the route of administration considerably affects the disposition of IVM. A significant difference in bioavailabilty and half‐life of elimination of IVM was observed after IM administration compared with oral administration. A close relationship between pharmacokinetic profiles and the clinical efficacy of IVM was established.
Concept and Realization of a Multimedia Program for Veterinary Physiology
Authors: Haschke G. , Diener M.
Published: July 2003

A multimedia program, a non‐linear system which supplements the traditional, linear way of learning (e.g. with a text book), was developed. Non‐linear systems allow the direct use of information in a free sequence. A problem of these systems is the danger that the reader becomes lost in detail. Therefore, a program was constructed which tries to combine the properties of linear and non‐linear teaching systems. Student groups were continuously involved during all stages of the project.

The program is organized in several levels. These are: (1) choice of chapters; (2) table of contents of one chapter; (3) summary; (4) text and (5) pictures, animations, simulations and video sequences.

The program can be used in different ways. In the linear mode, the reader selects via action words different levels of the program. The user can read either only on the level of the summaries or on detailed information (text, pictures, simulations and videos). In the non‐linear mode the user jumps via menu items or buttons to selected pictures, simulations or a searched term. In this way, more than 3500 screen pages are integrated into a multimedia program for veterinary physiology. The program is written in toolbook®, and can be used on a personal computer with Windows 95® or higher.
Blood Type A and B Frequencies in Turkish Van and Angora Cats in Turkey
Authors: Arikan S¸. , Duru S. Y. , Gurkan M. , Agaoglu Z. T. , Giger U.
Published: July 2003

Blood typing of domestic cats has been performed in domestic and purebred cats in various parts of the world and is important in clinical practice in order to prevent neonatal isoerythrolysis (NI) and acute haemolytic transfusion reactions. Prevalence of blood types vary greatly between breeds of cats. Turkish Van and Angora cats are different breeds that originated in geographically distinct regions of Turkey. The present survey determined the frequency of blood types in these Turkish pedigreed cats in Turkey. Ethylenediaminetetraacetic‐acid anti‐coagulated blood of a total of 113 Turkish Van and Angora cats were examined for blood typing using a slide and tube agglutination assay. Of the 85 Van cats surveyed, 40% had type A, and 60% had type B blood. Of the 28 Turkish Angora cats, 53.6% had type A, and 46.4% had type B blood. No type AB cats were found between both breeds. There was no significant association between blood types and gender of both Angora and Van cats or eye colours of Van cats (P > 0.05). Although these are limited surveys, the overall prevalence of type B cats in these two breeds was very high compared with the results of previous studies worldwide. It appears likely that blood type incompatibilities responsible for feline NI and transfusion reactions are occurring in these breeds. The risk of transfusion incompatibility in Turkish Angora and Van cats was 46.4 and 60%, respectively. It is therefore strongly recommended to breeders and clinicians that blood typing be performed prior to breeding and transfusing cats.
Effects of Hyperosmolar Ionic and Low Osmolar Non‐ionic Contrast Media on Coagulation Times and Some Blood Parameters in Dogs: anIn VivoStudy
Authors: Izci̇ C. , Ogurtan Z. , Ceylan C.
Published: July 2003

The purpose of this study is to evaluate the effects of hyperosmolar ionic contrast media (CM) (diatzioate) and low osmolar non‐ionic CM (iohexol and ioxilan) on coagulation time and some blood parameters in dogsin vivo. The animals were divided into three groups in equal numbers. The dogs in groups I, II and III received diatrizoate, iohexol and ioxilan at the dose of 700 mgI/kg intravenously (IV) as a bolus, respectively. Administration of contrast media and blood samples were collected from vena cephalica antebrachii prior to CM administration and thereafter at 3, 15, 30, 60, 90 and 180 min and 24 h to measure the coagulation factors [activated partial thromboplastin time (APTT), prothorombin time (PT), fibrinogen and fibrinogen degradation products] and some other blood parameters [red blood cells, platelet, white blood cells, haematocrit (Ht) and haemoglobin (Hb)]. While a statistically significant decrease was observed on APTT at 15 min in group III, no significant differences were found in groups I and II. All the groups had insignificant alterations for PT, fibrinogen and fibrinogen degradation product, following CM administration. Significant decreases were observed for platelet at 3 min in all groups. This decrease was also significant at 15‐ and 30‐ min intervals in group I. There were significant decreases for erythrocytes, Ht and Hb measurements within 30 min, and no significant alterations were observed for leucocytes within 60 min in all groups compared with baseline values. No differences were observed with regard to coagulation times and some blood parameters as far as long‐lasting and major effects of each CM are concerned.
Response of Dogs to Short‐term Infusions of Carbohydrate‐ or Lipid‐based Parenteral Nutrition
Authors: Zentek J. , Stephan I. , Kramer S. , Görig C. , Blum J. W. , Mischke R. , Nolte I.
Published: July 2003

Parenteral nutrition (PN) is used to support intensive care patients. The risk for adverse metabolic effects depends on the composition of infused solutions and the duration of application. The present study in dogs compares metabolic and endocrine effects of two infusion solutions, with either triglycerides or glucose being the major energy sources, administered in a comparatively short infusion period (10 h/day). PN was administered for 9 days to two groups of five adult dogs to meet energy maintenance requirements. In group PN‐LIP 61% of the total energy was derived from lipids and 22% from carbohydrates, compared with 21 and 62% in group PN‐GLUC. Among routine haematology and clinical chemistry the plasma levels of glucose, triglycerides, insulin, insulin‐like growth factor‐I (IGF‐I), glucagon, 3,5,3′‐triiodothyronine and thyroxin were measured in non‐infused dogs and at 2, 4, 6, and 8 h after the start of infusion at days 2 and 8 of the study. Infusions protocols did not cause gross metabolic aberrations. During the actual infusions glucose, triglyceride and insulin concentrations were elevated, each depending on the infusion solution. Concentrations of IGF‐I, glucagon, 3,5,3′‐triiodothyronine, thyroxin and cortisol did not change significantly. In conclusion short infusion periods of 10 h per day were tolerated by healthy dogs without adverse signs, which could improve practicability of PN also in clinical cases.
Comparison of the Techniques of Evaluation of Urine Dilution/Concentration in the Dog
Authors: Dossin O. , Germain C. , Braun J. P.
Published: July 2003

The objective of this study was to evaluate the quality of the measurement of dog urine dilution/concentration by comparing osmolality with three methods of specific gravity (USG) measurement, i.e. weighing, refractometry and test strips. In unselected urine samples from 182 dogs there was a better agreement between osmolality and USG determination by refractometry (r = 0.92) than by weighing (r = 0.82) or by test strips (r = 0.27). There was an almost linear relationship between osmolality and USG:

osmolality (mOsm/kg) = 36646(34318/38974) × (USGref − 1) + 25(−39/88); calculated osmolality differed from measured osmolality by more than 500 mOsm/kg in only 8 of 181 samples. There was a good agreement between USG determination by weighing and refractometry: USGref = 1.000(0.905/1.095) ×USGweighing − 0.0004(−0.0019/0.0027), with a moderate bias. Only 12% of the differences between the two methods exceeded 0.010. Test strip assessment of USG was unreliable because of systematic underestimation and should not be used for dog urine. Refractometry is the best technique for routine evaluation of urine concentration/dilution when osmometry is not available.
Analysis of ELA‐DQB Exon 2 Polymorphism in Argentine Creole Horses by PCR‐RFLP and PCR‐SSCP
Authors: Villegas‐Castagnasso E. E. , Díaz S. , Giovambattista G. , Dulout F. N. , Peral‐García P.
Published: July 2003

The second exon of equine leucocyte antigen (ELA)‐DQB genes was amplified from genomic DNA of 32 Argentine Creole horses by PCR. Amplified DNA was analysed by PCR‐restriction fragment length polymorphism (RFLP) and PCR‐single‐strand conformation polymorphism (SSCP). The PCR‐RFLP analysis revealed two HaeIII patterns, four RsaI patterns, five MspI patterns and two HinfI patterns. EcoRI showed no variation in the analysed sample. Additional patterns that did not account for known exon 2 DNA sequences were observed, suggesting the existence of novel ELA‐DQB alleles. PCR‐SSCP analysis exhibited seven different band patterns, and the number of bands per animal ranged from four to nine. Both methods indicated that at least two DQB genes are present. The presence of more than two alleles in each animal showed that the primers employed in this work are not specific for a unique DQB locus. The improvement of this PCR‐RFLP method should provide a simple and rapid technique for an accurate definition of ELA‐DQB typing in horses.
Fibrosarcomas at Presumed Sites of Injection in Dogs: Characteristics and Comparison with Non‐vaccination Site Fibrosarcomas and Feline Post‐vaccinal Fibrosarcomas
Authors: Vascellari M. , Melchiotti E. , Bozza M. A. , Mutinelli F.
Published: July 2003

Fifteen fibrosarcomas, surgically excised from presumed sites of injection in dogs, and 10 canine fibrosarcomas excised from sites not used for injection were histologically and immunohistochemically compared with 20 feline post‐vaccinal fibrosarcomas. Canine fibrosarcomas from presumed injection sites were of grade I (3), of grade II (4) and grade III (8). Two fibrosarcomas from non‐injection sites were of grade I, four of grade II and four of grade III. Feline samples were classified as grade I (2), grade II (4) and grade III (14). All fibrosarcomas from presumed injection sites of both species showed lymphocytic inflammatory infiltration located at the tumour periphery, while two canine fibrosarcomas from non‐injection sites showed perivascular inflammatory infiltration within the neoplasm. All samples were immunohistochemically examined for vimentin, smooth muscle actin, muscle specific actin and desmin expression. All tumours were positive for vimentin. Ten canine fibrosarcomas from presumed injection sites and all feline samples contained cells consistent with a myofibroblastic immunophenotype. Aluminium deposits were detected in eight canine fibrosarcomas from presumed injection sites and 11 feline post‐vaccinal fibrosarcomas by the aurintricarboxylic acid method. The present study identifies distinct similarities between canine fibrosarcomas from presumed injection sites and feline post‐vaccinal fibrosarcomas, suggesting the possibility of the development of post‐injection sarcomas not only in cats, but also in dogs.
Degenerative Myelopathy Associated with Cobalamin Deficiency in a Cat
Authors: Salvadori C. , Cantile C. , De Ambrogi G. , Arispici M.
Published: July 2003

A severe myelopathy was observed in a 9‐year‐old neutered male cat with a clinical history of chronic pancreatitis associated with deficiency of serum cobalamin and folates concentrations, and progressive spinal ataxia. The spinal cord lesions mainly involved the dorsal columns of the caudal cervical and cervico‐thoracic segments, and were characterized by diffuse vacuolated myelin sheaths and axonal degeneration, marked gliosis, fibrosis and presence of gitter cells. The pancreas showed severe atrophy of the exocrine tissue, periductular fibrosis and infiltration of inflammatory cells, consistent with chronic interstitial pancreatitis. This condition can be accountable for cobalamin deficiency, as the pancreas is the only source of intrinsic factor in cats. The spinal cord lesions in the cat of this report resembled the subacute combined degeneration of the spinal cord described in human beings with cobalamin deficiency and hence a similar pathogenetic mechanism is hypothesized.
Effects of Inter‐ and Intra‐Observer Variability on Echocardiographic Measurements in Awake Cats
Authors: Chetboul V. , Concordet D. , Pouchelon J. L. , Athanassiadis N. , Muller C. , Benigni L. , Munari A. C. , Lefebvre H. P.
Published: July 2003

The objective of this study was to determine intra‐ and inter‐observer variability of echocardiographic measurements in awake cats. Four observers with different levels of experience in echocardiography performed 96 echocardiographic examinations in four cats on four different days over a 3‐week period. The examinations were randomized and blinded. The maximum within‐day and between‐day CV values were 17.4 and 18.5% for inter‐ventricular septal thickness in diastole, 18.7 and 22.6% for left ventricular free‐wall thickness in diastole, 9.8 and 14.9% for left ventricular end‐diastolic diameter, 20.8 and 15.2% for left ventricular end‐systolic diameter, and 21.2 and 18.4% for left ventricular shortening fraction. The maximum within‐day CV values were most often associated with the least competent observer (i.e. the graduate student) and, the minimum CV values with the most competent observer (i.e. the associate professor in cardiology). A significant interaction between cat and observer was also evidenced. Thus, the most competent observer could not be replaced by any of the other observers.
Effects of preweaning doxazosin treatment on adult pressure in the spontaneously hypertensive rat
Authors: Boesen Erika I , Lewis Tamara V , Kett Michelle M , Anderson Warwick P
Published: July 2003

1. The neonatal/preweaning period appears to represent a critical period of involvement of the sympathetic nervous system in the development of hypertension in spontaneously hypertensive rats (SHR).

2. We tested whether α1‐adrenoceptor‐mediated effects during the preweaning period are involved in the development of hypertension in the adult SHR.

3. Male SHR were treated with the α1‐adrenoceptor antagonist doxazosin (10 mg/kg per day, s.c.) from postnatal day 1 to 21 inclusive. Direct conscious blood pressure and heart rate were measured via the caudal artery at 12 weeks of age.

4. Preweaning treatment with doxazosin had no significant effect on mean arterial blood pressure or heart rate in male SHR at 12 weeks of age.

5. These findings do not support the involvement of α1‐adrenoceptor‐mediated effects during the preweaning period in the development of hypertension in adult SHR.
Hypocholesterolaemic effects of an ethanol precipitate of Kabosu juice in stroke‐prone spontaneously hypertensive rats fed a cholesterol‐free diet
Authors: Ogawa Hiroshi , Mochizuki Satoshi
Published: July 2003

1. We have previously identified strong inhibitory effects of Kabosu (Citrus sphaerocarpa Hort.) juice precipitate (KJP) on cholesterol elevation in stroke‐prone spontaneously hypertensive rats (SHRSP) fed a cholesterol diet. In the present study, to elucidate the hypocholesterolaemic mechanism, we examined the effect of dietary KJP on lipid metabolism by using SHRSP fed a cholesterol‐free diet.

2. Compositions of the experimental diet containing 10% KJP powder were adjusted to those of the control diet. Seven‐week‐old male SHRSP were fed control or experimental diet for 2 weeks with free access to the diet and water.

3. Serum levels of cholesterol, phospholipid and triglyceride of the KJP group were significantly reduced, which was due to decreases in the very low‐density lipoprotein (VLDL), low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) fractions.

4. Serum concentrations of apolipoproteins A‐I and E (apoA‐I and E) of the KJP group were significantly lower than those of the control group, whereas no significant differences were observed in serum apoB and apoA‐IV between the two groups.

5. In liver, there were no significant differences in the contents of lipids or relative liver weight between the two groups. The activity of microsomal cholesterol 7α‐hydroxylase of the KJP group tended to increase, whereas that of microsomal acyl‐coenzyme A : cholesterol acyltransferase was significantly reduced, compared with the control group.

6. These results indicate that dietary KJP produces reductions of serum lipid levels, which are due to reductions in VLDL, apoE HDL and apoA‐I HDL, and may promote catabolism and excretion of hepatic cholesterol in SHRSP fed a cholesterol‐free diet.
Protective effect of coadministered superoxide dismutase and catalase against stress‐induced gastric muocsal lesions
Authors: Ohta Yoshiji , Nishida Keiji
Published: July 2003

1. There are conflicting reports as to the protective effect of coadministered native superoxide dismuatase (SOD) and catalase against gastric mucosal lesions in rats with water immersion restraint (WIR) stress. It is unclear how coadministered native SOD and catalase protect against WIR stress‐induced gastric mucosal lesions. Therefore, in the present study, we re‐examined the protective effect of coadministered native SOD and catalase against gastric mucosal lesions in rats with WIR stress.

2. Gastric mucosal lesions were induced in Wistar rats by 3 h WIR. Rats were injected subcutaneously with a mixture of purified bovine erythrocyte SOD and bovine liver catalase 1 h before the onset of WIR. Ulcer index, serum SOD, catalase and xanthine oxidase (XO), uric acid and gastric mucosal SOD, catalase, XO, myeloperoxidase (MPO; an index of tissue neutrophil infiltration), non‐protein sulfhydryl (NP‐SH) and thiobarbituric acid‐reactive substances (TBARS; an index of lipid peroxidation) were assayed in all rats used.

3. Rats with 3 h WIR showed gastric mucosal lesions. Pre‐administration of SOD plus catalase to rats with WIR prevented lesion formation. In the serum of rats with WIR alone, XO activity and uric acid concentration increased, whereas SOD and catalase activities did not change. Pre‐administration of SOD plus catalase to rats with WIR did not affect increased serum XO activity and uric acid concentration, but did increase serum SOD and catalase activities. In the gastric mucosa of rats with WIR alone, increases in MPO activity and TBARS concentration and a decrease in NP‐SH concentration occurred, whereas XO, SOD and catalase activities did not change. Pre‐administration of SOD plus catalase to rats with WIR attenuated the changes in gastric mucosal MPO activity and TBARS and NP‐SH concentrations, but did not affect gastric mucosal XO, SOD and catalase activities. Pre‐administration of SOD plus catalase (in an inactivated form) to rats with WIR had no effect on gastric mucosal lesion formation and the levels of serum and gastric mucosal parameters studied.

4. These results indicate that coadministered native SOD and catalase protect against gastric mucosal lesions in rats with WIR stress and suggest that this protective effect of coadministered native SOD and catalase could be due to their activity to scavenge XO‐derived active oxygen species that are increased in the blood.
Biochemical and morphological characterization of spontaneously hypertensive hyperlipidaemic rats
Authors: Kumai Toshio , Oonuma Shigeko , Kitaoka Yasushi , Tadokoro Mamoru , Kobayashi Shinichi
Published: July 2003

1. To develop and characterize a new animal model of hypertension and hyperlipidaemia, we cross‐bred spontaneously hypertensive rats (SHR) with spontaneously hyperlipidaemic rats (HLR).

2. A new strain of spontaneously hypertensive hyperlipidaemic rats (SHHR) was established at generation 10 through selective mating of brothers and sisters (systolic blood pressure > 150 mmHg, plasma cholesterol > 150 mg/dL). Cross‐bred Wistar‐Kyoto (WKY) rats and Sprague‐Dawley (SD) rats (SDWKY rats) were used as a control.

3. Adrenaline and noradrenaline levels in the plasma and adrenal medulla of male SHHR were significantly higher than those of male SDWKY rats. The tyrosine hydroxylase activity in the adrenal medulla of male SHHR was significantly higher than that of male SDWKY rats. Low‐density lipoprotein expression was found in the plasma of male and female SHHR and HLR. Cholesterol 7α‐hydroxylase mRNA expression in the liver of male SHHR was lower than that of male SDWKY rats. Endothelium lesions and lipid deposition under the endothelium were observed in the aorta of 24‐month‐old SHHR, especially female SHHR, but not in age‐matched HLR and SDWKY rats.

4. The hypertension of this new animal model of hypertension and hyperlipidaemia may be related to increased catecholamine activity and the hyperlipidaemia may be related to changes in the expression of cholesterol 7α‐hydroxylase mRNA and lipoprotein profiles. The SHHR may be valuable in the study of mechanisms of atherosclerosis and the evaluation of anti‐atherosclerosis drugs as a new strain of cardiovascular disease.
Cardiac hypertrophy: A matter of translation
Authors: Hannan RD , Jenkins A , Jenkins AK , Brandenburger Y
Published: July 2003

1. Left ventricular hypertrophy (LVH) of the heart is an adaptive response to sustained increases in blood pressure and hormone imbalances. Left ventricular hypertrophy is associated with programmed responses at the molecular and biochemical level in different subsets of cardiac cells, including the cardiac muscle cells (cardiomyocytes), fibroblasts, conductive tissue and coronary vasculature.

2. Regardless of the initiating cause, the actual increase in chamber enlargement is, in each case, due to an increase in size of a pre‐existing cardiomyocyte population, with little or no change in their number; a process referred to as cellular hypertrophy.

3. An accelerated rate of global protein synthesis is the primary mechanism by which protein accumulation increases during cardiomyocyte hypertrophy. In turn, increased rates of synthesis are a result of increased translational rates of existing ribosomes (translational efficiency) and/or synthesis and recruitment of additional ribosomes (translational capacity).

4. The present review examines the relative importance of translational capacity and translational efficiency in the response of myocytes to acute and chronic demands for increased protein synthesis and the role of these mechanisms in the development of LVH.
Effects of chronic hypobaric hypoxia on contractile properties of rat sternohyoid and diaphragm muscles
Authors: El‐Khoury R , O'Halloran KD , Bradford A
Published: July 2003

1. Chronic hypoxia occurs in a variety of circumstances, including respiratory disease and exposure to altitude, and is known to affect respiratory muscle structure. However, little is known about its effects on respiratory muscle contractile properties.

2. Rats were exposed to normoxia (n = 16) or hypobaric hypoxia (n = 16; barometric pressure 450 mmHg) for 6 weeks. Contractile properties were measured in isolated sternohyoid and diaphragm muscles in warmed, oxygenated Krebs' solution. Isometric twitch and tetanic tension, contraction time, half‐relaxation time and tension–frequency relationship were determined using field stimulation with platinum electrodes. Fatigue was induced by stimulation at 40 Hz with 300 msec trains of 0.5 Hz for 5 min.

3. Chronic hypoxia had no effect on bodyweight, but did increase haematocrit. Chronic hypoxia increased specific force development in both muscles and increased sternohyoid fatigue. Chronic hypoxia had no effect on contractile kinetics in either muscle, but shifted the tension–frequency relationship to the left in the diaphragm.

4. Therefore, chronic hypoxia alters rat respiratory muscle force and fatigue, either due to the direct effects of hypoxia or to increased muscle activation.
Effect of nitroglycerine in popliteal preparations from patients with peripheral occlusive arteriopathy precontracted with KCl or 5‐hydroxytryptamine
Authors: Ortega Ana , Avellanal Martin , España Gabriel , Flores Angel , Aleixandre Amaya
Published: July 2003

1. At the present time, there are no studies in isolated arteries from patients suffering from peripheral occlusive arteriopathy (POA). In the present study, we attempt to characterize the effect of nitroglycerine (GTN) in isolated popliteal preparations obtained after leg amputation in 60–90‐year‐old men and women suffering from POA.

2. After surgical operation, arterial samples were stored in a refrigerator at 4°C and, after 12–36 h, they were cut into rings and mounted in organ baths containing Krebs'–Henseleit solution at 37°C and gassed constantly with 95% CO2 and 5% O2. Because noradrenaline elicited very poor contractile responses in these preparations, in the present study we evaluated the concentration‐dependent contractions induced by KCl (15–90 mmol/L) and 5‐hydroxytryptamine (5‐HT; 10−7 to 10−4 mol/L) in arteriopathic popliteal rings and, when the corresponding maximum contractile effect had been obtained, we also evaluated the concentration‐dependent relaxing effect produced by GTN (10−10 to 10−5 mol/L) in all precontracted preparations. As a reference, similar experiments were performed in popliteal preparations obtained following surgery on non‐arteriopathic vascular tissue where it was necessary to resect a certain percentage of healthy vessel.

3. The responses to KCl and 5‐HT were greater in healthy vessel than in arteriopathic rings. The relaxing effect of GTN was greater in preparations precontracted with 5‐HT than in those preparations precontracted with KCl. In addition, preparations precontracted with KCl relaxed even less when they were obtained from patients with POA.

4. The present data indicate that GTN is a vasodilator with little effect on depolarized arteries. The results also indicate that the effect of this drug is even less in depolarized arteries from patients with POA.
ON BEING THE RIGHT SIZE: HEART DESIGN, MITOCHONDRIAL EFFICIENCY and LIFESPAN POTENTIAL
Authors: Dobson Geoffrey P
Published: July 2003

1. From the smallest shrew or bumble‐bee bat to the largest blue whale, heart size varies by over seven orders of magnitude (from 12 mg to 600 kg). This study reviews the scaling relationships between heart design, cellular bioenergetics and mitochondrial efficiencies in mammals of different body sizes.

2. The [31P]‐nuclear magnetic resonance‐derived [phosphocreatine]/[ATP] ratio in hearts of smaller mammals is significantly higher (2.7 ± 0.3 for mouse;n = 22) than in larger mammals (1.6 ± 0.3 for humans;n = 13).

3. The inverse of the free myocardial cytosolic [ADP] concentration and the cytosolic phosphorylation ratio ([ATP]/[ADP][Pi]) scales with heart size and with absolute mitochondrial and myofibrillar volumes, close to a quarter‐power (from −0.22 to −0.28;r = 0.99).

4. Assuming a similar mitochondrial P/O ratio and the same maximal amount of work required to convert 1 mol NADH to 0.5 mol O2(i.e. 212.25 kJ/mol), the higher [ATP]/[ADP][Pi] ratios or cellular driving forces (ΔG′ATP) in hearts of smaller mammals imply greater mitochondrial efficiencies in coupling ATP production to electron transport as body size decreases. For a P/O ratio of 2.5, the mitochondrial efficiency in the heart of a shrew, mouse, human and whale is 84, 82, 71 and 65%, respectively.

5. Higher cytosolic ATP]/[ADP][Pi] ratios and ΔG′ATPvalues imply that the hearts of smaller mammals operate further from equilibrium than hearts of larger mammals.

6. As a consequence of scaling relationships, a number of remarkable invariants emerge when comparing heart function from the smallest shrew to the largest whale; the total volume of blood pumped by each heart in a lifetime is approximately 200 million L/kg heart and the total number of heart beats is approximately 1.1 billion per lifetime.

7. Similarly, the metabolic potential (total O2consumed during adult lifespan per g bodyweight) for a 2 g shrew or a 100 000 kg blue whale is approximately 38 L O2consumed or 8.5 mol ATP/g body mass per lifetime.

8. The importance of quarter‐power scaling relationships linking structural, metabolic and bioenergetic design to the natural ageing process and maximum lifespan potential is discussed.
SPECIES‐INDEPENDENT METABOLIC RESPONSE TO AN INCREASE OF [Ca2+]i IN QUIESCENT CARDIAC MUSCLE
Authors: Ward Marie‐Louise , Cooper Patricia J , Hanley Peter J , Loiselle Denis S
Published: July 2003

1. The aim of the present investigation was to contrast the Ca2+ dependence of cardiac energy metabolism in two species with differential reliance on extracellular Ca2+ for excitation–contraction coupling.

2. We measured energy expenditure as the rate of oxygen consumption (V̇o2) of isolated, Langendorff‐perfused hearts of rats and guinea‐pigs during KCl arrest. In parallel experiments, we indexed intracellular Ca2+ concentration ([Ca2+]i) of isolated right‐ventricular trabeculae, using the Ca2+ fluorophore fura‐2 and ratiometric spectrofluorometry. By varying extracellular Na+ concentration ([Na+]o), V̇o2–[Na+]o and [Ca2+]i–[Na+]o relationships were constructed for each species.

3. Reduction of [Na+]o during K+ arrest caused pronounced species‐dependent elevations of both V̇o2 and [Ca2+]i. Despite the species dependence of both V̇o2 and [Ca2+]i on [Na+]o, a single species‐independent V̇o2–[Ca2+]i relationship obtained.

4. We infer that elevation of the metabolic rate of the arrested heart above its basal value is determined primarily by [Ca2+]i and is not species dependent.
Cardiac energetics: Sense and nonsense
Authors: Gibbs Colin L
Published: July 2003

1. The background to current ideas in cardiac energetics is outlined and, in the genomic era, the need is stressed for detailed knowledge of mouse heart mechanics and energetics.

2. The mouse heart is clearly different to the rat in terms of its excitation–contraction (EC) coupling and the common assumption that heart rate difference between mice and humans will account for the eightfold difference in myocardial oxygen consumption is wrong, because the energy per beat of the mouse heart is approximately one‐third that of the human heart.

3. In vivo evidence suggests that there may well be an eightfold species difference in the non‐beating metabolism of mice and human hearts. It is speculated that the magnitude of basal metabolism in the heart is regulatable and that, in the absence of perfusion, it falls to approximately one‐quarter of its in vivo rate and that in clinical conditions, such as hibernation, it probably decreases; its magnitude may be controlled by the endothelium.

4. The active energy balance sheet is briefly discussed and it is suggested that the activation heat accounts for 20–25% of the active energy per beat and cross‐bridge turnover accounts for the balance. It is argued that force, not shortening, is the major determinant of cardiac energy usage.

5. The outcome of recent cardiac modelling with variants of the Huxley and Hill/Eisenberg models is described. It has been necessary to invoke ‘loose coupling’ to replicate the low cardiac energy flux measured at low afterloads (medium to high velocities of shortening).

6. Lastly, some of the unexplained or ‘nonsense’ energetic data are outlined and eight unsolved problems in cardiac energetics are discussed.
CARDIAC ENERGETICS: FROM EMAX TO PRESSURE–VOLUME AREA
Authors: Suga Hiroyuki
Published: July 2003

1. To celebrate this Festschrift for Professor Colin Gibbs, as an invited speaker, I would like to review briefly my 35 year research career in cardiac physiology.

2. My career started in the late 1960s in Tokyo with my serendipitous discovery of Emax (ventricular end‐systolic maximum elastance) as a load‐independent contractility index based on the time‐varying elastance (E(t)) model of the ventricle. Professor K Sagawa at the Johns Hopkins University, USA, whom I joined in 1971, encouraged me to go further.

3. The next serendipitous event in my career was the discovery of ventricular pressure–volume area (PVA) as a measure of total mechanical energy of ventricular contraction in the late 1970s. The PVA concept was theoretically deducible from the E(t) and Emax concept and correlated surprisingly well with ventricular O2 consumption (Vo2).

4. Professor Gibbs' intuitive recognition of the significance of PVA in myocardial energetics in the 1980–1990s greatly encouraged me thereafter. The third serendipitous event in my career occurred in the mid 1990s and was my discovery of a novel integrative analysis method to assess the total amount of Ca2+ recruited in each excitation–contraction coupling from the decay rate of postextrasystolic potentiation, taking advantage of the Emax–PVA–Vo2 framework.

5. I am now hoping to experience one more serendipitous experience by developing an integrative analysis method of cross‐bridge cycling in a beating heart using the Emax and PVA concepts.
Force‐matching errors after eccentric exercise attributed to muscle soreness
Authors: Proske U , Weerakkody NS , Percival P , Morgan DL , Gregory JE , Canny BJ
Published: July 2003

1. Experiments were performed to test the ability of human subjects to match forces in their elbow flexor muscles following eccentric exercise of one arm and, in a second series, after biceps brachii of one arm had been made sore by injection of hypertonic saline.

2. In the force‐matching task, the elbow flexors of one arm, the reference arm, generated 30% of maximum voluntary contraction (MVC) under visual control. Subjects matched that level with their other arm, the indicator arm, without visual feedback.

3. After eccentric exercise of elbow flexors of the indicator arm, subjects felt they had achieved a satisfactory match while indicating forces that were significantly lower, by approximately 5%, than the reference level. Errors were in the opposite direction (i.e. forces were overestimated) when the reference arm was exercised.

4. Errors were reduced when matching forces were expressed as fractions of the sessional MVC rather than the pre‐exercise MVC. Residual errors from 24 h postexercise onwards were attributed to muscle soreness from the exercise.

5. In support of this view, a similar pattern of matching errors was observed when an unexercised arm was made sore by injection of hypertonic saline into the biceps.

6. It is concluded that muscle soreness can interfere with a subject's ability to match forces, perhaps as a result of a reduced excitability of motor cortex. It implies that muscle soreness may contribute to the weakness experienced after a period of unaccustomed eccentric exercise.
Relationship between isometric force and myofibrillar MgATPase at short sarcomere length in skeletal and cardiac muscle and its relevance to the concept of activation heat
Authors: Stephenson D George
Published: July 2003

1. This paper has been written in recognition of the seminal contributions to cardiac and skeletal muscle energetics made by Professor Colin Gibbs during his distinguished academic career.

2. The paper focuses on what is now known about the relationship between Ca2+‐activated isometric force production and myofibrillar MgATPase in intact and skinned (surface membrane rendered permeable) skeletal and cardiac muscle preparations at short sarcomere lengths.

3. The relevance of this relationship to understanding the interactions between the actin and myosin filaments at the cross‐bridge level in the region of double actin filament overlap and the cellular basis of ‘activation heat’ measurements in intact striated muscles is discussed.
Energy cost of contraction in rat urinary bladder smooth muscle during anoxia
Authors: Wendt Igor R , Paul Richard J
Published: July 2003

1. The aim of the present study was to investigate the effects of hypoxia on energy metabolism and contraction of rat urinary bladder smooth muscle, thereby gaining insight into the capacity of this smooth muscle to maintain contractile function when rendered hypoxic.

2. Isometric force, oxygen consumption, lactate production, heat production and unloaded shortening velocity were measured in isolated muscle strips under both aerobic and anaerobic conditions. Muscle strips were bathed in physiological saline solution with the anaerobic condition being created by replacing the oxygen bubbling the solution with nitrogen.

3. During contraction under anaerobic conditions, the rate of lactate production was increased 2.5‐fold above that observed under aerobic conditions. This, however, only provided for a rate of ATP production of approximately 30% of that measured under aerobic conditions. Despite this, force maintenance was only slightly depressed, indicating that the metabolic cost of contraction was reduced in hypoxia. In support of this, the rate of heat production during contractions in anoxia was only approximately half of that under aerobic conditions, whereas, again, force was only slightly lower. Unloaded shortening velocity was significantly lower in anoxia, suggesting a slower cross‐bridge turnover rate.

4. The results indicate that the economy of force maintenance is increased in bladder smooth muscle under hypoxic conditions and that this is due, at least in part, to a reduced rate of cross‐bridge cycling. This may help to preserve bladder contractile function during periods of ischaemia that may be associated with bladder filling and emptying.
Membranes as metabolic pacemakers
Authors: Else Paul L , Hulbert Anthony J
Published: July 2003

1. In the present review, we suggest that a few common processes linked to membranes consume the majority of energy used by most organisms.

2. Membranes may act as metabolic pacemakers through changes in lipid composition, altering membrane characteristics and the working environment of membrane proteins.

3. Experiments involving membrane exchanges show predictable changes in protein activities (sodium pump) that are dependent upon the type of membrane used.

4. Potential mechanisms discussed include fluidity, electrical fields, surface area requirements of lipids and peptide–lipid interactions.
Cardiovascular risk in dialysis patients: A comparison of risk factors and cardioprotective therapy between 1996 and 2001
Authors: CHOW Fiona YF , POLKINGHORNE Kevan R , CHADBAN Steven J , ATKINS Robert C , KERR Peter G
Published: July 2003

SUMMARY:  Cardiovascular disease (CVD) is the major cause of mortality in dialysis patients. Aspirin, beta‐blockers, statins, and angiotensin‐converting enzyme (ACE) inhibitors reduce CVD mortality in the general population, as may angiotensin II receptor antagonists. The prevalence of cardiovascular risk factors and usage rates of cardioprotective agents in end‐stage renal failure are unknown. A retrospective, cross‐sectional study of dialysis patients was performed to compare: (i) prevalence of cardiovascular risk factors (age, hypertension, hyperlipidaemia, diabetes mellitus, and smoking); (ii) use of cardioprotective agents; and (iii) prevalence of cardiovascular disease between the time‐points: 1996 (n = 262) versus 2001 (n = 369). We found an increase in the risk factors of age (53.6 ± 14.9 years in 1996 vs 58.4 ± 14.3 in 2001; P < 0.001) and hyperlipidaemia (45 vs 51.8%; P < 0.001) between the two time‐points, with a reduction in the prevalence of smoking (14.5 vs 8.1%; P = 0.016). There was no difference in the prevalence of cardiovascular disease (37.4 vs 40.7%; P = 0.44). Cardioprotective agents were underutilized, with improvement in prescribing practice between 1996 and in 2001, especially in the usage of statins (21.4 vs 38.7% in 2001; P = 0.019). In conclusion, CVD is the primary cause of mortality in our dialysis patients. Although traditional cardiovascular risk factors affect the majority of the dialysis population, underutilization of cardioprotective agents is common. Proof of efficacy of these agents in this population of enormous risk is urgently required.
Historical controlled trial of OKT3 versus basiliximab induction therapy in simultaneous pancreas–renal transplantation
Authors: CHOW Fiona YF , POLKINGHORNE Kevan , SAUNDER Alan , KERR Peter G , ATKINS Robert C , J CHADBAN Steven
Published: July 2003

SUMMARY: Simultaneous pancreas–kidney (SPK) transplant recipients are at high immunological risk of rejection. Antibody induction is beneficial but lymphocyte‐depleting therapy is associated with a high incidence of side‐effects. We performed a historical controlled trial to compare OKT3 versus anti‐CD25 antibody (basiliximab) induction therapy with regard to patient, kidney and pancreas survival, as well as to examine for any differences in acute rejection, graft function, and infective complications. Twenty‐eight consecutive SPK transplants were performed at the Monash Medical Centre between December 1997 and November 2001. Anti CD3 monoclonal antibody (OKT3) was used prior to March 2000 (n = 12) and basiliximab was used after (n = 16), both in combination with cyclosporin, mycophenolate, and prednisolone. A retrospective comparison of outcomes was performed. At 6 months, patient (100vs100%), kidney (91.7vs91.7%) and pancreas (75vs83.3%) survival were similar in the OKT3 and basiliximab groups, respectively. A minority of subjects in each group remained free from rejection (42% basiliximabvs25% on OKT3,P = NS). Renal function was superior in the basiliximab group (mean calculated creatinine clearance 79.4 ± 11.9vs54.5 ± 15.9 mL/min for  basiliximabvsOKT3,P < 0.001). The incidence of major opportunistic infection was lower in basiliximab‐treated patients (9vs50% in the OKT3 group,P = 0.033). Basiliximab was associated with similar 6‐month patient, kidney and pancreas survival, superior renal function and less opportunistic infection as compared with OKT3 induction therapy in SPK transplants. Basiliximab is at least as effective and is safer than OKT3 for induction therapy in SPK transplantation.
Ramipril prevents microtubular changes in proximal tubules from streptozotocin diabetic rats
Authors: OSICKA Tanya M , FORBES Josephine M , THALLAS Vicki , BRAMMAR Gail C , JERUMS George , COMPER Wayne D
Published: July 2003

SUMMARY:  This study has investigated the microtubular cytoskeleton in rat glomerular and proximal tubule cells in experimental diabetes. The effect of treatment with ramipril on the relationship between microtubule organization and albuminuria in diabetes has also been examined. Diabetes was induced in male Sprague–Dawley rats by administration of streptozotocin (50 mg/kg, i.v.). Rats were treated with or without ramipril in their drinking water for 12 weeks. Diabetes was characterized by an increase in blood glucose level, glomerular filtration rate, and albumin excretion rate. Treatment of diabetic rats with ramipril did not affect glycaemic control, but reduced systolic blood pressure and prevented the rise in albuminuria and glomerular filtration rate. Immunohistochemistry was performed by using the ARK Peroxidase method with α‐tubulin antibody. The regular, grainy staining pattern of the microtubules present in the renal proximal tubules from control kidneys was altered in diabetic animals, and appeared fragmented and striated. This was prevented by treatment with ramipril. Quantitative morphometric analysis revealed an increase in the percent proportional staining for α‐tubulin in the proximal tubules of untreated diabetic rats (33.3 ± 3.3%, n = 8, P < 0.05 vs control) compared with control rats (11.7 ± 1.7%, n = 6), which was reduced by ramipril treatment (26.7 ± 2.1%, n = 6, P < 0.05 vs untreated diabetic). Staining for α‐tubulin in glomerular cells was unchanged in all groups. There was no significant difference in renal α‐tubulin expression among all groups, as determined by real‐time reverse transcription–polymerase chain reaction. These results raise the possibility that diabetes‐induced changes in microtubules in the renal proximal tubules may contribute, in part, to the increase in albuminuria observed in diabetes.
Screening for intracranial aneurysms in autosomal dominant polycystic kidney disease
Authors: HUGHES Peter DV , BECKER Gavin J
Published: July 2003

SUMMARY:  Screening patients with autosomal dominant polycystic kidney disease (ADPKD) for asymptomatic intracranial aneurysms has been proposed as a method of reducing the morbidity and mortality associated with aneurysm rupture. However, recent studies have shown lower spontaneous rupture rates of small aneurysms and higher risks of significant complications with interventions than previously reported. Risk‐benefit analysis has not demonstrated any benefit of screening ADPKD patients without a history of subarachnoid haemorrhage (SAH) for intracranial aneurysms, and has suggested that screening might cause harm.