Anti-hypotensive treatment and endothelin blockade synergistically antagonize exercise fatigue in rats under simulated high altitude.

Rapid ascent to high altitude causes illness and fatigue, and there is a demand for effective acute treatments to alleviate such effects. We hypothesized that increased oxygen delivery to the tissue using a combination of a hypertensive agent and an endothelin receptor A antagonist drugs would limit exercise-induced fatigue at simulated high altitude. Our data showed that the combination of 0.1 mg/kg ambrisentan with either 20 mg/kg ephedrine or 10 mg/kg methylphenidate significantly improved exercise duration in rats at simulated altitude of 4,267 m, whereas the individual compounds did not. In normoxic, anesthetized rats, ephedrine alone and in combination with ambrisentan increased heart rate, peripheral blood flow, carotid and pulmonary arterial pressures, breathing rate, and vastus lateralis muscle oxygenation, but under inspired hypoxia, only the combination treatment significantly enhanced muscle oxygenation. Our results suggest that sympathomimetic agents combined with endothelin-A receptor blockers offset altitude-induced fatigue in rats by synergistically increasing the delivery rate of oxygen to hypoxic muscle by concomitantly augmenting perfusion pressure and improving capillary conductance in the skeletal muscle. Our findings might therefore serve as a basis to develop an effective treatment to prevent high-altitude illness and fatigue in humans.

Diminishment of respiratory sinus arrhythmia foreshadows doxorubicin-induced cardiomyopathy.

BACKGROUND: The development of a microcomputer-based device permits quick, simple, and noninvasive quantification of the respiratory sinus arrhythmia (RSA) during quiet breathing. METHODS AND RESULTS: We prospectively and serially measured the radionuclide left ventricular ejection fraction and the RSA amplitude in 34 cancer patients receiving up to nine monthly bolus treatments with doxorubicin hydrochloride (60 mg/m2). Of the eight patients who ultimately developed symptomatic doxorubicin-induced congestive heart failure, seven (87.5%) demonstrated a significant decline in RSA amplitude; five of 26 subjects without clinical symptoms of cardiotoxicity (19.2%) showed a similar RSA amplitude decline. On average, significant RSA amplitude decline occurred 3 months before the last planned doxorubicin dose in patients destined to develop clinical congestive heart failure. CONCLUSION: Overall, RSA amplitude abnormality proved to be a more specific predictor of clinically significant congestive heart failure than did serial resting radionuclide ejection fractions.

The effects of cadence and power output upon physiological and biomechanical responses to incremental arm-crank ergometry

The aim of this study was to examine the effects of cadence and power output on physiological and biomechanical responses to incremental arm-crank ergometry (ACE). Ten male subjects (mean +/- SD age, 30.4 +/-5.4 y; height, 1.78 +/-0.07 m; mass, 86.1 +/-14.2 kg) undertook 3 incremental ACE protocols to determine peak oxygen uptake (VO2 peak; mean of 3 tests: 3.07 +/- 0.17 L.min-1) at randomly assigned cadences of 50, 70, or 90 r.min-1. Heart rate and expired air were continually monitored. Central (RPE-C) and local (RPE-L) ratings of perceived exertion were recorded at volitional exhaustion. Joint angles and trunk rotation were analysed during each exercise stage. During submaximal power outputs of 50, 70, and 90 W, oxygen consumption (VO2) was lowest for 50 r.min-1 and highest for 90 r.min-1 (p < 0.01). VO2 peak was lowest during 50 r.min-1 (2.79 +/-0.45 L.min-1; p < 0.05) when compared with both 70 r.min-1 and 90 r.min-1 (3.16 +/-0.58, 3.24 +/-0.49 L.min-1, respectively; p > 0.05). The difference between RPE-L and RPE-C at volitional exhaustion was greatest during 50 r.min-1 (2.9 +/- 1.6) when compared with 90 r.min-1 (0.9 +/- 1.9, p < 0.05). At VO2 peak, shoulder range of motion (ROM) and trunk rotation were greater for 50 and 70 r.min-1 when compared with 90 r.min-1 (p < 0.05). During submaximal power outputs, shoulder angle and trunk rotation were greatest at 50 r.min-1 when compared with 90 r.min-1 (p < 0.05). VO2 was inversely related to both trunk rotation and shoulder ROM during submaximal power outputs. The results of this study suggest that the greater forces required at lower cadences to produce a given power output resulted in greater joint angles and range of shoulder and trunk movement. Greater isometric contractions for torso stabilization and increased cost of breathing possibly from respiratory-locomotor coupling may have contributed increased oxygen consumption at higher cadences.

Tiflocolitis syndrome acute for "Klebsiella" sp. in a spanish pure breed horse. A case report

Were study a horse (Equus caballus), Purebred Spanish Horse, 6 years old, intact male sex, weight about 550kg, from equestrian center in Fregenal Sierra-Extremadura, Spain. History of acute diarrhea, are apply conventional treatment (hydration, anti-inflammatory and antibiotic). Physical examination showed severe profuse, fetid diarrhea deep red, tachypnea. The physiological parameters were: heart rate 60 bpm, respiratory rate 39 rpm and mucous cyanotic. Temperature: 40°C. Hematological examination showed severe leucopenia, decreased total serum protein, albumin and globulin also diminished. Serum chemistry evidenced severe hyponatremia and hypokalemia, with high levels of chlorine indicating metabolic acidosis. A stool analysis, which was negative and showed no eggs or larvae in the samples studied was performed. The microbial culture allowed the isolation of Klebsiella sp. and susceptibility testing showed sensitivity to ampicillin, Cetafzidine, Ciprofloxacin, Cefepine, gentamicin, imipenem, meropenem, Piperaciclina, piperacillin / tazobactam and trimethoprim sulfa resistance. The horse presented systemic complications associated with endotoxemia and death 36 hours after the onset of diarrhea. At necropsy, severe bleeding was observed enterotiflocolitis. The histological sections showed proliferative enteritis characterized by lymphocyte and mononuclear inflammatory infiltrate plasmocytorious mucosa and submucosa, coagulation necrosis, bacteria and short rod type morphology with no specific grouping. In conclusion a case of acute syndrome enterotiflocolitis reported Klebsiella sp. on a horse Purebred Spanish.

The effect of videotapes of animals on cardiovascular responses to stress

Animals have long been noted for their ability to moderate cardiovascular responses to stress. To date, however, little attention has been directed towards the ability of videotapes of animals to buffer people from challenges. This study thus explored the effect of five video conditions (fish, bird, primate, control 1 [humans], control 2 [blank screen]) on the heart rate and blood pressure of 100 volunteers before and after exposure to a cognitive stressor. Twenty participants were randomly assigned to each of the video conditions. Both the heart rate and blood pressure (diastolic and systolic) of the participants were recorded after a 10 minute period of relaxation (phase 1), following 10 minutes of exposure to the appropriate video for that condition (phase 2) and again, following a 10 minute period of reading aloud, i.e. a cognitive stressor (phase 3). The videos encouraged relaxation, with participants in all conditions exhibiting significantly (p < 0.001) lower levels of heart rate and blood pressure in phase 2 than phases 1 or 3. Individuals exposed to the videos of birds, fish and primates showing significantly (p < 0.001) lower levels of heart rate and blood pressure in phase 3 than individuals exposed to the control videos. It is concluded that videotapes of certain animals can reduce cardiovascular responses to psychological stress and may help to buffer viewers from anxiety, at least in the short term.

The relationship of clinical and inflammatory markers to outcome in stable patients with cystic fibrosis

Decreased survival in patients with cystic fibrosis has been related to FEV1, BMI, and infection with Burkholderia cepacia complex (BCC). We have assessed the relationship of blood, sputum, and urine inflammatory markers to lung function, BMI, colonization with B cenocepacia (Bc), and patient survival. Thirty-nine stable cystic fibrosis (CF) patients (10 with Bc) were enrolled in a study to determine the effect of alpha-1-antitrypsin on airways inflammation. Pre-treatment measurements were used in this study. Demographics, sputum microbiology, heart rate, oxygen saturation, lung function were recorded. Blood samples were obtained for white blood count (WBC), C-Reactive Protein (CRP), and plasma neutrophil elastase/AAT complexes (pNEC). Neutrophil elastase (NE), neutrophil elastase/AAT complexes (sNEC), interleukin-8 (IL-8), TNF-receptor 1 (sTNFr), and myeloperoxidase (MPO) were measured in sputum and urinary desmosine concentration determined. Patients with Bc had significantly higher levels of pNEC, 332?±?91.4 ng/ml (mean?±?SEM) versus 106?±?18.2 ng/ml (P?=?0.0005) and sNEC, 369?±?76.6 ng/ml versus 197?±?36.0 ng/ml compared to those who were not. Five deaths were reported at the end of 1 year, (four with Bc) (P?=?0.011). Patients who subsequently died had significantly lower lung function FEV1, 1.2?±?0.2 L versus 2.0?±?0.1 L (P?=?0.03) and FVC, 2?±?0.3 L versus 3.1?±?0.2 L (P?=?0.01), compared to those that survived. There was significantly higher NE activity, 3.6?±?1.6 U/ml versus 1.5?±?0.6 U/ml (P?=?0.03), pNEC, 274?±?99 ng/ml versus 142?±?30 ng/ml (P?=?0.05), MPO, 163?±?62 mcg/ml versus 54?±?6.9 mcg/ml (P?=?0.03), and urinary desmosines 108?±?19.9 pM/mg creatinine versus 51.1?±?3.3 pM/mg creatinine (P?=?0.001), in those patients who subsequently died compared to those that survived. These data suggest there is increased neutrophil degranulation in patients infected with Bc and these patients have a poor outcome.

Role of creatine supplementation on exercise-induced cardiovascular function and oxidative stress

Many degenerative diseases are associated with increased oxidative stress. Creatine has the potential to act as an indirect and direct antioxidant; however, limited data exist to evaluate the antioxidant capabdities of creatine supplementation within in vivo human systems. This study aimed to investigate the effects of oral creatine supplementation on markers of oxidative stress and antioxidant defenses following exhaustive cycling exercise. Following preliminary testing and two additional familiarization sessions, 18 active males repeated two exhaustive incremental cycling trials (T1 and T2) separated by exactly 7 days. The subjects were assigned, in a double-blind manner, to receive either 20 g of creatine (Cr) or a placebo (P) for the 5 days preceding T2. Breath-by-breath respiratory data and heart rate were continually recorded throughout the exercise protocol and blood samples were obtained at rest (preexercise), at the end of exercise (postexercise), and the day following exercise (post24 h). Serum hypdroperoxide concentrations were elevated at postexercise by 17 +/- 5% above preexercise values (p = 0.030). However, supplementation did not influence lipid peroxidation (serum hypdroperoxide concentrations), resistance of low density lipoprotein to oxidative stress (t(1/2max) LDL oxidation) and plasma concentrations of non-enzymatic antioxidants (retinol, alpha-carotene, beta-carotene, alpha-tocopherol, gamma-tocopherol, lycopene and vitamin Q. Heart rate and oxygen uptake responses to exercise were not affected by supplementation. These findings suggest that short-term creatine supplementation does not enhance non-enzymatic antioxidant defence or protect against lipid peroxidation induced by exhaustive cycling in healthy males.

Validity and reliability of cardiorespiratory measurements recorded by the LifeShirt during exercise tests

The LifeShirt is a novel ambulatory monitoring system that records cardio respiratory measurements outside the laboratory. Validity and reliability of cardiorespiratory measurements recorded by the LifeShirt were assessed and two methods of calibrating the LifeShirt were compared. Participants performed an incremental treadmill test and a constant work rate test (65% peak oxygen uptake) on four occasions (>48 In apart) and wore the LifeShirt, COSMED system and Polar Sport Tester simultaneously. The LifeShirt was calibrated using two methods: comparison to a spirometer; and 800 ml fixed-volume bag. Ventilation, respiratory rate, expiratory time and heart rate recorded by the LifeShirt were compared to measurements recorded by laboratory equipment. Sixteen adults participated (6M: 10F); mean (SD) age 23.1 (2.9) years. Agreement between the LifeShirt and laboratory equipment was acceptable. Agreement for ventilation was improved by calibrating the LifeShirt using a spirometer. Reliability was similar for the LifeShirt and the laboratory equipment. This study suggests that the LifeShirt provides a valid and reliable method of ambulatory monitoring. (C) 2009 Elsevier B.V. All rights reserved.

Responses of calves to acute stress: Individual consistency and relations between behavioral and physiological measures

The present study examined the consistency over time of individual differences in behavioral and physiological responsiveness of calves to intuitively alarming test situations as well as the relationships between behavioral and physiological measures. Twenty Holstein Friesian heifer calves were individually subjected to the same series of two behavioral and two hypothalamo-pituitary-adrenocortical (HPA) axis reactivity tests at 3, 13 and 26 weeks of age. Novel environment (open field, OF) and novel object (NO) tests involved measurement of behavioral, plasma cortisol and heart rate responses. Plasma ACTH and/or cortisol response profiles were determined after administration of exogenous CRH and ACTH, respectively, in the HPA axis reactivity tests. Principal component analysis (PCA) was used to condense correlated measures within ages into principal components reflecting independent dimensions underlying the calves' reactivity. Cortisol responses to the OF and NO tests were positively associated with the latency to contact and negatively related to the time spent in contact with the NO. Individual differences in scores of a principal component summarizing this pattern of inter-correlations, as well as differences in separate measures of adrenocortical and behavioral reactivity in the OF and NO tests proved highly consistent over time. The cardiac response to confinement in a start box prior to the OF test was positively associated with the cortisol responses to the OF and NO tests at 26 weeks of age. HPA axis reactivity to ACTH or CRH was unrelated to adrenocortical and behavioral responses to novelty. These findings strongly suggest that the responsiveness of calves was mediated by stable individual characteristics. Correlated adrenocortical and behavioral responses to novelty may reflect underlying fearfulness, defining the individual's susceptibility to the elicitation of fear. Other independent characteristics mediating reactivity may include activity or coping style (related to locomotion) and underlying sociality (associated with vocalization). (c) 2005 Elsevier Inc. All rights reserved.

Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: potential therapeutic benefits beyond glycaemic control?

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by the small intestine in response to nutrient ingestion. It has wide-ranging effects on glucose metabolism, including stimulation of insulin release, inhibition of glucagon secretion, reduction of gastric emptying and augmentation of satiety. Importantly, the insulinotropic actions of GLP-1 are uniquely dependent on ambient glucose concentrations, and it is this particular characteristic which has led to its recent emergence as a treatment for type 2 diabetes. Although the major physiological function of GLP-1 appears to be in relation to glycaemic control, there is growing evidence to suggest that it may also play an important role in the cardiovascular system. GLP-1 receptors (GLP-1Rs) are expressed in the heart and vasculature of both rodents and humans, and recent studies have demonstrated that GLP-1R agonists have wide-ranging cardiovascular actions, such as modulation of heart rate, blood pressure, vascular tone and myocardial contractility. Importantly, it appears that these agents may also have beneficial effects in the setting of cardiovascular disease (CVD). For example, GLP-1 has been found to exert cardioprotective actions in experimental models of dilated cardiomyopathy, hypertensive heart failure and myocardial infarction (MI). Preliminary clinical studies also indicate that GLP-1 infusion may improve cardiac contractile function in chronic heart failure patients with and without diabetes, and in MI patients after successful angioplasty. This review will discuss the current understanding of GLP-1 biology, examine its emerging cardiovascular actions in both health and disease and explore the potential use of GLP-1 as a novel treatment for CVD.

Changes in muscle sympathetic nerve activity and vascular responses evoked in the spinotrapezius muscle of the rat by systemic hypoxia.

Responses evoked in muscle sympathetic nerve activity (MSNA) by systemic hypoxia have received relatively little attention. Moreover, MSNA is generally identified from firing characteristics in fibres supplying whole limbs: their actual destination is not determined. We aimed to address these limitations by using a novel preparation of spinotrapezius muscle in anaesthetised rats. By using focal recording electrodes, multi-unit and discriminated single unit activity were recorded from the surface of arterial vessels. This had cardiac- and respiratory-related activities expected of MSNA, and was increased by baroreceptor unloading, decreased by baroreceptor stimulation and abolished by autonomic ganglion blockade. Progressive, graded hypoxia (breathing sequentially 12, 10, 8% O2 for 2 min each) evoked graded increases in MSNA. In single units, mean firing frequency increased from 0.2 ± 0.04 in 21% O2 to 0.62 ± 0.14 Hz in 8% O2, while instantaneous frequencies ranged from 0.04–6 Hz in 21% O2 to 0.09–20 Hz in 8% O2. Concomitantly, arterial pressure (ABP), fell and heart rate (HR) and respiratory frequency (RF) increased progressively, while spinotrapezius vascular resistance (SVR) decreased (Spinotrapezius blood flow/ABP), indicating muscle vasodilatation. During 8% O2 for 10 min, the falls in ABP and SVR were maintained, but RF, HR and MSNA waned towards baselines from the second to the tenth minute. Thus, we directly show that MSNA increases during systemic hypoxia to an extent that is mainly determined by the increases in peripheral chemoreceptor stimulation and respiratory drive, but its vasoconstrictor effects on muscle vasculature are largely blunted by local dilator influences, despite high instantaneous frequencies in single fibres.

Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2 alpha gain-of-function mutation

The hypoxia-inducible factors (HIFs; isoforms HIF-1 alpha, HIF-2 alpha, HIF-3 alpha) mediate many responses to hypoxia. Their regulation is principally by oxygen-dependent degradation, which is initiated by hydroxylation of specific proline residues followed by binding of von Hippel-Lindau (VHL) protein. Chuvash polycythemia is a disorder with elevated HIF. It arises through germline homozygosity for hypomorphic VHL alleles and has a phenotype of hematological, cardiopulmonary, and metabolic abnormalities. This study explores the phenotype of two other HIF pathway diseases: classic VHL disease and HIF-2 alpha gain-of-function mutation. No cardiopulmonary abnormalities were detected in classic VHL disease. HIF-2 alpha gain-of-function mutations were associated with pulmonary hypertension, increased cardiac output, increased heart rate, and increased pulmonary ventilation relative to metabolism. Comparison of the HIF-2 alpha gain-of-function responses with data from studies of Chuvash polycythemia suggested that other aspects of the Chuvash phenotype were diminished or absent. In classic VHL disease, patients are germline heterozygous for mutations in VHL, and the present results suggest that a single wild-type allele for VHL is sufficient to maintain normal cardiopulmonary function. The HIF-2 alpha gain-of-function phenotype may be more limited than the Chuvash phenotype either because HIF-1 alpha is not elevated in the former condition, or because other HIF-independent functions of VHL are perturbed in Chuvash polycythemia.-Formenti, F., Beer, P. A., Croft, Q. P. P., Dorrington, K. L., Gale, D. P., Lappin, T. R. J., Lucas, G. S., Maher, E. R., Maxwell, P. H., McMullin, M. F., O'Connor, D. F., Percy, M. J., Pugh, C. W., Ratcliffe, P. J., Smith, T. G., Talbot, N. P., Robbins, P. A. Cardiopulmonary function in two human disorders of the hypoxia-inducible factor (HIF) pathway: von Hippel-Lindau disease and HIF-2 alpha gain-of-function mutation. FASEB J. 25, 2001-2011 (2011). www.fasebj.org

The cardiac responses of the scallop Pecten maximus (L.) to respiratory stress

Heart activity of Pecten maximus (L.) has been recorded during various forms of experimentally induced respiratory stress. There was considerable variation in the responses of individual scallops but bradycardia generally occurred in response to all forms of respiratory stress, with the rate of fall in heart rate dependent upon the severity of hypoxia. When oxygen tension declined slowly in a closed respirometer there was regulation of both heart rate and oxygen consumption. The critical tension, Pc, for oxygen consumption lay between 70 and 80 mm Hg, and corresponded with a slight regulatory upswing of the heart rate, whereas the Pc for heart rate was much lower at 20–30 mm Hg. Sudden transfer to deoxygenated water for 3 h resulted in very rapid bradycardia and there was a rapid recovery and initial overshoot of the normal rate on return to well-oxygenated sea water. Aerial exposure for 3 h produced more gradual bradycardia followed by gradual recovery on return to sea water. The results of this work are compared in some detail with previous work on other species of bivalve from different geographical areas and habitats, and the mechanisms controlling cardiac and respiratory regulation are discussed. It is concluded that there are few clear-cut general differences between littoral and sublittoral species in their behavioural and physiological adaptations to hypoxia; the main distinguishing feature of littoral-adapted species is their ability to control air-gaping. Changes in heart activity generally indicate variations in metabolic rate, the speed at which the metabolic rate may be altered reflecting the degree of adaptation to the littoral environment.

The initial mode of action of copper on the cardiac physiology of the blue mussel, Mytilus edulis

Previous studies have shown that low levels of copper (down to 0.8 muM) induce bradycardia in the blue mussel (Mytilus edulis) and that this is not caused by prolonged Valve closure. The aim of this study was to determine the precise mechanism responsible. To establish if copper was directly affecting heart cell physiology, recordings of contractions from isolated ventricular strips were made using an isometric force transducer, in response to copper concentrations (as CuCl2) ranging between 1 muM and 1 mM. Inhibition of mechanical activity only occurred at 1 mM copper, suggesting that the copper-induced bradycardia observed in whole animals cannot be attributed to direct cardiotoxicity. Effects of copper on the cardiac nerves were subsequently examined. Following removal of visceral ganglia (from where the cardiac nerves originate), exposure to 12.5 muM copper had no effect on the heart rate of whole animals. The effect of copper on the heart rate of mussels could not be abolished by depletion of the monoamine content of the animal using reserpine. However, pre-treatment of the animals with alpha -bungarotoxin considerably reduced the sensitivity of the heart to copper. These results indicated that the influence of copper on the heart of M. edulis might be mediated by a change in the activity of cholinergic nerves to heart. In the final experiments, mussels were injected with either benzoquinonium or D-tubocurarine, prior to copper exposure, in an attempt to selectively block the inhibitory or excitatory cholinoreceptors of the heart. Only benzoquinonium decreased the susceptibility of the heart to copper, suggesting that copper affects the cardiac activity of blue mussels by stimulating inhibitory cholinergic nerves to the heart. (C) 2001 Elsevier Science B.V. All rights reserved.

Automated interpulse-duration assessment (AIDA): A new technique for detecting disturbances in cardiac activity in selected macroinvertebrates

An Automated Interpulse Duration Assessment system (AIDA) is described which permits detection of irregularities in cardiac rhythms in selected invertebrates. The sensitivity of AIDA was demonstrated by its ability to detect handling stress in mussels (Mytilus edulis) that was not evident when measuring heart rate alone. Changes in cardiac activity patterns of crabs (Carcinus maenas) held in the laboratory for up to 10 wk was also examined using the new technique. The frequency distribution of interpulse duration changed significantly as the nutritional state changed. Potential applications of the AIDA system are discussed.