Resistance to Eimeria zuernii produced after chemotherapy of experimental infection in calves

Nineteen Holstein-Friesian bull calves were inoculated with 2.4 × 10⁶ sporocysts of Eimeria zuernii by stomach tube. The calves were divided into three groups 10 days after infection. The first group (seven calves) was treated with monensin (1 mg/kg body weight daily) from the 10th–20th day after infection; the second group (six calves) with amprolium (10 mg/kg body weight daily) for the same period of time and the third group (six calves) acted as infected controls. Both drugs were effective in preventing clinical signs, in reducing rates of weight gain and in suppressing oocyst production. The calves were reinfected with E. zuernii 35 days after the initial infection. The calves of all three groups were resistant to the second infection with E. zuernii as measured by rates of weight gain, fecal oocyst output and lack of clinical signs.     

Ascaris suum Infection in Calves I. Clinical Signs

Clinical signs consistent with those of atypical interstitial pneumonia (AIP) were induced in calves sensitized with infective Ascaris suum eggs at seven to 20 weeks of age and challenged at three-week intervals one or more times. These signs usually appeared on the sixth or seventh day postinfection and reached maximum severity between the tenth and 13th days following infection. Prominent signs were: dyspnea, often with expiratory grunt, coughing, mouth breathing and emphysema as well as increased respiration and heart rates. In general, the intensity of signs was dependent upon dose size, although a single small dose resulted in acute signs and death in one calf. Intermittent coughing and vesicular sounds were induced in calves given A. suum eggs continually over prolonged periods. No respiratory abnormalities resulted from challenge with Toxocara canis after sensitization with A. suum. Antihistamine therapy did not alter the clinical signs in A. suum infected calves.     

Sudden death of calves by experimental infection with Strongyloides papillosus. I. Parasitological observations.

Recently, an unknown disease, 'sudden death', in calves has been found in Japanese beef production farms. A previous study conducted by Taira and Ura indicated that sudden death can be effected in calves by hyperinfection of Strongyloides papillosus (SPL) and that the disease is possibly caused by SPL infection. In the present work, an experimental infection of SPL in calves was conducted to confirm the field occurrence. Fifteen Holstein Friesian calves, ranging from 45.5 to 85.6 kg in body weight, were divided into six groups. Calves of Groups A, B, C, D, E and F were infected once at the rate of 100,000, 320,000, 1,000,000, 3,200,000, 10,000,000 and 32,000,000 SPL larvae per 100 kg of body weight, respectively. Five calves were assigned to Group B, while two calves were assigned to the other groups. After showing no premonitory signs, sudden death of ten calves took place. The survival time of these calves was 27.4 and 16.8 days (Group B), 14.8 and 14.8 days (Group C), 13.3 and 14.2 days (Group D), 11.0 and 11.1 days (Group E) and 11.6 and 10.8 days (Group F). Three calves of Group B did not exhibit sudden death. The results of this study demonstrate that strongyloidiasis was the cause of sudden death.     

Efficacy of florfenicol in the treatment of experimentally induced infectious bovine keratoconjunctivitis.

OBJECTIVE: To evaluate efficacy of florfenicol in an induced model of infectious bovine keratoconjunctivitis, using a blinded randomized, controlled trial. ANIMALS: 48 male Holstein calves, 2 to 4 months old. PROCEDURE: Moraxella bovis infection was induced in all calves. When corneal ulcers developed, each calf was assigned randomly to 1 of 3 treatment groups, using a block design determined by corneal ulcer size (day 0). Calves were treated with florfenicol (20 mg/kg of body weight, IM) on days 0 and 2 (IM group; n = 16). Calves of a second group received a single dose of florfenicol (40 mg/kg, SC) on day 0 (SC group; n = 16). The third group of calves was not treated (control group; n = 16). Corneal ulcers were photographed, and each calf was assessed for 30 days after treatment for 10 clinical signs of infection. Corneal ulcer surface areas were measured, and clinical scores were calculated. Ocular secretions for microbiologic culture were obtained weekly from each eye. RESULTS: A Cox regression model indicated that, after adjustment for initial ulcer size, healing rates were 6.2 and 4.8 times greater in calves of the IM and SC groups, respectively, compared with the control group. Clinical scores and surface area measurements for treatment groups were significantly smaller than those for controls during posttreatment weeks 1 through 4. From day 8 through day 29, M bovis was isolated from ocular secretions of 14 of 16 control calves and 1 of 32 treated calves. CONCLUSIONS AND CLINICAL RELEVANCE: Parenterally administered florfenicol reduces corneal ulcer healing time, lessens clinical severity, and reduces the amount of bacterial shedding from calves infected with M bovis.     

Relationship between degree of viremia and disease manifestation in calves with experimentally induced bovine viral diarrhea virus infection.

OBJECTIVE: To compare degree of viremia and disease manifestations in calves with type-I and -II bovine viral diarrhea virus (BVDV) infection. ANIMALS: 16 calves. PROCEDURE: Colostrum-deprived calves obtained immediately after birth were assigned to 1 control and 3 treatment groups (4 calves/group). Calves in treatment groups were inoculated (day 0) by intranasal instillation of 10(7) median tissue culture infective dose BVDV 890 (type II), BVDV 7937 (type II), or BVDV TGAN (type I). Blood cell counts and virus isolation from serum and leukocytes were performed daily, whereas degree of viremia was determined immediately before and 4, 6, 8, and 12 days after inoculation. Calves were euthanatized on day 12, and pathologic, virologic, and immunohistochemical examinations were performed. RESULTS: Type-II BVDV 890 induced the highest degree of viremia, and type-I BVDV TGAN induced the lowest. Virus was isolated more frequently and for a longer duration in calves inoculated with BVDV 890. A parallel relationship between degree of viremia and rectal temperature and an inverse relationship between degree of viremia and blood cell counts was observed. Pathologic and immunohistochemical examinations revealed more pronounced lesions and more extensive distribution of viral antigen in calves inoculated with type-II BVDV. CONCLUSIONS AND CLINICAL RELEVANCE: Degree of viremia induced during BVDV infection is associated with severity of clinical disease. Isolates of BVDV that induce a high degree of viremia may be more capable of inducing clinical signs of disease. Strategies (eg, vaccination) that reduce viremia may control clinical signs of acute infection with BVDV.     

Experimental reproduction of respiratory tract disease with bovine respiratory syncytial virus

An experiment was conducted to reproduce respiratory tract disease with bovine respiratory syncytial virus (BRSV) in one-month-old, colostrum-fed calves. The hypothesized role of viral hypersensitivity and persistent infection in the pathogenesis of BRSV pneumonia was also investigated. For BRSV inoculation a field isolate of BRSV, at the fifth passage level in cell culture, was administered by a combined respiratory tract route (intranasal and intratracheal) for four consecutive days. Four groups of calves were utilized as follows: Group I, 6 calves sham inoculated with uninfected tissue culture fluid and necropsied 21 days after the last inoculation; Group II, 6 calves inoculated with BRSV and necropsied at the time of maximal clinical response (4-6 days after the last inoculation); Group III, 6 calves inoculated with BRSV and necropsied at 21 days after the last inoculation; Group IV, 6 calves inoculated with BRSV, rechallenged with BRSV 10 days after initial exposure, and necropsied at 21 days after the initial inoculation. Clinical response was evaluated by daily monitoring of body temperature, heart rate, respiratory rate, arterial blood gas tensions, hematocrit, total protein, white blood cell count, and fibrinogen. Calves were necropsied and pulmonary surface lesions were quantitated by computer digitization. Viral pneumonia was reporduced in each principal group. Lesions were most extensive in Group II. Disease was not apparent in Group I (controls). Significant differences (p less than 0.05) in body temperature, heart rate, respiratory rate, arterial oxygen tension, and pneumonic surface area were demonstrated between control and infected calves. Results indicate that severe disease and lesions can be induced by BRSV in one-month-old calves that were colostrum-fed and seropositive to BRSV. BRSV rechallenge had minimal effect on disease progression. Based on clinical and pathological response, results did not support viral hypersensitivity or persistent infection as pathogenetic mechanisms of BRSV pneumonia.     

Potential use of hematological and acute phase protein parameters in the diagnosis of acute Schmallenberg virus infection in experimentally infected calves

The initial viraemic phase of Schmallenberg virus (SBV) infection in bovine animals is characterized by the non-specific and inconspicuous clinical signs of pyrexia (>40 °C), drop in milk yield and sometimes diarrhea. As a result, the early detection of SBV epizootics can difficult, and typically only become apparent when the congenital form of the disease is observed. The aim of the study was to describe the course of the acute phase response and haematological findings in bovine calves following experimental SBV infection. No clinical signs except for increase in rectal temperature were observed in the calves inoculated subcutaneously with a Polish strain of SBV. Viral RNA was detected in serum at 2 and 4 days post inoculation (dpi). SBV antibodies were first detected by ELISA (9–21 dpi), and subsequently by virus neutralization test (14–32 dpi). The hematological parameters showed a reduction in mid-size leucocytes (MID), and also in red blood cell count (RBC). An increase in mean corpuscular hemoglobin was also observed in SBV infected calves. No significant difference in acute phase proteins (APP) was observed between experimentally infected and control calves, suggesting limited potential as diagnostic biomarker of acute SBV infection.     

Bovine herpesvirus-1 and parainfluenza-3 virus interactions: clinical and immunological response in calves.

Calves infected with bovine herpesvirus-1 (BHV-1) or both BHV-1 and parainfluenza-3 virus (PIV-3) developed clinical signs including fever, cough, and nasal and ocular discharges. Animals infected with both viruses appeared more depressed and showed higher rectal temperature, while calves inoculated with PIV-3 alone had a very mild clinical disease. Both BHV-1 and PIV-3 were recovered from nasal secretions up to six to eight days postinoculation. However, the virus titers were lower in calves with mixed infection. An increase in serum antibodies to both BHV-1 and PIV-3 was detected by serum neutralization and enzyme-linked immunosorbent assay. Antibody responses were delayed and significantly lower in calves given mixed infection than in calves infected with a single virus. Interleukin-2 activity in cultures of lymphocytes from BHV-1 and BHV-1 plus PIV-3 infected calves was higher compared to control calves.     

Efficacy of an inactivated respiratory syncytial virus vaccine in calves.

OBJECTIVE: To determine whether an inactivated bovine respiratory syncytial virus (BRSV) vaccine would protect calves from infection with virulent BRSV. DESIGN: Randomized controlled trial. ANIMALS: 27 nine-week-old calves seronegative for BRSV exposure. PROCEDURE: Group-1 calves (n = 9) were not vaccinated. Group-2 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing a minimum immunizing dose of antigen. Group-3 calves (n = 9) were vaccinated on days 0 and 21 with an inactivated BRSV vaccine containing an amount of antigen similar to that in a commercial vaccine. All calves were challenged with virulent BRSV on day 42. Clinical signs and immune responses were monitored for 8 days after challenge. Calves were euthanatized on day 50, and lungs were examined for lesions. RESULTS: Vaccination elicited increases in BRSV-specific IgG and virus neutralizing antibody titers and in production of interferon-gamma. Virus neutralizing antibody titers were consistently less than IgG titers. Challenge with BRSV resulted in severe respiratory tract disease and extensive pulmonary lesions in control calves, whereas vaccinated calves had less severe signs of clinical disease and less extensive pulmonary lesions. The percentage of vaccinated calves that shed virus in nasal secretions was significantly lower than the percentage of control calves that did, and peak viral titer was lower for vaccinated than for control calves. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the inactivated BRSV vaccine provided clinical protection from experimental infection with virulent virus and decreased the severity of pulmonary lesions. Efficacy was similar to that reported for modified-live BRSV vaccines.     

Longevity of protective immunity to experimental bovine herpesvirus-1 infection following inoculation with a combination modified-live virus vaccine in beef calves

OBJECTIVE: To determine whether a combination viral vaccine containing modified-live bovine herpesvirus-1 (BHV-1) would protect calves from infection with a recent field isolate of BHV-1. DESIGN: Randomized controlled trial. ANIMALS: Sixty 4- to 6-month-old beef calves. PROCEDURE: Calves were inoculated with a placebo 42 and 20 days prior to challenge (group 1; n = 10) or with the combination vaccine 42 and 20 days prior to challenge (group 2; 10), 146 and 126 days prior to challenge (group 3; 10), 117 and 96 days prior to challenge (group 4; 10), 86 and 65 days prior to challenge (group 5; 10), or 126 days prior to challenge (group 6; 10). All calves were challenged with BHV-1 via aerosol. Clinical signs, immune responses, and nasal shedding of virus were monitored for 14 days after challenge. RESULTS: Vaccination elicited increases in BHV-1-specific IgG antibody titers. Challenge with BHV-1 resulted in mild respiratory tract disease in all groups, but vaccinated calves had less severe signs of clinical disease. Extent and duration of nasal BHV-1 shedding following challenge was significantly lower in vaccinated calves than in control calves. In calves that received 2 doses of the vaccine, the degree of protection varied with the interval between the last vaccination and challenge, as evidenced by increases in risk of clinical signs and extent and duration of viral shedding. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that this combination vaccine provided protection from infection with virulent BHV-1 and significantly reduced nasal shedding of the virus for at least 126 days after vaccination.     

The Effect of Dexamethasone on Bovine Coccidiosis

When dexamethasone was administered intramuscularly to Hereford calves at the time of inoculation with Eimeria zurnii and E. bovis, there was no apparent effect on the resulting infection. Medication at the time of appearance of the clinical signs caused sufficient aggravation of the disease to result in the death of the animals. Administration of the drug after subsidence of the clinical signs did not cause a clinical relapse, but resulted in prolonged oocyst discharge in the feces. Treatment of uninoculated normal calves with dexamethasone caused a brief period of increased oocyst discharge without clinical signs.     

Effects of Jatropha curcas on calves.

Jatropha curcas seed was fed to six calves at doses of 2.5, 1 and 0.25 g/kg once and to two other calves at 0.025 g/kg up to 14 days. The onset of toxic manifestations in the six calves was rapid and death occurred within 19 hours of administration. The two calves that received daily the lowest dose of J. curcas showed signs of poisoning and died within 10 to 14 days. The clinical signs of diarrhoea, dyspnoea, dehydration and loss of condition were well correlated with the pathological findings. There was an increase in aspartate aminotransferase, ammonia and potassium and a decrease in total protein and calcium in the serum of jatropha-poisoned calves.     

Efficacy of a live Pasteurella multocida vaccine for the prevention of experimentally induced bovine pneumonic pasteurellosis

Seventeen Holstein-Friesian calves weighing an average of 139.8 +/- 13.5 (mean +/- standard deviation) kg were used in a study to determine the efficacy of a live vaccine containing of Pasteurella multocida A:3 and Pasteurella haemolytica A:1. Eleven calves received the vaccine by intramuscular injection in the right shoulder, whereas six calves received vaccine diluent and served as non-vaccinated controls. Fourteen days following vaccination (Day 15) all calves were inoculated deep intranasally with 3.6 X 10(7) TCID50 bovine herpes virus-1. On Day 16, calves were stressed by transports, and on Day 17 calves were challenged intratracheally with P. multocida A:3. On Day 22 calves were euthanized and necropsied, and tissues were collected for pathological and microbiological evaluations. Scores were assigned to each calf based on the severity of observed clinical signs. Macroscopic lung lesions were expressed as percentage of tissue involved relative to the total lung tissue of a calf. Plasma fibrinogen concentration, rectal temperature, serum antibody level, microscopic appearance of lung, and microbiologic results were also recorded for analyses. The control calves had significantly higher clinical-sign scores (P less than 0.05) and more severe gross lesions (P less than 0.05) than the vaccinated calves. Although the vaccinated calves had a slight increase of immunoglobulins M and G classes, the differences were not statistically significant (P greater than 0.05, P greater than 0.05). The results of the study indicate that the live Pasteurella vaccine is effective against experimental P. multocida infection in calves.     

Efficacy of tilmicosin in treatment of pulmonary infections in calves.

The efficacy of tilmicosin in the treatment of respiratory infections in calves was evaluated. According to a randomised block design, 58 calves with naturally occurring respiratory infections were treated with one of the following products: a single subcutaneous injection of tilmicosin (10 mg/kg liveweight) or daily intramuscular injections of 5 mg lincomycin and 10 mg spectinomycin/kg liveweight, for a minimum of three days. Both treatment groups initially showed similar clinical signs and their initial responses to the treatments were good. However, the tilmicosin treated calves improved more rapidly. Significantly greater improvements (P less than or equal to 0.05) were observed in their demeanour and appetite during the first 10 days after treatment began, and in their respiratory condition between five and 10 days after treatment began.     

Evaluation of severe disease induced by aerosol inoculation of calves with bovine respiratory syncytial virus

OBJECTIVE: To develop a model of bovine respiratory syncytial virus (BRSV) infection that induces severe disease similar to that seen in some cattle with naturally acquired BRSV infection. ANIMALS: 25 male Holstein calves, 8 to 16 weeks old. PROCEDURE: 17 calves were given a low-passage field isolate of BRSV by aerosolization; 8 control calves were given supernatant from noninfected cell culture. Disease was characterized by evaluating clinical signs, virus isolation and pulmonary function tests, and results of blood gas analysis, gross and histologic postmortem examination, and microbiologic testing. RESULTS: Cumulative incidence of cough, harsh lung sounds, adventitious sounds, and dyspnea and increases in rectal temperature and respiratory rate were significantly greater in infected calves. Three infected calves developed extreme respiratory distress and were euthanatized 7 days after inoculation. Virus was isolated from nasal swab specimens from all infected calves but not from mock infected calves. On day 7 after inoculation, mean PaO2 and PaCO2 were significantly lower, and pulmonary resistance was significantly higher, in infected calves. During necropsy, infected calves had varying degrees of necrotizing and proliferative bronchiolitis and alveolitis with syncytial formation. The 3 calves euthanatized on day 7 had emphysematous bullae in the caudal lung lobes; 1 had unilateral pneumothorax. CONCLUSION AND CLINICAL RELEVANCE: Severe disease similar to that seen in some cattle with naturally acquired BRSV infection can be induced in calves with a single aerosol exposure of a low-passage clinical isolate of BRSV. Our model will be useful for studying the pathogenesis of BRSV infection and for evaluating vaccines and therapeutics.     

Epidemiology of bovine dictyocaulosis in Denmark

A field experiment was conducted over two grazing seaons with calves on a permanent pasture in order to follow the pattern of infection with Dictyocaulus viviparus. Infective larvae persisted during the first, but not during the second, winter of observation. By means of the agar-bile herbage technique, a moderate first peak of infection was demonstrated in the pasture 2–3 weeks before the appearance of respiratory signs in the calves. Fluctuations in faecal larval output were reflected in the herbage contamination with infective larvae close to faecal pats. This, as well as the horizontal dispersion of larvae in the pasture, took place in less than a week. The proportion of lungworm larvae recovered away from faeces was low during a period of dry and hot weather while herbage sampling at two-hour intervals during two days showed an increase in herbage contamination with lungworm larvae, but not with trichostrongyle larvae between 10 a.m. and 12 noon.The infectivity of the pasture was monitored by tracer calves and compared with the results of the pasture sampling. The general course of the infection in the calves and in the pasture was the results of interaction between them. In addition, the pasture infection was influenced by climate and the infection in the calves by the development of immunity. The course of infection in individuals appeared to have an influence on the general course of the infection through the contamination of the pasture.     

Clinical infectious bovine rhinotracheitis in cattle fed organic iodine and urea.

The feeding of ethylenediamine dihydriodide (EDDI) at the dose levels of 50 and 500 mg/animal/day and urea at the dose level of 45 g/animal/day did not affect duration of clinical signs, body weight gain, magnitude or duration of fever, serum concentration of glutamic oxalacetic transaminase, packed cell volume, and differential white blood cell counts in feeder cattle experimentally infected with infectious bovine rhinotracheitis (IBR) virus. However, coughing and abundance of nasal discharge were significantly greater in calves fed EDDI before and during primary IBR virus infection. Those calves fed 500 mg of EDDI/day coughed more, had greater nasal discharge, and exhibited greater lacrimation than did those given the smaller dose. These 3 clinical signs were considered to reflect both the expectorant action of EDDI and the pathogenic effects of IBR virus. In all calves, including controls, the coughing, nasal discharge, and lacrimation were most prominent during the period of peak infection (7 to 14 days after the calves were given intranasal inoculation) of the IBR virus. Total serum iodine concentration became maximal (mean of 1,400 ng/ml) in 8 calves after they had been fed the larger dose of EDDI for 2 weeks. This value was maximal (about 300 ng/ml) in another 8 calves after 3 weeks' feeding of the smaller dose (50 mg/day). When EDDI exposure was maintained at the dose level of 50 mg/day for 5 weeks longer, mean serum iodine values remained at about 275 ng/ml, and those of control calves averaged 140 ng/ml.     

Effect of vaccination with the R mutant Escherichia coli (J5) antigen on morbidity and mortality of dairy calves

A prospective cohort study was undertaken to determine the efficacy of Escherichia coli 0111:B4 (J5) vaccination in dairy calves. Calves on 2 units were vaccinated when they were 2 to 3 days old and 2 weeks later with the J5 antigen or they were left unvaccinated, and were observed during the first 60 days of age for morbidity and mortality. Events recorded were death, the first case of illness, the first sign of a respiratory tract condition, the first sign of diarrhea, and the first treatment. The time to death or to a morbid event was examined as a function of vaccination status, using the Cox model of survival analysis, where serum IgG concentration at 2 to 3 days of age and gender of the calf were included to control confounding. Signs of morbidity in 517 calves were followed, 189 from unit 1 and 328 from unit 2. Vaccination was associated with a 2.15-fold reduction in risk of death on unit 2 (P = 0.042), but with a 2.43-fold increase in risk of death on unit 1 (P = 0.0035). The only association found between vaccination and morbidity was a 1.34-fold reduction in risk of respiratory tract signs for vaccinated calves on unit 2 (P = 0.055). Necropsy results and clinical investigations indicated that calves on unit 1 were poorly nourished and emaciated. Antibodies to J5 2 weeks after vaccination were significantly (P = 0.0002) lower in calves on unit 1 than in calves on unit 2. The findings offered a possible explanation for the adverse vaccination effect in calves on unit 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of IgE in the pathogenesis of bovine respiratory syncytial virus in sequential infections in vaccinated and nonvaccinated calves

A study was undertaken to evaluate the possible role of IgE in the pathogenesis of bovine respiratory syncytial virus (BRSV) infection. Fifteen calves were allotted at random to 3 treatment groups. One group of 6 calves was vaccinated with attenuated BRSV vaccine before live-virus challenge exposure, another group of 6 was not vaccinated before challenge exposure, and the remaining 3 calves served as controls (nonvaccinated, nonchallenge exposed). Calves of the 2 experimental groups were exposed to 2 live-virus aerosolizations (challenge exposure) 35 days apart. Histamine and BRSV-specific IgE (BRSV-IgE) concentrations in serum, lung lavage fluid, and nasopharyngeal exudate, as well as clinical signs of disease, were evaluated for 14 days after each challenge exposure. Vaccination before challenge exposure with live BRSV appeared to have little or no effect on the severity of the disease, but did appear to affect disease persistence. A correlation (P less than 0.02) existed between signs of disease and BRSV-IgE concentration measured in lung lavage fluid, but this was only true for vaccinated calves. Although no other correlations were found between clinical signs of disease and IgE concentration, analysis of the results additionally revealed a strong correlation (P less than 0.002) between disease signs and histamine concentration in nasopharyngeal exudate from calves of both experimental groups. Thus, indirect evidence implicated IgE in BRSV infection pathogenesis.     

The clinical pathology of heartwater. II. Studies on cardiac and pulmonary function in 4 calves with experimentally-induced heartwater

Studies to evaluate cardiac and pulmonary function were undertaken in 4 calves suffering from experimentally-induced heartwater. There was a marked variation in the course of the disease. Three of the calves recovered spontaneously after developing clinical signs. These included a rectal temperature in excess of 40 degrees C, anorexia and listlessness but no neurological signs. The remaining calf died 2 days after developing a fever and neurological signs. In the 3 calves that recovered, a mild hypoxemia developed during the acute stage of the disease. Arterial CO2 tension remained within normal limits, but there was a tendency towards an alkalosis. Increases in pulmonary dead space and fluctuations in venous admixture were observed. The calf that died showed similar mild changes in blood gas parameters, despite the presence of a marked reduction in minute volume, and a lung oedema was demonstrated on post-mortem examination. No marked changes in systolic and diastolic blood pressures and in right cardiac intraventricular pressures were observed. Terminally, however, there were marked decreases in stroke volume and cardiac output. These changes were associated with a sharp increase in heart rate. No primary cardiac pathology was observed on clinical and post-mortem examinations.