Production of cardiac muscle abnormalities in offspring of rats receiving triiodothyroacetic acid (triac) and the effect of beta adrenergic blockade.

As a part of a continuing study on the effects of thyroid hormones on heart muscle, triiodothyroacetic acid (triac), either alone or concurrently with propranolol, has been administered to rats during pregnancy. Control groups received either buffer or propranolol. Offspring, which were given no further treatment, were killed at intervals after birth and their hearts examined histologically, histochemically, and electron microscopically. At 2, 6, and 14 days, offspring of triac-treated rats showed cardiac hypertrophy and, at ultrastructural level, marked disarray of the myofibrils was present. By 28 days, arrangement of the myofibrils had become regular but hypertrophy persisted and was still found in rats examined at 56 days of age, after which time the myocardium was normal. Offspring of rats which had received propranolol at the same time as triac showed a similar pattern of hypertrophy but myofibrillar disarray was not found. Propranolol alone produced no abnormalities. These findings provide further evidence that thyroid hormone analogues can adversely affect heart muscle. When considered in conjunction with previous experiments which showed that thyroxine or triac cause severe hypertrophy but not disarray when given directly to growing rats, they suggest that thyroid hormones can produce a spectrum of abnormalities, thought to depend on the stage of myocardial development at which the stimulus is administered. In the present experiment, the triac-induced myofibrillar disarray but not the hypertrophy was prevented by propranolol, indicating that beta-adrenergic blockade or some other action of propranolol protects the developing myofibrils. Possible mechanisms for the adverse effects of thyroid hormones and the protective action of propranolol are discussed.

Effect of triac and beta-adrenergic blocking agents on the myocardium of developing rats.

Triiodothyroacetic acid, triac, when given to rats during pregnancy, causes hypertrophy and intracellular disarray in the hearts of their offspring and concurrent treatment with dl propranolol can prevent the latter abnormality. Further experiments have been carried out to test the effect of dl oxprenolol and d propranolol on triac-induced myofibrillar disarray. Administration of dl oxprenolol at the same time as triac prevented disarray but a higher dose than that of dl propranolol was required to produce this effect. Disarray was also prevented by d propranolol. Selective consideration of the membrane stabilising, beta blocking and agonist activities of dl oxprenolol and d and dl propranolol leads to the conclusion that although direct or indirect beta stimulation by triac may play a small part in its disruptive effect on the developing myocardium, its main deleterious action can be blocked by membrane stabilisation.

The production of cardiac hypertrophy by tri-iodothyroacetic acid.

Severe cardiac hypertrophy has been produced experimentally in rats by long-term, low-dose treatment with tri-iodothyroacetic acid. The dose used was insufficient to cause any apparent systemic or metabolic effect. It is suggested that similar iodinated substances in the blood in man, resulting from normal or abnormal thyroid hormone catabolism, may be causally related to some forms of cardiomyopathy.

Principal components analysis of haematological data from F344 rats with bladder cancer fed N-(ethyl)-all-trans-retinamide.

Several multivariate statistical methods are available which can alleviate the problems of analysing the large volumes of data generated from toxicological experiments. One such technique, principal components analysis, provides a method for exploring the relationships between a number of variables (such as blood parameters) and for eliminating redundant data if strong correlations exist between the characters. It also provides a method for clustering individuals, which may reveal similarities between animals in a treatment group or highlight individual 'outliers'. The application of principal components analysis to a set of haematological data from a trial evaluating the efficacy of a synthetic retinoid against carcinogen-induced bladder cancer in the rat has clearly shown, in two bivariate plots, that while some animals in the carcinogen-treated groups were normal, others were anaemic and that animals fed the synthetic retinoid and killed at 1 year had a microcytic anaemia. A full exploration of the data using conventional univariate statistical analysis would have involved at least 28 graphic representations of the data, as well as the interpretation of more than 130 means and SDs. Principal components analysis provides a valuable additional tool for the statistical analysis and exploration of toxicological data, but it must be used in conjunction with univariate or other multivariate methods if hypothesis testing is required. The use of multivariate techniques in toxicology may best be assessed by their practical application to toxicological data, and this paper presents such an evaluation with the aim of encouraging further exploration of the usefulness of principal components analysis. The raw data on which most analyses have been carried out are given.

Clinical hematology of the common marmoset Callithrix jacchus.

Hematological studies have been carried out on a group of 96 common marmosets (Callithrix jacchus) on which full clinical histories were available. The group included both healthy and sick animals. Reference values for red-cell, white-cell, and platelet counts; hemoglobin levels; packed cell volumes; red- and white-cell absolute values; reticulocyte counts; and fibrinogen levels were calculated from results obtained in 43 clinically normal individuals. These reference values have been used to identify hematological abnormalities in sick animals so that relationships between the blood picture and the clinical findings could be defined. Leucopenia, raised platelet counts, and high fibrinogen levels were found in animals with bacterial infections and carried poor prognosis. Heinz bodies occurred in a significant number of the group as a whole, and were associated with a variety of hematological and clinical abnormalities. These findings illustrate the diagnostic and prognostic value of clinical hematology in C. jacchus.

Cotton-top tamarins (Saguinus oedipus oedipus): Hematologic reference values and hemopathologic responses.

Hematologic reference values have been established for captive adult cotton-top tamarins (Saguinus oedipus oedipus) by carrying out full blood counts and fibrinogen estimation on 43 clinically normal animals. Females were shown to have significantly lower hemoglobin levels, red cell counts and packed cell volumes, and higher reticulocyte counts than males. The reference values were used to identify abnormal changes in the blood of 13 clinical cases. Marked neutrophilia was found in animals with localized bacterial infections, and a degenerative left shift was recorded in an individual with streptococcal septicemia. Three cases of unexplained progressive muscle wasting showed Heinz body anemia and abnormal white cell changes. These hematologic responses have been compared where possible with those recorded in other species of Callithricidae.

Red-bellied tamarins (Saguinus labiatus): Hematologic reference values and hemopathologic responses.

Hematologic reference values have been established for captive adult red-bellied tamarins (Saguinus labiatus) by carrying out full blood counts and fibrinogen estimations on 25 clinically normal animals. The only significant sex difference detected was in the reticulocyte count which was higher in females than in males. The reference values were used to identify abnormal changes in the blood of nine clinical cases. Hypochromic anemia, neutrophilia, and raised fibrinogen levels were found in animals with self-inflicted injuries, dermatitis, and ileocecal intussusception. Target cells and jaundiced plasma were noted in a case of yersiniosis. Two animals in which generalized muscle wasting was the main abnormal clinical sign were severely anemic, and in one of these cases a significant number of Heinz bodies was present. The findings in these two animals were compared with those in common marmosets (Callithrix jacchus) with possible wasting marmoset syndrome.

Normal haematological values of axis deer (Axis axis), Père David's deer (Elaphurus davidianus) and barasingha (Cervus duvauceli).

Full blood counts and fibrinogen estimations were carried out on a number of clinically normal adult axis deer (Axis axis), Père David's deer (Elaphus davidianus) and barasingha (Cervus duvauceli). Apart from the finding of higher total red cell counts and a lower mean red cell volume in axis deer than in Père David's deer and barasingha, there was little interspecies variation. Some individual Père David's deer showed eosinophilia, thought to be associated with subclinical intestinal nematode infestation. The findings should provide a useful reference base for monitoring health in these species.

Haematological reference values for adult pumas, lions, tigers, leopards, jaguars and cheetahs.

Normal haematological values and fibrinogen levels were obtained from a number of healthy adult Felidae in the collection of the Zoological Society of London. The group comprised 29 pumas (Felis concolor), 32 lions (Panthera leo), 27 tigers (P tigris), 19 leopards (P pardus), 18 jaguars (P onca) and 22 cheetahs (Acinonyx jubatus). The values provided a basis for identifying abnormalities in the blood of sick individuals of these species and for undertaking interspecies comparisons.

Haemolytic effect of Pasteurella haemolytica on blood from young mammals.

On agar plates containing young lamb blood, Pasteurella haemolytica produces a wide outer zone of partial haemolysis in addition to the narrow zone of complete clearing seen on adult sheep blood agar. To determine whether this phenomenon was limited to lamb blood, samples from young animals of 20 mammalian species were examined. Two species--the barbary sheep (Ammotragus lervia) and scimitar horned oryx (Oryx tao)--possessed blood that gave this effect provided that the samples were taken from young animals. The 18 species that gave negative results included an ovine species, the bighorn sheep (Ovis canadensis).

Haematological values in mouflon (Ovis musimon): influence of age, sex, season and vitamin E status.

Full blood counts, fibrinogen estimations and red cell osmotic fragility tests were carried out on a number of clinically normal captive mouflon (Ovis musimon) from various locations. Age related differences in red and white cell counts and sex related differences in red cell counts were demonstrated. There was also evidence for seasonal changes in red cell values in adult females. During this study, some mouflon were found to be deficient in vitamin E and were transferred to a vitamin E supplemented diet. Comparison of findings on vitamin E deficient and supplemented animals revealed no significant haematological differences.

Age related haematological changes in captive Barbary sheep (Ammotragus lervia).

Full blood counts were carried out on a number of clinically normal newborn, juvenile and adult Barbary sheep. Significant age related differences in the number and size of the red cells and in the absolute and relative numbers of neutrophils and lymphocytes were found. Fibrinogen levels and platelet counts were lowest in newborn animals. These differences could complicate the interpretation of haematological findings on sick Barbary sheep if not taken into account.

Changes in red cell volume distribution frequency after acute blood loss in goats (Capra hircus).

Red blood cell volume distribution frequency, red cell counts, packed cell volumes and reticulocyte counts were monitored during recovery from severe haemorrhagic anaemia in goats. During the first three weeks after haemorrhage there was a small transient reticulocyte response and the cells produced were significantly larger than normal. These large cells persisted in the circulation as a distinct subpopulation of macrocytes, so that the rate of red cell production during this phase could be measured. The findings suggest that red cell volume distribution measurement is a useful method for retrospective diagnosis of severe haemorrhage and for monitoring recovery. The technique also provided a means of assessing erythropoietic activity in a species in which the reticulocyte response to red cell loss is minimal.

Haematological findings in red-necked wallabies (Protemnodon rufogrisea) with necrobacillosis.

Results of blood counts on 17 red-necked wallabies (Protemnodon rufogrisea) with confirmed necrobacillosis have been compared with those of 36 clinically normal animals. The most common abnormality in infected animals was a raised fibrinogen level, found in all of the cases tested. Neutrophilia occurred in 10 individuals and neutrophil morphology was abnormal in 15. Some infected animals showed monocytosis, raised erythrocyte sedimentation rates, high platelet counts and changes in their red cells. The findings provide useful information about the response of the blood to severe bacterial infections in red-necked wallabies and demonstrate the potential diagnostic use of clinical haematology in this species.

Normal and clinical haematology in the yak (Bos grunniens).

Haematological examinations have been carried out on 21 clinically normal male and female adult yaks (Bos grunniens). Animals sedated with xylazine had significantly lower red cell counts, haemoglobin levels and packed cell volumes, fewer lymphocytes and higher monocyte counts than those bled while manually restrained. There were few significant sex differences. Several animals had eosinophilia associated with asymptomatic intestinal nematode infection. Haematological reference values were calculated for clinically normal, xylazine sedated and manually restrained yaks. These were used to identify haematological changes in 10 animals with various abnormal clinical signs. It was concluded that blood counts can provide valuable diagnostic information in this species.

The effects of age and anaesthetic on the blood picture of the cuis, Galea musteloides.

Blood samples from 25 adult and 6 immature cuis were examined. There were slight differences in red cell parameters (RBC, Hb, PCV, MCV, MCH, & MCHC) between cuis and guinea-pigs. The total white cell count of cuis was much lower. The neutrophils of the cuis, as of the guinea-pig, had eosinophilic granules and were therefore termed pseudoeosinophils. Kurloff bodies were not present in mononuclear cells. There were more platelets in cuis blood compared with guinea-pig blood. The choice of anaesthetic did not influence any of the red cell parameters of the cuis, but may have affected the relative numbers of pseudoeosinophils, the platelet count and the percentage of reticulocytes. Immature animals had a lower erythrocyte count, a higher MCH and fewer platelets than adults.

The influence of anaesthetics on the haematology of the patas monkey, Erythrocebus patas.

The effects of phencyclidine, ketamine and an alphaxalone-alphadolone mixture on the haematology of the patas monkeys have been compared. In animals sedated with phencyclidine or ketamine the only significant difference detected was in the mean cell volume. Statistically significant differences in white-cell count and blood coagulation and fibrinolytic activity were found in monkeys which had received alphaxalone-alphadolone. It is suggested that ketamine is a suitable alternative to phencyclidine for haematological studies in these monkeys.

Age-related changes in the haematology of female F344 rats.

As little comprehensive baseline data are available on age-related haematological changes in genetically-defined rat strains, the haematology of female F344 rats is described in animals sampled at 2, 4, 8, 20, 66 and 121 weeks of age. Values for Hb, RBC and PCV increased from 2 weeks of age to reach adult levels at 8 weeks, whereas MCV, MCH and reticulocyte counts were high initially but decreased to reach the adult range at 8 weeks. Between 66 and 121 weeks, reticulocyte counts were significantly increased and values for MCHC significantly decreased. Lymphocytes were the predominant white cell type in each age group. The absolute numbers of neutrophils and lymphocytes showed slight variations between 2 and 66 weeks and both cell types increased significantly between 66 and 121 weeks. Platelet counts showed no overall age-related trends. Fibrinogen values increased from 2 weeks of age to reach the adult level at 8 weeks. One animal of the 14 sampled at 121 weeks showed changes in the blood, liver and spleen consistent with a diagnosis of lymphoid leukaemia.

Susceptibility of tamarin (Saguinus labiatus) red blood cell membrane lipids to oxidative stress: implications for wasting marmoset syndrome.

Captive Callitrichids frequently suffer a fatal wasting disease, wasting marmoset syndrome (WMS), of unexplained cause. This paper describes studies on the erythrocytes from animals in a breeding colony of tamarins (Saguinus labiatus), in which deaths from anaemia and wasting were occurring, to seek evidence for biochemical changes which could lead to oxidative damage and premature cell lysis. In only one animal of 33 studied did the red blood cell lipids show an increased susceptibility to oxidative damage. This animal, with some degree of certainty, could be diagnosed as having WMS. It was concluded that evidence for a primary deficiency of antioxidants as a cause of unexplained deaths, or WMS, in the colony could not at present be substantiated.

Haematology of clinically normal and abnormal captive llamas and guanacoes.

Blood counts of healthy juvenile and adult llamas (Lama glama) and guanacoes (L guanacoe) showed that guanacoes have higher red cell counts, haemoglobin values and packed cell volumes than llamas. In both species, the numbers of lymphocytes and platelets were higher in juveniles than in adults. By reference to the values found in normal animals, abnormal haematological variations were detected in a number of sick individuals. Neutrophilia, hyperfibrinogenaemia and a tendency to develop regenerative hypochromic anaemia were observed in animals with acute and chronic inflammatory diseases and hypochromic macrocytic anaemia occurred in animals with parasitic infections. Many individuals in which subclinical intestinal parasitic infections were suspected had relatively high eosinophil counts although their other haematological values were normal.