Trials were performed in sheep and rats to elucidate the pathogenesis of the myocardial lesions in gousiekte. In the first trial the macro- and lightmicroscopical lesions and myofibre morphometrical changes were studied in ten sheep exposed daily to Pachystigma pygmaeum at 10 g/kg live body weight for 23 to 31 days. All the treated animals either died or were euthanased in extremis between 31 and 51 days after the commencement of dosing. In the second trial the myocardial ultrastructural lesions were studied in six sheep dosed with Fadogia homblei at a dosage rate of 10 g/kg per day live body weight for 22 to 23 days. All the treated animals either died or were euthanased in extremis between 34 and 57 days after the commencement of dosing. The main objective of the third trial was to compare the myocardial lesions in rats exposed to pavetamine with lesions recorded in sheep exposed to P. pygmaeum and F. homblei plant material. Seven rats were injected intraperitoneally with pavetamine at a dosage rate of 5 mg/kg on day 0 and three were killed on day 6. The remaining four were injected with a second dose of pavetamine at a dosage rate of 3 mg/kg on day 27 and euthanased on day 42. In the sheep exposed to P. pygmaeum pulmonary oedema and hydropericardium were present in eight, hydrothorax in four and ascites in two cases. In two sheep cardiac dilatation was associated with subendocardial pallor (fibrosis) and transmural myocardial mottling. Myofibre hypertrophy was recorded in all the sheep, myofibre necrosis and replacement fibrosis occurred in seven animals the latter being particularly evident in animals with medium to long latent periods. A mononuclear cellular infiltration that varied from mild to severe was evident in all the cases and endocardial thickening, which is an indication of cardiac dilatation, was present in seven animals. Myofibre atrophy occurred in eight animals and was the most striking lesion in a sheep with a short latent period. “Typical” gousiekte lesions, characterised by myofibre necrosis and atrophy, replacement fibrosis and an associated round cell infiltration in the subendocardial region, were present in eight of the sheep. “Atypical” lesions, characterised by hypertrophy of myofibres with multifocal coagulative necrosis or myofibre atrophy, were recorded in two sheep, both of which had short latent periods. The myofibre diameter and nuclear area in the affected animals differed statistically from those of the controls (larger) and anisocytosis and anisonucleosis were particularly striking in sheep with intermediate to long latent periods. The most striking ultrastructural lesions included breakdown of myofibrils, involving in particular what appeared to be thick (myosin) filaments; selective proliferation of organelles such as mitochondria and sarcoplasmic reticulum in areas previously occupied by myofibrils; excessive folding of the myofibre sarcolemma; and advanced myocardial injury characterised by complete loss of myofibrils with loss of intercellular connections and necrosis of myocardial cells. No lesions were present in the rats exposed to a single dose of pavetamine, although they became anorexic and lost weight. Rats exposed to pavetamine twice became anorexic within two to three days after the first exposure and regained weight within a few days (on about day 7). However, they kept on losing weight after the second exposure and continued to do so until termination of the experiment. As a general rule the myocardial lesions were mild in the rats dosed twice with pavetamine. Transmural multifocal myocardial necrosis, with an associated round cell infiltration and replacement fibrosis, was the most striking light- microscopical lesion. The lesions were comparable with “atypical” lesions in ruminants. Ultrastructural lesions in degenerative/necrotic fibres included karyolysis, swelling of the mitochondria and focal lysis of myofilaments. In rats exposed to pavetamine twice there was statistical evidence of myofibre atrophy. Based on the information emanating from this study and previous research the following deductions are made to explain the pathogenesis of the myocardial lesions: 1. Pavetamine has a prolonged effect on the myocardium owing to inhibition of protein synthesis, and also influences the energy production system, which affects the function of myocytes. The structure of the myocytes is not affected during the early stages of the latent period but eventually myofibre hypertrophy, atrophy, degeneration and necrosis are seen. 2. Replacement fibrosis in the subendocardial region is a sequel to the effect of pavetamine on myofibres and the consequence of ischaemia owing to impaired myocardial perfusion of, particularly, the subendocardial region, as a result of decreased myocardial contraction, increased diastolic pressure, tachycardia and myofibre hypertrophy. 3. Cardiac dilatation is a compensatory mechanism, a result of the myofibre damage inflicted by pavetamine and ischaemia (pathological dilatation). 4. Lesions in animals with gousiekte represent a final common pathway of cellular damage rather than a manifestation of a specific type of heart disease. Animals may die during any stage in the development of the lesions. “Atypical” lesions represent a manifestation of the disease in a progression that terminates with dilated cardiomyopathy if the animal does not die during the early stages. These deductions provide an explanation, for the first time, for the latent period between ingestion of the plant and the onset of illness in gousiekte. They also explain the wide range of lesions seen in experimental cases. It furthermore demonstrate that the “typical” lesions of gousiekte are not pathognomonic, and that the absence of “typical” lesions does not rule out a diagnosis of gousiekte in situations where exposure to the causative plants and the clinical history support such a diagnosis. / Thesis (PhD)--University of Pretoria, 2008. / Paraclinical Sciences / unrestricted
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:up/oai:repository.up.ac.za:2263/24366 |
| Date | 21 January 2009 |
| Creators | Prozesky, Leon |
| Contributors | Lawrence, John A., Botha, C.J. (Christoffel Jacobus), leon.prozesky@up.ac.za |
| Publisher | University of Pretoria |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
| Rights | ©University of Pretoria 2008 <D559/ |
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