Fourteen castrated male sheep of two breeds, the Mutton Merino (MMB) and Blackhead Suffolk cross breed (BSC), were exposed to an oral copper (Cu) intake of 3.7 mg/day per kg body weight for 84 days (high Cu group, HCu), and 11 castrated male sheep received a daily oral Cu intake of 0.16 mg/day per kg body weight (controls). Liver Cu concentration was measured in liver biopsies until 2.7 years after Cu overdose. Haematologic parameters, plasma Cu, enzymes and metabolites were analysed and post-mortem examinations were carried out. No haemolytic crises occurred. The highest liver Cu concentrations (133-677 mg/kg wet weight) were measured in HCu sheep around day 110 with significantly higher values in BSC than in MMB. The very slow decreases of liver Cu concentration of HCu sheep after day 215 showed individual half-life periods of 175 +/- 91 days. A progressive Cu retention in the liver of HCu sheep during Cu supplementation indicates strong Cu binding and storage in the liver. High values of glutamate dehydrogenase (20-940 U/l) measured frequently until day 700 and a diminished plasma clearance of bromosulphthalein as well as pathohistological findings of focal liver necrosis confirm the markedly chronic character of Cu poisoning.

Klinik fur kleine kkuentim, Ambulatorische Klinik undjrensiscbe Medien, lieraqtkcbe Hocbscbuk Hannover, Biscbofsholer Damm 15, 0 -3 0 173 Hannover, Gnnan_ySummary 214 ewes suffering from pregnancy toxaemia (ketosis) were examined. Clinical signs during onset and course of disease and laboratory findings were compared between animals that survived and those which died. In the latter the onset of ketosis was earlier in pregnancy (day 143 f 7 vs. day 146 f 8) and duration of the disease was shorter (10 f 13 vs. 14 f 9 days). The animals that died showed more severe clinical signs and higher values of 3-hydroxy-butyrate (4.3 f 3.6 vs. 3.5 f 2.6mmol/l) and cortisol (72 f 98 vs. 52 f 80 nmol/l) as well as lower values of insulin (37 f 12 vs. 66 f 42 pmol/l) and potassium (4.1 f 1.0 vs. 4.4 1.0 mmol/l) at onset of the disease than those which survived (aU of differences with P < 0.05). Glucose levels did not differ between groups.Treated animals with glucose plus fructose infusions (n = 56) or with oral application of glucose precursors plus electrolytes (n = 126) had survival rates of 53.6 Yo and 62.7 Yo, respectively. Oral treatment with glucose precursors plus electrolytes and an additional subcutaneous insulin treatment (n = 15) led to an enhanced survival rate of 86.7 YO (P < 0.05).Low insulin levels in ketotic pregnant sheep and the therapeutic effect of insuhn treatment support the hypothesis that insulin plays a causative role in the pathogenesis of ovine ketosis.

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In pigs, the serotonin-2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), 0.8 mg/kg, induced "psychotic" behaviour (e.g., grimacing, backward locomotion, blank stare) and a muscular syndrome, which is known as malignant hyperthermia (MH) in pigs and humans. This syndrome is characterized by generalized skeletal muscle rigidity, leading to an increase in body temperature, marked acidosis, hyperkaliaemia, cyanosis and elevation of lactate, carbon dioxide and the muscle enzyme creatine kinase (CK) in plasma. In pigs which were selectively bred for susceptibility to MH induction by known triggering agents, such as halothane, the administration of DOI was fatal in 3 out of 5 animals. In genetically susceptible pigs, MH was also induced by 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), 0.5-1.8 mg/kg, and D-lysergic acid diethylamide (LSD), 60-110 micrograms/kg. Furthermore, 5-MeO-DMT and LSD induced head shakes in the animals, which had not been observed after DOI and could not be blocked by 5-HT2-antagonists, ketanserin (0.5-5 mg/kg) and ritanserin (1-2.5 mg/kg). The psychotomimetic effects of 5-MeO-DMT could be blocked by ketanserin or ritanserin, which, depending on the dose, also reduced or totally prevented the hyperthermia and metabolic changes induced by 5-MeO-DMT in pigs. Administration of 5-MeO-DMT, 1.8 mg/kg, was fatal in 4 of 5 MH-susceptible pigs, whereas pigs injected with this dosage after pretreatment with ketanserin (0.5-5 mg/kg) or ritanserin (1-2.5 mg/kg) did not die. In pigs from MH-resistant littermates, administration of 5-MeO-DMT was not fatal. Comparison of metabolic changes in susceptible and non-susceptible pigs suggested that the marked increase in plasma potassium, which arises principally from damaged muscle cells, is primarily responsible for the fatal effect of DOI and 5-MeO-DMT in genetically susceptible individuals. In MH-susceptible pigs, which were anesthetized, relaxed and artificially ventilated, 5-MeO-DMT did not induce hyperthermia, thus substantiating that the marked hyperthermia observed in conscious pigs was a result of muscle activation and not due to effects on thermoregulation or blood pressure. The results indicate that hallucinogenic drugs with 5-HT2 agonistic effects trigger a life-threatening syndrome, MH, in genetically susceptible pigs. 5-HT2 antagonists, such as ketanserin or ritanserin, are capable of counteracting the fatality of this syndrome.

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