Hepatic metabolism during porcine malignant hyperthermia (MH) was investigated in seven Pietrain pigs. The estimated hepatic blood flow decreased during MH, but an increase in oxygen extraction enabled the splanchnic oxygen uptake to be maintained. There was a large release of glucose and potassium from the liver in MH which made an important contribution to the hyperglycaemia and hyperkalaemia. Measurement of hepatic uptake of the precursors of gluconeogenesis, lactate, glycerol and alanine, showed that glucose efflux from liver was derived mainly from glycogenolysis. Lactate uptake by the liver increased during MH, and there was no evidence of hepatic lactate production during the profound acidosis as suggested by in vitro studies with the isolated liver. There was no evidence of major abnormality of hepatic function during porcine MH.
Porcine malignant hyperthermia was studied in seven Pietrain pigs under standardized experimental conditions. In five animals malignant hyperthermia was triggered with suxamethonium and halothane, but in two pigs suxamethonium alone was used. Characteristic metabolic and physiological changes were found and these are discussed with regard to a possible mechanism to explain the malignant nature of the syndrome.
The pharmacokinetics and tissue penetration of five quinolones were studied in volunteers. The compounds were norfloxacin (400 mg po), enoxacin (400 mg iv and 600 mg po), ciprofloxacin (100 mg iv and 500 mg po), ofloxacin (600 mg po) and pefloxacin (400 mg iv). Of the oral agents studied ofloxacin and ciprofloxacin were the most rapidly absorbed (Tmax = 1.2 h) and enoxacin the least (Tmax = 1.9 h). The serum levels attained were highest in the case of ofloxacin (after allowing for the higher dose administered). The serum half-lives were norfloxacin 3.75 h, ciprofloxacin 3.9 h (po), 4.0 h (iv), ofloxacin 7.0 h, enoxacin 6.2 h (po), 5.1 h (iv) and pefloxacin 10.5 h. All agents penetrated blister fluid readily. The 24 h urine recovery was 62% for oral enoxacin, 46.4% for iv enoxacin (plus 12.2% for oxo-enoxacin), 27% for norfloxacin, 30.6% for oral ciprofloxacin, 75.7% for iv ciprofloxacin, 73% for ofloxacin and 4.9% for pefloxacin (plus 9.2% for the norfloxacin metabolite and 17.8% for pefloxacin N-oxide).
I .Two experiments were done with Pietrain and Large White pigs (about 50 kg bodyweight) to determine whether fat mobilization is enhanced in the stress-sensitive Pietrains (which also produce pale, soft, exudative (PSE) meat).2. In Expt I , plasma glucose and insulin concentrations and free fatty acid (FFA) concentrations and composition weremeasured in five Pietrains and five Large Whites after feeding, during an infusion of norepinephrine (2.5 yg/kg body-weight per rnin), 16 and 21 h after the withdrawal of food and following insulin administration (0.3 IU/kg body-weight). The entry rate of oleic acid was measured 4 h after feeding. Body composition and longissimus dorsi pH measurements were made on killing the pigs 4 d after the experiment.3. After feeding, the Pietrains tended to have lower concentrations of glucose and insulin in plasma compared with the Large Whites, and higher concentrations of FFA. The Pietrains also had a faster entry rate of oleic acid into body tissues. In fasting (16 h) these differences in hormone and metabolite concentrations were also present and relationships between them and body development could be detected. Pietrains had higher concentrations of FFA and lower concentrations of insulin than Large Whites at a particular stage of the development of fat and muscle (subcutaneous fat weight i longissimus muscle weight).4. The fatty acid composition of FFA resembled that of the backfat triglycerides in fasting and during norepinephrine infusion but not in the fed state. In particular the proportion of fatty acid 18 : I was low in the fed pigs and that of 18 : 2 was high. The contrast in FFA composition between the fed and stimulated state was greater in the Large Whites.5 . The Pietrains were less sensitive to the antilipolytic action of insulin. Glucose and FFA concentrations were similar in both breeds during the norepinephrine infusion although insulin concentrations were increased to a larger extent in the Large Whites at the termination of the infusion. .In Expt 2, anaesthetized Pietrain and Large White pigs were given constant infusions of norepinephrine alone (2.5 ,ug/kg body-weight per min) and norepinephrine 4-propranolol (2, 10 and 20 ,ug/kg body-weight per min) or phentolamine (2 and 10 yg/kg body-weight per min). The aim was to determine whether the breeds differed in their sensitivity to norepinephrine when conscious responses to the hormone were prevented.
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