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Effects of labetalol and pindolol on nitrogen balance in severe head injured patients
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COMBINED EFFECTS OF INSULIN AND ANAHOLIC STEROIDS ON BODY COMPOSITION IN RATS P.W. Emery, J.J.Choo. Nutrition Dept., Kings College, London University,U.K. It is known that administrationof insulin can reduce the magnitude of nitrogen loss from severely traumatisedpatients who are being supported with TPN (New Engl. J. Med.300:14).However insulin also promotes the undesirableaccumulation of body fat. We have found that the anabolic steroid Durabolin can improve the ratio of lean to fat tissue in rats of both sexes fed protein- and energyrestricted diets by maintaining protein deposition while supressing fat deposition. We therefore examined the effect of this drug in combination with exogenous insulin on the body compositionof rats. Groups of 6-8 rats weighing 200g (males) and 150g (females)were fed ad libitum on injected a semipurified diet (20% protein). Protamine zinc insulin was subcutaneously in doses increasing from 20-50 units/kg body weight/day for 12 days: this caused substantialincreases in food intake and weight gain in rats of Durabolin (nandrolone both sexes. Additional subcutaneous injections of phenylpropionate, a gift from Organon Ltd., 4 mg/kg/day) in insulin treated male rats caused a marked reduction in body fat content (70.2+7.3sdvs 49.4i6.49, P (0.01) but no change in body protein content (50.721.5vs 50.2+1.6g, P> 0.05). In insulin treated female rats additional subcutaneousinjections of Durabolin (2 mg/kg/day) caused a further 21% (P(O.01) increase in weight gain without affecting food intake: again body fat content was reduced (47.526.3vs 36.2+5.6g, P
P.2
EFFECTS OF LABETALOL #JD PINDOLOL CN NITROGEN BAI#ICE IN SEVERE HEAD INJURED PATIENTS. G. Pittoni, L. Zanardi, M. Agostini, G. Dauia’, A. Boninsegna” and Giron (Institute of Anesthesiology and Intensive Care and “Institute of Biochemistry - University of Padova - Italy)
G.
P.
Cathecolamines play a key role in the catabolic response to head injury, and the long-lasting overactivity of sympathetic nervous system shows d direct relationship with the sustained negative nitrogen balance (NB) that is thypical in these patients. We investigated the influence of two adrenergic neuron blocking agents on NB when administered to severe head-injured patients. Antiadrenergic therapy was started after that all patients reached a standard nutritional regimen of about 40-50 Cal/Kg bw /die and Nitrogen intake of about 0.25-0.30 g/Kg bw /die, given as enteral nutrition, that usually results in a positive NB only after 21 days of treatment, Two groups of five patients admitted to our intensive care unit with a Glasgow Coma Score < 8 at least one week after injury were treated respectively with pindolol 0.8-1.6 mg/die i.v. for 4 weeks and labetalol 50-200 mg/die i.v. for 2 weeks as continous infusion titrated to cardiovascular parameters. Caloric and Nitrogen intake, together with NB were calculated dayly for all patients throughout the study, and the values obtained were compared with the values observed in the same patients 4 days before and 4 days after pindolol or labetalol therapy. Hypercatabolic head-injuried patients treated with labetalol showed a NB improvement to positive values (~(0.01) after 5 days of therapy, reaching sustained positive values of 1-2 g N/die after B days of treatment. A significative return cp(O.01) to negative NB values of about - log N/die followed to the labetalol treatment interruption. In the pindolol group the effect of an early positive NB improvement did not occur and no further variation on NB was registered after the suspension of the treatment. This positive effect on NB obtained with labetalol treatment could be related to the non high-selective noradrenergic blockade of this drug, that seems to antagonize more specifically the metabolic effects of noradrenergic stimuli, resulting in a modulation of nitrogen catabolism.
97
COMBINED EFFECTS OF INSULIN AND ANAHOLIC STEROIDS ON BODY COMPOSITION IN RATS P.W. Emery, J.J.Choo. Nutrition Dept., Kings College, London University,U.K. It is known that administrationof insulin can reduce the magnitude of nitrogen loss from severely traumatisedpatients who are being supported with TPN (New Engl. J. Med.300:14).However insulin also promotes the undesirableaccumulation of body fat. We have found that the anabolic steroid Durabolin can improve the ratio of lean to fat tissue in rats of both sexes fed protein- and energyrestricted diets by maintaining protein deposition while supressing fat deposition. We therefore examined the effect of this drug in combination with exogenous insulin on the body compositionof rats. Groups of 6-8 rats weighing 200g (males) and 150g (females)were fed ad libitum on injected a semipurified diet (20% protein). Protamine zinc insulin was subcutaneously in doses increasing from 20-50 units/kg body weight/day for 12 days: this caused substantialincreases in food intake and weight gain in rats of Durabolin (nandrolone both sexes. Additional subcutaneous injections of phenylpropionate, a gift from Organon Ltd., 4 mg/kg/day) in insulin treated male rats caused a marked reduction in body fat content (70.2+7.3sdvs 49.4i6.49, P (0.01) but no change in body protein content (50.721.5vs 50.2+1.6g, P> 0.05). In insulin treated female rats additional subcutaneousinjections of Durabolin (2 mg/kg/day) caused a further 21% (P(O.01) increase in weight gain without affecting food intake: again body fat content was reduced (47.526.3vs 36.2+5.6g, P
P.2
EFFECTS OF LABETALOL #JD PINDOLOL CN NITROGEN BAI#ICE IN SEVERE HEAD INJURED PATIENTS. G. Pittoni, L. Zanardi, M. Agostini, G. Dauia’, A. Boninsegna” and Giron (Institute of Anesthesiology and Intensive Care and “Institute of Biochemistry - University of Padova - Italy)
G.
P.
Cathecolamines play a key role in the catabolic response to head injury, and the long-lasting overactivity of sympathetic nervous system shows d direct relationship with the sustained negative nitrogen balance (NB) that is thypical in these patients. We investigated the influence of two adrenergic neuron blocking agents on NB when administered to severe head-injured patients. Antiadrenergic therapy was started after that all patients reached a standard nutritional regimen of about 40-50 Cal/Kg bw /die and Nitrogen intake of about 0.25-0.30 g/Kg bw /die, given as enteral nutrition, that usually results in a positive NB only after 21 days of treatment, Two groups of five patients admitted to our intensive care unit with a Glasgow Coma Score < 8 at least one week after injury were treated respectively with pindolol 0.8-1.6 mg/die i.v. for 4 weeks and labetalol 50-200 mg/die i.v. for 2 weeks as continous infusion titrated to cardiovascular parameters. Caloric and Nitrogen intake, together with NB were calculated dayly for all patients throughout the study, and the values obtained were compared with the values observed in the same patients 4 days before and 4 days after pindolol or labetalol therapy. Hypercatabolic head-injuried patients treated with labetalol showed a NB improvement to positive values (~(0.01) after 5 days of therapy, reaching sustained positive values of 1-2 g N/die after B days of treatment. A significative return cp(O.01) to negative NB values of about - log N/die followed to the labetalol treatment interruption. In the pindolol group the effect of an early positive NB improvement did not occur and no further variation on NB was registered after the suspension of the treatment. This positive effect on NB obtained with labetalol treatment could be related to the non high-selective noradrenergic blockade of this drug, that seems to antagonize more specifically the metabolic effects of noradrenergic stimuli, resulting in a modulation of nitrogen catabolism.
97