The Journal of clinical investigation
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Chronic renal failure in rats leads to changes in hepatic protein synthesis and albumin metabolism at both the cellular and molecular level. In rats with chronic uremia (blood urea nitrogen greater than 45 mg/100 ml 1 mo after surgical reduction in renal mass), cell-free protein synthesis is reduced 30--40% in liver membrane-bound polyribosomes. Albumin synthesis by membrane-bound polysomes in uremia is reduced even more than the reduction in total protein synthesis. ⋯ There is also intracellular accumulation of albumin in liver of uremic rats and a concomitant decrease in serum albumin. In normal liver, most intracellular albumin is located in the microsomal fraction, whereas in liver from uremic animals the excess albumin is found in the free cytosol fraction. These results can be explained either by a defect in synthesis of albumin by membrane-bound polysomes with release of newly synthesized albumin into the cytosol or by a reduced ability of polysomes synthesizing albumin to associate with the membrane fraction in rats with chronic renal failure.
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The respiratory responses to hypercapnia alone and to hypercapnia and flow-resistive loading during inspiration were studied in normal individuals and in eucapnic and hypercapnic patients with chronic airways obstruction. Responses were assessed in terms of minute ventilation and occlusion pressure (mouth pressure during airway occlusion 100 ms after the onset of inspiration). Ventilatory responses to CO2 (deltaV/deltaPCO2) were distinctly subnormal in both groups of patients with airways obstruction. ⋯ Flow-resistive loading during inspiration reduced deltaV/deltaPCO2 both in normal subjects and in patients with airways obstruction. The occlusion pressure response to CO2 increased in normal subjects during flow-resistive loading but remained unchanged in both groups of patients with chronic airways obstruction. These results indicate that while chemosensitivity as determined by deltaP100/deltaPCO2 is impaired only in hypercapnic patients with chronic airways obstruction, an acute increase in flow resistance elicits a subnormal increase in respiratory efferent activity in both eucapnic and hypercapnic patients.
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The aims were to examine the gas exchange and arterial blood gas abnormalities among patients with scoliosis, and the correlation of these abnormalities with age and severity of deformity. Means among 51 patients were as follows: age 25.4 +/- 17.5 yr, angle of scoliosis 80.2 +/- 29.9 (SD), vital capacity 1.94 +/- 0.91 (SD) (i.e. 60.6 +/- 19.2% of predicted), PaO2 85.8 +/- 12.0 (SD), PaCO2 42.4 +/- 8.0, physiological dead space to tidal volume ratio 0.438 +/- 0.074 (SD), and alveolar-arterial oxygen difference breathing air 14.9 +/- 8.9 (SD). Statistically significant correlations were as follows: the PaCO2 and physiological dead space to tidal volume ratio increased with age, and the PaO2 and alveolar ventilation decreased with age. ⋯ PaCO2 was directly related to the elastance of the respiratory system. We conclude that ventilation-blood flow maldistribution as a result of deformity of the rib cage was the primary abnormality in gas exchange, and that with age there was progressive deterioration in gas exchange. The age-dependent increase in PaCO2 and decrease in alveolar ventilation were due to the increasing physiological dead space to tidal volume ratio and failure of a compensatory increase in ventilation.
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To see whether antihistamines could prevent and reverse histamine-induced pulmonary edema and increased lung vascular permeability, we compared the effects of a 4-h intravenous infusion of 4 mug/kg per min histamine phosphate on pulmonary hemodynamics, lung lymph flow, lymph and plasma protein content, arterial blood gases, hematocrit, and lung water with the effects of an identical histamine infusion given during an infusion of diphenhydramine or metiamide on the same variables in unanesthetized sheep. Histamine caused lymph flow to increase from 6.0+/-0.5 to 27.0+/-5.5 (SEM) ml/h (P less than 0.05), lymph; plasma globulin concentration ratio to increase from 0.62+/-0.01 to 0.67+/-0.02 (P less than 0.05), left atrial pressure to fall from 1+/-1 to -3+/-1 cm H2O (P less than 0.05), and lung lymph clearance of eight protein fractions ranging from 36 to 96 A molecular radius to increase significantly. ⋯ Metiamide (10 mg/kg per h) did not affect the histamine lymph response. We conclude that diphenhydramine can prevent histamine-induced pulmonary edema and can prevent and reverse increased lung vascular permeability caused by histamine, and that histamine effects on lung vascular permeability are H1 actions.
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The role of the renin-angiotensin-aldosterone system in the development of congestive failure has been assessed in the conscious dog by use of the nonapeptide converting enzyme inhibitor. Constriction of the pulmonary artery or thoracic inferior vena cava was maintained for 2 wk while daily measurements were made of plasma renin activity, plasma aldosterone, plasma volume, hematocrit, serum sodium and potassium concentrations, sodium and water balance, body weight, and arterial, caval, and atrial pressures. The initial response to constriction was a reduction in blood pressure, a rise in plasma renin activity, plasma aldosterone, and water intake, and nearly complete sodium retention. ⋯ Chronic infusion of the inhibitor in dogs with thoracic inferior vena caval constriction prevented the restoration of blood pressure and suppressed the rise in plasma aldosterone; sodium retention and volume expansion were less than in control experiments. Thus the renin-angiotensin-aldosterone system plays an essential role in the maintenance of blood pressure during the genesis of congestive failure. Initially, the restoration of blood pressure is dependent upon circulating angiotensin II; in the later stages, blood pressure is dependent upon the increase in plasma volume.