A baboon model to test physiological and adverse effects of human red cells loaded with inositol hexaphosphate (IHP).
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Biomedical subjects
Publications and source records attributed to P Prato.
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We have explored adverse pulmonary effects of mechanical ventilation at a peak inspiratory pressure of 30 cmH2O in paralyzed and anesthetized healthy sheep. A control group of eight sheep (group A) was mechanically ventilated with 40% oxygen at a tidal volume of 10 ml/kg, a frequency of 15 breaths/min, a peak inspiratory pressure less than 18 cmH2O, and a positive end-expiratory pressure of 3-5 cmH2O. During the ensuing 48 h, there were no measurable deleterious changes in lung function or arterial blood gases. Another 19 sheep were ventilated with 40% oxygen at a peak inspiratory pressure of 30 cmH2O under a different set of conditions and were randomly assigned to two groups. In group B, the respiratory rate was kept near 4 breaths/min to keep arterial PCO2 in the normal range; in group C, the frequency was kept near 15 breaths/min by including a variable dead space in the ventilator circuit to keep arterial PCO2 near baseline values. There was a progressive deterioration in total static lung compliance, functional residual capacity, and arterial blood gases. After some hours, there were abnormal chest roentgenographic changes. At time of death we found severe pulmonary atelectasis, increased wet lung weight, and an increase in the minimum surface tension of saline lung lavage fluid.
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Plasma amino acids profile is assumed to be a good index of whole body amino acids balance and in particular to give information on the actual control of the transplanted liver on protein metabolism. Variations in plasma amino acids profile were studied in 12 patients undergoing orthotopic liver transplantation. Total parenteral nutrition (TPN) was maintained at 26.05 +/- 1.53 kcal/kg and 0.117 +/- 0.01 gN/kg until the 7th postoperative day. Following this, an enteral nutrition (EN) was added as to maintain a mixed metabolic therapy at 30.28 +/- 2.76 kcal/kg and 0.198 +/- 0.01 gN/kg. Such a treatment completely satisfied the caloric needs, while nitrogen input was prudently kept low in accordance to the lack of data on the metabolic effectiveness of the transplanted liver. Amino acids profiles showed an early metabolic recovery of the new liver. Therefore nitrogen input could be higher and more adequate to nitrogen needs.
Variations in plasma levels of total carnitine (TC), free carnitine (FC), and acyl-carnitine (AC) were studied in 10 patients undergoing orthotopic liver transplantation. The postoperative values were higher than the preoperative ones and positively related to time flow. As exogenous carnitine was not supplied during the study, these data suggested a better biosynthetic activity in the transplanted liver, in spite of standard blood tests results. No positive correlation between carnitine levels and variations in serum transaminases, bilirubin, cholestasis related enzymes, pre-albumin and albumin supply was found. Carnitine plasma levels were not influenced either by nutritional caloric input or by methionine and lysine inputs. Our results show that variations in carnitine plasma levels are a specific and responsive index of functional recovery in the transplanted liver.
Using an animal model of acute respiratory failure (ARF), we evaluated two treatments: conventional mechanical pulmonary ventilation (MV) and continuous positive airway pressure (CPAP) with extracorporeal removal of CO2 by an artificial membrane lung. We developed a model of "mild" ARF and a model of "severe" ARF after ventilating healthy sheep at a peak inspiratory pressure of 50 cm H2O for various lengths of time. Sheep from either injury models were randomly assigned to one of the above treatment groups. All 16 sheep from the model with "severe" ARF died, with progressive deterioration in pulmonary function and multiorgan failure irrespective of the treatment. Of 11 sheep from the model with "mild" ARF treated by MV, only three survived, whereas all 11 sheep from the model with "mild" ARF treated with CPAP and extracorporeal removal of CO2 responded well, and nine sheep ultimately recovered. We conclude that CPAP with extracorporeal removal of CO2 provided a better environment for the recovery in our model with "mild" ARF than the conventional arrangement centered on MV alone. Our studies also suggest that lung injury can progress (i.e., model with "severe" ARF) to where neither of the two treatments can succeed.
We explored the pulmonary effects of continuous mechanical ventilation (MV) at a peak inspiratory pressure of 50 cm H2O in healthy, paralyzed, and anesthetized adult sheep during a period of 48 h. The 9 control sheep (Group A) were ventilated with 40% oxygen at a tidal volume of about 10 ml/kg and a peak inspiratory pressure of 15 to 20 cm H2O. All these animals remained stable throughout the 48 h of MV with no change in lung function. The 7 sheep in Group B were ventilated with 40% oxygen using a pressure-controlled ventilator at 50 cm H2O peak inspiratory pressure, at a VT of 50 to 70 ml/kg. All sheep in Group B developed severe respiratory failure and died or were killed within 2 to 35 h, and showed parenchymal consolidation at autopsy. The 9 sheep in Group C were ventilated as in Group B, except that 3.8% CO2 was added to the inspired gases: the Group C animals deteriorated more slowly, with little change in PaO2 but with a severely reduced FRC, VT, total static lung compliance, and grossly abnormal lungs at autopsy. We conclude that in this model, mechanical ventilation at peak airway pressure of 50 cm H2O will lead to progressive impairment in pulmonary mechanics, lung function, acute respiratory failure, and alveolar cellular dysfunction, as demonstrated by highly abnormal minimal surface tension values of saline lung lavage fluid in both study groups.
To investigate the effects of both positive end-expiratory pressure (PEEP) and mean airway pressure (Paw) on gas exchange, we used lung lavage to induce severe respiratory insufficiency in six lambs. The animals were then mechanically ventilated at constant tidal volume, respiratory rate, and inspired O2 fraction. PEEP levels were varied -5, +5 and +10 cm H2O around the pressure (Pflex) corresponding to a major change in slope of the inspiratory limb of the respiratory volume-pressure curve. In each animal the effects of the three PEEP levels were studied at two Paw levels, differing by 5 cm H2O. Increasing Paw significantly improved PaO2 and reduced venous admixture. A 5-cm H2O PEEP increase from +5 to +10 did not affect oxygenation; however, oxygenation was significantly better when PEEP was greater than Pflex. Both PaCO2 and anatomic dead space were higher at higher PEEP, and decreased with increasing Paw. Hence, Paw was a major determinant of oxygenation, although a PEEP greater than Pflex appeared necessary to optimize oxygenation at a constant Paw.
Changing attitudes to animals in research and practical considerations prompted the authors to evaluate whether the pig might be a suitable substitute for dog and baboons for single left lung transplants. Twenty-nine paired pigs were used. The first transplants on 13 pairs (group 1) were done to adapt the lung transplant technique to pigs; later transplants on 16 pig pairs (group 2) were done to evaluate operative survival, and function and histological modifications of the transplanted lung in the absence of immunosuppressive treatment. Surgical and anesthetic techniques for both donor and recipient are described in detail. The survival rate in group 2 was 68%. Hemodynamic and blood gas changes were assessed during operation. PaO2 did not drop significantly after occluding the right pulmonary artery by an inflatable cuff placed around it; this suggests that the function of the transplanted lung was preserved. The pigs were put down on the third postoperative day. Vascular and bronchial anastomoses were patent and intact, but the transplanted lung was macroscopically and microscopically altered. Lung transplants can be performed in pigs and the transplanted lung seems to be capable of functioning immediately after the operation. Alteration in the lung after 3 days is probably due to rejection.
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