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Biomedical subjects

J D Hardy

Publications and source records attributed to J D Hardy.

At least 91 records · Page 5Linked to original sources
PubMed1974

Organ specificity in hyperacute rejection of canine heart and kidney allografts.

To clarify the organ specific nature of hyperacute rejection, 14 puppies were presensitized by multiple skin grafts and spleen cell injections prior to receiving either a heart or kidney allograft from the respective donors. Of this group, 7 received orthotopic heart allografts and 7 received kidney allografts. All heart allografts were rejected between 3 and 28 hours, and all kidneys between 0 and 24 hours as judged by cessation of urine flow from the ureterostomies. In contrast, all 11 animals in a recent series of heart allografts in non-sensitized puppies survived the operation, and rejected between 7 and 17 days. There was a significant correlation in both groups between preoperative cytotoxic antibody titer in the recipient serum and graft survival time. The preoperative titers were all above 1:1,024 but were greatly reduced within 2 hours after transplantation. At the time of rejection, antibody could be eluted from the rejected organs. In contrast to the kidneys, in which 2 of 7 grafts ceased to function immediately after revascularization, all hearts resumed beating and functioned well for at least several hours. At autopsy, the myocardium was pale and edematous and histologically polymorphonuclear leukocytes were prevalent in and around the small vessels and among myofibers. Both IgG and IgM antibody was detected in sarcolemma of the myocardium and to a lesser extent in the intima and adventitia of the small vessels by the fluorescent antibody technique. Biopsies of the rejected kidneys showed polymorphonuclear leukocyte infiltration, typical of hyperacute rejection. Marked fluorescence of IgG and IgM in the glomeruli and peritubular capillaries was observed. This study indicates that both organs rejected hyperacutely in our experimental model and participation of the preformed antibody in effecting this change was strongly suggested.

Animals↗
PubMed1974

Fluid replacement monitoring: effect of dextran overload, norepinephrine drip, and positive pressure ventilation on systemic arterial, right atrial pulmonary wedge, and left atrial pressures in dogs.

The effects of dextran overload, norepinephrine drip and positive pressure ventilation upon right atrial, pulmonary wedge, left atrial and systemic arterial pressures were studied in 15 dogs. Rapid intravenous infusion of Dextran 70 invariably produced a marked and statistically significant (p < .001) rise in right atrial, pulmonary wedge and left atrial pressures. The rise in left atrial pressure invariably exceeded the rise in right atrial pressure, and the difference in maximum pressures averaged 10.8 mm Hg (p < .001). Thus acute fluid overload and pulmonary edema can be produced by rapid infusion of colloid solution in the absence of a marked rise in right atrial pressure, a point of considerable clinical importance. The rapid infusion of dextran produced a rise in systemic arterial blood pressure in all dogs so studied, though this rise was mild in some animals. This finding may explain in part the hypertension exhibited by patients in the recovery room who may have been overtransfused. A norepinephrine drip usually produced an increase in right atrial, wedge, left atrial and systemic arterial blood pressure (p < .01). When there was a significant rise in right atrial pressure and left atrial pressure, the maximum increase in left atrial pressure was always greater than the maximum increase in right atrial pressure (p < .005). This finding again emphasizes the fact that blood transfusion requirements cannot always be accurately assessed on the basis of right and left atrial pressure measurements when a vasopressor agent is being administered. Positive pressure ventilation increased both right and left atrial pressures, as expected. It was again confirmed that pulmonary wedge pressure, as measured with the Swan-Ganz catheter, is approximately equal to left atrial pressure over a wide range of induced variations. The Swan-Ganz catheter, introduced at the bedside in the intensive care unit when necessary, can provide highly useful information regarding left atrial pressure and left ventricular end-diastolic pressure.

Animals↗
PubMed1974

Histopathology of one-stage bilateral lung allografts.

Morphological features of modified and unmodified bilateral lung allografts were studied in 87 dogs. Immunosuppressive treatment consisted of various combinations of azathioprine, methotrexate, prednisolone, methylprednisolone and antilymphocyte serum. The classic acute rejection was observed in the unmodified dogs, which died between 4 and 9 days. Progression of the lesion was confined to a certain stage in these lung allografts charged with providing total pulmonary function, so that hemorrhagic necrosis was never encountered. Immunosuppressive drugs decrease the speed and intensity of classic rejection, and increase the complications of respiratory infection in the protracted course. Of 14 dogs surviving more than 14 days, 4 died of chronic rejection at 72, 84, 177, and 396 days after transplantation. Death of the remaining animals was attributed to acute rejection (3 dogs); severe anemia (3 dogs); pulmonary infection and sepsis (3 dogs); and arterial thromboembolism (1 dog). In these long-functioning lung allografts, the alveolar lining cells were frequently replaced by very atypical cells presumed to be type 2 pneumocytes. The bronchus was occluded by mucus plugs, and the alveolar surface was covered with hyaline membrane, or obliterated by organized fibrocellular precipitate. The alveolar walls and perivascular area were thickened by fibrosis. Obliterative intimal thickening of pulmonary arteries was not observed. Although the immunologic and non-immunologic mechanisms responsible for the development of these lesions are difficult to separate, these cumulative changes apparently accompany the deterioration of the vital function of the graft until ultimate death.

Animals↗
PubMed1974

The effect of spinal and skin temperatures on the firing rate and thermosensitivity of preoptic neurones.

1. In anaesthetized rabbits, preoptic single unit activity was recorded while preoptic, spinal cord and skin temperatures were independently manipulated.2. The units that were insensitive to preoptic temperature were characterized by low firing rates and also by a very low incidence of extrahypothalamic thermosensitivity.3. Thirty-seven units having positive coefficients to preoptic temperature were tested for their response to spinal or skin temperature. Of these, twenty-two units responded to extrahypothalamic temperature, seventeen with positive thermal coefficients. In addition, the incidence of extrahypothalamic thermosensitivity generally increased among the higher firing units.4. Twenty-two units had negative coefficients for preoptic temperature and were tested for their extrahypothalamic thermosensitivities. Of these, sixteen units had dual thermosensitivities, ten with negative coefficients for the extrahypothalamic temperatures. In addition, there was no correlation between the incidence of extrahypothalamic thermosensitivity and the level of firing rate.5. In the units having positive coefficients for preoptic temperature, an increased firing rate, due to extrahypothalamic temperature, generally resulted in a decreased preoptic thermosensitivity. Conversely, a decreased firing rate usually resulted in an increased preoptic thermosensitivity.6. In the units having negative coefficients for preoptic temperature, an increased firing rate, due to extrahypothalamic temperature, usually increased the preoptic thermosensitivity; while a decreased firing rate tended to decrease the sensitivity to preoptic temperature.

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