Small bowel transplantation in the dog using cyclosporine.

The effect of the new immunosuppressant cyclosporine on survival after total small intestinal allotransplantation (TSIA) was studied in a canine model. Successful TSIA was performed in 34 dogs. Eleven dogs were treated with cyclosporine, 25 mg/kg/day i.m., starting the day before the operation and continuing for four weeks. Thereafter the same dose was given orally. Thirteen dogs were given oral cyclosporine only, 25 mg/kg/day from the day after transplantation. Ten dogs served as controls. The dogs treated with intramuscular and oral cyclosporine survived a mean of 103.8 +/- 39.4 days (mean +/- S.E.M.). The longest survivor died after 432 days. Survival in this group was significantly longer than that of the control dogs, which survived 12.5 +/- 4.6 days. The orally treated dogs survived 30.4 +/- 7.6 days. All control dogs, and seven of the orally treated dogs, but only two of the intramuscularly treated dogs, died of acute rejection. It is concluded that cyclosporine is effective in prolonging survival after TSIA in the dog and reduces the incidence of acute rejection.

Structure and function of small bowel allografts in the dog: immunosuppression with cyclosporin A.

Pairs of mongrel dogs received orthotopic total small bowel allografts. Half were treated with the immunosuppressive agent cyclosporin A and the other half were not. Ten untreated dogs survived a mean of 12.5 days (range from 7 to 25 days). They lost up to 30% of their initial body weight and rejection with hemorrhagic necrosis was usually the cause of graft failure. The mean survival of 11 dogs treated with cyclosporin A was 90.6 days (range 9 to 286 days) with early deaths being due to pneumonia or volvulus. Intestinal mucosa appeared normal, but there was some smooth muscle hypertrophy. Reconnection of lymph vessels was complete in all dogs examined more than 21 days after allografting. Two dogs survived for 203 and 221 days, respectively, and one dog remains alive and well 287 days after operation. The long-term survivors remained healthy, with steady body weights, formed stools, normal plasma protein values and xylose absorption curves that did not differ from those of autografted dogs. Roentgenography after a barium meal and follow-through study showed normal mucosa. The transit time was around 60 minutes (normal 150 minutes). Late, acute episodes of rejection occurred in two dogs, when blood levels of cyclosporin A were low (less than 400 ng/ml). Bowel mucosa showed ulceration and villous atrophy, with lymphoid infiltration, leading to malabsorption as a terminal event. Cyclosporin A is effective in increasing the duration of survival in dogs with small bowel allografts while maintaining essentially normal bowel structure and good function.

Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers.

34 patients treated with cyclosporin A received 36 cadaveric organ allografts (32 kidneys, 2 pancreases, and 2 livers), 26 kidneys are still supporting life, 3 after more than a year; the pancreases and livers are also functioning. 20 patients are not receiving steroids, and 15 of these have not had any additional immunosuppressive agents. In these patients infectious complications have not been severe, but a gastroduodenal lymphoma has developed in 1 patient. 6 patients were given 'Cytimum' (a cyclophosphamide derivative) and steroids in addition to cyclosporin A: 5 of these died of infections and 1 also had a lymphoma. 11 patients received additional steroids: 1 of these died from septicaemia and lymphoma. Nephrotoxicity can be avoided by perioperative hydration and forced diuresis. Cyclosporin A is effective on its own and is a very potent immunosuppressive drug. Additional immunosuppressive agents may lead to severe complications.

Use of partial cardiopulmonary bypass during the anhepatic phase of orthotopic liver grafting.

Femoro-femoral partial cardiopulmonary bypass has been used in two patients under going orthotopic liver allografting who had severe cardiovascular disturbances on trial clamping of their venae cavae. Flows of 2-3 litres/min resulted in satisfactory cardiovascular control during the anhepatic phase in each ase. A third patient who tolerated caval clamping withstood the grafting without bypass. Having bypass available for use in critical cases could increase the safety of orthotopic liver transplantation.

Cyclosporin A in patients receiving renal allografts from cadaver donors.

Seven patients on dialysis with renal failure received transplants from mismatched cadaver donors and were treated with cyclosporin A (CyA), initially as the sole immunosuppressive agent. CyA was effective in inhibiting rejection but there was clear evidence of both nephrotoxicity and hepatotoxicity. A cyclophosphamide analogue was added to the CyA treatment in six of the patients. Five patients are out of hospital with functioning allografts, and two of these have received no steroids. One patient required an allograft nephrectomy because of pyelonephritis in the graft. Another died of systemic aspergillus and candida infection. Further careful study of this potentially valuable drug will by required before it can be recommended in clinical practice.

Effect of renal ischaemia in rats with obstructive jaundice.

The ability of kidneys to withstand renal ischaemia has been tested in jaundiced and non-jaundiced rats. No significant difference could be demonstrated between the two groups of animals except that renal weight increased greatly in the presence of jaundice. Both jaundiced and non-jaundiced animals showed a median lethal dose of renal ischaemia of approximately 120 min when renal function was tested by delayed opposite nephrectomy. It was shown that a recent laparotomy renders the kidney more susceptible to renal ischaemia.

Species differences in response to renal ischemia.

Different species appear to tolerate different amounts of renal ischemia. It is suggested that all kidneys are equally susceptible to ischemic damage, but that the whole animal response varies between species. Mice, rats, rabbits, and pigs were subjected to bilateral nephrectomy. Large animals had relatively smaller kidneys and survived longer than smaller animals. Therefore, the larger the animal, the more time available for recovery of a kidney damaged by ischemia. This adequately explains the apparent species differences in susceptibility to renal ischemia, which are only seen when the kidney is expected to support life immediately. Simple relationships are described, relating metabolic rate, body size, and survival time with no renal function.