James D. Hardy

Intestinal transplantation: Laboratory experience and report of a clinical case

Abstract The experimental intestinal transplantation in our laboratory and elsewhere is briefly reviewed. Replantation of the entire jejunoileum is compatible with long-term survival of experimental animals. Lymphatic pathways severed during the procedure fully regenerated within a few weeks. Contrary to the implication of earlier studies on this subject, it is now believed that intestinal allografts are rejected in the same manner as other organs, and the rejection response is definitely mitigated by immunosuppressive drugs. There is no conclusive evidence of a graft versus host reaction despite the fact that transplantation of the entire jejunoileum represents a large antigenic mass and transplantation of many mesenteric lymph nodes. The time necessary for regeneration of lymphatic pathways after allotransplantation is different from that after replantation. In an eight year old boy with surgical removal of the entire jejunum and ileum, repeated problems with infection at catheter sites precluded intravenous feeding after four months. A 3 foot length of terminal ileum from his mother (a class B match) was transplanted, both ostia being opened as mucous fistulas to the abdominal wall. On the seventh day the recipient was explored because of the necrotic appearance of the stomas and a perforated duodenal ulcer. The allograft was precariously perfused and of questionable viability. It was removed to forestall possible further intraabdominal complications. Microscopic examination revealed extensive ischemic necrosis. The large vessels were open but the small vessels contained little blood. It was the opinion of the pathologist that the alterations found represented acute rejection, but we believe that limited arterial perfusion may have contributed substantially to the atrophic changes observed.

Technical options in venous valve reconstruction

PURPOSE Several modifications and details of techniques that were found useful in venous valve reconstruction are described. Related technical outcome data are also presented. METHODS Five hundred eighty-two valve segments were reconstructed in 347 limbs using a variety of different techniques. RESULTS Intraoperative valve competence was achieved in 86% of 347 limbs. The incidence of technical stenosis was 4%, thrombosis of repair <1%, loss due to hematoma/infection <1%, and operative mortality 0%. Postoperative duplex competence was achieved fully in 78% and partially in 16%; 6% remained refluxive. Rapid postoperative healing of stasis ulcer occurred in 93%. CONCLUSIONS The expanded variety of technical options in valve reconstruction allows optimization for the individual patient. Regardless of pathology, a functional venous valve can be reconstructed in most patients utilizing one of the described techniques.

The first heart transplant in man

Abstract 1. 1. The first clinical heart transplantation was performed in the Hospital of the University of Mississippi on January 23, 1964. 2. 2. This clinical transplantation was preceded by extensive studies in animals and the clinical operation fully supported the value of the technics previously employed in the laboratory. 3. 3. The recipient was a 68 year old white man in preterminal shock from extremely severe atherosclerotic coronary artery disease. A chimpanzee heart was used when the prospective human donor remained alive supported by a respirator. The immunologic and clinical basis for use of the heart xenograft was the success others had achieved with kidney xenografts, one of which was still functioning well when that patient died nine months later from other causes. The cardiac output of the primate donor was 4.25 L./min., and the preshock output of the heart recipient was 3.6 L./min. 4. 4. During transplantation the donor heart was well preserved by retrograde coronary sinus perfusion and it was easily defibrillated. The strong quality of the myocardial contractions was recorded by motion pictures and the transplant functioned for almost two hours after defibrillation. The advanced state of preoperative metabolic deterioration of the recipient and the size of the donor organ both contributed to the ultimate decompensation of the transplanted heart. 5. 5. This first clinical experience clearly established the scientific feasibility of heart transplantation in man.

Replantation of the liver in dogs

Abstract 1. 1. The liver was replanted in 60 dogs: 37 survived longer than three days, 15 longer than one month. Three still survive at approximately 18 months, and one of these has delivered a litter of 12 puppies. The objective was to examine the effects of orthotopic autotransplantation as a prelude to the investigation of the immunological factors involved in orthotopic homotransplantation. 2. 2. Certain useful modifications of previously described liver transplantation techniques have been noted. The excised liver was perfused with cold solution without delay, but total body hypothermia was avoided. During replacement of the liver, the portal and caval blood was returned to the heart by means of a single external bypass from the caudal end of the divided portal vein to the external jugular vein, after the portal vein and infrahepatic vena cava had been temporarily joined by an autogenous vein graft. The arterial supply was restored by end-to-end anastomosis of the common hepatic artery. The incidence of vascular thrombosis was strikingly low. Anesthesia was achieved with repeated small intravenous doses of thiamylal sodium. 3. 3. Serum bilirubin levels remained normal in most animals. The blood glucose level frequently declined during the first postoperative day but then usually remained normal. The serum glutamic-oxalacetic transaminase level rose immediately in most animals but usually declined to normal after two weeks in chronic survivors. The serum alkaline phosphatase level rose within 48 hours following operation and usually declined in a few days, but in some instances it remained elevated for several months. 4. 4. The development of hepatic venous outflow block, abnormal bleeding, or subsequent ascites was rarely encountered when the organ had been well preserved with cold solution and trauma avoided by gentle handling. In contrast, when cold preservation was inferior or traumatic manipulation did occur, not only these complications but subsequent liver abscesses due to focal necrosis were observed. 5. 5. It is suggested that the results reported provide a description of the course of longterm survivors of canine liver replantation which was formerly lacking.

HEART TRANSPLANTATION IN INFANT CALVES: EVALUATION OF CORONARY PERFUSION TO PRESERVE ORGAN DURING TRANSFER*

The problems involved in successful transplantation of the heart have challenged many The study of heart, heart-lung, and lung transplants was begun in our laboratory in 1956 and more than 200 transplants of various types have been e v a l ~ a t e d . ~ ’ ~ The early series of heart transplants were performed in dogs, using profound hypothermia to preserve the organ during transfer. Initially, the veins were anastomosed individually, but in the later series the transatrial suture technique, described by Lower, Stofer, and Shumway,4 was employed. Much was learned from these early homotransplants, and survival well into the postoperative period was not infrequently obtained. Nevertheless, it gradually became apparent that profound hypothermia might not be the optimal method for heart preservation during transfer, for resuscitation of the transplanted heart was frequently disappointing as compared with the almost routine resuscitation of the temporarily arrested heart in patients undergoing operations upon the aortic valve. However, in a series of 65 dogs undergoing operations on the aortic valve in 1961, Hardy, Rodriguez, and AlicanI3 had previously found coronary perfusion in dogs to be somewhat undependable, due to the small size and anatomic variations of these vessels in such animals.

Arterio-enteric fistula following pelvic radiation: A case report

Abstract Two cases of arterial perforation into the small bowel are reported. Etiology was not determined in one case, but surgical trauma leading to localized infection in the irradiated tissue seemed responsible in the other. After the initial episode of hemorrhage, there was a symptom-free interval before its reappearance and vascular collapse. This is believed to be due to the distensibility of the large bowel. The site of arterial perforation was determined pre-operatively in one case by selective arteriography. Review of the recent literature relevant to transcatheter arterial embolization suggests that it may have potential in management of the arterio-enteric fistula as an alternative to or an aid in surgical correction by stabilizing the patient in a favorable condition.

Lung replantation--respiratory reflexes, vagal integrity, and lung function in chronic dogs.

Summary In order to assess the importance of nerve regeneration to the maintenance of adequate respiration by the replanted lung, bronchospirometric and blood gas analyses were made in 7 dogs 6 to 18 months after replantation of the left lung. Contralateral pneumonectomy was performed in 5 of these animals. Histologic regeneration of anatomically normal nerve fibers was demonstrated 6 to 18 months after replantation. However, these nerve fibers were functionally inadequate as evidenced by the absence of the Hering-Breuer reflex in all replanted lungs and of the cough reflex in the 2 dogs so tested. Respiratory rate and oxygen consumption were found to be dependent on the chemoreflexes initiated by the altered pO 2 and pCO 2 of the circulating blood. The replanted lungs exhibited substantial functional capacity but were unable to maintain normal oxygen exchange 6 to 18 months after surgery.

Relief of Abdominal Angina by Vascular Graft

Excerpt Abdominal angina represents the reaction of the intestinal tract to chronic vascular insufficiency. Chronic mesenteric arterial narrowing or occlusion manifests itself much as angina pector...

Prolonged suspended animation in puppies

Abstract Three groups of a total of 26 puppies were subjected to surface-induced hypothermia with or without limited left-heart bypass to seek recovery after 2.5-hr total circulatory arrest. In spite of various protective measures, surface-induced hypothermia which was carried out until the effective circulation ceased, failed to protect the animal from 2.5-hr circulatory arrest. With a combination of limited leftheart bypass, the central nervous tissue tolerated the procedure better than expected. Metabolic derangements, although severe immediately after the procedure, were reversible. Respiratory distress was a serious problem, which was considerably alleviated in the 3rd group of 10 puppies by perfusion of the lung with a solution approximating the intracellular electrolyte composition. Six puppies of this group survived the procedure, 5 without any persistent disorders. These results indicate the possibility of 2.5-hr hypothermie circulatory arrest.

Chronic stimulation of the gastric parietal cell mass

Summary 1. The effect of histamine, hydrocortisone and growth hormone on gastric parietal cells was investigated in rats by a continuous stimulation with these drugs. 2. Histamine was found to be effective in the production of mucosal hyperplasia and in increasing the parietal cell population. This increase was statistically significant at four sites at which the parietal cells were counted. None of these animals developed gastric ulceration during treatment. 3. Hydrocortisone was not effective in increasing the parietal cell mass. On the contrary there was a slight but not statistically significant decrease in the number of parietal cells associated with bleeding gastric ulcers in six of seven animals. This effect of hydrocortisone could be caused by increased pepsin secretion, by decreased mucus production or by increased susceptibility of the mucosa to acidpepsin digestion. 4. Growth hormone had no measurable effect on parietal cells. 5. It has been demonstrated that chronic stimulation with histamine can lead to an increase in the parietal cell mass in rats. However, the question whether the increased parietal cell mass observed in patients with the Zollinger-Ellison syndrome is caused by chronic gastrin stimulation or is genetically determined cannot be answered at this time.