Leonard S. Schultz

Problems in absorption and immunosuppression after entire intestinal allotransplantation

Abstract Orthotopic entire small intestine allografts were transplanted in twenty dogs. Ten of these animals received immunosuppressive drugs. Allograft function was compared with that of other dogs subjected to complete intestinal denervation and lymphatic interruption. Dogs with denervated intestine showed decreased d-xylose absorption with reversal to normal rates within four months. Groups receiving allografts also showed depressed function which persisted for up to five weeks. Interestingly, dogs with untreated allografts showed no significant pathologic changes even though survival ranged from one to four weeks. In contrast, some dogs who received immunosuppressive drugs showed manifestations of organ rejection. Although we could not clearly demonstrate a graft versus host reaction in untreated allografts, it appears that entire small intestinal allografts, in the absence of these immunosuppressive drugs, can precipitate such a reaction. This phenomenon is believed to be related to the abundant lymphatic tissue found in the intestine.

Pancreatic transplantation without duodenum in the dog

Abstract Our study has shown that it is possible to maintain normal exocrine and endocrine function in pancreatic heterotopic auto- and allotransplants without duodenum in the dog using a small periampullary duodenal cuff sutured directly to jejunal mucosa. The described technic has been used to prepare human cadaver donors and further clinical trials are anticipated.

Function studies after auto- and allotransplantation and denervation of pancreaticoduodenal segments in dogs

Abstract The functional and immunologic profiles of pancreaticoduodenal segments after auto- and allotransplantation or denervation were compared. Elevated serum amylase levels were seen immediately after surgery as a result of ischemic damage but statistically significant changes from the preoperative state did not occur. Hyperglycemia was not observed in allografted dogs until just prior to death. Rejection of pancreatic allografts was characterized by a late increase in serum amylase which was not observed in denervated or autografted dogs. Pancreatic denervation with lymphatic interruption or heterotopic autotransplantation resulted in only a temporary exocrine hypofunction whereas allotransplantation was associated with more permanent acinar damage. Islet cell function remained adequate in all groups. Pancreatic venous drainage directly into the systemic or portal systems did not significantly influence fasting blood glucose levels, although higher serum insulin levels resulted from pancreatic venous drainage into the systemic circulation.

Retrograde Perfusion as a Method for Myocardial Revascularization

Retroperfusion of the superficial coronary venous system was studied in 44 canine fibrillating in vivo, normothermic preparations, with exclusion of the systemic circulation using cardiopulmonary bypass techniques in order to assess its value as a method of myocardial revascularization. Perfusion of either the isolated aortic arch via a brachiocephalic cannula or of the coronary sinus through the free end of a vein anastomosed to the atrial rim of the sinus was performed for 1 h at 100 cm3/min in groups II-IV following 30 min of anoxia. Oxygen uptake, vascular resistance, venous outflow and venous enzyme levels (CPK, GDH) were studied. Group I controls (antegrade perfusion, no anoxia) showed continued aerobic metabolism in contrast to group II (antegrade perfusion) and III (retrograde perfusion) which displayed negative lactate balance. Oxygen consumption was greater in group III than II (p less than 0.01) with a higher oxygen extraction in III (p less than 0.005). Group IV, which was given intravenously 30 mg/kg methylprednisolone prior to anoxia and then retroperfused, showed continued aerobic metabolism with low GDH venous levels and adequate oxygen consumption. Three dogs were then subjected to aortoatrial rim coronary sinus vein grafts with ligation of the left common coronary artery at its bifurcation with distal left circumflex and anterior descending artery-internal mammary vein anastomoses for venous drainage. The right coronary artery was left intact. Arterial inflow into the coronary sinus was associated with a left ventricular pressure of 70-80 mm Hg for up to 1.5 h while regular sinus rhythm was maintained. We conclude that retroperfusion of the coronary sinus represents a surgically feasible technique for providing oxygen delivery to the ischemic myocardium.

The effects of alpha stimulation and alpha blockade on pulmonary vascular segment resistance in canine cardiogenic shock

Abstract We used an isolated lung perfusion technique to examine the effect of alpha stimulation and alpha blockade on the pulmonary precapillary ( R a ) and postcapillary ( R v ) resistances of cardiogenic-shocked dogs. Five groups of dogs (10/group) were used: (1) controls, (2) cardiogenic-shock, (3) cardiogenic shock treated with a continuous infusion of norepinephrine to maintain the arterial blood pressure, (4) cardiogenic-shock treated with 1 mg/kg of phenoxybenzamine, and (5) cardiogenic shock in dogs previously made tolerant to lethal injections of epinephrine (1 mg/kg). All cardiogenic-shock dogs were studied 3 hr after closed-chest coronary artery microsphere embolization. Precapillary ( P a ) and postcapillary ( P v ) pressures were monitored, and the capillary pressures at constant lobe weight ( P c i ) were measured by the stopflow technique. Precapillary and postcapillary resistances were calculated using R a = ( P a - P ci )/ Q and R v = ( P ci - P v )/ Q . The ratio of postcapillary to precapillary resistance was calculated as an index of capillary pressure. Both the precapillary and postcapillary resistances were increased 3 hr after cardiogenic shock. This increase indicated that pulmonary vascular reactivity exists even without an intact nerve supply. The ratio of postcapillary to precapillary resistance was increased with cardiogenic shock which indicated an elevated capillary pressure. The postcapillary resistance was not significantly lowered with alpha stimulation, whereas both precapillary and postcapillary resistances were significantly lowered with alpha blockade. The ratio of postcapillary to precapillary resistance was increased with alpha stimulation and decreased with alpha blockade. An increase in the ratio of postcapillary to precapillary resistance is associated with an increase of capillary pressure and could lead to pulmonary congestion and edema on a mechanical basis. These data may explain the pulmonary congestion and poor survival in cardiogenic-shocked dogs treated with alpha stimulation and the increased survival in cardiogenic-shocked dogs treated with alpha blockade.

Clinical Cardiogenic Shock. Vasopressor Versus Corticoid Therapy.

Excerpt Ninety-five patients in clinical cardiogenic shock (Group I: cardiac index, ≤ 2 litre/min·m2body surface area; systolic blood pressure, ≤ 90 mm Hg) and 20 in impending cardiogenic shock (Gr...

The Minnesota system for cardiorespiratory assistance: Test of a new system on dogs

Abstract Venoarterial extracorporeal partial bypass, with asynchronous and synchronous pulsatile perfusion with aortic arch coagulation, was studied in 17 sedated male dogs for up to 24 h, and they were followed up for i month. A specially developed preperfusion drug protocol is described, which allowed the use of homologous blood for both prime and fluid replacement. Five animals survived long-term asynchronous bypass, which was characterized by a reduction in mean aortic and peak left ventricular pressures, left ventricular work index, and tension-time index. Cardiac index was maintained throughout the bypass interval. Viscerocutaneous blood flow was increased and systemic arterial oxygenation was improved. Damage to formed elements of the blood or to coagulation factors was minimal. Synchronized pumping at flows 1200–2000 ml/min resulted in successful augmentation of diastolic pressure. Aortic root pressure curves indicated the presence of ‘ejection phenomenon’ in early diastole and an elastic recoil pressure wave in late diastole. As a result of these studies, we are now developing a mobile cardiorespiratory assistance unit which combines synchronous pulsatile perfusion with membrane oxygenation and monitoring sensors.