Hemodynamic Measurements after Administration of Aprotinin and/or Heparin during Pancreatic Cell Autotransplantation in the Dog, Pig, and Monkey

Abstract
Transient shock in the form of systemic hypotension and portal venous hypertension accompanied the portal vein infusion of pancreatic mixed cell autografts [to prevent surgically-induced diabetes following pancreatectomy] in human and canine recipients. The use of aprotinin and/or heparin was suggested as blocking agents for this vascular reaction. The supernatant from the collagenase-digested pancreatic cells contains the pancreatic shock factor (PSF). A total of 45 animals were studied: 15 mongrel dogs, 15 domestic pigs and 15 rhesus monkeys. Femoral artery pressure (FAP), portal venous pressure (PoVP) and cardiac output were recorded continuously. Each animal received 0.05 ml/kg of autologous PSF intravascularly. Each animal species was then divided into 3 study areas containing 5 animals with Study 1 receiving PSF plus increasing doses of aprotinin (2500, 5000 and 10,000 KIU/kg); Study 2, full heparinization and then PSF; and Study 3, full heparinization and then PSF plus aprotinin. The same vascular hemodynamic factors were measured. Aprotinin blocked the entire shock reaction in the pig (FAP and PoVP), only partially blocked the PoVP elevation in the dog and blocked neither FAP nor PoVP changes in the monkey. Heparinization did not change the shock reaction in any animal species nor did it change the response to aprotinin blockade in any species. A species response variability exists between the dog, pig and monkey when aprotinin is injected to block PSF obtained from the animal''s own pancreas. If the primate and human responses to aprotinin blockade are similar, aprotinin and/or hepartin should not prevent the transient shock associated with human pancreatic mixed cell autotransplantation.