Does excessive L-arginine cause pancreatic dysfunction in sheep

In rodents high dose L-arginine causes pancreatic dysfunction with the development of acute pancreatitis. We have attempted to confirm the relation between high dose L-arginine and pancreatic dysfunction in a large animal species in which hemodynamic paramenters can be monitored with the aim of establishing a new pancreatitis model in a large animal. Adult sheep with chronic vascular catheters placed in the carotid artery and jugular vein were utilized. Vascular pressures and cardiac output were monitored up to 3 days following the administration of 3.75 to 5 gm/kg of L-arginine into the abdominal cavity. One hour after instillation monitoring was initiated. The 5 gram dose lead to apparent cardiovascular collapse occuring within 12 to 24 hrs. Vascular fluid administration was initiated to treat the induced hypovolemia. Animals that survived 48 to 72 hours demonstrated increased amylase and lipase levels and histological evidence of pancreatic pathology was present. We conclude that lower doses are required to produce survival in sheep than in rats and that a form of pancreatic dysfunction is induced by high doses of L-arginine in sheep.