INCREASED SENSITIVITY OF INVIVO PLATELET-AGGREGATION IN RABBITS AFTER ALLOXAN OR STREPTOZOTOCIN

Abstract

In 14 rabbits previously injected i.v. with alloxan (dose 75-150 mg/kg) with subsequent hyperglycemia, intra-arteriolar aggregation of platelets at the sites of small standardized electrical injuries to cerebral cortical vessels showed an increased sensitivity (P < 0.001) to application of ADP in animals anesthetized with either urethane or Pentothal. I.v. streptozotocin injection (10 rabbits, dose 30-200 mg/kg) was not followed regularly by hyperglycemia, but many of these animals showed increased ADP sensitivity. After neither alloxan nor streptozotocin did the increased sensitivity correlate with the dose of agent used, the time between its injection and ADP testing, or changes in the rabbit''s body weight. ADP sensitivity did not correlate with the degree of hyperglycemia, hyperketonemia or hyperlactacidemia. There was no rapid change in ADP sensitivity after i.v. injection of glucose to produce hyperglycemia in normal rabbits, nor after parenteral or topical insulin administration. Use of a removable skull capsule allowed serial observations on individual animals and these, together with observations on rabbits injected first with alloxan and later with daily insulin, showed reversibility of the increased ADP sensitivity by regular insulin injection for at least 5 days; this effect did not depend upon return of blood glucose levels to normal. In cross-perfusion experiments the increased ADP sensitivity was dependent upon a blood factor for such sensitivity was shown by the head of a normal rabbit perfused with blood from a diabetic trunk. The results did not exclude a contribution of a mural factor to the results in intact animals after alloxan. The results are in keeping with in vitro observations of increased sensitivity to ADP of platelet aggregation in diabetic patients and demonstrate that such an effect holds within living blood vessels, as well as providing a model for further experiment.