Increased sensitivity of in vivo platelet aggregation in rabbits after alloxan or streptozotocin.

In 14 rabbits previously injected intravenously with alloxan (dose 75-150 mg/kg) with subsequent hyperglycaemia, intra-arteriolar aggregation of platelets at the sites of small standardized electrical injuries to cerebral cortical vessels showed an increased sensitivity (P is less than 0.001) to application of adenosine diphosphate (ADP) in animals anaesthetized with either urethane or Pentothal. Intravenous injection of streptozotocin (10 rabbits, dose 30-200 mg/kg) was not followed so regularly by hyperglycaemia but even so many of these animals also showed increased sensitivity to ADP. 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. Again, ADP sensitivity did not correlate with the degree of hyperglycaemia, hyperketonaemia or hyperlactacidaemia. There was no rapid change in ADP sensitivity after i.v. injection of glucose to produce hyperglycaemia in normal rabbits, nor after parenteral or topical administration of insulin. 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 found to be 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.