The release of clearing factor lipase (CFL) into the blood stream after heparin injection and from hearts during perfusion with a heparin-containing fluid was studied using normal and alloxan diabetic rats. In addition, the effect of alloxan diabetes on heart tissue lipase activity and the “repletion” of this enzyme in previous “depleted” animals by pre-injection of heparin were also investigated. The results show that the plasma CFL activity after an injection of a standard dose of heparin and that of the medium incubated with heart slices or homogenates in the presence of heparin was significantly decreased in alloxan diabetic rats. CFL release from isolated perfused hearts of alloxan diabetic rats was comparable to that from hearts of normal animals during the short perfusion period of five to ten minutes. However, the enzyme release from hearts of alloxan diabetic rats was considerably decreased during prolonged perfusion. Addition of insulin and glucose to the fluid perfusing hearts of diabetic animals did not correct the defect. Insulin treatment restored the CFL activity in plasma, heart slices, homogenates, and perfusates to normal levels. The CFL release into the blood stream or from perfused hearts of rats previously treated with heparin was decreased when rats were given a second injection of this agent or when rats were killed and hearts were perfused less than two hours after the first heparin administration. This decrease was more marked in diabetic than in normal rats. The “repletion” of CFL in hearts of normal rats was completed in three hours with an overshoot four hours after heparin injection. The CFL release from perfused hearts of diabetic rats remained at a low, depleted level even eight hours after heparin administration. The heart tissue lipase activity in rats with heparin pretreatment was also decreased; this decrease was more marked in diabetic than in normal animals. The “repletion” of tissue lipase was also much slower in diabetic rats. Omission of heparin in the incubation medium of heart slices and the perfusion fluid markedly decreased the lipase release especially that from the perfused heart; the decrease was very slight in the incubation medium of heart homogenates. Tissue and perfusate lipase were inhibited by sodium chloride and protamine.

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