S-9-9 Heparin and angiogenic therapy
M. Fujita College of Medical Technology, Kyoto University, Kyoto, Japan


@Using the repeated coronary occlusion model, we investigated the effect of heparin treatment on collateral development. In eight control dogs, 2 min coronary occlusions were repeated 129}44 times until acute occlusion was no longer accompanied by a reduction in systolic shortening of the ischemic area. In a further eight dogs pre-treated with heparin, however, only 81}33 occlusions were necessary to produce the same results. These findings indicate that heparin has the potential to accelerate and potentiate collateral development in vivo.

@ Ten patients with coronary artery disease and effort angina were exercised 10 to 20 min following pre-treatment with a single intravenous dose of heparin (5000 units) twice a day for 10 days. The rate-pressure product at the onset of 0.1 mV ST depression and anginal pain increased by 19% and 35%, respectively. The angiographic collateral score also increased in these patients. In contrast, none of these indexes changed significantly in patients with exercise alone.

@ In a subsequent randomized study, 52 patients with effort angina were randomly assigned to receive one of two intravenous doses of enoxaparin (40 mg or 60 mg) or a placebo. Each patient underwent 20 treadmill exercise sessions 10 to 20 min following pre-treatment with enoxaparin or a placebo. Only in patients who received 60 mg enoxaparin pretreatment, did the rate-pressure product at the onset of angina increase significantly, by 16%. The extent of angiographically demonstrable collateral circulation to the area perfused by the completely obstructed coronary artery increased in 47% of the enoxaparin-treated patients, but only in 25% of the placebo patients. These findings are compatible with a hypothesis that a combination of exercise and enoxaparin induces collateral growth to the jeopardized myocardium.

@ The clarification of the precise mechanisms of the interaction of angiogenic growth factors with heparin would provide a new therapeutic strategy for coronary artery disease.