The Effect of Heparin on the Haemodynamic and Structural Response in the Rat to Acute and Chronic Hypoxia

In the mouse, heparin administered intermittently, has been shown to reduce the right ventricular hypertrophy (RVH) caused by hypoxia. We have investigated in the rat the effect of heparin on the haemodynamic and pulmonary vascular structural remodelling produced by hypoxia, with special reference to the new muscularization of peripheral arteries. Heparin at one of two doses (30 and 50 u/kg/h) was administered by continuous intravenous infusion from a miniosmotic pump to rats during 10 days exposure to hypobaric hypoxia and its effect examined on mean pulmonary artery pressure (PPa), RVH and, using morphometric techniques, vascular structural remodelling. Hypoxia produced the haemodynamic and structural changes previously described in this model. Heparin had no significant effect on PPa; a slight reduction in RVH was seen in the high-dose heparin group. After heparin, the narrowing of the axial pulmonary artery lumen caused by hypoxia was less: heparin reduced the proportion of arteries that became muscularized, particularly at alveolar duct level where the pericyte is the precursor smooth muscle cell. Heparin did not diminish the increase in medial thickness or reduction in external diameter of muscular arteries. Some rats, after chronic hypoxia, did not respond to an acute hypoxic challenge yet were no different from 'responders' in other haemodynamic and structural features. Including all rats, the mean acute pressor response to hypoxia was unaffected by heparin: taking only responder rats, a trend was apparent that heparin reduced the rise in PPa on acute hypoxic challenge.