Effects of thrombocytopenia on monocrotaline pyrrole-induced pulmonary hypertension

Abstract

Monocrotaline pyrrole (MCTP) causes lung injury, pulmonary hypertension, and right ventricular hypertrophy in rats. To determine if platelets are involved in the cardiopulmonary effects of MCTP, the response to MCTP was determined in thrombocytopenic rats. Blood platelet count was reduced to 10-20% of normal for 48 h by ip administration of an antirat platelet serum (PAS) prepared in the goat. Rats were treated iv with either MCTP 5 mg/kg or dimethylformamide vehicle and with either PAS or preimmune serum. Fourteen days after MCTP, right ventricular hypertrophy and several indexes of lung injury were measured. MCTP treatment produced right ventricular hypertrophy, increased lactate dehydrogenase activity and protein concentration in bronchopulmonary lavage fluid, increased perfusion pressure in isolated lungs, and decreased pulmonary clearance and metabolism of perfused 5-hydroxytryptamine. Thrombocytopenia did not influence the changes in these indexes of lung injury produced by MCTP in this protocol. When PAS was given 12 h before MCTP, it did not affect right ventricular hypertrophy, but when PAS treatment was begun 3 or 6 days after MCTP, right ventricular hypertrophy was decreased by 19 or 41%, respectively. These results suggest that platelets help to mediate the development of pulmonary hypertension and the hypertrophic response of the right heart following MCTP administration.

Human platelets modulate edema formation in isolated rabbit lungs.

“…This ex vivo investigation may assist in interpreting previous conflicting whole animal studies demonstrating that platelets can either maintain normal pulmonary membrane permeability (39), augment lung injury (12), have no effect on membrane permeability (40), or generate pulmonary hypertension in models of acute lung injury (15,41). In models of injury that generate oxidant stress, the antioxidant capacity of the platelets may determine whether they neutralize toxic oxygen metabolites before membrane injury occurs or whether they participate in pathogenetic events by releasing vasoactive substances that augment underlying membrane permeability defects.…”

Tadalafil, a Long-Acting Inhibitor of PDE5, Improves Pulmonary Hemodynamics and Survival Rate of Monocrotaline-Induced Pulmonary Artery Hypertension in Rats

“…MCT is metabolized in the liver and changed to the active form (monocrotaline pyrrole) which, after a single subcutaneous injection, injures vascular endothelium of pulmonary vessels within several hours (26), activates platelets within 1 week (27,28), and causes enhanced reactivity of pulmonary vessels to vasoconstrictive substances (29) and muscular hypertrophy of the media of pulmonary vessels (30). Mortality due to right cardiac failure begins 3 to 4 weeks after the injection and the survival decreases to about 30% by 6 weeks after the injection.…”

Changes in Sequestered Leukocytes and Platelets in the Pulmonary Microvasculature of Rats with Monocrotaline-lnduced Pulmonary Hypertension

“…The inflammatory lesions of pulmonary capillaries, arterioles and arteries induced by MCT con tain WBCs, and a large number of WBCs and elevation of eieosanoids are also seen in bronchoalveolar lavage fluid [9J. H ¡Hiker et al [7,8] studied MCT rats and found data that strongly pointed to a role of PLTs in the development of pulmonary hypertension. The purpose of the present study was to investigate the sequestration ofWBCs and PLTs in pulmonary' capillaries during the development of Sequestered Leukocytes and Platelets in Monocrotaline Pulmonary Hypertension pulmonary' hypertension and RV hypertrophy.…”

“…A progressive rise in pulmo nary artery pressure and the development of right ventric ular (RV) hypertrophy appear to correlate with these pul monary vascular changes [4][5][6], Therefore, the type of pulmonary hypertension for which MCT-induced pulmo nary hypertension is used as a model need to be specified. In addition, time course studies in this MCT rat model have indicated that chronic lung inflammation precedes pulmonary hypertension and RV hypertrophy [7][8][9], In the present study, the sequestration of leukocytes (WBCs) and platelets (PLTs) in the pulmonary microvas culature was investigated by real-time confocal laser mi croscopy [10][11][12][13] tion of these cells to the development of cardiopulmonary changes in rats with MCT-induced pulmonary hyperten sion.…”