Chest
Volume 74, Issue 6, December 1978, Pages 648-653
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Experimental Approaches
Platelet-Mediated Pulmonary Hypertension and Hypoxia during Pulmonary Microembolism: Reduction by Platelet Inhibition

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The literature indicates that vasoactive substances released from platelets contribute to the pulmonary pressor response and hypoxemia during pulmonary microembolism. Hence, removal of the platelets or inhibition of their function should reduce these effects. The purpose of this study was, therefore, to investigate the pulmonary effects of experimental embolism with glass beads in dogs rendered thrombocytopenic with platelet antiserum and to compare these effects to the effects in dogs pretreated with sulfinpyrazone (Anturane) or heparin, both substances that affect the function of platelets, probably by inhibiting the release of platelets. In all three groups the pulmonary hypertension was reduced by more than half, and hypoxemia was lessened or abolished. The results of this study indicate the platelets contribute to the effects of pulmonary microembolism and that administration of sulfinpyrazone or heparin reduces the embolism-induced pulmonary hypertension to the same extent as the depletion of platelets. Platelet-inhibiting drugs might therefore be useful prophylactically in human pulmonary microembolism.

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MATERIALS AND METHODS

Twenty-eight mongrel dogs of either sex (mean weight, 21 ± 1 kg [46 ± 2 lb]) were anesthetized with pentobarbital sodium (30 mg/kg of body weight) and were allowed to breathe spontaneously of a mixture of 30 percent oxygen in nitrogen. Two polyethylene catheters (PE 200) were advanced from the femoral arteries to the descending aorta. Two catheters (PE 160) were placed in the superior vena cava via the right jugular vein, and another was placed in the pulmonary artery. A Swan-Ganz

Control Dogs

Pulmonary microembolism with 200μ glass beads increased pulmonary arterial pressure without changing pulmonary wedge pressure or cardiac output (Table 1). Pulmonary vascular resistance increased nearly threefold by five minutes after the embolism and slowly tended downward during the 30 minutes of observation (Fig 1). The PaO2 fell, and the PaCO2 rose. The arterial pH and systemic arterial pressure were unchanged.

Thrombocytopenic Dogs

In the five dogs given the platelet antiserum on the day of the experiment (more

DISCUSSION

Evidence gathered from numerous experimental approaches has indicated the importance of platelet-mediated humoral factors in experimental pulmonary embolism.3, 4, 9, 13, 14, 16, 18, 19 This possibility was first raised in 1953 by Comroe et al,20 who suggested that platelets might release serotonin during pulmonary embolism. This was further substantiated by the findings that serotonin released from platelets during the clotting of blood produced pulmonary hypertension8 and that thrombin, which

ACKNOWLEDGMENTS

We wish to thank Ms. Rosann Glas, Mr. Steve Hofmeister, Mr. Bruce Hookway, Mr. Don Jackson, Ms. Bea Kaplan, Mr. Leonard Latham, Ms. Mary Munroe, and Ms. Eva Toyos for their assistance in this study. We are also grateful to Ms. Susan Konkol for the preparation of the manuscript. Sulfinpyrazone (Anturane) was supplied by CIBA-GEIGY Corp., Summit, NJ.

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  • Cited by (0)

    Recipient of a Max Kade Research Fellowship and an award from the Perkins Memorial Fund of the American Physiological Society.

    Recipient of the Senior Investigator Award from the Colorado Heart Association

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