Low dose chronically infused hemoglobin induces pulmonary hypertension or excerbates hypoxia‐induced pulmonary hypertension

Abstract

Observations from examining past medical records from patients with sickle cell anemia or thalassemia suggest these diseases may be a risk factor for the development of severe pulmonary hypertension (PH). Recently it has been proposed that the chronic exposure to cell free hemoglobin is a major contributor to the development of PH in these patients. Therefore, we hypothesized that chronic infusion (3 and 6 wk) of cell free hemoglobin in rats would either induced or exacerbate PH in rats exposed to room air or hypoxia.MethodsMale, age matched (8–10 wk) Sprague dawley rats were treated with chronically infused free hemoglobin (500 ug/hr) or left untreated and either exposed to chronic hypoxia (18,000 ft; PB ~ 379 mm Hg;) or remained in normoxic conditions (5,280 ft; PB ~ 620 mm Hg). After wards, cardiac output (CO), mean pulmonary artery (Pa) and systemic pressures (MAP) and hemotocrit (Hct) were recorded, and RV/LV+S ratio was determined and lungs were examed as indication of the severity of PH.ResultsOverall, hemoglobin (Hb) infusion increased Pa pressures and lowered Hct compared to untreated cohorts. In the normoxic Hb infused animals MAP and Pa pressures increased between 3 and 6 weeks. Compared to hypoxic control rats, Pa pressures were greater at 3 and 6 wks, whereas MAP was greater only at 3 wk in Hb infused animals.ConclusionChronic infusion of CFH can induce or exacerbate hypoxic‐induced PH. However, whether CFH exerts this effect by oxidative damage, inflammation or NO scavenging is unknown.