Pediatric High Altitude Heart Disease: A Hypoxic Pulmonary Hypertension Syndrome

Previous studies suggest that Tibetans as the oldest mountainous population are better adapted to high altitude. We hypothesized that Tibetans have an unusually small degree of hypoxic pulmonary vasoconstriction (HPV) compared with Han newcomers from the lowlands acclimatized to high altitude. We have studied the pulmonary hemodynamics in healthy Tibetan highlanders and Han newcomers in Qinghai-Tibet. Data were collected from right cardiac catheterization. Cardiac output (CO), pulmonary artery wedge pressure and pulmonary artery pressure were measured in all volunteers at various altitudes. At a given altitude, Tibetans show a lower mean pulmonary artery pressure (MPAP) than Han subjects at rest. During exercise, MPAP in Tibetans increased slightly with a significantly increased cardiac output (CO), whereas the Han showed an obviously increased MPAP both at 2,261m and 3,950 m with a slightly increased CO. Tibetans have a much higher exhaled nitric oxide (NO) than lowlanders. The pulmonary hypertension was relived by oxygen breathing in Han newcomers who has migrated to altitude not more than one month previously indicated that the pulmonary hypertension was due to HPV. But with hypoxic pulmonary hypertension (HPH) in two-year Han immigrants the response to oxygen was less apparent because of vascular remodeling. The pulmonary arterial vasculature studies showed that in normal Tibetan infants over the age 4 months, their small pulmonary arteries are thin-walled and the pulmonary arterioles have thin walls consisting of single elastic laminae. In contrast, in Han Chinese children who were born and raised at high altitude in Tibet until the age of 4 years, the small pulmonary arteries retain a thick smooth muscle. It is usually noted that at high altitude the muscularity in Han infant pulmonary arteries fails to regress, as it does at sea level. The evolutionary pressure for the phenomenon of HPV presumably comes from its value in the perinatal period. We remain emphatic on the point that the pulmonary hypertension at high altitude has no useful function but in fact is deleterious because it is usually associated with several altitude diseases – high altitude pulmonary edema, subacute mountain sickness (infantile and adult) and chronic mountain sickness. Indeed, Tibetans having a normal PAP and a minimal HPV, as well as a marked increase in exercise CO is indicative of remarkable high altitude adaptation. Tibetans are though to have the longest residence at high altitude and more genetically homogenous than Han Chinese, suggesting an evolutionary effect on the genetic control of HPV.

Keywords: pulmonary hemodynamics, Tibetan natives, Han lowlanders, genetic adaptation