High altitude PH
The physiologic response of the pulmonary circulation to hypobaric and normobaric hypoxia is to increase pulmonary arteriolar resistance. Sites of hypoxic pulmonary vasoconstriction are small pulmonary arterioles and veins of a diameter less than 900 µm, the veins accounting approximately for 20 % of the total increase in pulmonary vascular resistance caused by hypoxia (Hakim et al., 1983, Audi et al., 1991). At altitudes between 3800 and 6100 m, the mean pulmonary artery pressure in healthy, acclimatized subjects ranged between 20 and 30 mmHg (Naeije, 1997, Reeves and Durmowicz, 1996). In non-acclimatized healthy volunteers who were exposed to an altitude of 4559 m for 24 hours, the average mean pulmonary artery pressure was 26 mmHg (range 20-35 mmHg), and the systolic pulmonary artery pressure 27 to 48 mmHg. A good correlation was found between the systolic pulmonary artery pressure assessed invasively and by echocardiography at high altitude (Maggiorini et al., 2001, Allemann et al., 2000). In a hypobaric chamber at a barometric pressure of 282 Torr (8840 m), acclimatized volunteers at rest had on average a mean pulmonary artery pressure of 34 mmHg (Groves et al., 1987).
However, among high-altitude residents, newcomers and visitors there are individuals who present with severe pulmonary hypertension. Some of them fall ill within a few days with high altitude pulmonary edema, or with congestive right heart failure of high altitude within 8 to 12 weeks. Catheter studies performed at altitudes between 3800 and 4500 m showed that in these subjects the mean pulmonary artery pressure can easily exceed the 40 mmHg mark. However, characteristic for this condition is that high altitude pulmonary hypertension resolves once these individuals ascend to low altitude (Naeije, 1997, Reeves and Durmowicz, 1996).
Among adult long-term high-altitude residents in South America, mean pulmonary artery pressures above 40 mmHg are reported in Monge’s disease, a syndrome that presents with progressive weakness, fatigue, dyspnea and impairment of intellect and higher mental function. Furthermore, patients with Monge’s disease are severely polycythemic with hematocrit values averaging 70 % (range 65-85 %) and hypoxemic with SaO2 around 70 % at an altitude of 4000-4500 m. Healthy residents at this altitude have hematocrit levels around 55-60 % and a SaO2 of 80-85 %. Symptoms of Monge’s disease disappear once the patients move to low altitude. Monge’s disease is also called “chronic mountain sickness“ (Hultgren, 1997a) and it is possibly caused by an inherited or acquired insensitivity to hypoxia and maybe to carbon dioxide. Signs of congestive right heart failure are rare in chronic mountain sickness but they are more frequent among newcomers moving from low to high altitude. Two months after they had moved to Lhasa, fatal congestive right heart failure was diagnosed among infants of Han descent born at low altitude at the average age of 9 months (Sui et al., 1988). Analog to these infants, acclimatized Indian soldiers developed progressive anasarca, distended jugular veins, hepatomegaly, ascites and cardiac findings consistent with pulmonary hypertension on the average 11 months after arrival at their military posts at altitudes between 5800-6700 m. These symptoms resolved spontaneously within 8 to 12 weeks after ascending to low altitude. In these soldiers, right heart catheterisation performed within three days after arrival at low altitude showed elevated pulmonary artery pressure and resistance and hematocrit values around 63 % (Anand et al., 1990). This complication of high altitude pulmonary hypertension in newcomers which leads to congestive right heart failure within a few months upon arrival to high altitude was called "subacute mountain sickness" of the infant and adult, respectively. Finally, excessive hypoxic pulmonary vasoconstriction leading to severe pulmonary hypertension is also a hallmark of individuals prone to develop high altitude pulmonary edema, a condition caused initially by elevated intravascular pressure in the pulmonary capillaries (Maggiorini et al., 2001). Characteristically, high altitude pulmonary edema develops after rapid ascent to high altitude in non-acclimatized individuals. Interestingly, high altitude pulmonary edema has also been described among long-term high-altitude residents with high altitude pulmonary hypertension after they return to high altitude after a few weeks spent at low altitude (Hultgren, 1997b). This condition is called reentry high altitude pulmonary edema. The incidence of high altitude pulmonary edema varies from 2-4 % for trekkers and climbers at the altitudes between 4000-4500 m to 15 % for troops rapidly transported to altitudes between 4000 and 5500 m. Subjects who have suffered from high altitude pulmonary edema once have a more than 50 % chance (relative risk 6-10) to repeat the condition if they re-expose themselves to an altitude above 4000 m without sufficient acclimatization (ascent within 24-48 hours) (Bärtsch, 1997).
In conclusion, the mechanisms leading to high altitude-associated pulmonary hypertension is unknown, but there is good evidence that some individuals are more prone to develop severe pulmonary hypertension than others at high altitude. High altitude polycythemia is a hallmark of chronic mountain sickness, however, not all patients with severe high altitude polycythemia have pulmonay hypertension. Thus, in susceptible individuals exaggerated hypoxic pulmonary vasoconstriction may cause in non-acclimatized individuals high altitude pulmonary edema and in newcomers as well as long-term high-altitude residents congestive right heart failure of high altitude. Characteristic for high altitude pulmonary hypertension and its complications is that they are reversible upon descent to low altitude.