Northern Pulmonary Hypertension: Personal Experience and Brief History

My focus here is to tell the personal and historical story about the discovery and characterization of pulmonary hypertension caused by extreme cold, a condition now recognized as Northern Pulmonary Hypertension (NPH). Residents of the Far North often experience increased fatigue, breathing difficulties, and gas exchange challenges—a condition known as “polar dyspnea”. While many attribute this to a lack of oxygen in the air, studies have shown that sufficient oxygen is present. Still, it is more tightly bound in winter, making gas exchange at the alveolar level more difficult. In April 1980, during my first expedition to Magadan, I experienced “polar dyspnea” firsthand while climbing a modest slope despite being in good physical condition. Later that year, during a trip to 3800 m above sea level, I struggled with pronounced shortness of breath when carrying water uphill. However, I could easily perform the same task after a week at altitude. These experiences illustrate the profound effects of cold and altitude on the human body, as well as the remarkable capacity for adaptation, which inspired me to undertake further studies on this topic. The groundwork for understanding the effects of cold climates on the cardiovascular system in the USSR was laid by N.R. Paleev, who was the first to compare the impacts of Arctic and Antarctic environments [1]. Diseases in Northern populations, particularly among newcomers, were found to have unique clinical and pathological features compared to those living in temperate zones. In 1965, during a meeting of the Geographical Society of the USSR, my mentor, academician A.P. Avtsyn (Figure 1A,B), reported on pioneering research initiated in Murmansk in 1961 by the “Research Institute of Human Morphology”. This study marked the beginning of systematic studies into human pathology in the North. In 1976, Avtsyn introduced the term “Northern Medicine”, which became the foundation for subsequent investigations into the diseases of Northerners and the processes of adaptation and maladaptation to the harsh conditions of the Far North at low altitude—basically at sea level or just low altitudes. Therefore, cold pulmonary hypertension exists without high-altitude hypoxia. NPH was first identified in 1972 by scientists at the Research Institute of Human Morphology in Magadan, Northeast Russia (Figure 1C). Its detailed characteristics were later described in monographs [2-4]. The primary environmental trigger for NPH is extreme cold. Additional factors include frequent fluctuations in atmospheric pressure and strong wind gusts, sometimes reaching 20–30 m/sec. NPH is a form of precapillary–capillary pulmonary hypertension that develops under conditions of alveolar hypoxia and arterial hypoxemia. Remarkably, this condition is often functionally asymptomatic and considered adaptive. Radiological and morphological studies revealed dilation of large pulmonary artery branches and thickening of their walls due to marked muscular hypertrophy. Notably, NPH becomes fixed after 8–10 years of exposure in newcomers to the North. Studies of Indigenous populations (Nenets and Chukchi) revealed similar changes in the pulmonary arteries. Furthermore, the comparable alterations observed in the lungs and pulmonary vasculature of reindeer underscored the role of environmental adaptation [5]. My friend Milovanov frequently referred to these findings as “pathologic changes of the pulmonary circulation in the visiting inhabitants of the North, Chukchi and reindeer [4].” In 1984, as a young researcher at the Research Institute of Human Morphology, I exposed white mongrel rats to daily cooling from +5°C to −20°C for 6 h in a refrigerated chamber. The temperature was lowered by 5°C each week, and the rats were housed individually to prevent mutual warming. My experiments reproduced the key features of NPH, including right heart hypertrophy [6]. NPH [7] remains poorly understood outside Russia due to the literature being primarily written in Russian, which affects people in extremely cold regions. Renewed interest in the impact of climate change on pulmonary circulation highlights the need to understand the effects of cold. Further studies are required to elucidate the specific clinical and molecular mechanisms of NPH. The author has nothing to report. The author has nothing to report. The author declares no conflicts of interest.