Northern Pulmonary Hypertension: A Forgotten Kind of Pulmonary Circulation Pathology

Abstract

Northern pulmonary hypertension (NPH) is a medical condition that is still enigmatic in non-Russian-speaking countries. The extant previous literature is mostly available in the Russian language and, therefore, not accessible to the rest of the world. The recent increased interest in climate changes and environmental effects on pulmonary circulation prompted us to summarize the knowledge from the past about the effects of cold on pulmonary vasculature. In this review, we, for the first time, describe, in detail, the pathological attributes of human NPH, a medical disorder that occurs in people living in extremely cold regions, in the English language. Briefly, NPH is characterized by the hyper-muscularization of the pulmonary arteries and de novo muscularization of the arterioles with the ultimate development of right ventricular hypertrophy. However, the profound molecular mechanisms of the NPH pathology are to be revealed in future comprehensive studies.

Keywords: Russian North; cold environments; polar regions; pulmonary circulation; pulmonary hypertension; pulmonary vasculature.

Figure 1

Scientific expedition to the northeast Russian city of Magadan. The photographs of the members of scientific expedition to the city of Magadan in 1981 are shown.

Figure 2

Increased pulmonary arterial pressure in people living in northeast regions of Russia. (A) Geographic locations of Moscow and northeast Russian human settlements (Magadan, Talaya and Anadyr) characterized by extreme cold are presented. The map is taken from www.maps-for-free.com (accessed on 20 January 2023) and further modified. (B) The values of systolic pulmonary arterial pressure (PAP) measured in people living in Moscow (control) and northeast regions of Russia are given. The data derived from one of the studies are taken from the following reference [1].

Figure 3

Time-dependent stages in the development of Northern pulmonary hypertension. Four stages of the development of Northern pulmonary hypertension are schematically presented by means of the changes in the values of systolic pulmonary arterial pressure (PAP). The circles symbolically represent the human population that spent the given time periods in extremely cold environments. Black-colored circles represent the portion of the population with increased values of the systolic PAP.

Figure 4

Morphological and histological changes of the cardiovascular and pulmonary systems in people living in extremely cold regions. Some of the alterations of the cardiovascular and pulmonary systems due to extreme and long-term cold exposure include (A) right ventricular (RV) hypertrophy, (B) “thinning” of the respiratory membrane in the lungs, (C) de novo muscularization and (D) hyper-muscularization of the pulmonary vessels. Legend: AECI: type I alveolar epithelial cells, EC: endothelial cells, RBC: red blood cells, SMC: smooth muscle cells.

Figure 5

Development of right ventricular hypertrophy in rats exposed to gradual decrease in temperature. The development and time-dependent progression of right ventricular hypertrophy is schematically presented by means of the changes in right ventricular size and cardiomyocyte size and density in rats exposed to cold environments. The circles symbolically represent the rat population gradually exposed to cold from 5 °C to −20 °C.