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Pulmonary Circulation and Right Ventricle in Hypoxia: From Molecular Mechanisms to Clinical Aspects

A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601). This special issue belongs to the section "Global Health".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 30438

Special Issue Editors

Dr. Akylbek Sydykov

E-Mail Website
Guest Editor
Universities of Giessen and Marburg Lung Center (UGMLC), Excellence Cluster Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Justus Liebig University of Giessen, 35392 Giessen, Germany
Interests: pulmonary hypertension; right ventricular hypertrophy; high altitude medicine and physiology
Special Issues, Collections and Topics in MDPI journals
Dr. Djuro Kosanovic

E-Mail Website
Co-Guest Editor
Department of Pulmonology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia
Interests: pulmonary hypertension; high-altitude medicine; lung fibrosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

High altitude hypoxia is one of the most important environmental factors with a well-known impact on pulmonary circulation during high altitude sojourns, long-term intermittent exposure, or permanent residence. Hypoxic pulmonary vasoconstriction and vascular remodeling are also important attributes of pulmonary hypertension in disease states at sea level. Despite significant progress in recent years, many aspects of the responses of the pulmonary circulation and right ventricle to hypoxia are still incompletely understood and need further research. We are, therefore, pleased to invite all investigators in the field to contribute to this Special Issue by presenting their most recent research related to molecular and cellular biology, pharmacology, physiology, and pathology of pulmonary circulation and right ventricle adaptation to acute, intermittent, and chronic hypoxia. Experimental and clinical papers, up-to-date review articles, and short commentaries are all welcome.

Dr. Akylbek Sydykov
Dr. Djuro Kosanovic
Guest Editors

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Keywords

  • High altitude
  • Acute hypoxia
  • Chronic Hypoxia
  • Intermittent hypoxia
  • Pulmonary circulation
  • Pulmonary hypertension
  • Right ventricle

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Published Papers (6 papers)

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Research

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15 pages, 2862 KiB  
Article
The Oxygen Transport Triad in High-Altitude Pulmonary Edema: A Perspective from the High Andes
by Gustavo Zubieta-Calleja and Natalia Zubieta-DeUrioste
Int. J. Environ. Res. Public Health 2021, 18(14), 7619; https://doi.org/10.3390/ijerph18147619 - 17 Jul 2021
Cited by 9 | Viewed by 5470
Abstract
Acute high-altitude illnesses are of great concern for physicians and people traveling to high altitude. Our recent article “Acute Mountain Sickness, High-Altitude Pulmonary Edema and High-Altitude Cerebral Edema, a View from the High Andes” was questioned by some sea-level high-altitude experts. As a [...] Read more.
Acute high-altitude illnesses are of great concern for physicians and people traveling to high altitude. Our recent article “Acute Mountain Sickness, High-Altitude Pulmonary Edema and High-Altitude Cerebral Edema, a View from the High Andes” was questioned by some sea-level high-altitude experts. As a result of this, we answer some observations and further explain our opinion on these diseases. High-Altitude Pulmonary Edema (HAPE) can be better understood through the Oxygen Transport Triad, which involves the pneumo-dynamic pump (ventilation), the hemo-dynamic pump (heart and circulation), and hemoglobin. The two pumps are the first physiologic response upon initial exposure to hypobaric hypoxia. Hemoglobin is the balancing energy-saving time-evolving equilibrating factor. The acid-base balance must be adequately interpreted using the high-altitude Van Slyke correction factors. Pulse-oximetry measurements during breath-holding at high altitude allow for the evaluation of high altitude diseases. The Tolerance to Hypoxia Formula shows that, paradoxically, the higher the altitude, the more tolerance to hypoxia. In order to survive, all organisms adapt physiologically and optimally to the high-altitude environment, and there cannot be any “loss of adaptation”. A favorable evolution in HAPE and pulmonary hypertension can result from the oxygen treatment along with other measures. Full article
(This article belongs to the Special Issue Pulmonary Circulation and Right Ventricle in Hypoxia: From Molecular Mechanisms to Clinical Aspects)
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Review

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20 pages, 4295 KiB  
Review
Role of the Purinergic P2Y2 Receptor in Pulmonary Hypertension
by Mazen Shihan, Tatyana Novoyatleva, Thilo Lehmeyer, Akylbek Sydykov and Ralph T. Schermuly
Int. J. Environ. Res. Public Health 2021, 18(21), 11009; https://doi.org/10.3390/ijerph182111009 - 20 Oct 2021
Cited by 3 | Viewed by 3858
Abstract
Pulmonary arterial hypertension (PAH), group 1 pulmonary hypertension (PH), is a fatal disease that is characterized by vasoconstriction, increased pressure in the pulmonary arteries, and right heart failure. PAH can be described by abnormal vascular remodeling, hyperproliferation in the vasculature, endothelial cell dysfunction, [...] Read more.
Pulmonary arterial hypertension (PAH), group 1 pulmonary hypertension (PH), is a fatal disease that is characterized by vasoconstriction, increased pressure in the pulmonary arteries, and right heart failure. PAH can be described by abnormal vascular remodeling, hyperproliferation in the vasculature, endothelial cell dysfunction, and vascular tone dysregulation. The disease pathomechanisms, however, are as yet not fully understood at the molecular level. Purinergic receptors P2Y within the G-protein-coupled receptor family play a major role in fluid shear stress transduction, proliferation, migration, and vascular tone regulation in systemic circulation, but less is known about their contribution in PAH. Hence, studies that focus on purinergic signaling are of great importance for the identification of new therapeutic targets in PAH. Interestingly, the role of P2Y2 receptors has not yet been sufficiently studied in PAH, whereas the relevance of other P2Ys as drug targets for PAH was shown using specific agonists or antagonists. In this review, we will shed light on P2Y receptors and focus more on the P2Y2 receptor as a potential novel player in PAH and as a new therapeutic target for disease management. Full article
(This article belongs to the Special Issue Pulmonary Circulation and Right Ventricle in Hypoxia: From Molecular Mechanisms to Clinical Aspects)
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9 pages, 746 KiB  
Review
Evidence for Multiple Origins of De Novo Formed Vascular Smooth Muscle Cells in Pulmonary Hypertension: Challenging the Dominant Model of Pre-Existing Smooth Muscle Expansion
by Xuran Chu, Negah Ahmadvand, Jin-San Zhang, Werner Seeger, Saverio Bellusci and Elie El Agha
Int. J. Environ. Res. Public Health 2021, 18(16), 8584; https://doi.org/10.3390/ijerph18168584 - 14 Aug 2021
Cited by 1 | Viewed by 2843
Abstract
Vascular remodeling is a prominent feature of pulmonary hypertension. This process involves increased muscularization of already muscularized vessels as well as neo-muscularization of non-muscularized vessels. The cell-of-origin of the newly formed vascular smooth muscle cells has been a subject of intense debate in [...] Read more.
Vascular remodeling is a prominent feature of pulmonary hypertension. This process involves increased muscularization of already muscularized vessels as well as neo-muscularization of non-muscularized vessels. The cell-of-origin of the newly formed vascular smooth muscle cells has been a subject of intense debate in recent years. Identifying these cells may have important clinical implications since it opens the door for attempts to therapeutically target the progenitor cells and/or reverse the differentiation of their progeny. In this context, the dominant model is that these cells derive from pre-existing smooth muscle cells that are activated in response to injury. In this mini review, we present the evidence that is in favor of this model and, at the same time, highlight other studies indicating that there are alternative cellular sources of vascular smooth muscle cells in pulmonary vascular remodeling. Full article
(This article belongs to the Special Issue Pulmonary Circulation and Right Ventricle in Hypoxia: From Molecular Mechanisms to Clinical Aspects)
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21 pages, 3505 KiB  
Review
Novel Therapeutic Targets for the Treatment of Right Ventricular Remodeling: Insights from the Pulmonary Artery Banding Model
by Argen Mamazhakypov, Natascha Sommer, Birgit Assmus, Khodr Tello, Ralph Theo Schermuly, Djuro Kosanovic, Akpay Sh. Sarybaev, Norbert Weissmann and Oleg Pak
Int. J. Environ. Res. Public Health 2021, 18(16), 8297; https://doi.org/10.3390/ijerph18168297 - 5 Aug 2021
Cited by 7 | Viewed by 3540
Abstract
Right ventricular (RV) function is the main determinant of the outcome of patients with pulmonary hypertension (PH). RV dysfunction develops gradually and worsens progressively over the course of PH, resulting in RV failure and premature death. Currently, approved therapies for the treatment of [...] Read more.
Right ventricular (RV) function is the main determinant of the outcome of patients with pulmonary hypertension (PH). RV dysfunction develops gradually and worsens progressively over the course of PH, resulting in RV failure and premature death. Currently, approved therapies for the treatment of left ventricular failure are not established for the RV. Furthermore, the direct effects of specific vasoactive drugs for treatment of pulmonary arterial hypertension (PAH, Group 1 of PH) on RV are not fully investigated. Pulmonary artery banding (PAB) allows to study the pathogenesis of RV failure solely, thereby testing potential therapies independently of pulmonary vascular changes. This review aims to discuss recent studies of the mechanisms of RV remodeling and RV-directed therapies based on the PAB model. Full article
(This article belongs to the Special Issue Pulmonary Circulation and Right Ventricle in Hypoxia: From Molecular Mechanisms to Clinical Aspects)
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33 pages, 1942 KiB  
Review
Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders
by Akylbek Sydykov, Argen Mamazhakypov, Abdirashit Maripov, Djuro Kosanovic, Norbert Weissmann, Hossein Ardeschir Ghofrani, Akpay Sh. Sarybaev and Ralph Theo Schermuly
Int. J. Environ. Res. Public Health 2021, 18(4), 1692; https://doi.org/10.3390/ijerph18041692 - 10 Feb 2021
Cited by 65 | Viewed by 10843
Abstract
Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring [...] Read more.
Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options. Full article
(This article belongs to the Special Issue Pulmonary Circulation and Right Ventricle in Hypoxia: From Molecular Mechanisms to Clinical Aspects)
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Other

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7 pages, 654 KiB  
Case Report
An Exaggerated Rise in Pulmonary Artery Pressure in a High-Altitude Dweller during the Cold Season
by Akylbek Sydykov, Abdirashit Maripov, Nadira Kushubakova, Kubatbek Muratali Uulu, Samatbek Satybaldyev, Cholpon Kulchoroeva, Djuro Kosanovic and Akpay Sarybaev
Int. J. Environ. Res. Public Health 2021, 18(8), 3984; https://doi.org/10.3390/ijerph18083984 - 10 Apr 2021
Cited by 7 | Viewed by 2717
Abstract
Chronic hypoxia-induced sustained pulmonary vasoconstriction and vascular remodeling lead to mild-to-moderate elevation of pulmonary artery pressure in high-altitude residents. However, in some of them, severe pulmonary hypertension may develop. Besides hypoxia, high-altitude residents also face other environmental challenges such as low ambient temperatures. [...] Read more.
Chronic hypoxia-induced sustained pulmonary vasoconstriction and vascular remodeling lead to mild-to-moderate elevation of pulmonary artery pressure in high-altitude residents. However, in some of them, severe pulmonary hypertension may develop. Besides hypoxia, high-altitude residents also face other environmental challenges such as low ambient temperatures. We describe a case of a 49-year-old woman of Kyrgyz ethnicity with abnormally increased pulmonary artery pressure, revealed by Doppler echocardiography. Significantly elevated pulmonary artery pressure was detected in late winter and this was not associated with right ventricular hypertrophy or right ventricular dysfunction. Repeat echocardiography performed in late summer disclosed a significant attenuation of pulmonary artery pressure elevation, with no changes in right ventricular performance parameters. This case illustrates that, in susceptible individuals, long-term cold exposure could induce an abnormal pulmonary artery pressure rise, which can be reversed during warm seasons as in our patient. In certain circumstances, however, additional factors could contribute to a sustained pulmonary artery pressure increase and the development of persistent pulmonary hypertension, which often leads to right heart failure and premature death. Full article
(This article belongs to the Special Issue Pulmonary Circulation and Right Ventricle in Hypoxia: From Molecular Mechanisms to Clinical Aspects)
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