Rr Kaliev Mm Mirrakhimov

National center for cardiology and internal medicine, Bishkek ( Kyrgyzstan) Abstract For a long time, investigations under the initiative of academician M. M. Mirrakhimov (1964 - 2004) used exogenous (hypobaric and high-altitude) hypoxia. The most attractive features of the application of hypoxia at chronic glomerulonephritis (ChGN) are its antihyperlipidemic, antihypertensive, immunomodulating and erythropoiesis-stimulating properties. Development of the new method of treatment for...

Tetrahydrobiopterin as a Therapeutic Target

Given the complex pathophysiology of pulmonary hypertension, targeting of multiple pathways with combination drug therapy may be necessary. The ability of BH4 to both augment NO synthesis and decrease superoxide production addresses two pathogenic mechanisms simultaneously. The data support evaluation of pharmacological or molecular strategies that target endothelial BH4 availability in patients with pulmonary hypertension. In this context it is interesting to note that HMG-CoA inhibitors...

Why does High Pulmonary Artery Pressure Cause HAPE

Recent studies performed in the Capanna Regina Margherita (4559 m) have shown that the leak of HAPE is caused by increased capillary pressure and not by an inflammatory process. The study of Maggiorini et al. using right-heart catheterization confirmed the abnormal increase of pulmonary artery pressure and a normal wedge pressure in individuals developing HAPE (figure 4) and in addition demonstrated by the single occlusion method that capillary pressure is also elevated to 20 - 25 mmHg 12 ,...

Info

By day 2 at simulated altitude, the proportion of muscularised arterioles increasing along with increasing PAP 41 . Interestingly, all these studies show that after return to normoxia, smooth muscle cells persist in normally nonmuscularised arterioles, suggesting that smooth muscle cells may remain for a long time after chronic exposure to hypoxia. The pulmonary vascular adventitia of neonatal calves has been found to contain multiple and functionally distinct subpopulations of fibroblasts 46 ....

References

Aldashev, A.A., Borbugulov U., Davletov B., Mirrakhimov M.M. (1989). Human adreno-ceptor system response to the development of high altitude pulmonary arterial hypertension. J Mol Cell Cardiol 21(suppl.1) 175-179. 2. Aldashev AA. (1993) High altitude pulmonary hypertension and signal transduction in the cardiovascular system. In J.S. Brody, D.M. Center, V.A. Tkachuk, eds. Signal Transduction in Lung Cells, Vol. 65. New-York Lung biology in health and disease, pp 459-482. 3. Aldashev A.A. (2000)...

Incidence and Importance

In Qinghai-Tibet the incidence or prevalence of PHAHD or ISMS is corresponding higher. From 1978 to 1985, an epidemiological study on PHAHD among 6,823 Han infants and children (after birth to 14 years of age) was carried out on the Qinghai-Tibetan plateau. The diagnosis of PHAHD was based on history, symptoms, clinical examination, electrocardiogra-phy (ECG), echocardiography, chest radiography, blood count and arterial oxygen saturation (see below). Incidence was 3.66 among Han infants and...

Discussion

The principal findings of this study are (a) the pulmonary artery pressure (Ppa), the ratio of right to left ventricular weight (RVW LVW) and hematocrit (Ht) increased in accordance with the height of living altitude in all mammals, whereas in mammals well-adapted to high altitude, such as pika, blue-sheep and Yachi-nezumi, showed significantly lower values compared to other mammals (b) when the mammals were exposed to simulated high altitude, hypoxic pulmonary vasoconstriction (HPV) in...

High Altitude Cor Pulmonale Definition And Clinical Picture

Kyrgyzian investigators do not have any publications under the name of CMS. Five decades ago they described a clinical picture named High Altitude Pulmonary Hypertension (HAPH), which may evolve to High Altitude Cor Pulmonale (HACP) and HF 36 . This clinical entity is observed in people living at the high altitudes of the Tien-Shan and Pamir Mountains (2800-4200 m) and its prevalence is 4.6 in the male population. HACP is characterized by a variable degree of PH, RVH and HF in the absence of...

Proposal For Classification Of High Altitude Pulmonary Hypertension

A revised clinical classification of PH was proposed by Simonneau et al. during the Third World Symposium on Pulmonary Arterial Hypertension, and HAPH was considered in item 3.5 as Chronic exposure to high altitude 69 . For those interested in high altitude medicine, we propose a more detailed classification of HAPH with the corresponding clinical conditions, as follows High Altitude Pulmonary Hypertension. 1. Healthy highlanders living above 3000m 2. Chronic high altitude diseases 2.1. Chronic...

Oxidative Stress in Pulmonary Hypertension

The association of oxidative stress with pulmonary hypertension is increasingly recognised. Markers of oxidative stress are increased in patients with pulmonary hypertension 6,16,59 . Superoxide mediates pulmonary smooth muscle cell proliferation after exposure to endothe-lin-1 85 , and pulmonary vasoconstriction after exposure to 5-HT 49 . Increased superoxide production from NADPH oxidase has been associated with pulmonary hypertension in foetal lambs after in-utero ductal ligation 8 ....

Chronic Hypoxic Pulmonary Hypertension

Chronic hypoxic pulmonary hypertension is the consequence of both pulmonary vasoconstriction and remodeling. The importance of each component is still disputed. It is usually considered that proliferation (or decreased apoptosis) of cells in the intima, media and adventitia causes the vessel wall to intrude upon the lumen and pose a fixed resistance to flow through the lungs. Supporting this contention is the repeated observation that after Figure 1. Effect of short-term (6 h shaded bars , 12 h...

Sildenafil And Hypoxic Pulmonary Hypertension

MIRRAKHIMOV2, NICHOLAS W. MORRELL3, MARTIN R. WILKINS4, ALMAZ A. ALDASHEV1 1 Institute of Molecular Biology and Medicine, Bishkek, Kyrgyzstan 2 National centre of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan 3 Cambridge University, Cambridge, United Kingdom 4 Imperial College of Medicine, London, United Kingdom Abstract We have previously demonstrated that sildenafil inhibits hypoxia-induced pulmonary vasoconstriction in healthy subjects. The aim of...

Mechanisms of Decreased Exercise Capacity at High Altitude

Altitude is associated with a decrease in inspired partial pressure of O2 because of a decrease in barometric pressure. Therefore, altitude decreases alveolar PO2, which limits the oxygenation of mixed venous blood in the pulmonary capillaries. As long as alveolar PO2 is maintained to values equal or higher than 55 to 60 mmHg, the oxygenation of hemoglobin is maintained at more than 90 and O2 delivery to the tissues is preserved. Altitude exposure is associated with a peripheral...

Tetrahydrobiopterin and Vascular Disease

Decreased endothelial NO and increased oxidative stress are both implicated in vascular disease. The role of BH4 in contributing to endothelial dysfunction has been the subject of considerable interest in recent years. Figure 3. Schematic diagram of NOS structure and function. Active NOS is a dimmer, with each monomer consisting of a reductase domain linked to an oxigenase domain. Electron are donated by NADPH, and transferred to FAD and FMN from the reductase domain of one NOS monomer, to the...

Clinical Features

As a consequence of the rich accumulation of epidemiological and clinical data, we have strong evidence that in Tibet, high altitude heart disease (HAHD) has no age limit and cases have been described in infants, children and adolescents as well as adults 21, 38, 40, 41, 44, 45 , with the highest incidence occurring in infants (89.5-92.0 of all cases ). Most infants and children affected by this illness were of Han origin (over 97 percent were of lowland Han ancestry) 21, 23 . PHAHD or ISMS...

Definition and Nomenclature

PHAHD, also named ISMS, is a syndrome, which is the occurrence of symptomatic, severe pulmonary hypertension in infants or young children who were born or brought up at high altitude above 3000 m symptoms result from an excessive increase in pulmonary artery pressure and right heart failure. These infants often died if continuously exposed to high altitude and autopsy revealed extreme medial hypertrophy of the pulmonary arteries and an increased muscularization of the pulmonary arterioles, as...

Methods

The effects of sildenafil 100 mg and placebo on the pulmonary vascular response to an acute hypoxic challenge were compared in 10 male volunteers aged 18 to 27 years in a randomized, double blind study. The volunteers attended the catheterization laboratory at the National Center of Cardiology in Bishkek (760 meters above sea level), Kyrgyz Republic, on 2 occasions, 1 week apart. All gave written, informed consent and were judged to be healthy on the basis of medical examination and routine...

Who Gets HAPE

Individuals who develop HAPE have an increased HPV. Pulmonary artery pressure is about 30 - 50 higher in individuals who are prone to HAPE compared with non-susceptible controls at an altitude of 4559 m, and this higher pressure precedes edema formation 5 (figure 2). The increased HPV can also be demonstrated at low altitude by a brief hypoxic challenge 6,7 . Furthermore, HAPE-susceptible individuals show also an abnormally high rise of pulmonary artery pressure during exercise in normoxia,...

Limitations And Expansion Of The Scoring System For Diagnosis Of Chronic Mountain Sickness

Subacute mountain sickness and high altitude pulmonary edema are clinical entities associated with moderate or severe PH but with a distinct time course. Therefore, these diseases should be out of the scope of the Scoring System for CMS. On the other hand, the Scoring System should not be l imited to CMS and should be extended to other chronic high altitude diseases such as HAHD and HACP, since PH is a common feature to all of them, without significant differences. Moreover, most of the...

Introduction

High altitude is associated with low temperature as well as low pressure, and this has a marked effect on animal distribution. Most mammals could not live permanently at extreme altitude exceeding 5800m above sea level 4 . There are species indigenous to high altitude, such as Llama Lama glama , Alapaca Lama pacos , Vicuna Lama vicugna and Guanaco Lama guan-icoe in the Andes. However, many species of mammal have been seen at great heights and Yak Bos grunnins , Pika Ochotona roylei and Blue...

Lung Vegf Expression During Pulmonary Hypertension Or During Exposure To Chronic Hypoxia

Vascular endothelial growth factor VEGF was first described as a potent and specific mitogen for endothelial cells and a vascular permeability factor 13 . It was then found to play an important role in normal as well as pathological ang-iogenesis. VEGF is a homodimeric 34- to 42-kDa heparin-binding glycoprotein, that fulfils its function on endothelial cells by binding to flt-1 and KDR flk-1, two highly specific tyrosine kinase receptors expressed almost exclusively on endothelial cells 13 ....

C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene

The MTHFR gene has been mapped to the chromosomal region 1p36.3 and is composed of 11 exons 26 . A common mutation of the MTHFR gene is the C to T transition, located at nucleotide 677 C677T . This results in the amino acid change alanine to valine. This mutation is associated with increased thermolability and reduced specific activity of the enzyme mean activity is 65 in the Ala Val heterozygote and 30 in the Val Val homozygous state, respectively compared to the mean activity in the Ala Ala...

Dante Penaloza

University Cayetano Heredia, Lima, Peru Abstract An expert consensus workshop group of the International Society for Mountain Medicine recently proposed a new classification of high altitude diseases. Chronic mountain disease or Monge's disease was defined as a separate entity on the assumption that pulmonary hypertension was not always identified in these patients. This may have to be revised. Healthy high altitude natives living above 3500 m have pulmonary hypertension and right ventricular...

Evidence for Unequivocal Genetic Effects

The best direct evidence is found in the literature on genetically engineered animals. These studies indicate that genetic background directly influences respiratory frequency, tidal volume, and or minute ventilation either at rest or with hypoxic challenge. The studies of nitric oxide synthase NOS are one example. There are three isoforms of NOS N S-1, NOS-2, and NOS-3 arising from three different regions of the genome and these enzymes are involved in the generation of nitric oxide NO , a...

Transgenic Gtpch Deficiency and Overexpression in Mouse

Using murine models with deficient BH4 biosynthesis, complemented by targeted transgenic animals with increased endothelial BH4 biosynthesis, we have revealed that BH4 plays a pivotal role in eNOS function and regulation of the pulmonary circulation Figure 4 . We first demonstrate that congenital BH4 deficiency in the hph-1 mouse results in the development of pulmonary hypertension and vascular remodelling in the adult under normoxic conditions and exacerbates the response to hypoxia 43 ....

Inder S Anand

Department of Cardiology, VA Medical Center and University of Minnesota, Minneapolis, USA Abstract The use of inhaled nitric oxide in acutely ill patients with high altitude pulmonary edema was first reported in 1998. We demonstrated that both nitric oxide and oxygen cause an acute decrease in pulmonary artery pressure, intrapulmonary shunting and improvement in oxygenation. There appears to be an additive effect on pulmonary hemodynamics and an even greater effect on gas exchange when both...