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International Hypoxia Symposium XVIII: 26 February–02 March 2013 Matiram Pun1,2* and Buddha Basnyat1,3,4,5

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International Hypoxia Symposium XVIII: 26 February–02 March 2013 Matiram Pun1,2* and Buddha Basnyat1,3,4,5 Pun and Basnyat Extreme Physiology & Medicine 2013, 2:32 http://www.extremephysiolmed.com/content/2/1/32 MEETING REPORT Open Access International hypoxia symposium XVIII: 26 February–02 March 2013 Matiram Pun1,2* and Buddha Basnyat1,3,4,5 Abstract The 18th International Hypoxia Symposia, Lake Louise, Alberta, Canada, February 26–March 02, 2013, covered molecular basis of hypoxic responses (e.g., hypoxia inducible factor, nitrite, nitrate, and hemoglobin) and integrative physiology (e.g., exercise physiology, cerebral blood flow responses, live-high train-low, and population genetics). Free communications and poster sessions covered scientific areas from controlled lab settings to field settings of high altitudes (Andes to Himalayas). Keywords: Hypoxia, Integrative physiology, Andes, Himalayas Background Chateau at the picturesque Lake Louise in the heart of Hypoxia is an inadequate supply of oxygen to our body Banff National Park in the Canadian Rockies during the which could be generalized (to a whole body) or localized week of the full moon (February–March of the year). (in a particular tissue). Although slight variation of arterial oxygen concentration in human tissue can be a normal Hypoxia XVIII: 2013 physiology, a significant desaturation for a longer period of The 18th International Hypoxia Symposia started on the time (hypoxia) is a pathological conditi on. Hypoxia occurs evening of the 26th of February, 2013 at Lake Louise, in many varied settings, e.g., intensive care units, stroke Alberta, Canada inside the luxurious Chateau Lake Louise units, in sleep-disordered breathing, high-altitude excur- with a welcome reception. The scientific program on the sions, and in cancer tissues. Hypoxia poses a significant following days was very exciting with a great mixture of la- threat to the human body and vital organs throughout life. boratory and field studies. Hence, better understanding of hypoxia pathophysiology is important in various disease management to achieve better 27 February, Wednesday outcome. The International Hypoxia Symposia that takes The first session in the morning was on chronic inter- place every 2 years has been a specialized but extremely vi- mittent hypoxia (CIH), the hallmark of sleep-disordered brant conference in the field of hypoxia. breathing especially obstructive sleep apnea, and its effect Currently, it is organized by Dr. Robert Roach and Dr. on cardiorespiratory system. The leaders in the field Peter Hackett (both from CO, USA). It was started in 1973 Dr. Nanduri Prabhakar (University of Chicago, Chicago, IL, in its earlier form by Dr. Charles Houston. The credit for USA), Dr. Gregg L Semenza and Dr. Larissa Shimoda (both founding this present day symposia goes to Charles Hous- from Johns Hopkins University School of Medicine, ton, Geoff Coates and John Sutton. Their vision behind this Baltimore, MD, USA) covered the topic in great depth. The symposium was to facilitate scientists, clinicians, mountain- primary focus was CIH-triggered transcriptional factors, α α eers and other interested individuals to share their experi- e.g., hypoxia inducible factors (HIF1 and HIF2 ), reactive ences on lack of oxygen in various settings. The Charlie oxygen species (ROS) and their perturbations in cardiore- Houston legacy has been maintained, and the quality of sci- spiratory homeostasis. While controlled experiments with ence is excellent. Since 2005, it has always been held at the intermittent hypoxia (IH) have promising results to under- stand physiological effects, they do not exactly reflect what * Correspondence: [email protected] real human patients, e.g., obstructive sleep apnea (OSA), 1 Mountain Medicine Society of Nepal (MMSN), C/O Nepal International Clinic suffer from especially in terms hypercapnia. The expe- (NIC), Lal durbar, GPO BOX 3596, Kathmandu, Nepal 2University of Calgary, 2500 University Dr. NW, AB T2N 1N4, Calgary, Canada rimental limitations were aptly raised by The experimental Full list of author information is available at the end of the article limitations were aptly raised by Dr. Barbara Morgan ©2013 Pun and Basnyat; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Pun and Basnyat Extreme Physiology & Medicine 2013, 2:32 Page 2 of 5 http://www.extremephysiolmed.com/content/2/1/32 (University of Wisconsin-Madison, Madison, WI, USA) CO, USA) presented interesting physiological experi- and Dr. Prabhakar highlighted the challenges of titrating ments from the high-altitude field. carbon dioxide in experimental animals. It highlights the In the evening, Dr. Steve Herrero (University of Calgary, need of experimental preparation that addresses true dis- Calgary, AB, Canada) provided an intriguing insight into ease picture in human. After coffee break, Dr. Jose Calbet the life and habitat of bears from the Canadian Rockies. (University of Las Palmas de Gram Canaria, Spain) pre- Dr. Herrero who has devoted his life in studying bears sented invasive and non-invasive experimental setups in highlighted the long and enduring effort of male bears to humans to tease out the role of oxygenation (both partial convince females for mating. pressure and blood oxygen saturation) during maximal ex- ercise. These sophisticated and invasive experiments are 28 February, Thursday important in understanding human and integrative physi- The morning session started with Tibetan physiology by ology, but there were few aspects, e.g., role of carbon mon- Dr. Peter Robbins (University of Oxford, Oxford, UK) who oxide in vascular level, that were not adequately elucidated provided an overview of the Tibetan plateau, hypoxia, and as raised by Dr. Mark Gladwin (University of Pittsburgh, inhabitation referring to genomic insights that came out in Pittsburgh,PA,USA).Dr.TatumSimonson(Universityof 2010–2011 which highlighted the adaptive responses to California at San Diego, La Jolla, CA, USA) discussed the high-altitude hypoxia especially the HIF pathway. He effect- genetic basis of high-altitude adaptation especially concen- ively correlated the hypo-responsive HIF pathway to limit trating on a number of publications which emerged in excessive red blood cell production, leading to polycy- 2010–2012, verifying (genetically) the early observations by themia. Then, there were some aspects with current Dr. Cynthia Beall from Case Western Reserve University, globalization and movement, i.e., some of the experimental Cleveland, Ohio, USA (normal range of hemoglobin level data among Tibetans who have been living at sea level for a among well-adapted Sherpas, Tibetans, and Andeas). Al- while. The genetic basis of these migrated Tibetans is prob- though there is remarkable progress and there are a num- ably maintained, but the physiological parameters will have ber of publications in this field, the momentum in search of to be carefully interpreted since many of them most likely genetic basis of high adaptation seems slowed down. There have already spent decades in lowland before they were are few other aspects, i.e., other markers of adaptations, assessed in Dr. Robbins' physiology lab. Dr. Josef Prchal sinceitislesslikelythattheyaretheonlyaspects.There (University of Utah, Salt Lake City, UT, USA) discussed the has not been much work on the different mechanisms of hematological aspects of hypoxia-induced transcriptional adaptations between Tibetan vs Andean high-altitude factors (both up- and down-regulating). Congenital defects dwellers. Similarly, there are other highlanders from and Chuvash polycythemia seem to be perfect examples of Ethiopia and Kyrgyzstan. We do not know if there are dif- hypoxia-sensing mechanism resulting in polycythemia. ferent genetic basis of high adaptations among these Dr. Don McClain (University of Utah, Salt Lake City, UT, groups. The final speaker of the session, Dr. Gladwin USA) covered the metabolic adaptation to high attitude. It (Pittsburgh), discussed the biochemical pathways of nitric seems that the adaptation mechanism has led to relative oxide (NO) and its intravascular oxidation which subse- ‘metabolic inflexibility,’ i.e., the narrow range in the ability quently converted it into an anion nitrite which he won- to shift between glucose and fatty acid oxidation. The car- derfully described how it contributes in physiological diovascular and hematological parameters are no doubt im- vasodilation, blood pressure regulation, and cellular re- portant aspects of physiological basis of high-altitude sponses to stresses like hypoxia and ischemia. The speaker adaptation. But at the same time, the data could be useful dissected the physiological roles of NO (along with nitrite in understanding other chronic lowland diseases, e.g., anion) in vascular and mucosal beds. The experiments Chuvashia polycythemia. After coffee break, ‘The Exercising and data looked promising for application in clinical trials. Hypoxic Brain’ theme began, and Dr. Peter Rasmussen The poster session (I) that day had a number of (University of Copenhagen, Copenhagen, Denmark) dis- topics which spanned from ventilatory responses to cussed about exercise-induced hypocapnia leading to de- hypoxia both in animals and humans (Dr. Barbara creased cerebral blood flow (CBF) based on the hypothesis Morgan, Dr. Jean-Paul Richalet, Dr. Ri-Li Ge, Dr. that fatigue might be from
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