Annual Update in Intensive Care and Emergency Medicine, 2015
Extreme exercise has been used to study how normal physiology responds to states that resemble cr... more Extreme exercise has been used to study how normal physiology responds to states that resemble critical illness, such as hypoxemia and hypovolemia. Studies of the Extreme Everest Research Group have shown that the body can tolerate hypoxemia by using adaptation mechanisms. One of these mechanisms was found in lowlanders who climbed Mount Everest, mirroring the hypoxemia in critical illness. There was an increase in nitric oxide (NO) in the blood in response to the hypoxic environment. These enhanced NO levels were associated with changes in microcirculatory blood flow, which may affect local tissue oxygen delivery (DO2) [1]. Indeed extreme exercise can protect the body by adapting to cope with the hypoxic environment. This is seen in skeletal muscle function, with high altitude hypoxia inducing skeletal muscle atrophy despite unchanged exercise metabolites [2]. Another adaptation is seen in gluco-insular regulation, in which, despite an increase in insulin resistance in sustained hypoxia, glucose levels remain stable [3]. From these considerations, it can be concluded that lessons can be learned, which may be relevant to critically ill patients who need to cope with tissue hypoxia. Indeed, fitness and exercise might even hold potential lessons on how to ‘train’ patients to cope with surgery and critical illness. This chapter explores this idea and speculates on how such insight might benefit patients in need of surgery and at risk for critical illness.
American Journal of Physiology-Cell Physiology, 1992
Glibenclamide, a known selective inhibitor of ATP-sensitive potassium channels, was infused into ... more Glibenclamide, a known selective inhibitor of ATP-sensitive potassium channels, was infused into the coronary vasculature of anesthetized dogs and of isolated perfused rabbit hearts to assess the role of this channel in the maintenance of basal coronary resistance. Infusion of glibenclamide at a concentration of 55-80 microM in the dogs resulted in a twofold steady-state increase in coronary resistance with resultant tissue ischemia. Infusion of 1 microM glibenclamide in the isolated hearts resulted in a 67% increase in coronary resistance with resultant tissue ischemia. The ischemic changes were reversible upon removal of the drug. These findings indicate that the ATP-sensitive K+ channel plays a significant role in the maintenance of basal coronary resistance in vivo. Higher concentrations of glibenclamide (80-100 microM) in the in vivo dog heart consistently gave rise to an oscillating pattern of coronary flow. These oscillations were either eliminated or decreased in amplitude a...
The ultimate purpose of fluid administration in states of hypovolemia is to correct cardiac outpu... more The ultimate purpose of fluid administration in states of hypovolemia is to correct cardiac output to improve microcirculatory perfusion and tissue oxygenation. Observation of the microcirculation using handheld microscopes gives insight into the nature of convective and diffusive defect in hypovolemia. The purpose of this article is to introduce a new platform for hemodynamic-targeted fluid therapy based on the correction of tissue and microcirculatory perfusion assumed to be at risk during hypovolemia. Targeting systemic hemodynamic targets and/or clinical surrogates of hypovolemia gives inadequate guarantee for the correction of tissue perfusion by fluid therapy especially in conditions of distributive shock as occur in inflammation and sepsis. Findings are presented, which support the idea that only clinical signs of hypovolemia associated with low microcirculatory flow can be expected to benefit from fluid therapy and that fluid overload causes a defect in the diffusion of oxyg...
Signal Transduction — Single Cell Techniques, 1998
Cell physiological investigations in single living cells have provided much insight into the unde... more Cell physiological investigations in single living cells have provided much insight into the underlying mechanisms of the functional activities of cells and their components in health and disease. The advantage of investigating living cells is that it provides the investigator with the opportunity of following the sequence of physiological events in time. This is in contrast to a histological approach in which a physiological process is frozen in time and analyzed in detail. In addition, physiological studies on populations of cells fail to detect the kinetics of these processes in the individual cell and the intercellular differences which are no doubt present.
The aim of this study was to test the hypothesis that obstructive sleep apnea syndrome (OSAS) exh... more The aim of this study was to test the hypothesis that obstructive sleep apnea syndrome (OSAS) exhibits oxidative stress and inflammation in patients who have a congenital, craniofacial anomaly.This prospective, cross-sectional cohort study included ambulant sleep study data to asses OSAS in patients with syndromic craniosynostosis and Treacher Collins syndrome. Laboratory analyses were performed including malondialdehyde, tumor necrosis factor α (TNF-α), interleukin 6, and high-sensitivity C-reactive protein.Forty-eight patients were included; 11 were adults; 37 were children. The patients' body mass indexes were normal, with a median (SD) of 0.7 (-1.82 to 2.48) in children and 20.5 (15.2-29.4) in adults. Obstructive sleep apnea syndrome was diagnosed in 23 of 48 patients. It was mild (median obstructive apnea-hypopnea index [oAHI], 2.3; oxygenation-desaturation index [ODI], 0.9) in 16 patients and moderate/severe in 7 patients (median oAHI, 10.8; ODI, 5.0). Neither oxidative stress nor inflammation had a correlation with the oAHI and ODI. Only TNF-α was found significantly higher in both the OSAS and non-OSAS groups compared with the reference values (median, 15.1 pg/mL and 12.3 pg/mL versus 4.05 [0.0-8.1 pg/mL], P < 0.001 and P < 0.001, respectively).Based on our findings we conclude that (mainly mild) OSAS, oxidative stress, as well as high-sensitivity C-reactive protein and interleukin 6 levels are not abnormal in the day time in a population of nonobese patients with a craniofacial anomaly. The increased level of TNF-α cannot be explained by OSAS. Future research should focus on mapping chronobiologic changes for further interpretation of the results.
Annual Update in Intensive Care and Emergency Medicine, 2015
Extreme exercise has been used to study how normal physiology responds to states that resemble cr... more Extreme exercise has been used to study how normal physiology responds to states that resemble critical illness, such as hypoxemia and hypovolemia. Studies of the Extreme Everest Research Group have shown that the body can tolerate hypoxemia by using adaptation mechanisms. One of these mechanisms was found in lowlanders who climbed Mount Everest, mirroring the hypoxemia in critical illness. There was an increase in nitric oxide (NO) in the blood in response to the hypoxic environment. These enhanced NO levels were associated with changes in microcirculatory blood flow, which may affect local tissue oxygen delivery (DO2) [1]. Indeed extreme exercise can protect the body by adapting to cope with the hypoxic environment. This is seen in skeletal muscle function, with high altitude hypoxia inducing skeletal muscle atrophy despite unchanged exercise metabolites [2]. Another adaptation is seen in gluco-insular regulation, in which, despite an increase in insulin resistance in sustained hypoxia, glucose levels remain stable [3]. From these considerations, it can be concluded that lessons can be learned, which may be relevant to critically ill patients who need to cope with tissue hypoxia. Indeed, fitness and exercise might even hold potential lessons on how to ‘train’ patients to cope with surgery and critical illness. This chapter explores this idea and speculates on how such insight might benefit patients in need of surgery and at risk for critical illness.
American Journal of Physiology-Cell Physiology, 1992
Glibenclamide, a known selective inhibitor of ATP-sensitive potassium channels, was infused into ... more Glibenclamide, a known selective inhibitor of ATP-sensitive potassium channels, was infused into the coronary vasculature of anesthetized dogs and of isolated perfused rabbit hearts to assess the role of this channel in the maintenance of basal coronary resistance. Infusion of glibenclamide at a concentration of 55-80 microM in the dogs resulted in a twofold steady-state increase in coronary resistance with resultant tissue ischemia. Infusion of 1 microM glibenclamide in the isolated hearts resulted in a 67% increase in coronary resistance with resultant tissue ischemia. The ischemic changes were reversible upon removal of the drug. These findings indicate that the ATP-sensitive K+ channel plays a significant role in the maintenance of basal coronary resistance in vivo. Higher concentrations of glibenclamide (80-100 microM) in the in vivo dog heart consistently gave rise to an oscillating pattern of coronary flow. These oscillations were either eliminated or decreased in amplitude a...
The ultimate purpose of fluid administration in states of hypovolemia is to correct cardiac outpu... more The ultimate purpose of fluid administration in states of hypovolemia is to correct cardiac output to improve microcirculatory perfusion and tissue oxygenation. Observation of the microcirculation using handheld microscopes gives insight into the nature of convective and diffusive defect in hypovolemia. The purpose of this article is to introduce a new platform for hemodynamic-targeted fluid therapy based on the correction of tissue and microcirculatory perfusion assumed to be at risk during hypovolemia. Targeting systemic hemodynamic targets and/or clinical surrogates of hypovolemia gives inadequate guarantee for the correction of tissue perfusion by fluid therapy especially in conditions of distributive shock as occur in inflammation and sepsis. Findings are presented, which support the idea that only clinical signs of hypovolemia associated with low microcirculatory flow can be expected to benefit from fluid therapy and that fluid overload causes a defect in the diffusion of oxyg...
Signal Transduction — Single Cell Techniques, 1998
Cell physiological investigations in single living cells have provided much insight into the unde... more Cell physiological investigations in single living cells have provided much insight into the underlying mechanisms of the functional activities of cells and their components in health and disease. The advantage of investigating living cells is that it provides the investigator with the opportunity of following the sequence of physiological events in time. This is in contrast to a histological approach in which a physiological process is frozen in time and analyzed in detail. In addition, physiological studies on populations of cells fail to detect the kinetics of these processes in the individual cell and the intercellular differences which are no doubt present.
The aim of this study was to test the hypothesis that obstructive sleep apnea syndrome (OSAS) exh... more The aim of this study was to test the hypothesis that obstructive sleep apnea syndrome (OSAS) exhibits oxidative stress and inflammation in patients who have a congenital, craniofacial anomaly.This prospective, cross-sectional cohort study included ambulant sleep study data to asses OSAS in patients with syndromic craniosynostosis and Treacher Collins syndrome. Laboratory analyses were performed including malondialdehyde, tumor necrosis factor α (TNF-α), interleukin 6, and high-sensitivity C-reactive protein.Forty-eight patients were included; 11 were adults; 37 were children. The patients' body mass indexes were normal, with a median (SD) of 0.7 (-1.82 to 2.48) in children and 20.5 (15.2-29.4) in adults. Obstructive sleep apnea syndrome was diagnosed in 23 of 48 patients. It was mild (median obstructive apnea-hypopnea index [oAHI], 2.3; oxygenation-desaturation index [ODI], 0.9) in 16 patients and moderate/severe in 7 patients (median oAHI, 10.8; ODI, 5.0). Neither oxidative stress nor inflammation had a correlation with the oAHI and ODI. Only TNF-α was found significantly higher in both the OSAS and non-OSAS groups compared with the reference values (median, 15.1 pg/mL and 12.3 pg/mL versus 4.05 [0.0-8.1 pg/mL], P < 0.001 and P < 0.001, respectively).Based on our findings we conclude that (mainly mild) OSAS, oxidative stress, as well as high-sensitivity C-reactive protein and interleukin 6 levels are not abnormal in the day time in a population of nonobese patients with a craniofacial anomaly. The increased level of TNF-α cannot be explained by OSAS. Future research should focus on mapping chronobiologic changes for further interpretation of the results.
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