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O2 Delivery (o2 + delivery)
Selected AbstractsThe effect of hypoxia on pulmonary O2 uptake, leg blood flow and muscle deoxygenation during single-leg knee-extension exerciseEXPERIMENTAL PHYSIOLOGY, Issue 3 2004Darren S. DeLorey The effect of hypoxic breathing on pulmonary O2 uptake (VO2p), leg blood flow (LBF) and O2 delivery and deoxygenation of the vastus lateralis muscle was examined during constant-load single-leg knee-extension exercise. Seven subjects (24 ± 4 years; mean ±s.d.) performed two transitions from unloaded to moderate-intensity exercise (21 W) under normoxic and hypoxic (PETO2= 60 mmHg) conditions. Breath-by-breath VO2p and beat-by-beat femoral artery mean blood velocity (MBV) were measured by mass spectrometer and volume turbine and Doppler ultrasound (VingMed, CFM 750), respectively. Deoxy-(HHb), oxy-, and total haemoglobin/myoglobin were measured continuously by near-infrared spectroscopy (NIRS; Hamamatsu NIRO-300). VO2p data were filtered and averaged to 5 s bins at 20, 40, 60, 120, 180 and 300 s. MBV data were filtered and averaged to 2 s bins (1 contraction cycle). LBF was calculated for each contraction cycle and averaged to 5 s bins at 20, 40, 60, 120, 180 and 300 s. VO2p was significantly lower in hypoxia throughout the period of 20, 40, 60 and 120 s of the exercise on-transient. LBF (l min,1) was approximately 35% higher (P > 0.05) in hypoxia during the on-transient and steady-state of KE exercise, resulting in a similar leg O2 delivery in hypoxia and normoxia. Local muscle deoxygenation (HHb) was similar in hypoxia and normoxia. These results suggest that factors other than O2 delivery, possibly the diffusion of O2, were responsible for the lower O2 uptake during the exercise on-transient in hypoxia. [source] Cardiovascular and Metabolic Effects of High-dose Insulin in a Porcine Septic Shock ModelACADEMIC EMERGENCY MEDICINE, Issue 4 2010Joel S. Holger MD Abstract Objectives:, High-dose insulin (HDI) has inotropic and vasodilatory properties in various clinical conditions associated with myocardial depression. The authors hypothesized that HDI will improve the myocardial depression produced by severe septic shock and have beneficial effects on metabolic parameters. In an animal model of severe septic shock, this study compared the effects of HDI treatment to normal saline (NS) resuscitation alone. Methods:, Ten pigs were randomized to an insulin (HDI) or NS group. All were anesthetized and instrumented to monitor cardiovascular function. In both arms, Escherichia coli endotoxin lipopolysaccharide (LPS) and NS infusions were begun. LPS was titrated to 20 ,g/kg/hour over 30 minutes and continued for 5 hours, and saline was infused at 20 mL/kg/hour throughout the protocol. Dextrose (50%) was infused to maintain glucose in the 60,150 mg/dL range, and potassium was infused to maintain a level greater than 2.8 mmol/L. At 60 minutes, the HDI group received an insulin infusion titrated from 2 to 10 units/kg/hour over 40 minutes and continued at that rate throughout the protocol. Survival, heart rate (HR), mean arterial pressure (MAP), pulmonary artery and central venous pressure, cardiac output, central venous oxygen saturation (SVO2), and lactate were monitored for 5 hours (three pigs each arm) or 7 hours (two pigs each arm) or until death. Cardiac index, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), O2 delivery, and O2 consumption were derived from measured data. Outcomes from the repeated-measures analysis were modeled using a mixed-effects linear model that assumed normally distributed errors and a random effect at the subject level. Results:, No significant baseline differences existed between arms at time 0 or 60 minutes. Survival was 100% in the HDI arm and 60% in the NS arm. Cardiovascular variables were significantly better in the HDI arm: cardiac index (p < 0.001), SVR (p < 0.003), and PVR (p < 0.01). The metabolic parameters were also significantly better in the HDI arm: SVO2 (p < 0.01), O2 delivery (p < 0.001), and O2 consumption (p < 0.001). No differences in MAP, HR, or lactate were found. Conclusions:, In this animal model of endotoxemic-induced septic shock that results in severe myocardial depression, HDI is associated with improved cardiac function compared to NS resuscitation alone. HDI also demonstrated favorable metabolic, pulmonary, and peripheral vascular effects. Further studies may define a potential role for the use of HDI in the resuscitation of septic shock. ACADEMIC EMERGENCY MEDICINE 2010; 17:429,435 © 2010 by the Society for Academic Emergency Medicine [source] Capillary Hemodynamics and Oxygen Pressures in the Aging MicrocirculationMICROCIRCULATION, Issue 4 2006DAVID C. POOLE ABSTRACT Healthy aging acts to redistribute blood flow (Q,) and thus O2 delivery (Q,O2) among and within the exercising muscles such that Q,O2 to highly oxidative muscle fibers may be compromised. Within the microcirculation of old muscles capillary hemodynamics are altered and the matching of Q,O2 to oxidative requirements (V,O2) is impaired such that at exercise onset the microvascular O2 pressure falls below that seen in their younger counterparts. This is important because the microvascular O2 pressure denotes the sole driving force for blood-myocyte O2 transfer and any compromise may slow V,O2 kinetics and reduce exercise tolerance. This review considers the microcirculatory evidence for a reduced perfusive (Q,O2) and diffusive O2 flux within aged muscle and highlights the pressing need for intravital microscopy studies of the muscle microcirculation during exercise. [source] On the mechanisms that limit oxygen uptake during exercise in acute and chronic hypoxia: role of muscle massTHE JOURNAL OF PHYSIOLOGY, Issue 2 2009José A. L. Calbet Peak aerobic power in humans () is markedly affected by inspired O2 tension (). The question to be answered in this study is what factor plays a major role in the limitation of muscle peak in hypoxia: arterial O2 partial pressure () or O2 content ()? Thus, cardiac output (dye dilution with Cardio-green), leg blood flow (thermodilution), intra-arterial blood pressure and femoral arterial-to-venous differences in blood gases were determined in nine lowlanders studied during incremental exercise using a large (two-legged cycle ergometer exercise: Bike) and a small (one-legged knee extension exercise: Knee) muscle mass in normoxia, acute hypoxia (AH) () and after 9 weeks of residence at 5260 m (CH). Reducing the size of the active muscle mass blunted by 62% the effect of hypoxia on in AH and abolished completely the effect of hypoxia on after altitude acclimatization. Acclimatization improved Bike peak exercise from 34 ± 1 in AH to 45 ± 1 mmHg in CH (P < 0.05) and Knee from 38 ± 1 to 55 ± 2 mmHg (P < 0.05). Peak cardiac output and leg blood flow were reduced in hypoxia only during Bike. Acute hypoxia resulted in reduction of systemic O2 delivery (46 and 21%) and leg O2 delivery (47 and 26%) during Bike and Knee, respectively, almost matching the corresponding reduction in . Altitude acclimatization restored fully peak systemic and leg O2 delivery in CH (2.69 ± 0.27 and 1.28 ± 0.11 l min,1, respectively) to sea level values (2.65 ± 0.15 and 1.16 ± 0.11 l min,1, respectively) during Knee, but not during Bike. During Knee in CH, leg oxygen delivery was similar to normoxia and, therefore, also in spite of a of 55 mmHg. Reducing the size of the active muscle mass improves pulmonary gas exchange during hypoxic exercise, attenuates the Bohr effect on oxygen uploading at the lungs and preserves sea level convective O2 transport to the active muscles. Thus, the altitude-acclimatized human has potentially a similar exercising capacity as at sea level when the exercise model allows for an adequate oxygen delivery (blood flow ×), with only a minor role of per se, when is more than 55 mmHg. [source] During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory levelTHE JOURNAL OF PHYSIOLOGY, Issue 1 2008Carsten Lundby To test the hypothesis that the increased sympathetic tonus elicited by chronic hypoxia is needed to match O2 delivery with O2 demand at the microvascular level eight male subjects were investigated at 4559 m altitude during maximal exercise with and without infusion of ATP (80 ,g (kg body mass),1 min,1) into the right femoral artery. Compared to sea level peak leg vascular conductance was reduced by 39% at altitude. However, the infusion of ATP at altitude did not alter femoral vein blood flow (7.6 ± 1.0 versus 7.9 ± 1.0 l min,1) and femoral arterial oxygen delivery (1.2 ± 0.2 versus 1.3 ± 0.2 l min,1; control and ATP, respectively). Despite the fact that with ATP mean arterial blood pressure decreased (106.9 ± 14.2 versus 83.3 ± 16.0 mmHg, P < 0.05), peak cardiac output remained unchanged. Arterial oxygen extraction fraction was reduced from 85.9 ± 5.3 to 72.0 ± 10.2% (P < 0.05), and the corresponding venous O2 content was increased from 25.5 ± 10.0 to 46.3 ± 18.5 ml l,1 (control and ATP, respectively, P < 0.05). With ATP, leg arterial,venous O2 difference was decreased (P < 0.05) from 139.3 ± 9.0 to 116.9 ± 8.4,1 and leg was 20% lower compared to the control trial (1.1 ± 0.2 versus 0.9 ± 0.1 l min,1) (P= 0.069). In summary, at altitude, some degree of vasoconstriction is needed to match O2 delivery with O2 demand. Peak cardiac output at altitude is not limited by excessive mean arterial pressure. Exercising leg is not limited by restricted vasodilatation in the altitude-acclimatized human. [source] Regulation of lactate production at the onset of ischaemia is independent of mitochondrial NADH/NAD+: insights from in silico studiesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Lufang Zhou Ischaemia decreases mitochondrial NADH oxidation, activates glycolysis, increases the NADH/NAD+ ratio, and causes lactate production. The mechanisms that regulate anaerobic glycolysis and the NADH/NAD+ ratio during ischaemia are unclear. Although continuous measurements of metabolic fluxes and NADH/NAD+ in cytosol and mitochondria are not possible in vivo with current experimental techniques, computational models can be used to predict these variables by simulations with in silico experiments. Such predictions were obtained using a mathematical model of cellular metabolism in perfused myocardium. This model, which distinguishes cytosolic and mitochondrial domains, incorporates key metabolic species and processes associated with energy transfer. Simulation of metabolic responses to mild, moderate and severe ischaemia in large animals showed that mitochondrial NADH/NAD+ was rapidly reset to higher values in proportion to the reduced O2 delivery and myocardial oxygen consumption . Cytosolic NADH/NAD+, however, showed a biphasic response, with a sharp initial increase that was due to activation of glycogen breakdown and glycolysis, and corresponded with lactate production. Whereas the rate of glycolysis and the malate,aspartate shuttle had a significant effect on the cytosolic NADH/NAD+, their effects on the mitochondrial NADH/NAD+ were minimal. In summary, model simulations of the metabolic response to ischaemia showed that mitochondrial NADH/NAD+ is primarily determined by O2 consumption, while cytosolic NADH/NAD+ is largely a function of glycolytic flux during the initial phase, and is determined by mitochondrial NADH/NAD+ and the malate,aspartate shuttle during the steady state. [source] Improved Outcomes in Islet Isolation and Transplantation by the Use of a Novel Hemoglobin-based O2 CarrierAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2006J. G. Avila During isolation, islets are exposed to warm ischemia. In this study, intraductal administration of oxygenated polymerized, stroma-free hemoglobin-pyridoxalated (Poly SFH-P) was performed to improve O2 delivery. Rat pancreata subjected to 30-min warm ischemia were perfused intraductally with collagenase in oxygenated Poly SFH-P/RPMI or RPMI (control). PO2 was increased by Poly SFH-P (381.7 ± 35.3 mmHg vs. 202.3 ± 28.2, p = 0.01) and pH maintained within physiological range (7.4,7.2 vs. 7.1,6.6, p = 0.009). Islet viability (77%± 4.6 vs. 63%± 4.7, p = 0.04) was improved and apoptosis lower with Poly SFH-P (caspase-3: 34,714 ± 2167 vs. 45,985 ± 1382, respectively, p = 0.01). Poly SFH-P improved islet responsiveness to glucose as determined by increased intracellular Ca2+ levels and improved insulin secretion (SI 5.4 ± 0.1 vs. 3.1 ± 0.2, p = 0.03). Mitochondrial integrity was improved in Poly SFH-P-treated islets, which showed higher percentage change in membrane potential after glucose stimulation (14.7%± 1.8 vs. 9.8 ± 1.4, respectively, p < 0.05). O2 delivery by Poly SFH-P did not increase oxidative stress (GSH 7.1 ± 2.9 nm/mg protein for Poly SFH-P vs. 6.8 ± 2.4 control, p = 0.9) or oxidative injury (MDA 1.8 ± 0.9 nmol/mg protein vs. 6.2 ± 2.4, p = 0.19). Time to reach normoglycemia in transplanted diabetic nude mice was shorter (1.8 ± 0.4 vs. 7 ± 2.5 days, p = 0.02), and glucose tolerance improved in the Poly SFH-P group (AUC 8106 ± 590 vs. 10,863 ± 946, p = 0.03). Oxygenated Poly SFH-P improves islet isolation and transplantation outcomes by preserving mitochondrial integrity. [source] Liposome-Encapsulated Hemoglobin Reduces the Size of Cerebral Infarction in Rats: Effect of Oxygen AffinityARTIFICIAL ORGANS, Issue 2 2009Dai Fukumoto Abstract Liposome-encapsulated hemoglobin (LEH) with a low oxygen affinity (l-LEH, P50 = 45 mm Hg) was found to be protective in the rodent and primate models of ischemic stroke. This study investigated the role of LEH with a high O2 affinity (h-LEH, P50 = 10 mm Hg) in its protective effect on brain ischemia. The extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving various doses of h-LEH as well as l-LEH. Both h-LEH and l-LEH significantly reduced the extent of cortical infarction. h-LEH remained protective at a lower concentration (minimal effective dose [MED]: 0.08 mL/kg) than l-LEH (MED: 2 mL/kg) in the cortex. h-LEH reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas l-LEH provided no significant protection. h-LEH provided better protection than l-LEH. The protective effect of both high- and low-affinity LEH may suggest the importance of its small particle size (230 nm) as compared to red blood cells. The superiority of h-LEH over l-LEH supports an optimal O2 delivery to the ischemic penumbra as the mechanism of action in protecting against brain ischemia and reperfusion. [source] HYPERBARIC OXYGENATION APPLIED IMMEDIATELY AFTER CORONARY OCCLUSION REDUCES MYOCARDIAL NECROSIS AND ACUTE MORTALITY IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2009Leonardo Dos Santos SUMMARY 1Because in ischaemia there is a critical lack of O2, it has been reasoned that increasing O2 delivery to the ischaemic myocardium could serve as adjunctive therapy for acute myocardial infarction (MI). Accordingly, in the present study, the effect of early hyperbaric oxygenation (HBO) on mortality and MI size after coronary occlusion was examined in rats. 2After coronary occlusion, male Wistar rats were randomly assigned to receive either HBO for 1 h in a hyperbaric chamber (100% O2 at 253 kPa; n = 106) or ambient O2 as the control (n = 111). The extent of myocardial necrosis was assessed (triphenyltetrazolium) immediately after treatment in the HBO (n = 50) and control (n = 47) groups. The remaining rats were evaluated 24 h after occlusion to enable calculation of MI size and mortality. 3Immediately after therapy, the size of the MI was significantly greater in the control group compared with that in the HBO group (40 ± 3 vs 27 ± 2% of the left ventricle (LV), respectively; P < 0.001). The 24 h mortality of control rats was higher than that of HBO rats (34 vs 16%, respectively; P = 0.02). Control rats that survived 24 h had a larger MI than did HBO rats that survived 24 h (40 ± 4 vs 29 ± 3% of the LV, respectively; P = 0.005). Furthermore, large necrotic areas (> 40% of the LV) were more frequent in control than HBO rats (55 vs 27% of infarcted hearts, respectively; P = 0.01). There was less pulmonary congestion observed in HBO rats compared with control rats. 4In conclusion, early therapy with HBO during the onset of an acute ischaemic event decreases the necrotic area and reduces acute mortality. These data support further investigation of HBO as an adjuvant therapy for acute MI. [source] | |||||||||||||