American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Aug 2007
Effects of erythrocyte flexibility on microvascular perfusion and oxygenation during acute anemia.
Responses to exchange transfusion using red blood cells (RBCs) with normal and reduced flexibility were studied in the hamster window chamber model during acute moderate isovolemic hemodilution to determine the role of RBC membrane stiffness in microvascular perfusion and tissue oxygenation. Erythrocyte stiffness was increased by 30-min incubation in 0.02% glutaraldehyde solution, and unreacted glutaraldehyde was completely removed. Filtration pressure through 5-microm pore size filters was used to quantify stiffness of the RBCs. ⋯ Microvascular tissue Po(2) was significantly lower for Dex70 and GRBC vs. RBC groups and the moderate hemodilution condition. Results were attributed to decreased oxygen uploading in the lungs and obstruction of tissue capillaries by rigidified RBCs, indicating that the effects impairing RBC flexibility are magnified at the microvascular level, where perfusion and oxygenation may define transfusion outcome.
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Am. J. Physiol. Heart Circ. Physiol. · Jul 2007
Evaluation of a noninvasive continuous cardiac output monitoring system based on thoracic bioreactance.
Noninvasive cardiac output (CO) measurement can be useful in many clinical settings where invasive monitoring is not desired. Bioimpedance (intrabeat measurement of changes in transthoracic voltage amplitude in response to an injected high-frequency current) has been explored for this purpose but is limited in some clinical settings because of inherently low signal-to-noise ratio. Since changes in fluid content also induce changes in thoracic capacitive and inductive properties, we tested whether a noninvasive CO measurement could be obtained through measurement of the relative phase shift of an injected current (i.e., bioreactance). ⋯ The measurements of noninvasive CO measurement and cardiopulmonary bypass pump correlated to each other (r = 0.84) despite the large variation in CO and temperatures. Similarly, in patients, mean CO values were 5.18 and 5.17 l/min as measured by SGC and the noninvasive CO measurement system, respectively, and were highly correlated over the range of values studied (r = 0.90). Preclinical and clinical data demonstrate the feasibility of using blood flow-related phase shifts of transthoracic electric signals to perform noninvasive continuous CO monitoring.
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Am. J. Physiol. Heart Circ. Physiol. · Jun 2007
Rho kinase activation plays a major role as a mediator of irreversible injury in reperfused myocardium.
Intracellular signal transduction events in reperfusion following ischemia influence myocardial infarct development. Here we investigate the role of Rho kinase (ROCK) activation as a specific injury signal during reperfusion via attenuation of the reperfusion injury salvage kinase (RISK) pathway phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric oxide (NO) synthase (eNOS). Rat isolated hearts underwent 35 min of left coronary artery occlusion and 120 min of reperfusion. ⋯ Inhibition of ROCK activation at reperfusion reduced the proportion of TUNEL-positive nuclei in the infarcted region. In conclusion, ROCK activation occurs specifically during early reperfusion. Inhibition of ROCK at reperfusion onset limits infarct size through an Akt/eNOS-dependent mechanism, suggesting that ROCK activation at reperfusion may be deleterious through suppression of the RISK pathway.
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Am. J. Physiol. Heart Circ. Physiol. · Jun 2007
Cardioprotection by adenosine A2A agonists in a canine model of myocardial stunning produced by multiple episodes of transient ischemia.
We sought to determine whether administration of a very low, nonvasodilating dose of a highly selective adenosine A(2A) receptor agonist (ATL-193 or ATL-146e) would be cardioprotective in a canine model of myocardial stunning produced by multiple episodes of transient ischemia. Twenty-four anesthetized open-chest dogs underwent either 4 (n=12) or 10 cycles (n=12) of 5-min left anterior descending coronary artery (LAD) occlusions interspersed by 5 or 10 min of reperfusion. Left ventricular thickening was measured from baseline through 180 min after the last occlusion-reperfusion cycle. ⋯ During occlusion, there was severe dyskinesis with marked LAD zone thinning in all animals. After 180 min of reperfusion following the last cycle, significantly greater recovery of LAD zone thickening was observed in A(2A) receptor agonist-treated vs. control animals in both the 4-cycle (91 +/- 7 vs. 56 +/- 12%, respectively; P<0.05) and the 10-cycle (65 +/- 9 vs. 8 +/- 16%, respectively; P<0.05) occlusion groups. The striking amount of functional recovery observed with administration of low, nonvasodilating doses of adenosine A(2A) agonist ATL-193 or ATL-146e supports their further evaluation for the attenuation of postischemic stunning in the clinical setting.
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Am. J. Physiol. Heart Circ. Physiol. · Jun 2007
Apoptotic signaling induces hyperpermeability following hemorrhagic shock.
Hemorrhagic shock (HS) disrupts the endothelial cell barrier, resulting in microvascular hyperpermeability. Recent studies have also demonstrated that activation of the apoptotic signaling cascade is involved in endothelial dysfunction, which may result in hyperpermeability. Here we report involvement of the mitochondrial "intrinsic" pathway in microvascular hyperpermeability following HS in rats. ⋯ This, along with the in vivo transfection of the proapoptotic peptide BAK (BH3), resulted in hyperpermeability (as visualized by intravital microscopy), release of mitochondrial cytochrome c into the cytoplasm, and activation of caspase-3. Conversely, transfection of the BAK (BH3) mutant had no effect on hyperpermeability. Together, these results demonstrate involvement of the mitochondrial intrinsic apoptotic pathway in HS-induced hyperpermeability and that the attenuation of this pathway may provide an alternative strategy in preserving vascular barrier integrity.