The purpose of this study is to test certain hypotheses regarding the acute and chronic effects of intermittent hypoxia on microvascular and parenchymal cell function through in vivo microcirculatory studies. Using the cremaster muscle preparation of the anesthetized rat, Specific Aim 1 will test the hypothesis that reduction of oxygen concentration in the inspired air in the range of 7 percent to 10 percent for 30 s to 3 min duration causes microcirculatory hypoxia and changes in blood flow and vascular tone due to neural influences and local regulatory mechanisms.
This aim will also test the hypothesis that chronic episodes of hypoxia alter normal control mechanisms that regulate vascular tone of arterioles in accordance with local oxygen levels; specifically prostaglandins, NO and metabolites of cytochrome P-450.
Specific Aim 2 will test the hypothesis that reduction of oxygen in the inspired air causes oxygen levels in tissue surrounding the venous portion of the microvascular network to fall below critical levels, causing a shift in the redox state of mitochondria in the parenchymal cells.
This aim will also test the hypothesis that intermittent hypoxia leads to tissue injury and increased expression of venular P-selectin, leukocyte adhesion and rolling oxidative stress, and parenchymal cell injury and death. Since some of the changes seen in sleep hypoxia are neural in origin, a subset of these studies will involve use of unanesthetized animals with an implanted window to study the microcirculation. By reproducing the hypoxic conditions in the microcirculation and tissue like present in sleep apnea, the investigators aim to identify key changes and provide a better rationale for treatment.
| Toth, Andras; Pal, Miklos; Intaglietta, Marcos et al. (2007) Contribution of anaerobic metabolism to reactive hyperemia in skeletal muscle. Am J Physiol Heart Circ Physiol 292:H2643-53 |
| Johnson, Paul C; Vandegriff, Kim; Tsai, Amy G et al. (2005) Effect of acute hypoxia on microcirculatory and tissue oxygen levels in rat cremaster muscle. J Appl Physiol 98:1177-84 |
| Saltzman, Darin J; Toth, Andras; Tsai, Amy G et al. (2003) Oxygen tension distribution in postcapillary venules in resting skeletal muscle. Am J Physiol Heart Circ Physiol 285:H1980-5 |
| Tsai, Amy G; Johnson, Paul C; Intaglietta, Marcos (2003) Oxygen gradients in the microcirculation. Physiol Rev 83:933-63 |
