Dissociation between skeletal muscle microvascular PO2 and hypoxia-induced microvascular inflammation

Systemic hypoxia (SHx) produces microvascular inflammation in mesenteric, cremasteric, and pial microcirculations. In anesthetized rats, SHx lowers arterial blood pressure ( MABP), which may alter microvascular blood flow and microvascular PO2 (PmO2) and influence SHx-induced leukocyte-endothelial adherence ( LEA). These experiments attempted to determine the individual contributions of the decreases in Pm-O2, venular blood flow and shear rate, and MABP to the hypoxia-induced increase in LEA. Cremaster microcirculation of anesthetized rats was visualized by intravital microscopy. Pm-O2 was measured by a phosphorescence-quenching method. SHx [inspired PO2 of 70 Torr for 10 min, MABP of 65 +/- 3 mmHg, arterial PO2 (Pa-O2) of 33 +/- 1 Torr] and cremaster ischemia (MABP of 111 +/- 7 mmHg, Pa-O2 of 86 +/- 3 Torr) produced similar Pm-O2: 7 +/- 2 and 6 +/- 2 Torr, respectively. However, LEA increased only in SHx (1.9 +/- 0.9 vs. 11.2 +/- 1.1 leukocytes/100 mum, control vs. SHx, P < 0.05). Phentolamine-induced hypotension (MABP of 55 +/- 4 mmHg) in normoxia lowered Pm-O2 to 26 +/- 6 Torr but did not increase LEA. Cremaster equilibration with 95% N-2-5% CO2 during air breathing (Pa-O2 of 80 +/- 1 Torr) lowered Pm-O2 to 6 +/- 1 Torr but did not increase LEA. On the other hand, when cremaster Pm-O2 was maintained at 60 - 70 Torr during SHx (Pa-O2 of 35 +/- 1 Torr), LEA increased from 2.1 +/- 1.1 to 11.1 +/- 1.5 leukocytes/100 mu m (P < 0.05). The results show a dissociation between Pm-O2 and LEA and support the idea that SHx results in the release of a mediator responsible for the inflammatory response.