Ischemia-reperfusion injury in the isolated rat lung. Role of flow and endogenous leukocytes.
Microvascular lung injury caused by ischemia-reperfusion (IR) may occur via leukocyte-dependent and leukocyte-independent pathways. Leukocyte-endothelial adhesion may be a rate-limiting step in IR lung injury. Leukocyte adhesion to microvascular endothelium occurs when the attractant forces between leukocyte and endothelium are greater than the kinetic energy of the leukocyte and the vascular wall shear rate. We hypothesized (1) that isolated, buffer-perfused rat lungs are not free of endogenous leukocytes, (2) that endogenous leukocytes contribute to IR-induced microvascular injury as measured by the capillary filtration coefficient (Kfc), and (3) that a reduction of perfusate flow rate would potentiate leukocyte-dependent IR injury. Sixty lungs were divided into four groups: (1) low-flow controls, (2) high-flow controls, (3) low-flow IR, and (4) high-flow IR. Microvascular injury was linearly related to baseline perfusate leukocyte concentrations at both low (r = 0.78) and high (r = 0.82) flow rates. Kfc in the high-flow IR group (0.58 +/- 0.03 ml/min/cm H2O/100 g) was less (p < 0.05) than Kfc in the low-flow IR group (0.82 +/- 0.07), and in both groups Kfc values were significantly greater than low-flow (0.34 +/- 0.03) and high-flow (0.31 +/- 0.01) control Kfc values after 75 min. Retention of leukocytes in the lung, evaluated by a tissue myeloperoxidase assay, was greatest in the low-flow IR group. We conclude (1) that isolated, buffer-perfused rat lungs contain significant quantities of leukocytes and that these leukocytes contribute to IR lung injury, and (2) that IR-induced microvascular injury is potentiated by low flow.
Seibert
A F
AF
Department of Medicine, University of South Alabama, Mobile.
Haynes
J
J
Taylor
A
A
D000704:Analysis of Variance; D000818:Animals; D066298:In Vitro Techniques; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008168:Lung / Q000098:blood supply* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D010477:Perfusion / Q000379:methods; D009195:Peroxidase / Q000032:analysis; D011669:Pulmonary Wedge Pressure; D051381:Rats; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology
D009195:Peroxidase