Microvascular transport and endothelial cell alterations preceding skeletal muscle damage in ischemia and reperfusion injury.
We determined the leakage of macromolecules using FITC-dextran-150 as a tracer and measured the extent of no-reflow phenomenon by video field analysis. The cremaster muscle of anesthetized rats was fashioned as a single layer, splayed on a lucite chamber and suffused with bicarbonate solution at 35 degrees C. After a 1 hour period of baseline data collection, ischemia was produced by cross-clamping the cremasteric vascular pedicle for periods of 30 minutes and 2 hours in separate experiments. Macromolecular leakage was visualized after reinstitution of perfusion. Leakage occurred at postcapillary venules 15 to 50 micron in diameter and quickly spread to the interstitium. The magnitude of leakage decreased as a function of time with continuous buffer suffusion, but remained higher than in the control period. No reflow occurred in approximately 30 percent of the muscle microvasculature upon reperfusion. The no-reflow values at 30 minute and 2 hour periods of ischemia were significantly different from the control values but were not from each other. Electron micrographs demonstrated endothelial cell swelling and migration of leukocytes and normal myocytes after 1 hour of reperfusion following 2 hours of ischemia. Our results demonstrate that permeability changes, occurrence of no reflow, and leukocyte migration precede the onset of damage to skeletal muscle in ischemia and reperfusion injury.
D000818:Animals; D002199:Capillary Permeability; D002465:Cell Movement; D003911:Dextrans; D004727:Endothelium / Q000473:pathology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins; D007511:Ischemia / Q000473:pathology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000473:pathology; D008854:Microscopy, Electron; D009132:Muscles / Q000098:blood supply*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D003911:Dextrans; D005452:Fluoresceins; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate