title: Systemic blood acidosis in low-flow ischemia induces capillary luminal narrowing.
abstract: Earlier studies demonstrated swelling of endothelial cells in skeletal muscle capillaries during hemorrhagic shock with involvement of a pH- and amiloride-sensitive Na+/H+ antiport. The aim of this study was to determine the degree to which diminished capillary perfusion and metabolic acidosis are mechanisms for capillary narrowing. Capillary luminal diameters and microcirculatory blood flow were measured in the rabbit tenuissimus and gastrocnemius muscles, respectively. In seven experiments, occlusion of the distal aorta produced a low-flow state in the hind limbs as assessed by laser Doppler flowmetry (LDF). The 68.5 +/- 12.2% reduction in LDF flow in this local model of skeletal muscle ischemia was comparable to that in shock. After 1 h, systemic blood pH stayed the same, yet local tissue pH (venous effluent) became acidic. There was no capillary narrowing in contrast to an approximate 20% decrease in diameter found in shock. In additional experiments to simulate shock acidosis, the blood pH was reduced over 1 h by jugular vein infusion of hydrochloric acid (1.2 M, 4 ml.min-1.kg-1), with (n = 5) and without (n = 6) pretreatment with an amiloride analog [5-(N,N-hexamethylene)amiloride] specific to block Na+/H+ exchange. Mean arterial blood pressure and LDF flow were essentially unchanged in both groups. Diameters of treated capillaries did not change, whereas those of untreated capillaries decreased by 18.0 +/- 3.5% which would greatly elevate flow resistance. These results taken together suggest that systemic blood acidosis, and not low flow per se, induces a capillary narrowing which we contend is due to endothelial cell swelling.
authors.affiliation: Institute for Biomedical Engineering, University of California at San Diego, La Jolla 92093-0412.
authors.forename: M C
authors.initials: MC
authors.lastname: Mazzoni
authors.forename: E J
authors.initials: EJ
authors.lastname: Cragoe
authors.forename: K E
authors.initials: KE
authors.lastname: Arfors
mesh_terms: D000138:Acidosis / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000473:pathology*; D002200:Capillary Resistance / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D007511:Ischemia / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation; D009132:Muscles / Q000098:blood supply*; D011817:Rabbits; D014661:Vasoconstriction
chemical_list: D000584:Amiloride