title: Cellular edema regulates tissue capillary perfusion after hemorrhage resuscitation.
abstract: BACKGROUND
  Hemorrhage-induced activation of endothelial cell Na+/H+ -exchanger results in cellular swelling, which physically impedes capillary filling and compromises gut perfusion. We hypothesized that correction of the vascular volume deficit by conventional resuscitation does not improve capillary filling unless cellular swelling is prevented. Also, we hypothesized that adjunctive direct peritoneal resuscitation (DPR) with topical peritoneal dialysis solution (Delflex; Fresenius USA, Inc., Ogden, Ut) enhances capillary filling and gut perfusion by mechanisms that are independent of the Na+/H+ function.
  
  
  METHODS
  In vivo intravital videomicroscopy and Doppler velocimeter were used by us to measure microvascular diameter and flow, capillary filling (index of functional capillary density, FCD), and endothelial cell function in the terminal ileum of anesthetized rats. Rats were bled to 50% mean arterial pressure for 60 min and resuscitated with the shed blood plus 2 volumes of saline (conventional resuscitation). Prevention of endothelial cell swelling was achieved with topical amiloride (specific Na+/H+ inhibitor) in the tissue bath before hemorrhage or simultaneously with conventional resuscitation. DPR was simulated by instillation of Delflex in the tissue bath as adjunctive to conventional resuscitation. Sham no hemorrhage group and a simulated DPR group that received topical amiloride treatment served as controls.
  
  
  RESULTS
  Conventional resuscitation from hemorrhagic shock restored and maintained central hemodynamics but caused progressive and persistent intestinal vasoconstriction and hypoperfusion associated with low FCD and endothelial cell dysfunction. Prevention of endothelial cell swelling when combined with conventional resuscitation, preserved endothelial cell function, and restored local intestinal microvascular variables to near-prehemorrhage levels. Simulated adjunctive DPR produced rapid, sustained, and generalized vasodilation associated with restoration of endothelial cell function, and maximum recruitment of FCD independent of the Na+/H+ -exchanger function.
  
  
  CONCLUSIONS
  Paradoxical endothelial cell swelling occurs early during hemorrhagic shock because of activation of the Na+/H+ exchanger. This cellular edema, which is not resolved by correction of the vascular volume deficit, explains the persistent postresuscitation endothelial cell dysfunction and gut hypoperfusion. Simulated adjunctive DPR in this study reversed endothelial cell swelling and enhanced gut perfusion by mechanisms that are independent of the Na+/H+ exchanger activity.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40292, USA. erzaka01@louisville.edu
authors.forename: El Rasheid
authors.initials: el R
authors.lastname: Zakaria
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Matheson
authors.forename: Richard N
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D002196:Capillaries / Q000502:physiology; D004487:Edema / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D007082:Ileum / Q000098:blood supply* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
chemical_list: D017923:Sodium-Hydrogen Exchangers