title: Direct peritoneal resuscitation from hemorrhagic shock: effect of time delay in therapy initiation.
abstract: BACKGROUND
  After conventional resuscitation from hemorrhagic shock, splanchnic microvessels progressively constrict, leading to impairment of blood flow. This occurs despite restoration and maintenance of central hemodynamics. The authors' recent studies have demonstrated that topical and continuous ex vivo exposure of the gut microvasculature to a glucose-based clinical peritoneal dialysis solution (Delflex), as a technique of direct peritoneal resuscitation (DPR), can prevent these postresuscitation events when initiated simultaneously with conventional resuscitation. This study aimed to determine whether DPR applied after conventional resuscitation reverses the established postresuscitation intestinal vasoconstriction and hypoperfusion.
  
  
  METHODS
  Male Sprague-Dawley rats were bled to 50% of baseline mean arterial pressure and resuscitated intravenously over 30 minutes with the shed blood returned plus two times the shed blood volume of saline. Initiation of ex vivo, topical DPR was delayed to 2 hours (group 1, n = 8), or to 4 hours (group 2, n = 8), respectively, after conventional resuscitation. Intravital microscopy and Doppler velocimetry were used to measure terminal ileal microvascular diameters of inflow A1 and premucosal A3 (proximal pA3, distal dA3) arterioles and blood flow in the A1 arteriole, respectively. Maximum arteriolar dilation capacity was obtained from the topical application, in the tissue bath, of the endothelium-independent nitric oxide-donor sodium nitroprusside (10M).
  
  
  RESULTS
  Hemorrhagic shock caused a selective vasoconstriction of A1 (-24.1% +/- 2.15%) arterioles from baseline, which was not seen in A3 vessels. This caused A1 blood flow to drop by -68.6% of the prehemorrhage value. Conventional resuscitation restored and maintained hemodynamics in all the animals without additional fluid therapy. In contrast, there was a generalized and progressive postresuscitation vasoconstriction of A1 (-21.7%), pA3 (-18.5%), and dA3 (-18.7%) vessels. The average postresuscitation A1 blood flow was -49.5% of the prehemorrhage value, indicating a persistent postresuscitation hypoperfusion. Direct peritoneal resuscitation reversed the postresuscitation vasoconstriction by 40.9% and enhanced A1 blood flow by 112.9% of the respective postresuscitation values.
  
  
  CONCLUSIONS
  Delayed DPR reverses the gut postresuscitation vasoconstriction and hypoperfusion regardless of the initiation time. This occurs without adverse effects on hemodynamics. Direct peritoneal resuscitation-mediated enhancement of tissue perfusion results from the local effects from the vasoactive components of the Delflex solution, which are hyperosmolality, lactate buffer anion, and, to a lesser extent, low pH. The molecular mechanism of this vasodilation effect needs further investigation.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville, Kentucky 40292, USA. drelzak@aol.com
authors.forename: El Rasheid
authors.initials: el R
authors.lastname: Zakaria
authors.forename: R Neal
authors.initials: RN
authors.lastname: Garrison
authors.forename: Touichi
authors.initials: T
authors.lastname: Kawabe
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Harris
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001783:Blood Flow Velocity; D001810:Blood Volume; D015314:Dialysis Solutions / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D005947:Glucose / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007082:Ileum / Q000098:blood supply / Q000187:drug effects; D007511:Ischemia / Q000209:etiology / Q000503:physiopathology; D007552:Isotonic Solutions / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation; D010530:Peritoneal Dialysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D013152:Splanchnic Circulation; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D015314:Dialysis Solutions; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D005947:Glucose