title: Mechanisms of parenchymal cell death in-vivo after microvascular hemorrhage.
abstract: OBJECTIVE
  In vitro studies suggest that microhemorrhages with escape of red cells into the tissue may be cytotoxic to parenchymal cells due to oxygen free radical formation. We examined in the rat mesentery the impact of microhemorrhages on parenchymal cell death, as detected by propidium iodide staining, using an intravital approach.
  
  
  RESULTS
  Postcapillary venules were punctured with a closed-end micropipette, permitting escape of blood cells and plasma into the mesentery interstitium. Over a period of 2 h, no significant increase in parenchymal cell death was encountered in tissues with hemorrhagic sites compared with nonhemorrhagic control sites. Interstitial microinjections of plasma derived from whole blood incubated for several hours with and without a combination of sodium azide (2 mM) and hydrogen peroxide (1 mM) led to significantly increased levels of cell death compared to control experiments. Interventions against the hydroxyl radical with dimethylthiourea (DMTU, 2 mM) or 2,2'-dipyridyl (DPD, 2 mM), a lipid soluble iron chelator, provided no protective effect against the parenchymal cell death. DMTU slightly delayed tile cytotoxic reaction.
  
  
  CONCLUSIONS
  These observations suggest that a newly formed microhemorrhage is not necessarily cytotoxic to parenchymal tissue cells. Interstitial microinjections of plasma, derived from whole blood after prolonged exposure to oxygen free radicals or just aging under in vitro conditions, may be cytotoxic to mesenteric parenchymal cells without effective blockade by interventions against the hydroxyl radical.
authors.affiliation: Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California-San Diego, La Jolla 92093-0412, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wilms
authors.forename: F A
authors.initials: FA
authors.lastname: Delano
authors.forename: G W
authors.initials: GW
authors.lastname: Schmid-Schönbein
mesh_terms: D015082:2,2'-Dipyridyl / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D006454:Hemoglobins / Q000737:chemistry; D006470:Hemorrhage / Q000473:pathology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical; D007502:Iron Chelating Agents / Q000494:pharmacology; D008297:Male; D008642:Mesenteric Veins / Q000293:injuries; D008643:Mesentery / Q000098:blood supply / Q000473:pathology; D008833:Microcirculation; D008845:Microinjections; D018384:Oxidative Stress; D010949:Plasma; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D019810:Sodium Azide / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014699:Venules / Q000293:injuries
chemical_list: D016166:Free Radical Scavengers; D005609:Free Radicals; D006454:Hemoglobins; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D015082:2,2'-Dipyridyl; C038983:1,3-dimethylthiourea; D019810:Sodium Azide; D006861:Hydrogen Peroxide; D013890:Thiourea