title: Microvascular and systemic effects following top load administration of saturated carbon monoxide-saline solution.
abstract: OBJECTIVE
  To determine how top loads with different doses of carbon monoxide (CO)-saturated saline solutions (CO-saline) affect microvascular and systemic hemodynamics and to delineate the corresponding biochemical mechanisms.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male Golden Syrian hamsters.
  
  
  METHODS
  Hamsters implemented with a dorsal window chamber were given different volumes (characterized as percent of blood volume, BV) by intravenous injection of CO-saturated saline.
  
  
  RESULTS
  Hamsters were observed until 90 mins after infusion of CO-saline solution. In the 20% BV CO-saline infusion group, observation was extended until 180 mins. Systemic variables measured included mean arterial pressure, heart rate, systemic arterial blood gases, and cardiac output and index. Microvascular hemodynamic measurements included vessel diameter, red blood cell velocity, and functional capillary density. Cyclic guanosine monophosphate (cGMP) content in the chamber tissue was measured by enzyme immunoassay. 10% BV of CO-saline increased flow maximally in the microcirculation at 30 mins after infusion (207% in arterioles and 238% in venules, p < .05 vs. baseline). Functional capillary density was significantly increased in both 10% and 15% groups (p < .05 vs. baseline), and cardiac index increased 130% (p < .05 vs. baseline) at 10 mins after 10% CO-saline infusion. There were no changes of microhemodynamic variables and functional capillary density with 2.5%, 5%, and 20% CO-saline infusion during the observation period. Microvascular hemodynamic changes by 10% CO-saline infusion were inhibited completely by L-NAME pretreatment and partially by 1H-[1,2,4]oxadiazole[4,3-a]quinoxqalin-1-one pretreatment. cGMP content in skin fold tissues was related to changes of vessel diameter.
  
  
  CONCLUSIONS
  Intravenous injection of CO-saturated saline caused vasodilation and improved microvascular hemodynamics in the hamster window chamber model in a dose-dependent manner. These changes were related to increased cardiac output and local cGMP content. These results support the possible use of CO-saturated solutions as a vasodilator in critical conditions.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA. nhangai@bioeng.ucsd.edu
authors.forename: Nanae
authors.initials: N
authors.lastname: Hangai-Hoger
authors.forename: Amy G
authors.initials: AG
authors.lastname: Tsai
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology*; D002263:Carboxyhemoglobin / Q000032:analysis; D002302:Cardiac Output / Q000187:drug effects; D006224:Cricetinae; D006152:Cyclic GMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012867:Skin / Q000098:blood supply; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D012965:Sodium Chloride; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester