title: Effects of almitrine bismesylate in a microswine model of hypoxemic hypothermia.
abstract: We have developed an anesthetized microswine model of hypoxemic hypothermia and rewarming for testing prophylaxes and treatments. The respiratory stimulant almitrine bismesylate (ALM) was considered as a potential field expedient therapy for hypoxemic hypothermia. Preliminary experiments demonstrated that five consecutive 100 micrograms.kg-1 ALM intravenous (i.v.) doses given to normothermic microswine 3-4 min apart increased minute ventilation from an average of 3.4 L.min-1 to 4.5 L.min-1 (n = 2). However, when either a single i.v. ALM dose of 150 micrograms.kg-1 (n = 1) or three consecutive 100 micrograms.kg-1 i.v. doses given 15 min apart (n = 1) to hypoxemic hypothermic microswine with a mean esophageal temperature (Tes) = 28.8 degrees C, and a mean arterial O2 partial pressure (PaO2) = 49 mmHg, the hypoxemia was potentiated (mean PaO2 = 32 mmHg) and respiratory arrest ensued. Other experiments using continuous ALM i.v. infusion (1.0 microgram.kg-1.min-1) in hypoxemic hypothermic microswine (n = 6, Tes = 30.6 +/- 0.5, PaO2 = 55.4 +/- 12.9) did not demonstrate significant (p < or = 0.05) cardiorespiratory differences (ventilation, heart rate, blood pressure, blood gases) when compared to hypoxemic hypothermic controls (n = 6, Tes = 30.7 +/- 0.5, PaO2 = 53.3 +/- 13.6). These results suggest that high dose i.v. bolus administration of ALM is not indicated as a potential field expedient therapy for hypoxemic hypothermia, while further work is required to assess the potential efficacy of other continuous low dose i.v. infusion regimens.
authors.affiliation: Animal Resources Branch, United States Army Research Institute of Environmental Medicine, Natick, MA, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Gentile
authors.forename: M J
authors.initials: MJ
authors.lastname: Durkot
authors.forename: B A
authors.initials: BA
authors.lastname: Krestel
authors.forename: I V
authors.initials: IV
authors.lastname: Sils
authors.forename: K A
authors.initials: KA
authors.lastname: Tartarini
authors.forename: D A
authors.initials: DA
authors.lastname: English
authors.forename: A M
authors.initials: AM
authors.lastname: Alkhyyat
mesh_terms: D015765:Almitrine / Q000627:therapeutic use*; D000532:Altitude Sickness / Q000150:complications / Q000188:drug therapy*; D000818:Animals; D001784:Blood Gas Analysis; D002344:Carotid Body / Q000187:drug effects; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007035:Hypothermia / Q000150:complications / Q000188:drug therapy*; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy*; D008887:Military Medicine; D012123:Pulmonary Ventilation / Q000187:drug effects; D019141:Respiratory System Agents / Q000627:therapeutic use*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D019141:Respiratory System Agents; D015765:Almitrine