Effects of almitrine bismesylate in a microswine model of hypoxemic hypothermia.
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.
Gentile
B J
BJ
Animal Resources Branch, United States Army Research Institute of Environmental Medicine, Natick, MA, USA.
Durkot
M J
MJ
Krestel
B A
BA
Sils
I V
IV
Tartarini
K A
KA
English
D A
DA
Alkhyyat
A M
AM
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
D019141:Respiratory System Agents; D015765:Almitrine