Hypothermia attenuates NO production in anesthetized rats with endotoxemia.
Sepsis is often associated with upregulation of nitric oxide production and fever, and it is common to control an excessive febrile response with antipyretic therapy and external cooling. Our aim was to evaluate the effect of hypothermia on NO production in a model of septic shock. Rats were anesthetized, ventilated, and instrumented for hemodynamic monitoring and divided into four groups. Normothermic controls (NC) received saline intravenously and were maintained at 37 °C. Hypothermic controls (HC) received saline but were allowed to become hypothermic. Normothermic endotoxic (NE) received Escherichia Coli lipopolysaccharides (LPS) intravenously to induce endotoxic shock and was maintained at 37 °C. Hypothermic endotoxic (HE) received LPS intravenously and was allowed to become hypothermic. Exhaled NO (NOe) was measured from mixed expired gas at time zero and every 30 min, for 5 h. After injection of LPS, NOe increased substantially in the NE group (700 ± 24 ppb), but increased only to 25 ± 2 ppb in the HE group. NOe increased to 90 ± 3 ppb in the NC group, and to 17.6 ± 3.1 ppb in the HC group after 5 h (P < 0.05), whilst blood pressure remained stable. In the HE group, blood pressure fell immediately after injection of the LPS, but thereafter remained stable despite the rise in NOe. In the NE group, the blood pressure fell gradually, and the animals became hypotensive. During the natural course of endotoxemia in anesthetized rats, allowing severe hypothermia to ensue by not actively managing temperature and hemodynamics resulted in significantly reduced expired NO concentrations, lung injury, and prolonged survival. The clinical benefits of such a finding currently remain unclear and merit further investigation.
Sleep Apnea Treatment Center, Phoenix, AZ, USA.
T S
TS
Hakim
A
A
Pedoto
J
J
Nandi
G
G
Bosco
A
A
Rubini
D
D
Mangar
A
A
Paoli
E M
EM
Camporesi
D000758:Anesthesia; D000818:Animals; D019446:Endotoxemia / Q000378:metabolism*; D007035:Hypothermia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000378:metabolism*
D009569:Nitric Oxide; D009195:Peroxidase