L-propionyl carnitine, an endogenous ester in fatty acid metabolism, exerts anti-shock and endothelial protective effects in rat splanchnic ischemia-reperfusion injury.
Splanchnic artery occlusion (SAO) results in a severe form of circulatory shock in which oxygen-derived free radicals play an important role. L-Propionyl carnitine (LPC), an endogenous ester that plays a crucial role in cellular fatty acid oxidation and metabolism, has been shown to exert a protective effect in myocardial ischemia/reperfusion injury. Our purpose was to investigate the effects of LPC in an SAO model of ischemia/reperfusion injury. Pentobarbital-anesthetized rats were subjected to 60 min of SAO followed by 120 min of reperfusion. An intravenous bolus of LPC (200 microg/kg) administered 2 min before reperfusion prolonged survival time (116+/-4 vs. 81+/-3 min in 1 mL/kg .9% NaCl vehicle, p < .01), increased survival rate (88 vs. 13.6%, p < .01), and attenuated the percent increase in hematocrits (27+/4% vs. 43+/-3%, p < .05), and the increases in tissue myeloperoxidase activity (1.76+/-.4 U/100 mg vs. 3.79+/-.2 U/100 mg, p < .05). In addition, LPC increased mean arterial blood pressures at 60 min (p < .05), 80 min (p < .05), 100 min (p < .05), and 120 min (p < .05) postreperfusion. Moreover, LPC markedly attenuated splanchnic artery endothelial dysfunction induced by SAO ischemia/reperfusion injury (maximal vasorelaxation to ACh, 74+/-2.7% vs. 57+/-1.9% in vehicle, p < .01). In this murine SAO model of ischemia/reperfusion injury, LPC affords significant protection that may be achieved through inhibiting leukocyte infiltration into intestinal tissue and preserving endothelial function, thereby decreasing microvascular permeability and maintaining tissue perfusion.
Stroh
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R
Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Christopher
T A
TA
Lopez
B L
BL
Guo
Y P
YP
Amico-Roxas
M
M
Ma
X L
XL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005227:Fatty Acids / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008641:Mesenteric Vascular Occlusion; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D012769:Shock / Q000188:drug therapy / Q000503:physiopathology*; D013152:Splanchnic Circulation; D015996:Survival Rate; D013997:Time Factors
D005227:Fatty Acids; C003223:propionylcarnitine; D009195:Peroxidase; D002331:Carnitine