Monophosphoryl lipid A preserves myocardial contractile function following multiple, brief periods of coronary occlusion in dogs.
The effects of a 1- or 24-hour pretreatment regimen with monophosphoryl lipid A (MLA, 35 micrograms/kg i.v.) on myocardial stunning produced by repetitive coronary occlusions were studied in barbital-anesthetized dogs. Regional segment function (%SS) and myocardial blood flow were measured by sonomicrometry and the radioactive microsphere technique, respectively. In controls, six 5-min periods of coronary occlusion interpersed with 10-min periods of reperfusion and ultimately followed by 2 h of reperfusion produced regional segment dysfunction. Pretreatment with MLA for 1 h prior to the first occlusion period had no effect on %SS, however, pretreatment with MLA 24 h prior to the first occlusion period resulted in a significant (p < 0.05) improvement in the recovery of %SS at all reperfusion periods as compared to the control group. In addition, segment dysfunction during each occlusion period was significantly less severe in animals receiving a 24-hour pretreatment with MLA as compared to the controls. These results are the first to demonstrate that MLA, a lipid A derivative of endotoxin, preserves contractile function of ischemic myocardium in an in vivo canine model and that its cardio-protection is time dependent.
Yao
Z
Z
Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Elliott
G T
GT
Gross
G J
GJ
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology*; D001784:Blood Gas Analysis; D001835:Body Weight / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008863:Microspheres; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects / Q000502:physiology
D008050:Lipid A; C048436:monophosphoryl lipid A