Cardioprotective effects of lazaroid U-74389G on ischemia-reperfusion injury in canine hearts

A lazaroid mitigates postresuscitation myocardial dysfunction

“…The cardioprotective effect of lazaroids against reperfusion injury has been demonstrated previously in both intact animals (17,(32)(33)(34) and isolated heart preparations (29,(35)(36)(37)(38). U-74389G also preserved both myocardial function (39) and ultrastructure (20) in transplanted hearts. The present study extends such beneficial effects of lazaroids to settings of global myocardial ischemia following cardiac arrest.…”

“…U-74389G (21-[4-(2, 6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-pregna-1, 4, 9 (11)-triene-3, 20-dione (2)-2-butenenedionate) is a representative lazaroid molecule. Takahashi et al (20) demonstrated that the administration of this lazaroid before reperfusion in a model of canine cardiac transplantation improved posttransplantation myocardial function provided that the lazaroid was administrated before reperfusion. The improvement in myocardial function associated with 21-aminosteroids also has been documented in endotoxemia (21,22) In the present study, our focus was on reperfusion of the heart following cardiac resuscitation.…”

Effect of the Free Radical Scavenger MCI-186 on Pulmonary Ischemia–Reperfusion Injury in Dogs

“…Their models of I/R demonstrated that 21-aminosteroids have the ability to scavenge oxygen radicals and are effective at inhibiting degranulation and tissue lipid peroxidation. In other studies, neutrophil infiltration was attenuated by 21-aminosteroids in myocardial 15 and liver 16 I/R injury models. In this study, MCI-186, which is an anti-lipid peroxidation agent, may have played a role in the attenuation of neutrophil activation, adherence and infiltration.…”

“…13 The microcirculation is injured under this condition, and pulmonary edema is promoted. Free radical scavengers, SOD, catalase 14 and lazaroid, 15,16 have been found to be effective at preventing tissue damage from I/R injuries. Free radicals and lipid peroxide play a key role in cerebral damage during an early ischemic phase.…”

The effects of lazaroid U-74389G in a rat sepsis model

“…These compounds have been shown, in addition to other therapeutic actions, to improve renal and intestinal blood flow [7,8] in septic shock, and myocardial function in ischemia-reperfusion injury [9][10][11][12][13][14].…”