Postischemic infusion of 17-beta-estradiol protects myocardial function and viability.
BACKGROUND
Females demonstrate improved cardiac recovery after ischemia/reperfusion injury compared with males. Attenuation of myocardial dysfunction with preischemic estradiol suggests that estrogen may be an important mediator of this cardioprotection. However, it remains unclear whether post-injury estradiol may have clinical potential in the treatment of acute myocardial infarction. We hypothesize that postischemic administration of 17beta-estradiol will decrease myocardial ischemia/reperfusion injury and improve left ventricular cardiac function.


METHODS
Adult male Sprague Dawley rat hearts (n = 20) (Harlan, Indianapolis, IN) were isolated, perfused with Krebs-Henseleit solution via Langendorff model, and subjected to 15 min of equilibration, 25 min of warm ischemia, and 40 min reperfusion. Experimental hearts received postischemic 17beta-estradiol infusion, 1 nm (n = 4), 10 nm (n = 4), 25 nm (n = 4), or 50 nm (n = 4), throughout reperfusion. Control hearts (n = 4) were infused with perfusate vehicle.


RESULTS
Postischemic recovery of left ventricular developed pressure was significantly greater with 1 nm (51.6% +/- 7.4%) and 10 nm estradiol (47.7% +/- 8.6%) than with vehicle (37.8% +/- 9.7%) at end reperfusion. There was also greater recovery of the end diastolic pressure with 1 nm (47.8 +/- 4.0 mmHg) and 10 nm estradiol (54.0 +/- 4.0) compared with vehicle (75.3 +/- 7.5). Further, 1 nm and 10 nm estrogen preserved coronary flow after ischemia and decreased coronary effluent lactated dehydrogenase compared with controls. Estrogen at 25 nm and 50 nm did not provide additional benefit in terms of functional recovery. Estrogen at all concentrations increased extracellular signal-regulated protein kinase phosphorylation.


CONCLUSIONS
Postischemic infusion of 17beta-estradiol protects myocardial function and viability. The attractive potential for the clinical application of postischemic estrogen therapy warrants further study to elucidate the mechanistic pathways and differences between males and females.
Terrell
Andrew M
AM
Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 203, Indianapolis, IN 46202, USA.
Crisostomo
Paul R
PR
Markel
Troy A
TA
Wang
Meijing
M
Abarbanell
Aaron M
AM
Herrmann
Jeremy L
JL
Meldrum
Daniel R
DR
D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D004958:Estradiol / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D014022:Tissue Survival / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects*
D002317:Cardiovascular Agents; D004958:Estradiol