TY - JOUR
T1 - Postischemic Infusion of 17-β-Estradiol Protects Myocardial Function and Viability
AU - Terrell, Andrew M.
AU - Crisostomo, Paul R.
AU - Markel, Troy A.
AU - Wang, Meijing
AU - Abarbanell, Aaron M.
AU - Herrmann, Jeremy L.
AU - Meldrum, Daniel R.
N1 - Funding Information:
This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program grant number C06 RR015481-01 from the National Center for Research Resources, National Institutes of Health.
Funding Information:
This work was supported in part by NIH R01GM070628, NIH R01HL085595, NIH K99/R00 HL0876077-01, NIH NRSA, AHA Grant in Aid, and AHA Postdoctoral Fellowship 0526008Z.
PY - 2008/5/15
Y1 - 2008/5/15
N2 - 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 17β-estradiol will decrease myocardial ischemia/reperfusion injury and improve left ventricular cardiac function. Materials and 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 17β-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 17β-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.
AB - 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 17β-estradiol will decrease myocardial ischemia/reperfusion injury and improve left ventricular cardiac function. Materials and 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 17β-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 17β-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.
KW - estrogen
KW - myocardial infarction
KW - recovery
KW - sex hormones
UR - http://www.scopus.com/inward/record.url?scp=41649112291&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2007.05.021
DO - 10.1016/j.jss.2007.05.021
M3 - Article
C2 - 17644110
AN - SCOPUS:41649112291
SN - 0022-4804
VL - 146
SP - 218
EP - 224
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -