Ovariectomy reinstates the infarct size-limiting effect of postconditioning in female rabbits.
Gender seems to interfere with the cardioprotective effect of ischemic preconditioning (PreC) and postconditioning (PostC); PreC-conferred protection is weaker or lost in female animals after ovariectomy (Ov), while the role of PostC is still in dispute. We sought to investigate the effect of PostC in female rabbits, its interaction with Ov, and the potential implicated intracellular pathways. Intact or Ov adult female rabbits (n = 46) were subjected to 30 min ischemia and reperfusion with PostC (PostC or OvPostC), which consisted of six cycles of 30-s ischemia/30-s reperfusion at the end of ischemia, or without PostC (Fem or OvFem). Infarct size (I) and area at risk (R) were determined by TTC staining and fluorescent particles, respectively, after 3-h reperfusion in 30 out of 46 animals. Plasma levels of estradiol and nitrite/nitrate (NO x ) were evaluated. ERKs, p38-MAPK, and Akt assessment was performed in excised hearts 1-min after starting the final reperfusion period in the remaining 16 animals. Infarct size was significantly reduced only in OvPostC group (I/R ratio, 25.3 ± 2.7, vs 48.1 ± 2.0, 43.6 ± 4.2 and 55.1 ± 5.6 % in Fem, OvFem, and PostC groups, p < 0.05). In ovariectomized rabbits, plasma estradiol and NO x levels were lower than in the normal ones. Akt phosphorylation in ischemic regions was significantly higher in OvPostC group, whereas ERK1/2 and p38-MAPK activation was observed in all ovariectomized animals irrespective of PostC. PostC is not effective in female rabbits, but the protection is reinstated after Ov potentially via the RISK pathway.
Second Department of Cardiology, Medical School, University of Athens, Attikon University Hospital, Athens, Greece.
Eftychia
E
Demerouti
Ioanna
I
Andreadou
Ioanna-Katerina
IK
Aggeli
Dimitrios
D
Farmakis
Anastasia
A
Zoga
Catherine
C
Gaitanaki
Isidoros
I
Beis
Maria
M
Anastasiou-Nana
Dimitrios Th
DT
Kremastinos
Efstathios K
EK
Iliodromitis
D000818:Animals; D003331:Coronary Vessels / Q000502:physiology*; D004958:Estradiol / Q000097:blood; D005260:Female; D006439:Hemodynamics; D057775:Ischemic Postconditioning; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010052:Ovariectomy; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011817:Rabbits; D015424:Reperfusion; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D009566:Nitrates; D009573:Nitrites; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases