A comparison of two progestins on myocardial ischemia-reperfusion injury in ovariectomized monkeys receiving estrogen therapy.
OBJECTIVE
It has been reported that the progestin medroxyprogesterone acetate (MPA), but not norethindrone acetate (NETA), inhibits the beneficial vascular effects of post-menopausal estrogen therapy, but their effects on the myocardium are unclear. The goal of this study is to compare the effects of these two progestins on post-ischemic myocardial damage.


METHODS
Ovariectomized monkeys were fed an atherogenic diet for 18 months while receiving, or not receiving (control, n=15), the monkey equivalent to a woman's dose of 5 mug ethinyl estradiol with either 1 mg NETA daily (n=15) or 2.5 mg MPA daily (n=15). The left anterior descending coronary artery was occluded for 1 h and then released to allow myocardial reperfusion for 4 h. Infarct size was quantified using the histochemical stain triphenyl-tetrazolium chloride. Regional myocardial blood flow was measured by 15 mum neutron-activated microspheres, blood pressure and heart rates with a pneumatic cuff, stroke volume by echocardiography, coronary output by thermodilution and neutrophil accumulation in the myocardium using myeloperoxidase (MPO) activity.


RESULTS
The infarct size (area of necrosis/area at risk) was similar between the control group (21+/-3%) and the MPA group (29+/-3%) (P<0.05) but significantly less in the NETA group (3+/-2%) than other groups (P<0.05). The hemodynamic myocardial function and regional myocardial blood values were similar among groups before, during and 4 h after reperfusion (all P-values >0.05). Similarly, there were no treatment effects on MPO activity (P>0.05).


CONCLUSIONS
NETA, but not MPA, diminished ischemia-reperfusion injury in estrogen-treated post-menopausal females. The mechanism(s) of this difference remains unclear.
Suparto
Irma H
IH
Primate Research Center, Bogor Agriculture University, Indonesia.
Koudy Williams
J
J
Fox
Jamie L
JL
Vinten-Johansen
Jakob
J
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004347:Drug Interactions; D004967:Estrogens / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D004997:Ethinyl Estradiol / Q000627:therapeutic use; D005260:Female; D000882:Haplorhini; D006339:Heart Rate / Q000187:drug effects; D008055:Lipids / Q000097:blood; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009640:Norethindrone / Q000031:analogs & derivatives / Q000494:pharmacology; D000077563:Norethindrone Acetate; D010052:Ovariectomy; D009195:Peroxidase / Q000187:drug effects; D011372:Progestins / Q000494:pharmacology*; D012107:Research Design; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D015415:Biomarkers; D003271:Contraceptive Agents, Female; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D008055:Lipids; D011372:Progestins; D004997:Ethinyl Estradiol; D000077563:Norethindrone Acetate; D017258:Medroxyprogesterone Acetate; D009195:Peroxidase; D009640:Norethindrone