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A comparison of two progestins on myocardial ischemia???reperfusion injury in ovariectomized monkeys receiving estrogen therapy

2005; Lippincott Williams & Wilkins; Volume: 16; Issue: 5 Linguagem: Inglês

10.1097/00019501-200508000-00007

1473-5830

Irma Herawati Suparto, J. Koudy Williams, Jamie L. Fox, Jakob Vinten‐Johansen,

Chemotherapy-induced cardiotoxicity and mitigation

In Brief 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 μg 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 μm 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). 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. The goal of this study is to measure the effects of progestins on post-ischemic myocardial damage. Two different co-administered progestins were given to ovariectomized monkeys receiving estrogen replacement. The amount of post-ischemic myocardial damage was more in the monkeys receiving the progestin medroxyprogesterone acetate (MPA) and less in monkeys receiving the progestin norethindrone acetate (NETA). Measurement of myocardial blood flow, hemodynamics andmyeloperoxidase did not reveal a mechanism explaining these results. It is concluded that NETA but not MPA diminished post-ischemic myocardial injury in estrogen-treated surgically menopausal monkeys, but the underlying mechanism remains unclear.