Effects of Estrogen in the Myocardium of Aged Ovariectomized Rats

BACKGROUND AND OBJECTIVES: The effects of estrogen in the myocardium of aged ovariectomized rats, relating to the estrogen replacement onset time following an ovariectomy, and the replacement duration have not yet been established. The object of this study was to investigate the effects of estrogen replacement in the myocardium of aged ovariectomized rats. MATERIALS AND METHODS: 52 Female Sprague Dawley rats, about 3 months old, were subjected to sham surgery only (Group 1 ; control, n=9) ; a bilateral ovariectomy (OVX) and maintained untreated for a period of 12 weeks following surgery (Group 2 ; OVX only, n=16) ; estrogen conjugate 25 microgram/kg daily for 4weeks from the 8th post ovariectomy week (Group 3 ; OVX+estrogen replacement therapy : ERT 4weeks, n=10) ; estrogen conjugate 25 microgram/kg daily p.o for 12weeks directly post ovariectomy (Group 4 ; OVX+ERT 12weeks, n=17). We measured the left ventricular wall thickness (LVWT), the number of cardiomyocytes and interstitial fibrosis, edema, using light and electron microscopy. RESULTS: The LVWT in group 4 was 2.25 mm, which was significantly decreased compared to groups 2 and 3, which were 2.45 mm (p=0.014) and 2.46 mm (p=0.008), respectively. The LVWT in group 4 was not significantly different to that of group 1. Interstitial edema was significantly decreased in group 4 (41.2%) compared to that of group 3 (62.0%) (p=0.019). The electron microscopic findings showed a decrease of crystae and a loss of matrix, resulting in a whitish discoloration of the mitochondria in groups 2 and 3. A similar finding was not observed in groups 1 and 4. CONCLUSION: These results suggest that early administration and maintenance of estrogen following a bilateral ovariectomy could prevent the myocardial changes caused by estrogen deficiency.

Relation between Coronary Flow Reserve and Myocardial Perfusion State and Change of Coronary Flow Reserve in Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: The state of the coronary microcirculation is one of the major determinants of the prognosis of patients who have had successful reperfusion for acute myocardial infarction (AMI). We investigated whether the vasodilatory reserve in the infarcted myocardium correlated with the perfusion state at early recovery phase in 12 anterior wall AMI patients. MATERIALS AND METHOD: We measured coronary flow variables with Doppler wire, after successful revascularizaiton by PTCA within 2 weeks following AMI and 13+/-0.5 months later, in the infarct related artery of AMI pts who received successful thrombolytic therapy. Myocardial perfuison state was evaluated by semiquantitative method (opacification score and opacification index) with myocardial contrast echocardiography (MCE) at the same time. Patients were divided into two groups according to initial perfusion status (perfusion defect group (PD (+), n=7), no-perfusion defect group (PD (-), n=5)). RESULTS: 10 minutes after completion of the intervention, the coronary flow reserve (CFR) was 2.0+/-0.4 (mean+/-SD): it increased to 2.7+/-0.7 (p=0.002) at follow up. The difference of initial CFR was not significant between PD (+) and PD(-) group. However, it significantly improved in the PD (-) group compared to PD (+) group at follow up (3.19+/-0.39 vs. 2.39+/-0.7, p=0.046). Opacification index and initial CFR were significantly correlated (r=0.79, p<0.05). CONCLUSION: The perfusion state of infarcted myocardium was significantly correlated with coronary flow reserve in anterior wall AMI and CFR was significantly improved in patients with relatively preserved myocardial perfusion.

Feasibility of Low-Molecular-Weight-Heparin (Fraxiparine) for Primary Stenting in Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: The optimal anti-thrombotic strategy for primary stenting in acute myocardial infarction (AMI) is still controversial. We evaluated prospectively the efficacy and safety of low-molecular-weight-heparin (LMWH) for primary stenting in AMI. MATERIALS AND METHOD: From 1/1997 to 7/1998, 54 AMI pts underwent primary stenting with 96% of procedural success rate (52/54). Of these, five pts were excluded from the study for warfarinization or use of GP II b/ III a inhibitor despite of successful stenting (TIMI 3 flow and less than 30% of residual stenosis). In 47 pts included in the study, 5,000-10,000 U of unfractionated heparin was administered (IV/bolus) bofore primary stenting. After sheath removal, LMWH(Fraxiparine, 7500 U/S.C.BID) maintained for 10.6+/-5.7 days. Aspirin and ticlopidine (500mg/day for > or =4 weeks) were given before stenting. Pts were followed to determine early (0-30 days) and late (31-180 days) major adverse cardiac events (MACE). Subsequent revascularization involving other coronary arteries did not constitute an end point. RESULTS: In 47 Pts (M:F=32:15, age=57.7+/-11.3 yrs, range: 37-88), 50 stents (Nir:38, micro:7, Jo:5, LAD:LCX:RCA-=24:9:14) were implanted. Their immediate post-stenting MLD and diameter-stenosis (%) were 2.9+/-0.4 mm, 4.3+/-8.7%, respectively. No patient showed sub-acute stent thrombosis or major bleeding requiring blood transfusion or surgery. During 0-30 days, the primary combined end point occurred in 2 (4.2%):one repeated angioplasty for in-stent restenosis; one hospital death for pump failure (1 of 2 Killip IV pts at admission). 44 patients were followed for 180 days and additional three TVR (3/44(6.8%), one CABG, one repeated angioplasty and one recurrrent myocardial infarction)occurred between 30-180 days due to recurrent ischemia. CONCLUSION:Anti-thrombotic therapy with LMWH (Fraxiparine) is safe and feasible for primary stenting in AMI. But to illuminate the impact on the clinical outcomes such as major adverse cardiac events and restenosis, we need more large and controlled study.

Effect of Parathyroid Hormone on Left Ventricular Hypertrophy in Aged Ovariectomized Rats

BACKGROUND: It has been well known that the bone and kidney are the principle organs of parathyroid hormine (PTH) actions. Although patients with primary hyperparathyroidism show a high incidence of LVH and trophic effects of PTH on adult rat ventricular cardiomyocytes were investigated in vitro, effect of PTH on the cardiac tissue in vivo is unknown. METHODS: We examined the effects of PTH on the cardiomyocyte and interstitial tissue using adult rat heart. Twenty-two female Sprague-Dawley rats were ovariectomized bilaterally at three months old and weighing in 250 - 300 gm in order to exclude the trophic effect of estrogen. We administrated human parathyroid hormone (20 ug subcutaneously 5 times per week) to 12 rats for 4 weeks after raising for 8 weeks (PTH group):the remaining 10 rats received only normal saline (control). We measured left ventricular thickness [IVS+LVPW)/2] and number of cardiomyocytes and interstitial fibrosis on LM (H & E and Masson's trochrome stain) and EM. RESULTS: 1) LV wall thickeness tended to increase in PTH group as compared with control (2.16+/-0.31 vs 1.12+/-0.21 mm, p=0.099). 2) The number of cardiomyocyte in PTH group was significantly less than that of control (61.2+/-13.1 vs 70.5+/-14.9, p=0.003, Magnification x 400). 3) There was no significant change of interstitial fibrosis between PTH group and control. CONCLUSION: These results shggest that PTH may produce left ventricular hypertrophic effects in aged ovariectomized rat that resulted form hypertrophy of cardiomyocyte without increase of interstitial connetive tissue.

Response of the Rat Heart to Bilateral Ovariectomy and Estrogen

BACKGROUND AND OBJECTIVES: Although ovarian estrogen is believed to decrease coronary heart disease by improving plasma lipoprotein and enhancing vasodilation, estrogen effect on heart tissue has not been shown yet. So we investigated the effect of the ovariectomy and estrogen on rat heart tissue. MATERIALS AND METHODS: Female Sprague Dawley rats, about 3 months of age, were subjected to sham surgery (n=9) or bilateral ovariectomy (n=20) and maintained untreated for 8 weeks after surgery. We administered estrogen (20 mg/Kg subcutaneously, 3 times/week) to 10 ovariectomized rats for 4weeks; the remaining ovariectmized rats received only saline. Animals were divided in 3 group:group 1 (control); sham op, group 2; ovariectomized only, group 3; ovariectomy+estrogen. We measured left ventricular thickness [IVS+LVPW)/2] and number of cardiomyocytes and interstitial fibrosis on light microscope (H & E and Masson's trochrome stain) and electron microscope. RESULTS: 1) LV wall thicknesses were significantly increased in group 2 and group 3 as compared with group 1 (2.45+/-0.1 and 2.46+/-0.11 vs 2.31+/-0.15 mm). 2) There were no significant change in the number of cardiomyocyte between group 1, group 2 and group 3 (54.3+/-5.7, 60.2+/-19.4, 52.5+/-14.1). 3) Group 2 and group 3 show more interstitial edema (44% and 62.5% vs 0%) on LM and more interstitial edema and the increase of number of mitochondria on EM than group 1. CONCLUSION: Bilateral ovariectomized rats show the increase of LV wall thickness, which was caused by interstitial edema without cardomyocyte hypertrophy and these changes were not reversed by the short-term administration of estrogen for 4 weeks.

A Case Report of Acute Myocardial Infarction in a Patient with Servere Aortic Stenosis and Normal Coronary Arteries

The incidence of angina pectoris(AP) in patients with severe aortic stenosis(AS) and normal coronary arteries has been reported to be 30 to 40%. The pathophysiologic mechanism suggests marked decrease in coronary rederve with left ventricular hypertrophy secondary AS and mismatched oxygen demand-supply by valvular pressure gradient, but only 1 case of acute myocardial infarction(AMI) was reported in severe AS and normal coronary arteries as far as we are concerned. We report a case of AMI occuring in a patient with severe AS and left ventricular hypertrophy. A coronary angiogram excluded coronary obstruction and spasm as the cause of AMI in this patient.

The Difference of Thrombogenic and Fibrinolytic Factors inPremenopausal and Menopausal Women

BACKGROUND: Thrombotic and fibrinolytic factors which change in women following menopause, may be of pathogenetic importance in atherogenetic and thrombotic cardiovascular diseases by altering fibrinolysis on vascular surfaces. We investigated whether parameters of thrombosis and fibrinolysis were different before and after menopause. METHODS: Thrombotic factors such as plasma plasminogen activator inhibitor type 1(PAI-1), fibrinogen, a2 antiplasmin, lipoprotein(a) were measured. In addition, fibrinolytic factors such as plasma tissue-type plasminogen activator(t-PA), plasminogen, antithrombin-III were also assessed in 41 premenopausal women, 174 menopausal women and 201 men. RESULTS: PAI-1 and fibrinogen and t-PA were significantly higher in menopausal women than in premenopausal women(13.1+/-6.6 vs 16.9+/-9.5ng/ml, p=0.046, 293.6+/-83.3 vs 347. 5+/-256.9mg/dl, p=0.001, 10.1+/-4.4 vs 12.5+/-5.6ng/ml, p=0.003). A positive significant correlation was found between PAI-1 and any other thrombogenic and fibrinolytic factors. CONCLUSIONS: PAI-1, fibrinogen, t-PA were higher in menopausal women than in premenopausal women. The findings suggest that increase of athersclerotic and thrombotic cardiovascular diseases after menopause may be influenced by these changes.