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.

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.

Effect of L-Arginine on Post-Ischemic Myocardial and Vascular Stunning in Open-Chest Dogs

BACKGROUND: Although recent studies have demonstrated that infusion of L-arginine reduces myocardial necrotic area during prolonged ischemia, its effects on transient postischemic myocardial dysfunction(myocardial stunning) and microvascular dyfunction(vascular stunning) are not well known. To investigate whether intravenous administration of L-arginine, physiological nitric oxide(NO) precursor, during reperfusion would attenuate postischemic myocardial dysfunction and microvascular dysfunction, 15 open-chest dogs were studied. METHODS: In 15 pentobarbital anesthesized open-chest dogs, left circumflex coronary artery was occluded for 20 minutes and was followed by a reperfusion for 60 minutes. L-Arginine(30mg/kg)(L-arginine group, n=8) or saline(control group, n=7) was given intravenously by a bolus 1 minute before reperfusion and was followed by a continuous infusion(10mg/kg/min) for 30 minutes during reperfusion. Before coronary occlusion and 60 minutes after reperfusion, coronary blood flow(CBF) and coronary vascular resistance(CVR) wre measured after intracoronary injection of each of acetylcholine(0.01/kg) and adenosine(1.5/kg), and reactive hyperemia with coronary occlusion(RH20) for 20 seconds was measured. Myocardial segment thickening in the area of ischemia-reperfusion was measured using 2D-echocardiography. The echocardiographic images were digitized and analyzed by cardiac image analyzer. RESULTS: The results obtained 60 minutes after reperfusion were as follows. 1) CBF was decreased by 41% in L-arginine group vs 30.1% in control group(p < 0.05) and CVR was increased by 83.9% in L-arginine group vs 19.3% in control group after 60 minutes of reperfusion, compared with pre-occlusion baseline values. 2) Percent change of CBF was decreased in control group(acetylcholine by 25.8%, adenosine by 29.2%, RH20 by 39.8%), while it was increased in L-arginine group(acetylcholine by 60%, adenosine by 22%, RH20 by 26.7%). Percent change of CVR was increased in control group(acetylcholine by 10.5%, adenosine by 6.9%, RH20 by 21%), but it was decreased in L-arginine group(acetylcholine by 10%, adenosine by 6.6%, RH20 by 1.6%). Increase of CBF and decrease of CVR were significant on acetylcholine and RH20 between control group and L-arginine group. 3) Fraction of myocardial segment thickening was significantly decreased in L-arginine group(by 80%) compared with control group(by 61.7%, p < 0.05). CONCLUSIONS: The finding that L-arginine depressed post-ischemic myocardial contractil function suggests that systemic infusion of L-arginine has unfavorable effect on myocardial stunning. In contrast, the finding that L-arginine improved CBF and CVR with acetylcholine and adenosine and reactive hyperemia indicates that L-arginine may exert a beneficial effect on vascular stunning. These results suggest that L-arginine may have independent effects on myocardial stunning and vascular stunning.

The Characteristics and Risk Factors of Coronary Artery Spasm Induced by Acetylcholine

BACKGROUND: Although there have been many studies on the risk factors for coronary artery disease, the etiology and risk factor of coronary artery spasm has not yet been determined. The objective of this study was to examine the risk factors for coronary vasospasm through a comparison of patients with angiographically determined vasospastic angina and patients without vasospasm and normal coronary artery. METHODS: Intracoronary injection of acetylcholine in order (20microg, 50microg, 100microg) were administered to all patients (Total 81:34 males, 47 females : mean age 50 years) who had a history of chest pain with normal or near normal coronary arteriographic fingings. After documentation of vasospasm in major epicardial coronary arteries by acetylcholine (Ach)-provocated dcoronary angiography, various risk factors (smoking, hypertension, diabetes, drinking and hyperlipidemia) were compared between patients with vasospasm and patients without vaspasm. RESULTS: 24 patients showed significant luminal narrowing (> or =75%)(Vasospasm group) and 57 patients showed no significant change (Control). Vasospasm group were suffered from typical chest pain in 92% of patients but control complained typical chest pain in 51% of subjects. The sites of vasoconstriction induced by Ach were LAD (11 cases), LCX (4 cases), RCA (11 cases) and vasoconstriction occurred 2 vessels (LAD and LCx) at the same time in two cases. The amount of Ach to provocate vasoconstriction was 20~50microg (90%) and there were no difference between left and right coronary arteries. The ratio of smoker was more frequent in the vasospasm group than control (58.3% vs 30.4%, p=0.046). But total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, apolipoprotein A, apolipoprotein B, lipoprotein (a), diabetes and body mass index, drinking were not statistically significant between two groups. CONCLUSION: Smoking appears to be a major risk factor for vasospastic angina by endotheilal dysfunction without significant coronary artery narrowing. But other fisk for coronary artery disease may not contribute to coronary vasospasm.