Different pattern of carotid and myocardial changes according to left ventricular geometry in hypertensive patients.

The relation between left ventricular (LV) hypertrophy and LV function is well known. However, less is known about the vascular changes influenced by LV geometry. We sought to investigate the relationship of LV geometry to carotid arterial and LV function. A total of 476 hypertensive patients were prospectively recruited. All subjects underwent echocardiography and carotid ultrasound. LV geometry is categorized into four groups according to relative wall thickness (RWT) and LV mass index (LVMI). Concentric LV geometry was associated with increased carotid intima-media thickness (IMT), ß-stiffness, and lower strain. All of the carotid parameters showed a stepwise change according to RWT of LV, whereas LV function was worse in hypertrophic geometry, as reflected by significantly lower systolic mitral annular velocity, higher left atrial volume index and E/E' ratio (P<0.001). By multivariate analysis after adjustment for clinical and laboratory parameters, IMT was independently associated with RWT, whereas myocardial function was independently associated with LVMI. Carotid arterial function and IMT showed worse values in concentric geometry, whereas LV systolic and diastolic function were worse in hypertrophic geometry, suggesting a discrepancy between carotid arterial and LV function in hypertensive patients.

Inhibition of nitric oxide synthesis increases apoptotic cardiomyocyte death and myocardial angiotensin-converting enzyme gene expression in ischemia/reperfusion-injured myocardium of rats.

Cardiomyocyte apoptosis is an important pathogenic mechanism in myocardial ischemia/reperfusion (I/R) injury. It has been shown that nitric oxide (NO) and the renin-angiotensin system (RAS) are closely related, and both systems regulate apoptotic cell death. However, the effects of NO modulation on myocardial apoptotic cell death and changes in the RAS in the I/R-injured myocardium have not been studied. Female Sprague-Dawley rats were randomized into three groups: NO synthesis inhibitor, N(G)-nitro-L-arginine-methyl ester (L-NAME, 10mg/kg); NO precursor, L-arginine (540mg/kg); and vehicle. The rats were then subjected to 45 min coronary occlusion followed by 4 h reperfusion. The TdT-mediated in situ nick and labeling (TUNEL) indices were 39.9%+/-0.8% at the border and 30.9%+/-1.2% at the center of the I/R area in the vehicle group. L-NAME administration significantly increased these TUNEL-positive cells to 45.3%+/-1.9% and 37.9%+/-1.3%, respectively (P < 0.05 each). L-arginine administration reduced the TUNEL index at the border zone with marginal significance (P = 0.08 vs vehicle group). I/R injury significantly reduced the angiotensin-converting enzyme (ACE) mRNA expression in the left (ventricular) free wall of vehicle group rats. However, ACE mRNA expression was 1.9 times greater in the L-NAME group than that in the vehicle group (P < 0.05). This study showed that the inhibition of NO synthesis increased apoptotic cardiomyocyte death and local ACE mRNA expression in the I/R-injured myocardium. Our observations indicate that NO, ACE, and apoptotic cardiomyocyte death are related to each other during I/R injury.

Ventricular remodeling and transforming growth factor-beta 1 mRNA expression after nontransmural myocardial infarction in rats: effects of angiotensin converting enzyme inhibition and angiotensin II type 1 receptor blockade.

With the application of early reperfusion therapy after acute MI, the incidence and importance of nontransmural infarction is increasing. In a rat model with nontransmural infarction, we evaluated 1) the changes of LV dimension, LV interstitial fibrosis and transforming growth factor-beta1 (TGF-beta1) mRNA expression and 2) the effects of angiotensin converting enzyme (ACE) inhibitor and angiotensin II type 1 (AT1) receptor antagonist treatment. Female Sprague-Dawley rats were subjected to 45 min of coronary occlusion followed by reperfusion, and five days after the operation the animals were randomized to untreated (n = 19), captopril-treated (n = 15) and losartan-treated (n = 14) groups. Twenty-six days after MI, echocardiographic examination revealed a remarkable dilatation of LV. Captopril or losartan treatment reduced the extent of LV cavity dilatation. Collagen volume fractions in noninfarcted septum as well as in peri-infarct area decreased with captopril or losartan treatment, compared to those of the untreated rats. In noninfarcted septum of untreated rats, TGF-beta1 mRNA expression increased more than two fold (P < 0.05 vs. pre-MI) 5 and 10 days after MI. Captopril or losartan treatment suppressed the acute induction of TGF-beta1 mRNA expressions. These results indicate that ACE inhibitor or AT1 receptor antagonist treatment after nontransmural infarction 1) attenuates LV remodeling as in transmural infarction and 2) decreases interstitial fibrosis at least partly by blocking the acute induction of TGF-beta1 mRNA expression.

Heart failure in Korean elderly patients - clinical features, prognosis and prognostic factors.

Heart failure (HF) is very common in the elderly but there are not sufficient data about the clinical characteristics and prognostic factors of HF among the Asian elderly patients. The aim of the study was to find out the clinical characteristics, survival, and prognostic factors of HF in Korean elderly patients. Among elderly patients admitted from February 1995 to February 1998, the patients with a discharge diagnosis of HF were enrolled. Through the medical record review, the diagnosis was confirmed and clinical parameters to affect survival were identified. Total number of the subjects was 104 [age: 77+/-7 years (65-96), male:female=36:68, follow-up duration: 20+/-14 months, LVEF: 46+/-16%]. Ischemic heart disease (IHD) was the most common cause of HF (42%) followed by valvular heart disease (28%), and hypertension (20%). The 1-year survival rate was 71.3%. Advanced age [risk ratio (RR): 1.41 per 5 years of age; 95% CI: 1.11-1.80] and reduced left ventricular ejection fraction (0.69 per 10%, 0.52-0.93), poor initial functional class (2.40, 1.15-5.00), diabetes (2.79, 1.30-5.97) and past history of HF (2.37, 1.10-5.10) badly affected the survival rates. When the Cox proportional hazard model was applied for multivariate analysis, only aging (1.64 per 5 years of age, 1.19-2.28) and diabetes (4.92, 1.83-13.23) predicted poor prognosis. Twenty-seven percent of the patients had diastolic HF (LVEF>45%, LVEDD<55 mm) who had higher survival rates with marginal significance (0.35, 0.10-1.17, P=0.09).

Reciprocal change in angiotensinogen mRNA expression in rat myocardium and liver after myocardial infarction.

The aim of this study was to analyze sequential change of angiotensinogen (Ao) mRNA expression in rat liver and noninfarcted myocardium after myocardial infarction (MI). Female sprague-Dawley rats were subjected either to left coronary artery occlusion or sham operation. Three weeks after MI, coronary artery ligation resulted in comparable infarct sizes. A hypokinetic thin anterior wall and remarkable dilatation of the left ventricle, as well as decreased contractility (left ventricular end-systolic dimension = 6.0+/-0.4, 3.3+/-0.2, LV end-diastolic dimension = 7.9+/-0.3, 5.9+/-0.2 mm, and fractional shortening = 25.3+/-3.1%, 45.1+/-3.3%) were shown in the MI and sham group, respectively, by echocardiography (P < 0.01). Experimental MI caused a significant fall in systolic blood pressure (MI 90+/-5.0, vs sham 130+/-7.5 mmHg; P< 0.01) and significantly higher left ventricular end-diastolic pressure (MI 21+/-1.5, vs sham 11+/-1.0 mmHg: P < 0.01). At 4, 18, and 24h after MI, liver Ao mRNA levels, as shown by Northern blot analysis, had increased by up to four times (Ao/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) = 1.4+/-0.1 and 6.0+/-0.2 at baseline and 4h after MI, respectively (P < 0.01). After sham surgery, however, the corresponding increase was slight (maximal 1.5-fold). Three days after MI, liver mRNA had returned to the baseline level. In contrast, ATG mRNA expression in noninfarcted myocardium, as shown by reverse transcription-polymerase chain reaction and Southern blotting, decreased transiently during the acute phase. It returned to its baseline level within 3 days, and then increased further (Ao/ GAPDH = 2.9+/-0.6, 0.3+/-0.1, 3.2+/-0.8, and 3.7+/-0.8 at baseline, 24h, 3 days, and 3 weeks after MI, respectively). In conclusion, it can be stated that after MI, the Ao gene contributes, acutely in the liver and chronically in the myocardium, to the maintenance of hemodynamic homeostasis during the acute phase and ventricular remodeling during the chronic phase.