High prevalence of myocardial ischemia and vasoconstrictive hormonal release in hypertension during chronic renal failure.

OBJECTIVE: Indexes of myocardial ischemia and vasoconstrictive hormonal release were evaluated in order to investigate the difference between essential hypertension and hypertension during chronic renal failure. BACKGROUND: Arterial hypertension induces several cardiovascular alterations that reflect themselves either on the heart and/or on the coronary blood flow enhancing the cardiovascular risk. Since chronic renal failure can influence the neuroendocrine response, various mechanisms involved in hypertension during chronic renal failure are still unclear. High endothelin 1 (ET-1) levels have been found both in arterial hypertension and during chronic renal failure. Interestingly, either ET-1 or catecholamines seem also to be implied in the pathogenesis of myocardial ischemia. METHODS: 20 hypertensive uremic and 20 essentially hypertensive patients underwent echocardiographic wall motion and wall thickening analysis performed at baseline and immediately after the end of exercise. Simultaneously, myocardial perfusion was evaluated by 99mTc-MIBI-SPECT. In addition, plasma norepinephrine and ET-1 concentrations were measured at baseline and at peak exercise. RESULTS: The segmental radionuclide analysis showed a greater ischemic degree in hypertensive uremic patients. Yet, we were able to identify one or more regions of the left ventricle in which both systolic thickening measurements and wall motion after exercise were impaired. After exercise, wall thickening impairment was correlated with both wall motion abnormalities (r = 0.72, p < 0.01) and MIBI ischemic grade (r = 0.82, p < 0.001). Basal and after-exercise plasmatic norepinephrine and endothelin levels were higher in hypertensive uremic than in essentially hypertensive patients. Moreover, there was a significant correlation between increments in norepinephrine concentration and MIBI perfusion defects, and between the increment in ET-1 concentration and both MIBI perfusion defects, or kinetic alterations assessed by wall motion as well as by wall thickening. CONCLUSIONS: This is the first cross-sectional study in which a higher degree of myocardial ischemia has been observed in hypertensive uremic patients combined with an enhanced plasma release of both norepinephrine and ET-1. This phenomenon may contribute to enhance the cardiovascular risk of these patients.

Relations between vasoactive hormones and diastolic function in hypertensive uraemic patients.

BACKGROUND: Arterial hypertension is a significant risk factor for the high rate of cardiovascular disease in chronic uraemic (CU) patients. Any role that hypertension may play in CU patient outcomes assumes added significance. The elevation of some hormonal factors in early clinical stage could represent a valuable marker of cardiac disease in CU. AIM: This study first investigated the role of several hormones on cardiac diastolic properties in CU patients. Moreover, the study investigated the association of hypertension with both diastolic function and release of vasoactive hormones in CU patients. RESULTS: We have reported that the early impairment of diastolic function is correlated with the elevation of both circulating plasma atrial natriuretic factor and endothelin-1 (ET-1) in hypertensive CU patients. Since the effect of ET-1 on diastolic function is still poorly understood, we have investigated also this issue. In eight additional patients with reduced E/A ratio, but without uraemia, hypertension or chronic heart failure, we have showed a high inverse correlation between the values of E/A ratio and ET-1 plasma concentrations. CONCLUSIONS: These results strongly suggest that the elevation in ET-1 levels was correlated with diastolic dysfunction in man. This phenomenon may have important pathophysiological implications suggesting the possibility of an early therapeutic approach in these patients.

Atrial natriuretic factor and sympathetic activation in human heart failure.

The neurohormonal changes occur early, have important prognostic value, and may play a role in the evolution and progression of heart failure in man. Atrial natriuretic factor (ANF) is a natriuretic and vasorelaxant peptide. Previous studies indicated that plasma ANF provides prognostic information and, ANF levels closely related to both severity of disease and catecholamine levels but, it is still unclear if high circulating levels of ANF, which are present in heart failure constantly, may be to correlate with sympathetic nervous activity in man. Thus, the aim of the present study was to investigate the relations between the release of ANF and the sympathetic system in human heart failure. We studied 18 patients with heart failure (CHF) and a control Group (n = 14) of healthy subjects. To induce adrenergic activation in physiologic way patients were underwent to a low-exercise by cycle-ergometer in supine position. Blood was collected at rest, and immediately after exercise for determination of plasma levels of ANF, norepinephrine and epinephrine levels. ANF values at rest were 35.9 +/- 19.2 pg/ml in controls and 190.7 +/- 34.2 pg/ml (p < 0.001 vs controls) in CHF patients. As well norepinephrine levels showed higher values in patients (295.7 +/- 47.8 pg/ml), than in normal subjects (143.5 +/- 33.3 pg/ml; p < 0.01). In CHF patients epinephrine levels were 100.1 +/- 21.2 pg/ml (p < 0.01 vs controls). ANF levels were in normal subjects 87.9 +/- 19.2 pg/ml (p < 0.01 vs rest) after exercise. In CHF patients ANF values were 275.3 +/- 59.8 pg/ml; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Histological findings and evidence of lipid conjugated dienes and malonyldialdehyde in human fetal aortas.

Recent evidence strongly suggests that peroxidative modification of lipids may play a significant role in atherogenesis. In our present research, we investigated if the oxidative stress mediated by oxygen free radicals was a pathophysiologic condition that occurred in the early stages of human development. Thus the aim of this research was to examine lipid peroxidation in human fetal aortas. Human fetal aortas and proximal iliac arteries (n = 8) were obtained from fetuses aged 7 +/- 2 months, immediately after autopsy. Lipids from the initial fatty streak lesions (LFS) and the vessels uninvolved (LUV) were extracted by the chloroform/methanol method. Lipid peroxidation levels were measured by two different methods: determination of lipid conjugate dienes (the spectrum trend was recorded from 320 to 200 nm with a spectrophotometer) and malonyldialdehyde (MDA) content (TBA method). We observed that lipid conjugated dienes were present in LFS, but not in LUV, with a characteristic absorption peak at 233 nm. In addition, MDA levels were significantly higher when the LFS = 3.85 +/- 0.91 nmol than when the LUV = 0.41 +/- 0.12 nmol (p < 0.001 versus LUV). The presence of lipid peroxidation in our samples could be mediated by free radical production in the first stages of human development. Thus these data suggest that LFS peroxidation mediated by free radicals occurs in the vascular circulation in the early stages of human development. This could influence the progression of vascular damage and atherosclerotic disease.

[Morphological and biochemical study of the lipid components of the fetal aorta]. / Studio morfologico e biochimico della componente lipidica della aorta fetale.

We made a biochemical and histochemical study of the lipidic component of intima of fetal aortas on 8 autopsy cases (7 +/- 2 months aged) arrived at our observation in the Pathology's Institute of II Faculty of Naples. We made a study with freeze-sections stained with Oil-Red 0 and after dissociation of the intima by the adventitia, it is valued biochemically the lipidic peroxidation studying the levels of malonyldialdehyde (MDA) like indirect marker of peroxidation. It is known that is present a lipidic component in the intima of fetal aorta whether intracellular or extracellular (Fig. 1, 2). Sometimes this component can accumulate until to determinate true lipidic striae. The aim of this study is a detection of MDA in lipids extracted from human fetal aortas. MDA levels was measured by Thiobarbituric method (TBA): lipids were extracted both intima and adventitia by Chloroform/methanol method, after surgery immediately. The results are expressed in nMoles/mg of lipids +/- Standard Deviation. Controls of spontaneous lipid peroxidation was take at a different times. It is known that in vitro incubation of LDL with cultured endothelial cells, smooth muscle cells or macrophages leads to peroxidation of LDL phospholipids and oxidatively modified LDL become atherogenic via foam cells production. In addition lipid peroxidation was formed by the direct peroxidation of unsaturated fatty acids and their esters are capable of further lipoperoxide production by oxygen free radical; chain reactions. In this context lipid peroxidation could be an important factor in the first stage of human pathophysiological development and this phenomenon may be related by an early free radical production.

[Clinico-pathological evaluation of patients with homozygous familial hypercholesterolemia]. / Valutazione clinico-patologica in pazienti affetti da ipercolesterolemia familiare omozigote.

The authors have studied 8 patients with Homozygous Familial Hypercholesterolemia (FHO) an autosomal genetic dominant disease due to mutation of the gene encoding a cell surface receptor for LDL. Anatomic and pathologic abnormalities caused by LDL-cholesterol and B-Apolipoprotein high plasma levels were found. We also measured malondialdehyde levels in plasma and atherosclerotic plaques of the only autoptic case observed. MDA-levels are an index of lipid peroxidation. Cutaneous xanthomatosis lesions and severe cardiovascular disease were also present.