Relationship between left ventricular mass and endothelium-dependent vasodilation in never-treated hypertensive patients.
(17/3311)
BACKGROUND: Hypertensive patients are characterized by development of both left ventricular hypertrophy (LVH) and endothelial dysfunction METHODS AND RESULTS: We enrolled 65 never-treated hypertensive patients (36 men and 29 women aged 45.6+/-6.0 years) to assess the possible relationship between echocardiographic left ventricular mass (LVM) and endothelium-dependent vasodilation. Left ventricular measurements were performed at end diastole and end systole according to the recommendations of the American Society of Echocardiography and the Penn Convention. LVM was calculated with the Devereux formula and indexed by body surface area and height raised to the 2.7th power. The endothelial function was tested as responses of forearm vasculature to acetylcholine (ACh), an endothelium-dependent vasodilator (7.5, 15, and 30 microg. mL-1. min-1, each for 5 minutes), and sodium nitroprusside (SNP), an endothelium-independent vasodilator (0.8, 1.6, and 3.2 microg. mL-1. min-1, each for 5 minutes). Drugs were infused into the brachial artery, and forearm blood flow (FBF) was measured by strain-gauge plethysmography. A negative significant relationship between indexed LVM and peak of increase in FBF was found during ACh infusions (r=-0. 554; P<0.0001). In addition, hypertrophic patients had a significantly lower responsive to ACh than patients without LVH (the peak increase in FBF was 9.9+/-3.7 versus 16.1+/-8.1 mL per 100 mL of tissue per minute; P<0.0001). No significant correlation was observed between LVM and FBF during SNP infusion. CONCLUSIONS: Our data provide the first evidence that echocardiographic LVM in hypertensive patients is inversely related to FBF responses to the endothelium-dependent vasodilating agent ACh, but it is likely that both endothelium and LVM are damaged by hypertension. (+info)
Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study.
(18/3311)
AIMS: To determine the prevalence of heart failure and symptomatic as well as asymptomatic left ventricular systolic dysfunction in the general population. METHODS AND RESULTS: In 5540 participants of the Rotterdam Study (age 68.9+/-8.7 years, 2251 men) aged 55-95 years, the presence of heart failure was determined by assessment of symptoms and signs (shortness of breath. ankle oedema and pulmonary crepitations) and use of heart failure medication. In 2267 subjects (age 65.7+/-7.4 years, 1028 men) fractional shortening was measured. The overall prevalence of heart failure was 3.9% (95% CI 3.0+/-4.7) and did not differ between men and women. The prevalence increased with age, with the exception of the highest age group in men. Fractional shortening was higher in women and did not decrease appreciably with age. The prevalence of left ventricular systolic dysfunction (fractional shortening <=25%) was approximately 2.5 times higher in men (5.5%, 95% CI 4.1-7.0) than in women (2.2%, 95% CI 1.4-3.2). Sixty percent of persons with left ventricular systolic dysfunction had no symptoms or signs of heart failure at all. CONCLUSIONS: The prevalence of heart failure is appreciable and does not differ between men and women. The majority of persons with left ventricular systolic dysfunction can be regarded as having asymptomatic left ventricular systolic dysfunction. (+info)
Congestive heart failure arising from diastolic dysfunction in the presence of normal left-ventricular systolic function.
(19/3311)
Congestive heart failure due to diastolic dysfunction is a common clinical entity, particularly in the elderly. As outlined, such patients fall into a larger group of all patients with CHF symptoms and normal systolic function. When finding "normal" systolic function, the clinician should embark upon a carefully outlined diagnostic work-up geared toward eliminating confounding or treatable contributing causes of dyspnea or typical CHF symptoms. The prognosis for CHF patients with primarily diastolic dysfunction is not as poor as for those with LV systolic dysfunction, although the prevalence, associated morbidity, and costs are great. In contrast to the large number of successful clinical trials that have guided treatment of LV systolic failure, an extremely limited number of trials have specifically addressed themselves to diastolic dysfunction. Marked symptomatic relief can often be provided with careful attention to tailored therapy, although little is known with regard to outcome. Refinements in noninvasive imaging methods and hemodynamic indices of diastolic function may lead to improved patient care. (+info)
Hemodynamic effects of direct biventricular compression studied in isovolumic and ejecting isolated canine hearts.
(20/3311)
BACKGROUND: Biventricular direct cardiac compression (DCC) can potentially support the failing heart without the complications associated with a blood/device interface. The effect of uniform DCC on left and right ventricular performance was evaluated in 7 isolated canine heart preparations. METHODS AND RESULTS: A computer-controlled afterload system either constrained the isolated heart to contract isovolumically or simulated hemodynamic properties of physiological ejection. Biventricular DCC was provided by a chamber surrounding the heart that allowed adjustment of the compression pressure, onset time, and duration. Through a series of ventricular preloads, the effect of DCC on the end-systolic pressure-volume relationship (ESPVR) was evaluated under isovolumic and ejecting conditions. Under both conditions, DCC shifted the ESPVR of the left and right ventricles upward by an amount approximately equal to the compression pressure. The augmentation of end-systolic pressure for each initial preload tested, however, was less under ejecting conditions, because reductions in end-systolic and end-diastolic volumes occurred with ejection. Nevertheless, the net effect was to increase stroke volume. Measurement of M&f1;O2 demonstrated that at a given ventricular volume, M&f1;O2 did not change with DCC; however, peak ventricular pressure increased substantially, so that the effective pressure-volume area increased. CONCLUSIONS: Biventricular DCC can augment end-systolic pressure with no added costs of M&f1;O2. Under ejecting conditions, this augmentation of ventricular contracting ability manifests as increases in stroke volume. Thus, DCC represents a feasible alternative form of ventricular assist, and devices that support the heart in this manner should be further explored. (+info)
Vascular endothelin-1 gene expression and synthesis and effect on renal type I collagen synthesis and nephroangiosclerosis during nitric oxide synthase inhibition in rats.
(21/3311)
BACKGROUND: The progression of hypertension during NO deficiency is associated with renal vascular fibrosis due to increased extracellular matrix (mainly collagen I) formation. The purpose of the present study was to investigate whether endothelin-1 (ET-1) is involved in this pathophysiological process. METHODS AND RESULTS: Treatment of rats for 4 weeks with the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) 50 mg. kg-1. d-1 increased systolic blood pressure to 159+/-12 mm Hg. In animals treated with L-NAME, histological evaluation of renal sections revealed an increased formation of extracellular matrix (Masson's trichrome), and specifically of collagens (Sirius red). A part of this fibrosis was attributed to abnormal collagen I presence, because mRNA expression of the collagen I alpha1 chain (reverse transcription-polymerase chain reaction) and procollagen I formation (radioimmunoassay) were increased 3- and 2.5-fold, respectively, in the renal resistance vessels of hypertensive animals. In subsequent experiments, we examined whether ET-1 was involved in activation of collagen I formation. mRNA expression (RNase protection assay) of preproET-1 and ET-1 content (radioimmunoassay) were 10-fold and 3-fold increased, respectively, in renal microvessels of rats treated with L-NAME. Interestingly, in these vessels, ET-1 (immunostaining) was colocalized with sudanophilic lesions. Bosentan, an ET receptor antagonist (20 mg. kg-1. d-1), coadministered with L-NAME canceled the increased mRNA expression and synthesis of collagen I and attenuated the severity of renal vascular lesions without affecting L-NAME-induced high blood pressure. CONCLUSIONS: These data demonstrate that ET-1 synthesis is increased in renal microvessels when NO production is suppressed. In this model of hypertension, ET-1 is a major activator of collagen I formation in renal resistance vessels and participates in the development of renal fibrosis without affecting systolic blood pressure. (+info)
Effect of NO donors on LV diastolic function in patients with severe pressure-overload hypertrophy.
(22/3311)
BACKGROUND: Previous experimental studies have shown that nitric oxide (NO) modulates cardiac function by an abbreviation of systolic contraction and an enhancement of diastolic relaxation. However, the response to NO donors of patients with severe pressure-overload hypertrophy and diastolic dysfunction is unknown. METHODS AND RESULTS: Intracoronary NO donors were given to 17 patients with severe aortic stenosis. A dose-response curve was obtained with nitroglycerin (30, 90, and 150 microg) in 11 patients and sodium nitroprusside (1, 2, and 4 microg/min) in 6. Left ventricular (LV) high-fidelity pressure measurements with simultaneous LV angiograms were performed at baseline and after the maximal dose of NO. The dose-response curve for intracoronary NO donors showed a marked fall in LV end-diastolic pressure, from 23 to 14 mm Hg (-39%; P<0.0001), whereas LV peak systolic pressure fell only slightly, from 206 to 196 mm Hg (-4%; P<0.01). End-diastolic chamber stiffness decreased from 0.12 to 0.07 mm Hg/mL (P<0.0001) and end-systolic stiffness from 1.6 to 1.3 mm Hg/mL (P<0.01). Heart rate, right atrial pressure, LV ejection fraction, the time constant of isovolumic pressure decay (tau), and LV filling rates remained unchanged. CONCLUSIONS: In patients with severe pressure-overload hypertrophy, intracoronary NO donors exert a marked decrease in LV end-diastolic pressure without affecting LV systolic pump function. Thus, the hypertrophied myocardium appears to be particularly susceptible to NO donors, with a marked improvement in diastolic function. (+info)
Clinically safe dosage of felypressin for patients with essential hypertension.
(23/3311)
Hemodynamic changes were evaluated in patients with essential hypertension when felypressin of various concentrations was administered. The parameters studied were systolic pressure, diastolic pressure, heart rate, left ventricular systolic phase, and endocardial viability ratio. Results showed that blood pressure tended to increase, and the value of 1/pre-ejection period2 (PEP2) tended to decrease, upon administration of 3 ml of 2% propitocaine containing 0.06 international units/ml (IU/ml) of felypressin. Significant increase of blood pressure and decrease in 1/PEP2 was noted upon administration of 3 ml of anesthetic solution containing 0.13 IU/ml of felypressin. No ischemic change of the myocardium was detected even with the highest felypressin concentration (3 ml of 2% propitocaine containing 0.25 IU/ml of felypressin). These results suggest that the clinically safe dosage of felypressin for patients with essential hypertension is approximately 0.18 IU. This amount is equivalent to 6 ml of 3% propitocaine with 0.03 IU/ml of felypressin, which is a commercially available local anesthetic for dental use. It seems that the decrease in 1/PEP2 that occurred during blood pressure increase was due to the increase in afterload caused by contraction of the arterioles. Although in the present study no ischemic change was noted, special care should be taken to prevent myocardial ischemia in patients with severe hypertension. (+info)
Factors underlying the increase in carotid intima-media thickness in borderline hypertensives.
(24/3311)
To define the role played by various risk and behavioral factors in the increase of carotid intima-media thickness (IMT) observed in borderline hypertensives. Using B-mode ultrasonography, we compared 97 borderline hypertensives enrolled in the HARVEST study to 27 normotensive controls. Intima-media thickness was measured in the right and left common carotid artery, bulb, and internal carotid artery. Mean IMT (m-IMT), maximum IMT (M-IMT), the mean of M-IMT (M-MAX), and the prevalence of raised lesions (IMT>1 mm) were established. Compared to the controls, higher systolic BP, diastolic BP, mean arterial blood pressure levels and body mass index (BMI) were present in the borderline hypertensives, whereas age, smoking, physical activity, serum cholesterol, and triglycerides were similar. After adjusting for age, sex, heart rate, BMI, smoking, serum cholesterol, triglycerides, and physical activity, higher values of m-IMT and M-IMT were present in most carotid segments of borderline hypertensives compared with controls. After further adjustment for systolic BP and diastolic BP, differences were no longer significant. The adjusted M-MAX was 0.59+/-0.12 in borderline hypertensives compared with 0.50+/-0.10 in controls (P<0.001). After adjustment for systolic BP and diastolic BP it was 0.58+/-0.11 in borderline hypertensives compared with 0.50+/-0.12 in controls (P<0.005). In the various carotid segments, the prevalence of raised lesions was 1. 2% in borderline hypertensives compared with 0.3% in controls (P<0. 001). In the multivariate analysis m-IMT, M-IMT, and M-MAX were related to ambulatory mean arterial pressure, systolic BP and diastolic BP, serum cholesterol and triglycerides, BMI, age, and physical activity. Higher IMT values were found in subjects who were physically active than in those who were sedentary. In borderline hypertensives, an increase in IMT takes place not only in the common carotid artery but also in the bulb and the internal carotid segment. Blood pressure levels are a main determinant of m-IMT while the interaction of BP with other risk factors such as age and plasma lipids is more relevant for advanced intima-media thickening such as M-MAX. (+info)