Left ventricular hypertrophy, blood pressure and ACE genotype in untreated hypertension

It has been suggested that the deletion polymorphism of the angiotensin-converting enzyme (ACE) genotype may be important in the development of left ventricular hypertrophy (LVH). In order to test this hypothesis we investigated the interaction between blood pressure (BP), LVH and ACE genotype in 86 previously untreated hypertensive patients. Each underwent two-dimensional and Doppler echocardiography and ACE genotyping. There were no significant differences in BP, the parameters of left ventricular structure (including left ventricular mass index) or diastolic function between the three genotype groups. Additionally, there were no significant differences in the relationship between systolic BP and left ventricular mass index among the three genotype groups (II genotype, r = 0.46, P = 0.02; ID genotype, r = 0.42, P = 0.01; DD genotype, r = 0.34, P = 0.10; F = 0.38). In contrast to some previous studies, we have found in this group of previously untreated hypertensive subjects no evidence to suggest that the deletion polymorphism of the ACE genotype is important in the development of LVH.     

Left ventricular hypertrophy and ambulatory blood pressure monitoring in chronic renal failure

BACKGROUND: Left ventricular hypertrophy (LVH) is both common and an important predictor of risk of death in end-stage renal failure (ESRF). In mild to moderate chronic renal failure (CRF), the timing of onset of LVH and the factors involved in its initial development have not been fully elucidated. The present study was undertaken to examine the prevalence and potential determinants of echocardiographically determined LVH in this connection, and to compare 24-h ambulatory blood pressure (BP) recordings with BP measured at a previous clinic visit. METHODS: From a cohort of 120 non-diabetic patients who had been attending a nephrology clinic, 118 agreed to participate in the study. Of these we selected for analysis 85 stable patients (37 male). Patients with known cardiovascular disease, those with a history of poor compliance with antihypertensive medication, and those in whom such medication had been changed in the previous 3 months were excluded. Clinic BP, 24-h ambulatory BP, echocardiography, body mass index (BMI), serum creatinine (SCr), creatinine clearance (CrCl), haemoglobin (Hb), fasting cholesterol (CHOL), triglyceride TRIGL), plasma glucose, calcium (Ca), phosphate (PO4), alkaline phosphatase (ALK PHOS), parathyroid hormone (PTH) concentrations, and 24-h urinary protein were assessed in all patients. Seventy-seven per cent were on antihypertensive medication. RESULTS: LVH was detected in 16% of patients with CrCL > 30 ml/min, and 38% of patients with CrCl < 30 ml/min. By stepwise regression analysis, ambulatory systolic BP (P < 0.0001), male gender (P < 0.0001), BMI (P < 0.0002), and Hb concentration (P < 0.002) were the only independent determinants of left ventricular (LV) mass. Nocturnal systolic BP (P < 0.02) was the main determinant of LVH in the group of patients with advanced CRF. The correlation between left ventricular mass index (LVMI) and mean 24-h ambulatory systolic BP (r = 0.52, 95% confidence interval 0.50-0.54) was statistically significantly stronger than with outpatient systolic BP (r = 0.25, 95% confidence interval 0.23-0.27). The same was true for the correlation between LVMI and mean 24-h ambulatory diastolic BP (r = 0.42, 95% confidence interval 0.40-0.44), and outpatient diastolic BP (r = 0.22, 95% confidence interval 0.20-0.24). CONCLUSIONS: Twenty-four hour ambulatory BP recording and echocardiography are required for accurate diagnosis of inadequate BP control and early LVH in patients with chronic renal impairment, independent determinants of which are hypertension, male sex, BMI, and anaemia.     

Association between blood pressure and circulating hormonal factors with left ventricular mass in patients with essential hypertension older than 55 years of age

BACKGROUND: The prevalence of left ventricular hypertrophy (LVH) is higher in elderly patients with hypertension than in normotensive patients. The factors relationed herewith are not well known. The first purpose was to analyse the relationship between the levels of blood pressure (BP) recorded by ambulatory blood pressure monitoring (ABPM) and the left ventricular mass index (LVMI) in a group of untreated patients older than 55 years with essential hypertension. Our second purpose was to observe the relationship between the concentration of several circulating hormones and the left ventricular mass index. SUBJECTS AND METHODS: The study included 31 untreated patients with mild to moderate essential hypertension and 37 healthy normotensives. Both groups were of similar age, sex and body mass index. We determined for both groups the casual arterial pressure (CAP), ambulatory BP monitoring (ABPM) throughout 24 h, daytime (07.00-23.00 h), nighttime (23.00-07.00 h), left ventricular mass index (LVMI) (following Devereux's formula) and circulating levels of endothelin-1, aldosterone, renine, free adrenaline and noradrenaline. RESULTS: The ILVM in hypertensive patients was 139.6 +/- 35.9 g/m2 and in 124.0 +/- 31.8 g/m2 in normotensive (p < 0.05). The percentage of patients with LVH was 63 and 43%, respectively (p < 0.05). The LVMI in hypertensive patients was correlated with the diastolic CAP (97 +/- 7 mmHg) (r = 0.41; p < 0.05), unlike with the systolic CAP (164 +/- 18 mmHg). The ILVM in normotense patients was not associated neither with the systolic CAP (126 +/- 10 mmHg) nor with the diastolic (79 +/- 6 mmHg). In hypertensive patients we found a slight association between the LVMI and the systolic ABPM (130 +/- 14 mmHg) during nighttime (r = 0.41; p < 0.05). The rest of average ambulatory BP and the hormonal values at study did not show a correlation with the LVMI in both groups. CONCLUSIONS: A slight correlation exists between BP (casual and determined with ambulatory blood pressure monitoring throughout 24 hours) and the left ventricular mass index in mild to moderate untrated hypertensive patients older than 55 years. We did not observe correlations between the circulating levels of endothelin-1, renin, aldosterone, free adrenaline and noradrenaline and the left ventricular mass. The average ventricular mass and the number of subjects with ventricular hypertrophy was significantly increased in hypertensives than in normotensives.     

Effects of verapamil on left ventricular diastolic dysfunction

To assess the effects of verapamil on left ventricular relaxation and filling dynamics in patients with left ventricular diastolic dysfunction (LVDD), Doppler echocardiography (DE) and cardiac catheterization (Cath) were simultaneously performed in 30 cases with LVDD. The left ventricular filling and relaxation indices were measured with DE and Cath respectively, before and after intravenous injection of verapamil. The result showed that after verapamil injection all left ventricular filling measured with DE were significantly improved in all cases, while left ventricular relaxation indices showed significant improvement only in patients with hypertrophic cardiomyopathy and hypertensive heart disease but no changes in patients with old myocardial infarction. There were no significant correlations between left ventricular filling and relaxation indices. It is concluded that the major mechanism of left ventricular filling improvement induced by verapamil is the reduction of left ventricular afterload and verapamil has different therapeutic effects on LVDD with different etiology.     

Left ventricular geometry as an independent predictor for extracardiac target organ damage in essential hypertension

Left ventricular hypertrophy (LVH) is an independent cardiovascular risk factor. It has not been established, however, whether left ventricular geometry is an independent predictor of extracardiac target organ damage in essential hypertension. Study groups were classified according to relative wall thickness: 27 patients with concentric LVH and 50 patients with eccentric LVH. Age and left ventricular mass indexes of two groups were matched. As indexes of extracardiac target organ damage, retinal funduscopic grade, and serum creatinine level were measured. The severity of hypertensive retinopathy and the renal involvement were more severe in patients with concentric LVH than in patients with eccentric LVH. Extracardiac target organ damage was consistently higher in patients with concentric LVH than in those with eccentric LVH. Systemic hemodynamics paralleled ventricular geometric patterns, with higher peripheral resistance and lower aortic compliance in patients with concentric LVH, whereas end-diastolic volumes and stroke volumes were higher in patients with eccentric LVH than in patients with concentric LVH. In addition, total peripheral resistance was related to retinal fundoscopic grade (r = 0.41, P < .01), and serum creatinine level (r = 0.28, P < .05). Even in the presence of an identical degree of LVH, echocardiographically determined left ventricular geometry may provide a further independent stratification of extracardiac target organ damage in essential hypertension.     

Chronic L-arginine treatment increases cardiac cyclic guanosine 5'-monophosphate in rats with aortic stenosis: effects on left ventricular mass and beta-adrenergic contractile reserve

OBJECTIVES: We tested the hypothesis that nitric oxide (NO) cyclic guanosine 5'-monophosphate (GMP) signaling is deficient in pressure overload hypertrophy due to ascending aortic stenosis, and that long-term L-arginine treatment will increase cardiac cyclic GMP production and modify left ventricular (LV) pressure overload hypertrophy and beta-adrenergic contractile response. BACKGROUND: Nitric oxide cyclic GMP signaling is postulated to depress vascular growth, but its effects on cardiac hypertrophic growth are controversial. METHODS: Forty control rats and 40 rats with aortic stenosis left ventricular hypertrophy ([LVH] group) were randomized to receive either L-arginine (0.40 g/kg/day) or no drug for 6 weeks. RESULTS: The dose of L-arginine did not alter systemic blood pressure. Animals with LVH had similar LV constitutive nitric oxide synthase (cNOS) mRNA and protein levels, and LV cyclic GMP levels as compared with age-matched controls. In rats with LVH L-arginine treatment led to a 35% increase in cNOS protein levels (p = 0.09 vs untreated animals with LVH) and a 1.7-fold increase in LV cyclic GMP levels (p < 0.05 vs untreated animals with LVH). However, L-arginine treatment did not suppress LVH in the animals with aortic stenosis. In contrast, in vivo LV systolic pressure was depressed in L-arginine treated versus untreated rats with LVH (163 +/- 16 vs 198 +/- 10 mm Hg, p < 0.05). In addition, the contractile response to isoproterenol was blunted in both isolated intact hearts and isolated myocytes from L-arginine treated rats with LVH compared with untreated rats with LVH. This effect was mediated by a blunted increase in peak systolic intracellular calcium in response to beta-adrenergic stimulation. CONCLUSIONS: Left ventricular hypertrophy due to chronic mechanical systolic pressure overload is not characterized by a deficiency of LV cNOS and cyclic GMP levels. In rats with aortic stenosis, L-arginine treatment increased cardiac levels of cyclic GMP, but it did not modify cardiac mass in rats with aortic stenosis. However, long-term stimulation of NO-cyclic GMP signaling depressed in vivo LV systolic function in LVH rats and markedly blunted the contractile response to beta-adrenergic stimulation.     

Coronary pressure as a determinant of B-type natriuretic peptide gene expression in isolated perfused adult rat heart

The role of coronary flow in the regulation of ventricular B-type natriuretic peptide (BNP) gene expression was studied in isolated perfused rat heart preparation. The increase of coronary flow from 5 ml/min to 20 ml/min for 2 h resulted in a 132+/-6 mm Hg increase in aortic perfusion pressure. The changes in BNP mRNA and immunoreactive BNP (IR-BNP) levels in response to hemodynamic stress were compared to those of c-fos and adrenomedullin (ADM) gene expression. The increase of coronary flow resulted in 1.5-fold increases in the left ventricular BNP mRNA (P < 0.001) and IR-BNP (P < 0.05) levels in 2-month old rats. There was also a 1.5-fold (P < 0.05) increase in ventricular c-fos mRNA levels, whereas ADM mRNA levels decreased by 74% (P < 0.001) in the left ventricle. In 18-month old rats, the increase in coronary flow decreased left and right ventricular BNP mRNA levels by 18% (P < 0.05) and 39% (P < 0.001), respectively. There were no changes in IR-BNP peptide and c-fos mRNA levels, whereas ADM mRNA levels decreased by 46% (P < 0.001) in the left ventricles. The results show that increased aortic perfusion pressure results in differential expression of cardiac genes including up-regulation of ventricular BNP and c-fos gene expression and down-regulation of ADM gene expression. Furthermore, aging seems to elevate the threshold at which hemodynamic stress of the heart results in a response at BNP gene level.     

Effect of the treatment with amlodipine on left ventricular hypertrophy in hypertensive patients

BACKGROUND: Left ventricular hypertrophy (LVH) is one of the physiopathological effects of hypertension and one of the main risk factors for sudden death, myocardial infarction and congestive heart failure. Drugs to treat hypertension must not only reduce blood pressure, but also modify the facts which lead to ventricular hypertrophy. This study has been designed to assess the effect of amlodipine, a calcium-antagonist, on LVH in hypertensive patients. METHODS: 20 hypertensive patients (mild to moderate, both sexes, mean age 45.0 yr) were included in a single-blind study. After an initial, four weeks placebo period, active treatment was given (amlodipine 5 mg a day). Dose titration was made after 4-8 weeks to 10 mg a day if necessary and continued until the end of the study. Systolic (SBP) and diastolic blood pressure (DBP), as well as pulse rate (PR) and adverse events were recorded at every visit. Blood and urine analysis, catecholamine, plasmatic renin activity and Mode M echocardiography were made at the beginning and the end of the study. RESULTS: Only one patient was excluded. SBP and DBP showed a significantly fall (p < 0.001). In 80% of patients DBP fell under 90 mm Hg. Every echocardiographic parameter, but left ventricular diastolic dimension, showed significantly reductions at the end of the study: septum thickness (p = 0.001), posterior wall thickness (p = 0.001), left ventricular systolic dimension (p = 0.014), wall relative thickness (p = 0.015), shortening fraction (p = 0.009), left ventricular mass (p = 0.001) and corrected left ventricular mass (p = 0.001). Blood parameters did not modify. CONCLUSIONS: Amlodipine has a beneficial effect on LVH and also is an effective and safe drug to treat mild to moderate hypertension.     

ACE inhibitors unmask incoordinate diastolic wall motion in restrictive left ventricular disease

OBJECTIVE: To assess the effect of ACE-inhibition on left ventricular filling and wall motion in patients with a clinical diagnosis of heart failure. DESIGN: Prospective examination of left ventricular systolic and diastolic function using M mode echocardiography and pulsed and continuous wave Doppler before and three weeks after starting an ACE inhibitor. SETTING: A tertiary referral centre for cardiac disease equipped with non-invasive facilities. SUBJECTS: 30 outpatients with a clinical diagnosis of heart failure in whom treatment with an ACE inhibitor was started; age 61 (SD 11) years; 27 male; 3 female; 21 healthy controls of similar age. RESULTS: Left ventricular cavity was dilated both at end systole and end diastole, and fractional shortening reduced. Although mean isovolumetric relaxation time (IVRT) and transmitral E (early) to A (late) filling velocity (E/A) ratio were not different from normal, a value of 1.0 on the normal frequency plot of the E/A ratio divided the patients bimodally into two groups: 20 patients (group A) with E/A ratio > 1.0 and 10 patients (group B) < 1.0. In group A patients, IVRT was short as was transmitral E wave deceleration time compared to normal (P < 0.001), fulfilling the criteria of restrictive left ventricular physiology. Left ventricular wall motion during IVRT was coordinate and left ventricular end diastolic pressure was raised on the apex-cardiogram (P < 0.001). In group B, E wave deceleration time was longer, relaxation incoordinate, and apexcardiogram normal. With an ACE inhibitor: in group A, left ventricular dimensions fell at end diastole (P < 0.05) and end systole (P < 0.01) but fractional shortening did not change; long axis total excursion (P < 0.01) and peak rate of shortening (P < 0.05) both increased; IVRT increased (P < 0.001) with the appearance of markedly incoordinate wall motion, minor axis lengthening, and long axis shortening (P < 0.001 for both); A wave amplitude also consistently increased (P < 0.001); finally, transmitral E wave velocity fell and A wave velocity increased. ACE inhibition did not alter any of the left ventricular minor and long axis or transmitral Doppler variables in patients in group B. CONCLUSIONS: Patients with a clinical diagnosis of heart failure differ in their presentation and response to ACE inhibition according to baseline haemodynamics. In restrictive left ventricular physiology, ACE inhibition reduces cavity size and prolongs IVRT, compatible with a fall in left atrial pressure. At the same time, ventricular relaxation becomes very delayed and incoordinate, greatly reducing early diastolic left ventricular filling velocity. Thus ACE inhibition unmasks major diastolic abnormalities in patients with restrictive left ventricular disease.     

Effects of antihypertensive therapy on left atrial function

OBJECTIVES: To investigate left atrial (LA) function as a reservoir, as a conduit and as a booster pump in essential hypertension (EH). LA volumes were echocardiographically measured in 28 untreated hypertensive patients and in 20 control subjects. BACKGROUND: LA makes a large contribution in left ventricular filling, especially in patients with impaired diastolic function. LA function is fundamental in left ventricular filling in hypertensive patients as hypertension results in left ventricular diastolic dysfunction. METHODS: Diagnosis of EH (blood pressure > 140/90 mm Hg) was based on three repeated readings of blood pressure (BP). Patients with myocardial infarction, cardiomyopathy, valvular or congenital heart disease were excluded. Doppler diastolic early (E) and late (A) velocity of mitral inflow were measured. The following indexes were calculated: left ventricular mass index (LVMI) using the Penn convention; left ventricular stroke volume (LVSV); LA reservoir volume (LARV = LA maximal volume at mitral valve opening minus minimal volume); LA conduit volume (LACV = LVSV-LARV). Atrial systolic function was assessed by calculating the active emptying fraction (volume at onset of atrial systole minus minimal volume/volume at onset of atrial systole, the E/A ratio and the LA ejection force (0.5 rho A2 MOA, where rho = the density of blood, MOA = mitral orifice area from the parasternal short axis view). Measurements were obtained in all hypertensive patients before and after 16 weeks administration of either enalapril (10 or 20 mg) or enalapril +/- chlorthalidone (20/25 mg) once a day. RESULTS: After 16 weeks of treatment, BP was reduced significantly (from 172/110 to 137/86 mm Hg, P < 0.001). LVMI decreased significantly as well (from 141 to 123 g/m2) although it was higher compared to controls (94 g/m2, P < 0.001). LARV decreased significantly (from 35.4 to 29.3 cm3, P < 0.05) while LACV increased significantly (from 43.8 to 51.3 cm3, P < 0.05), LA active emptying fraction and E/A ratio did not change. LA ejection force decreased significantly (from 20.9 to 18.1 kdynes, P < 0.05) but it was greater than controls (16.7 kdynes, P < 0.01). There was a positive relationship of LVMI to LARV (P < 0.01) in controls (r = 0.77) which held true in hypertensive patients, before (r = 0.72) and after treatment (r = 0.69). There was a negative relationship of LVMI to LACV (P < 0.01) in controls (r = -0.65), and in hypertensive patients untreated (r = -0.74) and after treatment (r = -0.72). CONCLUSIONS: Our results showed that in hypertensive patients, LA reservoir function increases and LA conduit function decreases, while LA ejection force increases. Antihypertensive treatment with enalapril and/or thiazide, induces normalisation of the LA function in parallel to left ventricular hypertrophy regression.     

Regulation of extracellular matrix proteins in pressure-overload cardiac hypertrophy: effects of angiotensin converting enzyme inhibition

OBJECTIVE: Left ventricular hypertrophy (LVH) is characterized by remodeling of both myocyte and interstitial compartments of the heart. The aim of this investigation was to study the effects of angiotensin converting enzyme (ACE) inhibition on alterations in the composition of the interstitium in chronic pressure-overload hypertrophy. DESIGN: LVH was induced in weanling rats by banding the ascending aorta. Animals with aortic banding received either vehicle (n = 20), hydralazine (20 mg/kg per day, n = 20), or the ACE inhibitor ramipril (10 mg/kg per day, n = 20) during weeks 6-12 after banding. RESULTS: Compared with sham-operated, untreated rats (n = 20), aortic-banded vehicle and hydralazine-treated rats displayed substantially increased left ventricular weights and myocyte diameters whereas ramipril significantly blunted the hypertrophic response at the myocyte level (each P < 0.001) as well as the increase in left ventricular weight (each P < 0.01). In addition, image analysis revealed a significant induction of perivascular and interstitial tissue accumulation in vehicle- and hydralazine-treated rats (2.5-fold, each P < 0.0001). In contrast, ramipril-treated rats displayed attenuated interstitial and perivascular fibrosis, both being significantly diminished compared with vehicle- and hydralazine-treated rats (each P< 0.001). Further, vehicle- and hydralazine-treated rats were characterized by elevated steady-state messenger (m)RNA levels of fibronectin (2.7- and 2.8-fold, P< 0.005), collagen I (2.0- and 1.8-fold, P < 0.0005), collagen III (both 2.2-fold, P < 0.001) and laminin B (1.6- and 1.6-fold, P < 0.005). In parallel, the corresponding immunohistochemical signals were markedly enhanced in these groups. In comparison, ramipril significantly blunted the induction of collagen I and III, laminin B and fibronectin at both the mRNA and protein levels. These morphological and molecular differences between the hydralazine and ramipril groups could not be attributed to differences in left ventricular-pressures, which were markedly elevated in all aortic stenosis rats (1.9-fold, each P < 0.001 versus sham). In fact, given that ramipril but not hydralazine blunted the hypertrophic response to pressure overload, the echocardiographic measurements revealed that left ventricular systolic wall stress was higher in the ramipril group (70 +/- 1 versus 34 +/- 0.7 kdyn/cm2; P < 0.02). CONCLUSIONS: ACE inhibition may limit both myocyte and interstitial remodeling despite ongoing cardiac pressure overload.     

Cardiac beta-adrenoceptors and adenylyl cyclase activity in human left ventricular hypertrophy due to pressure overload

The effect of left ventricular hypertrophy (LVH) due to chronic pressure overload on right atrial (RA) and left ventricular (LV) myocardial beta-adrenergic receptor (beta-AR) density and subtypes, adenylyl cyclase (AC) activity and ADP-pertussis toxin ribosylated proteins was investigated in humans with LVH due to aortic stenosis and in patients without LVH undergoing heart surgery for mitral stenosis or coronary artery disease taken as controls. Both groups presented normal systolic function or plasma catecholamine levels. In LVH and controls, beta-AR density was similar in RA (62 +/- 6 vs 77 +/- 12 fmol.mg-1 protein) and LV (39 +/- 7 vs 32 +/- 2 fmol.mg-1 protein). In LVH, beta 1-AR percentage was < than in controls in LV (35 +/- 11 vs 73 +/- 5%, P < 0.05) but not in RA (79 +/- 5 vs 73 +/- 8%). Basal AC activity in RA (19 +/- 4 vs 21 +/- 6 pmol.mg-1 protein) and LV (22 +/- 5 vs 27 +/- 3 pmol.mg-1 protein) was similar in LVH and in controls. Isoprenaline-induced stimulation of AC in RA was similar in LVH and in controls (51 +/- 18 vs 36 +/- 18%) but < in LV of LVH (7 +/- 6 vs 45 +/- 6%, P < 0.05). In the presence of ICI-118,551 (a beta 2-adrenoceptor antagonist), isoprenaline failed to induce any increase in cAMP in LVH. The quantification of ADP-pertussis toxin ribosylated proteins indicated a lower concentration of substrates in LV myocardial membranes from LVH. These data indicate that in LVH due to pressure overload, there is a down-regulation of beta 1-AR and an increase in beta 2-AR density. This is associated with alterations of the transmembrane signalling marked by a decreased capacity of isoprenaline to stimulate AC and an impaired expression of Gi proteins.     

Functional activity and expression of the myocardial postreceptor adenylyl cyclase system in pressure overload hypertrophy in rat

OBJECTIVE: The aim of the present study was to investigate the functional regulation of the myocardial postreceptor adenylyl cyclase (AC) system in compensated left ventricular hypertrophy (LVH) and the effect of long-term angiotensin converting enzyme (ACE) inhibition. METHODS: Pressure overload LVH was induced in rats by supravalvular aortic banding for 12 weeks. At 12 weeks left ventricular function and inner diameters were analyzed by echocardiography of anesthetized animals, and responsiveness to forskolin (systolic developed pressure) was determined in isolated perfused hearts. Functional activities of AC and the stimulatory G protein Gs were measured as well as mRNA expression (quantitative slot blot analyses) of AC type V, isoforms of Gs alpha and Gi alpha 2. G protein alpha-subunits were also quantified by immunoblotting. Rats were treated with ramipril (Ram, 10 mg/kg per day p.o.) during weeks 7 to 12 to induce regression of LVH or with vehicle (Veh, tap water). RESULTS: Pressure overload induced severe LVH (3.2 +/- 0.09 g/kg in Veh vs. 1.8 +/- 0.03 in sham; P < 0.05) which was significantly reduced by ramipril (2.7 +/- 0.09; P < 0.05 vs. Veh). In-vivo left ventricular function and diameters were unchanged in LVH. In contrast, in hearts with LVH, responsiveness of left ventricles to forskolin was attenuated and basal, GTP gamma S and forskolin as well as manganese chloride-stimulated adenylyl cyclase activity was significantly downregulated by approximately 40% (basal 20.8 +/- 1.9 pmol cAMP/mg per min vs. 34.0 +/- 2.2 in sham; P < 0.01). However, no significant changes of AC type V mRNA were found in hypertrophied left ventricles. Functional activity of the stimulatory G protein Gs was reduced in LVH (48 +/- 7 pmol cAMP/mg per min in Veh vs. 68 +/- 3 in sham), whereas mRNA expression of long and short Gs alpha-isoforms was not altered and that of Gi alpha 2 was only slightly increased in ramipril-treated animals. Western analysis showed no significant differences of Gs alpha or Gi alpha 2 subunits. Long-term blockade of the renin-angiotensin system had no effect on the activity of the adenylyl cyclase system. CONCLUSIONS: Functional desensitization of adenylyl cyclase and stimulatory G protein occurred in rat adaptive LVH prior to the onset of severe left ventricular dysfunction which was not restored by ACE-inhibitor treatment. The desensitization seems not to be mediated by significant changes of mRNA expression of AC type V or abundance of regulatory G proteins.     

Atherosclerosis and left ventricular hypertrophy: persisting problems in treated hypertensive patients

OBJECTIVES: First, to determine whether hypertensive patients managed in general practice have more advanced atherosclerosis and left ventricular hypertrophy than matched normotensive patients from the same practices. Second, to investigate the associations of several potentially modifiable factors with these vascular and cardiac outcomes. DESIGN AND METHODS: We performed a case-control study of 500 hypertensive cases (systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg or receiving treatment) and 506 age- (mean 61 years) and sex- (54% female) matched normotensive controls recruited from general practices. Carotid artery far wall thickness (CWT), assessed by B-mode ultrasound, and left ventricular mass (LVM), assessed by M-mode echocardiography, were the main study outcome measures. RESULTS: Mean systolic/diastolic blood pressure levels in the 399 treated cases (145/87 mmHg) were lower than those in untreated cases (158/94 mmHg) but higher than those in controls (133/82 mmHg, all P < 0.0001). Mean body mass index (BMI) and total triglyceride levels were higher and high-density lipoprotein cholesterol was lower in cases than in controls (all P < 0.0004). Mean CWT was 10% greater in cases than in controls and LVM was 14% greater (both P < 0.001), but both were similar in treated and untreated cases (P > 0.05). In multivariate analyses, blood pressure and BMI were both directly and independently related to CWT and LVM (both P < 0.0001). CONCLUSIONS: In this study, hypertensive patients managed in general practice - whether treated with antihypertensive drugs or not - had more advanced atherosclerosis and left ventricular hypertrophy than did matched normotensive patients. Efforts to lower blood pressure further and to reduce BMI could potentially reduce these differences, and this might lead to a reduction in the risk of major cardiovascular events.     

M-mode echocardiographic diagnosis of dilated cardiomyopathy in giant breed dogs

M-mode echocardiograms were recorded from 62 giant breed dogs without historical, clinical, electrocardiographic and roentgenologic signs of heart disease, from six dogs with asymptomatic dilated cardiomyopathy (DCM, NYHA class I), and 13 dogs with symptomatic DCM (NYHA class III-IV). There was a general trend that several echocardiographic parameters were significantly in control Great Danes as compared to Newfoundlands and Irish Wolfhounds. There were substantial differences in left ventricular size both in systole and diastole and in systolic indices of the left ventricle between the control group, the asymptomatic dogs and symptomatic dogs with DCM (P = 0.0001). There was also a significant decreased in the interventricular septum thickness (P = 0.0001) and left ventricular free wall thickness in systole (P = 0.002) and diastole (P = 0.005) between the three groups. Furthermore, the left atrial/aortic ratio was significantly different between the three groups (P = 0.0001). It was concluded that this study established echocardiographic reference values in giant breed dogs which may be useful in the study of heart diseases in giant breed dogs.     

Direct and continuous electrochemical measurement of noradrenaline-induced nitric oxide production in C6 glioma cells

1. This study examined the effect of an acute injection of contrast medium on generation of arrhythmias in diseased hearts in man.2. Subjects were 100 patients in sinus rhythm undergoing cardiac catheterization in whom good quality echocardiograms could be obtained. The subjects comprised 78 males and 22 females aged 37-83 years.3. Arrhythmia induced by left ventricular angiography ranged from nil to brief bursts of ventricular tachycardia. There was a strongly positive relationship between left ventricular internal dimension in diastole (LVIDd) and induced arrhythmia. Out of 26 patients, 25 developed arrhythmia when LVIDd>=5 cm (96%), but only 24 out of 74 patients developed arrhythmia when LVIDd<5 cm (32%) (P<0.001). In non-dilated hearts where K+<4.0 mmol/l, arrhythmia developed in 100% (10 out of 10) of those with left ventricular hypertrophy (LVH), but in only 40% (8 out of 20) without LVH (P<0. 005). Where K+>=4.0 mmol/l, no arrhythmia occurred in patients with LVH but was present in 52% (31 out of 60) of patients without LVH (P<0.005). There were no relationships with age, end-diastolic pressure, blood pressure, ischaemic heart disease or sex of patient. 4. These data support the view that acute injection of contrast medium in humans induces arrhythmias dependent upon the underlying state of the heart, with potentially complex interplay between left ventricular dimension, hypertrophy and potassium status, supporting similar observations in experimental animals.     

Excessive responsibility in obsessional concerns: a fine-grained experimental analysis

OBJECTIVE: To assess the relation between ventricular arrhythmias after myocardial infarction and left ventricular remodelling. DESIGN: Prospective study with consecutive patients. METHODS: 97 patients with acute myocardial infarction underwent serial echocardiographic examinations (days 1, 2, 3, and 7, and after 3 weeks) to determine end diastolic volume, end systolic volume, and ejection fraction; volumes were normalised for body surface area and expressed as indices. Holter monitoring was performed on the day of the final echocardiogram. Coronary angiography was performed in 88 patients before hospital discharge. RESULTS: Complex ventricular arrhythmias (defined as Lown class 3-5) were found in 16 of 97 patients. In logistic regression models, variables predictive of complex ventricular arrhythmias were end systolic volume index on admission (b = 0.054, P = 0.015) and end diastolic volume index after three weeks (b = 0.034, P = 0.012). Complex arrhythmias were also related to the increase of end diastolic and end systolic volume indices throughout the study (F = 5.62, P = 0.046, and F = 6.42, P = 0.017, respectively by MANOVA). A two stage linear regression model of ventricular volume versus time from infarct showed that both intercept (initial volume) and slope (rate of increase) were higher for patients with complex arrhythmias in both diastole and systole (P < 0.001 for all). CONCLUSIONS: Complex ventricular arrhythmias after myocardial infarction are related to the increase of left ventricular volume rather than to depressed ejection fraction. Complex arrhythmias may be an aetiological factor linking left ventricular remodelling with higher mortality, but larger follow up studies of patients with progressive left ventricular dilatation after myocardial infarction are necessary to answer these questions.     

Heart rate and blood pressure variabilities in mild to moderate hypertensive patients with or without left ventricular hypertrophy

AIM OF THE STUDY: To compare heart rate (HR) and blood pressure (BP) variability in hypertensives with or without left ventricular hypertrophy (LVH). METHODS: Thirty-three mild to moderate hypertensive patients, mean age 45 +/- 15 years, underwent an echocardiogram, a 24 hr ambulatory BP monitoring (ABPM), a 24 hr ECG monitoring and a continuous BP recording over 15 minutes both in supine and standing positions, by using digital plethysmography (Finapres device). Statistical analysis: non parametric tests. RESULTS: [table: see text] CONCLUSION: LVH is associated with a reduction in the markers of sympathetic activity and a decreased baroreflex sensitivity.     

Regression of left ventricular hypertrophy results in improvement of QT dispersion in patients with hypertension

OBJECTIVES: Increased QT dispersion has been considered as predisposing to ventricular arrhythmias in hypertrophic cardiomyopathy, congestive heart failure, and coronary artery disease. An increased QT dispersion has also been found in hypertensive patients with left ventricular hypertrophy (LVH). The data on the effect of LVH regression on QT dispersion are limited. METHODS AND RESULTS: To assess the relation of LVH regression and QT dispersion decrease, 68 patients (42 men and 26 women, mean age 56.3+/-9.5 years) with uncomplicated essential hypertension were studied. All underwent full electrocardiographic and echocardiographic studies at baseline and after 6 months of monotherapy, 29 with angiotensin-converting enzyme inhibitors and 39 with calcium antagonists. QT dispersion was calculated by subtracting the shortest QT from the longest QT, in absolute value (QTmax - QTmin). It was also corrected with Bazett's formula (QTc dispersion). Left ventricular mass index was assessed according to the Devereux formula. After treatment, LVH decreased with both angiotensin-converting enzyme inhibitors (from 155 to 130 g/m2, P < .001) and calcium antagonists (156 to 133/92/m2, P < .001). QT dispersion decreased both after angiotensin-converting enzyme inhibitor treatment (from 82 to 63 ms) and calcium antagonist treatment (from 77 to 63 ms, both P < .001 ). There was a significant correlation of QT dispersion and left ventricular mass after therapy (r = 0.36, P < .005). There was a correlation of the degree of LVH and QT dispersion decrease (r = 0.27, P < .05). CONCLUSIONS: It is concluded that LVH regression influences AQT favorably. Its prognostic value has yet to be determined.     

Increased left ventricular mass in salt-sensitive hypertensive patients

Clinical, biochemical and echocardiographic characteristics were evaluated from 50 essential hypertensive patients classified asccording to their salt-sensitivity status. Salt-sensitive hypertension was diagnosed by means of ambulatory blood pressure monitoring (ABPM) in 22 (44%) patients showing a significant increase in mean BP (P < 0.05) from a 7-day period of low salt (20 mmol NaCl/day) intake, to a 7-day period of high salt (260 mmol NaCl/day) intake. The remaining 28 (56%) patients were considered as having salt-resistant hypertension. Compared with salt-resistant patients, salt-sensitive ones showed an increased left ventricular mass index (P = 0.0118), septal (P = 0.0021) and posterior wall thickness (P = 0.0026), without differences in the internal diastolic diameter. Decreased values of HDL-cholesterol (P = 0.0475) and increased total cholesterol/HDL-cholesterol ratio (P = 0.0098) were also observed in the salt-sensitive, compared with the salt-resistant hypertensive patients. Age, gender, body mass index, systolic and diastolic BP, fasting plasma glucose, creatinine and uric acid did not differ between salt-sensitive and salt-resistant patients. We conclude that, at the same level of BP, salt-sensitive patients exhibit an increased prevalence of left ventricular hypertrophy and a worse lipid profile. These two aspects may confer to salt-sensitive patients an increased risk in terms of cardiovascular morbidity and mortality.