Roberto Ceravolo

Angiotensin-converting enzyme gene polymorphism is associated with endothelium-dependent vasodilation in never treated hypertensive patients

The response of the forearm vasculature to acetylcholine (7.5, 15, and 30 microg/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2 microg/min, each for 5 minutes) was evaluated in 32 never-treated hypertensive outpatients (17 men and 15 women, aged 43+/-7 years) and in 24 normotensive control subjects (14 men and 10 women, aged 42+/-6 years). Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. In both hypertensive and normotensive groups, a deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene was determined by polymerase chain reaction. The response to acetylcholine was significantly reduced in hypertensive patients versus control subjects: at the highest dose (30 microg/min), forearm blood flow was 13.9+/-6.3 mL x 100 mL tissue(-1) x min(-1) in hypertensives versus 27.1+/-9.7 mL x 100 mL tissue(-1) x min(-1) in the controls (P<.001); similarly, vascular resistance was 10.6+/-5.6 U in hypertensive patients and 4.9+/-1.9 U in normotensive subjects. In the hypertensive group, the patients with DD genotype showed significantly less endothelium-dependent vasodilation compared with ID+II genotypes (at the highest dose of acetylcholine, forearm blood flow was 12.1+/-4.2 versus 17.0+/-4.1 mL x 100 mL tissue(-1) x min(-1)) (P<.005). The vasodilator effect of sodium nitroprusside infusions was not statistically different in DD and ID+II hypertensive patients. In conclusion, our data suggest that ACE polymorphism affects endothelium-dependent vasodilation in hypertensive patients and confirm that hypertensive patients had a blunted response to the endothelium-dependent agent acetylcholine.

Deletion Polymorphism of Angiotensin-Converting Enzyme Gene and Left Ventricular Hypertrophy in Southern Italian Patients

OBJECTIVESnThis study sought to evaluate the possible association of polymorphism of the angiotensin-converting enzyme (ACE) gene with blood pressure and left ventricular mass index (LVMI).nnnBACKGROUNDnThe renin-angiotensin system seems to be involved in the pathogenesis of essential hypertension. Moreover, recent epidemiologic observations demonstrate that many subjects with left ventricular hypertrophy have normal blood pressure levels, suggesting that factors other than hemodynamic overload may contribute to the hypertrophy.nnnMETHODSnThe study included 140 untreated hypertensive outpatients who underwent ambulatory blood pressure monitoring, echocardiographic evaluation and analysis for insertion (I)/ deletion (D) polymorphism in intron 16 of the ACE gene by polymerase chain reaction. Blood pressure was measured at 24 h, and LVMI was calculated by the Devereux formula, in each patient.nnnRESULTSnLeft ventricular mass index values (mean +/- SD) were 137 +/- 28 g/m2 in patients with the DD genotype, 125 +/- 27 g/m2 in those with the ID genotype and 115 +/- 27 g/m2 in those with II genotype. The frequencies of the DD, ID and II genotypes were 45.71% (n = 64), 46.42% (n = 65) and 7.85% (n = 11), respectively, and were in Hardy-Weinberg equilibrium. The strongest association between left ventricular mass and DD genotype in our cohort appeared to be an independent cardiovascular risk factor (DD vs. ID: odds ratio [OR] 2.497, 95% confidence interval [CI] interval 1.158 to 5.412, p < 0.05; DD vs. II: OR 6.577, 95% CI 1.169 to 28.580, p < 0.02).nnnCONCLUSIONSnOur data show that the LVMI was significantly enhanced in patients with the DD genotype.

Comparison of endothelial function evaluated by strain gauge plethysmography and brachial artery ultrasound

Strain gauge plethysmography and brachial artery ultrasound are widely used to study endothelial function. No data on correlation between these two procedures are reported. The present study compared these two methods and investigated the correlation between vasodilation and brachial wall shear stress. In six healthy subjects and ten patients with hypertension or obesity, strain gauge plethysmography was performed in resting conditions and after infusion of 7.5,15 and 30 microg/min of acetylcholine, and brachial artery ultrasound in resting conditions and after 5 min hand ischemia. Wall shear stress was calculated as: blood viscosity x blood velocity/internal diameter. Forearm blood flow following acetylcholine infusion increased more in healthy subjects than in patients with hypertension or obesity. In addition, brachial artery dilated more in the former group. Change in brachial artery diameter correlated with change in forearm blood flow, calculated as area under the curve of acetylcholine infusion (r=0.739, P<0.001). Wall shear stress was higher in healthy subjects (67.8+/-20.0 dynes/cm(2)) than in patients with either hypertension or obesity (39.2+/-16.7, P<0.001), and correlated with variations of diameter (r=0.796, P<0.0002), and marginally of blood flow (r=0.516, P<0.05). The present findings demonstrate that there is a high correlation between endothelial function evaluated by strain gauge plethysmography and brachial artery ultrasound. Wall shear stress correlates with brachial artery diameter change following hand ischemia, and marginally with blood flow change following acetylcholine infusion.

Heart Rate Variability and Sudden Infant Death Syndrome

PERTICONE, F., ET AL.: Heart Rate Variability and Sudden Infant Death Syndrome. The sudden infant death syndrome (SIDS) is the most common cause of death in infancy. The pathophysiological mechanism leading to SIDS is still obscure. In the QT hypothesis, the mechanism must be an arrhythmogenic sympathetic imbalance: the infants die suddenly of cardiac arrhythmia. Recently, it has been suggested that analysis of heart rate variability (HRV), expressed as standard deviation or variance analysis, can provide adequate information on sympathovagal interaction. We studied 150 newborns enrolled in a previous prospective electrocardiographic study to evaluate the predictive value of QT interval for SIDS. We analyzed the ECGs recorded with infants alert on the fourth day of life and after 2 months. For each ECG, the HRV was calculated using the first standard deviation of of RR intervals (ms) measured for 1 minute. The average RR interval was 441 ± 71 ms at the fourth day and 420 ± 39 ms at the second month. The QTc and HRV mean values were 396 ± 23 and 23 ± 12 ms at the fourth day, 412 ± 19 and 15 ± 7 msec at the second month. Therefore, the SD values of heart rate were correlated with QTcin order to assess a possible relationship between the two variables. The correlation coefficient and regression equation were: ‐0.639 and y = 423.67 ‐ 2.18*× (P < 0.002) at the fourth day, ‐0.146 and y = 418.09 ‐ 0.37*× (NS) at the second month. In conclusion, our data seems to confirm a delayed maturation or impaired fuctioning of the autonomic nervous system in the first weeks of life, reflecting a direct correlation with QT prolongation.

Amlodipine versus Ramipril in the Treatment of Mild to Moderate Hypertension: Evaluation by 24-Hour Ambulatory Blood Pressure Monitoring

This study was designed to compare the efficacy and tolerability of amlodipine (AML) and ramipril (RAM) administered once a day in patients affected by mild to moderate primary systemic hypertension. Twenty outpatients, 12 men and 8 women (age range 35-64 years), were enrolled. The patients received single-blind placebo for 2 weeks and thereafter in a double-blind, randomized crossover sequence AML (10 mg) and RAM (5 mg), both for 4 weeks. At the end of each period, the patients underwent 24-hour noninvasive blood pressure monitoring with readings taken every 10 min during daytime (from 07.00 to 23.00 h) and 20 min during nighttime (from 23.00 to 07.00 h). Both AML and RAM induced a highly significant (p < 0.0001) decrease in blood pressure from 162/103 +/- 7/3 to 132/82 +/- 6/6 and 135/83 +/- 6/5 mm Hg, respectively. The mean blood pressure decreased from 122 +/- 5 to 99 +/- 6 (AML; p < 0.0001) and 100 +/- 5 mm Hg (RAM; p < 0.0001). No significant differences in heart rate were noted during drug administrations. Treatment did not have to be discontinued in any patient because of adverse reactions. In conclusion, both AML and RAM reduced the blood pressure markedly, even if AML proved to be significantly more effective than RAM.

A case of torsade de pointes occurring in a newborn with persistent 2:1 atrioventricular block.

A case of QT interval prolongation with ventricular tachycardia and torsade de pointes is reported. Arrhythmias occurred in a baby with persistent 2:1 atrioventricular block and long QT interval 2 days after birth and were self-limiting. No structural cardiac defect was present. Serum levels of sodium, potassium, magnesium and calcium were in the normal range. Finally, the pathogenetic mechanism of cardiac block is discussed.

Prolonged Magnesium Sulfate Infusion in the Treatment of Ventricular Tachycardia in Acquired Long QT Syndrome

SummaryTo confirm the antiarrhythmic effectiveness of magnesium sulfate given by slow infusion and evaluate its influence on ventricular repolarisation parameters, we enrolled 12 consecutive patients (9 men and 3 women; aged 49 to 78 years) with acquired prolonged QT interval (QTc = 500 to 640) and episodes of torsade de pointes (TdP). Five had chronic ischaemic heart disease, 2 acute myocardial infarction, 4 total atrioventricular block, and 1 systemic hypertension. Of the 12 patients, 5 were receiving class IA antiarrhythmic drugs (disopyramide in 2 patients; quinidine plus disopyramide in 1; quinidine in 2), one was treated with methyldopa plus chlorthalidone, and another was on diuretic therapy alone. Magnesium sulfate (MgSO4) infusions in 0.9% sodium chloride were instituted at 50 mg/min and continued for 2 hours after the disappearance of TdP. These were followed by prophylactic infusions of 30 mg/min for 90 minutes twice daily for the next 3 to 4 days. In all cases, episodes of arrhythmia disappeared within 20 to 30 minutes. However, arrhythmia suppression was not associated with significant modification of the QT interval. No adverse effects were observed, and both the heart rate and blood pressure remained unchanged from baseline values.

Side-Branch of Internal Mammary Artery Bypass Graft Causing Coronary Steal

A case of coronary steal syndrome caused by a large unligated branch of the left internal mammary artery in a patient who had undergone myocardial revascularization is described. The presence of recurrent angina, a positive exercise stress test, and repeat angiography showing a lateral branch of the mammary artery led to a diagnosis of the coronary steal phenomenon. Surgical ligation of the branch was performed and the patient became symptom-free with a negative exercise stress test.

354 THE CRIB DEATH: OF INTERVAL AND HR DURING THE FIRST YEAR OF LIFE

A prospective electrocardiographic study was performed in 2,572 newborns, 1,326 males and 1,246 females, to evaluate the predictive value of QT interval for sudden infant death syndrome (SIDS). Electrocardiograms, with babies asleep, were recorded at the ages of 4 days, 2, 4, 6 months, and 1 year. The QTc (mean±SD) was 391±23 at 4 days, 412±16 at 2 months (n=1,768) (p<.0001), 404±17 at 4 months (n=1,368), 401±16 at 6 months (n=1,225), and 397±16 at 1 year (n=915). QTc, calculated in males and females, resulted significantly longer (393 vs 391) (p<.01) at 4 days. QTc values longer than the mean plus 3 SD were considered prolonged. Heart rate values were 135 16 at 4 days, 145±15 at 2 months (p<.0001), 135±11 at 4 months, 133±11 at 6 months, and 129±9 at 1 year. In 71 babies (2.8%) the QTc was prolonged and 4 (0.16%) of these died suddenly: the first at 3 months (QTc=470, HR=147); the second after 7 weeks (QTc=514, HR=115); the third at 3 months (QTc=464, HR=140 at 4 days; the fourth at 2 months (QTc=401; HR=149). In conclusion, our data provide further information on the understanding of SIDS mechanisms.