Giuseppe Romanelli

Antihypertensive and humoral effects of verapamil and nifedipine in essential hypertension.

The aim of this study was to investigate and compare the effects of two calcium antagonist drugs, verapamil (VER) and nifedipine (NIF), on blood pressure (BP), heart rate (HR), plasma catecholamines (pCA), renin (PRA), plasma aldosterone (pALD), and plasma volume (PV) in a group of patients with mild to moderate essential hypertension. In 12 hypertensive patients on a fixed normal sodium and potassium intake, VER (80 mg t.i.d., per os) first and then NIF (10 mg, t.i.d. per os), or vice versa according to a random sequence, were each given for 8 days, with an interval of 5 days between the two treatments. Both NIF and VER significantly reduced BP (p less than 0.001); this reduction was quantitatively similar in both treatment schedules. Supine and standing PRA, pALD, and PV were not significantly affected by VER or NIF. HR and pCA were unchanged after VER, whereas they were significantly increased (p less than 0.05, at least) mainly in standing position after NIF treatment. The antihypertensive and metabolic effects of VER (80 mg t.i.d.) and NIF (10 mg t.i.d.) were maintained after chronic treatment (4 months with VER in 10 patients and 2 months with NIF in 12 patients). After 2 months of treatment with VER (160 mg t.i.d.) in 18 patients, BP was further reduced, while pCA were slightly increased. In conclusion, VER and NIF are effective and equipotent antihypertensive agents that do not induce significant renin stimulation or fluid retention; adrenergic stimulation seems to be greater with NIF, which should be taken into account in the clinical use of these drugs.

Cardiopulmonary performance during exercise in acromegaly, and the effects of acute suppression of growth hormone hypersecretion with octreotide.

We studied 10 adult patients with active acromegaly (4 men and 6 women, mean age 55 +/- 5 years and mean body mass index 27.9 +/- 1.1 kg/m2). Control values for the echocardiographic and exercise studies were obtained from 10 normal subjects matched for sex and age (5 men and 5 women, age 51.1 +/- 3.7 years and body mass index 25.3 +/- 1 kg/m2). Each patient underwent: (1) blood sampling for growth hormone (GH) assay every 3 hours; (2) a 2-dimensional, guided M-mode echocardiographic study; and (3) a cycloergometric exercise test at baseline and after treatment with a portable pump infusing octreotide, 500 micrograms/24 hours subcutaneously. All patients had left ventricular hypertrophy. Systolic function indexes did not significantly differ among normal subjects, whereas baseline Doppler studies showed abnormalities in left ventricular diastolic filling in acromegalic patients. At anaerobic threshold and at maximal exercise, acromegalic subjects sustained a significantly (p < 0.05) decreased workload (54 +/- 23 vs 94 +/- 11 and 87 +/- 37 vs 152 +/- 15 W) compared with control subjects. After octreotide, baseline heart rate (79 +/- 7 vs 87 +/- 8 beats/min, p < 0.05) and serum GH levels significantly decreased compared with levels before administration of octreotide. Systolic and diastolic functional indexes at rest significantly improved after octrotide in acromegalic patients. Both at anaerobic threshold and at maximal exercise, workload and oxygen consumption were significantly increased after octretide administration. Exercise capacity at anaerobic threshold was not significantly different in acromegalic subjects after octreotide when compared with normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic activity and left ventricular function during treatment of essential hypertension with calcium antagonists

The effects of 2 calcium antagonist drugs, verapamil and nifedipine, on blood pressure, heart rate (HR), plasma catecholamines, plasma renin activity and some echocardiographic indexes of left ventricular anatomy and function were studied in 67 patients with essential hypertension. The short- and long-term antihypertensive effect of verapamil was not associated with significant changes in HR, plasma catecholamines or plasma renin activity; the decrease in blood pressure after nifedipine was associated with a significant increase in HR and plasma catecholamines (mainly noradrenaline) (p less than or equal to 0.05). These findings were confirmed in a crossover comparison in 12 hospitalized patients treated with verapamil and nifedipine for 8 days each. The dose of isoproterenol that increased HR by 25 beats/min was significantly increased during verapamil treatment (p less than 0.05) and decreased during nifedipine treatment (p less than 0.01). Stroke volume and shortening fraction increased slightly but significantly (p less than 0.05) with 3 months of nifedipine treatment, while no change was detected with verapamil treatment. Left ventricular mass was significantly decreased after effective antihypertensive treatment for 3 months with verapamil or nifedipine (p less than or equal to 0.05).

QT dispersion and heart rate variability abnormalities in Alzheimer's disease and in mild cognitive impairment.

Objectives: To investigate the effect of cardiovascular changes (i.e., QT interval, QT dispersion (QTD), heart rate variability (HRV), and other cardiovascular measures) in subjects with Alzheimers disease (AD) and mild cognitive impairment (MCI).

Microvascular damage and platelet abnormalities in early Alzheimer's disease

Accumulating evidence from epidemiological and clinical studies suggests that vascular risk factors may be involved in Alzheimer disease (AD). Although the precise contribution of vascular disturbances to the pathogenesis of AD is still unclear, various biochemical and neuropathological data strengthen the view that cerebrovascular deficiencies such as reduced blood supply to the brain and disrupted microvascular integrity in brain parenchyma play a direct or intermediate role in the chain of events ending with a dementia syndrome. The present review focuses on platelet abnormalities and hemostatic alterations in AD. In particular, data from our group, along with current literature, are discussed with regard to the evidence of platelets amyloid precursor protein (APP) processing disturbances in early AD as well as to the recent observations of increased serum levels of thrombomodulin and sE-selectin, which are sensitive markers of endothelial dysfunction. These findings strongly indicate that platelet dysfunction and microvasculature deficiencies occur rather early during the course of AD, thus suggesting a further link between AD-related processes and vascular disorders.

Peripheral blood abnormalities in Alzheimer disease: evidence for early endothelial dysfunction.

Clinical and epidemiologic studies demonstrate that vascular risk factors may be involved in Alzheimer disease (AD). To evaluate whether vascular abnormalities are an early feature of AD, several parameters of coagulation and fibrinolysis were assessed. Thirty patients with mild AD and 30 age-matched control subjects entered the study. All subjects performed a standardized clinical and laboratory protocol. Persons with vascular risk factors and systemic diseases were excluded. AD patients present significant increased levels of thrombomodulin (p < 0.0001) and sE-selectin (p < 0.03). In contrast, no difference was found between the two diagnostic groups in the levels of &bgr;-thromboglobulin, prothrombin fragment 1+2, fibrinogen, and von Willebrand factor. No other association but diagnosis was found with thrombomodulin and sE-selectin. These findings suggest that endothelial dysfunction is an early event in AD patients.

Volume Reduction in Cerebral Blood Flow in Patients with Alzheimer’s Disease: A Sonographic Study

Neuroimaging techniques such as PET and SPECT demonstrated a consistent reduction of cerebral blood flow (CBF) in Alzheimer’s disease (AD). The aim of the study was to assess the potential role of ultrasonography for CBF measurement in AD patients and whether the CBF volume correlates positively with disease severity. Fifty patients who met the diagnostic criteria of probable AD (NINDS-ADRDA) were compared to 50 age-matched healthy elderly volunteers. The extracranial internal carotid arteries (ICAs) and the vertebral arteries (VAs) of the patients and controls were examined. Angle-corrected time-averaged flow velocity (TAV) and the diameter of the vessel were measured. Intravascular flow volumes were calculated as the product of TAV and the cross-sectional area of the circular vessel. CBF volume was calculated as the sum of flow volumes in the ICAs and VAs of both sides. All subjects underwent the MMSE. The mean global CBF (474.87 ± 94.085 vs. 744.26 ± 94.082 ml/min; p < 0.0001) was lower in AD patients than in healthy volunteers. A significant decline in global flow volumes (r = 0.48; p < 0.0007) with the degree of cognitive impairment was also present. The ability of ultrasonography to characterize flow decreases makes such a technique an attractive tool for the study of AD, for the evaluation of pharmacological therapies and, possibly, for early diagnosis.

Similarities and differences in the antihypertensive effect of two calcium antagonist drugs, verapamil and nifedipine

The short- and long-term effects of two calcium channel blocking drugs, verapamil and nifedipine, on blood pressure, heart rate, plasma catecholamines, plasma renin activity, plasma volume and cardiac performance (echocardiography) were studied in essential hypertensive patients and in normal subjects. Verapamil, 160 mg orally, reduced blood pressure within 60 minutes in 22 hypertensive patients, but not in 12 normotensive subjects. Nifedipine, 10 mg sublingually, reduced blood pressure within 15 minutes in 19 hypertensive patients, but not in 7 normotensive subjects. Plasma noradrenaline was significantly increased both in normal subjects and in hypertensive patients only after nifedipine was administered. Verapamil (80 mg three times a day) first, and nifedipine (10 mg three times a day) thereafter, or vice versa, were given to 12 hospitalized hypertensive patients on a fixed sodium and potassium intake; the drugs produced similar blood pressure reductions, but heart rate and plasma catecholamines were increased only after nifedipine (p less than 0.05). Neither drug affected plasma volume, aldosterone or plasma renin activity. Long-term ambulatory treatment with verapamil (80 or 160 mg three times a day for 2 to 4 months) or nifedipine (10 mg three times a day for 2 months) produced changes in all variables that were similar to those observed in the hospital (controlled) study. Shortening fraction was significantly increased after nifedipine (p less than 0.05) but no change was observed after verapamil. In conclusion, blood pressure is effectively reduced by both verapamil and nifedipine; an appreciable adrenergic stimulation may be caused by nifedipine, but usually not by verapamil, and fluid retention, renin release or myocardial depression is not observed during verapamil or nifedipine treatment.

Cardiovascular Effects of a Single Slow Release Lanreotide Injection in Patients with Acromegaly and Left Ventricular Hypertrophy

In our study we assessed the effects of a single i.m. injection of slow-release Lanreotide (30 mg) (SR-L), a new long-acting somatostain analog, on circulating GH levels, baseline cardiac function (M-mode, 2D guided, doppler-echocardiographic study) and cardiopulmonary response to exercise (cycloergometric test, performed using a computer drived, electrically braked cycle ergometer), tested at baseline, after 7 and 14 days from the injection in 10 acromegalic patients (5 M, 5 F, mean age 57.7 ± 3.1 yrs, body mass index (BMI) 27 ± 0.8 kg/m2, blood pressure 141 ± 6.5/82 ± 3 mmHg). SR-L administration decreased GH levels in acromegalic patients (mean±SEM) from 16.1 ± 6.9 to 10.8 ± 5.1 µg/L (p = 0.045) after 7 days and to 11.9 ± 5 µg/L (p = 0.078) after 14 days from the injection. Moreover, we observed a significant (p<0.05) decrease in systolic blood pressure and heart rate at the 7th (135 ± 6.1 vs 141 ± 6.5 mmHg, and 68 ± 2.1 vs 74 ± 2.1 bpm) and 14th (137 ± 6.2 vs 141 ± 6.5 mmHg, and 72 ± 2 vs 74 ± 2.1 bpm) day of the study with respect to the baseline values. After SR-L administration we also found an increase in ejection fraction (69 ± 2 vs 63 ± 2.3% at 7th day, p = 0.006; 65 ± 2.3 vs 63 ± 2.3% at the 14th day, p = 0.027) and shortening fraction (40.8 ± 1.8 vs 36.6 ± 1.9% at 7th day, p = 0.005; 38.7 ± 1.8 vs 36.6 ± 1.9% at the 14th day, p = 0.045). The positive acute cardiac response to SR-L injection was also demonstrated by the increase in A/E velocity ratios at 7th (1.14 ± 0.1 vs 0.98 ± 0.07, p = 0.016) and 14th (1.04 ± 0.08 vs 0.98 ± 0.07, p = 0.008) day of the study. After SR-L injection, exercise capacity and VO2 at anaerobic thresold were also increased with respect to the baseline test: 61.1 ± 8.2 vs 38.9 ± 6.8 watts (p = 0.002) and 1012.4 ± 71.5 vs 915.3 ± 77.8 mL/min (p = 0.033) after 7 days, and 61.4 ± 7.2 vs 38.9 ± 6.8 watts (p = 0.002) and 1010.1 ± 62.5 vs 915.3 ± 77.8 mL/min (p = 0.010) after 14 days from the injection. In conclusion, these results suggest that in acromegalic patients: (1) SR-L causes a rapid improvement in baseline cardiac function and in cardiopulmonary performance during exercise in acromegaly; (2) the endocrine (decrease in GH levels) and echocardiographic responses to SR-L are maximal after 7 days from the injection, whereas the effect of SR-L on the exercise performance are longer lasting.

Short-Term Administration of Captopril and Nifedipine and Exercise-Induced Albuminuria in Normotensive Diabetic Patients With Early-Stage Nephropathy

Recent studies have demonstrated that short-term angiotensin converting enzyme (ACE) inhibition with captopril can reduce urinary albumin excretion rate (UAER) after exercise in normotensive diabetic patients with early-stage nephropathy. The aim of this study was to investigate whether this effect of ACE inhibition was due to a systemic hypotensive action or a specific action at the intrarenal level. Thus, we compared the acute effects of captopril and the Ca2+-channel blocker nifedipine on exercise-induced UAER in normotensive (blood pressure <165/95 mmHg) diabetic patients who were normoalbuminuric or microalbuminuric at rest (stage 2 or 3 of diabetic nephropathy). Twenty-five stage 2 diabetic nephropathy patients, 39 stage 3 diabetic nephropathy patients, and 12 nondiabetic subjects performed five submaximal cycloergometric exercises (90% of theoretical heart rate) on nonconsecutive days. The first two exercises were performed in basal conditions; the next three exercises were performed 24 h after administration of captopril (25 mg twice daily) or nifedipine AR (20 mg twice daily) or placebo (1 tablet twice daily) according to a randomized double-blind crossover trial. After placebo, blood pressure and UAER did not change at rest or 1 h after exercise. After captopril, blood pressure at rest and during exercise was similar to that observed after placebo. UAER at rest was not modified, whereas 1 h after exercise, it was significantly decreased both in stage 2 and stage 3 diabetic nephropathy patients (P < 0.001). After nifedipine, blood pressure decreased significantly at rest and during exercise in respect to placebo and captopril. UAER at rest did not change significantly. UAER 1 h after exercise was significantly decreased both in stage 2 and stage 3 diabetic nephropathy patients (P < 0.01 vs. placebo), but it was significantly higher than that observed after captopril (P < 0.01). Captopril is more effective than nifedipine in reducing exercise-induced UAER in normotensive diabetic patients even though it does not influence blood pressure response to exercise. The effects of captopril on UAER induced by exercise may be due to a specific action at the intrarenal level.