Biomedical subjects
Publications and source records attributed to R Fariello.
Explore the source record for details and available documents.
It is not yet known how blood pressure variability contributes to the vascular changes associated with hypertension, but 2 possibly relevant factors are mean blood pressure levels over time and pressure peaks. It has been observed that patients in whom the variability in 24-hour blood pressure is low have a lower prevalence and severity of target organ damage. We carried out a whole-day continuous intraarterial blood pressure recording (Oxford method) in 12 essential hypertensive patients after a 2-week placebo period and after a 4-week felodipine treatment, administered in an extended release formulation, 10 mg once daily at 7 am. Felodipine significantly lowered systolic and diastolic blood pressure values throughout the 24 hours (p less than 0.005 to 0.001). Also, hourly variabilities of systolic and diastolic blood pressure during whole-day monitoring were significantly reduced (p less than 0.05 to 0.001), evaluated on the basis of the hourly means of standard deviation of systolic and diastolic blood pressure. In addition, felodipine significantly lowered the values of blood pressure reached during both dynamic exercise (bicycle ergometer, p less than 0.001) and isometric exercise (handgrip, p less than 0.001).
Vasodilator drugs lead to secondary baroreflex mediated chronotropic effects. The aim of the present study was to evaluate long term therapy with nicardipine, a calcium antagonist, on exercise performance and autonomic nervous system activity. Nicardipine was administered to 10 untreated mild-moderate essential hypertensive patients. Isometric (hand grip) and dynamic (bicycle ergometer) exercise, and parasympathetic activity evaluated on the basis of Variation of Heart Period (VHP) during regular breathing were determined. Blood pressure was significantly lowered by nicardipine both supine and standing (p less than 0.001). Heart rate did not change. The increase of blood pressure during isometric and dynamic exercise was similar both before and during nicardipine. The increase of heart rate during dynamic exercise was lowered by nicardipine. The lack of basal supine and standing chronotropic activation and the smaller increase of heart rate during bicycle ergometer could be explained by the observed increase in parasympathetic activity, as indicated by the rise of VHP.
Ibopamine, a dopamine derivative suitable for oral administration, is reported to improve cardiac function in patients with chronic heart failure. In order to evaluate the inotropic effect of ibopamine and to compare it with that of digoxin, we studied 10 patients with chronic heart failure (NYHA II-III). All patients were in sinus rhythm. After a washout period of 5 days, when the patients received a constant diuretic dosage and a placebo, ibopamine 100 mg t.i.d. or digoxin 0.25 mg o.d. was randomly given double-blind. The active treatment was continued for a 10-day period, and was followed by a second washout period of 5 days. Subsequently, the patients received digoxin if previously on ibopamine or ibopamine if previously on digoxin for 10 days. Diuretic was continued at the same dosage throughout the study. At the end of the two washout periods, all patients performed a static (hand grip) and a dynamic exercise (bicycle ergometer). Both ibopamine and digoxin improved cardiac response to both types of exercise compared to the washout periods. In particular, PEP/LVET decreased (p less than 0.001 for both drugs) and O2 consumption improved (from 586 +/- 48 to 716 +/- 35 ml/min for ibopamine and from 585 +/- 38 to 713 +/- 52 ml/min for digoxin). No difference was noted between the two drugs in the improvement of exercise tolerance. No side effects were noted with the two drugs. These data indicate that ibopamine could be a valid alternative to digoxin in heart failure patients in sinus rhythm when given for 10 days. More data are needed to evaluate the long-term efficacy of ibopamine.
Reduced parasympathetic activity has been reported in essential hypertension. Converting enzyme inhibition seems to increase parasympathetic tone. In order to evaluate the effects of enalapril on parasympathetic control of heart rate, the authors studied ten mild-to-moderate essential hypertensive patients (7 F, 3 M), treated for 2 weeks with placebo and for 1 month with enalapril. Compared to placebo, enalapril significantly reduced blood pressure (p less than 0.005 at least, both systolic and diastolic), without any change in heart rate. Enalapril enhanced parasympathetic activity as judged by the increased variation of heart period (VHP) during regular breathing. VHP was derived during continuous ECG recording by the difference between the mean of all maximum and minimum R-R intervals, taken as a measure of respiratory sinus arrhythmia: the higher the VHP, the higher the parasympathetic cardiac influence and vice versa. The response to exercise, used as an index of sympathetic stimulation, was not modified by enalapril: the heart rate peak reached during either static (hand grip) or dynamic (bicycle ergometer) exercise and the slope of the increase in blood pressure were unchanged. Therefore, enalapril appears to increase parasympathetic tone in essential hypertension, without any interference with sympathetic adaptation to stress.
Explore the source record for details and available documents.
Progabide, a recently introduced gamma-aminobutyric acid mimetic, is currently undergoing clinical evaluation for a variety of convulsive disorders. We describe a patient in whom severe hepatic failure developed after four weeks of Progabide therapy. The patient's course was marked by encephalopathy, jaundice, hypoglycemia, markedly elevated serum aminotransferase levels, and prolongation of the prothrombin time. Liver biopsy showed extensive hepatocellular necrosis. The patient recovered slowly after discontinuation of the drug. The finding of eosinophilia and increased serum IgE suggests an immunologically mediated mechanism for the Progabide-induced hepatic injury. Alternatively, the lipophilic moiety of Progabide may interact with hepatocyte cell membrane lipids leading to toxic injury. We conclude that Progabide may occasionally cause severe hepatic injury.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effects on cardiac function of captopril (CPT) and digoxin (D) were compared in a study of 16 patients with chronic heart failure due to ischemic heart disease (15) and to congestive cardiomyopathy (1) (New York Heart Association class II n.13 and class III n.3). All patients were normotensive and in sinus rhythm. CPT 25 mg every 8 hours (t.i.d.) or D 0.25 mg once daily was given in a single-blind crossover design: A placebo (PLC) t.i.d. was given for 5 to 10 days, then CPT or D, according to a random sequence, replaced three or one of the PLC tablets; after one month, CPT and D were switched to PLC for 5 to 10 days; subsequently, the PLC tablets were replaced by CPT in the patients who previously received D and vice versa, and both treatments were again continued for one month. PLC, CPT, and D tablets were all identical. Diuretics once daily were given throughout the study. Plasma renin activity (PRA), plasma aldosterone (ALDO), plasma noradrenaline (NA), and adrenaline (A) were determined at the end of the two PLC periods and the two active treatments. A hand grip and a bicycle exercise were performed at the end of the two PLC periods and the two active treatments. No difference was noted between the PLC periods. PRA increased with CPT and did not change with D. ALDO was decreased by both CPT and D. NA and A were similarly decreased by both drugs, both supine and standing.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular hypertrophy (LVH) and cuff blood pressure (BP) level are not as closely related as one might suppose. A better correlation was reported between LVH and continuous monitoring of BP. To analyze this relationship we performed continuous intra-arterial ambulatory monitoring (Oxford technique) in 10 patients with essential hypertension (EH) having LVH, and in 10 age-matched EH patients with normal left ventricles (NLV). Average cuff BP did not differ significantly between the two groups. The intra-arterial BP monitoring showed a significantly higher systolic BP in EH patients with LVH for the mean of the 24 hours (p less than .05) and in the 6 PM-6 AM (night) period (p less than .01); whereas the difference was not significant for the mean systolic BP of the 6 AM-6 PM (day) period and for the mean 24-hour diastolic BP. The heart rate was similar between the two groups; however, the variability of BP was not different. The night systolic BP correlated with the thickness of interventricular septum plus left ventricular posterior wall (LVPW) (r = 0.66; p less than .05). These results may have therapeutic implications, although they require confirmations in a larger series of patients.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Captopril 25 mg every 8 hours for 1 month appeared to improve dynamic effort tolerance and cardiac function under the stress of isometric exercise in patients with chronic heart failure, functional class II-III NYHA. The improvement was comparable to that obtained in the same subjects with digoxin 0.25 mg once a day given for a similar period of 1 month. Therefore, captopril with its lower toxicity and wider therapeutic range, might be considered as a valid alternative to digoxin for treatment of patients in sinus rhythm with mild to moderate heart failure.
Explore the source record for details and available documents.
Pinacidil, a new cyanoguanidine derivative, is an antihypertensive agent with arteriolar vasodilating properties, which acts on precapillary resistance vessels. A trial was carried out in 30 patients with essential hypertension WHO I-II. The treatment period was divided into three phases. Hydrochlorothiazide (HCTZ) and amiloride were administered for 4 weeks in Phase 1 and supine and standing blood pressure decreased significantly. During Phase 2 pinacidil was added to HCTZ/amiloride for the following 3 months. A further significant reduction in blood pressure was obtained. In the next period of treatment (Phase 3) patients were divided into two groups. For 1 month Group A (15 patients) received pinacidil alone and Group B (15 patients) received HCTZ/amiloride. Conventional laboratory blood tests in all patients remained unchanged during treatment. Reported side effects during Phase 2 were headache (2 patients), dizziness (3 patients), palpitations (2 patients) and ankle oedema (2 patients). Plasma renin activity was slightly increased at the end both of Phases 1 and 2. Plasma catecholamines were increased but not significantly at the end of Phase 2 as compared to Phase 1. The results indicate that pinacidil is effective in lowering blood pressure in mild to moderate essential hypertension.
A method for estimating cardiac output (CO) from the intra-arterial blood pressure profile ("contour method") was tested in 8 patients: 6 with essential hypertension, 1 with a pheochromocytoma and 1 with orthostatic hypotension. CO (1/min) was derived by the following formula: PSA (1+St/Dt) X HR 10(-3), where PSA is the area under the systolic portion of the pressure curve, St is the systolic and Dt the diastolic time, X is a correction factor, HR is the heart rate and 10(-3) is a conversion factor from ml/min to 1/min. The "contour method" was compared to the thermodilution CO method. The correlation between the 2 methods was highly significant: the r value in all patients during different conditions (supine, tilt, dynamic and static exercise) ranged from 0.91 to 0.97 with an intercept close to 0 and a slope close to 1. These results indicate that CO is properly measured from the intra-arterial blood pressure profile by the "contour method". A continuous hemodynamic monitoring can be derived applying the "contour method" to the intra-arterial blood pressure profile obtained with the Oxford technique.