RESUMEN
Systolic blood pressure (SBP) normally increases during exercise. This increase is frequently exaggerated in hypertensive individuals. The aim of our study was to evaluate the antihypertensive effects of losartan at peak exercise and on cardiac performance during the treadmill test in individuals with essential hypertension. Forty subjects with a mean age of 44.2 +/- 12.4 years and with mild-to-moderate essential hypertension were enrolled. After a 14-day washout period, all selected subjects were given a treadmill exercise test using the modified Bruce protocol for exercise. The test was performed at the end of the washout period (step 0), again after 1 month (step 1), after 3 months (step 2) and after 6 months (step 3) of losartan administration (50 mg/daily per oral). Heart rate, SBP and diastolic blood pressure (DBP) were measured at rest and at maximal exercise. Exercise duration and double product were also recorded. In all patients who completed the study, a significant reduction from baseline in SBP at rest was found at 3 and 6 months (p < 0.05). No significant reduction from baseline in SBP at peak exercise was observed. No significant changes from baseline were found in double product, DBP, heart rate or exercise time. The results of our study suggest that losartan is effective in reducing blood pressure only at rest but is unable to improve exercise BP response or cardiac performance in subjects with mild-to-moderate essential hypertension.
Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Prueba de Esfuerzo/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Losartán/farmacología , Adulto , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Prueba de Esfuerzo/estadística & datos numéricos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Humanos , Hipertensión/fisiopatología , Losartán/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
This double-blind crossover study was designed to compare the effects of felodipine and cilazapril on exercise performance in hypertensive patients. After a 2-week placebo run-in period, 40 patients with mild to moderate hypertension were randomized into two parallel groups to receive either felodipine (10 mg) or cilazapril (5 mg) for 4 weeks. After another 2-week washout period, treatments were then crossed over for a further 4-week study period. All patients were given an extensive rest and exercise evaluation at the end of the placebo period. Extensive rest and exercise evaluations were repeated after a 4-week treatment period and again after the second washout period and after the second 4-week treatment period. Before each exercise test, epinephrine, norepinephrine and dopamine plasma levels and plasma renin activity were measured. Two groups were similar at baseline for systolic and diastolic blood pressure and heart rate as well as for laboratory and hormonal variables and duration of exercise test. At the end of treatment diastolic blood pressure was significantly reduced in the felodipine group (p = 0.019). Duration of exercise test was longer than at baseline (p = 0.031) in the felodipine group. Plasma dopamine levels were significantly increased in the cilazapril group. Plasma renin activity significantly increased in the felodipine group. In conclusion, our data show that the two drugs have the same effectiveness in resting conditions but that felodipine is more effective in lowering maximum exercise diastolic blood pressure and in improving exercise time with an double product increase (not significant); it has no statistically significant effect on maximal exercise systolic blood pressure.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Cilazapril/uso terapéutico , Prueba de Esfuerzo , Felodipino/uso terapéutico , Hipertensión/tratamiento farmacológico , Estudios Cruzados , Método Doble Ciego , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión/fisiopatologíaRESUMEN
BACKGROUND: Diuretics, have been accepted as first-line treatment in refractory heart failure, but a lack of response is a frequent event. A randomised single blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory NYHA class IV congestive heart failure (CHF). MATERIALS AND METHODS: Sixty patients (21 F/39 M) with refractory CHF (NYHA class IV) of different etiologies, unresponsive to high oral doses of furosemide, ACE-inhibitors, digitalis, and nitrates, aged 65-90 years, were enrolled. They had to have an ejection fraction (EF) <35%, serum creatinine <2 mg/dl, BUN =60 mg/dl, a reduced urinary volume and a low natriuresis. The patients were randomised in two groups (single blind): group 1 (11 F/19 M) received an i.v. infusion of furosemide (500-1000 mg) plus HSS (150 ml of 1.4-4.6% NaCl) b.i.d. in 30 min. Group 2 (10 F/20 M) received an i.v. bolus of furosemide (500-1000 mg) b.i.d., without HSS, during a period lasting 6-12 days. Both groups received KCl (20-40 mEq.) i.v. to prevent hypokalemia. All patients underwent at entry a physical examination, measurement of body weight (BW), blood pressure (BP), heart rate (HR), evaluation of signs of CHF, and controls of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea and glycemia and daily during hospitalization, as well as the daily output of urine for, Na, K and Cl measurements. Chest X-ray, ECG and echocardiogram were obtained at entry during and at the discharge. During the treatment and after discharge the daily dietary Na intake was 120 mmol with a drink fluid intake of 1000 ml daily. An assessment of BW and 24-h urinary volume, serum and urinary laboratory parameters, until reaching a compensated state, were performed daily, when i.v. furosemide was replaced with oral administration (250-500 mg/day). After discharge, patients were followed as outpatients weekly for the first 3 months and subsequently once per month. RESULTS: The groups were similar for age, sex, EF, risk factors, treatment and etiology of CHF. All patients showed a clinical improvement. Six patients in both groups had hyponatremia (from 120 to 128 mEq./l) at entry. A significant increase in daily diuresis in both groups was observed (from 390+/-155 to 2100+/-626, and from 433+/-141 to 1650+/-537 ml/24 h, P<0.05). Natriuresis (from 49+/-15 to 198+/-28 mEq./24 h) was higher in group 1 vs. group 2 (from 53.83+/-12 to 129+/-39 mEq./24 h, P<0.05). Serum Na (from 135.9+/-6.8 to 142.2+/-3. 8 mEq./l, P<0.05) increased in the group 1 and decreased in the group 2 (from 134.7+/-7.9 to 130.1+/-4.3 mEq./l). Serum K was decreased (from 4.4+/-0.6 to 3.9+/-0.6, and 4.6+/-9 to 3.6+/-0.5 mEq. /l, P<0. 05) in both groups. BW was reduced (from 73.8+/-9.1 to 63. 8+/-8.8, and from 72.9+/-10.2 to 64.5+/-7.5 kg, P<0. 05) in both groups. Group 2 showed more patients in NYHA class III than group 1 (18 vs. 2 patients, P<0.05). Group 2 showed an increase of serum creatinine. Serum uric acid increased in both groups. BP values decreased, and HR was corrected to normal values in both groups. Group 2 showed a longer hospitalization time than group receiving HHS infusion (11.67+/-1.8 vs. 8.57+/-2.3 days, P<0.001). In the follow-up (6-12 months), none of the patients from group 1 were readmitted to the hospital and they maintained the NYHA class achieved at the discharge. Group 2 showed 12 patients readmitted to hospital and a higher class than at discharge. CONCLUSION: Our data suggest that the combination of furosemide with HSS is feasible and it appears that this combination produces an improvement of hemodynamic and clinical parameters, reduces the hospitalization time and maintains the obtained results over time in comparison with those receiving high-dose furosemide as bolus.
Asunto(s)
Diuréticos/administración & dosificación , Furosemida/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Solución Salina Hipertónica/administración & dosificación , Anciano , Anciano de 80 o más Años , Presión Sanguínea/efectos de los fármacos , Peso Corporal , Creatinina/sangre , Diuresis/efectos de los fármacos , Quimioterapia Combinada , Femenino , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Potasio/sangre , Potasio/orina , Cloruro de Potasio/administración & dosificación , Método Simple Ciego , Sodio/sangre , Sodio/orina , Ácido Úrico/sangreRESUMEN
Many authors have reported an association between the angiotensin-converting enzyme (ACE)-D allele and coronary heart disease and other cardiovascular diseases. The mechanism underlying the positive associations between the ACE-D alleles and diseases are not yet clear. Previous reports showed an association between migraine without aura and ACE-D allele polymorphism. The study is aimed to evaluate if the DD genotype could also be associated with the frequency and duration of migraine without aura. In 302 patients suffering from migraine without aura (at least for 1 year), with no history of cardiovascular diseases and major risk factors for ischemic events, the genotypes of the ACE gene, plasma ACE activity, and the frequency (weekly) and duration of migraine attacks were evaluated. No drugs were given before (4 weeks) and during the study. The same evaluations were performed in 201 subjects without migraine. The molecular biologist and the physician evaluating the patient data were blinded to the clinical history and ACE-DD gene determination. Genotypes were determined by polymerase chain reaction amplification. Plasma ACE activity was performed by the HPLC method. The groups were similar for sex, age and smoking habit (migraines: 302 patients (200 F/102 M), mean age 37.8 +/- 8.2 years; control: 201 subjects (127 F/74 M), mean age 37.5 +/- 9.3 years). Patients with migraine without aura showed higher incidence of the ACE-DD gene (48.34%) than control subjects (37.32%), p < 0.05. The frequency of migraine (average attacks per week) was higher in patients with DD (2.11 +/- 1.9) than in patients with ID (1.54 +/- 1. 44), p < 0.05. No difference in duration of migraine attacks (hours per week) was observed. Plasma ACE activity was increased in patients with the ACE-DD gene. Our data suggest that ACE-DD gene polymorphism could have an important role in determining migraine attacks and the frequency of these attacks. Further data are needed through further studies, especially on the biomolecular level.
Asunto(s)
Deleción Cromosómica , Trastornos Migrañosos/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Adulto , Alelos , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/enzimología , Peptidil-Dipeptidasa A/sangreRESUMEN
Recent reports show that sumatriptan administration increases blood pressure and vascular resistance both in systemic and pulmonary circulation. This study was performed to evaluate by echo-Doppler technique the hemodynamic effects of subcutaneous sumatriptan administration. Forty-one migraine subjects (26 males, 15 females), mean age 36 +/- 2 years (range 36-39 years), and 20 healthy control subjects (14 males, six females), mean age 36 +/- 2 years (range 36-39 years) were randomized (double-blind) to receiving sumatriptan (group A) or placebo (group B). After a 2-week complete pharmacological washout, clinical examination, electrocardiogram, and Doppler echocardiography were performed at baseline, 15, 30, 45, and 60 min after sumatriptan or placebo administration. No significant differences were found between the two groups regarding Doppler echocardiographic parameters (aortic integral, pulmonary integral, end-systolic and end-diastolic diameters) and heart rate; only a slight but not significant increase in arterial blood pressure was observed in group A. Our data show that succinate sumatriptan can be used with safety in patients without hypertension and other cardiovascular disease.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Ecocardiografía Doppler , Frecuencia Cardíaca/efectos de los fármacos , Trastornos Migrañosos/tratamiento farmacológico , Sumatriptán/uso terapéutico , Vasoconstrictores/uso terapéutico , Adulto , Método Doble Ciego , Evaluación de Medicamentos , Femenino , Humanos , Infusiones Parenterales , Masculino , Sumatriptán/efectos adversosRESUMEN
Sumatriptan, a selective 5-hydroxy-triptamine (5-HT1) receptor agonist, has been used recently in the treatment of acute migraine. Some in vitro experiments suggested that sumatriptan has vasoactive properties in vascular beds distinct from cerebral circulation. In view of this we investigated the vascular effects of the standard 6 mg subcutaneous (s.c.) dose of sumatriptan, on the surface areas of the head using thermography, a simple and reliable method for detecting temperature changes. The head temperature of 127 patients (double-blind), 102 migraines (52 during headache attack and 50 headache-free) and 25 healthy control subjects were evaluated using thermography in basal condition and 30, 60, 90, and 120 min after s.c. sumatriptan injection of placebo. During the entire observation period systemic blood pressure (SBP), heart rate (HR) and continuous electrocardiogram (ECG) were detected automatically. A significant head temperature decrease was observed after s.c. sumatriptan administration, in both healthy controls and migraine subjects; placebo administration did not show any change of temperature. In migraine patients during headache attack, head temperature reduction corresponded to the relief of headache symptoms. This vasoconstrictor effect detected with thermography is not isolated to cranial circulation but it is also systemic. In fact, we observed a significant increase (p < 0.05) in both systolic and diastolic systemic blood pressure. No significant changes in heart rate and ECG abnormalities were otherwise detected. These findings suggest that sumatriptan is effective in the treatment of migraine attack, but it must be used with caution in migraines with concomitant hypertension.