RESUMEN
The airway response and cardiovascular effects of salmeterol (SM) and salbutamol (SB) given as a single dose from metered-dose inhalers were studied in 10 patients with mild asthma. In a double-blind, randomized, cross-over, placebo-controlled study, the subjects received SM 100 micrograms (four puffs, 25 micrograms per actuation), SB 200 micrograms (four puffs, 50 micrograms per actuation) or placebo (P) (four puffs). SM caused a greater and longer lasting increase of peak expiratory flow rate (PEFR) value than SB and P. There was no significant difference either with P or the study drugs in heart rate, PR interval, QT interval corrected for heart rate (QTc), incidence of ventricular and supraventricular ectopics, and in echocardiogram evaluation. These findings show that at dosages based on those used in clinical practice salmeterol causes cardiovascular effects comparable to those induced by salbutamol and confirm the favourable cardiac safety profile of this drug.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Albuterol/farmacología , Asma/fisiopatología , Broncodilatadores/farmacología , Electrocardiografía/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Corazón/efectos de los fármacos , Administración por Inhalación , Agonistas Adrenérgicos beta/administración & dosificación , Adulto , Albuterol/administración & dosificación , Asma/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Estudios Cruzados , Método Doble Ciego , Ecocardiografía Doppler en Color , Femenino , Humanos , MasculinoRESUMEN
We investigated the effect of G 619, a dual thromboxane synthase inhibitor and thromboxane A2 (TxA2) receptor antagonist, in pentobarbital-anaesthetized rats subjected to left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham-operated rats were used as controls (sham MI/R). Survival rate, myocardial necrosis, myocardial myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and serum creatine phosphokinase (CPK) activity were studied. MI/R injury significantly reduced survival rate (45%), caused a marked myocardial necrosis, increased serum CPK activity (sham MI/R = 35 +/- 12 U/ml; MI/R = 205 +/- 13 U/ml) and produced an increase in myocardial MPO activity in the area at risk and in the necrotic area (6.3 +/- 0.5 and 6.6 +/- 0.9 U x 10(-3)/g tissue, respectively). The administration of G 619 significantly increased survival rate, lowered the area of necrosis, blunted the increase in serum CPK activity and reduced the increase in MPO activity in both the area at risk and the necrotic area. These data are consistent with an involvement of TxA2 in MI/R injury and suggest that G 619 may represent a novel therapeutic approach to the treatment of acute myocardial infarction.
Asunto(s)
Benzamidas/farmacología , Enfermedad Coronaria/terapia , Daño por Reperfusión Miocárdica/prevención & control , Neutrófilos , Picolinas/farmacología , Receptores de Tromboxanos/antagonistas & inhibidores , Tromboxano-A Sintasa/antagonistas & inhibidores , Animales , Enfermedad Coronaria/enzimología , Creatina Quinasa/sangre , Modelos Animales de Enfermedad , Recuento de Leucocitos , Masculino , Infarto del Miocardio/tratamiento farmacológico , Daño por Reperfusión Miocárdica/enzimología , Neutrófilos/metabolismo , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Tasa de Supervivencia , Tromboxano A2/metabolismoRESUMEN
We investigated the effect of BAY u3405, a thromboxane A2 receptor antagonist in pentobarbital anaesthetized rats subjected to left main coronary artery ligation (1 h) followed by reperfusion (1 h; MI/R). Sham operated rats were used as controls (Sham MI/R). Survival rate, myocardial necrosis, myocardial myeloperoxidase activity (investigated as an index of leukocyte adhesion and accumulation) and serum creatine phosphokinase activity were studied. Ischaemia-reperfusion injury significantly reduced the survival rate (45%), caused a marked myocardial necrosis, increased serum creatine phosphokinase activity (Sham MI/R = 26 +/- 10.2 U/ml; MI/R = 213 +/- 19 U/ml) and produced a rise in myocardial myeloperoxidase activity in the area-at-risk and in the necrotic area (6.1 +/- 0.4 U x 10(-3)/g tissue and 6.7 +/- 0.9 U x 10(-3)/g of tissue, respectively). The administration of BAY u3405 (30 and 60 mg/kg/i.v., 30 min before occlusion) significantly increased survival rate, lowered the area of myocardial necrosis, blunted the increase in serum creatine phosphokinase activity and reduced the increase in myeloperoxidase activity in both the area-at-risk and the necrotic area. Furthermore, the protective effect of BAY u3405 was dose-dependent. These data are consistent with an involvement of TXA2 in myocardial ischaemia-reperfusion injury and suggest that BAY u3405 may represent a novel therapeutic approach to the treatment of acute ischaemia-reperfusion injury.
Asunto(s)
Carbazoles/farmacología , Leucocitos , Infarto del Miocardio/patología , Miocardio/citología , Receptores de Tromboxanos/antagonistas & inhibidores , Sulfonamidas/farmacología , Tromboxano A2/biosíntesis , Animales , Creatina Quinasa/antagonistas & inhibidores , Creatina Quinasa/sangre , Hemodinámica/efectos de los fármacos , Masculino , Isquemia Miocárdica/patología , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Peroxidasa/metabolismo , Ratas , Ratas Sprague-Dawley , Tromboxano A2/antagonistas & inhibidoresRESUMEN
Twelve patients (9 males, 3 females, mean age 59.2 +/- 7.0 years) with hyperkinetic ventricular arrhythmias were treated for 30 days with 150 mg propafenone three times daily; the daily dosage was raised to 900 mg in non responders (< 85% reduction of ectopic ventricular beats/h). A 24-hour ECGD and mono- and bidimensional echocardiography were carried out at baseline, after 30 days on 450 mg, 30 days on 900 mg propafenone, and one week after drug withdrawal. Propafenone treatment was found to reduce significantly ectopic ventricular beats, especially with the higher dosage (44.9% reduction under 450 mg; 88.8% reduction under 900 mg). At the lower dosage, 25% of patients responded, under the higher dosage 88.9%; the latter dosage also induced a significant reduction of Lown class. Propafenone treatment was also accompanied by a reduction of maximum and mean heart rate, and by a lengthened PR interval which was almost always within the normal range, without changes of QTc. The two months of propafenone treatment did not induce significant changes of cardiac volume or left ventricular function; on the contrary, at the end of the treatment period an increase, albeit not a significant one, of the ejection fraction and a shortening of the circumference inversely proportional to the reduction in ectopic ventricular beats could be noted. In conclusion, propafenone was found to have a valid antiarrhythmic effect, especially at the 900 mg/day dosage without interfering with left ventricular function which was even found to improve under chronic treatment, probably as a result of improved compliance thanks to the reduction of ventricular ectopic beats.
Asunto(s)
Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Propafenona/uso terapéutico , Anciano , Antiarrítmicos/farmacología , Esquema de Medicación , Evaluación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Propafenona/farmacología , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
The aim of the study was to assess the role of altered autonomic regulation on changes in the QT interval. Fifty-three diabetic patients, comprising 32 men and 21 women with a mean age of 49.4 +/- 15.9 years (range 13-73 years), underwent sympathetic and parasympathetic stimulatory tests (changes in heart rate between clino- and orthostatism, lying to standing, while deep breathing, Valsalva's manoeuvre, changes of arterial pressure related to posture) to study cardiovascular reflexes. Patients who were positive for at least two of the tests were considered to be affected by autonomic neuropathy. Ten non-diabetic age-matched subjects (44.8 +/- 14.8 years) with no cardiovascular diseases were included in the study as a control group. The QTc interval was measured in basal conditions and during sympathetic and parasympathetic stimulatory tests, in clino- and orthostatism, during deep breathing and Valsalva's manoeuvre. A significantly greater QTc interval (p less than 0.05) was found in neuropathic patients compared to controls and non-neuropathic patients both in basal conditions and following stimulatory tests at the lowest heart rate (phase IV of Valsalva's manoeuvre and slow exhalation during deep breathing), while at a higher heart rate (orthostatism, L-S, deep inhalation during deep breathing, phase II of Valsalva's manoeuvre) there was no difference in QTc between controls, and neuropathic and non-neuropathic patients due to a lesser extension of the QTc in neuropathic patients. This difference appears to be the expression of autonomic dysregulation in neuropathic patients, given the lack of correlation with diabetes or duration of disease, and is only conditioned by the presence or absence of autonomopathic damage. Among other causes, the observed extension of the QT interval might therefore justify the increased frequency of sudden death in diabetic patients with cardiovascular autonomic neuropathy.
Asunto(s)
Enfermedades Cardiovasculares/fisiopatología , Complicaciones de la Diabetes , Electrocardiografía , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , PosturaRESUMEN
Eleven patients with uncomplicated mild-to-moderate hypertension (diastolic pressure 95-115 mmHg) were treated for four weeks with daily single quinapril doses of 20-40 mg. Already during the second week a significant reduction in blood pressure was observed without increase of heart rate; 27.3% of patients responded to the lower dose (diastolic blood pressure [90 mmHg], and 54.6% responded to the higher dose. Drug treatment led to reduced pressure increase in response to cold stimulation without influencing the adrenergic response both in basal conditions and after cold pressor test. The drug brought about peripheral vasodilatation as shown by increased perfusion index during Doppler ultrasound examination, and improved arterial reactivity with increased perfusion index and reduced recovery time after ischemia. The reduction of angiotensin and aldosterone plasma levels during treatment was not correlated to diminished blood pressure values, indicating that the antihypertensive effect can occur via pathways different from ACE inhibition. Tolerance was excellent as shown both by clinical and laboratory evidence.