Carlo Strozzi

Torsades de pointes as a manifestation of mexiletine toxicity

An episode of torsades de pointes, an unusual ventricular tachyarrhythmia, developed in a 59-year-old coronary patient who was treated with 100 mg. four times a day mexiletine orally. The PR, QRS, and QT intervals were normal. The ventricular arrhythmias resembled in part, the patients previous ventricular premature complexes, but there were some relevant morphological differences. The plasma electrolytes were within normal limits. Mexiletine, which is chemically and electrophysiologically similar to lidocaine, probably caused this arrhythmia. Although mexiletine is a useful antiarrhythmic drug, it should be added to the list of drugs associated with atypical ventricular tachycardia.

Effects of Captopril on the Physical Work Capacity of Normotensive Patients with Stable-Effort Angina pectoris

Twelve normotensive patients with coronary artery disease and stable effort-induced angina pectoris were selected: the antiischemic effect of captopril was studied. A maximal cycloergometer effort test was obtained before (base) and after administration of placebo or captopril (50 mg p.o.). The following parameters were measured: heart rate (HR), blood pressure (BP), maximal rate/pressure product (MRPP), maximal workload sustained, (MWS), maximal working time (MWT), and S-T depression at MRPP. The base and placebo were similar. Compared to them captopril augmented the MWT, increased the MWS, reduced S-T depression at MRPP, and decreased the number of patients with effort-induced angina pectoris. The antiischemic effect of captopril seems related both to its effect on HR and BP, and to a local enhancement of coronary blood flow.

Relationship between pharmacokinetic and pharmacodynamic behaviour of bufuralol and its metabolite Ro 3-7410 in hypertensive patients

SummaryThe relationship between the plasma concentrations of bufuralol and its major hydroxymetabolite (Ro 3-7410) and β-blocking activity was studied in 10 patients with uncomplicated essential hypertension. Blood samples and haemodynamic data were obtained during rest and after a single-level exercise test on a bicycle cycloergometer, prior to and up to 32 h after administration of a single oral dose of bufuralol 30 mg. Bufuralol was rapidly absorbed, following a first-order process with a lag time. The calculated maximal plasma concentration ranged from 44.6 to 200.3 ng/ml. The half-life of bufuralol was 2.75±1.15 h (mean±SD). Up to 50% of the parent drug was transformed into Ro 3-7410, which showed less interpatient variability in concentration and a fairly constant half-life, which was three times longer than that of the parent drug. In general, the heart rate (HR) was slightly decreased, although 2/10 patients showed an initial increase. The resting HR returned to its pre-treatment level within 6 h, the exercise HR took up to 32 h to return to the pre-treatment level. The drug reduced both resting and exercise blood pressure (BP). The former was reduced from 153.0±14.2/93.5±8.5 to 134.5±14.0/77.0±6.8 mmHg (systolic/diastolic BP; mean±SD) with 6 h after treatment. Similarly, the exercise BP was reduced from 199.0±15.2/98.5±8.8 to 171.0±9.9/88.5±8.5 mmHg at the 6th h post-dosing. The BP values had not returned to their pre-treatment levels even 32 h after treatment. Thus, bufuralol and its metabolite Ro 3-7410 induced a long-lasting antihypertensive effect and inhibited the cardio-acceleratory effect of exercise, and there was a good correlation between the pharmacokinetic and pharmacodynamic behaviour of the drug.

The Kinetocardiogram During the Isoproterenol Test for the Assessment of Coronary Heart Disease

50 patients, 20 without heart disease and 30 with coronary heart disease (CHD), were studied by kinetocardiography (KCG), before and after administration of isoproterenol (initial dose 2 microgram/min, maximum dose 6 microgram/min). In the control subjects the KCG was unaffected by the drug. In contrast, in most of the patients with CHD isoproterenol induced the appearance or the increase of paradoxical systolic bulges, which are regarded as the expression of ventricular dyskinesia resulting from isoproterenol-induced transient regional ischemia. This test is recommended as a valuable noninvasive method for the diagnosis of ischemic ventricular dyskinesia.

Tiapamil in the Management of Supra ventricular Arrhythmias Occurring after Acute Myocardial Infarction

18 patients with acute myocardial infarction and sustained supra ventricular arrhythmias were treated with tiapamil, in a dose of 1 mg/kg i.v. The drug was effective, i.e., the heart rate was reduced

Asymptomatic Myocardial Ischemia in Coronary Patients with Stable Angina Pectoris

Little information is available on the frequency and characteristics of transient myocardial ischemia (TMI) in patients with stable angina pectoris. We selected 40 coronary patients with stable and typical angina. The presence of coronary artery disease and the ejection fraction were evaluated by means of angiocardiography. Dynamic electrocardiographic monitoring (DCG) was performed with bichanne1 portable recorders for three 24 hour periods at 7-10-day intervals. The patients were on optimal and stable doses of βblockers and isosorbidi1ate throughout the whole study. The DCG analyzer and the method of analysis were especially adapted for this study (S-T segment analysis).

Clinical Use of Beta-Blockers and Calcium-Entry Blockers in Stable Angina Pectoris

Drug therapy of coronary artery disease (CAD) is intended to eliminate the disproportion between oxygen supply and demand. Available drugs act mainly by reducing myocardial work and thus oxygen consumption. Some drugs antagonize the coronary spasm, thereby decreasing coronary resistance and, in consequence, increasing coronary blood flow.