[The effect of nifedipine in hypertensive cardiopathy. An echocardiographic and electrocardiographic study]. / Effetto della nifedipina sulla cardiopatia ipertensiva. Studio ecocardiografico ed elettrocardiografico.

To assess whether antihypertensive therapy by nifedipine can reverse left ventricular (LV) hypertrophy, 15 hypertensive patients, mean age 47 years, were serially studied during 12 months of treatment with nifedipine in slow release (40-60 mg/day), by recordings of blood pressure (BP), ECG and echocardiogram. Blood pressure decreased from 161 +/- 6/104 +/- 3 mmHg to 131 +/- 3/89 +/- 1 mmHg, p < 0.001, and this fall first became statistically significant at 1 month. From the hemodynamic view point, BP decreased for a reduction in total peripheral resistance. The Sokolow-Lyon voltage decreased significantly after 6 months (from 33.5 +/- 2.7 to 28.1 +/- 2.1 mm, p < 0.01) without further changes in the subsequent months. Left ventricular mass, by echocardiography, decreased after 6 months (from 189 +/- 15 to 176 +/- 13 g/m2, p < 0.05) and further after 12 months (169 +/- 13 g/m2, p < 0.001). The reduction in LV mass was secondary to the decrease in wall thickness, particularly in posterior wall thickness. No significant changes were observed in LV fractional shortening throughout the study. Thus, nifedipine was an effective antihypertensive agent and reverted LV hypertrophy secondary to arterial hypertension without impairment of LV systolic function.

[The effect of nifedipine on arterial pressure and exercise tolerance in hypertensive patients]. / Effetto della nifedipina sulla pressione arteriosa e sulla tolleranza allo sforzo in pazienti ipertesi.

The aim of this research was to assess whether the antihypertensive therapy with nifedipine, a dihydropyridine calcium-antagonist, is able to control hypertension not only at rest but also during exercise. So, 20 male hypertensive patients, mean age 48 years, were evaluated by symptom limited bicycle exercise (10 W/min) before and after 6 and 12 months of therapy with nifedipine in a slow releasing form (40-60 mg/day). Exercise tolerance significantly increased after 12 months of antihypertensive therapy with nifedipine (from 146 +/- 5 to 153 +/- 4 W, p < 0.05). Systolic and diastolic blood pressure decreased after 6 and 12 months both at rest (from 160 +/- 6/109 +/- 9 mmHg to 132 +/- 3/91 +/- 3 and 135 +/- 4/93 +/- 1 mmHg, respectively, both p < 0.001) and during exercise (at end exercise: from 238 +/- 7/121 +/- 5 mmHg to 216 +/- 6/106 +/- 3 and 213 +/- 6/107 +/- 3 mmHg, respectively, both p < 0.001). No significant changes in heart rate were observed during antihypertensive therapy both at rest and during exercise test. In conclusion, long-term antihypertensive therapy with nifedipine was effective in the control of hypertension both at rest and during physical stress. Moreover, an improvement in effort tolerance was observed in hypertensive patients.

[Effects of benazepril, a new ACE inhibitor, in effort angina pectoris]. / Effetto del benazepril, nuovo inibitore dell'enzima di conversione, nell'angina pectoris da sforzo.

The aim of this study was to evaluate the anti-ischemic efficacy of 2 different doses of benazepril (B), a new ACE-inhibitor, 10 and 20 mg, given per os. Fifteen male patients gave informed, written consent; they were aged 40-67 years, with stable effort angina pectoris and were randomly given, in double-blind condition, a tablet containing B 10 mg, B 20 mg or placebo (PL), once a day, according to a 3 x 3 latin square design. Bicycle exercise tests were performed on the same day, 2 and 10 hours after the last drug intake. B 10 mg and B 20 mg, in patients with stable effort angina, compared to placebo, increased ischemic threshold and decreased ischemic ST depression at maximal work, after 2 hours but not after 10 hours. In conclusion B 10 mg and B 20 mg showed anti-ischemic activity 2 hours after drug intake.

[A new anti-ischemic drug for the treatment of stable effort angina pectoris: nicorandil. Comparison with placebo and isosorbide-5-mononitrate]. / Un nuovo farmaco antischemico nel trattamento dei pazienti affetti da angina pectoris da sforzo stabile: il nicorandil. Confronto con placebo ed isosorbide-5-mononitrato.

The aim of this study was to investigate antianginal and antiischemic activity and tolerance of a new nitrate derivative, nicorandil (N). This research has been carried out in 18 patients, aged 47-70 years, suffering from stable effort angina with fixed ischemic threshold. The study started with 10 days of washout, during which the patients exercised twice on bicycle to verify the reproducibility of the test. Then, they took N or isosorbide-5-mononitrate (ISM) for 14 days according to a double blinded cross-over balanced study. Between the 2 periods patients took placebo (PL) for 14 days. In the first day and in the last day of each period, 2 hours after the last drug intake, patients performed a stress test on bicycle. Like ISM, N significantly increased, versus PL, 1 mm of ST depression time (ischemic threshold) in the first and in the last day, without differences between the 2 drugs and between the days. Moreover, ST depression was significantly lower at maximal common work (MCW) versus PL. The rate-pressure product was not different from PL after N and ISM at maximal common work, but is was increased at the ischemic threshold. In conclusion, like ISM, N has shown antiischemic activity in patients suffering from stable angina pectoris on effort with fixed ischemic threshold. After 14 days of treatment there was no evidence of tolerance. The activity of N seems essentially due to an increase of coronary blood flow to ischemic zones.

[Transdermal nitroglycerin in stable effort angina. II. Administration of continuous high doses and alternate high-low doses. Absence of tolerance]. / La nitroglicerina transdermica nell'angina pectoris da sforzo stabile: II--Somministrazione a dosi alte continue e dosi alte-basse alternate. Assenza di tolleranza.

Aim of this study was to evaluate the efficacy of 2 different schedules of nitroglycerin (N), given by means of transdermal therapeutic system (TTS): continuous (20 mg patch at 8.00 am and at 8.00 pm NTTS/c) and high/low doses therapy (20 mg patch at 8.00 am and 10 mg at 8.00 pm NTTS/a), respectively. Eighteen volunteers, gave informed, written consent; male patients, aged 57 +/- 2 years, with stable effort angina pectoris, were randomly given, in double-blind condition, NTTS/c, NTTS/a or placebo (PL), each for 1 week period, according to a 3 x 3 latin square design. Bicycle exercise tests were performed on the first and on the last day of each period of the study, 12 hours after the last patch. NTTS/c and NTTS/a increased ischemic threshold and decreased the ischemic depression ST at maximal common work, compared to placebo, without differences between tests performed at 1 and 7 day. In conclusion, NTTS/a showed antiischemic activity after 7 days, so no tolerance was observed in those patients.

[Transdermal nitroglycerin in stable effort angina. I. Therapeutic effect and duration of the action of a single dose. Comparison with placebo and isosorbide dinitrate]. / La nitroglicerina transdermica nell'angina pectoris da sforzo stabile: I--Effetto terapeutico e durata d'azione della somministrazione singola. Confronto con placebo ed isosorbide dinitrato.

To assess the efficacy of 2 doses of a transdermal system for nitroglycerin, 10 and 20 mg (NTTS 10 and NTTS 20) and isosorbide dinitrate 40 mg (ISD 40) on exercise tolerance test, a double-blind within patients placebo (PL) controlled study was performed: 12 male patients, aged 47-71 years, with stable effort angina, with fixed ischemic threshold, received, according to a 4 x 4 latin square design, NTTS 10, NTTS 20, ISD 40 and PL, at 7.00 am on 4 consecutive days. Bicycle exercise tests were performed 4 and 12 hours post-dosing, after which the systems were removed. NTTS 10 and 20 and ISD 40 increased significantly ischemic threshold, anginal threshold and decreased maximal ST depression at the fourth hour. Only NTTS 10 and NTTS 20 showed antiischemic activity after 12 hours. During exercise, at the fourth and twelfth hour, there was no significant difference in rate-pressure product between placebo and NTTS 10 and 20 and ISD 40. Therefore the antiischemic activity of these drugs was not related to a decrease of myocardial oxygen consumption. In conclusion, in comparison with PL, NTTS 10, 20 and ISD 40 had antiischemic and antianginal activity at the fourth hour, while at the twelfth hour this activity was observed only after NTTS 10 and 20, without differences between the 2 doses.

[Effects of indenolol on left ventricular mass in patients with essential arterial hypertension]. / Effetti dell'indenololo sulla massa ventricolare sinistra nei pazienti affetti da ipertensione arteriosa essenziale.

This study evaluated the effect of long-term antihypertensive therapy with indenolol, a beta blocking agent with beta 2 stimulating activity, its antihypertensive hemodynamic mechanism and its effect on hypertensive left ventricular (LV) hypertrophy. Fourteen hypertensive patients, mean age of 48 years, were serially studied during 12- month therapy with indenolol (60-120 mg daily), by recording blood pressure, electrocardiogram and echocardiogram. Blood pressure, heart rate and cardiac output significantly decreased after 1 months of therapy, LV posterior wall thickness decreased after 6 months, interventricular septum thickness and LV mass decreased after 12 months. LV fractional shortening did not change throughout the study. Blood pressure normalized (less than or equal to 140/90 mmHg) in 50% of the patients; LV mass normalized in 40% of the patients. In conclusion, indenolol was an effective antihypertensive agent, also in the long-term treatment. Its antihypertensive hemodynamic effect seems to be due mainly to a reduction in cardiac output. Indenolol caused a regression of LV hypertensive hypertrophy without impairment of LV systolic function.

Propionyl carnitine in stable effort angina.

The aim of this study was to investigate the anti-ischemic activity of propionyl carnitine (PC) in 18 informed, volunteer male patients, aged 37-70, suffering from a typical stable effort angina. The study design was randomized, balanced, crossover, and double blinded. The study lasted 75 days. In the first 15 days of washout the patients performed two maximal symptom-limited bicycle tests to verify the repeatability of the parameters examined. Then one group received PC for 30 days 500 mg three times a day, and the other group received placebo (PL) three times a day. At the end of 30 days the groups exchanged treatments. At the end of each period, 2 hours after the last oral administration, the patients performed a maximal symptom-limited bicycle exercise test with increased loads of 10 watts/min. No significant differences were observed between the two tests performed during the wash-out period, for a 1 mm ST-segment depression time, for the time to the end of exercise, and for the rate x pressure product at the same experimental time. The oral administration of PC in coronary patients increased both the 1 mm ST-segment depression time and the time to the end of exercise. Furthermore, the drug reduced the ischemic depression of ST at maximal common work and at maximal work. After PC, the rate x pressure product was not significantly different in relation to placebo at submaximal and maximal exercise. Thus PC seems to have an antiischemiclike effect, probably related to its metabolic activity.

Effects of enalapril in normotensive patients with stable effort angina: a double blind, placebo controlled study.

To assess the anti-anginal and anti-ischaemic efficacy of the ACE-inhibitor enalapril in normotensive coronary patients, a double-blind, cross-over, placebo-controlled study was performed. Eight male patients, aged 45-68 years, with stable effort angina were given enalapril (10 mg) once a day or placebo for 7 days. Maximal exercise stress tests 10w/min in the upright position were performed at the end of each period. In comparison to placebo, enalapril increased significantly 1 mm of ST depression time and decreased significantly ST depression at maximal common work. Moreover, enalapril increased significantly the angina threshold and exercise duration. Three of the eight patients ended the exercise without pain. The rate-pressure product was not significantly modified at any time. Thus, the anti-ischaemic and anti-anginal activity may be due to an increase of coronary blood flow, rather than a reduction of MVO2 consumption.

Anti-ischaemic and anti-anginal activity of atenolol, nifedipine and their combination in stable, chronic effort angina.

To assess the anti-anginal and anti-ischaemic activity of the beta-blocker atenolol (ATN) and the calcium antagonist nifedipine (NIFE) and their combination in coronary patients, a double-blind, cross-over, placebo-controlled study was performed. Ten male patients (mean age: 58 +/- 2.9 years) suffering from a stable effort angina were studied. The study lasted 14 weeks: after 2 weeks of wash-out, patients were randomly assigned to ATN (100 mg/day) and placebo-NIFE, or placebo-ATN and NIFE (10 mg three times/day), or ATN (100 mg) plus NIFE (10 mg three times/day) for 4 weeks. Maximal symptom-limited stress tests on a bicycle (10 watt/min) during the wash-out period (on days 10 and 14) and at the end of each treatment period were performed. All treatments significantly increased the work load at 1 mm ST depression, the angina threshold and the total work, and reduced ST depression at the maximal common work and at the maximal work. Also the atenolol-nifedipine combination significantly reduced ST depression at maximal common work and maximal work as compared to ATN and NIFE alone. In conclusion, this study confirms the anti-ischaemic and anti-anginal activity of both atenolol and nifedipine in stable effort angina and shows that their combination is able to increase anti-ischaemic activity.