Acute hemodynamic and long-term clinical effects of isradipine in patients with coronary artery disease and chronic heart failure. A double-blind, placebo-controlled study.

To assess the acute hemodynamic and long-term clinical effects of isradipine, a calcium antagonist of the dihydropyridine class, we performed a double-blind, placebo-controlled parallel study in 19 patients with coronary artery disease (CAD) and stable chronic heart failure (CHF). Their mean age was 56 +/- 5 years, and left ventricular ejection fraction (LVEF) was 0.18 +/- 0.05. Patients were treated with diuretics and digoxin only. All were clinically stable and in sinus rhythm. The acute hemodynamic study showed that (intravenous) isradipine increased cardiac index (+36%) and stroke volume index (+30%) (both P < 0.001), while systemic vascular resistance (-33%) and mean arterial pressure (-10%) decreased (both P < 0.005). Filling pressures and heart rate were not affected. Of the 19 patients, 17 completed the 12 week study; 2 patients on placebo (1 death, 1 side-effects) but no patient on isradipine (5 mg 3 times daily) dropped out. After 12 weeks, peak oxygen consumption (VO2), LVEF, echocardiographic indices, and other clinical parameters were unaffected by treatment. Repeat invasive hemodynamic measurements showed that the initial improvement by isradipine was not present anymore. In conclusion, despite a beneficial acute hemodynamic effect, isradipine has no favorable clinical influence during prolonged treatment in patients with mild to moderate CHF.

Effects of isradipine on hemodynamic parameters and ventricular tachycardia in healed myocardial infarction.

The calcium-entry blocker isradipine was tested in a closed-chest pig model for chronic myocardial infarction. Ischemia was evoked in anesthetized pigs (25-35 kg) by inflating a catheter balloon in the left anterior descending coronary artery for at least 45 min. Hemodynamic monitoring and signal averaging of X, Y, and Z electrocardiographic leads were performed (150 beats, filtered at 50 Hz). After reperfusion, all animals developed an accelerated idioventricular rhythm and high creatine kinase (CPK) plasma levels. Coronary venous purines and catecholamines increased transiently. Two hours after reperfusion, heart rate was elevated from the initial 87.5 +/- 6.3 to 126 +/- 6.4 beats/min (p less than 0.01) and the pressure-rate product (PRP, an index of oxygen demand) from 9,530 +/- 630 to 11,950 +/- 790 mm Hg/min (p less than 0.05). After 2 weeks, six surviving pigs had a decreased stroke volume (98 +/- 18 versus the initial 124 +/- 14 microliters/kg, p less than 0.05), a prolonged high-frequency signal-averaged QRS duration (81.2 +/- 6.5 versus 65.7 +/- 2.9 ms, initially; p less than 0.05), and ventricular tachycardias (VTs), inducible by programmed electrical stimulation (PES). After the infusion of isradipine (1 microgram/kg/min for 30 min), the cardiac index increased from 92 +/- 14 to 133 +/- 8.7 ml/min.kg (p less than 0.02). Even at a higher heart rate, the PRP dropped from 12,600 +/- 1,900 to 10,560 +/- 1,400 mm Hg/min (p less than 0.05). Sustained monomorphic tachycardias were inducible in five pigs before and in three pigs after isradipine, and no deterioration of the signal-averaged electrocardiogram parameters was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Patency of arm vein grafts used in aorto-coronary bypass surgery.

Arm veins have been used in myocardial revascularisation procedures as a last resort bypass conduit because of their associated low patency. Nevertheless, leg veins and mammary arteries, which are the most commonly used, are sometimes not sufficient, leaving little choice as to the bypass conduit. To assess the properties of arm veins in bypass surgery, we compared a group of 28 patients that underwent an arm vein graft coronary bypass procedure with a matched group of patients in which leg veins were used. In 28 patients, 40 arm vein grafts with 77 distal anastomoses were used (mean 1.9 +/- 0.9; range 1-5). A cerebrovascular accident was the cause of the sole death (2%) during the study period. The mean follow-up was 4.6 years (Standard deviation, SD: 1.5 years). More antianginal medication was used in the arm vein group (P = 0.017). Additionally, the percentage of the expected maximal frequency during exercise testing was lower in the arm vein group as compared to the leg vein group. Digital subtraction angiography showed that the patency of the arm vein bypass grafts was 47% (70% confidence limits, CL: 32%-62%) while the patency of the leg vein grafts was 77% (CL: 64%-87%), which was statistically significant (P = 0.051). Comparison of these figures with the few published reports on arm veins used as coronary bypass grafts reveals similar results. We conclude that the arm vein as a coronary bypass graft is only to be used when mammary arteries and leg veins are not available.

Cardiac electrophysiologic properties of intravenous isradipine in patients with sick sinus syndrome.

Isradipine is a new dihydrophyridine calcium antagonist with powerful vasodilating properties. Although therapeutic concentrations do not affect myocardial contractility in vivo, in vitro studies have demonstrated a negative chronotropic action with only minor dromotropic influence. In humans with normal sinus and atrioventricular node function, even in the presence of beta-blockade, such a negative chronotropic effect could not be proved. No data are available on the effects of isradipine on a compromised sinus node. Therefore, the effect of intravenous isradipine at 0.3 microgram/kg/minute for 30 minutes was studied in seven patients with the clinical signs of a sick sinus syndrome. Mean arterial blood pressure decreased from 126 +/- 21 to 113 +/- 15 mm Hg (p less than 0.05). Spontaneous sinus cycle length decreased from 969 +/- 22 to 843 +/- 161 msec (p less than 0.05). Changes in sinoatrial conduction time, sinus node recovery time, and corrected sinus node recovery time were not significant. Changes in atrioventricular node function, as reflected by the atrioventricular node functional refractory period, the atrial-His interval, the His-ventricle interval, and Wenckebach point were not significant. Also, effective refractory periods of atrium and ventricle, and QRS duration changed but not significantly. The QT interval decreased (419 +/- 45 to 405 +/- 44 msec; p less than 0.05), and there was a slight (not significant) increase of QTc interval (429 +/- 41 to 443 +/- 37 msec; not significant). It is concluded that isradipine in hemodynamically effective doses has no depressant effect on sinus and atrioventricular node function in patients with sick sinus syndrome.