Effects of cholestyramine on vitamin E levels in patients treated with statins.

The aim of this study was to investigate the effects of cholestyramine in combination with statins on vitamin E levels and their concentration related to LDL-cholesterol (LDL-C) in patients with hyperlipidemia. In an open-label, randomized study of 25 patients with elevated LDL-C, 12 received cholestyramine (12 g/d) in addition to chronic statin therapy, which had been started at least 8 weeks prior to the study in all patients. At the start and end of the 12-week study period, vitamin E concentrations were measured by high-performance liquid chromatography and cholesterol and triglycerides enzymatically in all patients. Vitamin E levels remained virtually unchanged within normal range before (11.90 +/- 0.71 mg/l) and after 12 weeks (11.69 +/- 0.82 mg/l) of concomitant therapy with cholestyramine. However, the ratio of vitamin E/LDL-C increased from 7.48 +/- 0.56 to 8.58 +/- 0.75 (x 10(-2)) (p < 0.09) in the cholestyramine group but not in the control group. LDL-C concentrations decreased from 162.00 +/- 5.98 to 144.33 +/- 12.48 mg/dl. The authors conclude that cholestyramine 12 g/d given for 12 weeks in addition to chronic statin therapy did not lower vitamin E levels in hyperlipemic patients. However, antioxidant status (vitamin E/LDL-C ratio) seems to be improved by a cholestyramine-associated LDL-C decrease.

Preliminary evidence for the mechanism underlying the development of tolerance to prazosin in congestive heart failure: the alpha-agonistic properties of dobutamine unmasked by prazosin treatment.

The hemodynamic effects of acute and chronic treatment with different vasodilators were assessed in patients with chronic heart failure of New York Heart Association (NYHA) class III-IV. Each of 24 patients was randomly allocated; 6 to each of four groups: isosorbide dinitrate, dihydralazine, captopril, or prazosin. In addition, we evaluated the hemodynamic response to dobutamine by using increasing infusion rates of 2.5, 5.0, and 10.0 micrograms/kg/min at the start and end of a 3-month period of chronic therapy with either vasodilator. Dobutamine caused a dose-dependent increase in cardiac index and a decrease in mean pulmonary artery pressure (PAP) at the start of the vasodilatory treatment and maintained the effects during a 3-month period of chronic treatment with either isosorbide dinitrate, dihydralazine, or captopril. After 3-month therapy with 6 mg/day prazosin, however, mean PAP was increased above pretreatment value and dobutamine caused a further increase in PAP, thus reversing the initial effects. The dobutamine-induced increase in cardiac index remained virtually unchanged. We conclude that the reversal of the effects on PAP after chronic treatment with prazosin may be, at least in part, due to upregulation of alpha 1-adrenoceptors. This appears to be unmasked by the alpha 1-adrenoceptor agonist of the (-)-enantiomer of the racemic mixture of (+/-)-dobutamine.

[Posterior aortic wall motion in mitral valve disease (author's transl)]. / Die Bewegung der Aortenwand im präkordialen Echokardiogramm bei Patienten mit Mitralklappenerkrankungen.

The posterior aortic wall motion was studied in 60 patients, 39 patients with mitral valve disease and 21 normals. The motion of the posterior aortic wall was measured by using the amplitude of the posterior aortic wall motion from the beginning of left ventricular contraction to aortic valve closure and an atrial filling and emptying index. The latter two indices were used, because left atrial volume changes were reflected by the motion of the posterior aortic wall. It could be demonstrated that normals differed in their motion pattern of the posterior aortic wall to those with mitral valve disease. Furthermore, patients with mitral stenosis, mitral insufficiency and mixed mitral valve disease could be differentiated from each other in terms of these indices and an atrial filling-emptying ratio. Thus careful inspection of the posterior aortic wall motion by precordial echocardiography can be used as a parameter of mitral valve function.

Hemodynamic response to graded water immersion.

Hemodynamic response to graded immersion was studied in healthy male subjects in a thermoneutral bath in the sitting position. Pressures in the right heart and cardiac output were determined by means of a semifloating catheter with a thermistor probe. Pressures in the right atrium, pulmonary artery and in pulmonary wedge position increased with increasing depth of immersion, cardiac output was likewise augmented. Heart rate decreased from rest to hip immersion but remained constant from hip to head out water immersion. Plasma norepinephrine concentration remained constant throughout the experiment. The reported changes depend on the blood shift from capacitance vessels into the thoracic cavity. From this, preload increased and cardiac performance was improved. However, in patients with disturbed left ventricular function, immersion to the neck may be potentially hazardous due to augmented left ventricular filling pressure.

[Hemodynamic actions on alinidine during exercise in patients with coronary artery disease].

The effect of Alinidine (ST 567) on hemodynamics at rest and during exercise was studied in subjects with angiographically documented coronary artery disease and left ventricular dysfunction. Exercise tests were performed before and 30 min after intravenous administration of 20 mg of Alinidine. Significant decreases were observed for heart rate at rest and during exercise, for systolic and diastolic blood pressure. Pressures in the pulmonary artery and in capillary wedge position were significantly reduced after Alinidine by about 12 to 18% (mean PAP) and by about 19 to 28% (PCW). Cardiac output and stroke volume increased during exercise after Alinidine, but the differences were not significant. Depression of ST-segment in the exercise-ECG was significantly lower after Alinidine, angina pectoris occurred in all but one subject during control testing but in none after Alinidine. It is concluded that Alinidine is an effective antianginal drug. Intravenous administration of this agent even in a low dose improves cardiac performance during exercise in patients with impaired left ventricular function. Negative inotropic effects of Alinidine were not observed in this study. Bradycardia and in addition preload reduction are suggested to be the main mechanisms to improve left ventricular function and symptomatic status.

Posterior aortic wall motion and left atrial volume changes.

The motion characteristic of the posterior aortic wall has been used in precordial M-mode echocardiography as a parameter of cardiac function. However, the determinants of this characteristic motion pattern of the aorta are still unknown. In this study the posterior aortic wall motion was studied angiographically as it is related to left atrial volume changes. 21 patients with various heart diseases served as the study group. 18 patients were in sinus rhythm, 3 patients in atrial fibrillation. We found an excellent agreement between left atrial volume changes and the movement of the posterior aortic wall. The correlation coefficient between both parameters ranged from .73 to .95 irrespective of the underlying heart disease and heart rhythm. From this study one can conclude that left atrial volume changes are reflected by the motion of the posterior aortic wall.

Clinical electrophysiological properties of N-allyl-clonidine (ST 567) in man.

The electrophysiological properties of N-allyl-clonidine (ST 567) were studied in 18 patients. Four of these patients were pretreated with intravenous propranolol, 0.2 mg/kg, and atropine, 0.04 mg/kg, to induce autonomic blockade. ST 567 produces a sustained bradycardiac effect at a dose of 40 mg, i.v., in patients without (group I) and with (group II) autonomic blockade. The mean increase in Group I was 23% and in group II, 42%. The sinus node recovery time increased in both groups, from 1,151 +/- 73 to 1,310 +/- 81 msec in group I, and from 995 +/- 145 to 1,599 +/- 248 msec (means +/- SEM) in group II. The corrected sinus node recovery time was unaffected by ST 567 in Group I and increased from 165 +/- 50 to 427 +/- 117 msec in group II. The sinoatrial conduction time was unaffected by ST 567 in group I. The effective refractory period of the right atrium, the atrioventricular node and the right ventricle, as well as the functional refractory period of the atrioventricular node, were unaffected by ST 567 in patients without autonomic blockade. Intra-atrial, atrioventricular, and intraventricular conduction were also not altered by this drug. Thus, the electrophysiological profile of ST 567 differs from other bradycardia-inducing agents such as beta-blockers or calcium antagonists.

Haemodynamic effects of a single intravenous dose of lorcainide in patients with heart disease.

The cardiovascular effects of a single i.v. dose (2 mg/kg over 5 min) of lorcainide were studied in 14 patients with heart disease. In the haemodynamic part of the study (6 patients), the aortic and pulmonary systolic, diastolic and mean pressures, left ventricular systolic and end-diastolic pressures, cardiac output and the rate of rise of left ventricular pressure were measured before and for 30 min after administration of the drug. Lorcainide produced a slight and short-lasting decrease in the aortic and pulmonary systolic pressures, and all other pressure values remained unchanged. The cardiac output and systemic vascular resistance were not altered by lorcainide. It consistently depressed the rate of rise of left ventricular pressure (maximum mean decrease 19%). In the angiographic part of the study (8 patients), the ejection fraction and the mean velocity of circumferential fiber shortening were measured before and 5 min after lorcainide. In all but one patient, lorcainide decreased the ejection fraction (mean decrease 11.6%), and the mean velocity of circumferential fiber shortening was uniformly diminished by lorcainide (mean decrease 29.7%). Thus, lorcainide moderately impaired myocardial performance in patients with normal and reduced left ventricular function without producing hypotensive side effects.

[Motion of the posterior wall in the m-mode echocardiogram - a parameter of global left function (author's transl)]. / Die Bewegung der Aortenhinterwand im M-mode-Echokardiogramm: Ein Parameter der linksventrikulären Funktion.

The cardiac output was determined by thermodilution in 42 patients during heart catheterization and compared to the amplitude of the posterior aortic wall in the m-mode echocardiogram. The amplitude of the posterior aortic wall was measured at the time of the closure of the aortic cusps (KS) and at the time the maximal excursion of the posterior aortic wall occurred (GA). Both parameters correlated strongly to the cardia output (r = 0.84, KS; r = 0.76, GA) and to the forward stroke volume (r = 0.81, KS; r = 0.73, GA). Thus, the amplitude of the posterior aortic wall in the m-mode echocardiogram is a useful parameter in predicting left ventricular function especially in those patients, in whom determination of left ventricular function from the m-mode echocardiogram is limited due to left ventricular asynergy.

Wall motion characteristic of the right pulmonary artery in the suprasternal echocardiogram.

This study describes the motion pattern of the right pulmonary artery (RPA) as it can be assessed from the suprasternal echocardiogram. The motion characteristic of the RPA is dependent on hemodynamic factors within the lumen of the RPA and those within the left atrium and the aortic arch. During atrial contraction the superior wall of the left atrium separates from the inferior wall of the RPA (IWRPA) and produces an "a" dip in the wall motion of the IWRPA. During isovolumic contraction the RPA is shifted upward (IC point). The incisura in the pulmonary artery pressure curve reflecting pulmonic valve closure can be seen by a sudden decrease in the diameter of the RPA (PC point). In conditions coinciding with pulmonary arterial hypertension, the overall diameter of the RPA increases, and the IC and PC points are flattened or even absent. Thus, changes in hemodynamics caused by pulmonary or cardiac disease may be analyzed noninvasively on the basis of altered wall motion of the RPA.

Antiarrhythmic effect of lorcainide during chronic treatment.

The effect of oral N-(4-chlorophenyl)-N-[1-(1-methylethyl)-4-piperidinyl]benzene acetamide (lorcainide) was studied in 12 patients with frequent and stable ventricular arrhythmias resistant to a number of other antiarrhythmic agents. Ambulatory electrocardiograms were obtained before and during treatment with lorcainide and in some patients after discontinuation of the drug. Lorcainide suppressed ventricular premature contractions by more than 90% in all but one patient. The daily doses were 200 mg (N = 8), 300 mg (N = 1), 400 mg (N = 1)and 600 mg (N = 2). Plasma concentrations of lorcainide and of the dealkylated metabolite ranged from 0.13 to 0.27 microgram/ml and 0.25 to 0.95 microgram/ml, respectively. Side effects such as insomnia and excessive perspiration were seen in 7 and 3 patients, respectively. Lorcainide is an effective antiarrhythmic agent against ventricular arrhythmias otherwise difficult to treat.

Electrophysiological actions of lorcainide in patients with cardiac disease.

Lorcainide is a new antiarrhythmic agent which effectively suppresses ventricular premature contractions. Its electrophysiological actions were studied in 15 cardiac patients with and without cardiac conduction abnormalities. In a dose of 2 mg/kg body weight, lorcainide decreased the sinus cycle length (SCL) and increased the corrected sinus node recovery time. The intra-atrial, atrioventricular (AV), and intraventricular conduction times were prolonged. A third-degree AV block developed in 2 patients with pre-existing conduction abnormalities. QRS widening showed that intramyocardial conduction was also affected. The effective refractory period of the atrioventricular node (ERP-AVN) was shortened, whereas the effect on the functional refractory period of the AVN was variable. The decrease in SCL and ERP-AVN may be due to a possible anticholinergic effect of the drug. The accessory pathway was blocked in 3 patients with a Wolff-Parkinson-White syndrome. The ERP of the ventricle was slightly prolonged. The electrophysiological profile of the drug, i.e., slowing of conduction velocity throughout the heart combined with shortening of SCL and ERP-AVN, differs from other antiarrhythmic agents.