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Biomedical subjects

H Just

Publications and source records attributed to H Just.

At least 217 records · Page 12Linked to original sources
PubMed1990

Incidence and clinical relevance of QT prolongation caused by the new selective serotonin antagonist ketanserin. Multicenter Ketanserin Research Group.

Efficacy and safety of ketanserin was studied prospectively in a randomized and double-blind trial involving 221 patients treated for hypertension and/or coronary artery disease. Since ketanserin has been suggested to cause QTc prolongation, we investigated the incidence and severity of this effect, as well as its influence on the incidence of malignant ventricular arrhythmias during Holter monitoring. After a 1-week run-in-period, all patients were examined, measuring blood pressure, electrocardiogram (ECG) and 24-hour Holter ECG. Two thirds of the patients (n = 147) were then randomized to ketanserin, 1 week 20 mg b.i.d. followed by 3 weeks 40 mg b.i.d.; one third of the patients (n = 74) received placebo b.i.d. for 4 weeks. After 4 weeks of treatment, blood pressure, ECG and 24-hour Holter ECG were performed. In hypertensive patients, ketanserin resulted in a significant reduction of systolic (mean reduction: -17 +/- 2 mm Hg; p less than 0.0001) and diastolic blood pressure (-12 +/- 1 mm Hg; p less than 0.0001) as compared to baseline, and to the placebo group (p less than 0.005 for systolic and diastolic blood pressure). The QTc interval was prolonged with ketanserin (mean value: 400 to 418 ms; p less than 0.01) but not with placebo (399 vs. 402 ms). In the ketanserin group 30% of patients and in the placebo group 8% of patients had QTc prolongation greater than 30 ms (p less than 0.01). QTc was not prolonged to greater than 500 ms in any patient. During Holter monitoring 128/147 patients (ketanserin group) and 61/74 patients (placebo group) had ventricular premature beats; in 42 (ketanserin group) and 13 patients (placebo group) ventricular pairs and tachycardia were documented. Incidence and severity of the ventricular arrhythmias after 4 weeks of treatment were not different between the ketanserin and placebo groups. No sustained ventricular tachycardia occurred in any patient after ketanserin treatment. Thus, though ketanserin prolonged QTc in one third of the patients, the drug was not arrhythmogenic or antiarrhythmic.

Aged↗
PubMed1990

[Effect of atrial natriuretic factor on coronary vascular tone].

To test whether atrial natriuretic factor (ANF) may be involved in the modulation of coronary vasomotor tone, ANF was injected into angiographically normal left coronary arteries. Measurement of epicardial diameters of the circumflex (Cx) and left anterior descending artery (LAD) were made from biplane angiograms by an automatic contour-detection system. Bolus injection of ANF (0.07 micrograms/kg, diluted in 1 ml 0.9% NaCl, n = 7) increased diameter of proximal segments of LAD (11 +/- 4%) and Cx (10 +/- 4%) (p less than 0.02 each vs control) without altering heart rate and mean arterial pressure (MAP). Intracoronary nitroglycerin (NTG, 0.3 mg) increased diameters of identical LAD and Cx segments by 18 +/- 3% and 20 +/- 4%. Intracoronary ANF infusion (0.02 micrograms/kg/min over 5 min, followed by 0.1 micrograms/kg/min, n = 10) exerted dose-dependent increases in diameters of LAD and Cx (low dose: + 5 +/- 2%, p less than 0.05 vs control; high dose: + 13 +/- 3%, p less than 0.01 vs control). ANF-infusion increased arterial plasma ANF levels from 280 +/- 80 pg/ml during control to 894 +/- 82 pg/ml (low dose; + 614 pg/ml vs control) and to 2290 +/- 228 pg/ml (high dose). Severe ischemia in four patients undergoing angioplasty exerted substantial increase in arterial ANF levels (160 +/- 60 to 608 +/- 111 pg/ml; + 448 pg/ml vs control), similar to the increase elicited by low dose ANF infusion in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1990

[How are tachycardic cardiac arrhythmias modified by therapy of congestive heart failure?].

Previous studies have demonstrated the high prevalence of frequent and complex ventricular arrhythmias in patients with severe congestive heart failure. It has been claimed that these arrhythmias are independent risk factors of prognosis. Moreover in severely depressed left ventricular function frequent and repetitive arrhythmias may deteriorate the hemodynamic situation. Recent clinical studies have drawn increasing attention to the possibility that the desired therapeutic effect of Class I antiarrhythmic agents may be complicated by their ability to aggravate the arrhythmia or to provoke new arrhythmias. These "proarrhythmical effects" were more frequent in patients with life-threatening arrhythmias and in those with severely depressed left ventricular function. Prevention trials with Class I antiarrhythmic agents have failed to show beneficial effects on the arrhythmia profile and on the prognosis of those patients. On the other hand, it is now well recognized that the incidence of cardiac death can be reduced by the use of ACE-inhibitors in this patient population. Accordingly, there is evidence of a reduced incidence of complex ventricular arrhythmias during treatment with these drugs in some of the patients with congestive heart failure. The influence of digitalis on the arrhythmia profile and the cardiac mortality in these patients is still a matter of debate. On the other hand, there is evidence that newer positive inotropic agents such as phosphodiesterase-inhibitors rather increase the number of arrhythmias and the prevalence of sudden cardiac death in this patient population.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

[Transesophageal echocardiography in the assessment of the severity of aortic valve stenosis].

The aortic valve orifice area was measured in 95 patients with valvular aortic stenosis by means of transthoracic and transesophageal echocardiography. These results were compared to invasively determined measurements. The aortic-valve orifice area could be measured by transesophageal echocardiography in 87 patients (92%), and in 13 patients (14%) by the transthoracic approach. A comparison of the valve-orifice area determined by transthoracic and transesophageal echocardiography revealed a correlation coefficient of r = 0.91. There was also a good agreement when the aortic-valve orifice area determined by transesophageal echocardiography was compared to the invasive findings (r = 0.82; p less than 0.001). The morphology of the aortic valve could be better delineated with the transesophageal approach.

Adult↗
PubMed1990

[Transesophageal and Doppler ultrasound studies before and following percutaneous balloon valvuloplasty of the aortic valve].

Transesophageal and Doppler-echocardiography were performed in 25 patients with severe valvular aortic stenosis before and after percutaneous balloon valvuloplasty. The maximal systolic gradient over the aortic valve determined during invasive measurements before and after valvuloplasty decreased from 71 +/- 24 mm Hg to 36 +/- 14 mm Hg; the mean systolic gradient decreased from 53 +/- 18 mm Hg to 28 +/- 10 mm Hg. The aortic orifice area increased from 0.67 +/- 0.2 to 0.94 +/- 0.2 cm2. During transesophageal echocardiography the aortic orifice area was calculated by direct planimetry. The aortic valve area increased from 0.52 +/- 0.21 cm2 before the valvuloplasty to 0.72 +/- 0.17 cm2 after intervention. After valvuloplasty small thrombotic vegetations were observed in four patients and valvular lesions in two patients. Using Doppler-echocardiographic measurements to quantify the aortic valve stenosis the maximal instantaneous gradient decreased from 94 +/- 30 before valvuloplasty to 66 +/- 25 mm Hg after valvuloplasty; the mean instantaneous gradient changed from 52 +/- 17 to 37 +/- 14 mm Hg. The aortic orifice area increased from 0.5 +/- 016 to 0.76 +/- 0.21 cm2. These results confirm that transesophageal and Doppler-echocardiography are appropriate to control the success of percutaneous balloon valvuloplasty.

Aged↗
PubMed1990

[Predictive value of programmed electrostimulation in patients with spontaneous idiopathic ventricular tachycardia].

In contrast to patients with organic heart disease, there are only few data available on the incidence and type of inducible arrhythmias during programmed electrical stimulation (PES) in patients with spontaneous ventricular tachycardia (VT) but without evidence of underlying heart disease. Additionally, no consensus has been achieved in these patients on the most appropriate stimulation protocol required to reproduce the clinical arrhythmia. In a prospective study we analyzed in 40 patients without idiopathic VT, incidence and type of inducible VT, as well as the mode of initiation during a right ventricular PES protocol with 1-2 (part I) and three extrastimuli (part II). Twelve patients had spontaneous sustained monomorphic VT (group A), 28 patients were studied with spontaneous non-sustained VT (group B). During PES, a non-sustained polymorphic VT was induced in 3/12 patients (group A, 25%) and in 10/28 patients (group B, 36%); a non-sustained monomorphic VT was induced in 5/12 patients (group A, 41%) and in 4/28 patients (group B, 14%). In all 7/12 patients (59%) of group A with inducible sustained monomorphic VT, the arrhythmia was initiated with 1-2 extrastimuli. In group B, only 2/28 patients (7%) were induced to a sustained monomorphic VT. When the clinical arrhythmia was exercise-related, 5/6 patients (83%) in group A and 7/13 patients (54%) in group B were induced to a VT, while 2/6 patients (33%) in group A and 1/13 (8%) patients in group B were induced to a sustained monomorphic VT. Isoprenaline was not effective to increase the incidence of sustained monomorphic VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

[Transfemoral, transatrial double-balloon valvuloplasty of rheumatic mitral stenosis].

A percutaneous transfemoral, transatrial double-balloon valvuloplasty was performed on 21 patients (53 +/- 14 years) with rheumatic mitral stenosis. An open commissurotomy was performed in six patients, 20 +/- 9 years previously; in three patients an arterial embolism had occurred previously. Balloon valvuloplasty resulted in a reduction of the mean diastolic gradient from 16 +/- 7 to 8 +/- 3 mm Hg (p less than 0.001), and the mitral valve orifice area increased from 1.1 +/- 0.3 to 2.2 +/- 0.8 cm2 (p less than 0.001). Mitral insufficiency increased in three patients and was first observed after valvuloplasty in four patients. Complications were seen in three patients: a left ventricular perforation resulting in pericardial tamponade occurred in two patients, which required cardiothoracic intervention. In one patient a pulmonary embolism occurred five days after the invasive procedure. The study shows that percutaneous transfemoral balloon valvuloplasty can successfully be performed in patients with severe or even calcified mitral valve stenosis. The risk of severe complications is, however, not negligible.

Adult↗
PubMed1989

Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium.

The coronary vasomotor response to the cold pressor test was studied with use of quantitative coronary angiography in 32 patients without evidence of coronary artery disease and 55 patients with such disease; in a subset of 22 patients (9 with normal coronary arteries and 13 with coronary artery disease), the effects of the cold pressor test were compared with the effects of the endothelium-dependent vasodilator acetylcholine with simultaneous intracoronary Doppler flow velocity measurements to assess the influence of endothelial dysfunction. The cold pressor test induced vasodilation of 8.9 +/- 5.7% in all 77 analyzed vessel segments of the group with normal arteries (p less than 0.01). In contrast, in patients with coronary artery disease, the 52 analyzed stenotic segments were constricted by -12.1 +/- 9.5% (p less than 0.01), the 57 analyzed vessel segments with luminal irregularities were constricted by -8.9 +/- 5.2% (p less 0.01) and 40 (85%) of 47 angiographically normal segments also were constricted by -7.0 +/- 4.9% (p less than 0.05). Preserved vasodilating capability was demonstrated by intracoronary nitroglycerin in all analyzed segments. In nine patients with normal coronary arteries, the analyzed vessel segments were dilated in response to both the cold pressor test and intracoronary acetylcholine by 10.9 +/- 5.4% and 13.4 +/- 4.7%, respectively. In contrast, in all 13 patients with coronary artery disease, vasoconstriction of identical vessel segments by -9.1 +/- 3.7% and -23 +/- 10.4%, respectively, was observed after both the cold pressor test and intracoronary acetylcholine. Intracoronary propranolol did not significantly affect either the vasodilative response in 11 normal coronary arteries (11.3 +/- 4.4% before and 8.6 +/- 4.3% after beta-blockade) or the vasoconstrictor response in 8 atherosclerotic coronary arteries (-11.4 +/- 4.6% before and -14.6 +/- 5.3% after beta-blockade). The dilation of normal and the constriction of atherosclerotic coronary arteries with cold pressor testing exactly mirror the response to the endothelium-dependent dilator acetylcholine. Endothelial dysfunction in coronary atherosclerosis resulted in a loss of normal dilator function and permitted vasoconstrictor responses to sympathetic stimulation. Thus, coronary vasomotion of large epicardial arteries in response to sympathetic stimulation by the cold pressor test in humans is intimately related to the integrity of endothelial function.

Acetylcholine↗
PubMed1989

Incidence and clinical relevance of QT prolongation caused by the new selective serotonin antagonist ketanserin.

Efficacy and safety of ketanserin were studied prospectively in a randomized, double-blind trial involving 221 patients treated for hypertension or coronary artery disease, or both. Since ketanserin has been suggested to cause QTc prolongation, the incidence and severity of this effect were investigated, as was the incidence of malignant ventricular arrhythmias during Holter monitoring. After a 1-week run-in period, all patients were examined: blood pressure was measured and electrocardiograms and 24-hour Holter electrocardiograms were obtained. Two thirds of the patients (n = 147) were then randomized to receive ketanserin for 1 week (20 mg twice daily) followed by 3 weeks of 40 mg twice daily; one third of the patients (n = 74) received placebo (twice daily) for 4 weeks. After 4 weeks of treatment, blood pressure, electrocardiograms and 24-hour Holter electrocardiograms were repeated. In hypertensive patients, ketanserin significantly reduced systolic (mean reduction 17 +/- 2 mm Hg, p less than 0.0001) and diastolic blood pressure (12 +/- 1 mm Hg, p less than 0.0001) compared to baseline, and to the placebo group (p less than 0.005 for systolic and diastolic blood pressure). The QTc interval was prolonged with ketanserin (mean 400 to 418 ms, p less than 0.01) but not with placebo (399 vs 402 ms). In the ketanserin group 30% of patients and in the placebo group 8% of patients had QTc prolongation greater than 30 ms (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Comparison of twice daily with thrice daily administered encainide for benign or potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy of encainide administered 2 (group A) or 3 times daily (group B) was evaluated in a randomized, placebo-controlled trial involving 101 patients with benign or potentially malignant ventricular arrhythmias. In group A, encainide was titrated at dosages of 35, 50 and 75 mg twice daily and in group B at dosages of 25, 35 and 50 mg 3 times daily. Drug efficacy, as judged by repeated ambulatory monitoring, was defined as greater than 75% reduction in ventricular premature complexes combined with a greater than 90% abolition of pairs and runs of nonsustained ventricular tachycardia. In group A, 27 of 52 patients (52%) had their arrhythmia suppressed by the drug compared with 34 of 49 (69%) in group B (difference not significant). There was a trend toward better arrhythmia control in group B if a total daily dose of greater than 100 mg was necessary for arrhythmia suppression. Side effects were frequent in both groups (24 vs 28%, difference not significant). Thus, encainide administered twice daily effectively suppresses ventricular arrhythmias in this patient population.

Adult↗
PubMed1989

Influence of isoproterenol on myocardial energetics. Experimental and clinical investigations.

The influence of isoproterenol on myocardial performance and energetics was investigated in normal guinea pig myocardium and in patients with normal left ventricular function. The in vitro experiments were performed by simultaneous isometric force and heat measurements using sensitive antimony-bismuth thermopiles. Following the application of isoproterenol (10(-8) M) isometric peak twitch tension and tension-time integral increased significantly by 185% and 142%, respectively. Tension-independent heat which reflects high energy phosphate hydrolysis of excitation-contraction coupling increased by 183%. Tension-dependent heat reflecting the high energy phosphate hydrolysis of the crossbridges increased by 417%. The ratio of tension-dependent heat to tension-time integral increased by 131%. The recovery/initial heat ratio, reflecting the efficiency of the recovery metabolism, and the resting metabolism did not significantly change. In the patients the effect of isoproterenol on myocardial energetics was evaluated in terms of myocardial efficiency. Following isoproterenol administration, left ventricular systolic stress-time integral decreased by 49% due to reductions in end-diastolic pressure, end-diastolic volume and duration of systole. Pressure-volume work remained unchanged. Myocardial oxygen consumption per minute increased in proportion to heart rate. The ratio of myocardial oxygen consumption per beat to left ventricular systolic stress-time integral increased significantly by 95%. External myocardial efficiency was unaltered. Thus, isoproterenol increases the energy turnover of excitation-contraction coupling and increases the energy consumption of the crossbridges disproportionately to developed tension-time integral in the guinea pig heart.

Adult↗
PubMed1989

Dopexamine in congestive heart failure: how do the pharmacological activities translate into the clinical situation?

Dopexamine is a newly developed sympathetic catecholamine which combines dopaminergic (DA-1) and beta 2-adrenergic agonist activity with only minor beta 1-adrenergic action. Thereby, this compound exerts systemic and preferential renal vasodilation, causing afterload reduction, increases in cardiac output, and improved renal perfusion in animals and normal volunteers. Short-term administration of dopexamine in congestive heart failure established beneficial effects in central hemodynamics, that is, reduction of systemic and pulmonary vascular resistance, combined with a decrease in LV-filling pressures and increased renal blood flow. The effect on central hemodynamics are comparable to sodium nitroprusside. With higher doses, however, heart rate may increase substantially with dopexamine along with increased myocardial oxygen consumption. Experiences with prolonged administration of this drug are scarce and have, so far, yielded conflicting results. Thus, dopexamine appears to be a promising agent in the short-term management of congestive heart failure. However, its ultimate value for prolonged administration remains to be established.

Adrenergic Agonists↗
PubMed1989

Clinical relevance of long-term therapy with levodopa and orally active dopamine analogues in patients with chronic congestive heart failure.

Beneficial effects of long-term treatment with dopamine analogues in patients with congestive heart failure may result from their vasodilating properties, in particular from renal artery vasodilation. Oral application of levodopa results in increased dopamine plasma levels and can improve cardiac performance and renal function in patients with congestive heart failure. A daily levodopa dosage of at least 4 g appears to a prerequisite for long-term response to the drug. Because of frequent side effects including nausea, vomiting, and dyskinesia at this dosage, the clinical usefulness of levodopa seems to be limited to a minority of patients. Ventricular arrhythmias have been shown to increase significantly during long-term levodopa therapy, probably due to stimulation of myocardial beta receptors. Increased ventricular arrhythmias or significant central nervous side effects have not been observed after administration of ibopamine and fenoldopam, which are orally active analogues of dopamine. Both agents exhibit potent arterial vasodilating properties and have been shown to increase cardiac performance in patients with congestive heart failure after short-term administration. The long-term beneficial effects of ibopamine and fenoldopam in the treatment of congestive heart failure have not yet been clarified. However, available results are encouraging and warrant further clinical evaluation of these agents, as well as the development of new analogues of dopamine, in particular of potent vascular dopamine agonists.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Influence of the calcium-sensitizer UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy. Comparison with nitroprusside.

UDCG-115 is a new cardiotonic agent which in vitro increases the sensitivity of the contractile proteins to calcium ions, inhibits the activity of phosphodiesterase, and prolongs the duration of the action potential. The influence of UDCG-115 (i.v.) on hemodynamics and myocardial energetics was investigated in patients with idiopathic dilated cardiomyopathy (NYHA II-III) and compared to the effects of the pure vasodilator nitroprusside. UDCG-115 increased cardiac index from 3.2 +/- 0.4 to 4.2 +/- 0.8 l/min/m2 (p less than 0.01) and decreased left ventricular end-diastolic wall stress (preload) from 52 +/- 21 to 28 +/- 18 10(3) dyn/cm2 (p less than 0.01) and end-systolic wall stress (afterload) from 201 +/- 61 to 129 +/- 43 10(3) dyn/cm2 (p less than 0.01) compared to control conditions. Compared to nitroprusside, for a similar decrease in preload and afterload. UDCG-115 increased cardiac index by 40% (p less than 0.01), stroke volume index by 37% (p less than 0.01) and maximum rate of left ventricular pressure rise by 23% (p less than 0.05). Heart rate did not significantly change with either drug. Myocardial oxygen consumption per beat decreased by 33% (p less than 0.05) with UDCG-115 and by 30% (p less than 0.01) with nitroprusside. With both drugs, the decrease of myocardial oxygen consumption correlated significantly with the decrease of left ventricular systolic stress-time integral. The slopes of the respective linear regression lines were not significantly different. Thus, UDCG-115 given intravenously in patients with idiopathic dilated cardiomyopathy and moderate congestive heart failure exhibits significant inotropic and vasodilating properties. The systemic hemodynamic actions are associated with favorable effects on myocardial energetics.

Adult↗
PubMed1989

Separation between vasodilation and positive inotropism by assessment of myocardial energetics in patients with dilated cardiomyopathy.

Phosphodiesterase inhibitors have vasodilating and positive inotropic properties, and these compounds may have energy saving effects due to vasodilation and energy consuming effects due to inotropism. In order to differentiate between the effects, it is necessary to relate myocardial oxygen consumption to its hemodynamic determinants. Myocardial oxygen consumption per beat was related to the following parameters: dp/dtmax, mean velocity of fiber shortening, pressure-volume work, peak developed wall stress, and stress-time integral. The best linear relationship was found between myocardial oxygen consumption per beat and the corresponding stress-time integral (r = 0.71; p less than 0.001) in patients with idiopathic dilative cardiomyopathy. Using i.v. nitroprusside as a pure vasodilator, myocardial oxygen consumption per beat and stress-time integral decreased along this established relationship. In contrast, the phosphodiesterase inhibitor enoximone given intravenously decreased the stress-time integral significantly more than the myocardial oxygen consumption per beat. We conclude from these data that phosphodiesterase inhibitors possess vasodilating properties which reduce the myocardial oxygen demand. In addition, they do have positive inotropic effects which increase the myocardial oxygen demand. Myocardial oxygen consumption always reflects the sum of both effects. The balance between the energy saving and the energy consuming effects may determine the efficacy of phosphodiesterase inhibitors, especially in the long-term treatment of chronic heart failure.

Cardiomyopathy, Dilated↗
PubMed1989

Influence of UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy.

The influence of the new inotropic and vasodilating agent UDCG-115 on hemodynamics and myocardial oxygen metabolism was investigated in 11 patients with idiopathic dilated cardiomyopathy (New York Heart Association class II to III). After intravenous administration of UDCG-115, cardiac index increased from 3.03 +/- 0.68 to 3.76 +/- 1.07 L/min/m2 (p less than 0.01), left ventricular ejection fraction increased from 31 +/- 13 to 39 +/- 16% (p less than 0.01), and maximum rate of left ventricular pressure rise increased from 935 +/- 248 to 1056 +/- 284 mm Hg/sec (p less than 0.05). Left ventricular end-diastolic wall stress (index of preload) and left ventricular end-systolic wall stress (index of afterload) decreased by 41% (p less than 0.01) and 34% (p less than 0.001), respectively. Heart rate did not change significantly. With UDCG-115 myocardial oxygen consumption decreased from 14.3 +/- 5.1 to 10.6 +/- 3.8 ml/min/100 gm (p less than 0.05), and the ratio of myocardial oxygen supply to myocardial oxygen demand increased from 1.40 +/- 0.08 to 1.53 +/- 0.17 (p less than 0.05). Thus intravenous UDCG-115 improves left ventricular function by increasing inotropism and reducing preload and afterload in patients with idiopathic dilated cardiomyopathy and moderate congestive heart failure. The systemic hemodynamic actions are associated with favorable effects on myocardial energetics.

Cardiomyopathy, Dilated↗