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Biomedical subjects

M Schlepper

Publications and source records attributed to M Schlepper.

At least 73 records · Page 4Linked to original sources
PubMed1990

[Effect of the class IA anti-arrhythmic agents ajmaline on end-systolic pressure-volume relations (conductance technique)].

To evaluate cardiodepressive risks of antiarrhythmic treatment with ajmaline, we monitored, in addition to conventional hemodynamic parameters, end systolic pressure-volume relations (ESPVR) to assess potential negative inotropic effects. Twelve patients (CAD without ischemia; EF = 60 +/- 3%) underwent hemodynamic analysis with and without the influence of ajmaline (1 mg/kg, i.v.) both 1) at rest (paced heart rate of 90 bpm) and 2) during tachycardia of 160 bpm. As a result, LV-pump function was found to have diminished moderately: EF by 23% vs 10%, respectively; stroke volume by 10% vs 0%; cardiac work by 5% vs 16%, and dP/dtmax by 14% vs 19%. While preload increased under the influence of ajmaline (LVEDP by 17% vs 30%), the LV-volumes increased (EDV by 18% vs 12%; ESV by 58% vs 21%), afterload remained unchanged. Ajmaline caused the loops of the ESPVR to move rightward and the slope k of the ESPVR to decrease, thus indicating loss of inotropy during the influence of the antiarrhythmic agent. Thus, ajmaline showed a tendency to generate cardiodepressive effects in patients with normal LV-function, and to depress contractility in single cases that clinically had no consequences. The conductance technique proved useful and safe in the assessment of inotropic drug effects by analyzing the ESPVR within the catheterization laboratory routine.

Aged↗
PubMed1990

[The assessment of myocardial perfusion using contrast echocardiography].

A brief survey is given on the state of the art of qualitative and quantitative myocardial contrast echocardiography as well as on the contrast agents used. Exact qualitative assessment of coronary perfusion areas is possible. In addition, myocardial areas of collaterals of less than 100 microns in diameter can be visualized and measured that were not seen by routine coronary angiography. Quantitative analysis was done in 5 normal subjects and 16 patients with coronary artery disease before and after right ventricular stimulation (170 bpm over 75 s). While decay half time (T1/2) remained unchanged in normal subjects before and after pacing (7 +/- 4 s vs 7 +/- 5 s), it increased significantly from 5 +/- 1 to 16 +/- 1 s in patients with coronary stenoses between 50% and 75%. Stenotic area reduction greater than 75% had significant prolongations of T 1/2 = 12 +/- 7 s already at rest with further prolongation to 36 +/- 17 s (p less than 0.05) after pacing. Regional wall motion in these areas, however, was not significantly altered either in the fixed axis or floating axis system. Following dipyridamole hyperaemia (0.56 mg/kg i.v.), normal subjects showed a significant shortening of T 1/2 (6 +/- 2 vs 1.6 +/- 1; p less than 0.01; n = 5), while T 1/2 of patients with multiple vessel disease was prolonged from 9 +/- 6 to 15 +/- 6 s (p less than 0.01; n = 7). This prolongation was not uniform, since some myocardial areas were found to be hyperaemic after dipyridamole. One patient showed an opening of antegrade collaterals following dipyridamole. In first results myocardial contrast echocardiography proved capable of recognizing ischaemic and hyperaemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Pimobendan increases calcium sensitivity of skinned human papillary muscle fibers.

The calcium sensitizing effects of the cardiotonic agent pimobendan on force production were investigated on chemically skinned human papillary muscle fibres. The papillary muscles were obtained from patients undergoing mitral valve replacement operations. Tension was produced by different free calcium concentrations and 100 mumol/l of pimobendan shifted the pCa-tension relationship significantly to the left. The effects of pimobendan were concentration dependent (10-300 mumol/l) but additionally also correlated with the state of left ventricular performance of the patients. Skinned papillary muscle fibres obtained from patients with reduced ventricular performance were more sensitive to calcium as well as pimobendan compared with fibres from patients with normal left ventricular performance. No differences in response to pimobendan were observed between fibres from NYHA II and NYHA III heart failure patients.

Calcium↗
PubMed1989

The vasopressor system in patients with heart failure due to idiopathic dilated cardiomyopathy--influence of the clinical stage of disease and of chronic drug treatment.

Alterations in the vasopressor system found in cardiac failure are part of compensatory measures that may modify pharmacologic-therapeutic response. Therefore, in 64 patients with dilated cardiomyopathy, we investigated its enhanced activity in different clinical stages of the disease as compared to normal controls. Patients in NYHA class II (n = 20) demonstrated increased activity of the sympathico-adrenal, renin-angiotensin-aldosterone, vasopressin, and atrial natriuretic factor systems, while maximum values were found in patients of NYHA class IV (n = 24). In these patients, noradrenaline was enhanced by a factor of 7, adrenaline by a factor of 2, plasma-renin-activity by a factor of 7, angiotensin II by a factor of 2.5, aldosterone by a factor of 5, vasopressin by a factor of 1.5, and ANF by a factor of 4 as compared to normal controls. Clinical NYHA classes correlated to a certain degree with the various plasma hormones. Patients treated with an aldosterone inhibitor in addition to digitalis and diuretics revealed significantly higher values for aldosterone, vasopressin, and angiotensin II as compared to those who received digitalis and diuretics alone. The addition of ACE-inhibitor therapy resulted in a decrease of angiotensin II, aldosterone, and vasopressin. Plasma catecholamines and ANF, however, did not change under the influence of cardiac medication. Diuretic treatment in NYHA class II patients reduced plasma volumes (p less than 0.01). Plasma volume in NYHA class IV patients only was found to be higher than in normal controls. Thus, analysis of the neurohumoral system can aid both in the identification of the clinical degree of dilated cardiomyopathy and in its optimal therapy.

Adult↗
PubMed1989

Influence of the new class I antiarrhythmic agent diprafenone on the end-systolic pressure-volume relationship (conductance technique).

To evaluate cordiodepressive risks of antiarrhythmic treatment with diprafenone, we monitored, in addition to conventional hemodynamic parameters, end-systolic pressure-volume relations to assess potential negative inotropic effects. Thirteen patients underwent hemodynamic analysis with and without the influence of diprafenone 1.5 mg/kg, both a) at rest (paced heart rate of 90 beats/min and b) during tachycardia (paced tachycardia of 160 beats/min). Left ventricular volumes increased under the influence of diprafenone, both at rest (end-diastolic volume by an average of 12%, end-systolic volume by 21%) and during tachycardia (by 15% and by 47%, respectively). Diprafenone induced a depression of left ventricular function during tachycardia only: Ejection fraction fell by an average of 25% and stroke work by 19%, while end-diastolic pressure increased by an average of 28% and systemic vascular resistance by 34%. Diprafenone caused the loops of the end-systolic pressure-volume relationship to move rightward and decreased the slope k, indicating negative entropy, both at rest and during tachycardia. Thus, since under the influence of diprafenone negative inotropic effects and depressed left ventricular function were found (while determinants of preload and afterload increased), diprafenone should not be used as an antiarrhythmic agent in patients with advanced cardiac failure.

Anti-Arrhythmia Agents↗
PubMed1989

Cardiovascular effects of forskolin and phosphodiesterase-III inhibitors.

In the first part of this presentation, data is reported on the hemodynamic effects of forskolin given to patients with dilated cardiomyopathy in a concentration of 3 micrograms/kg/min and 4 micrograms/kg/min. At the lower dosage, forskolin had no effect on dP/dtmax, cardiac index, ejection fraction, or myocardial oxygen consumption. With small dosages of dobutamine, however, an increase of all four parameters has been observed in the same group of patients. Systemic vascular resistance and left ventricular enddiastolic pressure fell with forskolin given at the lower concentration. Forskolin administered at a dosage of 4 micrograms/kg/min induced an increase in dP/dtmax by 19% and a 16% rise in heart rate. However, these changes were associated with symptomatic flush syndromes. Therefore, forskolin may serve as a vasodilating substance in lower concentrations, but cannot be used as a positive inotropic compound because of the subjective symptoms. In the second part, a study is reported in which an anti-ischemic effect of the phosphodiesterase inhibitor enoximone was observed in patients with proven significant coronary heart disease. With respect to the hemodynamic parameters, the most striking findings were the decreases in left ventricular enddiastolic pressure and systemic vascular resistance. Furthermore, when left ventricular stroke work index was plotted as a function of the left ventricular enddiastolic pressure, enoximone shifted the left ventricular function curve to the left. Therefore, the anti-ischemic effect of enoximone may not only be due to a reduction in preload and afterload but may rather reflect an effect on diastolic compliance. Studies with intracoronary injections of enoximone and animal experiments support this hypothesis.

Animals↗
PubMed1989

Hemodynamic, antiischemic, and neurohumoral effects of enoximone in patients with coronary artery disease.

To evaluate the risk of ischemia in 17 patients with significant coronary artery disease, the influence of enoximone was analyzed under the following conditions: (1) at rest (RC) and during exercise (ExC) under control conditions and (2) at rest (RE) and during exercise (ExE) after administration of enoximone (0.75 mg/kg, intravenously). During ExC all patients had ischemia (angina, and ST segment alterations); metabolic markers of ischemia (MMI) increased, as did the mean pulmonary artery pressure, from 19 to 41 mm Hg. However, during ExE ischemia was abolished (no angina, decrease in mean pulmonary artery pressure to 24 mm Hg, and improvement in MMI) and there was some improvement in left ventricular pump function, whereas pre- and afterload decreased (pulmonary artery pressure by 40%, systemic vascular resistance by 10%), and heart rate, arterial pressure, and myocardial oxygen consumption (MVO2) were all unchanged (p greater than 0.05). Comparative hemodynamics at RE vs RC showed a decrease in pulmonary artery pressure (by 25%) and pulmonary vascular resistance (by 19%) and an increase in heart rate (by 11%), whereas arterial pressure and MVO2 were unchanged (p greater than 0.05). Enoximone did not induce changes in plasma catecholamine, prostaglandin, or thromboxane levels (p greater than 0.05), whereas the atrial natriuretic factor decreased (by 15%), probably because of unloading of the atria during exercise. We concluded that enoximone induces beneficial hemodynamic effects in coronary artery disease without causing ischemia, probably by enhancing myocardial contractility, vasodilation, and improved diastolic properties.

Atrial Natriuretic Factor↗
PubMed1989

AF-DX 116 discriminates heart from gland M2-cholinoceptors in man.

The M2-cholinoceptor subtype selective antagonist AF-DX 116 was compared with atropine with respect to effects on heart rate and salivary flow in healthy volunteers. These effects were related with in vitro occupancy of M-cholinoceptor subtypes in radioreceptor assays of plasma samples. Radioreceptor assays comprised M1-cholinoceptors in bovine cerebral cortex and M2-cholinoceptors in pig heart and rat salivary gland membranes. 3H-pirenzepine served as a label in the cerebral cortex 3H-N-methyl-scopolamine in the heart and gland preparations. Oral administration of 240 mg AF-DX 116 led to a time dependent increase in heart rate with a maximum effect comparable to atropine 40 micrograms/kg i.v. The effects of both drugs on heart rate were matched by a greater than 80% occupancy of heart M2-cholinoceptors in the radioreceptor assay of plasma samples. In contrast to the complete inhibition of salivary flow after atropine, AF-DX 116 induced an increase of salivation. The effects on salivary flow coincided with a greater than 80% occupancy of glandular M2-cholinoceptors after atropine but no detectable occupancy after AF-DX 116. Occupancy of the M1-subtype amounted to 61.7% after AF-DX 116 and a blockade of inhibitory, presynaptic M1-autoreceptors at missing postsynaptic blockade of glandular M2-cholinoceptors might explain the hypersalivation induced by AF-DX 116.

Adult↗
PubMed1989

Cardiodepressive effects of antiarrhythmic drugs.

Negative inotropic effects of antiarrhythmic drugs are ultimately mediated by alterations of intracellular Ca++. With class I antiarrhythmic drugs a strong correlation between the Na+ inward current and the Ca++ influx exists whereby Ca++ influx is changed by an exponent, n, of approximately 3. Generally, the longer the duration of Na+ -channel blockade the more pronounced is negative inotropy. Antiarrhythmic drugs of class I may be subdivided into those with a short recovery time of Na+ channels (lidocaine-type), those with an intermediate recovery time, such as quinidine and newer antiarrhythmics such as flecainide and propafenone, and those with a recovery time greatly exceeding 1 s, such as disopyramide and prajmaline. The degree of cardiodepression is modulated by peripheral circulatory effects such as vasoconstriction and vasodilation. In order to differentiate between general cardiodepressive effects and true negative inotropy, sophisticated methods, for example, volume-pressure relationship curves, have to be applied to determine the degree of pre- and afterload alterations, also accounting for cardiodepressive effects. The net effect of cardiodepression is due to several factors: true negative inotropy, additional influences on the peripheral circulation, the functional state of the myocardium, and the beneficial or detrimental effects on the prevailing arrhythmia. Based on these theoretical considerations, combined drug therapy of arrhythmias has to be installed under the aspect of cardiodepressive side-effects, especially in an already impaired heart.

Anti-Arrhythmia Agents↗
PubMed1989

The influence of various degrees of cardiac failure, chronic medical treatment, and acute additional enoximone application on the parameters of the vasopressor system.

The characteristics of norepinephrine and epinephrine as well as plasma renin activity, angiotensin II, aldosterone, vasopressin, and atrial natriuretic factor (ANF) were examined in 64 patients (mean age of 52 +/- 16 years) with dilated cardiomyopathy. The findings were grouped according to the NYHA classification and compared with a normal cohort of 38 patients (mean age of 42 +/- 10 years). Furthermore, the influence of different cardioactive substances used in the treatment of cardiac failure was analyzed in more detail. Patients in NYHA class II already demonstrated an increased activity of the sympathicoadrenal, renin-angiotensin-aldosterone system (RAAS), vasopressin, and ANF system. The highest values were found in patients of NYHA class IV. In these patients, norepinephrine was enhanced by a factor of 7, epinephrine by a factor of 2, plasma renin activity by a factor of 7, angiotensin II by a factor of 2.5, aldosterone by a factor of 5, vasopressin by a factor of 1.5, and ANF by a factor of 4 compared with those in normal subjects. The highest correlation coefficient was found for norepinephrine (r = 0.84). The acute application of 1-2 mg/kg of body weight of enoximone in patients with dilated cardiomyopathy (n = 15) resulted only in a significant lowering of the atrial natriuretic factor as an indicator for drug-induced unloading effects (venous pooling). All the parameters showed only a tendency; in none could statistical significance be established. Application of 0.75 mg/kg of body weight of enoximone i.v. in patients with coronary artery disease (n = 17) has no direct influence either on the sympathoadrenal, the ANF, or the prostaglandin systems. It could be demonstrated that the mode of medical treatment influences the parameters of vasoconstrictor systems in different ways.

Adult↗
PubMed1989

Present use of positive inotropic drugs in heart failure.

Cardiac failure is treated with increasing success by phosphodiesterase-III (PDE-III) inhibitors such as amrinone, milrinone, and enoximone. While relatively pure positive inotropic substances (e.g., dopamine and dobutamine) are limited by tolerance development and MVO2 increase, the efficacy of PDE inhibitors is maintained by avoiding catecholamine and beta-receptors. They have positive inotropic, positive lusitropic, and vasodilatatory properties; myocardial oxygen consumption remains unaltered. PDE-III inhibitors act by selectively inhibiting PDE-III, leading to an increased cAMP concentration in myocardial and smooth muscle cells. In contrast, forskolin increases intracellular cAMP by activation of adenylate cyclase. It could be shown that parenteral administration of the PDE inhibitors sulmazole, amrinone, and enoximone resulted in preload and afterload reduction due to vasodilation with concomitant decrease of peripheral and pulmonary vascular resistance; they also led to elevated cardiac output and ejection fraction as well as a significant increase in dp/dtmax, while left ventricular filling pressures were markedly lowered. Pulmonary pressure values fell significantly, whereas heart rate and myocardial oxygen consumption showed no clinically relevant alterations. In patients with angiographically documented coronary artery disease, the anti-ischemic efficacy of enoximone could be proven both during exercise and stress pacing. The decrease of the pathologically elevated pulmonary pressures during ischemia was accompanied by reduced ST-segment depression following enoximone without changing MVO2 significantly. First tests after intracoronary application of enoximone confirmed its direct myocardial efficacy, indicating its positive inotropic and lusitropic properties. Thus, patients in cardiac failure have useful therapeutic alternatives at their disposal when taking PDE inhibitors. The anti-ischemic properties of these drugs need further evaluation.

Cardiotonic Agents↗
PubMed1989

Selective antagonists reveal different functions of M cholinoceptor subtypes in humans.

Effects of atropine and of the subtype selective mAChR antagonists pirenzepine (PZ) and AF-DX 116 were studied in humans. Dose- or time-response curves were established for heart rate and salivary flow. Plasma samples were drawn in parallel with the effect measurements and analysed for drug concentrations. Subtype-selective radioreceptor assays of the samples served to estimate the respective receptor occupancy in vivo. It is shown that low doses of PZ (M1-selective blockade) cause cholinomimetic effects indicated by bradycardia and increase in salivary flow. After high doses of PZ or atropine, tachycardia and inhibition of salivary flow are observed in parallel with occupancy of both the M2 and M3 subtypes. AF-DX 116 induces a tachycardia together with an increased salivary flow in agreement with its selectivity profile (M2 greater than M1 greater than M3). The diagnostic and therapeutic applications of M1- or M2-selective blockade by low dose PZ or AF-DX 116 respectively are discussed.

Humans↗
PubMed1988

Long-term efficacy and safety of flecainide for supraventricular tachycardia.

Eighty-three patients with paroxysmal supraventricular tachycardia (Wolff-Parkinson-White syndrome in 47 patients and atrioventricular nodal reentry in 36 patients) underwent electrophysiologic study before and after intravenous administration of flecainide. Sixty-seven of these 83 patients entered an open clinical trial to evaluate the efficacy and safety of long-term oral treatment with flecainide. Efficacy was evaluated by a patient diary of spontaneously occurring attacks during flecainide treatment and periods of withdrawal. In 24 patients, electrophysiologic study was repeated during oral therapy. During a mean follow-up of 22.8 months, the therapeutic response to flecainide (mean dose 263 mg/day) was good in 48 patients (71%) and fair in 7 patients (10%). In 8 patients (10%), an arrhythmogenic effect was seen (increased number and prolonged duration of supraventricular tachycardia episodes in 4 patients, spontaneous episodes of atrial fibrillation in 2 patients and sinoatrial block in 2 patients). No consistent abnormalities were seen in the laboratory tests. Extracardiac side effects were of minor importance and usually subsided spontaneously or disappeared after reduction of dosage. It is concluded that flecainide is a useful addition to the drugs already available for short- and long-term treatment of supraventricular tachycardia due to Wolff-Parkinson-White syndrome and atrioventricular nodal reentry.

Cardiac Pacing, Artificial↗
PubMed1988

Echocardiographic imaging of the left ventricle by peripheral intravenous injection of echo contrast agent.

With the use of a new echo contrast agent (ECA) that consists of a suspension with microbubbles (100% less than 3.9 micron in a moving system), we were able to opacify the left ventricle by peripheral intravenous injection in 124 of 130 patients (95%) without shunt connection. In 12 patients with aortic valve disease we measured the opacification of the right and left ventricles videodensitometrically by means of increasing doses. Dose 1 (8.7 ml ECA) and dose 4 (50 ml ECA) led to no significant difference in intensity in the right ventricle (168 +/- 32 vs 184 +/- 16 units, respectively; p greater than 0.05); however, opacification of the left ventricle was significantly more evident after dose 4 (60 +/- 60 vs 88 +/- 62 units, respectively; p less than 0.05). On the basis of the farthest distance reached by the regurgitant microbubbles from the aortic valve, the severity of regurgitation was graded on a four-point scale; the results were compared with those of aortography. A significant correlation (r = 0.98, n = 9) was found between ECA grading and aortography in the evaluation of the severity of aortic insufficiency. In addition, flow characteristics in patients with mitral stenosis, aortic insufficiency, and the regurgitation jet in incompetent aortic prosthesis in connection with diastolic inflow over the mitral valve were described. Moreover, it was possible to differentiate between inflow of ECA into the left atrium via an atrial septal defect and across the pulmonary vascular bed. No adverse effects were reported by the patients. Left ventricular end-diastolic volume index, end-systolic volume index, stroke volume index, and ejection fraction were determined before and after intravenous injection of increasing doses of ECA by means of the area-length method of Sandler and Dodge. Even after dose 4 we observed no significant changes in left ventricular function. The values before and after injection were in the range of intra- and interobserver reproducibility. Only three patients reported a slight taste sensation. In nine patients with a history of allergies there were no side effects.

Aortic Valve Insufficiency↗
PubMed1988

[Torsade de pointes ventricular tachycardia in idiopathic QT syndrome: successful treatment with AAI pacing].

A 30-year-old woman with an idiopathic long QT-syndrome developed recurrent episodes of torsade de pointes ventricular tachycardia. Therapy with beta blocking agents and exhairesis of the left ganglion stellatum had failed to suppress these life-threatening tachyarrhythmias. After implantation of an AAI pacemaker system these ventricular arrhythmias disappeared. The patient remained without ventricular arrhythmias up to the time of discharge and during a 5 months' follow-up.

Adult↗
PubMed1988

[Hemodynamic, anti-ischemic, metabolic and neurohumoral effects of enoximone (MDL 17,043) in patients with coronary disease].

The hemodynamic, anti-ischemic, metabolic, and neurohumoral effects of the phosphodiesterase inhibitor enoximone were investigated in 17 patients (mean age 58 +/- 2 years) with coronary heart disease as established by coronary angiography and positive exercise tests after i.v. application of 0.75 mg/kg body weight. Whereas administration of enoximone resulted in a significant increase in heart rate from 75 +/- 17 to 83 +/- 14 per minute (p less than 0.01), exercise heart rate, blood pressure and myocardial oxygen consumption did not change significantly (p greater than 0.05). At rest, enoximone led to a significant decrease of mean right atrial pressure from 5.7 +/- 2.3 to 3.8 +/- 1.2 mm Hg (p less than 0.01). During exercise there was a significant fall in pulmonary pressure (PAm from 40 +/- 7 to 24 +/- 7 mm Hg, p less than 0.001; PCm from 24 +/- 7 to 14 +/- 6 mm Hg, p less than 0.001) caused by preload reduction and concomitant inotropic increase; there was also a significant rise in cardiac output from 12.7 +/- 5 to 13.8 +/- 5 mm Hg (p less than 0.01) and a decrease of ST-segment depression from 1.97 +/- 0.76 to 0.53 +/- 0.51 mm (p less than 0.001). With improved peripheral and probably coronary blood flow, a concomitant decrease of the metabolic ischemic markers was detected during exercise (potassium 4.44 +/- 0.29 vs. 4.31 +/- 0.30 mval, p less than 0.05; lactate 19 +/- 9 vs. 18 +/- 7 mg/dl; pH 7.28 +/- 0.27 vs. 7.36 +/- 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗