Biomedical subjects

W Rudolph

Publications and source records attributed to W Rudolph.

At least 19 recordsLinked to original sources

PubMed1995

Haemodynamic evaluation of two regimens of molsidomine in patients with chronic congestive heart failure.

We investigated the extent and duration of the haemodynamic effects of two regimens of molsidomine, i.e. two tablets of a standard regimen consisting of 4 mg given 6 h apart and one tablet of 16 mg in sustained-release form once daily in 13 patients with chronic congestive heart failure using a placebo-controlled, randomized, double-blind and crossover protocol over a period of 12 h. Both regimens significantly affected systolic, mean and diastolic pulmonary arterial pressure (reductions of up to 15%), right atrial pressure (reductions of up to 35%) and total pulmonary resistance (reductions of up to 18%). The lower dose achieved its maximum action after about 1 h and remained effective for 2 h, whereas the higher dose in sustained-release form showed maximal efficacy at 2 h and remained active even at 12 h. In contrast, only minor changes in arterial blood pressure, systemic vascular resistance and cardiac output were observed on both regimens, almost exclusively at 2 h. Heart rate was not affected by either of the regimens tested. Neither regimen led to any untoward adverse effects. Thus, molsidomine is a potent vasodilating agent which, apart from its effects on preload, also acts on pulmonary arterial and right atrial pressures, leaving systemic circulation largely unaffected on the regimens tested. Administered on its own, it is therefore suitable for treatment of congestive heart failure.

Administration, Oral↗

PubMed1995

Anti-ischemic effects of first and second dose of 20 mg isosorbide dinitrate administered 5 hours apart: attenuation of effects despite rising plasma concentration.

Based on evidence that there may be early tolerance development even within the first daily cycle of treatment, this study was undertaken to evaluate the duration and extent of the antiischemic effects of two 20 mg doses of isosorbide dinitrate as used in a well-established regimen documented to maintain effectiveness during long-term treatment. Ischemia parameters were analyzed at 2 and 4 1/2 hours after the first dose as well as at 2 and 7 hours after the second dose given 5 hours later. The studies were performed in 10 male patients with documented coronary artery disease using bicycle ergometry and a double-blind, randomized, placebo-controlled, crossover protocol. ST-segment depression was reduced by 59% (p < 0.0005) at 2 hours and by 42% (p < 0.01) at 4 1/2 hours after the first tablet and by 38% (p < 0.005) at 2 hours and by 15% (p < 0.05) at 7 hours after the second tablet. Increments in ischemia-free workload capacity amounted to 112% (p < 0.005) and to 41% (p < 0.05) after the first tablet and 68% (p < 0.05) and 38% (p < 0.05) at 2 and 7 hours after the second tablet. At 2 and 4 1/2 hours after the first tablet, plasma concentrations of isosorbide dinitrate were 8.4 and 5.9 ng/ml, and those of isosorbide-5-mononitrate were 166.6 and 130.3 ng/ml. At 2 and 7 hours after the second tablet, the concentrations of isosorbide dinitrate were 9.1 and 5.9 ng/ml, and those of isosorbide-5-mononitrate were 224.5 and 148.1 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1995

Acute alterations of oxygen uptake and symptom-limited exercise time in patients with mitral stenosis after balloon valvuloplasty.

STUDY OBJECTIVES: To determine the acute influence of improvement in orifice area in mitral stenosis by percutaneous transluminal valvuloplasty (PTVP) on cardiopulmonary exercise capacity, treadmill walking time (TWT), oxygen uptake parameters at maximum exercise as well as at highest comparable workloads and parameters of breathing work were assessed pre- and post-PTVP. PATIENTS AND INTERVENTIONS: PTVP was carried out in 16 patients who had moderately severe mitral stenosis, bringing about an average increase in mitral valve orifice area from 1.0 +/- 0.1 cm2 to 2.2 +/- 0.5 cm2 (p < 0.0005). Based on standardized conditions, the patients (six in functional class A, five in class B, and five in class C according to Weber's classification) underwent symptom-limited treadmill cardiopulmonary exercise testing before as well as 2 days after PTVP. In addition, subgroup analysis (eight patients in sinus rhythm, eight patients in atrial fibrillation) was performed to determine a potential influence of the underlying cardiac rhythm on cardiopulmonary exercise parameters. To rule out a PTVP-independent training effect, a control group of ten patients with mitral stenosis underwent the same kind of cardiopulmonary exercise testing on 2 consecutive days. MEASUREMENTS AND RESULTS: After-PTVP, TWT augmented by 19% (p < 0.0005) in all patients. Maximum oxygen uptake in percent of predicted maximal values at peak exercise and at anaerobic threshold was enhanced by 10% (p < 0.005). Ventilation at highest comparable workload was diminished by 10% (p < 0.025), whereas oxygen uptake and oxygen pulse at highest comparable workload did not differ, reflecting both unaltered cardiac output at comparable workloads and a more economic ventilation, respectively. Furthermore, PTVP-mediated alterations of TWT, but not of oxygen uptake at peak exercise were more pronounced in patients in sinus rhythm than in those in atrial fibrillation, reflecting more effective economization of cardiac work and ventilation in the former subgroup. Except for a statistically significant increase of TWT of 5%, no clinically relevant differences between both exercise tests were found with respect to oxygen uptake in the control group. CONCLUSIONS: Impaired cardiopulmonary fitness in patients with moderately severe mitral stenosis is improved substantially by PTVP immediately after the intervention, mainly the result of acute reduction of pulmonary congestion and subsequent decrease in dead space to tidal volume ratio. Adherence to standardized conditions is considered crucial for comparability of cardiopulmonary data.

Adult↗

PubMed1993

Pharmacokinetics and additional anti-ischaemic effectiveness of amlodipine, a once-daily calcium antagonist, during acute and long-term therapy of stable angina pectoris in patients pre-treated with a beta-blocker.

Amlodipine 10 mg was evaluated for additional anti-ischaemic and anti-anginal efficacy in 14 patients pre-treated with a beta-blocker who had documented coronary artery disease, stable angina pectoris, and > or = 2 mm of exercise-induced ST segment depression. For 2 days the patients received open-label amlodipine and then, according to a randomized, placebo-controlled, cross-over and double-blind protocol, they were treated with amlodipine or placebo, respectively, once a day for 3 weeks each. Exercise tests and blood sampling for plasma concentrations of amlodipine were performed at 8 and at 24 h after dosing on both days of acute testing as well as on day 18 of chronic treatment. During chronic treatment, when plasma concentrations fluctuated between 23.5 ng.ml-1 at 8 h and 14 ng.ml-1 at 24 h post-dosing, ST segment depression at an individually comparable workload was significantly decreased by 28% compared with placebo (P < 0.005) at both points in time. Increases in ischaemia-free workload capacity amounted to 76% (P < 0.005) and to 81% (P < 0.01) at 8 and at 24 h, respectively. The number of anginal attacks was reduced by 39% (P < 0.05). Conversely, after initial dosing, i.e. when plasma concentrations declined from 4.7 ng.ml-1 to 3.9 ng.ml-1, influences upon ischaemic parameters compared to control values were markedly less at 24 h as opposed to 8 h. There were no untoward side effects observed at any point in time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1992

Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure.

OBJECTIVES: This study was undertaken to determine if a standard dose of aspirin interacts relevantly with the circulatory effects of enalapril in severe heart failure. BACKGROUND: The frequent association of heart failure with coronary artery disease confers potential for combined treatment with an angiotensin-converting enzyme inhibitor and the prostaglandin synthesis inhibitor aspirin, the pharmacodynamic actions of which are, in part, mutually opposed. METHODS: In 18 patients, on 3 consecutive days, hemodynamic measurements were performed at baseline and 4 h after administration of a double placebo, enalapril (10 mg) plus placebo and enalapril plus aspirin (350 mg) according to a double-blind, randomized, crossover protocol. RESULTS: Enalapril given before aspirin led to significant decreases in systemic vascular resistance, left ventricular filling pressure and total pulmonary resistance together with a significant increase in cardiac output. When given with or on the day after aspirin, enalapril did not elicit significant changes in any of these variables. There was a clear tendency to lower values for pulmonary artery pressure on all regimens, and slowing of the heart rate was incurred whether or not aspirin had been given. Chi-square analysis of the individual responses showed that the probability of effecting a decrease in systemic vascular resistance > or = 300 dynes.s.cm-5 was six times greater when enalapril was given without aspirin (p < 0.01). CONCLUSIONS: In severe heart failure, the prostaglandin synthesis inhibition by aspirin counteracts the systemic arterial vasodilation of angiotensin-converting enzyme inhibition with enalapril and substantiates its dependence on the integrity of prostaglandin metabolism. Trends toward reductions of pulmonary artery pressure and slowing of the heart rate were still observed, presumably subsequent to lowered norepinephrine concentrations indicating maintenance of prostaglandin-independent actions of angiotensin-converting enzyme inhibition.

Adult↗

PubMed1992

Spaceflight and growth effects on muscle fibers in the rhesus monkey.

Spaceflight causes considerable atrophy in hindlimb muscles of the rat. The purpose of this study was to investigate the effect of a 14-day spaceflight (COSMOS 2044) on selected morphological and metabolic properties of single muscle fibers in a nonhuman primate, Macaca mulatta. Biopsies were taken from the soleus (Sol), medial gastrocnemius (MG), and tibialis anterior (TA) muscles of two rhesus monkeys 107 days before flight and 24 h after return from flight. Muscle biopsies were taken from two independent sites in each muscle by use of a small (3-mm OD) Bergstrom biopsy needle. The biopsies weighed 8-14 mg and contained 100-200 fibers, of which an average of 40 fibers were acceptable for metabolic and size analyses. The 14-day spaceflight had little effect on fiber size in the Sol and MG muscles, whereas there appeared to be a slight decrease in size in the TA. In each of the flight animals, the mean fiber size in the postflight biopsies increased relative to preflight values. An increase in fiber size over the same period of time was also observed in four control monkeys that were the same age and approximately the same weight as the flight monkeys. The relative increase in size was related to the body weight of the monkey at the time of the pre- and postflight biopsies. The mean fiber succinate dehydrogenase activity appeared to decrease in the MG, whereas there was no apparent effect of spaceflight on the Sol and TA muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

[Function of the right ventricle in patients with dilated cardiomyopathy].

To analyze right-ventricular size and function and their relationship to left-ventricular dimensions in patients with dilated cardiomyopathy (DCM), biplane cineventriculography was performed in 57 patients. The results were compared to 15 normals (N). In patients dilatation of the right ventricle (RVEDVI: DCM: 126.5 +/- 41.4 ml/m2, N: 90.5 +/- 9.2 ml/m2, 2 p < 0.05) was less pronounced than dilatation of the left ventricle (LVEDVI: DCM: 136.0 +/- 45.8 ml/m2, N: 76.7 +/- 7.9 ml/m2, 2 p < 0.05). Left-ventricular ejection fraction (LVEF: DCM: 36.1 +/- 10.2%, N: 64.4 +/- 3.8%, 2 p < 0.05) was more reduced than right-ventricular ejection fraction (RVEF: DCM: 39.7 +/- 11.5%, N: 58.3 +/- 3.3%, 2 p < 0.05). Concerning the individual patient, a good correlation was found between right- and left-ventricular stroke volume (r = 0.74), whereas ejection fraction (r = 0.58), enddiastolic (r = 0.52) and endsystolic volume (r = 0.55) of the left and right ventricle correlated only moderately. Twenty-three of the 57 patients showed pronounced differences between right- and left-ventricular ejection fraction. The difference RVEF-LVEF was < = -10% in six patients, i.e., right-ventricular ejection fraction was markedly more reduced than left-ventricular ejection fraction. Right-ventricular myocardial biopsy was performed in five of these six patients with histologic evidence of dilated cardiomyopathy and, also, no signs of right-ventricular dysplasia (no lipomatous tissue replacement).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Fibre size and type adaptations to spinal isolation and cyclical passive stretch in cat hindlimb.

Impulse activity is known to have a strong influence in determining the characteristics that distinguish skeletal muscle fibres into types. The control of muscle proteins by the neural systems that innervate the muscles, however, is not complete (Edgerton et al. 1985, 1990). The purpose of the present study, therefore, was to determine the effects of inactivity for 6 months on the size and fibre type composition of selected cat hindlimb muscles. Inactivity was produced by isolating the lumbar region of the spinal cord, i.e. transecting the cord at T12-T13 and again at L7-.S1 and then performing a bilateral dorsal rhizotomy between the transection sites (SI). In each SI cat, one hindlimb was passively manipulated for 30 min per day through a range of motion at the ankle mimicking a step cycle. SI resulted in an atrophic response in most muscles, with predominantly slow extensors showing the largest effect. In general, the predominant fibre type, which also had the largest mean size, in each muscle atrophied the most. The mean fibre size of all fibre types were similar after SI, suggesting that there may be a minimal size for inactive intact fibres. In comparison with control animals, all muscles in the SI cats had a higher proportion of fast fibres. Further, the relative contribution of the slow fibres to the total cross-sectional area of the muscle was decreased following SI. Some slow fibres in each muscle, however, were resistant to change. These data demonstrate the extent to which size and myosin type of mammalian muscle fibres are independent of activation characteristics.

Adaptation, Physiological↗

PubMed1991

Enhanced effectiveness of combined sustained-release forms of isosorbide dinitrate and diltiazem for stable angina pectoris.

In 14 patients with documented coronary artery disease, the extent and duration of acute anti-ischemic, antianginal and hemodynamic effects of monotherapies with 120 mg of sustained-release isosorbide dinitrate and diltiazem were compared; their combined therapy administered once daily in the morning with diltiazem given again in the evening were also compared according to a randomized, double-blind, crossover, placebo-controlled protocol including exercise testing for assessment of ST-segment depression (ST decreases) at an identical work load, exercise capacity and determination of plasma concentrations of both substances. Comparison of individual substances revealed more marked and sustained effects of isosorbide dinitrate (ST decreases at 2 hours, -66%; at 6 hours, -50%; p less than or equal to 0.05 for both), remaining statistically significant up to 12 hours (-24%) than of diltiazem (2 hours, -30%; 6 hours, -16%; p less than 0.05). Combined therapy resulted in increased effects (ST decreases at 2 hours, -80%; 6 hours, -76%; 12 hours, -30%; p less than or equal to 0.05) as opposed to individual substances for a period of up to 12 hours. However, therapeutic coverage over 24 hours could not be demonstrated, even with renewed administration of sustained-release diltiazem in the evening. Plasma concentrations of isosorbide-5-mononitrate were greater than 250 ng/ml for 12 hours on days when isosorbide dinitrate was given, decreasing to less than 100 ng/ml at 24 hours. On days when diltiazem was given, plasma levels greater than 50 ng/ml were detected only at 2 and at 6 hours, and at 24 hours only after a second tablet was given.

Angina Pectoris↗

PubMed1991

High-performance liquid chromatographic determination of phenylacetic acid in human plasma extracted with ethyl acetate.

This paper describes a high-performance liquid chromatographic method with ultraviolet detection for measuring plasma phenylacetic acid. This simple and reliable method consists of an acid hydrolysis of conjugated phenylacetic acid before extraction with an organic solvent: washed ethyl acetate saturated in sodium chloride. The recovery of extraction was estimated by internal standardization with phenylpropionic acid, and validated by addition of phenylacetic acid standards. A preliminary application to plasma phenylacetic acid in patients suffering from depression is described.

Acetates↗

PubMed1991

Clinical comparison of nitrates and sydnonimines.

Organic nitrates and the sydnominine-derivative, molsidomine, exhibit similar pharmacodynamic actions. Venous vasodilatation leads to a decrease in ventricular pressures and volumes and, consequently, to a reduction in myocardial oxygen requirement; coronary vasodilatation enhances myocardial oxygen supply to hypoperfused poststenotic regions. At the molecular level, relaxation of vascular smooth muscle is due to nitric oxide (NO) delivery; with nitrates, this is coupled to the presence of thiol groups, the depletion of which is considered the cause of nitrate tolerance. At least one further site in the nitrate bioconversion cascade, possibly at the level of NO generation appears to be involved in tolerance development, which may also affect the non-nitrate vasodilator SIN-1. Nitrate tolerance is a clinically relevant problem incurred with multiple daily doses or continuous nitrate administration which lead to nearly constant, high plasma concentrations. Effective long-term therapy with nitrates can only be carried out with an interval treatment which is associated with relatively low and substantially fluctuating plasma concentrations. In contrast, during long-term treatment with molsidomine, tolerance development is not a clinically-relevant problem, so that with multiple daily doses, an effect can be provided over 24 h. With regard to maximal anti-ischaemic and haemodynamic effects, organic nitrates and molsidomine are similar. Molsidomine represents an alternative to nitrate interval treatment, or, respectively can be used as an adjunct to interval treatment should it be necessary to bridge the therapeutic gap.

Coronary Disease↗

PubMed1991

Architectural and fiber type distribution properties of selected rhesus leg muscles: feasibility of multiple independent biopsies.

In experiments involving primates, e.g. before and after spaceflight, needle biopsies were thought to be a logical and feasible means of obtaining metabolic and morphological information from skeletal muscles. However, the feasibility of obtaining consistent, repeatable biopsies from individual muscles had to be demonstrated prior to the acceptance of this procedure. To study this approach, the architectural properties and the fiber type distributions at three levels and two regions along the proximo-distal axis of the soleus, medial gastrocnemius and tibialis anterior of adult rhesus monkeys were determined. In each muscle, biopsies were taken from specific regions where the fiber type distribution was determined. Within each region of each muscle, the fiber type populations were similar at the three levels studied. The percentage of fast or oxidative fibers in the biopsies and in the regions of the same muscle were highly correlated, i.e. r = 0.98 for both comparisons. In addition, based on normalized values (z scores), 25/26 and 22/26 biopsies were within the 95% confidence interval, i.e. the biopsies were a representative sample of the mean fiber type population of that region of the muscle. In all muscles, the mean fiber lengths were no more than one third the length of the muscle. Together, these data indicate the feasibility of obtaining independent, repeated biopsies having similar fiber types from each of the muscles studied.

Animals↗

PubMed1990

Long-acting, marked antiischemic effect maintained unattenuated during long-term interval treatment with once-daily isosorbide-5-mononitrate in sustained-release form.

In 18 patients with documented coronary artery disease, the antiischemic effect of 50 and 100 mg isosorbide-5-mononitrate (IS-5-MN) in sustained-release (SR) form was investigated using a randomized, double-blind, crossover, placebo-controlled protocol. After the initial administration of both dosages, compared to placebo there were significant reductions in exercise-induced ST-segment depression and significant increases in ischemia-free exercise time at all times of testing. At 12 hours, the 100-mg dosage still amounted to greater than 50% of its maximum and was significantly more marked than the 50 mg dose. Accordingly, the 100-mg dosage can be assumed to confer a longer duration of action. At the end of 3 weeks of long-term treatment, the significant antiischemic effects were not diminished versus those observed after initial administration. There was no evidence of tolerance development with either dosage. The IS-5-MN plasma concentration during long-term administration displayed, within the 24-hour treatment cycle, a clear decrease to low baseline values and a marked 5- to 7-fold increase after the daily dose in accordance with the response known to be prerequisite to successful interval treatment. Thus, the once-daily administration of IS-5-MN SR with dosages of 50 mg and, more markedly, 100 mg, provides effective antiischemic protection throughout the daily period of most physical activities in patients with stable angina pectoris.

Blood Pressure↗

PubMed1990

[Treatment of myocardial ischemia with molsidomine].

Explore the source record for details and available documents.

Angina Pectoris↗

PubMed1990

[Effectiveness of various combination therapies in patients with coronary heart disease].

There is only a limited number of studies available comparing the effectiveness of various combinations of anti-ischemic and antianginal substances in the same patients with coronary artery disease and stable angina pectoris and even these are restricted to either only a few drugs or a single point in time for testing. Accordingly, this study was undertaken to determine to what extent the combination of two or three drugs with different anti-ischemic mechanisms of action such as the long-acting form of the beta-blocker metoprolol and isosorbide dinitrate (ISDN) in sustained-release form as well as the calcium channel blockers nisoldipine and diltiazem in sustained-release form, which previously have not been tested in combination, are capable of enhancing effectiveness and prolonging duration of action. In a double-blind, randomized, crossover study in eleven patients with documented coronary artery disease and stable angina pectoris the effects of monotherapy with 200 mg metoprolol in long-acting form were compared with those of combined treatment with 120 mg ISDN sustained-release or 10 mg nisoldipine or 120 mg diltiazem sustained-release as well as ISDN and nisoldipine and finally, ISDN and diltiazem by means of an intraindividual analysis. For assessment of anti-ischemic and antianginal effects, symptom-limited exercise testing was carried out before as well as three, eight, twelve and 24 hours after medication. The parameters analyzed were ST-segment depression at the highest comparable workload, ischemia-free and symptom-free exercise capacity (one minute prior to ST-segment depression of 1 mm or onset of angina pectoris) as well as the systolic blood pressure--heart rate product at the highest comparable workload and at the highest ischemia-free workload, that is one minute prior to an ischemic reaction of 1 mm. Based on the ST-segment depression, all combinations of two drugs (metoprolol and ISDN at three hours; metoprolol and diltiazem at eight hours) led to a significant or at least relative increase of effectiveness. On comparison of the various double combinations, those with nisoldipine showed an early dissipation of action which, twelve hours after administration, was significantly less marked than those with diltiazem. Of the two tested triple combinations, metoprolol, ISDN and diltiazem was either significantly more effective than the various double combinations (metoprolol and ISDN or metoprolol and nisoldipine, both at eight and twelve hours; metoprolol and diltiazem, twelve hours) or relatively more effective and showed clear prolongation of the effects in excess of twelve hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗

PubMed1990

Nitrate therapy in patients with coronary artery disease--preparations and doses with and without development of tolerance.

Rapid tolerance development with respect to hemodynamic, anti-anginal and anti-ischemic effects is a relevant clinical problem associated with any longterm treatment with nitroglycerin, isosorbide dinitrate or isosorbide 5-mononitrate. Tolerance occurs with any dosing regimen that results in nitrate accumulation in the plasma or nearly-constant plasma concentrations, as is the case with multiple daily doses of oral nitrates or continuous application of transdermal patch systems. Nitrate tolerance can be prevented by the interval treatment. This encompasses incorporation of an application-free interval which prevents meaningful nitrate accumulation such that, from a low baseline level, renewed drug administration leads to an increase in the nitrate plasma concentration greater than 2.5-fold. From controlled studies, dosing regimens for interval treatment proven to be effective have been designated for isosorbide dinitrate and isosorbide 5-mononitrate, as well as for transdermal nitroglycerin patch systems. The early attenuation of nitroglycerin, seen within the first 12 h of its use, according to the results of a recently completed study, can be counteracted through continuously increasing plasma concentrations during this period. Interval treatment does not enable 24-h therapeutic protection. Studies with ST-Holter monitoring, however, have shown that adequate coverage can be provided for the period during which the vast majority of ischemic episodes occur. Clinically-relevant rebound phenomena do not occur during interval treatment. Pharmacological approaches to prevent nitrate tolerance, on the basis of the limited and, in part, conflicting data available, do not provide an alternative to interval treatment.

Administration, Cutaneous↗

PubMed1990

[Nitrates in the treatment of heart failure].

Organic nitrates were the first peripherally-active vasodilators to be used for the treatment of heart failure. Currently, three nitrate derivatives, glycerol trinitrate, isosorbide dinitrate and isosorbide 5-mononitrate as well as the nitrate-like substance molsidomine are employed clinically. For treatment of heart failure, the decisive hemodynamic effect is a meaningful reduction in ventricular filling pressures with maintenance or even a slight increase in cardiac output. The individual response to nitrates is variable. An important indicator for the effect achievable for a certain dose or for the necessary dosage to affect a defined reduction in ventricular filling pressures, is the magnitude of right atrial pressure. It can be assumed that the latter statement is also valid for the nitrate-like substance molsidomine. An inherent problem with any long-term treatment with nitrates is the incurrence of tolerance. This can be expected with any dosing regimen which leads to nitrate cumulation in the plasma or to nearly-constant, high, plasma concentrations as rendered by multiple daily administration of orally-active nitrates or with continuous transdermal or intravenous nitrate administration. The cause of nitrate tolerance is regarded as an insufficient or absent stimulation of guanylate cyclase and, consequently, inadequate generation of cyclic GMP due to availability of thiol substrate. Since the nitrate-like substance molsidomine appears to be able to stimulate guanylate cyclase independent of thiol groups, tolerance development may not be a limiting factor with this agent. Comparable reduction of diastolic pulmonary artery pressure after acute administration and at the end of one week of treatment with 4 mg molsidomine four times daily has been reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Relationship, Drug↗

PubMed1990

[Can sudden cardiac death be prevented by treatment with anti-arrhythmia drugs?].

Sudden cardiac death is defined as death due to a primary cardiac cause or mechanism, occurring within one hour of the onset of acute illness in a person thought to be free of, or with symptomatically mild, heart disease, or simply prehospital death. Of persons dying suddenly, 90% have coronary artery disease, less commonly, dilated cardiomyopathy or hypertrophic cardiomyopathy, preexcitation syndrome, long QT-syndrome, conduction disturbances, congenital or valvular heart disease as well as cardiac tamponade are responsible. In the USA, the incidence of sudden cardiac death is approximately 450,000 per year, in the Federal Republic of Germany the number lies at about 70,000 to 80,000. The most important risk factors for sudden cardiac death are impaired left ventricular ejection fraction, myocardial ischemia and arrhythmias. In general, sudden cardiac death is caused by ventricular fibrillation which arises mainly by degeneration of ventricular tachycardia (VT). The terminal arrhythmia, it is assumed, is precipitated by premature ventricular beats originating in an arrhythmogenic substrate. MEDICAL ANTIARRHYTHMIC TREATMENT IN PATIENTS WITH CORONARY ARTERY DISEASE AFTER MYOCARDIAL INFARCTION: STUDIES WITH CLASS I DRUGS: The results of nine large, randomized , controlled studies are available in which the mortality of patients on antiarrhythmic treatment has been studied (Table 1). Two studies each were carried out with aprindine, phenytoin, mexiletine and tocainide as well as one study with endainide, flecainide or morizicine. With the exception of the CAST study, no study showed a significant difference between treated patients and the control group with respect to mortality or incidence of sudden cardiac death. The CAST study was terminated after ten months because the administration of flecainide and encainide led to overall mortality of 7.7% vs. 3.0% in the control group and the rate of sudden cardiac death at 4.5% was significantly higher in the treatment group than the 1.2% incidence found in controls (Table 2). For nearly all of the studies described, the patient groups were not sufficiently large and subgrouping according to patient characteristics was not carried out such that possibly, inhomogeneity of the entire collective may not have been recognized precluding identification of some individuals who may have shown benefit from antiarrhythmic treatment. The necessity for treatment in many of those receiving drugs is questionable since generally the rhythm profile of the patients was not taken into consideration for the decision to treat. Proarrhythmic effects, accordingly, were also not assessed. Individual treatment and dosage adjustment by monitoring with effectiveness criteria was carried out in one study only in which, even here, criteria for effectiveness were arbitrarily capable of eliciting antiarrhythmic actions. Calculation of mortality rates was carried out on the basis of the total number of deaths in the respective groups without taking into consideration that by the end of the study, in the treatment group the medication had been discontinued in up to 40% of the patients. STUDIES WITH CLASS II DRUGS: For treatment with beta-receptor blockers there are 15 large, controlled, randomized, long-term studies available in which total mortality and the incidence of sudden cardiac death were studied.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Arrhythmia Agents↗