Search PubMed⌕ Search

Biomedical subjects

G Lehmann

Publications and source records attributed to G Lehmann.

At least 55 records · Page 3Linked to original sources
PubMed1998

PICP as bone formation and NTx as bone resorption marker in patients with chronic renal failure.

UNLABELLED: Renal bone disease which develops in patients with chronic renal failure (CRF) is not a uniform metabolic disorder. Although bone histomorphometry is accepted to be the gold standard for characterizing the state of disease progression, the techniques involved are cumbersome and expensive so that it cannot be used routinely. As a result, numerous biochemical markes have been developed to measure bone formation and resorption. The purpose of this study was to evaluate the suitability of procollagen type-I C-terminal peptide (PICP) in serum as an indicator of bone formation and cross-linked amino-terminal telopeptide of type I collagen (NTx) in urine as an indicator of bone degradation processes, and to investigate their relation to histomorphometric and other biochemical parameters. 77 patients with CRF and 49 patients on intermittent hemodialysis treatment (DT) were investigated. PICP was measured in serum and NTx in urine. In addition, iPTH, phosphate, calcium, alkaline phosphatase (APH), osteocalcin and creatinine in serum were determined. Bone biopsies were obtained from the anterior, superior iliac crest, and the histomorphometric parameters were measured and expressed according to the standardized nomenclature. Patients with CRF and DT had significantly higher PICP and NTx levels as compared to controls. In the CRF group significant correlations could be obtained between PICP and histomorphometric parameters of bone formation as well as between NTx and histomorphometric indices of bone resorption. In this group, PICP levels were positively correlated to iPTH, phosphate and creatinine levels and negatively to calcium concentrations. Furthermore, there were significant correlations between NTx values and those of both iPTH and APH. In the group of dialysis patients, levels of PICP and NTx did not correlate with any of the histomorphometric parameters or the classical humoral markers. CONCLUSIONS: The results suggest that PICP as bone formation and NTx as bone resorption markers are of potential use for screening bone turnover in predialysis chronic renal failure patients. But in patients undergoing dialysis, neither PICP nor NTx yielded any substantial information as noninvasive markers of bone histology.

Adult↗
PubMed1998

Unexpected recurrence of sinus rhythm in chronic atrial fibrillation due to sick sinus disease.

A 60-years old patient with symptomatic sick sinus disease was implanted a dual-chamber pacemaker that did well during the following 13 years. Thereafter, the pacemaker had to be explanted because of a systemic infection, with the patient in constant chronic atrial fibrillation in the meantime. After another asymptomatic year, 6 arrhythmogenic syncopes occurred, apparently due to pre-automatic pauses prior to spontaneous conversions to sinus rhythm. Subsequently, the patient was implanted a VVI pacemaker, whereupon he did well henceforth. This case demonstrates the possibility of recurrence of sinus rhythm even after long-standing chronic atrial fibrillation.

Arrhythmia, Sinus↗
PubMed1998

Increasing nitroglycerin release from patches enables circumvention of early nitrate tolerance.

Continuous treatment with transdermal nitroglycerin leads to tolerance development within the first day of application. Effective long-term therapy can be provided by interval treatment with nightly patch removal, but even during the hours of intermittent patch application there is rapid attenuation of initial effects. To assess whether an unattenuated antiischemic and antianginal efficacy during the hours of intermittent dosing can be maintained, a modified drug-release profile with increasing plasma concentrations was evaluated using a double-blind, placebo-controlled crossover protocol. Eleven patients with documented coronary artery disease received, in a randomized order, a total of four low-dose nitroglycerin patches (5 mg/24 h each) or placebo, respectively, at intervals of 3 hours. After a treatment interval of 12 hours, all patches were removed for an equally long patch-free interval prior to renewed application of one patch the next morning. At a comparable workload, reductions of ST-segment depression of 65%, 63%, and 56% were found at 2.5 hours, 8 hours, and 12 hours after application of the first patch on day 1, respectively (all significant vs. placebo; 2.5 hours vs. 12 hours, n.s.). On day 2, the comparable reduction of 63% at 2.5 hours after renewed application indicates prevention of tolerance development during subchronic treatment. Effects on exercise capacity and angina pectoris paralleled those on exercise-induced ST-segment depression. Plasma concentrations of nitroglycerin increased from 223 pg/mL to 558 and 803 pg/mL on day 1 and amounted to 205 ng/mL at 2.5 hours on day 2. Thus, interval therapy with increasing nitroglycerin concentrations provides unattenuated antiischemic and antianginal efficacy during the hours of treatment and circumvention of early tolerance during subchronic application. This modified pharmacokinetic profile can be regarded as a model for an improved dosage regimen in nitrate interval therapy.

Adult↗
PubMed1998

Clinical comparison of antiischemic efficacy of isosorbide dinitrate and molsidomine.

In 16 patients with documented coronary artery disease, the extent and duration of acute antiischemic and hemodynamic effects of monotherapies with 120 mg of sustained-release isosorbide dinitrate once daily and 8 mg of sustained-release molsidomine 3 times daily were compared according to a randomized, double-blind, cross-over and placebo-controlled protocol including exercise testing for assessment of ST-segment depression (ST) at an identical workload and determination of plasma concentrations of both substances. Up to 8 h after dosing in the morning, more marked and sustained effects were observed with the nitrate (ST at 2 h, -82%; p < 0.001; at 8 h, -64%; p < 0.01) than with molsidomine (2 h, -68%; p < 0.001; at 8 h, -9%; NS). At 12 h, no more meaningful actions were detectable with isosorbide dinitrate (-13%, NS) despite plasma concentrations still within a range otherwise considered therapeutically effective, whereas with molsidomine, at 4 h after renewed dosing, this parameter was reduced by 38% (p < 0.01). However, therapeutic coverage over a 24-h period could be demonstrated on neither regimen, in the case of the nitrate because of the development of early tolerance, and in the case of molsidomine with its meaningfully shorter half-life because of the necessity of increasing the dosing frequency even further. No meaningful adverse effects were observed with either regimen. Nonresponders, overall a minority on one treatment, responded completely to the alternative regimen and vice versa.

Blood Pressure↗
PubMed1998

Infusions with molsidomine and isosorbide-5-mononitrate in congestive heart failure: mechanisms underlying attenuation of effects.

The use of nitrates for treatment of heart failure is encumbered by tolerance, caused by whatever mechanism, which has been reported only in a few instances with sydnonimines. Accordingly, we compared molsidomine (6 mg/h) and isosorbide-5-mononitrate (3.75 mg/h) with respect to maximal hemodynamic effects, rapidity and extent of attenuation, and underlying mechanisms by means of constant infusions over 24 h each in 15 patients with chronic congestive heart failure (NYHA II-III) with a placebo-controlled, double-blind, randomized, crossover protocol. Hemodynamic measurements and determinations of neurohormones were performed at baseline and at 2, 8, and 24 h after the beginning of infusions. With molsidomine, reductions of diastolic pulmonary artery pressure by 29% (p < 0.001), by 24% (p < 0.01), and by 24% (p < 0.01) versus placebo were found at 2, 8, and 24 h, which amounted to 19% (p < 0.01), 10% (NS), and 14% (NS) with the nitrate. Cardiac output was meaningfully affected only with molsidomine (+5%, NS, at 2 h; +9%, p < 0.05, at 8 h; and +15%, p < 0.05, at 24 h), as was systemic vascular resistance (-13%, p < 0.05; -9%, NS; and -18%, p < 0.01) at the corresponding times. Increases in renin activity amounted to 130% (p < 0.001), 117% (p < 0.001), and 112% (p < 0.001) with molsidomine, and to 14, 16%, and 0 (each NS) with the nitrate at the corresponding times. Hematocrit was reduced by 5% (p < 0.001), 7% (p < 0.001), and 12% (p < 0.01) with molsidomine and by 5% (NS), 5% (p < 0.05), and 5% (NS) with the nitrate. We conclude that neurohumoral counterregulation or fluid shift, which is even more pronounced with molsidomine despite longer-lasting effects, has no essential role in nitrate-tolerance development. With molsidomine, such a role cannot be ruled out, although alternatively, a fluid shift from arterial to the low-pressure arm of circulation during the later course of infusion would be even more likely.

Adult↗
PubMed1998

Efficacy of a new balloon catheter for internal cardioversion of chronic atrial fibrillation without anaesthesia.

OBJECTIVE: To compare a new internal cardioversion system incorporated into a balloon guided catheter with a conventional two electrode system in patients with atrial fibrillation (AF). DESIGN: Prospective study. PATIENTS: 74 patients with chronic AF treated by internal cardioversion. MATERIALS: A 7.5 F balloon catheter with high energy electrode arrays each consisting of six 0.5 cm platinum rings. Brachial vein access enables one electrode array to be placed in the left pulmonary artery (distal pole) and the other at the lateral right atrial wall (proximal pole). The conventional two electrode system consists of 6 F electrodes placed in the proximal left pulmonary artery (anode) and the lower right atrium. INTERVENTIONS: Internal cardioversion was performed by shocks delivered in 40 V incremental steps from an external defibrillator. Shocks were applied by the new device to 32 patients (group A) and by the conventional system to 42 patients (group B). RESULTS: The groups differed with respect to system positioning (9.2 (7.3) upsilon 12.3 (8.1) minutes, p < 0.05) and fluoroscopy times (1.7 (1.0) v 3.3 (2.1) minutes, p < 0.01). Sinus rhythm was restored in 30 patients of group A and in 39 of group B (NS) with mean (SD) energy requirements of 8.4 (3.1) J and 7.2 (3.1) J, respectively (NS). CONCLUSIONS: This new method of internal cardioversion has comparably high primary success rates and low sedation requirements with single and two lead systems.

Adult↗
PubMed1998

Blood pressure and aortic elastic properties--verapamil SR/trandolapril compared to a metoprolol/hydrochlorothiazide combination therapy.

The effects of 2 fixed antihypertensive combination drugs on blood pressure and aortic elastic properties were compared in 2 parallel groups. Twenty-six patients for 6 months received a calcium antagonist plus ACE inhibitor (verapamil SR 180 mg/trandolapril 1 mg (Vera/Tran)) and 25 patients a beta-adrenoceptor antagonist plus diuretic (metoprolol 100 mg/hydrochlorothiazide 12.5 mg (Meto/HCTZ)). In addition to blood pressure (SBP, DBP), carotidofemoral pulse wave velocity (PWV) was assessed non-invasively. Total peripheral resistance (TPR) was determined from cardiac output derived by electrical impedance cardiography. Sitting DBP decreased for -14.4 mmHg following Vera/Tran compared with -9.2 mmHg following Meto/HCTZ (p = 0.02 for difference between treatments). Blood pressure was normalized (i.e. DBP < 90 mmHg) in 69% of patients with Vera/Tran and in 52% with Meto/HCTZ. PWV was lowered with Vera/Tran to a higher extent than with Meto/HCTZ (differences between group means -0.46 to -0.98 m/sec, statistically not significant). Vera/Tran induced a decrease in TPR of about 15% of baseline values, whereas Meto/HCTZ showed no influence. Treatment-related adverse events following Meto/HCTZ were bradycardia and associated symptoms; following Vera/Tran these were cough and edema in 1 case each. In the Meto/HCTZ group, there were more withdrawals/drop-outs (9/25) than in the Vera/Tran group (2/26). The somewhat more intense reduction in PWV with Vera/Tran is indicative of an increase in aortic elastic properties associated with the more potent decrease in BP. In the present study, the combination of calcium antagonist plus ACE inhibitor was found to be an effective and well tolerated antihypertensive regimen and in these respects appears to have some advantages compared with a combination of beta-blocker plus diuretic.

Adrenergic beta-Antagonists↗
PubMed1997

Characterization of a 200-kDa diatom protein that is specifically associated with a silica-based substructure of the cell wall.

The cell wall of a diatom is made up of a silica-based scaffold and organic macromolecules. Proteins located in the cell wall are believed to control morphogenesis of the species-specific silica structures of the scaffold. However, data that correlate distinct silica elements and specific proteins within the diatom cell wall have not been reported. Here, the cell wall protein HEP200 (200-kDa HF-extractable protein) from the diatom Cylinidrotheca fusiformis is identified and characterized. HEP200 is tightly associated with a substructure of the silica scaffold. It is a member of a new protein family, of which two more members are identified. Each member displays the same bipartite structure. The N-terminal part consists of a variable number of a repeated sequence motif (PSCD domain), whereas the C-terminal part is unique. Immunolocalization experiments revealed the arrangement of different proteins within the cell wall. Frustulins, a previously described group of glycoproteins, constitute the outer coat of the cell wall and exhibit a ubiquitous distribution. In contrast, HEP200 is specifically located at a subset of about six silica strips in intact cell walls, shielded by frustulins. This study therefore identifies a diatom cell wall protein (HEP200) that is associated with a distinct substructure of the silica scaffold.

Algal Proteins↗
PubMed1997

Effect of electrode position on outcome of low-energy intracardiac cardioversion of atrial fibrillation.

The aim of this study was to evaluate the new method of low-energy, catheter-based intracardiac cardioversion in patients with chronic atrial fibrillation (AF) and to compare 2 different lead positions. Accordingly, we prospectively studied 80 consecutive patients with chronic AF (9.8 +/- 7.9 months) who were randomly assigned to undergo internal cardioversion either via defibrillation electrodes placed in the right atrium and coronary sinus (coronary sinus group) or via defibrillation electrodes placed in the right atrium and left pulmonary artery (pulmonary artery group). Intracardiac shocks were delivered by an external defibrillator synchronized to the QRS complex. After conversion, all patients were treated orally with sotalol (mean daily dose, 189 +/- 63 mg/day). For conversion to sinus rhythm, the overall mean energy requirement was 5.6 +/- 3.1 J. In the coronary sinus group, cardioversion was achieved in 35 of 38 patients at a mean energy level of 4.1 +/- 2.3 J (range 1.0 to 9.9), and in the pulmonary artery group in 39 of 42 patients with 7.2 +/- 3.1 J (range 2.5 to 14.8). Although there was no difference with regard to success rate, the energy differed significantly between the 2 groups (p < 0.01). Mean lead impedance was 56.4 +/- 7.0 omega and 54.6 +/- 8.5 omega, respectively (p = NS). No serious complications were observed in either lead group. At a mean follow-up of 14.2 +/- 7.0 months, 54% and 56%, respectively, of patients who had been converted successfully remained in sinus rhythm. Thus, low-energy biphasic shocks delivered between the right atrium and coronary sinus or pulmonary artery are equally effective for cardioversion of patients with chronic AF. The energy requirements for conversion from a pulmonary artery electrode position are higher than for the coronary sinus position.

Administration, Oral↗
PubMed1997

Patient characteristics and underlying heart disease as predictors of recurrent atrial fibrillation after internal and external cardioversion in patients treated with oral sotalol.

The aim of this study was to identify predictors for recurrent atrial fibrillation after internal and external cardioversion in 157 patients. After cardioversion, patients were treated orally with sotalol (174 +/- 54 mg/day). Univariate predictors for recurrence included coronary artery disease (p < 0.05) and advanced age (p < 0.05). Multivariate adjusted risk for relapse increased with the presence of coronary artery disease (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.6 to 8.0), presence of atrial fibrillation > 2 months before cardioversion (OR 2.3; 95% CI 1.4 to 4.5), left atrial diameter > 60 mm (OR 2.1; 95% CI 1.2 to 3.1), and age > 65 years (OR 1.6; 95% CI 1.3 to 3.3). In 26% of patients with lone atrial fibrillation, recurrence was observed compared with 51% of patients with underlying structural heart disease (p < 0.05). The mode of conversion, internal or external, had no impact on the recurrence rate. These findings might be useful for selection of the most appropriate therapy for the individual patient.

Administration, Oral↗
PubMed1997

A comparison of treatment of atrial fibrillation with low-energy intracardiac cardioversion and conventional external cardioversion.

AIM: Low-energy (1 to 15 J), catheter-based intracardiac cardioversion was compared with transthoracic external cardioversion (360 J) in a prospective, cross-over clinical trial. METHODS AND RESULTS: In 187 consecutive patients with chronic atrial fibrillation, over a period of a mean of 10.0 +/- 7.3 (SD) months, 217 cardioversion attempts were made. Intracardiac shocks were randomly applied between two 6-F catheters located in either the right atrium and coronary sinus or between the right atrium and left pulmonary artery. When a cardioversion attempt with one method failed, the other method was implemented. After cardioversion, all patients were treated orally with sotalol with a mean daily dose of 174 +/- 54 mg. Internal cardioversion was more effective than external cardioversion (65/70 = 93% vs 92/117 = 79%, P < 0.01). The mean energy for successful cardioversion was 5.8 +/- 3.2 J for the internal and 313 +/- 71 J for the external cardioversion group. At a mean follow-up of 12.5 +/- 6.4 months, 48% (38%) of the patients treated with internal (external) cardioversion were in sinus rhythm (P < 0.05). In 22 of 25 patients in whom external cardioversion failed, sinus rhythm was restored with internal cardioversion at a mean energy of 6.5 +/- 3.0 J. Overweight patients had twice the risk of unsuccessful external cardioversion. CONCLUSIONS: Internal cardioversion is effective in restoring sinus rhythm. It might be indicated in patients in whom external cardioversion had failed or in whom external cardioversion is assumed to be difficult or even contraindicated.

Adult↗
PubMed1997

Pain threshold for low energy intracardiac cardioversion of atrial fibrillation with low or no sedation.

UNLABELLED: Recent studies have shown that internal cardioversion of atrial fibrillation is safe and effective. In this randomized prospective study, we have tried to evaluate the influence of different waveforms on the perception of pain during internal cardioversion in patients with chronic atrial fibrillation. METHODS: Internal cardioversion was performed with minimal or no sedation in 31 consecutive patients. R wave triggered, biphasic shocks of 6 ms/6 ms or 3 ms/3 ms duration (randomly selected) and approximately 65% tilt were used starting with a 50-V test shock. The shock intensity was increased in 40-V steps up to a maximum voltage of 520 V Shocks were applied via two custom-made catheters (Elecath, Rahway, NJ). In 16 patients (3 females, age 61 +/- 11 years, left atrium diameter 58 +/- 5 mm, duration of atrial fibrillation 4 +/- 4 months), 6/6 waveforms were used, and in 15 patients (1 female, age 62 +/- 5 years, left atrium diameter 59 +/- 4 mm, duration of atrial fibrillation 5 +/- 2 months), 3/3 waveforms were used. After cardioversion, each patient was asked to quantify their pain on a scale from 0-10 (0 = no pain, 10 = intolerable). Fourteen of the 15 patients in the 3/3 ms and 15 of the 16 patients in the 6/6 ms group were successfully cardioverted. Patients from the 6/6 waveform group were cardioverted with a lower mean voltage of 254/92 versus 355/127 V (P < 0.02), at lower pain score 1.8 +/- 1.3 versus 4.2 +/- 2.2 (P < 0.05) with equivalent energy (6.8 +/- 2.8 versus 6.2 +/- 1.5 J, n.s.) and required lower doses of midazolam of 2.2 +/- 1.9 versus 4.0 +/- 1.8 mg IV (P < 0.02). The waveform used in internal cardioversion seems to have a major impact on the patients' perception of pain. These results imply that energy determines the success of a shock, but voltage determines the pain perceived by the patient. The use of waveforms that deliver greater energy at lower peak voltages offers the possibility of internal cardioversion with less sedation and greater patient tolerance.

Atrial Fibrillation↗
PubMed1997

Evaluation of a new treadmill exercise protocol.

STUDY OBJECTIVES: To confirm that a newly drafted treadmill exercise protocol designed on a theoretical basis to span a range of 0 to 200 W with approximately 25-W increments by alteration of either speed or grade from one stage to the next should correspond to a standard bicycle protocol consisting of 25-W steps. DESIGN: Randomized, crossover study to compare both exercise test modes. STUDY PARTICIPANTS: Twenty-one consecutive healthy volunteers. INTERVENTIONS: Subjects underwent both exercise tests until either exhaustion or completion of the respective protocol, and cardiopulmonary exercise parameters were assessed during either of them. For comparison, correlation coefficients (r) were calculated. RESULTS: Exercise tolerance time was 9% higher on the treadmill (p<0.05). Ten subjects completed the bicycle program, whereas 18 subjects did so on the treadmill. With both protocols, there were comparably linear increases in heart rate (r=0.885), oxygen uptake (r=0.925), oxygen uptake per body weight (r=0.944), carbon dioxide output (r=0.937), and minute ventilation (r=0.914). For the 2-min stage duration, a plateau in oxygen uptake was achieved with neither protocol. The ventilatory equivalent for oxygen, which is not linear, showed its minimum at comparable workloads, at the point of surpassing the anaerobic threshold. Correlation of oxygen pulse was fair (r=0.896). CONCLUSIONS: There was an excellent correlation of the parameters with respect to both measured values at identical workloads and slopes of both protocols, thus enabling comparability of treadmill and bicycle ergometry. Due to its practical handling, the new protocol may facilitate acceptance, especially when used for elderly or disabled patients.

Adult↗
PubMed1996

Reproducibility of cardiopulmonary exercise parameters in patients with valvular heart disease.

STUDY OBJECTIVES: To determine the degree of reproducibility of exercise parameters in patients with chronic heart failure. Parameters such as treadmill walking time (TWT), oxygen uptake (Vo2), heart rate, oxygen pulse, minute ventilation (VE) ventilatory equivalents for oxygen uptake (VE/Vo2) and carbon dioxide output (Vco2), and respiratory quotient at both anaerobic threshold (AT) and peak exercise (PE) each were assessed. DESIGN: Using the Naughton-Weber protocol, two repeated cardiopulmonary treadmill exercise tests were performed after detailed instructions prior to the first test and on strict adherence to standardized investigational conditions, viz, at the same time of day and at the same ambient temperature, receiving constant medication, and while in a 12-h fasting state. PATIENTS: The studies were carried out in 17 patients with chronic heart failure due to valvular heart disease considered candidates for intervention because of symptoms. According to Weber's classification of functional capacity, 10 patients were in class A (Vo2 max > 20 mL O2/min/kg), 5 patients were in class B (16 to 20 mL O2/min/kg), and the remaining 2 were in class C (10 to 16 mL O2/min/kg). MEASUREMENTS: Parameters assessed were TWT, Vo2, heart rate, oxygen pulse, VE and ventilatory equivalents for oxygen (VE/Vo2) and carbon dioxide (VE/Vco2) both at AT and at PE. To reflect reproducibility, correlation coefficients (r) were calculated. RESULTS: An excellent reproducibility was found for TWT (r = 0.963, p < 0.0001), Vo2 at AT in percent of predicted Vo2max (r = 0.984, p < 0.0001), Vo2 at PE (r = 0.996, p < 0.0001), heart rate at AT (r = 0.943, p < 0.0001) and at PE (r = 0.928, p < 0.0001), oxygen pulse at AT (r = 0.980, p < 0.001) and at PE (r = 0.991, p < 0.0001), VE at AT (r = 0.949, p < 0.0001) and at PE (r = 0.912, p < 0.0001) as well as VE/Vo2 at AT (r = 0.942, p < 0.0001) and at PE (r = 0.781, p < 0.0002) and VE/Vco2 at AT (r = 0.995, p < 0.0001) and at PE (r = 0.943, p < 0.0001), respectively. CONCLUSIONS: On adherence to standardized conditions, an excellent reproducibility existed for TWT, Vo2 (reflecting cardiac output), ventilation, and heart rate as well as derived parameters, rendering cardiopulmonary exercise testing a reliable means of quantification of heart failure as a prerequisite for enabling diagnostic or therapeutic decisions.

Adult↗
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↗