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Biomedical subjects

H Tillmanns

Publications and source records attributed to H Tillmanns.

At least 73 records · Page 4Linked to original sources
PubMed1996

Cyclosporine a inhibits tissue factor expression in monocytes/macrophages.

Accelerated coronary atherosclerosis in cardiac allografts is the major limiting factor for long-term survival after heart transplantation. There is growing evidence that activation of the coagulation mechanism is involved in the development of transplant atherosclerosis. Tissue factor (TF) expression by cells of the monocyte/macrophage system may represent an important mechanism underlying the fibrin deposition in the affected vessels. In the present study, we investigated the effect of cyclosporine A (CsA) on the lipopolysaccharide (LPS)-induced procoagulant activity (PCA) in human monocytes/macrophages. CsA exerted a dose-dependent inhibitory effect on LPS-induced monocyte/macrophage PCA, which was identified as TF activity based on functional and immunologic characterization. As shown by reverse transcriptase-polymerase chain reaction, CsA reduced the transcription of the TF gene in LPS-stimulated monocytes/macrophages. Electrophoretic mobility shift assay showed that CsA inhibited the LPS-induced activation of the nuclear factor kappa B (NF-kappa B). As shown by Western blot analysis, CsA treatment decreased the nuclear translocation of NF-kappa B, thereby suggesting the mechanism for the inhibitory effect of CsA on TF induction. Hence, a nonimmunologic effect of CsA may contribute to its successful use in transplant medicine.

Biological Transport↗
PubMed1995

Gene polymorphism but not catalytic activity of angiotensin I-converting enzyme is associated with coronary artery disease and myocardial infarction in low-risk patients.

BACKGROUND: An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been postulated to be associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI). METHODS AND RESULTS: In the present study, the effects of I/D gene polymorphism and of ACE activity on CAD and MI were investigated in 920 individuals who underwent coronary angiography for diagnostic purposes. In the total population and in all CAD and MI groups, a strong association was observed between the gene polymorphism and ACE activities; DD genotypes had approximately twofold higher ACE activities than II genotypes. Although classic risk and protective factors of CAD and MI were identified, associations of ACE genotype and of ACE activity to CAD and MI were not detected in the total population. Among subjects defined to be at lower risk of MI by low body mass index and low cigarette consumption, however, an association of the DD genotype with MI was found. Exclusion of individuals with triglyceride levels > 140 mg/dL and cholesterol levels > 180 mg/dL revealed an association of the DD genotype with CAD. An association of the ACE activity with CAD or MI could not be demonstrated in any of the low-risk populations. CONCLUSIONS: Increased ACE activity obviously is not a risk factor of CAD or MI. The importance of the deletion polymorphism for the development of CAD and MI may be restricted to individuals without classic risk factors.

Case-Control Studies↗
PubMed1995

Residual 201Tl activity in irreversible defects as a marker of myocardial viability. Clinicopathological study.

BACKGROUND: The objective of the present study was to characterize the relation between the residual 201Tl activity in irreversible perfusion defects and the extent of irreversible myocardial damage indicated by the volume fraction of myocardial interstitial fibrosis in patients with chronic coronary artery disease. METHODS AND RESULTS: Stress planar 201Tl scintigraphy with tracer reinjection at rest was performed in 37 patients with > or = 75% stenosis of the left anterior descending coronary artery, and anteroseptal 201Tl activity was quantified by computer-assisted placement of regions of interest from the serial myocardial images. During coronary artery bypass grafting (performed within 6 +/- 3 weeks after scintigraphy), two transmural biopsy specimens were taken from the anterior wall of the left ventricle and the amount of interstitial fibrosis was assessed by use of light microscopic morphometry. A wide spectrum of interstitial fibrosis was obtained, ranging from 15 vol% to 60 vol%. Interstitial fibrosis was similar in patients with reversible (n = 11) or irreversible (n = 15) tracer defects in conventional stress-redistribution images. However, interstitial fibrosis was significantly lower in patients who had enhanced regional 201Tl activity after tracer reinjection compared with those who did not have enhancement of tracer activity after reinjection (28 +/- 8 vol%, n = 7, versus 41 +/- 12 vol%, n = 8; P = .031). The correlation between relative poststenotic 201Tl activity and interstitial fibrosis after tracer reinjection was significantly improved compared with conventional redistribution images (r = -.622 versus r = -.851, n = 15; P < .01). CONCLUSIONS: The present data demonstrate that the level of regional 201Tl activity in redistribution and, in particular, reinjection images is significantly related to the mass of preserved viable myocytes in poststenotic left ventricular myocardium. Therefore, the residual 201Tl activity provides information about viability within irreversible perfusion defects and may itself serve as marker of myocardial viability.

Biopsy↗
PubMed1995

Preservation of myocardial blood flow by calcium antagonists does not prevent attenuation of regional myocardial function after repetitive brief periods of myocardial ischaemia in the rat heart.

The aim of this study was to assess the effect of two different calcium channel blockers on myocardial blood flow and function in a rat model of myocardial 'stunning' by repeated short episodes of ischaemia ('repetitive ischaemia'). In an open chest rat model, the left anterior descending coronary artery was ligated for 10 min followed by 15 min reperfusion. In total, five periods of ischaemia and reperfusion were performed. Myocardial blood flow was assessed by the hydrogen clearance technique and systolic thickening fraction by pulsed Doppler. After five episodes of ischaemia, myocardial blood flow adn myocardial thickening in the ischaemic area were reduced by 60 +/- 8% and 52 +/- 7% (n=9), respectively, as compared to baseline. Continuous intravenous infusion of the calcium channel blockers nifedipine (n=6) and gallopamil (n=6), started 20 min prior to onset of ischaemia, attenuated the ischaemia-induced decrease of myocardial perfusion. Nifedipine was the most effective with only 5 +/- 2% reduction in blood flow after five ischaemic episodes, whereas reduction of myocardial blood flow was 30 +/- 4% in the presence of gallopamil. However, neither nifedipine nor gallopamil were able to prevent regional ventricular dysfunction induced by repetitive ischaemia. Despite the preservation of myocardial blood flow following repetitive ischaemia, calcium channel blockers do not prevent ischaemia-induced reduction of myocardial function in the ischaemic area.

Animals↗
PubMed1994

Release of chemoattractants and neutrophil activation in acute myocardial infarction immediately after successful recanalization of the infarct-related vessel by angioplasty.

The study investigated inflammatory responses in evolving myocardial infarction. Fifteen patients with acute myocardial infarction, who had undergone balloon recanalization of the infarct-related coronary artery within 4 h after onset of symptoms, were examined. Blood samples were obtained through the guiding catheter and from the pulmonary artery before and immediately after successful recanalization. After recanalization, plasma from the pulmonary artery was 47% (quartiles: 19%, 78%; P = 0.001) more chemotactic to neutrophils from normal donors than before recanalization. Furthermore, significant changes in neutrophil function were found in the pulmonary artery. Compared to the values before recanalization, the nitroblue tetrazolium score rose by 31% (quartiles: 4%, 37%; P = 0.003), FMLP-stimulated superoxide anion production by 10% (quartiles: 0%, 39%; P = 0.020), and chemotaxis by 46% (quartiles: 0%, 81%; P = 0.011), while neutrophil filterability decreased by 28% (quartiles: 15%, 47%; P = 0.010). No significant changes in neutrophil parameters were found in the arterial blood. The study indicates that chemoattractants are released in the early reperfusion period of evolving myocardial infarction. These chemoattractants may act as inflammatory mediators causing neutrophil activation.

Aged↗
PubMed1994

Verapamil treatment after coronary angioplasty in patients at high risk of recurrent stenosis.

OBJECTIVE: To evaluate the efficacy of high-dose verapamil treatment (240 mg twice daily) in the prevention of angiographic restenosis after primary successful coronary angioplasty in patients at high risk of recurrent obstruction. DESIGN: A placebo controlled, double blind trial in which patients with stable angina pectoris and patients with unstable angina or non-Q wave infarction treated with 330 mg aspirin and 75 mg dipyridamole twice daily were randomised to a verapamil group or a control group. Follow up angiography was performed 6 months after angioplasty or sooner if signs of recurrent ischaemia developed. SETTING: University department of cardiology. PATIENTS: 196 consecutive patients undergoing coronary angioplasty from the beginning of April 1987 to the end of March 1989 and meeting the selection criteria that included the presence of at least one of six predefined risk factors for restenosis. At the time of coronary angioplasty 113 patients had unstable angina or non-Q wave infarction and 83 had stable angina pectoris. RESULTS: In 89 (91%) patients in the verapamil group and in 83 (85%) control patients follow up angiograms were available. The restenosis rate was lower in the verapamil group (48.3%) than in the placebo group (62.7%) (odds ratio 0.56, 95% confidence interval (CI) 0.303 to 1.025 p = 0.059). Of the 172 patients in whom follow up angiograms were available, 24 (13 taking verapamil and 11 taking placebo) did not comply with the trial for more than 40 (34) days (mean (1 SD)). For the remaining 148 patients the restenosis rate was 47.4% in the verapamil group and 63.9% in the placebo group (odds ratio 0.52, 95% CI 0.271 to 0.993, p = 0.046). In the 97 patients with unstable angina or non-Q wave infarction the restenosis rate was not significantly influenced by verapamil (55.8% with verapamil v 62.2% with placebo, odds ratio 0.77, 95% CI 0.339 to 1.728, p = 0.520). In the 75 patients with stable angina pectoris the restenosis rate dropped from 63.2% with placebo to 37.8% with verapamil (odds ratio 0.36, 95% CI 0.137 to 0.917, p = 0.038). CONCLUSION: The observed beneficial effect of high-dose verapamil treatment on the angiographic restenosis rate in patients with stable angina pectoris and at increased risk of recurrent obstruction requires confirmation in further prospective studies.

Aged↗
PubMed1994

[Heart rhythm after conversion of ventricular tachyarrhythmia by internal shock delivery].

The purpose of this retrospective study is the analysis of dysrhythmias following internal cardioversion/defibrillation of ventricular tachycardia (VT) or fibrillation (VF) and to discuss their relevance to the therapy with automatic implantable devices. Therefore, 304 internal conversions of VT/VF during and/or after implantation of automatic defibrillators were evaluated in 51 patients. Significant post-shock arrhythmias (bradycardia, atrial fibrillation, non-sustained VT of > or = 10 cycles) were absent after 89% of internal shocks. Pauses of > 2 s were observed in 2/9 patients without VVI-back-up pacing. The heart rate was > or = 50 bpm in 10/51 patients. Atrial fibrillation occurred in 7 patients. Non-sustained, mostly polymorphic VT consisting of > or = 10 cycles followed 18/304 (6%) internal shocks in 13 patients. The VT rate was > or = 200/min in 17/18 episodes and triggered an inadequate shock once. The incidence of non-sustained VT post-shock was unrelated to shock energy, type, and duration of the converted arrhythmia. In conclusion, automatic implantable devices should provide back-up pacing. Tachycardic rhythms can mislead automatic interpretation of the effect of internal shocks.

Adult↗
PubMed1993

In vitro and ex vivo effects of aspirin in patients on a low-dose aspirin therapy.

In 19 patients on a low-dose aspirin therapy with 100 mg/d, an insufficient effect of aspirin was observed in five patients (aggregations induced by arachidonic acid and collagen, thromboxane B2-formation in serum and after collagen). Aspirin added in vitro increased the inhibition to a degree comparable to that seen in the other 14 patients, i.e. the insufficient effect could be due to a lack of compliance or to a reduced availability of the drug. In another 20 patients there was a good inhibitory effect of aspirin; additional aspirin did not increase the inhibition of arachidonic acid-induced aggregation and serum-thromboxane B2, but slightly increased collagen-induced aggregation and thromboxane B2 formation. The effect was the same, whether the aspirin was given in vivo or added in vitro.

Adult↗
PubMed1993

In-hospital experience with multiprogrammable implantable antitachycardia/antifibrillation devices.

Multiprogrammable, automatic internal defibrillators with (n = 45) and without (n = 15) antitachycardia pacing features were implanted in 60 consecutive patients with refractory, malignant ventricular tachycardia (VT) (n = 42) or fibrillation (VF) (n = 18). Left ventricular (LV) ejection fraction was reduced to 39% +/- 12% as a result of structural heart disease in 56 patients. The complexity of the systems caused no additional risks to the surgical procedure or postoperative management. VT/VF detection parameters were individually adjusted to the arrhythmia type (detection cycle length 323 +/- 40 ms in patients with VF vs 405 +/- 40 ms for VT patients, P < 0.05) and incidence (longer detection periods if frequent nonsustained VT was also present). Shock energy was reduced in patients with VT as compared to VF (11J vs 24J, P < 0.05). Antitachycardia pacing was activated in 19/28 (68%) patients with well tolerated VT. Signal, telemetry, as detected by the device, combined with programmability allowed the device to be checked for correct decisions (these were inappropriate in four patients in three of whom corrections were non-invasive) prior to discharge. In conclusion, in the automatic tachyarrhythmia control devices we studied, programmability and flexibility appeared to be clinically safe and useful. Prolonged observation periods are required, however, to evaluate the true clinical safety and persistent efficacy of device programmability and flexibility.

Algorithms↗
PubMed1993

Cardiac release of chemoattractants after ischaemia induced by coronary balloon angioplasty.

OBJECTIVE: To investigate the release of chemoattractants after myocardial ischaemia during balloon angioplasty. DESIGN: Sampling of femoral arterial and coronary sinus blood before and immediately after the first balloon inflation during angioplasty. In a study group of 16 patients the balloon was kept expanded for two minutes, whereas in a control group of eight patients the first balloon inflation was brief (< 10 s). MAIN OUTCOME MEASURES: Chemotaxis of neutrophils from healthy donors towards patient plasma (Boyden chamber), superoxide anion production by normal neutrophils after incubation with patient plasma (cytochrome C reduction). RESULTS: In the study group, coronary sinus plasma after balloon deflation was more chemoattractive to normal neutrophils (median relative increase 24% (quartiles: 4%, 45%), p = 0.008) and induced a higher superoxide anion production in normal neutrophils (44% (10%, 97%), p = 0.013) than arterial plasma. Concomitantly, the degree of activation of patient neutrophils was increased in coronary sinus blood compared with arterial blood, as shown by an increased proportion of neutrophils reducing nitro-blue tetrazolium (21% (9%, 38%), p = 0.006) and a decreased neutrophil filter-ability (-16%(-3%, -40%), p = 0.003) in coronary sinus blood. In the study group before balloon inflation and in the control group before and after balloon inflation differences between arterial and coronary sinus blood were not significant. Signs of ischaemia (lactate release, ST segment changes) were only detected in the study group. CONCLUSION: After transient myocardial ischaemia during balloon angioplasty there is a local release of chemoattractants, associated with neutrophil activation.

Angioplasty, Balloon, Coronary↗
PubMed1993

Activation of neutrophils in the microvasculature of the ischaemic and reperfused myocardium.

In 11 rats, the microcirculation of the repeatedly ischaemic (stunned) left ventricular myocardium was studied using in vivo fluorescence microscopy. Stunning was provoked by six subsequent 10 min ligations of the left anterior descending coronary artery, each of them followed by a 20 min reperfusion period. In the stunned myocardium showing hypokinetic wall motion, myocardial blood flow dropped by 55%; in this region, leukocytes often appeared in slow-flow capillaries plugging capillary branches. Closely linking to leukocyte adherence, a rise of microvascular permeability was documented by extravascular clouds of fluorescent dextran. After nifedipine treatment, in ischaemic regions marked dilatation of larger A1 and A2 arterioles was noted, in addition to the ischaemia-induced dilatation of smaller A3 and A4 arterioles. Furthermore nifedipine and nisoldipine reduced the number of adherent leukocytes in post-capillary venules and capillaries of the repeatedly ischaemic myocardium. In 12 patients with coronary one-vessel disease and without previous transmural myocardial infarction, elective coronary angioplasty (PTCA) was performed (balloon inflation for 2 min). After elective PTCA of the LAD, a significant rise in the proportion of activated neutrophils was noted. After elective 2 min PTCA of the LAD, coronary sinus blood samples showed a marked rise of FMLC stimulated superoxide anion production, whereas passive deformability decreased considerably. Furthermore, an increase in chemotactic activity in coronary sinus blood samples was observed.

Angioplasty, Balloon, Coronary↗
PubMed1992

Myocardial scintigraphy with iodine-123 phenylpentadecanoic acid and thallium-201 in patients with coronary artery disease: a comparative dual-isotope study.

To characterise the clinical usefulness of serial myocardial scintigraphy with iodine-123 phenylpentadecanoic acid (IPPA) in comparison with thallium-201, dual-isotope investigations were performed in 41 patients with angiographically documented coronary artery disease. Both tracers were administered simultaneously during symptom-limited ergometry. Planar scintigrams were acquired immediately after stress, and delayed imaging was performed after 1 h for IPPA and 4 h for 201Tl. Scintigrams were evaluated both qualitatively and quantitatively using a newly developed algorithm for automated image superposition. Initial myocardial uptake of both tracers was closely correlated (r = 0.75, p < 0.001). Both tracers also revealed a similar sensitivity for the identification of individual coronary artery stenoses > or = 75% (IP-PA: 70.0%, 201Tl: 66.3%, P = NS) with identical specificity (69.8%). The number of persistent defects, however, was significantly higher with IPPA (P = 0.021), suggesting that visual analysis of serial IPPA scintigrams may overestimate the presence of myocardial scar tissue. On the other hand, previous Q wave myocardial infarction was associated with a decreased regional IPPA clearance (29% +/- 11% vs 44% +/- 11% in normal myocardium, P < 0.05). The data indicate that serial myocardial scintigraphy with IPPA is essentially as sensitive as scintigraphy with 201Tl for the detection of stress-induced perfusion abnormalities. Quantitative analysis of myocardial IPPA kinetics, however, is required for the evaluation of tissue viability.

Algorithms↗
PubMed1992

Reduction of myocardial ischemia by gallopamil: a dual-isotope study with thallium-201 and iodine-123 phenylpentadecanoic acid.

The present study was performed for characterizing the effect of chronic oral treatment with the calcium antagonist gallopamil on regional myocardial perfusion and free fatty acid utilization in poststenotic human myocardium. Twenty-two patients with angiographically documented coronary artery disease and stable angina pectoris underwent consecutive dual-isotope studies following simultaneous injection of 80 MBq thallium-201 and 200 MBq iodine-123 phenylpentadecanoic acid (IPPA) during a symptom-limited stress test. Radionuclide studies were performed after 1 week of placebo treatment (baseline), 4 weeks after oral treatment with 50 mg of gallopamil t.i.d. and again after 1 week of double-blind treatment with gallopamil or placebo. As compared to baseline, initial (poststress) uptake of both tracers in poststenotic myocardial segments was significantly improved after 4 weeks of treatment with gallopamil [thallium-201, +9.0%; p < 0.001; 95% confidence interval (CI), 4.3-13.6%; IPPA, +11.8%; p = 0.003; 95% CI, 4.2-19.3%]. Poststenotic IPPA-clearance was likewise significantly increased (+28.2%; p < 0.001; 95% CI, 12.4-44.0%) indicating a considerably enhanced myocardial fatty acid oxidation after treatment. In the final double-blind phase, myocardial uptake of both tracers as well as IPPA clearance remained enhanced in the subgroup of patients receiving gallopamil and returned to baseline values in patients receiving placebo. Thus, in poststenotic myocardium, chronic treatment with gallopamil provokes an improvement of both regional myocardial perfusion (as demonstrated by an increased tracer uptake in poststress scintigrams) and regional myocardial fatty acid utilization (as demonstrated by an increased uptake and clearance of IPPA).

Algorithms↗
PubMed1992

Effect of gallopamil on neutrophil function: experimental and clinical studies.

The purpose of the study was to investigate whether gallopamil interferes with neutrophil activation. In vitro, gallopamil caused a dose-dependent reduction in phorbol myristate acetate-stimulated superoxide anion production by neutrophils as measured by the superoxide dismutase inhibited reduction of cytochrome C [concentration of 50% inhibition (IC50) = 9.5 x 10(-6) mol/L]. Furthermore, gallopamil reduced the platelet-activating factor-induced loss of neutrophil deformation, which was assessed by filtrometry (IC50 = 4.3 x 10(-6) mol/L). The effect of gallopamil was assessed in 24 patients during elective balloon angioplasty. Gallopamil (0.4 mg) or placebo (double-blind conditions) was administered by intracoronary application during the 10-min interval between the first two balloon inflations. In the placebo group, blood samples obtained simultaneously from the coronary sinus and from the femoral artery revealed an increase in the proportion of activated neutrophils in the coronary sinus blood after the second balloon inflation [nitro blue tetrazolium (NBT) score, NBT test: 15 +/- 9% relative coronary sinus and arterial blood difference, p < 0.05]; these changes in NBT score were similar to those after the first balloon inflation. In the gallopamil-treated group, however, significant arterial and coronary sinus blood differences in NBT scores were not found after the second balloon inflation. Gallopamil may, thus, attenuate the local neutrophil activation during balloon angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1992

Intracoronary gallopamil during percutaneous transluminal coronary angioplasty.

The present study was designed to investigate the effect of the calcium-channel antagonist gallopamil on myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA). Twenty-four adult patients with coronary artery disease and significant proximal stenosis of the left anterior descending coronary artery (LAD) were randomly assigned to receive gallopamil or placebo under double-blind conditions. Patients with recent myocardial infarction, apparent collateralization of the LAD, myocardial failure, sinoatrial or atrioventricular block, severe hepatic disease, or renal failure were excluded from the study. PTCA was performed with use of at least two balloon inflations, each of 2 min in duration. Gallopamil (0.4 mg) or placebo (0.9% sodium chloride) was administered during the 10-min interval between the two inflations. For determination of myocardial lactate and hypoxanthine release, blood samples were taken simultaneously from the great cardiac vein and the femoral artery before and immediately after each inflation. Electrocardiogram changes were analyzed by measuring ST-segment deviations (80 ms after the J point) and maximal T-wave deviations of the leads I, II, III, and V2, V4, and V6. The most sensitive leads for identification of myocardial ischemia in the LAD area were V2 and V4. If compared to the first balloon inflation, the degree of ST-segment/T-wave changes induced by the second inflation was significantly reduced only in the presence of gallopamil. Furthermore, if compared to placebo, ischemia-induced lactate and hypoxanthine release was decreased in the presence of gallopamil. These results suggest that intracoronary application of gallopamil attenuates myocardial ischemia during PTCA.

Adult↗
PubMed1991

Hemodynamic and neuroendocrine response to acute administration of the phosphodiesterase inhibitor BM14.478 in patients with congestive heart failure.

The benzimidazol analogue BM14.478 is a phosphodiesterase inhibitor with both vasodilator and positive inotropic properties. Hemodynamic parameters and plasma hormone levels of 8 patients (1 female, 7 male) with chronic congestive heart failure NYHA Classes II-IV (1 patient with coronary artery disease, 7 patients with primary dilated cardiomyopathy) were assessed before and until 6 h after the intravenous application of 1.0 mg BM14.478. There was a significant decrease of mean pulmonary artery pressure (28 +/- 11 vs. 23 +/- 11 mmHg; p less than 0.05), mean right atrial pressure (8.6 +/- 5.2 vs. 5.0 +/- 4.7 mmHg; p less than 0.02), and systemic vascular resistance (1651 +/- 484 vs. 1206 +/- 252 dynes.s.cm-5; p less than 0.05) as early as 10 min after injection of BM14.478. Pulmonary vascular resistance also was reduced (128 +/- 86 vs. 61 +/- 39 dynes.s.cm-5, 30 min after injection; p less than 0.02). Simultaneously there was a significant increase of cardiac index (2.3 +/- 0.7 vs. 3.1 +/- 0.8 l.min-1.m-2, 10 min after injection; p less than 0.02), and stroke volume index (28.8 +/- 11.7 vs. 33.9 +/- 8.5 ml.min-1.m-2; 30 min after injection; p less than 0.05). Although mean heart rate did not change significantly, some patients reacted with a transient increase. There was also a slight but insignificant increase of the double product. No serious side effects were observed. The hemodynamic improvement was followed by a delayed reduction of plasma levels of epinephrine (51 +/- 20 vs. 41 +/- 21 pg/ml; p less than 0.02; 30 min after injection) and atrial natriuretic peptide (229 +/- 283 vs. 121 +/- 168 pg/ml; p less than 0.05; 1 h after injection). Mean levels of plasma norepinephrine, however, did not change significantly and individual responses showed large variations, which could not be predicted by the behavior of the hemodynamic parameters. Three of eight patients (2 of these with elevated baseline filling pressures) even showed a marked increase of plasma norepinephrine levels after BM14.478. Response of plasma renin activity and plasma vasopressin levels to BM14.478 also was heterogeneous. According to the results of this study, acute administration of the phosphodiesterase inhibitor BM14.478 has an immediate beneficial hemodynamic effect in patients with severe congestive heart failure by reducing both preload and afterload, and by increasing cardiac index and stroke volume. However, this improvement of hemodynamic parameters is not necessarily accompanied by a favorable short-term response of plasma hormones, and therefore does not allow any conclusions on survival of these patients.

Adult↗