Biomedical subjects

W Kiowski

Publications and source records attributed to W Kiowski.

At least 73 records · Page 4Linked to original sources

PubMed1997

Lack of cross-tolerance to short-term linsidomine in forearm resistance vessels and dorsal hand veins in subjects with nitroglycerin tolerance.

BACKGROUND: Therapy with nitroglycerin is widely used in the treatment of angina pectoris, but development of tolerance is a major problem. Nitrovasodilators other than nitroglycerin may be less prone to induce vascular tolerance. This investigation was designed to test whether the alternative nitric oxide donor linsidomine maintains its vasodilator effects in the presence of nitroglycerin tolerance. METHODS: We tested the vascular effects of nitroglycerin and linsidomine (SIN-1) in forearm resistance arteries (venous occlusion plethysmography) and hand veins (venous compliance technique) using a randomized, double-blind placebo-controlled regimen in 33 healthy subjects (age range, 22 to 38 years; mean age, 26 years) before and after 7 days of assignment to either 1 week of nitroglycerin administration (0.83 mg/hr) for induction of tolerance or placebo administration. RESULTS: Vascular responses of both vascular beds to nitroglycerin (in veins: mean difference, 42.3%; confidence interval [CI], 3% to 81.7%; p < 0.05; in arteries: mean difference, 65.0%; CI, 38.9% to 91.1%; p < 0.01) but not to linsidomine (in veins: mean difference, -13.8%; CI, -53.5 to 25.8%; not significant; in arteries: -19.7%; CI, -33.7% to -5.6%; not significant) were attenuated in the nitroglycerin patch group, whereas the placebo group showed no differences to either nitroglycerin (in arteries: mean difference, -7.5%; CI, -44.6% to 29.6%; in veins: -10.6%; CI, -58.2% to 36.9%) or linsidomine (in arteries: 4.5%; CI, -12.8% to 21.7%; in veins: -13.1%; CI, -4.5% to 29.8%). CONCLUSION: These results suggest that short-term administration of sydnonimines can overcome the loss of vascular relaxation associated with long-term nitroglycerin therapy.

Adult↗

PubMed1997

Functional and biochemical analysis of angiotensin II-forming pathways in the human heart.

Blockade of the renin-angiotensin system by inhibition of angiotensin-converting enzyme (ACE) is beneficial for the treatment of hypertension and congestive heart failure. However, it is unclear how complete the blockade by ACE inhibitors is and if there is continuing angiotensin II (Ang II) formation during chronic treatment with ACE inhibitors. Indeed chymase, a serine protease, which is able to form angiotensin II from angiotensin I (Ang I) and cannot be blocked by ACE inhibitors, has been shown to be present in human heart. The goal of the present study was to evaluate the extent of renin-angiotensin system blockade and the Ang II-forming pathways in cardiac tissue of patients chronically treated with ACE inhibitors or in patients without ACE inhibition therapy. Our studies indicate an incomplete ACE inhibition in human heart tissue after chronic ACE inhibitor therapy. Moreover, ACE contributes only a small portion to the total Ang I conversion, as shown in biochemical studies in ventricular and coronary homogenates or functionally as Ang I contractions in isolated rings of coronary arteries. A serine protease was responsible for the majority of Ang II production in both the membrane preparation and Ang I-induced contractions of isolated coronary arteries. In humans, the serine protease pathway is likely to play an important role in cardiac Ang II formation. Thus, drugs such as renin inhibitors and Ang II receptor blockers might be able to induce a more complete blockade of the renin-angiotensin system, providing a more efficacious therapy.

Adult↗

PubMed1997

[Hemodynamically-induced syncope].

Hemodynamic syncope is caused by an impediment to a necessary increase of the cardiac output; therefore, hemodynamic syncopes most often occur during or shortly after exercise. However, a syncope at rest does not exclude a hemodynamic cause. Moreover, arrhythmias which may directly lead to syncope or accentuate the hemodynamic impediment are often present in cardiac diseases causing hemodynamic syncope. Hemodynamic syncopes are responsible for 2 to 3% of all syncopes leading to medical evaluation. Of these, more than half are caused by aortic stenosis and about one quarter by pulmonary embolism. Other reasons are rare. Hypertrophic cardiomyopathy is more often associated with arrhythmic than with hemodynamic syncope. Syncope in primary pulmonary hypertension is often preceded by dizziness, epigastric distress and faintness. Since the medical therapy may lead to hemodynamic deterioration, it must be started under invasive observation. Primary tumors of the heart are rare; secondary cardiac neoplasms are 6 to 40 times more common. Myxoma is the most common primary tumor of the heart. It is important to promptly undertake surgery in order to improve prognosis. Various other diseases may provoke hemodynamic syncope; however, other symptoms are by far more common.

Cardiovascular Diseases↗

PubMed1997

Endothelial function as intermediary endpoint in hypertension: comments.

The attractiveness of endothelial function as an intermediary or surrogate endpoint in hypertension and antihypertensive therapy, respectively, is obviously based on the widely accepted response-to-injury theory. According to the theory, endothelial functions are disturbed early on in the development of atherosclerosis and, by inference, an improvement of endothelial function should be, at least in theory, an important step towards prevention or retardation of the atherosclerotic process. However, when scrutinizing studies performed to this end in hypertension a number of unresolved issues remain.

Antihypertensive Agents↗

PubMed1996

Natural course of moderate cardiac allograft rejection (International Society for Heart Transplantation grade 2) early and late after transplantation.

BACKGROUND: The significance of International Society for Heart Transplantation (ISHT) grade 2 cardiac allograft rejection has been questioned, and the medical community is not in complete agreement as to its clinical management. We therefore retrospectively analyzed the follow-up of all available endomyocardial biopsy samples obtained from 161 transplant patients since introduction of the ISHT nomenclature at our institution. METHODS AND RESULTS: Of 2868 biopsies performed 3 days to 8.9 years after transplantation, 420 biopsies had no follow-up or were preceded by intensified immunosuppression and were excluded from analysis. Of the remaining 2448 biopsies, 374 (15.3%) were repeat biopsies performed 7 to 10 days after prior ISHT 2 rejection without change of treatment. Of these, 70 (18.7%) had progressed to > or = ISHT 3A, whereas 82 (21.9%) remained unchanged and 222 (59.4%) resolved. In contrast, follow-up of 2074 biopsies with lower-grade rejection showed graft rejection classified as > or = ISHT 3A in 153 (7.4%), ISHT 2 in 240 (11.6%), and < or = ISHT 1B in 1681 (81.1%) biopsy samples (P < .0001). In univariate analysis, the odds ratio (OR) of graft rejection > or = ISHT 3A after ISHT 2 rejection was 2.89. Other univariate predictors of rejection > or = ISHT 3A were time after transplantation (OR = 0.96 per month, P < .0001), blood group type B (OR = 1.62, P < .005), "Quilty" lesion on previous biopsy (OR = 1.70, P < .005), number of HLA mismatches (OR = 1.27 per mismatch, P < .005), female sex (OR = 1.55, P < .05), and serum creatinine level (OR = 0.93 per 10 mumol/L, P < .005). Young age of recipients was a risk factor during long-term (> or = 2 years) follow-up (P < .002), and lower cyclosporine level was a risk factor during the first month after transplantation (P < .01). In multivariate logistic regression analysis, ISHT 2 rejection on previous biopsy remained the strongest predictor of rejection > or = ISHT 3A (OR = 2.40, P < .0001). CONCLUSIONS: Several factors independently increase the risk of rejection classified as > or = ISHT 3A. The strongest predictor of a grade of > or = ISHT 3A was ISHT 2 rejection on the previous biopsy obtained 7 to 10 days earlier. Therefore, ISHT 2 graft rejection is of clinical significance, and short-term follow-up appears to be warranted even late after transplantation.

Adolescent↗

PubMed1996

[Bone density and laboratory parameters of bone metabolism in patients with terminal heart disease].

PURPOSE: The purpose of this study was to assess bone mineral density (BMD) and parameters for bone metabolism in patients with end-stage heart disease awaiting heart transplantation to determine whether these patients are at increased risk of bone disease. PATIENTS AND METHODS: 39 adult men (mean age 52.3, range 21-65 years) with ischemic (41%), idiopathic (43.5%), valvular (2.5%) and diverse (13%) end-stage heart disease were studied prior to heart transplantation. BMD was measured using dual-energy x-ray absorptiometry at the lumbar spine (L2-L4) and at the upper femur (Ward's triangle and femoral neck). Renal and bone biochemical profiles, parathyroid hormone (PTH), 25-OH-vitamin D3, testosterone, alkaline bone phosphatase, osteocalcin, and deoxypyridinoline and calcium excretion were measured. RESULTS: No fractures were found. Mean z-scores were -1.06 +/- 2.02 (mean +/- SD) at the lumbar spine, -1.12 +/- 2.03 at the femoral neck and -0.25 +/- 1.06 at Ward's triangle. Significantly decreased values were seen at the lumbar spine and at the femoral neck compared to age matched healthy controls. Mean values of serum creatinine and parathyroid hormone were elevated (114.4 +/- 29.5 mumol/l and 84.3 +/- 67.8 ng/l, respectively). 7 (18%), 10 (26%) and 22 (56%) of the 39 patients had values beneath the normal range of 25-OH-vitamin D3, testosterone and osteocalcin respectively. Mean urinary deoxypyridinoline/creatinine ratios were elevated (9.46 +/- 8.52 nmol/mmol, normal range 2.5-5). No correlation existed between osteocalcin and urinary deoxypyridinoline/creatinine ratio. Using a multiple linear regression model, serum PTH and cardiac ejection fraction (EF) weakly predicted BMD at the femoral neck (r2 = 0.26). CONCLUSIONS: (1.) Lumbar spine and femoral neck BMD are low in patients awaiting heart transplantation. (2.) A low EF and a high PTH weakly correlate with a decrease in BMD at the femoral neck. (3.) In patients with end-stage heart failure the coupling of bone formation to bone resorption is frequently disturbed. (4.) Testosterone and 25-OH-vitamin D3 levels are low in a number of patients and in such cases replacement therapy may be appropriate.

Absorptiometry, Photon↗

PubMed1996

Toxoplasmosis in heart transplant recipients.

In cardiac transplant recipients, infection with Toxoplasma gondii may be transmitted with the transplanted organ to immunosuppressed recipients or may be due to reactivation under immunosuppression in cases of pretransplant infection. In the present study the incidence of infection with Toxoplasma gondii and the clinical presentation of the infection in 121 consecutive heart transplant recipients were investigated. Data on IgG and IgM antibodies for Toxoplasma gondii measured by a semiquantitative microparticle immunoassay of donors and recipients were collected prospectively in 121 patients. Infection with Toxoplasma gondii was defined as IgM seroconversion with proven pre-transplant seronegativity (primary infection) or at least a fourfold increase of IgG antibodies (reactivation). Infection with Toxoplasma gondii occurred in 16 of 121 patients (13%) whereas overt clinical disease occurred in 5 of 121 patients (4%). Organ-transmitted infection was more frequent (11/18, 61%) and more often associated with acute disease than reactivation of latent infection (5/69 patients, 7%) (p < 0.01), although one case of Toxoplasma retinochoroiditis occurred in a patient with recrudescence of latent pretransplant infection. Treatment with pyrimethamine and sulfadiazine was efficient in all patients with acute disease and in controlling disease in patients with evidence of acute infection.

Animals↗

PubMed1996

Pretransplant malignancy in candidates and posttransplant malignancy in recipients of cardiac transplantation.

BACKGROUND: Malignancy is generally considered a contraindication for cardiac transplantation, whereas secondary malignancy has been described under chronic immunosuppression. PATIENTS AND METHODS: We report here the frequency of malignancy encountered among the 495 patients evaluated at our cardiac transplant centre as well as the incidence and the course of post-transplant malignancy among 129 consecutive patients who underwent cardiac-transplantation, with a subsequent minimum follow-up of 6 months. RESULTS: A total of 10 out of 495 patients (2%) evaluated for heart transplantation presented with a history of previous malignancy: 3 of them underwent transplantation (2 survive, 1 died) whereas in the remaining 7 patients neoplasia was considered a contraindication for cardiac transplantation, and all 7 died (4 cardiac, 3 tumor-related deaths). Post-transplant malignancy was diagnosed in 10 of 129 patients (9%) 35 +/- 15 months after transplantation (6 skin cancers, 1 lymphoproliferative disease, 3 solid tumors). No significant association was found between post-transplant malignancy and primary prophylaxis with antithymocyte globulin (ATG) or murine antihuman T-cell monoclonal antibodies (OKT3). CONCLUSION: These results confirm that pre-transplant malignancy is not an absolute contraindication for cardiac transplantation and that post-transplant follow-up must include careful monitoring of post-transplant malignancy.

Adolescent↗

PubMed1996

Clinical benefit of angiotensin-converting enzyme inhibitors in chronic heart failure.

The ideal therapy for patients with chronic heart failure should reduce symptoms related to pulmonary congestion or low perfusion, prevent the progression of left ventricular dysfunction and, ultimately, should reduce mortality. Extensive studies in humans have investigated the effects of angiotensin-converting enzyme (ACE) inhibitors on these goals of therapy. As an example, the ACE inhibitor cilazapril significantly improved exercise tolerance, as borne out by a meta-analysis of six placebo-controlled, randomized 3-month trials. Comparison of the effects of cilazapril and captopril vs. placebo in one of the trials documented similar improvement in exercise tolerance (14 vs. 17%). Results from other randomized comparative trials suggest that the improvement in symptoms represents a class effect of ACE inhibitors. A beneficial effect of ACE inhibition on the progression of left ventricular dysfunction has also been demonstrated in the SOLVD trial, and a reduction of mortality has been amply documented in several mortality trials (CONSENSUS I, SOLVD, V-HeFT-II, SAVE, AIRE, SMILE) in patients with or without preceding myocardial infarction. Reports that ACE inhibitors also reduce the incidence of reinfarction after myocardial infarction have not been confirmed in all studies but raise the interesting concept that ACE inhibition may interact, in a beneficial but thus far not well-understood way, with key processes in the development of atherosclerosis, thereby preventing plaque rupture, thrombus formation, and myocardial infarction. Taken together, a large database convincingly demonstrates that ACE inhibitors are effective not only in improving symptoms but also in the prevention of progression of left ventricular dysfunction, in the reduction of mortality, and possibly in stabilizing the atherosclerotic disease process.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Up-regulation of endothelin-B receptors in atherosclerotic human coronary arteries.

Both endothelin-A (ETA) and endothelin-B (ETB) receptors are known to be present in human coronary arteries. However, their absolute and relative amounts, functional roles, and the influence of pathology are uncertain. The goal of the present study was to characterize endothelin receptors mediating constriction in human coronary arteries and to assess the influence of cardiomyopathy (CMP) and coronary artery disease (CAD) on ET receptors in human tissue. For comparison, porcine coronary arteries were evaluated in parallel. Competition binding experiments using [125I]ET-1 and different selective and nonselective ETA- and ETB-receptor agonists or antagonists revealed similar relative densities (relative Bmax) of ETA and ETB receptors in coronary arteries from human cardiomyopathic hearts (83% ETA and 17% ETB; n = 5) and porcine hearts (78% ETA and 22% ETB; n = 5). In marked contrast, the relative Bmax of ETB receptors were significantly higher in coronary arteries from human atherosclerotic hearts (51% ETA and 49% ETB; n = 3). Total receptor density (Bmax; fmol/mg protein) was highest in porcine (385 +/- 29) arteries, followed by human CAD (253 +/- 41) and CMP (174 +/- 20) coronary arteries. The relative and absolute Bmax values for ETA and ETB receptors in coronary arteries from a donor heart were similar to those obtained in CMP hearts. There were no significant differences in affinity constants (KD) values for ET-1, ET-3, Sarafotoxin S6c (SRTX S6c), BQ-123, and bosentan (Ro 47-0203) between tissues. In human coronary arteries from CMP hearts, ET-induced constriction seemed to be solely mediated via ETA receptors. In contrast, in porcine coronary arteries 20% of the maximal effect mediated by ET-1 could be attributed to ETB receptors, in agreement with the binding data. The functional role of ETB receptors in CAD tissue could not be evaluated because of the occurrence of spontaneous phasic contractions. We conclude that ETB receptors are up-regulated in human atherosclerotic coronary arteries. Further studies are needed to determine the pathophysiological importance of these receptors.

Acetylcholine↗

PubMed1996

Effects of cilazapril on vascular structure and function in essential hypertension.

Hypertension is associated with an altered design of resistance vessels and decreased endothelium-dependent vasodilator response to acetylcholine. A role of angiotensin II in both defects is suggested by animal experiments in which angiotensin-converting enzyme inhibition reverted structural and functional changes. We investigated the effects of 20 weeks of therapy with the angiotensin-converting enzyme inhibitor cilazapril (5 mg twice daily) on the endothelium-dependent response to brachial artery infusions of acetylcholine and the endothelium-independent vascular relaxation after sodium nitroprusside in 22 subjects with mild to moderate essential hypertension. In addition, we measured minimal forearm vascular resistance (ratio of mean arterial pressure and forearm blood flow after heating, ischemia, and ischemic exercise) as an indirect estimate of vascular structure. Cilazapril decreased blood pressure (151 +/- 14/99 +/- 7 mm Hg during placebo to 138 +/- 17/89 +/- 8 mm Hg after cilazapril treatment, P<.01) and baseline (42.2 +/- 12.6 to 37.1 +/- 10.6 U, P<.05) and minimal (3.0 +/- 1.1 to 2.4 +/- 0.7 U, 15.9 +/- 20.2%; P<.05) forearm vascular resistances. The change in minimal forearm vascular resistance was unrelated to age, duration of hypertension, or changes in blood pressure. Sodium nitroprusside increased forearm blood flow from 2.6 +/- 1.0 to 11.4 +/- 5.9 mL/min per 100 mL and acetylcholine to 21.5 +/- 17.8. Both responses did not change after cilazapril. The data provide indirect evidence that cilazapril therapy may improve vascular structure in human hypertension. The lack of relationship between vascular and blood pressure changes would be compatible with experimental evidence supporting a role for angiotensin II in the development and regression of vascular changes, but this needs further study. Therapy with cilazapril for 20 weeks, like other antihypertensive therapy, does not seem to influence endothelial vasodilator function in humans to a significant degree.

Adult↗

PubMed1996

Low-dose cyclosporine treatment fails to prevent coronary luminal narrowing after heart transplantation.

BACKGROUND: Cyclosporine has been reported to induce endothelial dysfunction, arterial vasculitis, and accelerated atherosclerosis in experimental models. The purpose of the present study was to evaluate whether low-dose cyclosporine treatment started 1 year after heart transplantation reduces graft coronary artery narrowing compared with conventional cyclosporine doses. METHODS: One year after heart transplantation, 30 patients were randomly assigned to receive low-dose cyclosporine A (whole-blood polyclonal cyclosporine target trough levels 200 to 400 micrograms/L; group A; n = 15) or usual cyclosporine dosage (target levels 400 to 600 micrograms/L; group B; n = 15). Proximal and distal diameters of the left anterior descending, circumflex, and right coronary arteries were measured by quantitative coronary angiography at baseline (1 year after transplantation) and at 2 and 3 years after transplantation. RESULTS: One major cardiac event occurred in group A (retransplantation) and two in group B (sudden deaths). Moderate to severe allograft rejection (International Society for Heart and Lung Transplantation score 3A or higher) occurred in seven patients in group A and five in group B during the study period. Mean biopsy sample rejection score during the same period was increased in group A compared with that in group B (1.44 +/- 0.63 versus 1.05 +/- 0.59; p < 0.05). New angiographic evidence of vascular disease was observed in four patients of group A and in one patient of group B. Proximal coronary artery diameter was slightly, although not significantly, reduced in both groups at follow-up angiography. Distal segments showed a significant diameter reduction, which was greater in group A than in group B (-9.7% +/- 1.1% and -5.2% +/- 1.3%, respectively; p < 0.05). CONCLUSIONS: Cyclosporine dose reduction started 1 year after heart transplantation is ineffective in reducing coronary luminal narrowing and may be associated with an increased prevalence of cardiac allograft vasculopathy, especially in the distal coronary tree. Low-dose cyclosporine treatment may slightly enhance the risk of allograft rejection. Further investigations are needed to evaluate the effects of cyclosporine dose reduction started at an earlier time after heart transplantation.

Adult↗

PubMed1995

Evidence for endothelin-1-mediated vasoconstriction in severe chronic heart failure.

Heart failure is commonly associated with high plasma concentrations of endothelin-1, a powerful vasoconstrictor produced by endothelium. The role of endogenously released endothelin-1 in the maintenance of vascular tone in chronic heart failure was assessed by acute administration of an endothelin receptor antagonist, bosentan. 24 patients with chronic heart failure received randomly and double blind two intravenous infusions of either placebo or bosentan (100 mg followed after 60 min by 200 mg). Systemic haemodynamics and plasma endothelin-1 and big-endothelin-1 concentrations were determined before and repeatedly during the 120 min observation period. Baseline endothelin-1 and big-endothelin-1 concentrations, which were above the normal range in all patients, correlated directly with the extent of pulmonary hypertension, with left and right heart filling pressures, and with pulmonary vascular resistance and inversely with cardiac index. Compared with placebo, bosentan reduced mean arterial pressure by 7.7% (95% CI 7.1-9.7), pulmonary artery pressure by 13.7% (10.5-16.9), right atrial pressure by 18.2% (12.0-24.4), and pulmonary artery wedged pressure by 8.6% (5.3-12.0); it increased cardiac index by 13.6% (9.1-18.2), decreased systemic vascular resistance by 16.5% (13.2-19.8), and decreased pulmonary vascular resistance by 33.2% (22.4-44.0). Heart rate did not change. Plasma endothelin-1 concentrations rose more than twofold from baseline in bosentan recipients while big-endothelin-1 concentrations were unchanged. These findings indicate that, in patients with chronic heart failure who have high circulatory endothelin-1 concentrations, this peptide contributes to maintenance of vascular tone. The acute haemodynamic effects of bosentan suggest that chronic endothelin antagonism could be beneficial in such patients.

Adult↗

PubMed1995

Reduced epicardial coronary vasodilator capacity in patients with left ventricular hypertrophy.

BACKGROUND: Enlargement of the epicardial coronary arteries occurs in left ventricular (LV) hypertrophy as an adaptation to the increased coronary blood flow. METHODS AND RESULTS: Vasodilator capacity of the epicardial coronary arteries was determined in 44 patients. The dose-response relation of intracoronary nitroglycerin was assessed in 14 patients (7 control subjects and 7 patients with aortic stenosis [study A]) using quantitative coronary angiography. In a second study (B), vasodilator capacity of the epicardial coronary arteries was determined in 15 control subjects and 15 patients with valvular heart disease. In study A, a curvilinear dose-response relation with maximal vasodilation after 90 micrograms intracoronary nitroglycerin was found in both control subjects and patients with aortic stenosis. Vasodilator capacity was reduced in those with aortic stenosis, although sensitivity to nitroglycerin was similar in both groups. In study B, coronary circumferential length at baseline was larger in those with LV hypertrophy (12.2 +/- 2.2 mm) than in control subjects (8.6 +/- 1.5 mm; P < .001); after 100 micrograms intracoronary nitroglycerin, it increased to 12.9 +/- 2.2 mm (6 +/- 5%) in those with LV hypertrophy and to 10.3 +/- 1.5 mm (21 +/- 8%; P < .001) in control subjects. An inverse relation between baseline circumferential length and its percent increase after nitroglycerin was found (r = -.71, P < .001). CONCLUSIONS: Vasodilator capacity of the epicardial coronary arteries is reduced in patients with LV hypertrophy, although sensitivity to nitroglycerin is normal. This may be due to a flow-mediated decrease in coronary vasomotor tone and/or the occurrence of vascular remodeling with an enlargement of the coronary arteries.

Adult↗

PubMed1995

Images in cardiovascular medicine. Idiopathic hypereosinophilic vasculitis.

Explore the source record for details and available documents.

Adult↗

PubMed1995

Stereoselective vascular effects of the (R)- and (S)-enantiomers of propranolol and atenolol.

All beta-adrenergic antagonists have an asymmetric carbon atom, and most commercially available beta-blockers consist of (R)- and (S)-enantiomers in a fixed 1:1-ratio. The drugs are believed to be contraindicated when peripheral vascular disease exists, presumably due to unopposed alpha-adrenergic vasoconstriction. However, little is known about direct vascular effects of beta-blockers or of stereoselective effects on peripheral arteries. Therefore, we investigated the effects on forearm blood flow (FBF) of brachial artery infusions of the (R)- and (S)- enantiomers of propranolol and atenolol (2, 10, and 50 micrograms/min each) and their inhibitory effects on isoprenaline (Iso)-induced vasodilatation by forearm venous occlusion plethysmography in 12 healthy subjects. Only (R)-propranolol caused an increase in FBF (+21%, p < 0.05), whereas (S)-propranolol and (R)- and (S)-atenolol had no direct effect on peripheral arteries. Vasodilatation induced by Iso was abolished by (S)-propranolol and reduced by (R)-propranolol (-56%, p < 0.05) and (S)-atenolol (-68%, p < 0.05), whereas (R)-atenolol had no effect. Our results indicate that the optically pure (R)- and (S)-enantiomers of propranolol and atenolol do not exert direct vasoconstrictive effects. Furthermore, our results confirm that predominantly (S)-enantiomers have beta-adrenoceptor blocking effects, but they also show that neither the non-beta-blocking (R)-enantiomer of propranolol nor the (S)-enantiomer of the beta 1-selective agent atenolol is completely devoid of blocking effects on vascular beta 2-adrenoceptors.

Adult↗

PubMed1995

Double-blind comparison of antihypertensive treatment with ramipril and piretanide, given alone or in combination.

In a double-blind, randomized, multicenter trial, we compared the efficacy and safety of the fixed combination of 5 mg ramipril and 6 mg piretanide and the respective component monotherapies in hypertensive patients [supine diastolic blood pressure (DBP) 100-114 mm Hg]. After a single-blind run-in period on placebo, 611 patients were randomized to ramipril (n = 209), piretanide (n = 201), or the combination therapy (n = 201). At randomization, the three groups had the same characteristics (51% men, age 55 +/- 10 years, BP 165 +/- 18/104 +/- 6 mm Hg). At 4 weeks, BP decreased more with combined therapy than with monotherapy. As compared with piretanide monotherapy, the gain in the antihypertensive effect in the supine position averaged 2.1 mm Hg [90% confidence interval (CI) -0.8-5.0 mm Hg; p = 0.07] systolic BP (SBP) and 1.9 mm Hg (CI 0.3-3.5 mm Hg, p = 0.02) DBP and, as compared with ramipril monotherapy, these differences were 4.2 mm Hg (CI 1.3-7.0 mm Hg, p = 0.008) and 2.0 mm Hg (CI 0.5-3.6 mm Hg, p = 0.009). The incidence of adverse events (AE) and the changes in biochemical measurements were similar in the three treatment groups with the exception of spontaneously reported polyuria and serum uric acid concentration. Polyuria was reported more frequently (p < 0.001) with piretanide therapy (n = 23) and combined therapy (n = 19) than with ramipril therapy (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Pseudoaneurysm following aortic homograft: clinical implications?

OBJECTIVE: To determine the prevalence of pseudoaneurysm formation after aortic (left ventricular outflow tract) homograft implantation and to evaluate predisposing factors. METHODS: Echocardiographic data were analysed in 30 patients for evidence of pseudoaneurysm formation after homograft implantation. Pseudoaneurysm was characterised as a perfused echo-free space between the homograft and the native aortic wall communicating with the left ventricular outflow tract. Clinical data were analysed for potential predisposing factors for pseudoaneurysm formation. RESULTS: Pseudoaneurysms were found in 22 of 30 patients. Mean age, length of follow up after surgery, aortic systolic pressure gradient (15 (SD 12) v 10 (4) mm Hg), aortic root diameter, and size of the homografts were comparable in patients with and without pseudoaneurysm. preoperative infection, operating techniques, and whether first or reoperation did not affect pseudoaneurysm formation. However, pseudoaneurysms were often localised at the site of an abscess or a paravalvular leak after eradicated prosthetic valve endocarditis. CONCLUSIONS: (1) Doppler echocardiography demonstrates that pseudoaneurysm formation is common after aortic homograft implantation. (2) A prospective study is needed to clarify the prognostic importance of pseudoaneurysms. (3) The high incidence of pseudoaneurysm formation may lead to an improvement of surgical technique (application of fibrin glue).

Adult↗