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Biomedical subjects

G Hasenfuss

Publications and source records attributed to G Hasenfuss.

At least 19 recordsLinked to original sources
PubMed2006

The influence of cardiovascular and antiinflammatory drugs on thiazide-induced hemodynamic and saluretic effects.

OBJECTIVE: Thiazide diuretics are known to induce a transient fall of the glomerular filtration rate (GFR), which, in turn, reduces tubular Na(+) load. This tubuloglomerular feedback (TGF) curtails the natriuretic effect of this class of diuretics. Cardiovascular and antiinflammatory therapeutics may interfere with TGF and thereby influence the effect of thiazides once co-administration is clinically indicated. METHODS: The effects on GFR and saluresis of hydrochlorothiazide (HCT; 25 mg) monotherapy were measured in healthy volunteers and compared to those obtained during co-administration of the thiazide and a second therapeutic. RESULTS: In the presence of the ACE inhibitor enalapril (10 mg), the transient fall in the GFR induced by HCT was almost abolished, and Na(+) excretion increased by approximately 30 % as compared to HCT monotherapy. K(+) excretion, however, remained unchanged. Similar results were obtained with the AT II type 1 receptor antagonist candesartan (8 mg): GFR remained stable, Na(+) excretion rose by 35 % and K(+) excretion was not changed. The effect of the Ca(2+) channel blocker amlodipine (5 mg) on GFR and HCT-induced Na(+) excretion equalled that obtained with the AT(1) blocker, yet with this treatment K(+) excretion rose in proportion to Na(+) excretion. The beta-blockers propranolol (80 mg) or bisoprolol (5 mg) reduced GFR but maintained TGF. HCT-induced Na(+) excretion was significantly reduced in the presence of a beta-blocker, whereas K(+) excretion was not changed. The inhibition of cyclooxygenase by diclofenac (50 mg) or rofecoxib (25 mg) significantly reduced the diuretic/natriuretic effect of HCT, but K(+) excretion was unchanged, and TGF was still demonstrable. CONCLUSION: In conclusion, AT(1) receptors, as well as the Ca(2+) channels in the smooth muscle cells of the afferent arteriole, are considered prerequisites for TGF function; their blockade increases the diuretic/natriuretic efficacy of thiazide diuretics. In contrast, beta-blockers and COX inhibitors do not interfere directly with TGF. These first dose effects reflect the primary response of the kidney to the drugs. They cannot, however, predict the benefits of long-term treatment.

Adrenergic beta-Antagonists↗
PubMed2006

[Efficacy of a cognitive-behavioral program with pharmacological support to achieve smoking cessation].

BACKGROUND AND OBJECTIVE: In Germany over 30% of the population are smokers. Only very few smokers succeed in giving up smoking, because of the addictive nature of nicotine use. The objective of the present study was to evaluate a smoking cessation program which was recently established at a tertiary care clinic. PATIENTS AND METHODS: The median age of the 275 participants was 45.5 years; 60.4% of participants were female. Participants had tobacco dependence of 5.1 (Fagerstrom scale). The cognitive-behavioral smoking cessation program implemented in this clinic consisted of 8 sessions. Pharmacological support was recommended. A standardized evaluation was carried out after 6 and 12 months. RESULTS: All 275 smokers took part in the program over a period of 21 months. At the end of the course, 72% of participants had become non-smokers, after 6 months 37.6% and after 12 months 27.1% had stopped smoking. Those who have not yet been evaluated 12 months after the end of the program demonstrated a point prevalence of 45.7% after 6 months. The cigarette consumption of participants who were smoking at the end of the course was reduced to less than half. 6 months later they smoked an average of 18.0 cigarettes /day; 12 months after ending the course, 19.0 /day were consumed (p<0,001). Costs of about 250 Euro per gained life year were approximated. CONCLUSION: It is possible to establish a smoking cessation program at a large clinic. The results correspond to international published experiences and confirm that such a program is efficacious and cost-effective.

Adolescent↗
PubMed2006

Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled trial.

In chronic obstructive pulmonary disease (COPD), the sympathetic nervous system, as well as the renin-angiotensin system, is activated with possible negative systemic effects on skeletal muscles. Angiotensin II type-1 receptor blockers inhibit the sympathetic and renin-angiotensin systems and might improve skeletal and respiratory muscle strength in patients in whom these systems are activated. The effects of the angiotensin receptor blocker irbesartan given over 4 months was evaluated in 60 patients with COPD and a forced expiratory volume in one second of <50% of the predicted value and without obvious cardiovascular disease that would necessitate the administration of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Irbesartan was well tolerated, but did not exert a significant effect on the primary end-point maximum inspiratory pressure. Spirometric results were not affected, but total lung capacity was reduced. Irbesartan led to a significant decrease in haematocrit (46.4+/-3.6 to 43.9+/-4.3% versus 47.5+/-2.4 to 48.7+/-3.0% with placebo). In conclusion, respiratory muscle strength in chronic obstructive pulmonary disease patients was not influenced by angiotensin II receptor blockade. However, the changes in haematocrit and total lung capacity following irbesartan raise the possibility that well-known cardiovascular drugs can produce unanticipated beneficial effects in chronic obstructive pulmonary disease patients.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Over-expression of FK506-binding protein FKBP12.6 alters excitation-contraction coupling in adult rabbit cardiomyocytes.

This study investigated the function of FK506-binding protein (FKBP12.6) using adenoviral-mediated gene transfer to over-express FKBP12.6 (Ad-FKBP12.6) in adult rabbit ventricular cardiomyocytes. Infection with a beta-galactosidase-expressing adenovirus (Ad-LacZ) was used as a control. Peak-systolic intracellular [Ca(2+)] (measured with Fura-2) was higher in the Ad-FKBP12.6 group compared to Ad-LacZ (1 Hz field stimulation at 37 degrees C). The amplitude of caffeine-induced Ca(2+) release was also greater, indicating a higher SR Ca(2+) content in the Ad-FKBP12.6 group. Voltage clamp experiments indicated that FKBP12.6 over-expression did not change L-type Ca(2+) current amplitude or Ca(2+) efflux rates via the Na(+)-Ca(2+) exchanger. Ca(2+) transients comparable to those after Ad-FKBP12.6 transfection could be obtained by enhancing SR Ca(2+) content of Ad-LacZ infected cells with periods of high frequency stimulation. Line-scan confocal microscopy (Fluo-3 fluorescence) of intact cardiomyocytes stimulated at 0.5 Hz (20-21 degrees C) revealed a higher degree of synchronicity of SR Ca(2+) release and fewer non-responsive Ca(2+) release sites in the Ad-FKBP12.6 group compared to control. Ca(2+) spark morphology was measured in beta-escin-permeabilized cardiomyocytes at a free [Ca(2+)](i) of 150 nm. The average values of the spark parameters (amplitude, duration, width and frequency) were reduced in the Ad-FKBP12.6 group. Increasing [Ca(2+)](i) to 400 nm caused coherent propagating Ca(2+) waves in the Ad-FKBP12.6 group but only limited Ca(2+) release events were recorded in the control group. These data indicate that FKBP12.6 over-expression enhances Ca(2+) transient amplitude predominately by increasing SR Ca(2+) content. Moreover, there is also evidence that FKBP12.6 can enhance the coupling between SR Ca(2+) release sites independently of SR content.

Adenoviridae↗
PubMed2004

[Acute cor pulmonale in pulmonary embolism. An important prognostic factor and a critical parameter for the choice of a therapeutic strategy].

Venous thromboembolism remains one of the most frequent and threatening acute cardiovascular syndromes. Its incidence has remained constant over the last several years, both in Europe and the United States, accounting for approximately 1.5 cases per 1000 inhabitants per year. Every year about 100 cases of venous thromboembolism per 100,000 inhabitants are admitted to the hospital, and 10% of these patients die during the hospital stay. Particularly alarming is the fact that in 50-70% of all patients who die from an acute pulmonary embolism the diagnosis is only made after death. These facts emphasize not only the relevance of the problem of "acute pulmonary embolism," but also the need for optimization of current diagnostic and therapeutic strategies. Rapid identification of acute cor pulmonale with echocardiography and cardiac biomarkers has recently proven to be especially helpful in this regard.

Algorithms↗
PubMed2004

[Differential therapy of heart failure. Which drug for which patient?].

The implementation of guidelines for medical therapy of heart failure may be problematic for the following reasons: 1. Elderly patients and women were underrepresented in large clinical trials which may limit their therapeutic impact in these patients. 2. Therapeutic decisions are influenced by co-morbidities like renal failure, obstructive airway disease (COLD, Asthma), stroke, and diabetes mellitus. We therefore discuss the differential therapy of heart failure in view of particular patient subgroups.

Adrenergic beta-Antagonists↗
PubMed2003

The functional effect of adenoviral Na+/Ca2+ exchanger overexpression in rabbit myocytes depends on the activity of the Na+/K+-ATPase.

OBJECTIVES: The functional consequences of Na+/Ca2+ exchanger (NCX) overexpression in heart failure have been controversially discussed. NCX function strongly depends on intracellular sodium which has been shown to be increased in heart failure. METHODS AND RESULTS: We investigated the Na+/K+-ATPase (NKA) inhibitor ouabain (0.5-16 micromol/l) in electrically stimulated, isotonically contracting adult rabbit cardiocytes overexpressing NCX after adenoviral gene transfer (Ad-NCX-GFP, 48 h culture time). Myocytes transfected with adenovirus encoding for green fluorescent protein (Ad-GFP) served as a control. Contractions were analyzed by video-edge detection. In the Ad-NCX-GFP group, the maximum inotropic response was significantly reduced by 50.7% (P<0.05). This was a result of an enhanced susceptibility to contracture after exposure to the drug (median concentration (25-75%): 4 (4-8) vs. 8 (6-16) micromol/l, P<0.05). When analyzing relaxation before contracture, the maximum relaxation velocity was reduced (0.15+/-0.04 vs. 0.27+/-0.04 microm/s, P<0.05) and the time from peak shortening to 90% of relaxation was increased (298+/-39 vs. 185+/-15 ms, P<0.05). No differences in systolic and diastolic parameters were observed with the Na+ channel modulator BDF9198 (1 micromol/l). CONCLUSIONS: Inhibition of NKA by ouabain induces a combined diastolic and systolic dysfunction in NCX overexpressing rabbit myocytes. This may be the consequence of cytoplasmic Ca2+ overload due to inhibition of forward mode or induction of reverse mode Na+/Ca2+ exchange. In end-stage failing human myocardium and during digitalis treatment this mechanism may be of major importance.

Adenoviridae↗
PubMed2003

Myosin light chain composition in non-failing donor and end-stage failing human ventricular myocardium.

The increased Ca(2+)-responsiveness in end-stage human heart failure cannot be attributed to contractile protein isoform changes, but rather is the complex resultant of changes in degree of phosphorylation of VLC-2 and TnI. Despite the decreased basal level of VLC-2 phosphorylation the response to VLC-2 dephosphorylation is enhanced in failing myocytes, which might result from differences in endogenous phosphorylation of thin and thick filament proteins between donor and failing hearts. Taken together decreased VLC-2 phosphorylation in end-stage human heart failure might represent a compensatory process leading to an improvement of myocardial contractility by opposing the detrimental effects of increased Ca(2+)-responsiveness of force and impaired Ca(2+)-handling on diastolic function.

Animals↗
PubMed2003

The effect of myosin light chain 2 dephosphorylation on Ca2+ -sensitivity of force is enhanced in failing human hearts.

OBJECTIVE: Phosphorylation of the myosin light chain 2 (MLC-2) isoform expressed as a percentage of total MLC-2 was decreased in failing (21.1+/-2.0%) compared to donor (31.9+/-4.8%) hearts. To assess the functional implications of this change, we compared the effects of MLC-2 dephosphorylation on force development in failing and non-failing (donor) human hearts. METHODS: Cooperative effects in isometric force and rate of force redevelopment (K(tr)) were studied in single Triton-skinned human cardiomyocytes at various [Ca(2+)] before and after protein phosphatase-1 (PP-1) incubation. RESULTS: Maximum force and K(tr) values did not differ between failing and donor hearts, but Ca(2+)-sensitivity of force (pCa(50)) was significantly higher in failing myocardium (Deltap Ca(50)=0.17). K(tr) decreased with decreasing [Ca(2+)], although this decrease was less in failing than in donor hearts. Incubation of the myocytes with PP-1 (0.5 U/ml; 60 min) decreased pCa(50) to a larger extent in failing (0.20 pCa units) than in donor cardiomyocytes (0.10 pCa units). A decrease in absolute K(tr) values was found after PP-1 in failing and donor myocytes, while the shape of the K(tr)-Ca(2+) relationships remained unaltered. CONCLUSIONS: Surprisingly, the contractile response to MLC-2 dephosphorylation is enhanced in failing hearts, despite the reduced level of basal MLC-2 phosphorylation. The enhanced response to MLC-2 dephosphorylation in failing myocytes might result from differences in basal phosphorylation of other thin and thick filament proteins between donor and failing hearts. Regulation of Ca(2+)-sensitivity via MLC-2 phosphorylation may be a potential compensatory mechanism to reverse the detrimental effects of increased Ca(2+)-sensitivity and impaired Ca(2+)-handling on diastolic function in human heart failure.

Adult↗
PubMed2002

Importance of sympathetic activation for the expression of Na+-Ca2+ exchanger in end-stage failing human myocardium.

AIMS: In end-stage heart failure, an alteration in the expression of the Na+-Ca2+ exchanger has been reported. Regulation of its expression is largely unknown. We sought to find out whether Na+-Ca2+ exchanger in human heart failure is regulated by sympathetic activation. In addition, since Na+-Ca2+-exchange is electrogenic, we conjectured whether increased expression of Na+-Ca2+ exchanger is associated with an increased incidence of cardiac arrhythmias. METHODS AND RESULTS: Twenty-three patients suffering from end-stage cardiac failure were examined in the hours preceding cardiac transplantation. Plasma levels of norepinephrine, epinephrine, atrial natriuretic peptide, renin activity, aldosterone, tumour necrosis factor (TNF)-alpha, and TNF-receptors were measured. All parameters were elevated relative to 21 healthy control subjects. As determined by immunoblots, protein levels of the Na+-Ca2+ exchanger were increased by 56% and protein levels of sarcoplasmic reticulum (SR) Ca2+-ATPase were decreased by 20% in left ventricles of the explanted failing hearts. A significant correlation between protein and neurohumoral levels was exclusively found for the Na+-Ca2+ exchanger with norepinephrine (r=0.64; P=0.01). Recent Holter ECGs revealed that patients with sustained or non-sustained ventricular tachycardia (more than three consecutive beats) had significantly higher Na+-Ca2+ exchanger protein and plasma norepinephrine levels than patients with a maximum of two consecutive beats (Na+-Ca2+ exchanger: 109+/-10 vs 83+/-7, n=11 each, P<0.05; norepinephrine: 1359+/-159 vs 656+/-88 pg. ml(-1), n=9 each, P<0.001). CONCLUSIONS: Sympathetic activation may enhance the expression of Na+-Ca2+ exchanger in end-stage heart failure. The data support the hypothesis that increased Na+-Ca2+-exchange could favour malignant ventricular arrhythmias.

Biological Transport↗
PubMed2002

Load-dependent induction of apoptosis in multicellular myocardial preparations.

Increased mechanical load has been proposed as an inductor of apoptosis, but it is unknown whether this can occur in the range of pre- and afterloads that prevail in the beating heart. We investigated apoptosis in cultured rabbit multicellular myocardial preparations over several days. Muscles contracted in absence of pre- and afterload (unloaded isotonic), in absence of preload but in presence of afterload (unloaded isometric), or in presence of both (loaded isometric). After up to 48 h of continuous contractions, apoptosis was assessed by TdT-mediated nick-end labeling (TUNEL) assay and DNA ladder analysis. In muscles that contracted loaded isometric, apoptosis was detected after 6-24 h. After 48 h, apoptosis was most prominent in this group, reflected by a high level of DNA ladder intensity (DLI; 27.8 +/- 11.5), whereas Bcl-xL (on RNA level) was significantly downregulated, and Fas remained unchanged. In unloaded isometric preparations, apoptosis was significantly less (6.9 +/- 5.9 DLI) and very similar to those contracting unloaded isotonic (6.1 +/- 5.1 DLI). We conclude that load-dependent apoptosis can occur at sarcomere lengths achievable in vivo and may mainly result from increased preload.

Animals↗
PubMed2001

Marked sympathetic activation in patients with chronic respiratory failure.

The autonomic nervous system may be disturbed in chronic respiratory failure. We tested the hypothesis that there is increased sympathetic activity in patients with chronic hypoxemia. Furthermore, we examined the effect of short-term oxygen on muscle sympathetic nerve activity (MSNA) in these patients. We performed microneurography of the peroneal nerve in 11 patients with hypoxemia due to chronic obstructive pulmonary disease (COPD, n = 6) or lung fibrosis (n = 5) and in 11 healthy subjects matched for age and sex. MSNA was measured during normal breathing in all subjects. In eight patients and in seven control subjects, MSNA was also measured during nasal oxygen (4 L/min). MSNA was higher in the patients with chronic respiratory failure compared with the healthy subjects during normal breathing (61 +/- 5 versus 34 +/- 2 bursts/min, mean +/- SEM; p = 0.0002, paired t test). During oxygen administration, MSNA decreased from 63 +/- 6 to 56 +/- 6 bursts/min in the patients (p = 0.0004, ANOVA); there was no change in sympathetic activity in the control subjects. For the first time, there is direct evidence of marked sympathetic activation in patients with chronic respiratory failure. This is partly explained by arterial chemoreflex activation and may play an important role in the pathogenesis of the disease.

Adult↗
PubMed2001

[Symptoms of primary endocardial fibroelastosis in a young adult].

HISTORY AND ADMISSION FINDINGS: A 21-year-old woman with known endocardial fibroelastosis diagnosed when aged 3 months was admitted because of progressive dyspnoea. The physical examination revealed symptoms of heart failure, with pulmonary rales, mild hepatomegaly, and tachyarrhythmia. INVESTIGATIONS: The electrocardiogram showed atrial fibrillation, complete right bundle branch block and right ventricular hypertrophy. Echocardiography indicated hypertrophy and dilatation of the right ventricle (61 mm) with tricuspid regurgitation and hypoplasia of the left ventricle. Heart catheterization confirmed pulmonary hypertension (60/46 mmHg) as well as dilatation and hypokinesia of the right ventricle. Right ventricular biopsy showed severe myocardial hypertrophy resulting from secondary pulmonary hypertension, while no evidence of myocarditis or idiopathic dilated cardiomyopathy was found. TREATMENT AND COURSE: Symptoms of heart failure improved under medical treatment with digitalis, angiotensin-converting enzyme inhibitor and diuretics. CONCLUSION: Primary endocardial fibroelastosis of the contracted type must be included in the differential diagnosis of heart failure occurring in young adults.

Adult↗
PubMed2001

Overexpression of FK506-binding protein FKBP12.6 in cardiomyocytes reduces ryanodine receptor-mediated Ca(2+) leak from the sarcoplasmic reticulum and increases contractility.

The FK506-binding protein FKBP12.6 is tightly associated with the cardiac sarcoplasmic reticulum (SR) Ca(2+)-release channel (ryanodine receptor type 2 [RyR2]), but the physiological function of FKBP12.6 is unclear. We used adenovirus (Ad)-mediated gene transfer to overexpress FKBP12.6 in adult rabbit cardiomyocytes. Western immunoblot and reverse transcriptase-polymerase chain reaction analysis revealed specific overexpression of FKBP12.6, with unchanged expression of endogenous FKBP12. FKBP12.6-transfected myocytes displayed a significantly higher (21%) fractional shortening (FS) at 48 hours after transfection compared with Ad-GFP-infected control cells (4.8+/-0.2% FS versus 4+/-0.2% FS, respectively; n=79 each; P:=0.001). SR-Ca(2+) uptake rates were monitored in beta-escin-permeabilized myocytes using Fura-2. Ad-FKBP12.6-infected cells showed a statistically significant higher rate of Ca(2+) uptake of 0.8+/-0.09 nmol/s(-)(1)/10(6) cells (n=8, P:<0.05) compared with 0.52+/-0.1 nmol/s(-)(1)/10(6) cells in sham-infected cells (n=8) at a [Ca(2+)] of 1 micromol/L. In the presence of 5 micromol/L ruthenium red to block Ca(2+) efflux via RyR2, SR-Ca(2+) uptake rates were not significantly different between groups. From these measurements, we calculate that SR-Ca(2+) leak through RyR2 is reduced by 53% in FKBP12.6-overexpressing cells. Caffeine-induced contractures were significantly larger in Ad-FKBP12.6-infected myocytes compared with Ad-GFP-infected control cells, indicating a higher SR-Ca(2+) load. Taken together, these data suggest that FKBP12.6 stabilizes the closed conformation state of RyR2. This may reduce diastolic SR-Ca(2+) leak and consequently increase SR-Ca(2+) release and myocyte shortening.

Adenoviridae↗
PubMed2001

Influence of mild hypothermia on myocardial contractility and circulatory function.

Myocardial contractility depends on temperature. We investigated the influence of mild hypothermia (37-31 degrees C) on isometric twitch force, sarcoplasmic reticulum (SR) Ca2+-content and intracellular Ca2+-transients in ventricular muscle strips from human and porcine myocardium, and on in vivo hemodynamic parameters in pigs. In vitro experiments: muscle strips from 5 nonfailing human and 8 pig hearts. Electrical stimulation (1 Hz), simultaneous recording of isometric force and rapid cooling contractures (RCCs) as an indicator of SR Ca2+-content, or intracellular Ca2+-transients (aequorin method). In vivo experiments: 8 pigs were monitored with Millar-Tip (left ventricle) and Swan-Ganz catheter (pulmonary artery). Hemodynamic parameters were assessed at baseline conditions (37 degrees C), and after stepwise cooling on cardiopulmonary bypass to 35, 33 and 31 degrees C. Hypothermia increased isometric twitch force significantly by 91 +/- 16 % in human and by 50 +/- 9 % in pig myocardium (31 vs. 37 degrees C; p < 0.05, respectively). RCCs or aequorin light emission did not change significantly. In anesthetized pigs, mild hypothermia resulted in an increase in hemodynamic parameters of myocardial contractility. While heart rate decreased from 111 +/- 3 to 73 +/- 1 min(-1), cardiac output increased from 2.4 +/- 0.1 to 3.1 +/- 0.31/min, and stroke volume increased from 21 +/- 1 to 41 +/- 3 ml. +dP/dtmax increased by 25 +/- 8% (37 vs. 31 degrees C; p < 0.05 for all values). Systemic and pulmonary vascular resistance did not change significantly during cooling. Mild hypothermia exerts significant positive inotropic effects in human and porcine myocardium without increasing intracellular Ca2+-transients or SR Ca2+-content. These effects translate into improved hemodynamic parameters of left ventricular function.

Aequorin↗
PubMed2001

Increased basal contractility of cardiomyocytes overexpressing protein kinase C epsilon and blunted positive inotropic response to endothelin-1.

OBJECTIVE: Protein kinase C (PKC) is thought to be involved in the regulation of the mammalian cardiac excitation-contraction coupling process by vasoactive peptides like endothelin-1 (ET-1). However, the demonstration of a causal link between activation of specific PKC isoforms and the increase in contractility mediated by ET-1 is still inferential. METHODS: By means of adenovirus-mediated gene transfer, we specifically overexpressed PKC epsilon in cultured adult rabbit ventricular myocytes (Ad-PKC epsilon). Myocyte shortening and [Ca2+]i transients under basal and ET-1-stimulated conditions were measured in Ad-PKC epsilon and Ad-LacZ control transfected cells. RESULTS: Infection with Ad-PKC epsilon resulted in a strong, virus dose-dependent increase in PKC epsilon protein levels, whereas protein expression of other PKC isoforms remained unchanged. Using a multiplicity of infection of 100 plaque-forming units/myocyte, basal and cofactor-dependent PKC epsilon kinase activity was increased 28- and 90-fold, respectively, when compared to control. Myocyte basal fractional shortening and [Ca2+]i transient amplitude were both increased by 21% (P < 0.05 each) in Ad-PKC epsilon transfected myocytes when compared to Ad-LacZ transfected control myocytes. The positive inotropic effect of ET-1 in control myocytes was markedly blunted in PKC epsilon-overexpressing myocytes. CONCLUSION: Specific overexpression of PKC epsilon in rabbit ventricular myocytes increases basal myocyte contractility and [Ca2+]i transients, and modifies their responsiveness to ET-1.

Adenoviridae↗
PubMed2001

Protective role of nebivolol in hydroxyl radical induced injury.

Increased oxidative stress has been postulated as one of the main mechanisms underlying stunned myocardium, and may play an important role in and during development of heart failure. Pharmacological interventions may attenuate or prevent detrimental effects of oxygen free radicals on the myocardium. Nebivolol has been shown to attenuate contractile dysfunction in hydroxyl radical mediated injury, but the mechanism(s) remain unknown. It was investigated whether nebivolol could partly attenuate the contractile dysfunction through a direct effect on the myofilaments. In demembranized muscles from explanted human hearts, nebivolol induced a slight desensitization of the myofilaments to calcium. Therefore, during the calcium overload that occurs during reperfusion after an ischemic event, the contractile dysfunction is less severe in the presence of nebivolol. We conclude that the protection of nebivolol in hydroxyl radical induced contractile dysfunction is mediated in part through a direct effect on the myofilaments, in addition to the previously shown preservation of sarcoplasmic reticulum function.

Actin Cytoskeleton↗