Biomedical subjects

Georg Ertl

Publications and source records attributed to Georg Ertl.

At least 19 recordsLinked to original sources

PubMed2004

Dobutamine induces ineffective work in regional ischaemic myocardium: an experimental strain rate imaging study.

In the present study, we sought to investigate the effects of differing inotropic conditions on regional myocardial function in ischaemic segments. In an experimental pig model ( n =11), the regional deformation parameters peak systolic strain rate [SR(SYS) (peak velocity of thickening)], systolic strain [epsilon(SYS) (systolic wall thickening)] and post-systolic strain [epsilon(PST) (ongoing wall thickening after end of systole)] were measured during normal perfusion and regional ischaemia of the posterior wall. These parameters were compared with global contractility [E(ES) (end-systolic elastance)] measured by a conductance catheter. Ischaemia was induced by an active coronary hypoperfusion in the circumflex coronary artery. Measurements were done at baseline, during dobutamine and during esmolol infusion. In normal perfused hearts, SR(SYS) (4.8+/-0.2 s(-1) at baseline) increased during dobutamine infusion, decreased during esmolol infusion and correlated significantly with global E(ES). In addition, epsilon(SYS) averaged 93+/-3% at baseline and there was almost no epsilon(PST) (4+/-1%) in normal myocardium. In ischaemic myocardium, SR(SYS) and epsilon(SYS) were significantly reduced compared with normal myocardium at baseline (SR(SYS)=2.8+/-0.3 s(-1), and epsilon(SYS)=43+/-6%; P <0.001 compared with normal perfused hearts), whereas global E(ES) was unchanged. In contrast, epsilon(PST) was significantly increased in regional ischaemic segments compared with the non-ischaemic myocardium (15+/-2%; P <0.001). During the dobutamine infusion, SR(SYS) remained unchanged. In contrast, epsilon(SYS) decreased (25+/-5%; P <0.001) and epsilon(PST) increased (25+/-4%; P <0.05) significantly during dobutamine infusion in ischaemic myocardium. In ischaemic segments, an inotropic stimulation with dobutamine resulted in a shift of strain from systole (epsilon(SYS)) to post-systole (epsilon(PST)). Thus dobutamine induced ineffective myocardial work in ischaemic segments.

Adrenergic beta-Antagonists↗

PubMed2003

Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion.

Chemokines released by the endothelium have proaggregatory properties on platelets. Fractalkine, a recently discovered membrane-bound chemokine with a transmembrane domain, is expressed in vascular injury; however, the effects of fractalkine on platelets have not yet been investigated. Blood was taken from healthy Wistar-Kyoto rats and the expression of the fractalkine receptor on platelets was demonstrated. The modulation of surface expression of P-selectin was assessed by flow cytometry. P-selectin expression was significantly enhanced by in vitro stimulation with recombinant rat fractalkine compared with baseline levels. Selectively inhibiting the function of recombinant fractalkine by an antagonizing antibody or the disruption of the G-protein-coupled intracellular signaling cascade of the fractalkine receptor by pertussis toxin (PTX) completely prevented fractalkine-mediated platelet activation. Preincubation with apyrase significantly attenuated the fractalkine-induced degranulation. In a flow chamber model of platelet adhesion, stimulation with fractalkine significantly enhanced platelet adhesion to collagen and fibrinogen. Similar to P-selectin expression, enhanced adhesion could be prevented by the antagonizing antibody or preincubation of platelets with PTX. Fractalkine, which is overexpressed in atherosclerosis and vascular injury, contributes to platelet activation and adhesion and hence is likely to play a pathophysiologically important role for increased thrombogenesis in vascular diseases.

Analysis of Variance↗

PubMed2003

Improvement of cardiac function during enzyme replacement therapy in patients with Fabry disease: a prospective strain rate imaging study.

BACKGROUND: Enzyme replacement therapy (ERT) has been shown to enhance microvascular endothelial globotriaosylceramide clearance in the hearts of patients with Fabry disease. Whether these results can be translated into an improvement of myocardial function has yet to be demonstrated. METHODS AND RESULTS: Sixteen patients with Fabry disease who were treated in an open-label study with 1.0 mg/kg body weight of recombinant alpha-Gal A (agalsidase beta, Fabrazyme) were followed up for 12 months. Myocardial function was quantified by ultrasonic strain rate imaging to assess radial and longitudinal myocardial deformation. End-diastolic thickness of the left ventricular posterior wall and myocardial mass (assessed by magnetic resonance imaging, n=10) was measured at baseline and after 12 months of ERT. Data were compared with 16 age-matched healthy controls. At baseline, both peak systolic strain rate and systolic strain were significantly reduced in the radial and longitudinal direction in patients compared with controls. Peak systolic strain rate increased significantly in the posterior wall (radial function) after one year of treatment (baseline, 2.8+/-0.2 s(-1); 12 months, 3.7+/-0.3 s(-1); P<0.05). In addition, end-systolic strain of the posterior wall increased significantly (baseline, 34+/-3%; 12 months, 45+/-4%; P<0.05). This enhancement in radial function was accompanied by an improvement in longitudinal function. End-diastolic thickness of the posterior wall decreased significantly after 12 months of treatment (baseline, 13.8+/-0.6 mm; 12 months, 11.8+/-0.6 mm; P<0.05). In parallel, myocardial mass decreased significantly from 201+/-18 to 180+/-21 g (P<0.05). CONCLUSIONS: These results suggest that ERT can decrease left ventricular hypertrophy and improve regional myocardial function.

Adult↗

PubMed2003

Chronic coronary artery stenosis induces impaired function of remote myocardium: MRI and spectroscopy study in rat.

Our purpose was to study morphological, functional, and metabolic changes induced by chronic ischemia in myocardium supplied by the stenotic vessel and in the remote area by MR techniques. A new technique of image fusion is proposed for analysis of coronary artery stenosis involving coronary MR angiography and spectroscopic imaging. Cine-MRI was performed 2 wk after induction of coronary stenosis. Global heart function and regional wall thickening were determined in 11 Wistar rats with stenosis and compared with 7 control rats. Two weeks after stenosis was induced, spin-labeling MRI for measurement of perfusion was performed in 14 isolated hearts. In eight isolated hearts with coronary stenosis, MR spectroscopy was performed, followed by angiography. 31P metabolite maps were fused with three-dimensional coronary angiograms. Induction of stenosis led to reduced segmental wall thickening (control: 75 +/- 9%, ischemic region: 9 +/- 3%, P < 0.05 vs. control) but also to impaired function of the remote region and lower cardiac output. Perfusion was reduced by 74.9 +/- 4.0% within ischemic segments compared with a septal control region. The phosphocreatine (PCr)/ATP ratio as a marker of ischemia was reduced in the region associated with stenosis (1.09 +/- 0.09) compared with remote (1.27 +/- 0.08) and control hearts (1.43 +/- 0.08; P < 0.05). The histological fraction of fibrosis within the ischemic region (12.8 +/- 1.4%) correlated to ATP signal reduction from remote to the ischemic region (r = 0.71, P < 0.05), but not to reduced wall thickening. Coronary narrowing caused declining function accompanied by diminished PCr/ATP, indicating impaired energy metabolism. Neither decline of function nor PCr signal decline correlated to fraction of fibrosis in histology. In contrast, reduction of ATP correlated to fibrosis and therefore to loss of viability. Impaired function within the ischemic region is associated with decreased PCr. Function of the remote region was affected as well. The fusion of PCr metabolite maps and the coronary angiogram may help to assess coronary morphology and resulting metabolic changes simultaneously.

Animals↗

PubMed2003

Addition of the selective aldosterone receptor antagonist eplerenone to ACE inhibition in heart failure: effect on endothelial dysfunction.

OBJECTIVES: To investigate the effects of adding the selective aldosterone receptor antagonist eplerenone to ACE inhibition on endothelium-dependent vasodilation in rats with chronic heart failure (CHF). BACKGROUND: Addition of the non-selective aldosterone antagonist spironolactone to ACE-inhibitors reduces mortality and morbidity in CHF and improves endothelial vasomotor dysfunction, but is associated with considerable side-effects. METHODS: Starting 10 days after extensive myocardial infarction (MI) or sham-operation, Wistar rats were treated either with placebo, the ACE inhibitor trandolapril (TR, 0.3 mg/kg body weight per day), the selective aldosterone receptor antagonist eplerenone (EPL, 100 mg/kg per day) or a combination of both for 9 weeks. RESULTS: Maximum acetylcholine-induced, nitric oxide-dependent relaxation was significantly attenuated in aortic rings from rats with CHF compared with sham-operated animals (R(max) 55% vs. 87%). EPL alone slightly and TR significantly improved NO-mediated relaxation (CHF-EPL 66%; CHF-TR: 78%), while treatment with both EPL and TR completely restored endothelium-dependent vasorelaxation (CHF-EPL-TR: 83%). Aortic superoxide formation was significantly increased in rats with CHF compared with sham-operated animals, but was normalised by treatment with EPL or TR-EPL. Expression of the endothelial nitric oxide synthase was decreased in CHF and normalised in all treatment groups. CONCLUSIONS: In experimental CHF, the selective aldosterone antagonist EPL reduced the increased vascular superoxide formation. Although a combination of TR and EPL normalised endothelium-dependent relaxation, ACE inhibition as a monotherapy was almost equally effective.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Susceptibility-sensitive magnetic resonance imaging detects human myocardium supplied by a stenotic coronary artery without a contrast agent.

OBJECTIVES: Evaluation of the severity of a coronary artery stenosis is of paramount importance for therapy. A relevant stenosis provokes post-stenotic microvascular dilation with capillary recruitment. This autoregulatory response was investigated in the present study by use of susceptibility-sensitive magnetic resonance imaging (MRI) without contrast agents. BACKGROUND: Functional alterations of the microvascular system may be studied noninvasively and without a contrast agent by susceptibility-sensitive MRI, which is based on the paramagnetic property of deoxyhemoglobin. This effect, also referred to as the "blood oxygenation level-dependent (BOLD) effect," is investigated by phase relaxation (T(2)*) measurements. METHODS: In patients (n = 16) with single-vessel coronary artery disease, no history of myocardial infarction, normal left ventricular function at rest, and a positive stress echocardiogram, the susceptibility-sensitive parameter T(2)* was assessed in the myocardium. RESULTS: In regions associated with the stenotic artery, T(2)* was significantly lower than in residual myocardium (p < 0.01). This difference in T(2)* increased after application of the vasodilator dipyridamole (p < 0.001). In patients being re-investigated after therapeutic interventions, the microvascular dilation was partly removed. CONCLUSIONS: For the first time, we could show that myocardial BOLD MRI detects post-stenotic capillary recruitment dependent on coronary artery stenosis.

Adult↗

PubMed2003

Increased myocardial oxygen consumption by TNF-alpha is mediated by a sphingosine signaling pathway.

The present study investigated the effect of tumor necrosis factor (TNF)-alpha on myocardial energy metabolism as estimated by myocardial oxygen consumption (MVo(2)). MVo(2) of electrically stimulated isolated trabeculae of right ventricular Wistar rat myocardium was analyzed using a Clark-type oxygen probe. After the initial data collection in the absence of TNF-alpha, measurements were repeated after TNF-alpha stimulation. In separate experiments, pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) or the ceramidase inhibitor n-oleoylethanolamine (NOE) was done to investigate NO/sphingosine-related effects. TNF-alpha impaired myocardial economy at increasing stimulation frequencies without altering baseline MVo(2). Incubation with TNF-alpha in the presence of l-NAME further impaired myocardial economy. NOE preincubation abrogated the TNF-alpha effect on myocardial economy. Moreover, the negative inotropic effect of TNF-alpha was observed in NOE-pretreated but not l-NAME-pretreated muscle fibers. Exogenous sphingosine mimicked the TNF-alpha effect on mechanics and energetics. We conclude that TNF-alpha impairs the economy of chemomechanical energy transduction primarily through a sphingosine-mediated pathway.

Amidohydrolases↗

PubMed2003

NCAM(CD56) and RUNX1(AML1) are up-regulated in human ischemic cardiomyopathy and a rat model of chronic cardiac ischemia.

Chronic myocardial ischemia is the leading cause of impaired myocardial contractility and heart failure. To identify differentially expressed genes in human ischemic cardiomyopathy (ICM), we constructed a subtracted cDNA library using specimens of ICM compared to normal human heart. Among 100 randomly sequenced clones, seven sequences represented recently identified candidate genes for differential expression in cardiac hypertrophy. A further clone without a known hypertrophy-association coded for the adhesion molecule NCAM(CD56). RNase protection assay, immunohistochemistry, and Western blotting revealed strong overexpression of NCAM(CD56) in all hearts with ICM (n = 14) compared to normal hearts (n = 8), whereas in congestive cardiomyopathy (CCM) (n = 8), hypertrophic obstructive cardiomyopathy (n = 2), myocarditis (n = 4), and sarcoidosis (n = 2), at most slight overexpression of NCAM(CD56) was observed. NCAM(CD56) overexpression abnormally involved the whole cell membrane and the cytoplasma of cardiomyocytes only inside and adjacent to ischemia-induced cardiac scars. Normal or hypertrophic fibers at a distance from ischemic scars were devoid of NCAM overexpression. Identical alterations were observed in an experimental rat ICM model, but not in normal nor in spontaneously hypertensive rat hearts. In search of NCAM(CD56)-related transcription factors we found RUNX1(AML1) up-regulation in ICM and detected RUNX1(AML1) binding within the NCAM(CD56) promoter by electromobility shift assay. We concluded that strong overexpression of NCAM(CD56) and RUNX1(AML1) is a constant and characteristic feature of cardiomyocytes within or adjacent to scars in ICM.

Adult↗

PubMed2003

Effect of testosterone on post-myocardial infarction remodeling and function.

BACKGROUND: Men and women are differently affected by coronary artery disease, suggesting an important role of sex steroids. Moreover, testosterone (T) treatment is increasingly used in elderly males. Therefore, we examined effects of chronic anabolic T administration on left ventricular (LV) remodeling after myocardial infarction (MI). METHODS: Adult male rats were treated with intramuscular placebo, testosterone undecanoate (T), or were orchiectomized. After 2 weeks, animals underwent sham-operation (sham) or left coronary artery ligation. Left ventricular remodeling and function was assessed by serial magnetic resonance imaging (MRI) at weeks 2 and 8 and hemodynamic investigation at week 8. RESULTS: In sham operated animals T administration increased serum T levels and led to cardiac hypertrophy, but not to an upregulation of ANP mRNA. The alpha/beta-MHC ratio was significantly higher after T treatment due to an increase in alpha-MHC. As a potential mechanism for this "physiologic" form of hypertrophy, IGF-1 mRNA expression was significantly increased in T treated animals. After coronary artery ligation, infarct size and mortality were similar among the groups. Left ventricular hypertrophy was enhanced by T treatment. However, in vivo LV end-diastolic pressure and wall stress were decreased by T, whereas other hemodynamic parameters (mean arterial pressure, cardiac output, etc.) remained unchanged. CONCLUSION: Chronic anabolic T treatment led to a specific "physiologic" pattern of myocardial hypertrophy with a significant increase in LV weight, but without differences in ANP and with an upregulation in alpha/beta-MHC, possibly mediated by IGF-1. Testosterone treatment had no detrimental effects following MI. Reduced wall stress and LVEDP may even improve long-term outcome.

Animals↗

PubMed2003

Sustained activation of nuclear factor kappa B and activator protein 1 in chronic heart failure.

OBJECTIVE: Innate immune response proteins such as inflammatory cytokines, inducible nitric oxide synthase, and toll like receptors are implicated in myocardial depression and left ventricular (LV) remodeling after myocardial infarction (MI). Although all these innate immunity proteins share the downstream activation of the transcription factor NF-kappaB (nuclear factor kappa B) and activator protein 1 (AP-1), the involvement of NF-kappaB and AP-1 in LV remodeling has not been demonstrated so far. METHODS AND RESULTS: Nuclear translocation of NF-kappaB and AP-1 was studied by electrophoretic mobility shift assays and ELISA 10 weeks after large experimental MI in rats, the chronic phase of LV remodeling. In the non-infarcted myocardium of MI rats, NF-kappaB and AP-1 were significantly activated (2.5-fold) as compared to sham-operated animals. Immunohistochemistry demonstrated NF-kappaB activation mainly in cardiac myocytes. Treatment with the ACE (angiotensin converting enzyme) inhibitor trandolapril led to a further 2-fold increase in the activation of NF-kappaB and AP-1 when compared to placebo-treated animals with the same MI size (P<0.001). Human failing hearts explanted at the time of heart transplantation exhibited marked nuclear translocation of NF-kappaB in cardiac myocytes when compared to control hearts. NF-kappaB as well as AP-1 were both significantly activated in congestive heart failure due to ischemic or dilated cardiomyopathy. CONCLUSION: In experimental and human heart failure, both NF-kappaB and AP-1 are chronically activated in cardiac myocytes. These findings suggest an important involvement of NF-kappaB and AP-1 in the cardiac remodeling process.

Adult↗

PubMed2003

CB(1) cannabinoid receptor antagonism promotes remodeling and cannabinoid treatment prevents endothelial dysfunction and hypotension in rats with myocardial infarction.

1. To study the long-term effects of altered cannabinoid receptor activity on myocardial and vascular function, Wistar rats were treated with the selective CB(1) antagonist AM-251 (0.5 mg kg(-1) d(-1)), the potent synthetic cannabinoid HU-210 (50 micro g kg(-1) d(-1)) or vehicle for 12 weeks after coronary artery ligation or sham operation. 2. AM-251 further reduced the pressure-generating capacity, shifted the pressure volume curve to the right (P<0.05) and increased the left-ventricular operating volume (AM-251: 930+/-40 micro l vs control: 820+/-40 micro l vs HU-210: 790+/-50 micro l; P<0.05) in rats with large myocardial infarction (MI). 3. Left-ventricular CB(1) immunoactivity in rats 12 weeks after large MI was unaltered as compared with noninfarcted hearts. 4. Cannabinoid receptor activation through HU-210, a cannabinoid that alters cardiovascular parameters via CB(1) receptors, increased the left-ventricular end-diastolic pressure (LVEDP, P<0.05). However, it prevented the drop in left-ventricular systolic pressure (HU-210: 142+/-5 mm Hg; P<0.05 vs control: 124+/-3 mm Hg; and P<0.001 vs AM-251: 114+/-3 mm Hg) and prevented endothelial dysfunction (ED) in aortic rings of rats with large MI (P<0.05). 5. Compared with AM-251, HU-210 prevented the decline in the maximal rate of rise of left-ventricular pressure and the maximum pressure-generating ability (P<0.05). In rats with small MI, HU-210 increased cardiac index (P<0.01) and lowered the total peripheral resistance (P<0.05). 6. The study shows that during the development of congestive heart failure post-large MI, cannabinoid treatment increases LVEDP and prevents hypotension and ED. Presumed CB(1) antagonism promotes remodeling despite unchanged myocardial CB(1) expression.

Animals↗

PubMed2003

Cytokine response after percutaneous coronary intervention in stable angina: effect of selective glycoprotein IIb/IIIa receptor antagonism.

BACKGROUND: It is unclear whether modulation of inflammatory markers by glycoprotein IIb/IIIa receptor inhibition after percutaneous coronary intervention (PCI) is caused by an interaction with the alpha(v)beta3 and alpha(M)beta2 receptor or it correlates with ischemic events during PCI. This study investigates the inflammatory profile after elective, nonacute PCI and whether and how administration of the glycoprotein IIb/IIIa receptor antagonist tirofiban modulates the postinterventional inflammatory myocardial response. METHODS: The time course of inflammatory parameters (C-reactive protein [CRP], interleukin-1 [IL-1], interleukin-6 [IL-6], and tumor necrosis factor alpha [TNF-alpha]) of patients receiving peri- and postinterventional placebo (n = 46) or tirofiban infusion (n = 50) was analyzed by use of enzyme-linked immuno assays. Samples were collected before and 30 minutes, 2.5 hours, 6.5 hours, 12 hours, 24 hours, and 48 hours after elective PCI. RESULTS: Among the inflammatory markers analyzed, TNF-alpha, IL-6, and CRP levels increased significantly. However, the latter markers followed individual time courses in patients given placebo and patients treated with tirofiban after PCI, compared with pre-PCI levels (P <.01), with no significant differences between the placebo and tirofiban-treated groups. However, by subgroup analysis, significant differences were revealed in TNF-alpha, IL-6, and CRP levels of patients who were troponin T-positive versus patients who were troponin T-negative after PCI. CONCLUSIONS: The administration of the selective glycoprotein IIb/IIIa receptor antagonist tirofiban has no direct impact on the inflammatory profile after elective PCI. Change of the inflammatory profile was only related to the presence or absence of postinterventional troponin.

Angina Pectoris↗

PubMed2003

Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle.

Cannabinoids elicit hypotension mainly via activated CB(1) receptors and show complex cardiovascular actions. Effects on human heart muscle have not been studied yet. Isolated human atrial heart muscle preparations were stimulated by electrical field with 1 Hz to contract isometrically at optimal length and were challenged with the endogenous cannabinoid arachidonyl ethanolamide (anandamide), the metabolically stable analogue R-methanandamide, and the potent synthetic CB(1) receptor agonist HU-210. Anandamide dose-dependently decreased systolic force (82.2 +/- 4.8% and 60.8 +/- 6.8% of maximal systolic force for 0.1 and 1 microM, respectively, P < 0.05). The selective CB(1) receptor antagonist AM-251 (1 microM, P < 0.05), but not the CB(2) receptor antagonist, AM-630 (1 microM), the nitric oxide synthase inhibitor N omega-nitro-l-arginine methyl ester (l-NAME) (500 microM), or the cyclooxygenase inhibitor indomethacin (100 microM), prevented the effect. Contrary to indomethacin, l-NAME alone showed negative inotropic effects (72.1 +/- 3.54%, P < 0.001). The R-methanandamide (1 microM: 50.4 +/- 3.5%, P < 0.001) and HU-210 (1 microM: 60.1 +/- 3.8%, P < 0.001) had similar negative inotropic effects. The existence of CB(1) receptors on heart muscle was verified using Western blot analysis and immunofluorescence staining. The conclusion is that anandamide, R-methanandamide, and HU-210 decrease contractile performance in human atrial muscle via CB(1) receptors.

Atrial Function↗

PubMed2002

Impact of hydroxymethylglutaryl coenzyme a reductase inhibition on left ventricular remodeling after myocardial infarction: an experimental serial cardiac magnetic resonance imaging study.

OBJECTIVES: We sought to assess the influence of long-term hydroxymethylglutaryl coenzyme A reductase inhibition (statin) therapy on left ventricular (LV) remodeling after myocardial infarction (MI) by use of serial cardiac magnetic resonance imaging (CMRI) studies. BACKGROUND: Statin therapy has been shown to reduce cardiac hypertrophy in vitro and in vivo, but the influence on LV post-MI remodeling is largely unknown. METHODS: The CMRI measurements were taken four and 12 weeks after left coronary artery ligation in a 7.05-tesla Biospec. The MI size, LV mass and volumes, cardiac output (CO), and ejection fraction were determined. Rats were treated for 12 weeks with either placebo (P), cerivastatin (C; 0.6 mg/kg body weight per day) as a dietary supplement, or cerivastatin plus the nitric oxide synthase (NOS) inhibitor N-methyl-L-arginine methyl ester (L-NAME, 76 mg/100 ml) and hydralazine (8 mg/100 ml) in drinking water (CLH) to assess the contribution of endogenous nitric oxide formation. RESULTS: Administration of cerivastatin attenuated hypertrophy after MI, and this effect was completely abolished by NOS inhibition (increase of LV mass from 4 to 12 weeks after MI: 235.3 +/- 33.7 mg with P vs. 59.8 +/- 20.5 mg with C vs. 239.5 +/- 16.0 mg with CLH; p < 0.05 vs. P and CLH). Left ventricular dilation was not changed (increase of end-diastolic volume from 4 to 12 weeks after MI: 108.7 +/- 28.8 with P vs. 126.6 +/- 20.5 with C vs. 173.7 +/- 25.1 with CLH; p = NS). The CO was higher in the cerivastatin group (12 weeks: 76.1 +/- 2.9 ml/min with P vs. 95.8 +/- 4.8 ml/min with C; p < 0.05). The effects of cerivastatin were abolished by NOS inhibition in the CLH group (CO at 12 weeks: 69.3 +/- 2.8 ml/min, p < 0.05 vs. C). CONCLUSIONS: Left ventricular remodeling was profoundly changed by statin treatment. Hypertrophy was attenuated, and global function was improved. These positive effects were abolished by NOS inhibition.

Animals↗

PubMed2002

Functional properties and [Ca(2+)](i) metabolism of creatine kinase--KO mice myocardium.

One major function of the creatine kinase system is to maintain energy demand of myofibrillar contraction processes. Loss of the CK-system led to adaptations in skeletal muscle. To analyze the impact on myocardial function contractile parameters and intracellular calcium metabolism of transgenic mice lacking mitochondrial CK (ScCKmit(-/-)) alone or both mitochondrial and cytoplasmic ScCK (CK(-/-)) were investigated compared to wild type at various workload conditions using isolated intact muscle fibers. Force development at baseline conditions, force-frequency relationship (60-600/min), and rapid frequency switch (60-600/min) were unaltered in myocardium of transgenic mice compared to wild type. Intracellular calcium metabolism revealed unchanged amplitude of the intracellular calcium transients (ICT), refilling of the sarcoplasmic reticulum (calcium reuptake, post-rest behavior) in the ScCKmit(-/-) and CK(-/-) mice. The results demonstrate the effectiveness of myocardial energy-recruiting compensatory mechanisms at baseline as well as under stress conditions in CK depleted myocardium of transgenic mice.

Adaptation, Physiological↗

PubMed2002

Time course of right ventricular remodeling in rats with experimental myocardial infarction.

Right ventricular (RV) weight increases dependent on time after myocardial infarction (MI) and on MI size. The sequential changes in RV volume and hemodynamics and their relations to left ventricular (LV) remodeling after MI are unknown. We therefore examined the time course of RV remodeling in rats with LV MI. MI was produced by left coronary artery ligation. Four, eight, and sixteen weeks later, LV and RV hemodynamic measurements were performed and pressure-volume curves were obtained. For serial measurement of RV volumes and performance, cine-MRI was performed 2 and 8 wk after MI. The ratios of beta-myosin heavy chain (MHC) to alpha-MHC and skeletal to cardiac alpha-actin were determined for the RV and LV after large MI or sham operation. RV weight increased in rats with MI, as did RV volume. RV pressure-volume curves were shifted toward larger volumes 16 wk after large MI. RV systolic pressure increased gradually over time; however, the gain in RV weight was always in excess of RV systolic pressure. The ratios of skeletal to cardiac alpha-actin and beta-MHC to alpha-MHC were increased after MI in both ventricles in a similar fashion. Because RV wall stress was not increased after infarction, mechanical factors may not conclusively explain hypertrophy, which maintained balanced loading conditions for the RV even after large LV infarction.

Animals↗

PubMed2002

Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial).

OBJECTIVES: The Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release. BACKGROUND: No data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel. METHODS: After bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h. RESULTS: A total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05). CONCLUSIONS: Troponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.

Angioplasty, Balloon, Coronary↗

PubMed2002

Trauma induced by nontraumatic coronary devices and its impact on vascular reactivity and morphology.

This study evaluated the impact of low-pressure balloon devices on coronary morphology and function. An active coronary perfusion catheter (2.5-mm balloon diameter, inflation with 1 bar for 30 min) was placed in the left anterior descending coronary artery of 12 German landrace pigs under general anesthesia. After 3 mo, coronary segments with balloon contact were compared with control segments taken from the right coronary artery as to histology, vascular reactivity, and expression of endothelial nitric oxide synthase. Thirty-three balloon treated segments were analyzed. Twenty of these segments (61%) showed neointima formation. In these segments endothelium-independent relaxation induced by sodium nitroprusside was preserved. However, endothelium-dependent bradykinin-induced relaxation was significantly attenuated compared with both the control segments and the balloon-treated segments without neointima formation. In >60% of the ballooned arterial segments examined, low-pressure balloon devices induced neointima formation accompanied by reduced endothelium-dependent relaxation. Thus interventions with so-called nontraumatic coronary devices can induce relevant vascular injury, with potential adverse clinical consequences.

Angioplasty, Balloon, Coronary↗