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Biomedical subjects

Georg Ertl

Publications and source records attributed to Georg Ertl.

At least 37 records · Page 2Linked to original sources
PubMed2005

Left ventricular remodeling after myocardial infarction in mice with targeted deletion of the NADPH oxidase subunit gp91PHOX.

BACKGROUND: Oxidative stress is involved in progression of left ventricular hypertrophy and heart failure. Since NADPH oxidases are a major source of reactive oxygen species in the heart, we studied left ventricular remodeling after myocardial infarction in mice with targeted deletion of the NADPH oxidase subunit gp91(phox). METHODS AND RESULTS: gp91(phox) knockout (KO) and wild-type (WT) animals underwent coronary artery ligation. Mortality was significant higher in the gp91(phox) KO mice. However, transthoracic echocardiography performed at days 1, 7, and 56 at mid-papillary levels revealed that progression of left ventricular remodeling was not influenced by the genotype. Moreover, systemic oxidative stress was not reduced in gp91(phox) KO mice as indicated by a significant increase in lipid peroxides potentially mediated by an increase of the NADPH subunit nox-1 in gp91(phox) KO mice. CONCLUSION: Targeted deletion of the NADPH subunit gp91(phox) does not affect left ventricular remodeling following myocardial infarction and does not decrease the production of oxidative stress. However, the final role of the different NADPH subunits in the heart under pathophysiologic conditions remains to be determined.

Animals↗
PubMed2005

Suppression of endothelial progenitor cells in human coronary artery disease by the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine.

OBJECTIVES: We tested the hypothesis that asymmetric dimethylarginine (ADMA) may be an endogenous inhibitor of endothelial progenitor cells (EPCs). BACKGROUND: Endothelial progenitor cells play a pivotal role in regeneration of injured endothelium, thereby limiting the formation of atherosclerotic lesions. Reduced numbers of EPCs may affect progression of coronary artery disease. Regulation of EPC mobilization and function is mediated in part by nitric oxide (NO). Endogenous inhibitors of NO synthases, such as ADMA, contribute to endothelial dysfunction and injury. METHODS: We used flow cytometry and in vitro assays to investigate the relationship between EPC number and function with ADMA plasma levels in patients with stable angina. RESULTS: The plasma concentration of ADMA was related to the severity of coronary artery disease and correlated inversely with the number of circulating CD34+/CD133+ progenitor cells (r = -0.69; p < 0.0001) and endothelial colony forming units (CFUs) (r = -0.75; p < 0.0001). Adjusting for all patient characteristics, we confirmed these findings in multivariate regression analyses. In vitro differentiation of EPCs was repressed by ADMA in a concentration-dependent manner. Compared with untreated cells, ADMA reduced EPC incorporation into endothelial tube-like structures to 27 +/- 11% (p < 0.001). Asymmetric dimethylarginine repressed the formation of CFUs from cultured peripheral blood mononuclear cells to 35 +/- 7% (p < 0.001). Asymmetric dimethylarginine decreased endothelial nitric oxide synthase activity in EPCs to 64 +/- 6% (p < 0.05) when compared with controls. Co-incubation with the hydroxymethyl glutaryl coenzyme A reductase inhibitor rosuvastatin abolished the detrimental effects of ADMA. CONCLUSIONS: Asymmetric dimethylarginine is an endogenous inhibitor of mobilization, differentiation, and function of EPCs. This contributes to the cardiovascular risk in patients with high ADMA levels and may explain low numbers and function of EPCs in patients with coronary artery disease.

Arginine↗
PubMed2005

The estrogen receptor-alpha agonist 16alpha-LE2 inhibits cardiac hypertrophy and improves hemodynamic function in estrogen-deficient spontaneously hypertensive rats.

OBJECTIVE: Cardiac mass increases with age and with declining estradiol serum levels in postmenopausal women. Although the non-selective estrogen receptor-alpha and -beta agonist 17beta-estradiol attenuates cardiac hypertrophy in animal models and in observational studies, it remains unknown whether activation of a specific estrogen receptor subtype (ERalpha or ERbeta) might give similar or divergent results. Therefore, we analyzed myocardial hypertrophy as well as cardiac function and gene expression in ovariectomized, spontaneously hypertensive rats (SHR) treated with the subtype-selective ERalpha agonist 16alpha-LE2 or 17beta-estradiol. METHODS AND RESULTS: Long-term administration of 16alpha-LE2 or 17beta-estradiol did not affect elevated blood pressure, but both agonists efficiently attenuated cardiac hypertrophy and increased cardiac output, left ventricular stroke volume, papillary muscle strip contractility, and cardiac alpha-myosin heavy chain expression. The observed effects of E2 and 16alpha-LE2 were abrogated by the ER antagonist ZM-182780. Improved left ventricular function upon 16alpha-LE2 treatment was also observed in cardiac MRI studies. In contrast to estradiol and 16alpha-LE2, tamoxifen inhibited cardiac hypertrophy but failed to increase alpha-myosin heavy chain expression and cardiac output. CONCLUSIONS: These results support the hypothesis that activation of ERalpha favorably affects cardiac hypertrophy, myocardial contractility, and gene expression in ovariectomized SHR. Further studies are required to determine whether activation ERbeta mediates redundant or divergent effects.

Animals↗
PubMed2005

Effects of ischemia on myocardial function during rapid left ventricular pacing.

INTRODUCTION: Coronary artery disease is often accompanied with deterioration in left ventricular function. Left ventricular pacing has been shown to improve cardiac function in chronic heart failure. However, data are limited about left ventricular pacing during acute ischemia. Therefore, we studied the effects of acute myocardial ischemia on myocardial function during left ventricular pacing. METHODS: In 8 anesthetized dogs, the left ventricle was rapidly paced (180 bpm) from a basolateral and apicoseptal site during normal perfusion and mild and severe ischemia of the left anterior descending coronary artery. Effects on myocardial function were measured at each level of ischemia before and during pacing. RESULTS: Significant differences (p < 0.05) between basolateral and apicoseptal pacing were found for segmental shortening (12.1+/-1.6 vs. 10.8+/-1.6%), and QRS duration (77.3+/-4.1 vs. 85.7+/-3.8 ms) at normal coronary perfusion. During mild ischemia, significant differences (p < 0.05) were seen for myocardial contractility dP/dt(max) (1277+/-197 vs. 1158+/-156 mm Hg/s), segmental shortening (10.3+/-1.9 vs. 8.1+/-1.7%), left ventricular end-systolic pressure (76.9+/-7.5 vs. 69.6+/-7.9 mm Hg), and QRS duration, and for myocardial contractility dP/dt(max) (1033+/-209 vs. 917+/-207 mm Hg/s) and left ventricular end-systolic pressure (69.2+/-13.5 vs. 62.2+/-15.0 mm Hg) during severe ischemia. There were no significant differences in coronary blood flow during pacing from both sites. CONCLUSIONS: During acute myocardial ischemia, depression of left ventricular function was lowest, when pacing from a left ventricular basolateral site. The effects of rapid left ventricular pacing were amplified by reduced coronary perfusion pressures. The choice of pacing site did not relevantly influence coronary blood flow.

Animals↗
PubMed2005

Pioglitazone reverses down-regulation of cardiac PPARgamma expression in Zucker diabetic fatty rats.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPARgamma in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPARgamma agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPARgamma, glucose transporter-4 and alpha-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPARgamma, glut-4, and alpha-MHC expression levels in diabetic ZDF rats. Cardiac [(18)F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPARgamma agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPARgamma expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin.

Animals↗
PubMed2005

Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction.

OBJECTIVES: The mechanisms underlying the clinical benefits of mineralocorticoid receptor antagonism in patients with left ventricular (LV) dysfunction and heart failure (CHF) after myocardial infarction (MI) are poorly understood. METHODS: We investigated whether long-term (9 weeks) aldosterone antagonism with eplerenone (100 mg/kg/day) provides additional benefit to angiotensin II type 1 (AT1) receptor inhibition with irbesartan (50 mg/kg/day) on cardiac remodeling after MI in rats. RESULTS: Eplerenone monotherapy, like AT1 receptor blockade, significantly reduced LV end-diastolic pressure (LVEDP), end-systolic volume (LVESV) and end-diastolic volume (LVEDV) compared to placebo. Improvement of LV dilation by aldosterone antagonism was associated with a significant reduction of increased AT1 receptor, angiotensin-converting enzyme (ACE) and endothelin-1 gene expression in the noninfarcted LV myocardium. Combination therapy with irbesartan led to a substantial further leftward shift of the LV pressure-volume curve and decrease in LVEDP, LVESV and LVEDV. Moreover, combination therapy significantly improved LV systolic and diastolic function and reversed LV alterations of alpha- and beta-myosin heavy-chain isoforms, ANF and SERCA2 ATPase expression more effectively than monotherapies. LV collagen type I and type III expression as well as interstitial fibrosis were substantially increased in placebo CHF rats, similarly decreased by eplerenone and irbesartan, and further reduced by eplerenone/irbesartan. However, no additive effects of eplerenone/irbesartan on myocardial AT1 receptor, ACE and endothelin-1 mRNAs were observed. CONCLUSIONS: Aldosterone receptor antagonism provides additional benefit to AT1 receptor blockade on LV function and remodeling associated with improvement of molecular alterations responsible for progressive contractile dysfunction post-MI.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Healing after myocardial infarction.

Wounding and healing are archaic principles, prerequisite for survival of any biologic material. However, strategies to cope with wounding may be quite different among organisms, species, or among various organs of one species. Today, myocardial infarction and the consequent loss of fully functional myocardium is the major aetiology for heart failure. Despite aggressive primary therapy, prognosis remains serious in patients with large infarction and severe left ventricular dysfunction. Thus, it would be highly desirable to influence healing of the cardiac wound to maintain structure and function of the heart. Herein, we review different, important factors of cardiac healing including reperfusion, mechanical stress, gender, and neurohormonal factors as well as specific factors essential for healing which may be genetic or acquired, emphasizing similarities and discrepancies between different organs and species.

Age Factors↗
PubMed2005

Increased mortality and aggravation of heart failure in estrogen receptor-beta knockout mice after myocardial infarction.

BACKGROUND: Lower mortality rates among women with chronic heart failure than among men may depend in part on the action of female sex hormones, especially estrogens. The biological effects of estrogens are mediated by 2 distinct estrogen receptor (ER) subtypes (ERalpha and ERbeta). The present study was undertaken to determine the role of ERbeta in the development of chronic heart failure after experimental myocardial infarction (MI). METHODS AND RESULTS: Female ERbeta null mice (BERKO(Chapel Hill)) and wild-type littermates (WT) were ovariectomized, given 17beta-estradiol, and subjected to chronic anterior MI (MI; BERKO n=31, WT n=30) or sham operation (sham; BERKO n=14, WT n=14). At 8 weeks after MI, both genotypes revealed left ventricular remodeling and impaired contractile function at similar average infarct size (BERKO-MI 32.9+/-5% versus WT-MI 33.0+/-4%); however, BERKO mice showed increased mortality (BERKO-MI 42% versus WT-MI 23%), increased body weight and fluid retention (P<0.01), higher ventricular pro-ANP expression (BERKO-MI 27.9-fold versus sham, WT-MI 5.2-fold versus sham; BERKO-MI versus WT-MI P<0.001), higher atrial natriuretic peptide serum levels, and increased phospholamban expression (P<0.05) compared with WT mice. CONCLUSIONS: Systemic deletion of ERbeta in female mice increases mortality, aggravates clinical and biochemical markers of heart failure, and contributes to impaired expression of Ca(2+)-handling proteins in chronic heart failure after MI. Further studies are required to delineate the relative importance of cardiac and vascular effects of ERbeta and the role of ERalpha in the development of heart failure.

Animals↗
PubMed2005

Rosuvastatin reduces platelet activation in heart failure: role of NO bioavailability.

OBJECTIVES: Endothelial dysfunction and platelet activation are part of the cardiovascular phenotype in congestive heart failure (CHF). We investigated whether 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibition would beneficially modulate vascular NO bioavailability and platelet activation in experimental CHF. METHODS AND RESULTS: Chronic myocardial infarction was induced by coronary ligation in male Wistar rats. Animals were either treated with placebo or the HMG-CoA reductase inhibitor rosuvastatin. After 10 weeks, hemodynamic assessment was performed and endothelial function was determined in organ bath studies. NO bioavailability was assessed by in vivo platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Markers of platelet degranulation (surface expression of P-selectin and glycoprotein 53) were determined as well as the amount of circulating platelet-leukocyte aggregates. Endothelium-dependent, acetylcholine-induced vasorelaxation was significantly impaired in aortic rings from CHF rats and improved by rosuvastatin. In parallel, in vivo VASP phosphorylation reflecting NO bioavailability was significantly attenuated in platelets from CHF rats and normalized by rosuvastatin. Platelet activation, which was increased in CHF, was reduced by treatment with rosuvastatin. CONCLUSIONS: HMG-CoA reductase inhibition improved endothelial function, increased systemic NO bioavailability and inhibited exaggerated platelet activation in CHF rats. These mechanisms may contribute to the beneficial effects of statin treatment in CHF.

Animals↗
PubMed2005

The variation of morphological and functional cardiac manifestation in Fabry disease: potential implications for the time course of the disease.

AIMS: The aim of this clinical cross-sectional study was to investigate the cardiac interrelation of morphological and functional abnormalities in patients with Fabry disease. METHODS AND RESULTS: Fifty-one patients (5-78 years) were compared with 25 controls (8-77 years). In all subjects, end-diastolic thickness of the left ventricle was measured by echocardiography and ultrasonic peak systolic strain rate (SR) was extracted to assess regional myocardial function. Magnetic resonance imaging was performed to assess late-enhancement for the detection of myocardial fibrosis in Fabry patients (n=39). In patients, women <20 years of age had no hypertrophy, no late-enhancement, and normal radial and longitudinal function (SR longitudinal=-1.7+/-0.5 s(-1); P=n.s. compared with controls). Ten women, >20 years of age, had no hypertrophy, no late-enhancement, normal radial and longitudinal function in the septal wall, but reduced longitudinal function in the lateral wall (SR=-1.4+/-0.5 s(-1)). All male patients without hypertrophy and no late-enhancement had normal radial function but reduced longitudinal function in both the septal and lateral walls (SR=-1.3+/-0.3 s(-1)). Patients with hypertrophy but without late-enhancement (n=13) had reduced radial and longitudinal function. Twelve patients displaying hypertrophy and late-enhancement had severely reduced radial and longitudinal function (SR=-1.1+/-0.5 s(-1)). Two of them with the worst impairment of regional function (SR=-0.8+/-0.6 s(-1)) died in the follow-up period. CONCLUSION: These results illustrate the variation of morphological changes and its functional consequences in Fabry cardiomyopathy.

Adolescent↗
PubMed2005

Myocardial contractile efficiency increases in proportion to a fetal enzyme shift in chronically infarcted rat hearts.

Changes in creatine kinase (CK) and lactate dehydrogenase (LDH) isoform expression occur in residual tissue after myocardial infarction. It is unknown how these changes correlate with cardiac remodeling, contractile performance and efficiency. Rats were subjected to left coronary artery ligation (MI) or sham operation (sham). Left ventricular end-diastolic pressure (EDP) was measured in vivo 8 weeks later. Hearts were isolated, buffer-perfused (Langendorff) at constant pressure and isovolumetric left ventricular (LV) pressure-volume (PV) curves were recorded. LV PV areas (PVA) were calculated and related to oxygen consumption. Biopsies of intact left ventricular tissue were taken for biochemical measurements. Correlations between in vivo EDP and biochemical parameters were found: Total CK activity (r = -.47, p = .022), CK isoenzyme percentage for BB (r = +.57, p = .004), MB (r = +.54, p = .006) and CK-mito (r = -.51, p = .012), total creatine content (r = -.61, p = .002) and the ratio of LDH5/LDH1 (r = .49, p = .016). Correlations were also detected for left ventricular volume and PVAs at in vivo EDP demonstrating that the extent of CK and LDH system alterations correlate with the extent of LV dilatation and mechanical energy requirements. The slope of the MVO(2)-PVA relation decreased significantly with increasing values of in vivo EDP (r = -.68, p = 0.0003) indicating increased contractile ef.ciency. Improved efficiency correlated with the increase in fetal CK isoenzyme expression. Thus, contractile efficiency increases parallel to the extent of left ventricular dilatation and dysfunction. CK and LDH system changes in residual intact myocardium also occur proportional to LV dysfunction.

Animals↗
PubMed2005

Creatine kinase knockout mice show left ventricular hypertrophy and dilatation, but unaltered remodeling post-myocardial infarction.

OBJECTIVE: Creatine kinase (CK) is responsible for the transport of high-energy phosphates in excitable tissue and is of central importance in myocardial energy homeostasis. Significant changes in myocardial energetics have been reported in mice lacking the various CK isoenzymes. Our hypothesis was that ablation of CK isoenzymes leads to cardiac hypertrophy, impaired function, and aggravation of left ventricular remodeling post-myocardial infarction. METHODS: CK-deficient mice (CK KO) were examined by cardiac magnetic resonance imaging (MRI) to determine left ventricular volumes, ejection fraction, and mass: ten wild-type (WT), 6 mitochondrial CK KO (Mito-CK-/-), 10 cytosolic CK KO (M-CK-/-), and 10 mice with combined KO (M/Mito-CK-/-). RESULTS: While ejection fraction was similar in all groups, there was significant LV dilatation with a approximately 30% increase in LV end-diastolic volumes in Mito-CK-/- and in M/Mito-CK-/-. Compared to WT, there was a striking 73% and 64% increase of LV mass in Mito-CK-/- and in M/Mito-CK-/- mice, respectively, but no significant increase of LV mass (+33%; p=n.s.) in M-CK-/-. Furthermore, significant re-expression of beta-MHC, a marker of myocardial hypertrophy, was found in all CK-deficient hearts. LV remodeling was investigated by MRI in hearts of 7 WT and 10 M/Mito-CK-/- mice 4 weeks postmyocardial infarction (MI). Four weeks post-LAD ligation (MI size approximately 32%), WT and M/Mito-CK-/- showed a similar degree of cardiac dysfunction, dilatation, and hypertrophy. CONCLUSION: Mito-CK-/- and M/Mito-CK-/- mice show significant LV dilatation and marked LV hypertrophy, but LV remodeling post-MI is not aggravated. CK ablation leads to substantial adaptational changes in heart.

Animals↗
PubMed2005

Repetitive postprandial hyperglycemia increases cardiac ischemia/reperfusion injury: prevention by the alpha-glucosidase inhibitor acarbose.

Protective effects of the alpha-glucosidase inhibitor acarbose have been reported for various diabetic complications. In the STOP-NIDDM study, even patients without overt diabetes, but with impaired glucose tolerance, had a reduction in cardiovascular events when treated with acarbose. Therefore, we investigated the effect of repetitive postprandial hyperglycemia on the cardiac ischemia/reperfusion injury in vivo. Mice were treated daily by single applications of placebo, sucrose (4 g/kg body weight), or sucrose + acarbose (10 mg/kg body weight) by gavage for 7 days. Acarbose treatment significantly reduced the sucrose-induced increase in plasma glucose concentration. Subsequently, animals underwent 30 min of ischemia by coronary artery ligation and 24 h of reperfusion in vivo. In the sucrose group, ischemia/reperfusion damage was significantly increased (infarct/area at risk, placebo vs. sucrose, 38.8+/-7.5% vs. 62.2+/-4.8%, P<0.05). This was prevented by acarbose treatment (infarct/area at risk 30.7+/-7.2%). While myocardial inflammation was similar in all groups, oxidative stress as indicated by a significant increase in lipid peroxides was enhanced in the sucrose, but not in the sucrose + acarbose group. In summary, repetitive postprandial hyperglycemia increases ischemia/reperfusion damage. This effect can be prevented by treatment with the alpha-glucosidase inhibitor acarbose.

Acarbose↗
PubMed2005

Impaired resting perfusion in viable myocardium distal to chronic coronary stenosis in rats.

Chronic coronary artery stenosis results in patchy necrosis in the dependent myocardium and impairs global and regional left ventricular (LV) function in rats in vivo. The aim of the present study was to compare regional myocardial blood flow (RMBF) and function (F) in poststenotic myocardium by using magnetic resonance imaging (MRI) and to compare MRI blood flow changes to histological alterations to assess whether RMBF in the viable poststenotic tissue remains normal. MRI was performed in 11 anesthetized Wistar rats with 2-wk stenosis of the left coronary artery. Postmortem, the extent of fibrotic tissue was quantified. Poststenotic RMBF was significantly reduced to 2.21 +/- 0.30 ml.g(-1).min(-1) compared with RMBF in the remote myocardium (4.05 +/- 0.50 ml.g(-1).min(-1)). A significant relationship between the poststenotic RMBF (%remote area) and the poststenotic F (%remote myocardium) was calculated (r = 0.61, P < 0.05). Assuming perfusion in scar tissue to be 32 +/- 5% of perfusion of remote myocardium, as measured in five additional rats, and that in remote myocardium to be 114 +/- 25% of that in normal myocardium, as assessed in five sham rats, the calculated perfusion in partially fibrotic tissue samples (35.7 +/- 5.2% of analyzed area) was 2.88 +/- 0.18 ml.g(-1).min(-1), whereas measured MRI perfusion was only 1.86 +/- 0.24 ml.g(-1).min(-1) (P < 0.05). These results indicate that resting perfusion in viable poststenotic myocardium is moderately reduced. Alterations in global and regional LV function are therefore secondary to both patchy fibrosis and reduced resting perfusion.

Animals↗
PubMed2005

23Na MRI combined with contrast-enhanced 1H MRI provides in vivo characterization of infarct healing.

Although (23)Na MRI has been shown to delineate acute myocardial infarction (MI), the time course of in vivo (23)Na MRI during infarct healing remains unknown. In this study (23)Na MRI was combined with contrast-enhanced (CE) (1)H MRI to noninvasively characterize infarct healing in vivo. Serial in vivo 3D (23)Na MRI and (1)H MRI were performed for up to 9 weeks postinfarction in 10 dogs. Radioactive microspheres were used to measure myocardial perfusion, and Hematoxylin-Eosin (H&E) and Masson's trichrome (MT) staining were used to assess interstitial cell infiltrate and collagen content. In vivo (23)Na MRI accurately delineated infarct size up to day 5 postinfarction in comparison with (1)H MRI (8.9% +/- 8.1% vs. 8.6% +/- 7.9% on day 1 postinfarction, P = NS; and 6.3% +/- 6.2% vs. 6.2% +/- 6.2% on days 4/5 postinfarction, P = NS). The in vivo (23)Na MRI signal intensity, expressed as the signal intensity ratio of infarcted tissue vs. noninfarcted tissue (MI/R) peaked on day 1 of infarction (2.04 +/- 0.23) but decreased significantly to 1.27 at 9 weeks postinfarction (P < 0.05) due to granulation tissue infiltrate and collagen deposition. To confirm the MI/R decrease during scar formation ex vivo, we performed (23)Na MRI in 12 rats on day 3 post-MI (N = 5) and after 6 weeks (N = 7). H&E and Picrosirius Red staining confirmed granulation tissue infiltrate on day 3 and scar formation after 6 weeks. MI/R decreased significantly from 1.91 +/- 0.45 on day 3 post-MI to 1.3 +/- 0.09 after 6 weeks. Thus, in vivo (23)Na MRI accurately delineates infarct size up to day 5 postinfarction. In vivo (23)Na MRI signal intensity decreases during infarct healing as a result of the underlying infarct healing process.

Analysis of Variance↗
PubMed2005

Noninvasive imaging of angiogenesis inhibition following nitric oxide synthase blockade in the ischemic rat heart in vivo.

OBJECTIVE: Nitric oxide synthase inhibition has anti-angiogenic properties. Magnetic resonance (MR) imaging was used to image the functional significance of these microvascular changes in a rat model of chronic ischemic myocardium in vivo. METHODS: The authors quantitatively determined myocardial perfusion and regional blood volume, left ventricular geometry, and function using MR imaging. Animals received either L-NAME + hydralazine or no treatment and were investigated 1 and 2 weeks after induction of coronary artery stenosis or sham operation at rest and during vasodilatation. Double-labeling immunohistochemistry was used to visualize angiogenesis and to compare with data obtained by MR imaging. RESULTS: Left ventricular mass and end-diastolic volumes were comparable in both groups 2 weeks after treatment. However, basal and maximum perfusion in animals with L-NAME + hydralazine treatment were reduced compared to animals not treated (p < .05). Basal regional blood volume remained constant in all groups, whereas maximum regional blood volume was reduced by L-NAME + hydralazine (p < .05). Endothelial cell proliferation, a direct marker for angiogenesis, was reduced by L-NAME + hydralazine (p < .01). CONCLUSIONS: MR imaging allows noninvasive quantification of functional microcirculation and angiogenesis in the rat heart in vivo. Nitric oxide synthase blockade results in changes in functional microcirculation and in an inhibition of angiogenesis in both ischemic and nonischemic myocardial tissue.

Animals↗
PubMed2005

Functional and metabolic recovery of the right ventricle during Bosentan therapy in idiopathic pulmonary arterial hypertension.

An impaired high-energy phosphate metabolism might play a critical role in the pathogenesis of right ventricular (RV) failure due to chronic pulmonary arterial hypertension (PAH). 31P-NMR spectroscopy is well established for measurements of high-energy phosphate metabolites in various left ventricular heart diseases, however, mainly for technical and sensitivity reasons, its successful transfer for measurements in the RV is currently missing. In the present study, the usefulness of this non-invasive approach is not only shown in RV failure due to PAH but also tested during subsequent therapy.

Antihypertensive Agents↗