Certainties and Uncertainties of Cardiac Magnetic Resonance Imaging in Athletes.

Prolonged and intensive exercise induces remodeling of all four cardiac chambers, a physiological process which is coined as the "athlete's heart". This cardiac adaptation, however, shows overlapping features with non-ischemic cardiomyopathies, such as dilated, arrhythmogenic and hypertrophic cardiomyopathy, also associated with athlete's sudden cardiac death. Cardiac magnetic resonance (CMR) is a well-suited, highly reproducible imaging modality that can help differentiate athlete's heart from cardiomyopathy. CMR allows accurate characterization of the morphology and function of cardiac chambers, providing full coverage of the ventricles. Moreover, it permits an in-depth understanding of the myocardial changes through specific techniques such as mapping or late gadolinium enhancement. In this narrative review, we will focus on the certainties and uncertainties of the role of CMR in sports cardiology. The main aspects of physiological adaptation due to regular and intensive sports activity and the application of CMR in highly trained athletes will be summarized.

Is cardiac involvement prevalent in highly trained athletes after SARS-CoV-2 infection? A cardiac magnetic resonance study using sex-matched and age-matched controls.

OBJECTIVES: To investigate the cardiovascular consequences of SARS-CoV-2 infection in highly trained, otherwise healthy athletes using cardiac magnetic resonance (CMR) imaging and to compare our results with sex-matched and age-matched athletes and less active controls. METHODS: SARS-CoV-2 infection was diagnosed by PCR on swab tests or serum immunoglobulin G antibody tests prior to a comprehensive CMR examination. The CMR protocol contained sequences to assess structural, functional and tissue-specific data. RESULTS: One hundred forty-seven athletes (94 male, median 23, IQR 20-28 years) after SARS-CoV-2 infection were included. Overall, 4.7% (n=7) of the athletes had alterations in their CMR as follows: late gadolinium enhancement (LGE) showing a non-ischaemic pattern with or without T2 elevation (n=3), slightly elevated native T1 values with or without elevated T2 values without pathological LGE (n=3) and pericardial involvement (n=1). Only two (1.4%) athletes presented with definite signs of myocarditis. We found pronounced sport adaptation in both athletes after SARS-CoV-2 infection and athlete controls. There was no difference between CMR parameters, including native T1 and T2 mapping, between athletes after SARS-CoV-2 infection and the matched athletic groups. Comparing athletes with different symptom severities showed that athletes with moderate symptoms had slightly greater T1 values than athletes with asymptomatic and mildly symptomatic infections (p<0.05). However, T1 mapping values remained below the cut-off point for most patients. CONCLUSION: Among 147 highly trained athletes after SARS-CoV-2 infection, cardiac involvement on CMR showed a modest frequency (4.7%), with definite signs of myocarditis present in only 1.4%. Comparing athletes after SARS-CoV-2 infection and healthy sex-matched and age-matched athletes showed no difference between CMR parameters, including native T1 and T2 values.

The impact of Wilson disease on myocardial tissue and function: a cardiovascular magnetic resonance study.

BACKGROUND: Systemic effects of altered serum copper processing in Wilson Disease (WD) might induce myocardial copper deposition and consequently myocardial dysfunction and structural remodeling. This study sought to investigate the prevalence, manifestation and predictors of myocardial tissue abnormalities in WD patients. METHODS: We prospectively enrolled WD patients and an age-matched group of healthy individuals. We applied cardiovascular magnetic resonance (CMR) to analyze myocardial function, strain, and tissue characteristics. A subgroup analysis of WD patients with predominant neurological (WD-neuro+) or hepatic manifestation only (WD-neuro-) was performed. RESULTS: Seventy-six patients (37 years (27-49), 47% women) with known WD and 76 age-matched healthy control subjects were studied. The prevalence of atrial fibrillation in WD patients was 5% and the prevalence of symptomatic heart failure was 2.6%. Compared to healthy controls, patients with WD had a reduced left ventricular global circumferential strain (LV-GCS), and also showed abnormalities consistent with global and regional myocardial fibrosis. WD-neuro+ patients presented with more severe structural remodeling and functional impairment when compared to WD-neuro- patients. CONCLUSIONS: In a large cohort, WD was not linked to a distinct cardiac phenotype except CMR indexes of myocardial fibrosis. More research is warranted to assess the prognostic implications of these findings. TRIAL REGISTRATION: This trial is registered at the local institutional ethics committee (S-188/2018).

Presence of contractile impairment appears crucial for structural remodeling in idiopathic left bundle-branch block.

BACKGROUND: To differentiate effects of ventricular asynchrony from an underlying hypocontractile cardiomyopathy this study aimed to enhance the understanding of functional impairment and structural remodeling in idiopathic left bundle-branch block (LBBB). We hypothesize, that functional asynchrony with septal flash volume effects alone might not entirely explain the degree of functional impairment. Hence, we suggest the presence of a superimposed contractile cardiomyopathy. METHODS: In this retrospective study, 53 patients with idiopathic LBBB were identified and matched to controls with and without cardiovascular risk factors. Cardiovascular magnetic resonance (CMR) was used to evaluate cardiac function, volumes and myocardial fibrosis using native T1 mapping and late gadolinium enhancement (LGE). Septal flash volume was assessed by CMR volumetric measurements and allowed to stratify patients with systolic dysfunction solely due to isolated ventricular asynchrony or superimposed contractile impairment. RESULTS: Reduced systolic LV-function, increased LV-volumes and septal myocardial fibrosis were found in patients with idiopathic LBBB compared to healthy controls. LV-volumes increased and systolic LV-function declined with prolonged QRS duration. Fibrosis was typically located at the right ventricular insertion points. Subgroups with superimposed contractile impairment appeared with pronounced LV dilation and increased fibrotic remodeling compared to individuals with isolated ventricular asynchrony. CONCLUSIONS: The presence of superimposed contractile impairment in idiopathic LBBB is crucial to identify patients with enhanced structural remodeling. This finding suggests an underlying cardiomyopathy. Future studies are needed to assess a possible prognostic impact of this entity and the development of heart failure. TRIAL REGISTRATION: This study was retrospectively registered.

Echocardiographic calcification score in patients with low/intermediate cardiovascular risk.

PURPOSE: Calcification of aortic valve and mitral annulus is associated with cardiovascular risk factors, morbidity and mortality. Assessment of cardiac calcification with echocardiography is feasible, however, only few structured scoring systems have been established so far with limited prognostic data. This study aimed to evaluate an echocardiographic calcification score (echo-CCS) in patients with low/intermediate cardiovascular risk. METHODS: Digitally stored echocardiography studies of 151 patients (median age 64, 49.7% male) from February 2008 to December 2009 were retrospectively reviewed for calcifications of the aortic valve, aortic root, mitral annulus, papillary muscles and ventricular septum. A calcification score ranging from 0 to 5 was assigned to every patient and its relation to computed tomography calcium score, coronary stenosis and ESC SCORE was assessed. Follow-up data were collected from 149 patients (98.7%) with a median of 6.2 years. Logistic regression and Kaplan-Meier analysis were performed to assess the association of the echo-CCS with significant coronary artery disease (≥ 50% stenosis) and risk for cardiac events and all-cause mortality. RESULTS: An association of the echo-CCS with the ESC SCORE (ρ = 0.5; p < 0.001) and a good correlation of the echo-CCS with the Agatston score (ρ = 0.73; p < 0.001) can be observed. Univariate regressions revealed that echo-CCS is a significant predictor for cardiac events [OR = 5.1 (CI: 1.7-15.0); p = 0.003], coronary intervention [OR = 2.8 (CI: 1.3-5.7); p = 0.006], hospitalisation for cardiac symptoms [OR = 2.0 (CI: 1.2-3.4); p = 0.007], all-cause mortality [OR = 2.6 (CI: 1.3-5.5); p = 0.01] and significant CAD [OR = 3.2 (CI: 1.9-5.4); p < 0.001]. CONCLUSIONS: We demonstrated the prevalence of an easily obtainable, radiation-free calcification score in patients with low/intermediate cardiovascular risk. The strong association with CT-calcium scoring may evoke its potential as an alternative method in CV risk assessment.

Cardiovascular magnetic resonance of cardiac morphology and function: impact of different strategies of contour drawing and indexing.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is the gold standard for the quantitative assessment of cardiac volumes, mass and function. There are, however, various strategies for establishing endocardial borders, the cardiac phase used for measurements and the body dimensions used for indexing these results. The aim of the study was to assess the impact of different strategies on reference values. METHODS AND RESULTS: 362 healthy volunteers (190 men, mean age 51 ± 13 years) underwent a standard CMR protocol. Left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes and LV mass (LV-M) were measured at end systole and end diastole in SSFP sequences using two methods, one of which included papillary muscles and trabecular tissue in the LV-M ("include" approach), while the other excluded this tissue ("exclude" approach). There was a strong correlation between the results for LV volumes and LV ejection fraction (LV-EF) between the "include" and the "exclude" approach, while the mean values were different: LV-EDV: 149.7 ± 32.5 ml vs 160.5 ± 35.0 ml, p < 0.0001; LV-ESV: 48.7 ± 14.5 ml vs 56.4 ± 16.7 ml, p < 0.0001; LV-EF: 67.7 ± 5.4% vs 65.1 ± 5.6%, p < 0.0001. When comparing end-systolic with end-diastolic data, values for LV-M were significantly higher in end systole irrespective of whether papillary muscles and trabecular tissues were included or not. Furthermore, LV-M missed overweight-induced LV hypertrophy when indexed to body surface area (BSA) instead of height. CONCLUSION: Quantitative assessment of LV volumes and mass with inclusion of papillary muscles and trabeculae to myocardial mass resulted in significantly different values, while indexing to BSA and not height may miss LV hypertrophy in terms of overweight.

Systolic pulmonary artery pressure assessed during routine exercise Doppler echocardiography: insights of a real-world setting in patients with elevated pulmonary pressures.

Pulmonary hypertension is a marker of disease severity. Exercise Doppler echocardiography (EDE) has proven to be feasible and reliable to assess pulmonary pressure. Increase in systolic pulmonary artery pressure (sPAP) has diagnostic and prognostic value in controlled studies. However, its value when assessed during routine examination in patients with cardiopulmonary diseases and resting sPAP > 35 mmHg is not clearly defined. Clinical documentation and offline reevaluation of digitally stored EDE examinations of patients with appropriate clinical indications for EDE were analyzed. N = 278 patients with sPAP at rest > 35 mmHg met inclusion criteria. One patient was lost to follow-up. Mean age of patients was 72 ± 10 years, 178 (64%) of the study population were men. There were no relevant differences among survivors and non-survivors concerning comorbidities. Exercise performance (3.6 ± 1.2 vs. 4.9 ± 1.4 MET, p < 0.001) was lower, whereas sPAP during exercise was higher (67.3 ± 14.7 vs. 62.1 ± 13.2 mmHg, p = 0.027) in non-survivors. Univariate predictors of all-cause mortality were NYHA functional class III (HR = 2.56, p < 0.001), ≥ 2-vessels coronary artery disease (CAD) (HR = 1.93, p = 0.04), left atrial diameter > 45 mm (HR = 2.58, p < 0.001), rest sPAP > 42 mmHg (HR = 1.94, p = 0.010) and ΔsPAP increase ≥ 0.23 mmHg/Watt (HF = 1.92, p = 0.010). After multivariate analysis, NYHA functional class III (HR = 2.35, p < 0.001), LA diameter (HR = 2.28, p = 0.003) and sPAP increase ≥ 0.23 mmHg/Watt (HF = 2.19, p = 0.002) remained significant predictors of mortality, whereas a double product (HR = 0.42, p = 0.005) was associated with better prognosis. sPAP assessment during routine EDE provides relevant prognostic information comparable to findings in studies in selected populations. A higher sPAP increase at lower exercise performance shows significant association with increased of mortality.

Unidimensional Longitudinal Strain: A Simple Approach for the Assessment of Longitudinal Myocardial Deformation by Echocardiography.

BACKGROUND: Impaired left ventricular (LV) longitudinal function (LF) is a known predictor of cardiac events in patients with heart failure, but two-dimensional strain imaging, the reference method to measure myocardial deformation, is not always feasible or available. Therefore, reliable and reproducible alternatives are needed. The aim of the present study was to evaluate unidimensional longitudinal strain (ULS) as a simple echocardiographic parameter for the assessment of LV LF. METHODS: Two hundred two patients with dilated cardiomyopathy who had their first presentation in the authors' cardiology department, as well as the same number of age- and gender-matched control subjects, were prospectively included in this study. ULS was compared with global longitudinal strain (GLS), the current gold standard for LV LF assessment by echocardiography. Uni- and multivariate Cox regression analyses were conducted to evaluate the prognostic value of ULS. RESULTS: LV LF was higher in the control group compared with patients: GLS -19.5 ± 1.7% versus -12.6 ± 4.8% and ULS -16.3 ± 1.5% versus -10.2 ± 3.9% (P < .001 for each). Correlation between ULS and GLS was excellent (r = 0.94), while Bland-Altman plots revealed lower values for ULS (bias -2.76%, limits of agreement ±3.31%). During a mean follow-up time of 39 months, the combined end point of cardiovascular death or hospitalization for acute cardiac decompensation was reached by 28 patients (13.9%). GLS (hazard ratio, 1.21; 95% CI, 1.10-1.34; P < .001) and ULS (hazard ratio, 1.24; 95% CI, 1.12-1.39; P < .001) had comparable prognostic impact on patient outcomes. CONCLUSIONS: ULS might be an alternative echocardiographic method for the assessment of LV LF, with similar diagnostic and prognostic value compared with GLS.

Association between VEGF Gene Polymorphisms and In-Stent Restenosis after Coronary Intervention Treated with Bare Metal Stent.

Background. In-stent restenosis (ISR) is the gradual narrowing of the vessel lumen after coronary stent implantation due to the increase in vascular smooth muscle cell proliferation. Vascular endothelial growth factor (VEGF) protein plays an important role in this process. Our aim was to analyze the association of single nucleotide polymorphisms of the VEGF gene (rs2010963 and rs6999447) with the occurrence of ISR after coronary artery bare metal stent (BMS) implantation. Methods. 205 patients with a history of BMS implantation and a repeated coronarography were prospectively enrolled. Patients were assigned to diffuse restenosis group (n = 105) and control group (n = 100) and VEGF genotypes were determined. Results. Diffuse ISR was significantly more frequently observed in patients with homozygous normal genotype of rs2010963 polymorphism, and this polymorphism was independently associated with diffuse ISR. Conclusions. RS2010963 is associated with higher incidence of development of diffuse coronary ISR in patients treated with BMS implantation.

High rate of in-stent restenosis after coronary intervention in carriers of the mutant mannose-binding lectin allele.

BACKGROUND: In-stent restenosis occurs in 10-30% of patients following bare metal stent (BMS) implantation and has various risk factors. Mannose-binding lectin (MBL) is known to have effect on the progression of atherosclerosis. Single nucleotide polymorphisms (SNP) of the MBL2 gene intron 1 (codon 52, 54, 57) are known to modulate the bioavailability of the MBL protein. Our aim was to identify the association of these polymorphisms of the MBL gene in the occurrence of in-stent restenosis after coronary artery bare metal stent implantation. METHODS: In a non-randomized prospective study venous blood samples were collected after recoronarography from 225 patients with prior BMS implantation. Patients were assigned to diffuse restenosis group and control group based on the result of the coronarography. MBL genotypes were determined using quantitative real-time PCR. Proportion of different genotypes was compared and adjusted with traditional risk factors using multivariate logistic regression. RESULTS: Average follow-up time was 1.0 (+ - 1.4) year in the diffuse restenosis group (N = 117) and 2.7 (+ - 2.5) years in the control group (N = 108). The age, gender distribution and risk status was not different between study groups. Proportion of the MBL variant genotype was 26.8% (29 vs. 79 normal homozygous) in the control group and 39.3% (46 vs. 71 normal homozygous) in the restenosis group (p = 0.04). In multivariate analysis the mutant allele was an independent risk factor (OR = 1.96, p = 0.03) of in-stent restenosis. CONCLUSIONS: MBL polymorphisms are associated with higher incidence of development of coronary in-stent restenosis. The attenuated protein function in the mutant allelic genotype may represent the underlying mechanism.

S100A6 Regulates Endothelial Cell Cycle Progression by Attenuating Antiproliferative Signal Transducers and Activators of Transcription 1 Signaling.

OBJECTIVE: S100A6, a member of the S100 protein family, has been described as relevant for cell cycle entry and progression in endothelial cells. The molecular mechanism conferring S100A6's proliferative actions, however, remained elusive. APPROACH AND RESULTS: Originating from the clinically relevant observation of enhanced S100A6 protein expression in proliferating endothelial cells in remodeling coronary and carotid arteries, our study unveiled S100A6 as a suppressor of antiproliferative signal transducers and activators of transcription 1 signaling. Discovery of the molecular liaison was enabled by combining gene expression time series analysis with bioinformatic pathway modeling in S100A6-silenced human endothelial cells stimulated with vascular endothelial growth factor A. This unbiased approach led to successful identification and experimental validation of interferon-inducible transmembrane protein 1 and protein inhibitors of activated signal transducers and activators of transcription as key components of the link between S100A6 and signal transducers and activators of transcription 1. CONCLUSIONS: Given the important role of coordinated endothelial cell cycle activity for integrity and reconstitution of the inner lining of arterial blood vessels in health and disease, signal transducers and activators of transcription 1 suppression by S100A6 may represent a promising therapeutic target to facilitate reendothelialization in damaged vessels.

Effects of soluble guanylate cyclase activation on heart transplantation in a rat model.

BACKGROUND: The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway is an important key mechanism to protect the heart from ischemia/reperfusion injury. However, this pathway is disrupted in several cardiovascular diseases as a result of decreased NO bioavailability and increased NO-insensitive forms of sGC. Cinaciguat preferentially activates these NO-insensitive, oxidized forms of sGC. METHODS: We assessed the hypothesis that targeting NO-unresponsive sGC would protect the graft against ischemia/reperfusion injury in a rat heart transplantation model. Before explantation, donor Lewis rats received methylcellulose (1%) vehicle or cinaciguat 10 mg/kg. The hearts were excised, stored in cold preservation solution, and heterotopically transplanted. We evaluated in vivo left ventricular function of the graft. RESULTS: After transplantation, decreased left ventricular systolic pressure (77 ± 3 mm Hg vs 123 ± 13 mm Hg, p < 0.05), dP/dt(max) (1,703 ± 162 mm Hg vs 3,350 ± 444 mm Hg, p < 0.05), and dP/dt(min) (995 ± 110 mm Hg vs 1,925 ± 332 mm Hg, p < 0.05) were significantly increased by cinaciguat. Coronary blood flow was significantly higher in the cinaciguat group compared with the control group. Additionally, cinaciguat increased adenosine triphosphate levels (1.9 ± 0.4 µmol/g vs 6.6 ± 0.8 µmol/g, p < 0.05) and improved energy charge potential. After transplantation, increased c-jun messenger RNA expression was downregulated, whereas superoxide dismutase-1 and cytochrome-c oxidase mRNA levels were upregulated by cinaciguat. Cinaciguat also significantly decreased myocardial DNA strand breaks induced by ischemia/reperfusion during transplantation and reduced death of cardiomyocytes in a cellular model of oxidative stress. CONCLUSIONS: By interacting with NO-unresponsive sGC, cinaciguat enhances the protective effects of the NO/cGMP pathway at different steps of signal transduction after global myocardial ischemia/reperfusion. Its clinical use as pre-conditioning agent could be a novel approach in cardiac surgery.

Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction.

The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia. Rats were pretreated with ASA (75 mg/kg) or Zn(ASA)2 (100 mg/kg) orally for five consecutive days. Isoproterenol (85 mg/kg, subcutaneously [s.c.]) was applied to produce myocardial infarction. After 17-22 h, animals were anesthetized with sodium pentobarbital (60 mg/kg, intraperitoneally [i.p.]) and both electrical and mechanical parameters of cardiac function were evaluated in vivo. Myocardial histological and gene expression analyses were performed. In isoproterenol-treated rats, Zn(ASA)2 treatment normalized significantly impaired left-ventricular contractility index (Emax 2.6 ± 0.7 mmHg/µL vs. 4.6 ± 0.5 mmHg/µL, P < 0.05), increased stroke volume (30 ± 3 µL vs. 50 ± 6 µL, P < 0.05), decreased systemic vascular resistance (7.2 ± 0.7 mmHg/min/mL vs. 4.2 ± 0.5 mmHg/min/mL, P < 0.05) and reduced inflammatory infiltrate into the myocardial tissues. ECG revealed a restoration of elevated ST-segment (0.21 ± 0.03 mV vs. 0.09 ± 0.02 mV, P < 0.05) and prolonged QT-interval (79.2 ± 3.2 ms vs. 69.5 ± 2.5 ms, P < 0.05) by Zn(ASA)2. ASA treatment did not result in an improvement of these parameters. Additionally, Zn(ASA)2 significantly increased the mRNA-expression of superoxide dismutase 1 (+73 ± 15%), glutathione peroxidase 4 (+44 ± 12%), and transforming growth factor (TGF)-ß1 (+102 ± 22%). In conclusion, our data demonstrate that oral administration of zinc and ASA in the form of bis(aspirinato)zinc(II) complex is superior to ASA in preventing electrical, mechanical, and histological changes after acute myocardial ischemia. The induction of antioxidant enzymes and the anti-inflammatory cytokine TGF-ß1 may play a pivotal role in the mechanism of action of Zn(ASA)2.

An altered pattern of myocardial histopathological and molecular changes underlies the different characteristics of type-1 and type-2 diabetic cardiac dysfunction.

Increasing evidence suggests that both types of diabetes mellitus (DM) lead to cardiac structural and functional changes. In this study we investigated and compared functional characteristics and underlying subcellular pathological features in rat models of type-1 and type-2 diabetic cardiomyopathy. Type-1 DM was induced by streptozotocin. For type-2 DM, Zucker Diabetic Fatty (ZDF) rats were used. Left ventricular pressure-volume analysis was performed to assess cardiac function. Myocardial nitrotyrosine immunohistochemistry, TUNEL assay, hematoxylin-eosin, and Masson's trichrome staining were performed. mRNA and protein expression were quantified by qRT-PCR and Western blot. Marked systolic dysfunction in type-1 DM was associated with severe nitrooxidative stress, apoptosis, and fibrosis. These pathological features were less pronounced or absent, while cardiomyocyte hypertrophy was comparable in type-2 DM, which was associated with unaltered systolic function and increased diastolic stiffness. mRNA-expression of hypertrophy markers c-fos, c-jun, and ß-MHC, as well as pro-apoptotic caspase-12, was elevated in type-1, while it remained unaltered or only slightly increased in type-2 DM. Expression of the profibrotic TGF-ß 1 was upregulated in type-1 and showed a decrease in type-2 DM. We compared type-1 and type-2 diabetic cardiomyopathy in standard rat models and described an altered pattern of key pathophysiological features in the diabetic heart and corresponding functional consequences.

Q50, an iron-chelating and zinc-complexing agent, improves cardiac function in rat models of ischemia/reperfusion-induced myocardial injury.

BACKGROUND: Reperfusion of ischemic myocardium may contribute to substantial cardiac tissue damage, but the addition of iron chelators, zinc or zinc complexes has been shown to prevent heart from reperfusion injury. We investigated the possible beneficial effects of an iron-chelating and zinc-complexing agent, Q50, in rat models of ischemia/reperfusion (I/R)-induced myocardial infarction and on global reversible myocardial I/R injury after heart transplantation. METHODS AND RESULTS: Rats underwent 45-min myocardial ischemia by left anterior descending coronary artery ligation followed by 24h reperfusion. Vehicle or Q50 (10 mg/kg, IV) were given 5 min before reperfusion. In a heart transplantation model, donor rats received vehicle or Q50 (30 mg/kg, IV) 1h before the onset of ischemia. In myocardial infarcted rats, increased left ventricular end-systolic and end-diastolic volumes were significantly decreased by Q50 post treatment as compared with the sham group. Moreover, in I/R rat hearts, the decreased dP/dtmax and load-independent contractility parameters were significantly increased after Q50. However, Q50 treatment did not reduce infarct size or have any effect on increased plasma cardiac troponin-T-levels. In the rat model of heart transplantation, 1h after reperfusion, decreased left ventricular systolic pressure, dP/dt(max), dP/dt(min) and myocardial ATP content were significantly increased and myocardial protein expression of superoxide dismutase-1 was upregulated after Q50 treatment. CONCLUSIONS: In 2 experimental models of I/R, administration of Q50 improved myocardial function. Its mechanisms of action implicate in part the restoration of myocardial high-energy phosphates and upregulation of antioxidant enzymes.

Chemical etching of nitinol stents.

At present the main cause of death originates from cardiovascular diseases. Primarily the most frequent cause is vessel closing thus resulting in tissue damage. The stent can help to avoid this. It expands the narrowed vessel section and allows free blood flow. The good surface quality of stents is important. It also must have adequate mechanical characteristics or else it can be damaged which can easily lead to the fracture of the implant. Thus, we have to consider the importance of the surface treatment of these implants. In our experiments the appropriate design was cut from a 1.041 mm inner diameter and 0.100 mm wall thickness nitinol tube by using Nd:YAG laser device. Then, the stent was subjected to chemical etching. By doing so, the burr created during the laser cutting process can be removed and the surface quality refined. In our research, we changed the time of chemical etching and monitored the effects of this parameter. The differently etched stents were subjected to microscopic analysis, mass measurement and in vivo environment tests. The etching times that gave suitable surface and mechanical features were identified.

Nitric oxide- and heme-independent activation of soluble guanylate cyclase attenuates peroxynitrite-induced endothelial dysfunction in rat aorta.

Oxidative stress interferes with nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) signalling pathway through reduction of endogenous NO and formation of the strong intermediate oxidant peroxynitrite and leads to vascular dysfunction. We evaluated the effects of oral treatment with NO- and heme-independent sGC activator cinaciguat on peroxynitrite-induced vascular dysfunction in rat aorta. Sprague-Dawley rats were treated orally 2 times at an interval of 17 hours with vehicle or with cinaciguat (10 mg/kg). One hour after the last treatment, the animals were anesthetized, the thoracic aorta was removed, and the aortic segment preparations were incubated with and without the reactive oxidant peroxynitrite (200 µmol/L, 30 minutes). Endothelium-dependent (acetylcholine), -independent (sodium nitroprusside) vasorelaxations were investigated, and histopathological examination was performed. Incubation of aortic rings with peroxynitrite significantly attenuated the maximal endothelium-dependent relaxation (R (max)) to acetylcholine (peroxynitrite, 44.5% ± 5.9% vs control, 93.2% ± 2.0%, P < .05) and decreased pD(2) values (-logEC(50), EC(50) being the concentration of acetylcholine that elicited 50% of the maximal response) for the concentration-response curves as compared to control segments. Treatment of rats with cinaciguat significantly improved the decreased acetylcholine-induced vasorelaxation after exposure of aortic rings to peroxynitrite (cinaciguat + peroxynitrite, 67.1% ± 3.5% vs peroxynitrite, 44.5% ± 5.9%, P < .05). Incubation of aortic segments with peroxynitrite caused a significant shift of the sodium nitroprusside concentration-response curves to the right without any alterations in the R (max). Moreover, exposure of aortic rings to peroxynitrite resulted in increased nitro-oxidative stress and DNA breakage which were improved by cinaciguat. Treatment of rats with cinaciguat significantly increased intracellular cGMP levels in the aortic wall. Our results show under conditions of nitro-oxidative stress when signalling in the NO/sGC/cGMP pathway is impaired, acute activation of sGC by cinaciguat might be advantageous in the treatment of endothelial dysfunction in cardiovascular disease.

Acute ethanol exposure increases the susceptibility of the donor hearts to ischemia/reperfusion injury after transplantation in rats.

BACKGROUND: Many donor organs come from youths involved in alcohol-related accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. The aims of this work were 1) to evaluate in rats the time-course cardiac effects of acute ethanol-exposure and 2) to explore how its abuse by donors might affect recipients in cardiac pump function after transplantation. METHODS: Rats received saline or ethanol (3.45 g/kg, ip). We evaluated both the mechanical and electrical aspects of cardiac function 1 h, 6 h or 24 h after injection. Plasma cardiac troponin-T and glucose-levels were measured and histological examination of the myocardium was performed. In addition, heart transplantation was performed, in which donors received ethanol 6 h or 24 h prior to explantation. Graft function was measured 1 h or 24 h after transplantation. Myocardial TBARS-concentration was measured; mRNA and protein expression was assessed by quantitative real-time PCR and Western blot, respectively. RESULTS: Ethanol administration resulted in decreased load-dependent (-34 ± 9%) and load-independent (-33 ± 12%) contractility parameters, LV end-diastolic pressure and elevated blood glucose levels at 1 h, which were reversed to the level of controls after 6 h and 24 h. In contrast to systolic dysfunction, active relaxation and passive stiffness are slowly recovered or sustained during 24 h. Moreover, troponin-T-levels were increased at 1 h, 6 h and 24 h after ethanol injection. ST-segment elevation (+47 ± 10%), elongated QT-interval (+38 ± 4%), enlarged cardiomyocyte, DNA-strand breaks, increased both mRNA and protein levels of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase and metalloproteinase-9 were observed 24 h following ethanol-exposure. After heart transplantation, decreased myocardial contractility and relaxation, oxidative stress and altered protein expression were observed. CONCLUSIONS: These results demonstrate acute alcohol abuse increases the susceptibility of donor hearts to ischemia/reperfusion in a rat heart transplant model even though the global contractile function recovers 6 h after ethanol-administration.

Enhancement of myocardial and vascular function after phosphodiesterase-5 inhibition in a rat model.

BACKGROUND: Recent studies have shown the potential of PDE-5 inhibition on acute and chronic heart failure. Nevertheless it remained unclear, how far load-reducing properties and direct effects on myocardial contractility are responsible for these observations. In the present study, we investigated the effects of vardenafil on myocardial contractility and vascular function in a dose-response study. METHODS: We performed left ventricular pressure-volume analysis in young adult rats by using a Millar microtip conductance catheter. Pressure-volume loops were recorded before and after intravenous injection of vardenafil (3, 10, 30, 100, 300 µg/kg, n = 6/group). RESULTS: Treatment with vardenafil resulted in a significant (p < 0.05) increase in the load-independent cardiac contractility parameters reaching its maximum at the dose of 100µg/kg (ESPVR: 2.15 ± 0.15 vs. 3.29 ± 0.26 mm Hg/µL; PRSW: 93.28 ± 4.04 vs. 134.90 ± 6.27 mm Hg; peak positive dP/dt/EDV: 38.73 ± 7.97 vs. 53.02 ± 3.74 mm Hg·s-1·µL-1; before versus after 100 µg/kg vardenafil). Results of the in vitro organ-bath experiments showed an augmented vasorelaxation of precontracted aortic rings after vardenafil treatment. CONCLUSION: Our data supports the hypothesis that the usage of vardenafil as "inodilators" could have beneficial effects in heart failure patients.