The matrix metalloproteinases (MMPs) play a key role during cardiac remodeling. The aim of the study was to investigate the changes in collagenous proteins and MMPs in the model of non-ischemic, anthracycline-induced chronic cardiomyopathy in rabbits using both biochemical and histological approaches. The study was carried out in three groups of Chinchilla male rabbits: 1) daunorubicin (3 mg/kg, once weekly for 10 weeks), 2) control (saline in the same schedule), 3) daunorubicin with the cardioprotectant dexrazoxane (60 mg/kg, before each daunorubicin). Morphological changes in the myocardium of daunorubicin-treated animals were characterized by focal myocardial interstitial fibrosis of different intensity. The subsequent proliferation of the fibrotic tissue was marked by an increased content of both collagen types I and III, which resulted in their typical coexpression in the majority of bundles of fibers forming either smaller or larger scars. Biochemical analysis showed a significantly increased concentration of hydroxyproline, mainly in the pepsin-insoluble fraction of collagenous proteins, in the daunorubicin-treated group (1.42±0.12 mg/g) as compared with the control (1.03±0.04 mg/g) and dexrazoxane (1.07±0.07 mg/g) groups. Dexrazoxane co-administration remarkably reduced the cardiotoxic effects of daunorubicin to the extent comparable with the controls in all evaluated parameters. Using zymography, it was possible to detect only a gelatinolytic band corresponding to MMP-2 (MMP-9 activity was not detectable). However, no significant changes in MMP-2 activity were determined between individual groups. Immunohistochemical analysis revealed increased MMP-2 expression in both cardiomyocytes and fibroblasts. Thus, this study has revealed specific alterations in the collagen network in chronic anthracycline cardiotoxicity in relationship to the expression and activity of major MMPs., M. Adamcová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution., C. Vetter ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The objective of this study was to find out the implication of QRS duration in dogs with rapid pacing-induced heart failure. Sixteen Beagle dogs were implanted with transvenous cardiac pacemakers and underwent rapid right ventricular pacing for 3 weeks at 260 bpm to induce hear t failure. Dogs were divided into two groups according to the QRS duration: 9 with normal QRS duration (<100 ms) and 7 wi th prolonged QRS duration (≥100 ms). Cardiac systolic functi on and size was analyzed by real time 3-dimensional echocardiography and left ventricular dyssynchrony was assessed by speckle tracking strain imaging. Congestive heart failure developed 3 weeks after rapid right ventricular pacing. Dogs with prolonged QRS duration showed more extensive radial strain and circumferential strain dyssynchrony than dogs with norm al QRS duration. At the end of 4-week recovery, greater improvemen t of left ventricular ejection fraction and left ventricular end-systolic volume was detected in dogs with normal QRS duration. The findings suggested that left ventricular dyssynchrony, indicated by a prolonged QRS duration, predicted an unsatisfying recovery in dogs with rapid pacing- induced heart failure. QRS duration had the potential to be a prognostic indicator for dogs with heart failure., Y. Wang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The geometry of the distal anastomosis of a femoropopliteal bypass influences local hemodynamics and formation of intimal hyperplasia. We hypothesized that the distal anastomosis of an above-knee femoropopliteal bypass undergoes remodeling that results in displacement of the original course of the popliteal artery and change in the anastomosis angle. We identified 43 CT angiography examination with proximal femoropopliteal bypass and either a preserved contralateral popliteal artery or previous CTA before construction of the bypass for comparison. In these examinations, we measured the displacement distance and angle at the level of the distal anastomosis and compared these measurements with clinical and imaging data. The displacement distance was 8.8±4.9 mm (P<0.0001) and the displacement angle was -1° (IQR=44°). The angle between the inflow and outflow artery was 153±16° (P<0.0001). There was a negative association between the displacement angle and the angle between the bypass and the outflow artery (r=-0.318, P=0.037). Patients with reversed venous grafts had a greater displacement of the anastomosis (14.7±3.0 mm) than patients with prosthetic grafts (8.0±4.5 mm, P=0.0011). We conclude that construction of a distal anastomosis of proximal femoropopliteal bypass results in displacement of the original course of the popliteal artery towards the bypass and this effect is more pronounced in reversed venous grafts.
Varied causative and risk factors can lead to cardiac dysfunction. Cardiac dysfunction often evolves into heart failure by cardiac remodeling due to autonomic nervous system disturbance and neurohumoral abnormalities, even if the detriment factors are removed. Renal sympathetic nerve activity plays a pivotal regulatory role in neurohumoral mechanisms. The present study was designed to determine the therapeutic eff ects of renal sympathetic denervation (RSD) on cardiac dysfunction, fibrosis, and neurohumoral response in transverse aortic constriction (TAC) rats with chronic pressure overload. The present study demonstrated that RSD attenuated myocardial fibrosis and hypertrophy, and structural remodeling of the left atrium and ventricle, up -regulated cardiac β adrenoceptor (β -AR, including β 1 AR and β 2 AR) and sarco -endoplasmic reticulum Ca 2+ -ATP ase (SERCA) while down -regulated angiotensin II type 1 receptor (AT 1 R), and decreased plasma B -type natriuretic peptide (BNP), norepinephrine (NE) , angiotensin II (Ang II), and arginine vasopressin (AVP) levels in TAC rats with chronic pressure overload. We conclude that RSD attenuates myocardial fibrosis, the left atrial enlargement, and the left ventricular wall hypertrophy; inhibits the overdrive of the sympathetic ner vous system (SNS), renin- angiotensin -aldosterone system (RAAS), and AVP system in TAC rats with chronic pressure overload . RSD could be a promising non -pharmacological approach to control the progression of cardiac dysfunction., Z.-Z. Li, H. Jiang, D. Chen, Q. Liu, J. Geng, J.-Q. Guo, R.-H. Sun, G.-Q. Zhu, Q.-J. Shan., and Obsahuje bibliografii