Bilateral sympathectomy improves postinfarction left ventricular remodeling and function.

To evaluate the influence of bilateral or left sympathectomy on left ventricular remodeling and function after myocardial infarction in rats. Myocardial infarction was induced in rats by ligation of the left anterior descending coronary. Seven days later, rats were divided into 4 groups: the myocardial infarction, myocardial infarction with left sympathectomy, myocardial infarction with bilateral sympathectomy, and sham groups. After 8 weeks, left ventricular function was evaluated with the use of a pressure-volume conductance catheter under steady-state conditions and pharmacological stress. Infarct size and extracellular matrix fibrosis were evaluated, and cardiac matrix metalloproteinases and myocardial inflammatory markers were analyzed. The myocardial infarction and left sympathectomy group had an increased end diastolic volume, whereas the bilateral sympathectomy group had a mean end-diastolic volume similar to that of the sham group (P < .002). Significant reduction in ejection fraction was observed in the myocardial infarction and left sympathectomy group, whereas it was preserved after bilateral sympathectomy (P < .001). In response to dobutamine, left ventricular contractility increased in sham rats, rising stroke work, cardiac output, systolic volume, end-diastolic volume, ejection fraction, and dP/dt max. Only bilateral sympathectomy rats had significant increases in ejection fraction (P < .001) with dobutamine. Fibrotic tissue and matrix metalloproteinase expression decreased in the bilateral sympathectomy group compared to that in the myocardial infarction group (P < .001) and was associated with left ventricular wall thickness maintenance and better apoptotic markers in noninfarcted myocardium. Bilateral sympathectomy effectively attenuated left ventricular remodeling and preserved systolic function after myocardial infarction induction in rats.

Zanoni FL ，Simas R ，da Silva RG ，Breithaupt-Faloppa AC ，Coutinho E Silva RD ，Jatene FB ，Moreira LF ... -  《-》

Possible mechanism by which renal sympathetic denervation improves left ventricular remodelling after myocardial infarction.

What is the central question of this study? The enzyme system that is responsible for extracellular matrix (ECM) turnover is the matrix metalloproteinases (MMPs), which can be blocked by the tissue inhibitors of MMPs (TIMPs). Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction left ventricular remodelling through attenuation of ECM via regulation of MMP activity and/or the MMP-TIMP complex remains unknown. What is the main finding and its importance? Renal sympathetic denervation has therapeutic effects on post-myocardial infarction left ventricular remodelling, probably by attenuating the ECM through regulation of the MMP9-TIMP1 complex in the transforming growth factor-β1 (a profibrotic cytokine that accelerates ECM remodelling after ischaemia) signalling pathway. Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction (post-MI) left ventricular (LV) remodelling by attenuation of the extracellular matrix via regulation of matrix metalloproteinase (MMP) activity and/or the MMP-tissue inhibitor of matrix metalloproteinase (TIMP) complex remains unknown. Sixty-five Sprague-Dawley rats were randomly divided into the following four groups: normal (N, n = 15), RSD (RSD, n = 15), myocardial infarction (MI, n = 15) and RSD 3 days after MI (MI3d+RSD, n = 20). The bilateral renal nerves were surgically denervated 3 days after MI had been induced by coronary artery ligation. Left ventricular function was assessed using echocardiography and a Millar catheter at 6 weeks post-MI. Plasma noradrenaline, angiotensin II and aldosterone, collagen volume fraction, transforming growth factor-β1 (TGF-β1), MMP2, MMP9 and TIMP1 in heart tissue were measured 6 weeks after MI. In rats with MI3d+RSD compared with MI rats, RSD improved systolic and diastolic function, resulting in an improvement in ejection fraction (P < 0.05), fractional shortening (P < 0.05) and LV internal dimension in systole (P < 0.05) and diastole (P < 0.05). Additionally, RSD treatment decreased left ventricular end-diastolic pressure (P < 0.05) and increased LV systolic pressure (P < 0.05) and maximal and minimal rate of LV pressure (both P < 0.05). Meanwhile, RSD reduced collagen content (P < 0.01). TIMP1 was upregulated (P < 0.05), whereas MMP2, MMP9 and TGF-β1 were downregulated in the LV of RSD-treated animals (P < 0.05). Renal sympathetic denervation has therapeutic effects on post-MI LV remodelling, probably owing to effects on the extracellular matrix by regulation of the MMP9-TIMP1 balance in the TGF-β1 signalling pathway. Renal sympathetic denervation may be considered as a non-pharmacological approach for the improvement of post-MI cardiac dysfunction.

Zheng XX ，Li XY ，Lyu YN ，He YY ，Wan WG ，Zhu HL ，Jiang XJ ... -  《-》

The role of Parkin protein in cardiac function and ventricular remodeling in myocardial infarction rats.

Zhang SX ，Zhuang LL ，Liu J ，Jing YY ，Sun J ，Gong L ，Liu XY ... -  《-》

Decellularized amniotic membrane attenuates postinfarct left ventricular remodeling.

Placenta and amnion have been suggested as sources of juvenile cells and tissues for use in surgical regenerative medicine. We previously determined the impact of amniotic epithelial cells induced to undergo epithelial-to-mesenchymal transition (EMT) on myocardial remodeling processes and now evaluated the effects of naïve and processed amniotic membrane (AM) on postischemic left ventricular (LV) geometry and function. Human AM was used in unmodified form (AM), after EMT induction by transforming growth factor β (EMT-AM), and after decellularization (Decell-AM). After characterization by histology, electron microscopy, splenocyte proliferation assay, and cytokine release, myocardial infarction was induced in 6-8-week old male BALB/c mice by permanent left anterior descending coronary occlusion, and AM patches were sutured to the anterior LV surface (n = 10 per group). Infarcted hearts without AM or sham-operated mice were used as controls (n = 10 each). After 4 weeks, LV pressure-volume curves were recorded using a conductance catheter before the animals were sacrificed and the hearts analyzed by histology. TGF-ß treatment induced EMT-like changes in amniotic epithelial cells but increased AM xenoreactivity in vitro (splenocyte proliferation) and in vivo (CD4+ cell invasion). Moreover, in vitro interleukin-6 release from AM and from cardiac fibroblasts co-incubated with AM was 300- or 100-fold higher than that of interleukin-10, whereas Decell-AM did not release any cytokines. AM- and Decell-AM-treated hearts had smaller infarct size and greater infarct scar thickness than infarct control hearts, but there was no difference in myocardial capillary density or the number of TUNEL positive apoptotic cells. LV contractile function was better in the AM and EMT-AM groups than in infarcted control hearts, but dP/dt max, dP/dt min, stroke work, and cardiac output were best preserved in mice treated with Decell-AM. Volume-based parameters (LV end-systolic and end-diastolic volume as well as LV ejection fraction) did not differ between AM and Decell-AM. Decellularized AM supports postinfarct ventricular dynamics independent of the actual regeneration processes. As a cell-free approach to support the infarcted heart, this concept warrants further investigation.

Roy R ，Haase T ，Ma N ，Bader A ，Becker M ，Seifert M ，Choi YH ，Falk V ，Stamm C ... -  《-》

Angiotensin type 2 receptor stimulation ameliorates left ventricular fibrosis and dysfunction via regulation of tissue inhibitor of matrix metalloproteinase 1/matrix metalloproteinase 9 axis and transforming growth factor β1 in the rat heart.

Lauer D ，Slavic S ，Sommerfeld M ，Thöne-Reineke C ，Sharkovska Y ，Hallberg A ，Dahlöf B ，Kintscher U ，Unger T ，Steckelings UM ，Kaschina E ... -  《-》