Changes in Metalloproteinase and Tissue Inhibitor of Metalloproteinase during Tachycardia-Induced Cardiomyopathy by Rapid Atrial Pacing in Dogs

Abstract

Background: It was the aim of this study to investigate the variation in metalloproteinase and tissue inhibitor of metalloproteinase (TIMP) connexin levels during tachycardia-induced cardiomyopathy (TIC). Methods: Canine models of TIC were established by rapid right atrial pacing at 350–400 beats per min for 8 weeks in 11 dogs, with another 6 dogs acting as sham operation group. Echocardiography, left ventricular pressure and its first derivation with time (positive and negative maximum, dp/dt_max and –dp/dt_max), as well as intracardiac electrograms were recorded before and after rapid pacing at 1, 4 and 8 weeks. Data were acquired in sinus rhythm. Ultrastructural changes in left ventricular tissue were observed by transmission electron microscope. The relative abundance of matrix metalloproteinase (MMP)-9 and TIMP-1 was studied by immunoblotting. Results: The following hemodynamic changes were detected after 8 weeks of rapid pacing: the TIC group had decreased dp/dt_max (p < 0.05), the left ventricular relaxation time constant (τ) was prolonged (p < 0.05), both left ventricular end-diastolic volume and left ventricular end-systolic volume were decreased (p <0.05), left ventricular end-diastolic pressure was significantly increased (p <0.05), and –dp/dt_max was significantly decreased (p <0.001) compared with the control group; no statistical differences in the left ventricular ejection fraction between weeks 1, 4 or 8 (p >0.05) were observed, but left ventricular ejection fraction was significantly decreased after 1 week of pacing (p < 0.05). The left ventricular end-diastolic volume was increased after 1 week of pacing compared with the control group (24.15 ± 8.15 vs.11.19 ± 4.41 ml; p <0.05), as shown by echocardiography. Compared with the control group, MMP-9 was significantly higher (0.217 ± 2.16 E-02 vs. 0.314 ± 5.263 E-02; p < 0.001), while TIMP-1 was decreased (0.230 ± 8.944 E-02 vs. 0.120 ± 9.258 E-03; p < 0.001). Conclusions: Ventricular dilatation and systolic dysfunction occurred after 1 week of rapid right atrial pacing. Enlarged and disarrayed fibers and mitochondria with disintegrated crystal and an anarchic pattern were observed. Additionally, moderate dilation of the rough endoplasmic reticulum and intercalated disk discontinuity were seen after 8 weeks of pacing, and MMP-9 was increased and TIMP-1 was decreased after the same time period.

Noninvasive Limb Ischemic Preconditioning Protects Against Myocardial I/R Injury in Rats

“…The mechanism through which NLIP protects against myocardial I/R injury is sophisticated and could involve many things, such as pathways (hormonal and nervous mechanisms) [9][10][11], levels (cellular and molecular levels) [5,12,13], factors (activators, mediators, and effectors) [14][15][16], and targets (cardiomyocytes, extracellular matrix) [17,18].…”

Preparation of a reduced graphene oxide/SiO2/Fe3O4UV-curing material and its excellent microwave absorption properties

“…Previous reports demonstrate that combination of GO with Fe 3 O 4 nanoparticles would enhance its microwave absorbing properties. [2][3][4][26][27][28][29] Graphene-supported composites usually have a problem of poor dispersion, which greatly hinders the further design of porous structures. [30][31][32][33][34][35][36][37][38][39][40][41][42] The magnetic nanocrystals/ reduced graphene hybrids employed in the above studies were usually hydrophilic or easily oxidized, which restricts their potential applications in some specic environments like humid climates.…”

Injection of Matrix Metalloproteinase-9 Leads to Ventricular Remodeling

“…The current study examined an experimental ventricular remodeling model that resulted from infusion of exogenous MMP-9 rather than examining MMP-9 ventricular remodeling in a disease state (for example, experimental myocardial infarction [15][16][17] and tachycardia cardiomyopathy caused by a cardiac pacemaker [18,19]) or caused by the injection of other drugs [20][21][22] (such as adriamycin [23,24]). Therefore, the results are not affected by a primary disease or the confounding effects of other drugs.…”

“…Secondly, the current model is easy to generate. Modeling based on rapid cardiac pacing requires cardiac pacing equipment and the catheter technique [ 18 , 19 ]. While the catheter technique generally applies to large animals, it is more difficult to implant cardiac pacing wires into mice or rats.…”