Short-term disruption in regional left ventricular electrical conduction patterns increases interstitial matrix metalloproteinase activity.
Increased matrix metalloproteinase (MMP) abundance occurs with adverse left ventricular (LV) remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained aberrant electrical activation of the LV, with consequent dyskinesia, alters interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n = 10, 30-35 kg) was achieved by pacing (150 beats/min) at left atrial and LV sites such that normal atrioventricular activation (60 min) was followed by regional early LV activation for 60 min within 1.5 cm of the paced site and restoration of normal atrioventricular pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the LV pacing site and a remote LV site were monitored at 30-min intervals. During aberrant electrical stimulation, interstitial MMP activity at the paced site was increased (122 +/- 4%) compared with the remote region (100%, P < 0.05). Restoration of atrioventricular pacing after the 60-min period of aberrant electrical activation normalized segmental shortening (8.5 +/- 0.4%), but MMP activity remained elevated (121 +/- 6%, P < 0.05). This study demonstrates that despite the restoration of mechanical function, disturbances in electrical conduction, in and of itself, can cause acute increases in regional in vivo MMP activation and, therefore, contribute to myocardial remodeling.
Mukherjee
Rupak
R
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. mukherr@musc.edu
Zavadzkas
Juozas A
JA
Rivers
William T
WT
McLean
Julie E
JE
Chang
Eileen I
EI
Bouges
Shenikqua
S
Matthews
Robert G
RG
Koval
Christine N
CN
Stroud
Robert E
RE
Spinale
Francis G
FG
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004562:Electrocardiography; D004789:Enzyme Activation; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate; D006352:Heart Ventricles / Q000201:enzymology / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D020127:Recovery of Function; D013552:Swine; D013997:Time Factors; D015854:Up-Regulation; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
D020782:Matrix Metalloproteinases
J Cell Physiol. 1998 Aug;176(2):374-82
9648925
Cardiovasc Res. 2006 Feb 15;69(3):666-76
16426590
Cardiovasc Res. 2000 May;46(2):225-38
10773226
Circ Res. 2005 May 27;96(10):1110-8
15860759
Circulation. 2005 Mar 8;111(9):1166-74
15723986
Eur J Heart Fail. 2008 Sep;10(9):878-83
18768351
J Am Coll Cardiol. 2006 Jan 3;47(1):163-72
16386681
J Card Fail. 2002 Dec;8(6 Suppl):S344-8
12555143
Circulation. 2003 Feb 4;107(4):618-25
12566376
Circulation. 2007 Sep 4;116(10):1162-9
17709639
Am J Physiol Heart Circ Physiol. 2003 Jan;284(1):H122-32
12485818
Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2216-28
16766634
Circulation. 2008 Sep 9;118(11):1202-11
18779456
Congest Heart Fail. 2007 Jan-Feb;13(1):9-15
17268205
J Cardiovasc Transl Res. 2009 Mar;2(1):126-9
20559976
Am J Physiol Heart Circ Physiol. 2003 Jan;284(1):H364-71
12388239
Philos Trans A Math Phys Eng Sci. 2009 Jun 13;367(1896):2311-31
19414457
Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1080-7
15486029
J Am Coll Cardiol. 2009 Apr 7;53(14):1192-3
19341859
Circulation. 1995 Oct 1;92(7):1954-68
7671380
Am J Physiol Regul Integr Comp Physiol. 2007 Nov;293(5):R1898-907
17686880
Congest Heart Fail. 2007 Sep-Oct;13(5):275-9
17917494