Post-ischemic Myocardial Dysfunction (Stunning)Results From Myofibrillar Edema

Thanjavur Bragadeesh ¹, Ananda Jayaweera ¹, Marco Pascotto ¹, Antonio Micari ¹, Elizabeth Le ¹, Christopher Kramer ², Fred Epstein ² and Sanjiv Kaul ^1*

¹ OHSU, United States
² UVA, United States

^* To whom correspondence should be addressed. E-mail: kauls{at}ohsu.edu.

Accepted 15 May 2007

Abstract

Objective To test the hypothesis that myocardial stunning is due to myofibrillar edema.

Design We performed experiments in anesthetized closed-chest pigs. In Group 1 pigs (n=15), we produced myocardial stunning by repetitive ischemia and reperfusion and studied 5 pigs each 2 hr, 2 days, and 5 days later. Circumferential left ventricular (LV) mid-wall myocardial strain (Ecc) was estimated in-vivo using tagged magnetic resonance imaging. Myocardial water content (MWC) was measured post-mortem from which inter-filament lattice distance (d) was calculateed. In Group 2 pigs (n=6), we produced myocardial dysfunction by intracoronary administration of a mast cell degranulator. Animals were euthanized immediately upon induction of regional LV dysfunction, so as not to allow inflammation to develop. In Group 3 pigs (n=4) we performed transmission electron microscopy (EM) to quantify d in stunned versus normal myocardium.

Results In Group 1 pigs, MWC was elevated in the stunned compared to normal myocardium (p<0.02) and decreased over time. There was an inverse relation between Ecc and MWC in the stunned myocardium (r=-0.76) and an excellent inverse relation were noted between Ecc and d (r=-0.90). A similar relation was also noted between wall thickening and increase in MWC in Group 2 (r=-0.84) pigs. In the Group 3 pigs, d on EM was 40&±3 nM in the normal myocardium, which was significantly (p<0.001) lower than that in the stunned myocardium (46.4±4 nM).

Conclusions Ischemia-reperfusion results in myocardial edema, with consequent myocyte swelling and myofibrillar edema. The latter leads to an increase in d causing myosin heads to either fail to latch on or to latch improperly on the actin filament with poor force generation, leading to myocardial dysfunction. As the myocardial edema abates, myocyte function improves.

Keywords: myocardial edema, myocardial function, myocardial stunning

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