CORONARY ARTERY DISEASE

Post-ischaemic myocardial dysfunction (stunning) results from myofibrillar oedema

T Bragadeesh¹, A R Jayaweera¹, M Pascotto¹, A Micari¹, D E Le¹, C M Kramer², F H Epstein², S Kaul¹

¹ Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, Oregon, USA
² Department of Radiology, University of Virginia, Charlottesville, Virginia, USA

Dr S Kaul, Division of Cardiovascular Medicine, OHSU, UHN62, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA; kauls{at}ohsu.edu

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

Methods: Experiments were performed in anaesthetised closed-chest pigs. In 15 pigs (group 1), myocardial stunning was produced by repetitive ischaemia and reperfusion; 5 pigs each were studied at 2 hours, 2 days, and 5 days later. Circumferential left ventricular (LV) mid-wall myocardial strain (E_cc) was estimated in vivo using tagged magnetic resonance imaging. Myocardial water content (MWC) was measured post mortem, from which interfilament lattice distance (d) was calculated. In 6 pigs (group 2), myocardial dysfunction was produced by intracoronary administration of a mast cell degranulator. Animals were euthanised immediately upon induction of regional LV dysfunction to avoid development of inflammation. In 4 pigs (group 3), transmission electron microscopy (EM) was performed to quantify d in stunned versus normal myocardium.

Results: In group 1 pigs, MWC was raised in the stunned compared with normal myocardium (p<0.02) and decreased over time. An inverse relation was found between E_cc and MWC in the stunned myocardium (r = –0.81) and between E_cc and d (r = –0.90). A similar relation was noted between wall thickening and increase in MWC in group 2 (r = –0.84) pigs. In group 3 pigs, d on EM was significantly lower (40 (3) nmol/l) in normal myocardium than in stunned myocardium (46.4 (4) nmol/l), p<0.001.

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

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