Post-ischaemic myocardial dysfunction (stunning) results from myofibrillar oedema.
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.
Bragadeesh
T
T
Division of Cardiovascular Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.
Jayaweera
A R
AR
Pascotto
M
M
Micari
A
A
Le
D E
DE
Kramer
C M
CM
Epstein
F H
FH
Kaul
S
S
D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology; D004487:Edema / Q000209:etiology; D009204:Myocardial Revascularization / Q000009:adverse effects; D017682:Myocardial Stunning / Q000209:etiology* / Q000473:pathology; D009210:Myofibrils / Q000473:pathology*; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology; D013552:Swine