Biochemical mechanism(s) of stunning in conscious dogs.
The mechanism(s) underlying contractile dysfunction in cardiac stunning is not completely understood. The expression and/or the phosphorylation state of cardiac Ca(2+) homoeostasis-regulating proteins might be altered in stunning. We tested this hypothesis in a well-characterized model of stunning. Conscious dogs were chronically instrumented, and the left anterior descending artery (LAD) was occluded for 10 min. Thereafter, reperfusion of the LAD was initiated. Tissues from reperfused LAD (stunned) and Ramus circumflexus (control) areas were obtained when left ventricular regional wall thickening fraction had recovered by 50%. Northern and Western blotting revealed no differences in the expression of the following genes: phospholamban, calsequestrin, sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a, and the inhibitory subunit of troponin I (TnI). However, the phosphorylation state of TnI and phospholamban were reduced in the LAD area. Fittingly, cAMP levels were reduced by 28% (P < 0.05). It is concluded that the contractile dysfunction in cardiac stunning might be mediated in part by decreased levels of cAMP and subsequently a reduced phosphorylation state of phospholamban and TnI.
Lüss
H
H
Institut für Pharmakologie und Toxikologie, Universität Münster, D-48149 Münster, Germany.
Meissner
A
A
Rolf
N
N
Van Aken
H
H
Bokník
P
P
Kirchhefer
U
U
Knapp
J
J
Läer
S
S
Linck
B
B
Lüss
I
I
Müller
F U
FU
Neumann
J
J
Schmitz
W
W
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics; D000252:Calcium-Transporting ATPases / Q000235:genetics; D002155:Calsequestrin / Q000235:genetics; D003243:Consciousness; D003331:Coronary Vessels / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation; D006439:Hemodynamics; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D019210:Troponin I / Q000235:genetics; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002155:Calsequestrin; D000242:Cyclic AMP; D019210:Troponin I; D000099211:Phospholamban