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PMID: 3818956 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts.

The Journal of clinical investigation ·Vol. 79 ·No. 3 ·1987-03-00 ·Pages 950-61

Kusuoka H, Porterfield JK, Weisman HF, Weisfeldt ML, Marban E

Abstract

Contractile dysfunction in stunned myocardium could result from a decrease in the intracellular free [Ca2+] transient during each beat, a decrease in maximal Ca2+-activated force, or a shift in myofilament Ca2+ sensitivity. We measured developed pressure (DP) at several [Ca]0 (0.5-7.5 mM) in isovolumic Langendorff-perfused ferret hearts at 37 degrees C after 15 min of global ischemia (stunned group, n = 13) or in a nonischemic control group (n = 6). At all [Ca]0, DP was depressed in the stunned group (P less than 0.001). Maximal Ca2+-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was decreased after stunning (P less than 0.05). Normalization of the DP-[Ca]0 relationship by corresponding MCAP (Ca0 sensitivity) revealed a shift to higher [Ca]0 in stunned hearts. To test whether cellular Ca overload initiates stunning, we reperfused with low-[Ca]0 solution (0.1-0.5 mM; n = 8). DP and MCAP in the low-[Ca]0 group were comparable to control (P greater than 0.05), and higher than in the stunned group (P less than 0.05). Myocardial [ATP] observed by phosphorus NMR failed to correlate with functional recovery. In conclusion, contractile dysfunction in stunned myocardium is due to a decline in maximal force, and a shift in Ca0 sensitivity (which may reflect either decreased myofilament Ca2+ sensitivity or a decrease in the [Ca2+] transient). Our results also indicate that calcium entry upon reperfusion plays a major role in the pathogenesis of myocardial stunning.

MeSH Terms
Adenosine Triphosphate/physiology Animals Calcium/pharmacology,physiology Cardiomyopathies/etiology,pathology,physiopathology Carnivora/physiology Coronary Vessels/physiopathology Ferrets/physiology Heart Ventricles/physiopathology Ischemia/complications Male Myocardial Contraction/drug effects Myocardium/pathology Perfusion
Chemicals
Adenosine Triphosphate Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kusuoka H
Porterfield J K
Weisman H F
Weisfeldt M L
Marban E
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39 references, click to expand
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI112906
Published
1987-03-00
Pages
950-61
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC424246
Subset
IM
Grants
PHS HHS · 17655-11 · United States
NHLBI NIH HHS · K04 HL01872 · United States
External Links
PubMed source DOI: 10.1172/JCI112906 PMC Full Text View journal details
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