Dataset Information

Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression.

ABSTRACT:

Aims

Regional heterogeneities in contraction contribute to heart failure with reduced ejection fraction (HFrEF). We aimed to determine whether regional changes in myocardial relaxation similarly contribute to diastolic dysfunction in post-infarction HFrEF, and to elucidate the underlying mechanisms.

Methods and results

Using the magnetic resonance imaging phase-contrast technique, we examined local diastolic function in a rat model of post-infarction HFrEF. In comparison with sham-operated animals, post-infarction HFrEF rats exhibited reduced diastolic strain rate adjacent to the scar, but not in remote regions of the myocardium. Removal of Ca2+ within cardiomyocytes governs relaxation, and we indeed found that Ca2+ transients declined more slowly in cells isolated from the adjacent region. Resting Ca2+ levels in adjacent zone myocytes were also markedly elevated at high pacing rates. Impaired Ca2+ removal was attributed to a reduced rate of Ca2+ sequestration into the sarcoplasmic reticulum (SR), due to decreased local expression of the SR Ca2+ ATPase (SERCA). Wall stress was elevated in the adjacent region. Using ex vivo experiments with loaded papillary muscles, we demonstrated that high mechanical stress is directly linked to SERCA down-regulation and slowing of relaxation. Finally, we confirmed that regional diastolic dysfunction is also present in human HFrEF patients. Using echocardiographic speckle-tracking of patients enrolled in the LEAF trial, we found that in comparison with controls, post-infarction HFrEF subjects exhibited reduced diastolic train rate adjacent to the scar, but not in remote regions of the myocardium.

Conclusion

Our data indicate that relaxation varies across the heart in post-infarction HFrEF. Regional diastolic dysfunction in this condition is linked to elevated wall stress adjacent to the infarction, resulting in down-regulation of SERCA, disrupted diastolic Ca2+ handling, and local slowing of relaxation.

SUBMITTER: Roe AT

PROVIDER: S-EPMC6432054 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression.

Røe Åsmund T ÅT Ruud Marianne M Espe Emil K EK Manfra Ornella O Longobardi Stefano S Aronsen Jan M JM Nordén Einar Sjaastad ES Husebye Trygve T Kolstad Terje R S TRS Cataliotti Alessandro A Christensen Geir G Sejersted Ole M OM Niederer Steven A SA Andersen Geir Øystein GØ Sjaastad Ivar I Louch William E WE

Cardiovascular research 20190301 4

<h4>Aims</h4>Regional heterogeneities in contraction contribute to heart failure with reduced ejection fraction (HFrEF). We aimed to determine whether regional changes in myocardial relaxation similarly contribute to diastolic dysfunction in post-infarction HFrEF, and to elucidate the underlying mechanisms.<h4>Methods and results</h4>Using the magnetic resonance imaging phase-contrast technique, we examined local diastolic function in a rat model of post-infarction HFrEF. In comparison with sham ...[more]

PMID: 30351410

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Dataset Information

Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression.

Aims

Methods and results

Conclusion

Publications

Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression.

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