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Effect of Ischemia Duration and Protective Interventions on the Temporal Dynamics of Tissue Composition After
Rodrigo Fernández-Jiménez1, Carlos Galán-Arriola1, Javier Sánchez-González1
1From the Department of Clinical Research, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain (R.F.-J., C.G.-A., J.A., G.J.L.-M., S.G.-T., J.G.-P., A.B., A.M.-I., I.G.-L., G.P., J.S., V.L., B.I.); Centro de Investigación Biomédica en Red de enfermedades CardioVasculares (CIBERCV) (R.F.-J., C.G.-A., J.A., S.G.-T., J.G.-P., M.B.-P., A.M.-G., I.G.-L., G.P., P.L.S., B.I.); Department of Cardiology, The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (R.F.-J., J.S., V.L.); Department of Clinical Research, Philips Healthcare, Madrid, Spain (J.S.-G.); Department of Cardiology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Spain (M.B.-P., A.M.-G., P.L.S.); Department of Cardiology, Hospital Universitario Quiron (I.G.-L.) and Complejo Hospitalario Ruber Juan Bravo (G.P.), European University of Madrid, Spain; and Department of Cardiology, IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain (S.G.-T., B.I.).
Insights
Cardioprotective strategies and ischemia duration significantly alter myocardial tissue composition after ischemia/reperfusion (I/R). Imaging protocols for assessing I/R injury should be standardized to account for these dynamic changes.
Area of Science:
- Cardiovascular Research
- Medical Imaging
- Translational Medicine
Background:
- The impact of cardioprotective strategies and ischemia duration on post-ischemia/reperfusion (I/R) myocardial tissue composition remains incompletely understood.
- Key tissue components affected include edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction.
Purpose of the Study:
- To investigate the temporal dynamics of myocardial tissue composition following I/R.
- To assess the effects of varying ischemia durations and cardioprotective interventions using advanced imaging in a translational animal model.
Main Methods:
- Utilized serial cardiac magnetic resonance (CMR) imaging for tissue characterization at multiple time points post-I/R.
- Assessed myocardium at risk using multidetector computed tomography during index coronary occlusion.
- Quantified myocardial water content and performed histology post-excision for validation.
Main Results:
- Edema formation exhibited a bimodal pattern in prolonged ischemia groups, with the hyperacute wave reduced by cardioprotection.
- CMR-detected edema was minimal by 24 hours post-reperfusion; the deferred wave was blunted by cardioprotection.
- Infarct size decreased progressively, while salvage, hemorrhage, and microvascular obstruction varied significantly based on timing, ischemia duration, and intervention.
Conclusions:
- Both cardioprotective therapies and ischemia duration profoundly influence the temporal changes in myocardial tissue composition post-I/R.
- Standardization of imaging techniques and protocols is crucial for accurate assessment of I/R injury markers.
Rationale:
The impact of cardioprotective strategies and ischemia duration on postischemia/reperfusion (I/R) myocardial tissue composition (edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction) is not well understood.
Objective:
To study the effect of ischemia duration and protective interventions on the temporal dynamics of myocardial tissue composition in a translational animal model of I/R by the use of state-of-the-art imaging technology.
Methods And Results:
Four 5-pig groups underwent different I/R protocols: 40-minute I/R (prolonged ischemia, controls), 20-minute I/R (short-duration ischemia), prolonged ischemia preceded by preconditioning, or prolonged ischemia followed by postconditioning. Serial cardiac magnetic resonance (CMR)-based tissue characterization was done in all pigs at baseline and at 120 minutes, day 1, day 4, and day 7 after I/R. Reference myocardium at risk was assessed by multidetector computed tomography during the index coronary occlusion. After the final CMR, hearts were excised and processed for water content quantification and histology. Five additional healthy pigs were euthanized after baseline CMR as reference. Edema formation followed a bimodal pattern in all 40-minute I/R pigs, regardless of cardioprotective strategy and the degree of intramyocardial hemorrhage or microvascular obstruction. The hyperacute edematous wave was ameliorated only in pigs showing cardioprotection (ie, those undergoing short-duration ischemia or preconditioning). In all groups, CMR-measured edema was barely detectable at 24 hours postreperfusion. The deferred healing-related edematous wave was blunted or absent in pigs undergoing preconditioning or short-duration ischemia, respectively. CMR-measured infarct size declined progressively after reperfusion in all groups. CMR-measured myocardial salvage, and the extent of intramyocardial hemorrhage and microvascular obstruction varied dramatically according to CMR timing, ischemia duration, and cardioprotective strategy.
Conclusions:
Cardioprotective therapies, duration of index ischemia, and the interplay between these greatly influence temporal dynamics and extent of tissue composition changes after I/R. Consequently, imaging techniques and protocols for assessing edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction should be standardized accordingly.
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