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Updated: Jul 6, 2026
Model of Ischemia and Reperfusion Injury in Rabbits
Published on: November 3, 2023
Characterization of the structural and functional changes in the myocardium following focal ischemia-reperfusion
Navdeep Ojha1, Sashwati Roy, Jared Radtke
1Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA.
Abstract:
High-resolution (11.7 T) cardiac magnetic resonance imaging (MRI) and histological approaches have been employed in tandem to characterize the secondary damage suffered by the murine myocardium following the initial insult caused by ischemia-reperfusion (I/R). I/R-induced changes in the myocardium were examined in five separate groups at the following time points after I/R: 1 h, day 1, day 3, day 7, and day 14. The infarct volume increased from 1 h to day 1 post-I/R. Over time, the loss of myocardial function was observed to be associated with increased infarct volume and worsened regional wall motion. In the infarct region, I/R caused a decrease in end-systolic thickness coupled with small changes in end-diastolic thickness, leading to massive wall thickening abnormalities. In addition, compromised wall thickening was also observed in left ventricular regions adjacent to the infarct region. A tight correlation (r2 = 0.85) between measured MRI and triphenyltetrazolium chloride (TTC) infarct volumes was noted. Our observation that until day 3 post-I/R the infarct size as measured by TTC staining and MRI was much larger than that of the myocyte-silent regions in trichrome- or hematoxylin-eosin-stained sections is consistent with the literature and leads to the conclusion that at such an early phase, the infarct site contains structurally intact myocytes that are functionally compromised. Over time, such affected myocytes were noted to structurally disappear, resulting in consistent infarct sizes obtained from MRI and TTC as well as trichrome and hematoxylin-eosin analyses on day 7 following I/R. Myocardial remodeling following I/R includes secondary myocyte death followed by the loss of cardiac function over time.
Insights
High-resolution cardiac MRI and histology reveal that myocardial damage after ischemia-reperfusion (I/R) involves functional impairment of intact myocytes early on, followed by cell death and cardiac dysfunction over time.
Area of Science:
- Cardiovascular Research
- Medical Imaging
- Pathology
Background:
- Ischemia-reperfusion (I/R) injury is a significant cause of myocardial damage.
- Understanding the temporal evolution of I/R-induced secondary damage is crucial for developing effective treatments.
Purpose of the Study:
- To characterize secondary myocardial damage following ischemia-reperfusion (I/R) injury in mice.
- To correlate imaging findings with histological assessments of myocardial injury over time.
Main Methods:
- High-resolution (11.7 T) cardiac magnetic resonance imaging (MRI) was used to assess infarct volume and cardiac function.
- Histological analyses (TTC, trichrome, H&E staining) were performed at multiple time points post-I/R (1 h, day 1, 3, 7, 14).
Main Results:
- Infarct volume increased from 1 hour to day 1 post-I/R, with associated loss of myocardial function and regional wall motion abnormalities.
- Early infarcts (up to day 3) showed functionally compromised myocytes within structurally intact regions, a finding consistent across MRI, TTC, and histological stains.
- By day 7, infarct size measurements converged as affected myocytes structurally disappeared, indicating progressive myocardial remodeling and cell death.
Conclusions:
- Myocardial remodeling after I/R involves initial functional impairment of myocytes, followed by secondary cell death and progressive loss of cardiac function.
- High-resolution cardiac MRI provides a reliable, non-invasive method to quantify infarct volume and track I/R-induced myocardial changes over time.
- The study highlights the dynamic nature of I/R injury, with distinct phases of myocyte dysfunction and structural loss contributing to long-term cardiac impairment.
