Ischemic myocardial slices exhibited a 60.2% reduction in contractile performance compared to 43.6% reduction after 5 hours versus 8 hours of ischemia, respectively.
Living myocardial slices from human heart failure patients can serve as a viable ex vivo model to study ischemia-reperfusion injury and contractile dysfunction.
Absolute Event Rate: 0% vs 0%
Abstract Background Ischemia-reperfusion injury (IR) remains a leading cause of myocardial dysfunction following restoration of blood flow to the heart after acute myocardial infarction or cardiac surgery. Despite extensive research, effective therapies are lacking, particularly due to limitations in existing preclinical models. Living myocardial slices (LMS) preserve the multicellular architecture, extracellular matrix, and contractile function of human myocardium, offering a novel and physiologically relevant platform to model IR injury ex vivo. Objective To establish a LMS-based model of myocardial IR, enabling assessment of functional, structural, and molecular responses to IR, as well as potential therapeutical approaches. Methods LMS were prepared from ventricular tissue of end-stage heart failure patients undergoing transplantation (Fig. 1). Following adaptation for 3-5 days, slices were exposed to two IR protocols: 5 or 8 hours of ischemia followed by 20 hours of reperfusion. To increase workload, the electrical stimulation frequency was raised from 0.5 to 1.5 Hz during ischemia, also in control slices. Throughout the protocol, contractile performance was continuously assessed, including contraction force, contraction duration, time to peak (TTP), time to relaxation (TTR), and contraction kinetics (±dF/dt) (Fig. 2F). After completion of the experimental protocol, myocardial slices were harvested for assessment of mitochondrial respiratory capacity using high-resolution respirometry. Results Ischemic slices exhibited impaired contractile performance during ischemia, which partially recovered during reperfusion but remained reduced overall. This impairment tended to be more pronounced following prolonged ischemia (60.2 ± 17.3% vs. 43.6 ± 19.6%). Contraction kinetics showed a similar trend, with both the maximal rates of contraction (+dF/dt: 64.1 ± 14.8% vs. 50.0 ± 25.1%) and relaxation (−dF/dt: 70.3 ± 20.4% vs. 51.4 ± 22.8%) declining with increasing ischemic duration. TTP and TTR both shortened during ischemia and returned to baseline levels following reperfusion, with a slight prolongation observed at the end of reperfusion in slices subjected to extended ischemic duration (TTP: 94.9 ± 12.7% vs. 111.6 ± 22.9%; TTR: 94.3 ± 11.1% vs. 140.0 ± 47.8%) (Fig. 2A-H). Mitochondrial respiratory capacity remained unchanged across the different IR protocols and relative to controls (Fig. 2I). The absence of detectable differences may be related to reduced expression of mitochondrial respiratory genes after prolonged slice culture. Conclusion This study presents an ex vivo model of myocardial IR using LMS, with initial data suggesting sensitivity of contractile function and contraction kinetics to ischemia duration. This platform may serve as a translational tool to study IR and therapeutic strategies. Future perspective: The effect of IR on structural remodelling, mitochondrial DNA release, and expression of apoptotic markers is currently ongoing.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.
Cius et al. (Sun,) reported a other. Ischemic myocardial slices exhibited a 60.2% reduction in contractile performance compared to 43.6% reduction after 5 hours versus 8 hours of ischemia, respectively.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: