Abstract 16959: A Youthful Cardiomyocyte Phenotype Drives Enhanced Cardiac Recovery in Adult Spiny Mice

Introduction: Adult mammals, including humans, experience limited recovery following myocardial infarction (MI). Recently, our group has uncovered a unique ability for enhanced cardiac recovery in adult spiny mice ( Acomys ). Methods and Results: Our preliminary studies have established appropriate similarities in heart structure and coronary anatomy between Acomys and Mus . Following the same permanent left artery descending (LAD) ligation surgery, Acomys and Mus showed a similar degree of early cardiac injury. Echocardiography and histological analyses showed more robust cardiac recovery and smaller scar area in Acomys . Moreover, Acomys exhibited a higher survival rate compared to Mus with no evidence of cardiac rupture or hypertrophy (measured by increasing heart/body weight) after MI. To investigate the mechanisms underlying this phenomenon, we isolated and quantified the size, nuclei number, and ploidy of adult cardiomyocytes (CMs) in both species (n=5 animals/group) using the Langendorff perfusion technique. Acomys CMs are significantly smaller in size compared to Mus and Acomys hearts have higher percentage of mononucleated cardiomyocytes. Using flow cytometry, we found that Acomys possess a higher percentage of diploid CMs compared to Mus . A closer examination of cardiomyocytes using electrophysiology revealed the presence of a T-type calcium current in adult Acomys CMs; a characteristic which is usually found in highly proliferative embryonic ventricular cardiomyocytes. Lastly, Acomys CMs demonstrated higher proliferative rates after injury compared to Mus . Conclusion: Taken together, our data provide strong evidence for enhanced cardiac repair in an adult mammalian model. Our results strongly suggest that Acomys maintain proliferative adult cardiomyocytes as adults and thus provide a cellular mechanism for their enhanced cardiac recovery after AMI.

Improved cardiac protection with Sabax cardioplegia in Langendorff isolated rat hearts

Objective: Cardioplegia is an important step to facilitate cardiac surgery while limiting intraoperative myocardial injury. Although recent advances in cardioplegic arrest methods have significantly contributed to better postoperative outcomes, there is still controversy regarding the optimal composition and temperature of the cardioplegic solution. Accordingly, we aimed to assess whether cold or lukewarm Sabax cardioplegia offer improved myocardial protection compared with the classical Krebs-Henseleit solution. Methods: The hearts of 40 male Wistar rats were isolated and submitted to constant-flow retrograde perfusion using a Langendorff perfusion apparatus. The hearts were randomly assigned to cold Krebs-Henseleit (K-H), cold Sabax, or lukewarm Sabax cardioplegia. The ECG, heart rates, and left ventricular systolic pressures (LVSP) were recorded pre- and post-cardioplegia. The time needed for cardioplegia induction and post-cardioplegia recovery were also noted. Results: Both cold and lukewarm Sabax cardioplegia insured faster induction and faster recovery following isothermic reperfusion compared to the standard K-H solution (both p< 0.01). With K-H cardioplegia, the hearts presented a 21.7% force loss after reperfusion (p< 0.001), whilst Sabax cardioplegia was associated with a slight increase in ventricular mechanical activity (3% LVSP increase with lukewarm Sabax cardioplegia, p< 0.001 and 2% LVSP increase with cold Sabax cardioplegia, p = 0.02). With Sabax cardioplegia the hearts displayed considerably less major arrhythmic events and presented less significant bradycardia. Conclusions: The present data suggest that Sabax cardioplegia may be superior to the classical cold crystalloid K-H solution in preserving mechanical activity of the heart and may provide superior protection against major arrhythmias.