Early postnatal rat ventricle resection leads to long-term preserved cardiac function despite tissue hypoperfusion

Abstract

One‐day‐old mice display a brief capacity for heart regeneration after apex resection. We sought to examine this response in a different model and to determine the impact of this early process on long‐term tissue perfusion and overall cardiac function in response to stress. Apical resection of postnatal rats at day 1 (P1) and 7 (P7) rendered 18 ± 1.0% and 16 ± 1.3% loss of cardiac area estimated by magnetic resonance imaging (MRI), respectively (P > 0.05). P1 was associated with evidence of cardiac neoformation as indicated by Troponin I and Connexin 43 expression at 21 days postresection, while in the P7 group mainly scar tissue replacement ensued. Interestingly, there was an apparent lack of uniform alignment of newly formed cells in P1, and we detected cardiac tissue hypoperfusion for both groups at 21 and 60 days postresection using SPECT scanning. Direct basal cardiac function at 60 days, when the early lesion is undetectable, was preserved in all groups, whereas under hemodynamic stress the degree of change on LVDEP, Stroke Volume and Stroke Work indicated diminished overall cardiac function in P7 (P < 0.05). Furthermore, the End‐Diastolic Pressure–Volume relationship and increased interstitial collagen deposition in P7 is consistent with increased chamber stiffness. Taken together, we provide evidence that early cardiac repair response to apex resection in rats also leads to cardiomyocyte neoformation and is associated to long‐term preservation of cardiac function despite tissue hypoperfusion.

Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model

“…Neonatal heart regeneration was first demonstrated in 2011 using an apical resection model in P1 mice [22]. Similar observations have also been reported in P1 rats after apical resection [23]. This injury model is focused on cardiomyocyte replacement in a mechanically disrupted cardiac apex, which provides compelling evidence for new tissue growth, but is not clinically or translationally relevant.…”

“…Endogenous or natural heart regeneration is well-described in adult urodele amphibians (e.g., newts) and teleost fish (e.g., zebrafish), resulting impressively in minimal or no scar formation after LV apical resection injury [20,21]. Natural heart regeneration after LV apical resection has also been reported in neonatal mice and rats as well [22,23]. Using a more clinically-relevant MI injury model, however, our team and others have demonstrated that, after acute MI in newborn mice, an intrinsic neocardiomyogenic process is naturally activated in response to tissue ischemia, resulting in minimal scar formation and preservation of normal LV geometry and function at 3 weeks post-MI [24][25][26].…”

Ascending Aortic Constriction Promotes Cardiomyocyte Proliferation in Neonatal Rats

“…A previous study indicated that neonatal rat heart regenerates following apical resection in a manner similar to that of neonatal mouse hearts. 9) We hypothesized that neonatal rat heart will also respond with CM proliferation to pressure overload. In this study, ascending aortic constriction (AAC) in neonatal rats was used to serve as a model of pressure overload.…”

Stage-dependent cardiac regeneration inXenopusis regulated by thyroid hormone availability

“…Nonamniote vertebrates, such as urodeles or teleosts-with the exception of medaka (6)-possess robust lifelong cardiac regenerative capacity (5,7). Conversely in mammals, cardiac lesions lead to scar formation rather than regeneration, as observed for adult humans (2), as well as adult mice (8), rats (9), sheep (10), pigs (11), and in rabbits after birth (12,13). However, the neonatal mouse heart regenerates efficiently (8).…”