Clearance of senescent cells during cardiac ischemia-reperfusion injury improves recovery.

A key component of cardiac ischemia-reperfusion injury (IRI) is the increased generation of reactive oxygen species, leading to enhanced inflammation and tissue dysfunction in patients following intervention for myocardial infarction. In this study, we hypothesized that oxidative stress, due to ischemia-reperfusion, induces senescence which contributes to the pathophysiology of cardiac IRI. We demonstrate that IRI induces cellular senescence in both cardiomyocytes and interstitial cell populations and treatment with the senolytic drug navitoclax after ischemia-reperfusion improves left ventricular function, increases myocardial vascularization, and decreases scar size. SWATH-MS-based proteomics revealed that biological processes associated with fibrosis and inflammation that were increased following ischemia-reperfusion were attenuated upon senescent cell clearance. Furthermore, navitoclax treatment reduced the expression of pro-inflammatory, profibrotic, and anti-angiogenic cytokines, including interferon gamma-induced protein-10, TGF-ß3, interleukin-11, interleukin-16, and fractalkine. Our study provides proof-of-concept evidence that cellular senescence contributes to impaired heart function and adverse remodeling following cardiac ischemia-reperfusion. We also establish that post-IRI the SASP plays a considerable role in the inflammatory response. Subsequently, senolytic treatment, at a clinically feasible time-point, attenuates multiple components of this response and improves clinically important parameters. Thus, cellular senescence represents a potential novel therapeutic avenue to improve patient outcomes following cardiac ischemia-reperfusion.

Interatrial rupture of a non-coronary sinus of Valsalva aneurysm: a rare presentation of a rare disorder.

A 65-year-old male was referred to our team after the incidental finding of a large non-coronary sinus of Valsalva aneurysm on computed tomography (CT)-scan of the thorax. Further imaging with transesophageal echocardiography (TOE) excluded intracardiac shunting. Unusually, the aneurysm had ruptured into the interatrial septum and was seen to be compressing both atria. At operative intervention, a 20 mm defect which had replaced the non-coronary sinus was repaired using a patch graft. An aneurysm of an aortic sinus is a rare disorder, and a rupture of a non-coronary sinus typically results in the formation of a fistulous tract in the right atrium. These images highlight an unusual case of a non-coronary sinus of Valsalva aneurysm which ruptured into the interatrial septum (IAS), and demonstrate the benefit of multi-modality cardiac imaging in guiding surgical repair.