gms | German Medical Science

Objective: Subarachnoid hemorrhage (SAH) is associated in up to 30% with cardiac dysfunction, including troponemia, ECG changes, and cardiomyopathy. This effect, known as neurogenic stunned myocardium, may lead to systemic complications. Recently, light has been shed on extracellular RNA (eRNA) acting as danger-associated molecular signals and potent cofactors in cardiovascular inflammation. The aim of the study was to describe an in-vivo model to investigate cardiac function after experimental SAH, as well as to study the potential role of eRNA as a possible mediator in the brain-heart axis.

Methods: Experimental SAH was induced via a filament perforation model in male C57Bl/6 mice and verified via Magnetic Resonance Imaging, while Sham operation was performed for the corresponding control group. Mice were treated with RNase1 (42 μg/kg) intravenoulsy, an antagonist of endogenous eRNA; NaCl was used for the control group. Transthoracic cardiac echocardiography was performed to elicit diastolic and systolic function on day 1, 7, and 14 (n=6 for each subgroup; ntotal=72). Diastolic function was assessed by determining mitral inflow patterns (E/E’ ratio) and mitral annulus velocities (E/A ratio); left ventricular ejection fraction (LVED) was measured for systolic function. Furthermore, heart weight at each time point was determined following sacrifice of animals. Cardiomyocyte size was quantified using Hematoxylin/Eosin stainings.

Results: In SAH, impaired diastolic function was observed as demonstrated by reduced E/A ratio in the setting of SAH (Sham vs. SAH: 2,3 vs. 1,5; p=0,04), while LVED was not affected. Heart weight increased in SAH mice by 11,7% (Sham vs. SAH: 136 mg vs. 152 mg; p<0,05). Concomitantly, cardiomyocyte size was also significantly increased in SAH mice (Sham vs. SAH: 114 mm2 vs. 141 mm2; p<0,01). Cardiomyocyte hypertrophy was reversed by inhibiting endogenous eRNA via RNAse1 treatment after 14 days (SAH vs. SAH+RNase1: 141 mm2 vs. 122 mm2; p=0,04).

Conclusion: Our in-vivo model can be utilized to examine the brain-heart axis in the setting of SAH. Impaired diastolic dysfunction is observed after inducing SAH injury, paralleled by an increase in heart weight and cardiomyocyte size. RNAse1 treatment can rescue cardiac hypertrophy after SAH. Targeting eRNA may present a potential strategy in reducing cardiac complications in the setting of SAH, but further studies are needed to investigate the detailed pathophysiological patterns that underlie this brain-heart axis.