Splenectomy‐Induced Diastolic Dysfunction With Normal Ejection Fraction

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BackgroundUnderstudied and often disregarded, the spleen is perceived as redundant, non‐vital or even a vestigial organ. Conversely, epidemiological studies indicate splenectomy (or splenic injury) increase the prevalence of cardiovascular diseases and associated risk factors, suggesting the physiological function of the spleen is not yet realized. Recent investigations have examined the role of the spleen in experimental heart failure, however, the effect of long‐term splenectomy on cardiac function in healthy models remains to be determined. Thus, the aim of this study was to reconcile the observations made in the epidemiological studies by investigating cardiac function and morphology following splenectomy in healthy rodents.MethodsSplenectomized and sham male Wistar rats were assessed at 5, 9, and 18 weeks post‐surgery by echocardiography, invasive hemodynamics, cardiac histology, and thromboelastography. Serum IL‐10 was measured by ELISA and left ventricular free wall was used for the analysis of select molecular markers.ResultsSplenectomy caused progressive left ventricular diastolic dysfunction (i.e., increases in dP/dt min, Tauw, and LVEDP), with no evidence of cardiac decompensation or systolic dysfunction. Left ventricular remodeling (fibrosis, hypertrophy and decreases in capillary to myocyte cross sectional area) were associated with decreases in serum IL‐10 and ventricular BNP expression. Increases in blood coagulability following splenectomy are associated with increased risk of developing thromboembolic pulmonary hypertension. In our model however, we found no evidence of pulmonary arterial hypertension or lung remodeling despite a ~2‐fold increase in coagulability.ConclusionsSplenectomy in healthy rodents caused progressive diastolic dysfunction and significant cardiac remodeling (i.e., fibrosis, hypertrophy and decreased capillary density), demonstrating an underappreciated role of the spleen in cardiac homeostasis. Future studies need to characterize the mechanism(s) by which the spleen contributes to a healthy cardiovascular phenotype.Support or Funding InformationThis work was supported by the J.P. Bickell Foundation (to JA Simpson), the Natural Sciences and Engineering Research Council (to JA Simpson and KR Brunt), and the Ontario Veterinary College Pet Fund (to SL Blois). JA Simpson is a new investigator with the H&SF of Ontario.