No abstract

SummaryCardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of tissue resident (CCR2−) macrophages. Herein, we identify an essential role for CCR2− macrophages in the chronically failing heart. Depletion of CCR2− macrophages in mice with dilated cardiomyopathy accelerated mortality and impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2− macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4) dependent pathway that controlled growth factor expression. These findings establish a role for tissue resident macrophages in adaptive cardiac remodeling and introduce a new mechanism of cardiac macrophage activation.

Acute kidney injury (AKI) in deceased organ donors is increasing due to the escalation in anoxic brain‐deaths. The management of an organ donor with oligoanuric AKI is frequently curtailed due to hemodynamic and electrolyte instability. Although continuous renal replacement therapy (CRRT) corrects the effects of AKI, it is rarely started after the diagnosis of brain‐death (BD). Since 2017, we have initiated CRRT in organ donors with oligoanuric AKI to allow more time to stabilize the donor and improve the function of the thoracic organs. We now report our experience with the first 27 donors with oligoanuric AKI that received CRRT after the diagnosis of BD, with organs transplanted as the primary outcome. The average duration of CRRT was 30.1 ± 14.4 h and the mean ultrafiltration volume was 5141 ± 4272 ml. The time from BD declaration to cross clamp was significantly longer in the CRRT group versus a historical cohort with oligoanuric AKI that was not dialyzed (62.8 ± 18.3 vs. 37.1 ± 14.9 h; P < .01). The mean number of total organs transplanted per donor in the CRRT group was greater than the historical cohort, 2.9 ± 1.7 vs. 1.4 ± .6 (P = .< 01), respectively. The mean number of thoracic organs transplanted per donor also increased between the two groups, 1.4 ± 1.2 versus .6 ± .9 (P = .02). Thirty‐seven percent of the kidneys were successfully transplanted with a mean serum creatinine of 1.4 mg/dl at 6 months. We suggest that OPOs consider starting CRRT in organ donors with oligoanuric AKI to possibly increase the number of organs transplanted.