Abstract
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Objectives: Cardiorenal syndrome is an increasingly recognized clinical entity, characterized by bidirectional interaction between the failing heart and the kidneys. We speculated that inflammation contributes to this crosstalk and sought to obtain further mechanistic insights by preclinical analysis of CXCR4-targeted images after myocardial infarction (MI).
Methods: Serial whole-body CXCR4-targeted Ga-68-pentixafor PET was obtained in mice (n=65) after coronary artery occlusion MI or sham surgery at 1d, 3d, 7d, and 6 wks. Tracer retention was determined in the kidneys and compared to infarct signal and cardiac function, as measured independently by magnetic resonance.
Results: CXCR4 signal was significantly elevated in the MI region at 1d (% injected dose (ID)/g; heart: 1.12±0.20 vs 0.59 ±0.12 for sham, P<0.0001), returning to sham level at 7d. Renal CXCR4 signal was unchanged at 1d but reduced at 7d compared to sham (%ID/g, 1.23±0.17 vs 1.07±0.2 for sham, P<0.05). Cardiac and renal signal were directly correlated (r=0.62, p<0.0001), suggesting an inflammatory link between heart and kidneys. Ex-vivo autoradiography confirmed a significant correlation between tracer retention in MI region and kidneys (r=0.9, P<0.01). Of note, early in-vivo CXCR4 signal in kidneys at 7d was inversely proportional to cardiac function at 6 weeks after MI, particularly among animals with more severe contractile dysfunction (ejection fraction <30%, R=-0.79, p<0.05).
Conclusions: Systems-based PET analysis confirms inflammatory crosstalk between the injured heart and kidneys early after MI. This may contribute to adverse outcome for both organs. The present analysis provides a foundation for further imaging studies in cardiac and renal injury, to assess inter-organ communication in progressive chronic disease. Acknowledgement. This project was supported by PRACTIS - Clinician Scientist Program, funded by the German Research Foundation (DFG, ME 3696/3-1) and the clinical research group KFO311.
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