Objective: Interstitial fluid flow through vascular adventitia has been disclosed recently. However, its kinetic pattern was unclear. Methods and Results:We used histological and topographical identifications to observe ISF flow along venous vessels in rabbits. By MRI in alive subjects, the inherent ISF flow pathways in legs, abdomen and thorax were enhanced by paramagnetic contrast from ankle dermis. By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed, the perivascular and adventitial connective tissues (PACT) along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from ankle dermis, which coincided with the findings by MRI.By confocal microscopy and histological analysis, the stained PACT pathways were verified to be the fibrous connective tissues and consisted of longitudinally assembled fibers. By usages of nanoparticles and surfactants, a PACT pathway was found to be accessible for a nanoparticle under 100nm and contain two parts: a tunica channel part and an absorptive part. In real-time observations, the calculated velocity of a continuous ISF flow along fibers of a PACT pathway was 3.6-15.6 mm/sec. Conclusion:These data further revealed more kinetic features of a continuous ISF flow along vascular vessel. A multiscale, multilayer, and multiform "interstitial/interfacial fluid flow" throughout perivascular and adventitial connective tissues was suggested as one of kinetic and dynamic mechanisms for ISF flow, which might be another principal fluid dynamic pattern besides convective/vascular and diffusive transport in biological system.

Background Subclinical infection of cardiac implantable electronic devices (CIEDs) is a common condition and increases the risk of clinical infection. However, there are limited studies focused on risk stratifying and prognostic analysis of subclinical CIED infection. Methods and Results Data from 418 consecutive patients undergoing CIED replacement or upgrade between January 2011 and December 2019 were used in the analysis. Among the patients included, 50 (12.0%) were detected as positive by bacterial culture of pocket tissues. The most frequently isolated bacteria were coagulase‐negative staphylococci (76.9%). Compared with the noninfection group, more patients in the subclinical infection group were taking immunosuppressive agents, received electrode replacement, or received CIED upgrade and temporary pacing. Patients in the subclinical infection group had a higher PADIT (Prevention of Arrhythmia Device Infection Trial) score. Univariable and multivariable logistic regression analysis found that use of immunosuppressive agents (odds ratio [OR], 6.95 [95% CI, 1.44–33.51]; P =0.02) and electrode replacement or CIED upgrade (OR, 6.73 [95% CI, 2.23–20.38]; P =0.001) were significantly associated with subclinical CIED infection. Meanwhile, compared with the low‐risk group, patients in the intermediate/high‐risk group had a higher risk of subclinical CIED infection (OR, 3.43 [95% CI, 1.58–7.41]; P =0.002). After a median follow‐up time of 36.5 months, the end points between the subclinical infection group and noninfection group were as follows: composite events (58.0% versus 41.8%, P =0.03), rehospitalization (54.0% versus 32.1%, P =0.002), cardiovascular rehospitalization (32.0% versus 13.9%, P =0.001), CIED infection (2.0% versus 0.5%, P =0.32), all‐cause mortality (28.0% versus 21.5%, P =0.30), and cardiovascular mortality (10.0% versus 7.6%, P =0.57). Conclusions Subclinical CIED infection was a common phenomenon. The PADIT score had significant value for stratifying patients at high risk of subclinical CIED infection. Subclinical CIED infection was associated with increased risks of composite events, rehospitalization, and cardiovascular rehospitalization.