Regulating of Koisio technology-produced fluid on Vascular Adventitial Interstitial Fluid flow and its Effect on heart rate by delivering Esmolol

Acupoint-originated interstitial fluid (ISF) circulatory network along the vasculature has been demonstrated to play a role as an extravascular drug delivery pathway. We aim to reveal the regulation of Koisio technology-produced fluid (KF), which is rich in Ultra-small Particle Size Nanobubbles (UsNBs), on vascular adventitial ISF flow and its Effect on heart rate by delivering Esmolol. In animal experiments, using real-time fluorescent imaging technology, it was found that: when normal saline-fluorescent liquid was given at Kunlun acupoint, the velocity of the adventitial ISF along the femoral vein was measured to be about 600 m/sec, and the width of the tunica ISF channel on the adventitia surface of the femoral vein was about 210m; when KF-fluorescent liquid was injected into the subcutaneous tissue of Kunlun acupoint, the velocity of the adventitia ISF slowed down by about 24% compared with before; the width of the tunica ISF channel on the adventitia surface of the femoral vein increased by about 35% compared with before; When 150L of KF with high-concentration UsNBs was injected into Kunlun acupoint, it was observed that the adventitial ISF flow velocity was decreased by 43%, and recovered after 30 minutes. Administration of normal saline-esmolol solution at Kunlun acupoint caused the heart rate to drop from 410 bpm to 380 bpm, a decrease of 7.3%, which continued for 5 minutes before recovery. Administration of KF-esmolol solution at Kunlun acupoint caused the heart rate to drop from 410 bpm to 371 bpm, a decrease of 9.5%, which continued for 15 minutes before recovery. Thus, acupoint injection of KF can regulate the velocity of the adventitia ISF flow along the femoral vein and increase the width of the tunica ISF channel. These results may reveal a new mechanism of the physiological effect of Koisio drinking water rich in ultra-small particle size nanobubbles. KF may not only regulate the acupoint-originated ISF circulatory system, but also play a role in adventitial drug delivery, nutrient supply, and waste removal.