Dependence of the Rate and Completeness of Fibrin Clot Destruction on the Acoustic Dose and Ultrasound Intensity

Abstract

The kinetics of fibrin clot destruction under catheter-delivered 32- to 45-kHz ultrasound (US) has been studied at 36°C-38°C in isotonic saline solution. A pseudo-first-order rate constant increased linearly from 0.06/min to 0.57/min with increasing US intensity I₀ from 21.6 to 51.2 W/cm². At I₀ = 4.4 and 11.4 W/cm², the degree of clot destruction did not exceed 11%-15% regardless of the time of US exposure. Starting from I₀ = 21.6 W/cm², the maximum achievable level of clot destruction increased linearly with US intensity, reaching 68% at I₀ = 51.2 W/cm² after 3 min of US exposure. Thus, US intensity is a key parameter determining the maximum achievable level of clot destruction. However, an increase in US intensity above 30 W/cm² is limited by the intensified negative sonochemical effect on the enzymatic system of hemostasis caused by an increase in inertial cavitation. The best effect can be achieved with ultrasound of a sufficiently high intensity that ensures a large contribution of stable cavitation, generating microstreaming flows, and a minimum contribution of inertial cavitation, generating microjets and shock waves.

Keywords: Acoustic cavitation; Catheter-derived ultrasound; Fibrin clot; Kinetics; Stable and inertial (transient) cavitation; Thrombolysis.