Effect of blood viscosity and thrombus composition on sonoreperfusion efficacy

Abstract

Embolization during stenting for myocardial infarction (MI) causes microvascular obstruction (MVO). We demonstrated that ultrasound (US) and microbubble (MB) therapy [sonoreperfusion (SRP)] resolves MVO from venous microthrombi at plasma viscosity. However, blood is more viscous than plasma, and arterial microthrombi are mechanically distinct from venous clot. We tested whether blood viscosity and arterial microthrombi decrease SRP efficacy in our in vitro model of MVO. Lipid MB in plasma and blood viscosity PBS were passed through a 40 μm pore mesh. Arterial microthrombi were formed in a Chandler loop. Venous microthrombi were made statically. MVO was created by occluding the mesh with microthrombi until upstream pressure reached 40 mmHg. US (1 MHz; 5000 cycles; 0.33 Hz PRF; 0.6, 1.0, and 1.5 MPa peak negative pressure) was delivered with a single focused element transducer. MVO caused by arterial thrombi at increased viscosity resulted in less upstream pressure drop during therapy. PCD showed a decrease in inertial cavitation (IC) when viscosity was increased. SRP efficacy is less with arterial thrombi compared to venous thrombi, and higher viscosity further reduces SRP efficacy by decreasing IC. These findings could help guide the selection of US parameters for in vivo optimization of SRP.