Quantifying the Reduction in Microcirculation Perfusion After Extracorporeal Circulation

Abstract

Extracorporeal circulation (ECC) is utilized in patients in critical care undergoing procedures such as extracorporeal membrane oxygenation or cardiopulmonary bypass. While most of these procedures are used to take over function of critical organs and provide oxygen to the organism, there is a lack of quantitative models established microcirculatory changes resulting from volume redistribution and changes in vascular pressure during and post ECC. To address this problem, we have combined an intravital microscopy model using the hamster dorsal window model with a custom ECC setup. Briefly, the customized ECC setup drains blood from the left jugular vein and reinfusing into the right carotid artery using a peristaltic pump. The pump is primed with either lactate ringers (LR), polymerized human hemoglobin (PolyhHb, concentration of 10 g/dL), or polymerized human methemoglobin (PolyhMetHb). Flow rate is gradually increased up to 15% of the animal's cardiac output (CO), maintained for 90 minutes, and then gradually decreased. Systemic parameters of pressure (MAP), heart rate (HR), and blood chemistry are monitored during the study. Microcirculatory measures of diameter, velocity, and flow are taken in the dorsal window model. Microcirculatory distribution of oxygen saturation is assessed using hyperspectral imaging. All the aforementioned measurements were taken at baseline, 0 hours, 2 hours, and 24 hours post ECC. After the 24 hour time point, tissues, plasma and urine were taken to assess markers of inflammation, organ function and injury, and hemoglobin and iron toxicity. Preliminary results indicate that arterioles show a markedly decreased diameter and velocity, and consequently blood flow, and venules show an increase in diameters with a drastic decrease in blood velocity. We project that decreases in MAP and HR along with respiratory acidosis will rectify by the 24 hr time point. We project that the LR group will have the worst microcirculatory flow due to the lack of proteins and low viscosity, followed by the PolyhMethb due to its high viscosity, but no oxygen carrying capacity, and the PolyhHb having the best flow due to the high viscosity and the ability to capture and carry oxygen. We expect that these flow parameters and decreased distribution of oxygen in the microcirculation will increase post-ECC, but will still be statistically significant at the 24 hour as compared to the baseline measurements. ECC redistributes blood flow and changes pressure redistribution due to the ECC circuit and pump, which cause changes in myogenic, metabolic, and endothelial mechanisms in smaller vessels in the microcirculation, affecting blood volume to organs and tissues. These studies will further our understanding of ECC impacts on the microcirculation and increase the success rate of these procedures.