BIO2: Microcirculation Perfusion is Impaired up to 24 Hours after Veno-arterial Extracorporeal Circulation.

Abstract

Extracorporeal circulation (ECC) procedures, such as extracorporeal membrane oxygenation (ECMO) and cardiopulmonary bypass (CPB), are used to replace the function of the heart and lung, but they induce complications in the form of acute kidney failure, bleeding, heart arrhythmias or thromboembolic complications. This study aimed to quantify the changes in microvascular perfusion and oxygenation that occur after veno-arterial ECC (VA-ECC). Male Golden Syrian hamsters were instrumented with a dorsal window chamber to study their microcirculation and an exteriorized carotid artery catheter for blood pressure and blood gas measurements. After baseline (BL) measurements were taken, the hamster underwent surgery under isoflurane to insert a drainage catheter into the jugular vein. A heparin bolus (0.05 IU/g) was then provided, and the animal was connected to the VA-ECC circuit, which consists of a peristaltic pump and bubble trap. The VA-ECC circuit was primed with either lactated ringers (LR) or 5% human serum albumin in saline (HSA). Blood flow was ramped up over 15 minutes, maintained at 15% of the animal’s cardiac output for 60 minutes, then ramped down over 15 minutes. Sham animals underwent cannulation surgery and heparinization but were not connected to the VA-ECC circuit. The animals were surgically closed, placed on a heating pad, and allowed at least 30 minutes to wake up from the anesthetic plane before taking measurements at 1, 2, and 24 hours after VA-ECC. Results show that flow in arterioles and venules (Figure 1) at all post-ECC timepoints statistically decreased in LR and HSA groups compared to Sham. LR and HSA failed to recover flow in arterioles and venules back to BL levels post-ECC. Interestingly, venule perfusion statistically increased at 1 and 2 hrs in the HSA group compared to the LR group. Functional capillary density (FCD, Figure 2) showed a statistical reduction in capillary perfusion for both ECC groups, with the HSA group maintaining higher levels compared to the LR group. Microvascular hemoglobin (Hb) oxygen (O2) saturation (Figure 3), in venules was statistically reduced post-ECC for both LR and HSA compared to Sham and BL. The microvascular perfusion results, combined with the consistent drop in hematocrit (Hct) post-ECC suggest an imbalance in oncotic pressure that slowly rectifies after ECC. Via Starling’s law of filtration, the priming volume dilutes protein content within the blood, causing the intravascular oncotic pressure to drop, resulting in ultrafiltration at the capillary level. Additionally, the drop in venule Hb O2 saturation and the reduced microvascular perfusion suggest a reduced O2 delivery and potentially a repayment of an O2 debt post-ECC. This study shows that microvascular sequelae could potentially cause ischemic injury in ECC procedures, which can lead to organ damage and inflammation.Figure 1. Microcirculatory hemodynamics. Diameter, velocity, and volumetric blood flow are shown from top to bottom, while arterioles (Sham: n = 38, LR: n = 33; HSA: n = 33) and venules (Sham: n = 38, LR: n = 30, HSA: n = 33) are shown from the left to right columns. All values are normalized to baseline (BL, before ECC) measurements for each vessel. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between groups at each timepoint. † P<0.05 compared to BL, within each group.Figure 2. Functional capillary density (FCD). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between groups. † P<0.05 compared to baseline (BL). N = 6 for all groups.Figure 3. Microvascular Hemoglobin Oxygen Saturation Changes. The top row shows arterioles (Sham: n = 19, LR: n = 13, HSA: n = 16), while the bottom row shows venules (Sham: n = 21, LR: n = 19, HSA: n = 22). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 between groups. † P<0.05 compared to baseline (BL).