The Use of Priming Solutions to Scavenge Free Hb and Free Hb Catabolism Byproducts Reduces Hemolysis-Induced Hypertension in Venovenous Extracorporeal Circulation
Authors: Govender Krianthan , Buehler Paul , Palmer Andre , Owens Robert , Cabrales Pedro 
Published: May 2023

Extracorporeal circulation procedures often utilize a pump as part of the circuit to drive blood flow, which subjects red blood cells (RBCs) to excessively high shear stresses, resulting in hemolysis and free hemoglobin (Hb). Plasma Hb (pHb) is not stable within the circulation, and can degrade into toxic byproducts, resulting in NO scavenging, vasoconstriction, inflammation, and increased production of reactive oxygen species (ROS). The goal of this study is to determine whether a protein complex containing apohemoglobin and haptoglobin (ApoHb-Hp) can alleviate the sequelae associated with hemolysis induced with a model of venous-venous extracorporeal circulation. Male Golden Syrian hamsters instrumented with window chambers underwent surgery with isoflurane anesthetic to insert two venous cannulas; the drainage cannula was positioned in the inferior vena cava, while the reinfusion cannula was inserted into the left jugular vein. To monitor mean blood pressure (MAP), heart rate (HR), hematocrit (Hct), and pHb, an arterial line was placed into the left carotid artery. After surgery, the animal was heparinized (2.5 IU/g), and the cannulas connected to an extracorporeal circuit consisting of a roller pump and a bubble trap. The circuit was randomly primed with one of three solutions tested: 5% human serum albumin (HSA) solution, ApoHb-Hp complex solution, or a protein solution containing hemopexin (3.05 mg/mL), transferrin (29.3 mg/mL), and haptoglobin (8.25 mg/mL) (protein cocktail). The experimental procedure after surgery lasted a total of 2 hours and was broken down into seven stages. First, baseline measurements were taken after hemodilution by slow infusion of the extracorporeal circuit volume at 0.2 mL/min. Then, the flow rate was ramped up to 50% of the animal’s cardiac output (CO), and maintained at this flow rate for 35 minutes. The flow was then ramped down to 0.2 mL/min, and maintained for an additional 15 minutes to help equilibrate the blood within the animal with that contained in the circuit. Lastly, the flow was stopped for 15 minutes, placing the animal off pump support. Results show that MAP was significantly elevated in the HSA group as compared to the apoHb-Hp group during the ramp up phase, the equilibration phase, and the off pump phase at the end. The MAP for the protein cocktail group was significantly lower than the HSA group at all timepoints after flow rate was ramped up. While an increase in pHb was expected for all groups tested, the protein cocktail group was significantly lower than the HSA group at the end of the ramp up, equilibration, and off-pump phase. Interestingly, the protein cocktail group displayed a significantly lower pHb level when compared to the apoHb-Hp group at the end of the experiment. These results taken in conjunction suggest that the use of Hb and heme scavenging solutions as a priming fluid for extracorporeal circulation procedures can help reduce hemolysis-induced hypertension.

This work was supported by funding from NIH/NHLBI grants R01HL162120, R01HL159862.

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.