SUPPRESSION OF BLOOD COAGULATION BY NITRIC OXIDE GAS ADDED TO THE SWEEP GAS DURING VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION

Clot formation in the membrane oxygenator is a serious complication in long-term extracorporeal membrane oxygenation (ECMO). In the blood vessels, nitric oxide (NO) generated by nitric oxide synthase on the endothelial cells suppresses both aggregation/activation of platelets and adhesion/activation of leukocytes. Therefore, biocompatibility of the membrane oxygenator may be improved by the addition of NO gas to the sweep gas. The objective of the present study was to determine, using a rat ECMO model, whether addition of NO gas to the blood can suppress blood coagulation. Male Sprague Dawley rats weighing 350 to 400 g were used for the experiments. After the rats were anesthetized, extracorporeal circulation was established by guiding the blood from the right jugular vein into the left femoral vein. Heparin was administered by bolus injection (0.7 unit/g-rat) only at the start of the ECMO. Polymethyl pentene membranes were used for the oxygenator. The sweep gas (NO: 0, 100 or 200 ppm, O2: 30%, CO2: 5%, N2: balance) was added to the blood via the oxygenator. During the experiment, the arterial pressure, oxygenator inlet pressure, venous pressure, activated whole blood clotting time (ACT), and methemoglobin (Met-Hb) concentration were measured. After circulation, the hemoglobin (Hb) content and lactate dehydrogenase (LDH) activity in the eluate from the residual blood in the oxygenator were measured. Extracorporeal circulation was stably performed for 4 hours. There were no differences in the ACT during the experiment among the three groups. The amount of Met-Hb was below 10% in the NO group. The Hb content and LDH activity in the eluate were significantly lower in the 200-ppm NO group than those in the 0 ppm NO. The amount of Met-Hb in the NO group indicates that there is no adverse effect related to Met-Hb. The Hb content and LDH activity indicate that the NO contained in the sweep gas inhibited blood coagulation in this rat extracorporeal circulation model.