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Thrombosis and bleeding are major complications in cases of prolonged extracorporeal lung assist (ECLA) with an artificial-membrane lung. Antithrombogenic treatment of the artificial-membrane oxygenator and circuits is indispensable for safe ECLA. The efficacy of a new heparin-coated membrane lung with minimal systemic heparinization was evaluated for 7 days and compared with a nonheparin-coated membrane lung in goats. The animals were randomly assigned to either the heparin-coated membrane group (HM group, n = 5) or nonheparin-coated membrane group (NHM group, n = 5). Activated coagulation time (ACT) during ECLA was controlled to below 150 s in the HM group, and to near 200 s in the NHM group. All goats in the HM group were sustained on ECLA for 7 days, but two goats in the NHM group died on the 4th and 6th days, respectively. The mean systemic administration rate of heparin during ECLA was 22.4 +/- 4.4 U/kg/h in the HM group and 39.0 +/- 10.0 U/kg/h in the NHM group. There was a significant difference between the two groups (P < 0.05). The oxygen transfer rate, the Pco(2) difference, the perfusion resistance, and platelet counts showed no significant changes. There was no plasma leakage from the artificial lung. Although several clots were observed in the stagnant areas of the artificial lung, they did not lead to deterioration of the function of the artificial lung. The excellent antithrombogenicity, gas exchange ability, and durability of this new artificial lung with circuits might contribute to successful prolonged ECLA with minimal systemic heparinization.

Heparin was covalently bonded to a new hollow-fiber dense membrane artificial lung and extracorporeal circuit using a silane coupling agent and polyethyleneimine. This study investigated whether prolonged, venoarterial bypass extracorporeal lung assist (V-A bypass ECLA) could be sustained in a goat by the combination of the new membrane lung and minimal systemic heparinization. We maintained ECLA with the hollow-fiber lungs (surface area, 0.8 m2) and circuits by titrating the activated clotting time (ACT) to below 150 s with minimal systemic heparinization in 5 goats. The outcome was assessed from the function of the artificial lung via macro and microscopic examinations after the experiments and the incidence of systemic complications. The 5 goats were maintained on ECLA for 6 to 27 days. The bypass flow rate, blood gases at the return and drainage sites, platelet counts, and platelet aggregation activity were well maintained. Although the hemoglobin concentration, hematocrit, and plasma protein at the start of the ECLA were significantly lower than the pre-ECLA values due to hemodilution, the values remained stable during ECLA. A cerebral infarction occurred in 1 goat. However, in the other 4 goats, no complications such as bleeding, thrombosis, or plasma leakage from the artificial lung were observed. Although several thrombi were observed in the stagnant area of the artificial lung, these local thrombi did not cause the function of the artificial lung to deteriorate. We found that this new type of highly biocompatible, dense membrane artificial lung, when combined with minimal systemic heparinization, prolonged ECLA without the deterioration of the artificial lung function and was suitable for prolonged ECLA.

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We report on the experimental application of nafamostat mesilate (NM, 6‐amidino‐2‐naphthyl p‐guanidinobenzoate dimethanesulfonate, FUT®), a new anticoagulant, to extracorporeal lung assist (ECLA) with an artificial membrane lung. Venovenous ECLA, from the jugular vein to the femoral vein, was performed with a hollow‐fiber membrane lung at a blood flow rate of approximate 82 ml kg‐1 min‐1 for 24 h in 7 dogs under anesthesia and hypoventilation. Heparin (10 U ml‐1 in a priming lactated Ringer solution of 140 ml, and 200 U kg‐1) was administered before blood access cannulation. After start of ECLA, however, no heparin was used, and nafamostat mesilate was continuously infused into the drainage line of the bypass circuit to control activated coagulation time (ACT) at about 150 to 200s. To maintain the prolonged ACT, 8:0 ± 1.7 mg kg‐1 h‐1 of NM was required. Arterial blood pressure and pulse rate decreased significantly. Though fibrin monomer test revealed hypercoagulability after 6 h of ECLA, platelet counts did not significantly decrease. Total blood loss remained less than 40 g. The artificial membrane lung sustained a good gas exchange and low flow resistance throughout ECLA. Macroscopic examination revealed small spotty thrombi in the artificial lung but no major pathologic changes of the visceral organs in the all dogs at autopsy. High‐dose NM administration could control blood coagulation and decrease blood loss during ECLA for 24 h without deterioration of the artificial lung and systemic complication other than mild hypotension and bradycardia.