Cardiopulmonary hemodynamic responses to the small injection of hemoglobin vesicles (artificial oxygen carriers) in miniature pigs

Intravenous injection of liposomes into pigs reportedly induces anaphylactoid reactions at a small dose, resulting in circulatory disorder. Hemoglobin vesicles (HbVs) are artificial oxygen carriers encapsulating Hb solution in liposomes. It is not known how pigs respond to HbV injection. We aimed to analyze the cardiopulmonary responses to small injections of HbV and empty vesicle (EV) and compare them with a conventional liposome (CL) with a different lipid composition containing phosphatidylglycerol (PG). PG is known to induce an anaphylactoid reaction in pigs. Nine male miniature pigs were used for HbV, EV, and CL injections. The anesthetized pig received 0.05 and 0.5 mL/kg of a test fluid for the first and second injection with a 70 min interval. Results show that CL repeatedly induced significant increases in systemic and pulmonary arterial pressures and vascular resistances and decreases in heart rate and cardiac output (CO). HbV and EV at the first injection-induced pulmonary hypertension, with significantly smaller changes in systemic arterial pressure and CO. No remarkable response was visible at the second injection in spite of a larger dosage. Only CL repeatedly induced thrombocytopenia, leukocytopenia, and plasma thromboxane B₂ increase resulting from complement activation, although HbV and EV showed smaller changes. Transmittance electron micrograph of pulmonary intravascular macrophages (PIMs) showed phagocytosis of HbV, indicating the possibility that nonspecific phagocytosis by PIMs relates to the responses observed after the first injection. HbV does not induce a significant anaphylactoid reaction in pigs compared with CL because of the different lipid composition.