One-year observation of Wistar rats after intravenous infusion of hemoglobin-vesicles (artificial oxygen carriers)

Hemoglobin-vesicles (HbV) or liposome-encapsulated Hb are artificial oxygen carriers. Our previous studies of the bolus infusion of HbV into Wistar rats showed that HbV was captured by the reticuloendothelial system from the blood stream and degraded completely with no deteriorative effect for 2 weeks. However, one authority on artificial organs research suggested conducting a one-year observation because he experienced, with one lipid-emulsified perfluorocarbon (PFC), that rats died within one year from a pulmonary abnormality after receiving the PFC emulsion due to the unstable dispersion state (personal communication). We thought this would never happen for HbV because the dispersion state of HbV is stable with PEG-modification. To confirm this, we made one-year observations after HbV infusion as suggested. Five male Wistar rats intravenously received 20 ml/kg HbV suspended in saline ([Hb] = 10 g/dL). They were housed in separated cages and provided with food and water ad libitum. All rats survived one year, and were apparently healthy. Their body weights (821 +/- 75 g) reflected obesity from their confinement in small cages. No histopathological abnormality was found in the lung. Plasma biochemical analyses showed overall normal organ functions. In our previous report, plasma lipid levels increased transiently at 1 or 2 days; then they reverted to the control level at 7 days. One year later, the rats showed much higher plasma lipid levels, a symptom of hyperlipidemia that is attributable to obesity and aging. It seemed the transient increases at the early days had no impact compared with the levels of hyperlipemia of the old rats.