PURPOSE: Post-cardiopulmonary bypass (CPB) acute lung injury is responsible for significant morbidity and mortality in cardiopulmonary surgery. In a simulated extracorporeal circulation model, we have previously reported the activation of polymorphonuclear leukocytes (PMN) or monocytes, which are originated from either the circulating pool or new cells released from the bone marrow (BM). The present study was focused on these BM-derived leukocytes and designed to investigate their recruitment into the lung using of our established primate CPB model.
METHODS: Leukocyte precursors were labeled in the BM of cynomolgus monkeys (Macaca fascicularis) in vivo by an intravenous injection (100mg/kg) of 5’-bromo-2’-deoxyuridine (BrdU) at 24 hrs before the surgery, and their release into the circulation and recruitment into the lung were monitored by flow cytometric analysis. Monkeys (N=3) were placed on cardiopulmonary bypass for 2 hrs through a median sternotomy. Blood and bronchial alveolar lavage (BAL) samples were obtained before (baseline), during and at 24 to 72 hrs after the operation.
RESULTS: BrdU-positive PMN first appeared in the circulation 24 hrs after labeling with BrdU (baseline) and increased gradually, followed by a rapid increase at 48 hrs when 24.8 ± 5.8% of PMN were labeled (at 24hrs: 3.3 ± 1.5%, at 72 hrs: 31.8 ± 3.9%). The fraction of BrdU-positive monocytes increased earlier than PMN (at 24 hrs: 6.7 ± 3.0%, at 48 hrs: 35.9 ± 2.1%, at 72 hrs: 38.5 ± 3.4%). The first BrdU-positive leukocytes appeared in BAL 24 hrs after the operation, and then increased (at 48 hrs: 7.5 ± 2.6%, at 72 hrs: 28.1 ± 2.7%).
CONCLUSION: We developed a novel primate CPB model to study the behavior of BM-derived leukocytes (PMN and monocytes) using flow cytometric analysis and showed that leukocytes released from the BM recruit into the lung through the circulation associated with CPB.
CLINICAL IMPLICATIONS: An elevated production and newly release of leukocytes from the BM after the operation with CPB play an important role in the pathogenesis of post-cardiopulmonary bypass acute lung injury.
DISCLOSURE: Yukinobu Goto, No Financial Disclosure Information; No Product/Research Disclosure Information