First Report of Red Blood Cell Lifespan in a Marine Mammal: An Insight Into Endogenous Carbon Monoxide (CO) Production

Abstract

Deep-diving marine mammals are known to have high concentrations of hemoglobin (Hb), experience hypoxemia from extended breath-holds, and ischemia-reperfusion events in tissues from the physiological dive response. However, certain deep-diving seals (e.g., elephant and Weddell seals) are known to have levels of carbon monoxide (CO) in their blood that are similar to those seen in chronic cigarette smokers (>10% carboxyhemoglobin; COHb). The source of the high CO in the seals is currently unknown. The gas is naturally produced in humans and lab animals as a byproduct of heme degradation, by heme oxygenase enzymes. Therefore, CO production is tightly correlated with red blood cell (RBC) lifespan and associated Hb degradation, as shown by higher COHb (average 1.9%, maximum 9.7%) in patients with shortened RBC lifespans due to hemolytic anemia. Although normally considered a toxic gas, low levels of CO are naturally produced in most mammals (≤ 1% COHb in healthy humans), and exposure to moderate concentrations of exogenous CO has shown to elicit cytoprotective effects (e.g., anti-inflammation) in tissues exposed to hypoxia or ischemia-reperfusion events. Therefore, there is a desire to ascertain the mechanisms behind the regulation of elevated CO in marine mammals. Similar to humans, the production of high concentrations of CO in marine mammals is hypothesized to be directly related to their RBC lifespan. The RBC lifespan has been determined in a variety of terrestrial vertebrates, but never reported for any marine mammal species. In terrestrial mammals, there is an allometric relationship with larger animals having longer RBC lifespans (RBC lifespan (days) = (body mass (kg)0.132) (68) + 49). This study reports the first measurements of RBC lifespan in a marine mammal, the shallow-diving bottlenose dolphin (mass = 216 ± 23 kg, Hb = 14 g/dl). We hypothesize that the bottlenose dolphin would have a RBC lifespan that is similar to healthy humans (~120 days). Our results show the RBC lifespan of the bottlenose dolphin is 165.7 ± 18.4 days. Like humans, bottlenose dolphins also had low levels of CO in their blood (1.6 ± 0.5 % COHb) and exhaled breath (2.4 ± 1.0 ppm). Ongoing measurements in larger, deeper-diving mammals (e.g., beluga whales, 747 ± 244 kg, Hb = 21 g/dl), will further reveal the impact of heme stores and body mass on RBC lifespan and endogenous CO production in mammals.