Hypoxia and anoxia tolerance of vertebrate hearts: an evolutionary perspective

Extreme changes in environmental oxygen (O(2)) is a constant issue that ectotherm vertebrates have to deal with, whereas for endotherms severe hypoxia and reoxygenation are usually related to a pathological state. The physiological mechanisms of hypoxia tolerance in ectotherms are based on biochemical evolutionary adaptations and may serve in understanding endogenous phenomena of protection against diminished O(2) availability in the heart. In this review, we will, therefore, describe different species of fish, amphibian, and reptile that are well-known examples of cardiac tolerance to O(2) deficiency. We will then focus on a subset of Antarctic fishes which have lost physiological transporters of O(2) such as hemoglobin and myoglobin (Mb) and that have reached a surprising adaptation to this extreme environment. Moreover, we will concentrate on the cardio-protective effects of the interaction between Mb and nitric oxide with particular emphasis on the nitrite-reductase function of Mb. Finally, the role of a recently described gasotransmitter, the free diffusible hydrogen sulfide, will be briefly discussed in relation to hypoxia. This evolutionary and comparative perspective may provide a useful and heuristic stimulus for medically oriented research aimed at elucidating the environmental and genetic risk factors underlying the vulnerability of the human heart.