Tissue hypoxia during acute hemorrhage

Abstract

Calzia and colleagues argue [1] that tissue hypoxia in a rat model of hemorrhage that led to an oxygen deficit of 120 ml/kg with hyperlactacidemia [2] may be modest, and may not affect hydrogen sulfide oxidation since '... the arterial oxygen partial pressure was still normal ...' [1]. This contention requires clarification. A relative hyperventilation is the rule in most experimental models of hemorrhage [2,3], since the reduction in oxygen uptake/consumption V˙O2 is always larger than that in alveolar ventilation V˙A. Alveolar oxygen partial pressure therefore increases during hemorrhage, as it is the ratio between V˙O2 and V˙A (and not the absolute level of V˙A) that dictates the partial pressure of oxygen in the alveolar gas (PAO2): PAO2 = PIO2-kV˙O2/V˙A This tells us very little about the level of tissue hypoxia. In all of the models used to study an acute hemorrhage, the baseline oxygen delivery rate (DO2=Q˙CaO2) is three to four times higher than V˙O2, despite a large discrepancy in V˙O2 per kilogram between a 500 g rat, a 20 kg pig or a human being: cardiac output, DO2 and V˙O2 do share a similar allometric function with body weight, so that the blood oxygen content is the same in most species. Q˙drops dramatically during hemorrhage, reducing DO2. The level of DO2 decreases up to 10 times while V˙O2 drops by four times regardless of the size of animal chosen [3,4] so that both DO2 and V˙O2 reach one-third of the baseline metabolic rate at the end of a severe hemorrhage! This should certainly lead to one of the most severe forms of tissue hypoxia - with normal arterial blood oxygen partial pressure - unless a decrease in oxygen demand contributes significantly to the reduction in V˙O2 induced by the decline in DO2. Indeed, although the relationship between DO2 and V˙O2 is similar across species, the meaning of a reduction in V˙O2 can greatly differ among animal models according to their ability to decrease the oxygen demand [3,5] - a phenomenon present during hemorrhage in small mammals [3]. It is eventually this ability to modify oxygen demand during a hemorrhage, in keeping with DO2, which controls the level of tissue hypoxia, and not the absolute levels of PaO2, DO2 or V˙O2.