When D_O2 to skeletal muscle is progressively reduced by graded systemic hypoxia, V_O2 is maintained constant until a critical level of D_O2 (D_O2,crit) below which V_O2 falls directly with D_O2 (Samsel & Schumacker, 1988; Edmunds & Marshall, 2001). Concomitantly, there is muscle vasodilatation such that in the rat hindlimb, femoral vascular conductance (FVC) increases progressively. This increase in FVC, which can be attributed to dilatation of the proximal arterioles is nitric oxide (NO) dependent and is partly attributable to adenosine acting on A1 receptors. Moreover, blockade of NO synthesis or A1 receptors increased D_O2,crit, indicating it is determined by A1 and NO-dependent dilatation of terminal arterioles (Edmunds & Marshall, 2000, 2001) In the present study, we have tested the relationship between D_O2 and V_O2 when D_O2 is reduced by haemodilution.

In 16 rats anaesthetised with Saffan (7-12 mg kg^-1 h^-1 I.V.), up to eleven 1 ml volumes of blood were removed at 10 min intervals, each being simultaneously replaced by infusion of Hetastarch (Sigma, 6 % in saline). Arterial and venous samples were analysed for haemoglobin (Hb) content and O₂ content and femoral blood flow was recorded to allow calculation of D_O2 and V_O2. The arterial partial pressures of O₂ and CO₂ were also measured. At the end of the experiments the animals were humanely killed with an anaesthetic overdose.

The Hb content fell from 13 ± 0.49 to 3.8 ± 0.15 g l^-1 (mean ± S.E.M.) by the 11th dilution. Meanwhile, D_O2 fell progressively from 1 ± 0.48 to 0.29 ± 0.06 ml O₂ min^-1 kg^-1 (P < 0.05, ANOVA) and there was a biphasic relationship between D_O2 and V_O2 allowing D_O2,crit to be calculated as 0.78 ± 0.08 ml O₂ min^-1 kg^-1. However, FVC did not change: 0.020 ± 002 before the 1st and 0.025 ± 0.003 ml min^-1 mmHg^-1 after the 11th haemo-dilution, respectively. P_a,O2 and P_a,CO2 were 71.4 and 39 ± 1.0 mmHg, respectively, and remained constant until the 4-6th dilution. P_a,O2 then increased progressively to 97 ± 5.0 mmHg while P_a,CO2 fell to 27.5 ± 1.5 mmHg (P < 0.05 in each case) indicating hyperventilation. In a further 12 rats the A1 receptor antagonist DPCPX (0.1 mg kg^-1 I.V.) given before haemodilution decreased the D_O2,crit to 0.596 ± 0.032 ml O₂ min^-1 kg^-1 (P < 0.05 control vs. DPCPX) and revealed a significant increase in FVC to a maxmimum of 0.34 ± 0.004 ml min^-1 mmHg^-1 at the 11th dilution (P < 0.01 control vs. DPCPX).

These results indicate that when D_O2 to skeletal muscle is progressively reduced by haemodilution, V_O2 is initially maintained and then decreases in a biphasic manner as occurs during progressive systemic hypoxia. They also suggest that in contrast with systemic hypoxia, haemodilution does not increase FVC. In as much as D_O2,crit is determined by dilatation of the terminal arterioles, the present results suggest that in contrast to systemic hypoxia, adenosine released during haemodilution, acting on A₁ receptors limits dilatation of the terminal arterioles and the proximal arterioles that mainly contribute to changes in FVC. We propose that the mechanisms that sense and respond to changes in O₂ levels are different when D_O2 is reduced by changing the O₂ content of arterial blood (haemodilution), rather than by reducing P_a,O2 (systemic hypoxia).

Edmunds, N.J. & Marshall, J.M. (2000). J. Physiol. 525.P, 15-16P.

Edmunds, N.J. & Marshall, J.M. (2001). J. Physiol. 532, 251-259. abstract

Samsel, R.W. & Schumacker, P.T. (1988). J. Appl. Physiol.. 64, 2074-2082.