Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.)

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The objective of this study is to compare the effectiveness of metabolic signals derived from erythrocytes and derived from the vessel wall for regulating blood flow in heterogeneous microvascular networks. A theoretical model is used to simulate blood flow, mass transport, and vascular responses. The model accounts for myogenic, shear-dependent, and metabolic flow regulation. Metabolic signals are assumed to be propagated upstream along vessel walls via a conducted response. Arteriolar tone is assumed to depend on the conducted metabolic signal as well as local wall shear stress and wall tension, and arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model shows that under certain conditions metabolic regulation based on wall-derived signals can be more effective in matching perfusion to local oxygen demand relative to regulation based on erythrocyte-derived signals, resulting in higher extraction and lower oxygen deficit. The lower effectiveness of the erythrocyte-derived signal is shown to result in part from the unequal partition of hematocrit at diverging bifurcations, such that low-flow vessels tend to receive a reduced hematocrit and thereby experience a reduced erythrocyte-derived metabolic signal. The model simulations predict that metabolic signals independent of erythrocytes may play an important role in local metabolic regulation of vascular tone and flow distribution in heterogeneous microvessel networks.

In striated muscle, the number of capillaries containing moving red blood cells increases with increasing metabolic demand. This phenomenon, termed capillary recruitment, has long been recognized, but its mechanism has been unclear. Here, a theoretical model for metabolic blood flow regulation in a heterogeneous network is used to test the hypothesis that capillary recruitment occurs as a result of active control of arteriolar diameters, combined with unequal partition of hematocrit at diverging microvascular bifurcations. The network structure is derived from published observations of hamster cremaster muscle in control and dilated states. The model for modulation of arteriolar diameters includes length-tension characteristics of vascular smooth muscle and responses of smooth muscle tone to myogenic, shear-dependent, and metabolic stimuli. Blood flow is simulated including nonuniform hematocrit distribution. Convective and diffusive oxygen transport in the network is simulated. Oxygen-dependent metabolic signals are assumed to be conducted upstream from distal vessels to arterioles. With increasing oxygen demand, arterioles dilate, blood flow increases, and the numbers of flowing arterioles and capillaries, as defined by red blood cell flux above a small threshold value, increase. Unequal hematocrit partition at diverging bifurcations contributes to recruitment and enhances tissue oxygenation. The results imply that capillary recruitment, as observed in the hamster cremaster preparations, can occur as a consequence of local control of arteriolar tone and the resulting nonuniform changes in red blood cell fluxes, and provide an explanation for observations of sequential recruitment of individual capillaries in response to modulation of terminal arteriolar diameter.