Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O2 extraction during septic shock

Derangements of microvascular blood flow distribution might contribute to disturbing O2 extraction by peripheral tissues. We evaluated the dynamic relationships between the mesenteric O2 extraction ratio ([Formula: see text]) and the heterogeneity of microvascular blood flow at the gut and sublingual mucosa during the development and resuscitation of septic shock in a swine model of fecal peritonitis. Jejunal-villi and sublingual microcirculation were evaluated using a portable intravital-microscopy technique. Simultaneously, we obtained arterial, mixed-venous, and mesenteric blood gases, and jejunal-tonometric measurements. During resuscitation, pigs were randomly allocated to a fixed dose of dobutamine (5 µg·kg−1·min−1) or placebo while three sham models with identical monitoring served as controls. At the time of shock, we observed a significant decreased proportion of perfused intestinal-villi (villi-PPV) and sublingual percentage of perfused small vessels (SL-PPV), paralleling an increase in [Formula: see text] in both dobutamine and placebo groups. After starting resuscitation, villi-PPV and SL-PPV significantly increased in the dobutamine group with subsequent improvement of functional capillary density, whereas [Formula: see text] exhibited a corresponding significant decrease (repeated-measures ANOVA, P = 0.02 and P = 0.04 for time × group interactions and intergroup differences for villi-PPV and [Formula: see text], respectively). Variations in villi-PPV were paralleled by variations in [Formula: see text] ( R2 = 0.88, P < 0.001) and these, in turn, by mesenteric lactate changes ( R2 = 0.86, P < 0.001). There were no significant differences in cardiac output and systemic O2 delivery throughout the experiment. In conclusion, dynamic changes in microvascular blood flow heterogeneity at jejunal mucosa are closely related to the mesenteric O2 extraction ratio, suggesting a crucial role for microvascular blood flow distribution on O2 uptake during development and resuscitation from septic shock. NEW & NOTEWORTHY Our observations suggest that dynamic changes in the heterogeneity of microvascular blood flow at the gut mucosa are closely related to mesenteric O2 extraction, thus supporting the role of decreasing functional capillary density and increased intercapillary distances on alterations of O2 uptake during development and resuscitation from septic shock. Addition of a low-fixed dose of dobutamine might reverse such flow heterogeneity, improving microcirculatory flow distribution and tissue O2 consumption.

Microcirculatory dysfunction in sepsis: pathophysiology, clinical monitoring, and potential therapies

Abnormal microvascular perfusion, including decreased functional capillary density and increased blood flow heterogeneity, is observed in early stages of the systemic inflammatory response to infection and appears to have prognostic significance in human sepsis. It is known that improvements in systemic hemodynamics are weakly correlated with the correction of microcirculatory parameters, despite an appropriate treatment of macrohemodynamic abnormalities. Furthermore, conventional hemodynamic monitoring systems available in clinical practice fail to detect microcirculatory parameter changes and responses to treatments, as they do not evaluate intrinsic events that occur in the microcirculation. Fortunately, some bedside diagnostic methods and therapeutic options are specifically directed to the assessment and treatment of microcirculatory changes. In the present review we discuss fundamental aspects of septic microcirculatory abnormalities, including pathophysiology, clinical monitoring, and potential therapies.

A dynamic model of oxygen transport from capillaries to tissue with moving red blood cells

Most oxygen required to support the energy needs of vertebrate tissues is delivered by diffusion from microvessels. The presence of red blood cells (RBCs) makes blood flow in the microcirculation highly heterogeneous. Additionally, flow regulation mechanisms dynamically respond to changes in tissue energy demand. These spatiotemporal variations directly affect the supply of oxygen to parenchymal cells. Due to various limiting assumptions, current models of oxygen transport cannot fully capture the consequences of complex hemodynamic effects on tissue oxygenation and are often not suitable for studying unsteady phenomena. With our new approach based on moving RBCs, the impact of blood flow heterogeneity on oxygen partial pressure (Po2) in the tissue can be quantified. Oxygen transport was simulated using parachute-shaped solid RBCs flowing through a capillary. With the use of a conical tissue domain with radii 19 and 13 μm, respectively, our computations indicate that Po2 at the RBC membrane exceeds Po2 between RBCs by 30 mmHg on average and that the mean plasma Po2 decreases by 9 mmHg over 50 μm. These results reproduce well recent intravascular Po2 measurements in the rodent brain. We also demonstrate that instantaneous variations of capillary hematocrit cause associated fluctuations of tissue Po2. Furthermore, our results suggest that homogeneous tissue oxygenation requires capillary networks to be denser on venular side than on arteriolar side. Our new model for oxygen transport will make it possible to quantify in detail the effects of blood flow heterogeneity on tissue oxygenation in realistic capillary networks.

Pulmonary blood flow and its distribution in highly trained endurance athletes and healthy control subjects

Pulmonary blood flow (PBF) is an important determinant of endurance sports performance, yet studies investigating adaptations of the pulmonary circulation in athletes are scarce. In the present study, we investigated PBF, its distribution, and heterogeneity at baseline and during intravenous systemic adenosine infusion in 10 highly trained male endurance athletes and 10 untrained but fit healthy controls, using positron emission tomography and [15O]water at rest and during adenosine infusion at supine body posture. Our results indicate that PBF at rest and during adenosine stimulation was similar in both groups (213 ± 55 and 563 ± 138 ml·100 ml−1·min−1 in athletes and 206 ± 83 and 473 ± 212 ml·100 ml−1·min−1 in controls, respectively). Although the PBF response to adenosine was thus unchanged in athletes, overall PBF heterogeneity was reduced from rest to adenosine infusion (from 84 ± 18 to 70 ± 19%, P < 0.05), while remaining unchanged in healthy controls (77 ± 16 to 85 ± 33%, P = 0.4). Additionally, there was a marked gravitational influence on general PBF distribution so that clear dorsal dominance was observed both at rest and during adenosine infusion, but training status did not have an effect on this distribution. Regional blood flow heterogeneity was markedly lower in the high-perfusion dorsal areas, both at rest and during adenosine, in all subjects, but flow heterogeneity in dorsal area tended to further decrease in response to adenosine in athletes. In conclusion, reduced blood flow heterogeneity in response to adenosine in endurance athletes may be a reflection of capillary reserve, which is more extensively recruitable in athletes than in matched healthy control subjects.