Fixing skeletal muscle PO2 eliminates hyperinsulinemic microvascular blood flow response.

OBJECTIVE: To determine if insulin-mediated hyperemia is partially dependent on local muscle oxygen concentration. METHODS: Sprague-Dawley rats were anesthetized, and the extensor digitorum longus (EDL) was reflected onto an inverted microscope. Intravital video microscopy sequences were recorded during baseline and hyperinsulinemic euglycemia. The muscle was reflected over a glass stage insert (Experiment 1a and 1b), or over a gas exchange chamber (Experiment 2), and microvascular capillary blood flow was recorded during sequential changes (7%-12%-2%-7%) of oxygen (O2 ) concentration. Blood flow was measured by the red blood cell supply rate (SR) in number of cells per second. All animal protocols were approved by Memorial University's Institutional Animal Care Committee. RESULTS: In Experiment 1a, SR increased from 8.0 to 14.0 cells/s at baseline to euglycemia (p = .01), while no significant SR variation was detected after performing a sham hyperinsulinemic euglycemic clamp (Experiment 1b). In Experiment 2, SR decreased at 12% O2 and increased at 2% O2 , compared to 7% O2 , under both experimental conditions. Magnitude of SR responses to oxygen oscillations during euglycemia were not different to those at baseline at each O2 concentration (p > .9). CONCLUSIONS: Our results suggest that increased blood flow observed in response to insulin is eliminated if tissue oxygen microenvironment is fixed at a given oxygen concentration.

Appropriate Use Criteria for paediatric echocardiography in an outpatient practice: a validation study.

BACKGROUND: Although transthoracic echocardiography is the dominant imaging modality in CHD, optimal utilisation is unclear. We assessed whether adherence to the paediatric Appropriate Use Criteria for outpatient transthoracic echocardiography could reduce inappropriate use without missing significant cardiac disease. METHODS: Using the Appropriate Use Criteria, we determined the indication and appropriateness rating for each initial echocardiogram performed at our institution during calendar year 2014 (N=1383). Chart review documented ordering provider training, patient demographics, and study result, classified as normal, abnormal, or abnormal motivating treatment within a 2-year follow-up period. We tested whether provider training level or patient age correlated with echocardiographic findings or appropriateness rating. RESULTS: We found that 83.9% of echocardiograms were normal and that 66.7% had an appropriate indication. Nearly all abnormal results and all results motivating treatment were in appropriate studies, giving an odds ratio of 2.73 for an abnormal result if an appropriate indication was present (95% confidence interval 1.92-3.89, p<0.001). None of the remaining initial abnormal results with less than appropriate indications became significant, resulting in treatment over 2 years. Results suggest a potential reduction in imaging volume of as much as 33% with application of the criteria. Cardiologists ordered nearly all studies resulting in treatment but also more echocardiograms with less appropriate indications. Most examinations were in older patients; however, most abnormal results were in patients younger than 1 year. CONCLUSIONS: The Appropriate Use Criteria can be used to safely reduce echocardiography volume while still detecting significant heart disease.

Dynamics of capillary blood flow responses to acute local changes in oxygen and carbon dioxide concentrations.

Objectives: We aimed to quantify the magnitude and time transients of capillary blood flow responses to acute changes in local oxygen concentration ([O2]), and carbon dioxide concentration ([CO2]) in skeletal muscle. Additionally, we sought to quantify the combined response to both low [O2] and high [CO2] to mimic muscle microenvironment changes at the onset of exercise. Methods: 13 Sprague Dawley rats were anaesthetized, mechanically ventilated, and instrumented with indwelling catheters for systemic monitoring. The extensor digitorum longus muscle was blunt dissected, and reflected over a microfluidic gas exchange chamber in the stage of an inverted microscope. Four O2 challenges, four CO2 challenges, and a combined low O2 (7-2%) and high CO2 (5-10%) challenges were delivered to the surface with simultaneous visualization of capillary blood flow responses. Recordings were made for each challenge over a 1-min baseline period followed by a 2-min step change. The combined challenge employed a 1-min [O2] challenge followed by a 2-min change in [CO2]. Mean data for each sequence were fit using least-squared non-linear exponential models to determine the dynamics of each response. Results: 7-2% [O2] challenges decreased capillary RBC saturation within 2 s following the step change (46.53 ± 19.56% vs. 48.51 ± 19.02%, p < 0.0001, τ = 1.44 s), increased RBC velocity within 3 s (228.53 ± 190.39 µm/s vs. 235.74 ± 193.52 µm/s, p < 0.0003, τ = 35.54 s) with a 52% peak increase by the end of the challenge, hematocrit and supply rate show similar dynamics. 5-10% [CO2] challenges increased RBC velocity within 2 s following the step change (273.40 ± 218.06 µm/s vs. 276.75 ± 215.94 µm/s, p = 0.007, τ = 79.34s), with a 58% peak increase by the end of the challenge, supply rate and hematocrit show similar dynamics. Combined [O2] and [CO2] challenges resulted in additive responses to all microvascular hemodynamic measures with a 103% peak velocity increase by the end of the collection period. Data for mean responses and exponential fitting parameters are reported for all challenges. Conclusion: Microvascular level changes in muscle [O2] and [CO2] provoked capillary hemodynamic responses with differing time transients. Simulating exercise via combined [O2] and [CO2] challenges demonstrated the independent and additive nature of local blood flow responses to these agents.