Microvascular Autoregulation in Skeletal Muscle Using Near-Infrared Spectroscopy and Derivation of Optimal Mean Arterial Pressure in the ICU: Pilot Study and Comparison With Cerebral Near-Infrared Spectroscopy.

IMPORTANCE: Microvascular autoregulation (MA) maintains adequate tissue perfusion over a range of arterial blood pressure (ABP) and is frequently impaired in critical illness. MA has been studied in the brain to derive personalized hemodynamic targets after brain injury. The ability to measure MA in other organs is not known, which may inform individualized management during shock. OBJECTIVES: This study determines the feasibility of measuring MA in skeletal muscle using near-infrared spectroscopy (NIRS) as a marker of tissue perfusion, the derivation of optimal mean arterial pressure (MAPopt), and comparison with indices from the brain. DESIGN: Prospective observational study. SETTING: Medical and surgical ICU in a tertiary academic hospital. PARTICIPANTS: Adult critically ill patients requiring vasoactive support on the first day of ICU admission. MAIN OUTCOMES AND MEASURES: Fifteen critically ill patients were enrolled. NIRS was applied simultaneously to skeletal muscle (brachioradialis) and brain (frontal cortex) while ABP was measured continuously via invasive catheter. MA correlation indices were calculated between ABP and NIRS from skeletal muscle total hemoglobin (MVx), muscle tissue saturation index (MOx), brain total hemoglobin (THx), and brain tissue saturation index (COx). Curve fitting algorithms derive the MAP with the lowest correlation index value, which is the MAPopt. RESULTS: MAPopt values were successfully calculated for each correlation index for all patients and were frequently (77%) above 65 mm Hg. For all correlation indices, median time was substantially above impaired MA threshold (24.5-34.9%) and below target MAPopt (9.0-78.6%). Muscle and brain MAPopt show moderate correlation (MVx-THx r = 0.76, p < 0.001; MOx-COx r = 0.69, p = 0.005), with a median difference of -1.27 mm Hg (-9.85 to -0.18 mm Hg) and 0.05 mm Hg (-7.05 to 2.68 mm Hg). CONCLUSIONS AND RELEVANCE: This study demonstrates, for the first time, the feasibility of calculating MA indices and MAPopt in skeletal muscle using NIRS. Future studies should explore the association between impaired skeletal muscle MA, ICU outcomes, and organ-specific differences in MA and MAPopt thresholds.

Reduction in Serum LDL Cholesterol Using a Nutrient Compendium in Hyperlipidemic Adults Unable or Unwilling to Use Statin Therapy: A Double-Blind Randomized Crossover Clinical Trial.

BACKGROUND: Many hyperlipidemic patients prescribed ß-hydroxy-ß-methylglutaryl coenzyme A reductase inhibitors (statins) are unable or unwilling to take them. A hedonically acceptable snack-based solution formulated from cholesterol-lowering food ingredients could represent a therapeutic alternative but has not been tested in this population. OBJECTIVES: To evaluate the effect of snacks containing a compendium of functional bioactives on fasting LDL cholesterol in statin candidates unwilling to use or intolerant to ≥1 statin drug. Secondary outcomes included changes in circulating total cholesterol (TC), triglycerides, HDL cholesterol, fasting glucose, insulin, and high-sensitivity C-reactive protein concentrations, as well as effects of single-nucleotide polymorphisms (SNPs) on outcome. METHODS: This multicenter, randomized, double-blind, free-living crossover study was composed of 2 regimented phases of 4 wk each, separated by a 4-wk washout. Eighteen men and 36 women, with a mean ± SD age of 49 ± 12 y and mean ± SD LDL cholesterol of 131 ± 32.1 mg/dL,  were instructed to ingest a variety of ready-to-eat snacks twice daily as a substitute for something they were consuming already. Other behavior changes were actively discouraged. Treatment products provided ≥5 g fiber, 1000 mg ω-3 (n-3) fatty acids, 1000 mg phytosterols, and 1800 µmol antioxidants per serving. Control products were calorie-matched like-items drawn from the general grocery marketplace. Serum lipids were measured at baseline and the end of each phase and compared using the ANOVA model. Compliance to study foods was confirmed by serum 18:3n-3 concentration assessment. RESULTS: Comparing intervention phase endpoints, LDL cholesterol was reduced a mean ± SD of 8.80 ± 1.69% (P < 0.0001), and TC was reduced a mean ± SD of 5.08 ± 1.12% (P < 0.0001) by treatment foods compared with control foods, whereas effects on other analytes did not differ between treatments. SNPs were not significantly related to outcomes (P ≥ 0.230). Compliance with study foods was 95%. CONCLUSIONS: Consumption of hedonically acceptable snacks containing a compendium of cholesterol-lowering bioactive compounds can rapidly and meaningfully reduce LDL cholesterol in adult patients unable or unwilling to take statin drugs. This trial was registered at clinicaltrials.gov as NCT02341924.