Search

Background: Cardiogenic shock (CS) presents a medical challenge with limited treatment options. Positive end-expiratory pressure (PEEP) during mechanical ventilation has been linked with clinical benefits in patients with CS. This study investigated whether increasing PEEP levels could unload the left ventricle (LV) in CS in a large animal model of LV-CS., Methods: Left ventricle cardiogenic shock was induced in 26 female pigs (60 kg) by microsphere injections into the left main coronary artery. In one study, protocol PEEP was increased (5, 10, and 15 cm H2O) and then reverted (15, 10, and 5 cm H2O) in 3-min intervals. In another protocol, PEEP increments with higher granularity were conducted through 3-min intervals (5, 8, 10, 13, and 15 cm H2O). Hemodynamic measurements were performed at all PEEP levels during a healthy state and in LV-CS with LV pressure-volume loops. The primary endpoint was pressure-volume area. Secondary endpoints included other mechanoenergetic parameters and estimates of LV preload and afterload., Results: Cardiac output (CO) decreased significantly in LV-CS from 4.5 ± 1.0 to 3.1 ± 0.9 l/min (P < 0.001). Increasing PEEP resulted in lower pressure-volume area, demonstrating a 36 ± 3% decrease in the healthy state (P < 0.001) and 18 ± 3% in LV-CS (P < 0.001) at PEEP 15 cm H2O. These effects were highly reversible when PEEP was returned to 5 cm H2O. Although mean arterial pressure declined with higher PEEP, CO remained preserved during LV-CS (P = 0.339). Increasing PEEP caused reductions in key measures of LV preload and afterload during LV-CS. The right ventricular stroke work index was decreased with increased PEEP. Despite a minor increase in heart rate at PEEP levels of 15 cm H2O (71 beats/min vs. 75 beats/min, P < 0.05), total mechanical power expenditure (pressure-volume area normalized to heart rate) decreased at higher PEEP., Conclusions: Applying higher PEEP levels reduced pressure-volume area, preserving CO while decreasing mean arterial pressure. Positive end-expiratory pressure could be a viable LV unloading strategy if titrated optimally during LV-CS., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.)

Lactate may inhibit lipolysis and thus enhance insulin sensitivity, but there is a lack of metabolic human studies. This study aimed to determine how hyperlactatemia affects lipolysis, glucose- and protein metabolism, and insulin sensitivity in healthy men. In a single-blind, randomized, crossover design, eight healthy men were studied after an overnight fast on two occasions: 1 ) during a sodium-lactate infusion (LAC) and 2 ) during a sodium-matched NaCl infusion (CTR). Both days consisted of a 3-h postabsorptive period followed by a 3-h hyperinsulinemic-euglycemic clamp (HEC). Lipolysis rate, endogenous glucose production (EGP), and delta glucose rate of disappearance (ΔRd glu ) were evaluated using [9,10- 3 H]palmitate and [3- 3 H]glucose tracers. In addition, whole body- and forearm protein metabolism was assessed using [ 15 N]phenylalanine, [ 2 H 4 ]tyrosine, [ 15 N]tyrosine, and [ 13 C]urea tracers. In the postabsorptive period, plasma lactate increased to 2.7 ± 0.5 mmol/L during LAC vs. 0.6 ± 0.3 mmol/L during CTR ( P < 0.001). In the postabsorptive period, palmitate flux was 30% lower during LAC compared with CTR (84 ± 32 µmol/min vs. 120 ± 35 µmol/min, P = 0.003). During the HEC, palmitate flux was suppressed similarly during both interventions ( P = 0.7). EGP, ΔRd glu , and M value were similar during LAC and CTR. During HEC, LAC increased whole body phenylalanine flux ( P = 0.02) and protein synthesis ( P = 0.03) compared with CTR; LAC did not affect forearm protein metabolism compared with CTR. Lactate infusion inhibited lipolysis by 30% under postabsorptive conditions but did not affect glucose metabolism or improve insulin sensitivity. In addition, whole body phenylalanine flux was increased. Clinical trial registrations: NCT04710875. NEW & NOTEWORTHY Lactate is a decisive intermediary metabolite, serving as an energy substrate and a signaling molecule. The present study examines the effects of lactate on substrate metabolism and insulin sensitivity in healthy males. Hyperlactatemia reduces lipolysis by 30% without affecting insulin sensitivity and glucose metabolism. In addition, hyperlactatemia increases whole body amino acid turnover rate.