Cardiovascular Effects of Increasing Positive End-expiratory Pressure in a Model of Left Ventricular Cardiogenic Shock in Female Pigs

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 H 2 O) and then reverted (15, 10, and 5 cm H 2 O) 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 H 2 O). 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 H 2 O. These effects were highly reversible when PEEP was returned to 5 cm H 2 O. 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 H 2 O (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.