Portal hyperperfusion after major liver resection and associated sinusoidal damage is a therapeutic target to protect the remnant liver.

Extended liver resection results in loss of a large fraction of the hepatic vascular bed, thereby causing abrupt alterations in perfusion of the remnant liver. Mechanisms of hemodynamic adaptation and associated changes in oxygen metabolism after liver resection and the effect of mechanical portal blood flow reduction were assessed. A pig model (n = 16) of extended partial hepatectomy was established that included continuous observation for 24 h under general anesthesia. Pigs were randomly separated into two groups, one with a portal flow reduction of 70% compared with preoperative values, and the other as a control (n = 8, each). In controls, portal flow [mean (SD)] increased from 74 (8) mL·min-1·100 g-1 preoperatively to 240 (48) mL·min-1·100 g-1 at 6 h after resection (P < 0.001). Hepatic arterial buffer response was abolished after resection. Oxygen uptake per unit liver mass increased from 4.0 (1.1) mL·min-1·100 g-1 preoperatively to 7.7 (1.7) mL·min-1·100 g-1 8 h after resection (P = 0.004). Despite this increase in relative oxygen uptake, total hepatic oxygen consumption (V̇o2) was not maintained, and markers of hypoxia and anaerobic metabolism were significantly increased in hepatocytes after resection. Reduced postoperative portal flow was associated with significantly decreased levels of aspartate aminotransferase and bilirubin and increased hepatic clearance of indocyanine green. In conclusion, major liver resection was associated with persistent portal hyperperfusion, loss of the hepatic arterial buffer response, decreased total hepatic V̇o2 and with increased anaerobic metabolism. Portal flow modulation by partial portal vein occlusion attenuated liver injury after extended liver resection.NEW & NOTEWORTHY Because of continuous monitoring, the experiments allow precise observation of the influence of liver resection on systemic and local abdominal hemodynamic alterations and oxygen metabolism. Major liver resection is associated with significant and persistent portal hyperperfusion and loss of hepatic arterial buffer response. The correlation of portal hyperperfusion and parameters of liver injury and dysfunction offers a novel therapeutic option to attenuate liver injury after extended liver resection.

Right atrial pressure and venous return during cardiopulmonary bypass.

The relevance of right atrial pressure (RAP) as the backpressure for venous return (QVR) and mean systemic filling pressure as upstream pressure is controversial during dynamic changes of circulation. To examine the immediate response of QVR (sum of caval vein flows) to changes in RAP and pump function, we used a closed-chest, central cannulation, heart bypass porcine preparation (n = 10) with venoarterial extracorporeal membrane oxygenation. Mean systemic filling pressure was determined by clamping extracorporeal membrane oxygenation tubing with open or closed arteriovenous shunt at euvolemia, volume expansion (9.75 ml/kg hydroxyethyl starch), and hypovolemia (bleeding 19.5 ml/kg after volume expansion). The responses of RAP and QVR were studied using variable pump speed at constant airway pressure (PAW) and constant pump speed at variable PAW Within each volume state, the immediate changes in QVR and RAP could be described with a single linear regression, regardless of whether RAP was altered by pump speed or PAW (r2 = 0.586-0.984). RAP was inversely proportional to pump speed from zero to maximum flow (r2 = 0.859-0.999). Changing PAW caused immediate, transient, directionally opposite changes in RAP and QVR (RAP: P ≤ 0.002 and QVR: P ≤ 0.001), where the initial response was proportional to the change in QVR driving pressure. Changes in PAW generated volume shifts into and out of the right atrium, but their effect on upstream pressure was negligible. Our findings support the concept that RAP acts as backpressure to QVR and that Guyton's model of circulatory equilibrium qualitatively predicts the dynamic response from changing RAP.NEW & NOTEWORTHY Venous return responds immediately to changes in right atrial pressure. Concomitant volume shifts within the systemic circulation due to an imbalance between cardiac output and venous return have negligible effects on mean systemic filling pressure. Guyton's model of circulatory equilibrium can qualitatively predict the resulting changes in dynamic conditions with right atrial pressure as backpressure to venous return.

Effect of PEEP, blood volume, and inspiratory hold maneuvers on venous return.

According to Guyton's model of circulation, mean systemic filling pressure (MSFP), right atrial pressure (RAP), and resistance to venous return (RVR) determine venous return. MSFP has been estimated from inspiratory hold-induced changes in RAP and blood flow. We studied the effect of positive end-expiratory pressure (PEEP) and blood volume on venous return and MSFP in pigs. MSFP was measured by balloon occlusion of the right atrium (MSFPRAO), and the MSFP obtained via extrapolation of pressure-flow relationships with airway occlusion (MSFPinsp_hold) was extrapolated from RAP/pulmonary artery flow (QPA) relationships during inspiratory holds at PEEP 5 and 10 cmH2O, after bleeding, and in hypervolemia. MSFPRAO increased with PEEP [PEEP 5, 12.9 (SD 2.5) mmHg; PEEP 10, 14.0 (SD 2.6) mmHg, P = 0.002] without change in QPA [2.75 (SD 0.43) vs. 2.56 (SD 0.45) l/min, P = 0.094]. MSFPRAO decreased after bleeding and increased in hypervolemia [10.8 (SD 2.2) and 16.4 (SD 3.0) mmHg, respectively, P < 0.001], with parallel changes in QPA Neither PEEP nor volume state altered RVR (P = 0.489). MSFPinsp_hold overestimated MSFPRAO [16.5 (SD 5.8) vs. 13.6 (SD 3.2) mmHg, P = 0.001; mean difference 3.0 (SD 5.1) mmHg]. Inspiratory holds shifted the RAP/QPA relationship rightward in euvolemia because inferior vena cava flow (QIVC) recovered early after an inspiratory hold nadir. The QIVC nadir was lowest after bleeding [36% (SD 24%) of preinspiratory hold at 15 cmH2O inspiratory pressure], and the QIVC recovery was most complete at the lowest inspiratory pressures independent of volume state [range from 80% (SD 7%) after bleeding to 103% (SD 8%) at PEEP 10 cmH2O of QIVC before inspiratory hold]. The QIVC recovery thus defends venous return, possibly via hepatosplanchnic vascular waterfall.

Collapsibility of caval vessels and right ventricular afterload: decoupling of stroke volume variation from preload during mechanical ventilation.

Collapsibility of caval vessels and stroke volume and pulse pressure variations (SVV, PPV) are used as indicators of volume responsiveness. Their behavior under increasing airway pressures and changing right ventricular afterload is incompletely understood. If the phenomena of SVV and PPV augmentation are manifestations of decreasing preload, they should be accompanied by decreasing transmural right atrial pressures. Eight healthy pigs equipped with ultrasonic flow probes on the pulmonary artery were exposed to positive end-expiratory pressure of 5 and 10 cmH2O and three volume states (Euvolemia, defined as SVV < 10%, Bleeding, and Retransfusion). SVV and PPV were calculated for the right and PPV for the left side of the circulation at increasing inspiratory airway pressures (15, 20, and 25 cmH2O). Right ventricular afterload was assessed by surrogate flow profile parameters. Transmural pressures in the right atrium and the inferior and superior caval vessels (IVC and SVC) were determined. Increasing airway pressure led to increases in ultrasonic surrogate parameters of right ventricular afterload, increasing transmural pressures in the right atrium and SVC, and a drop in transmural IVC pressure. SVV and PPV increased with increasing airway pressure, despite the increase in right atrial transmural pressure. Right ventricular stroke volume variation correlated with indicators of right ventricular afterload. This behavior was observed in both PEEP levels and all volume states. Stroke volume variation may reflect changes in right ventricular afterload rather than changes in preload.NEW & NOTEWORTHY Stroke volume variation and pulse pressure variation are used as indicators of preload or volume responsiveness of the heart. Our study shows that these variations are influenced by changes in right ventricular afterload and may therefore reflect right ventricular failure rather than pure volume responsiveness. A zone of collapse detaches the superior vena cava and its diameter variation from the right atrium.

Right ventricular stroke volume assessed by pulmonary artery pulse contour analysis.

BACKGROUND: Stroke volume measurement should provide estimates of acute treatment responses. The current pulse contour method estimates left ventricle stroke volume. Heart-lung interactions change right ventricular stroke volume acutely. We investigated the accuracy, precision, and trending abilities of four calibrated stroke volume estimates based on pulmonary artery pulse contour analysis. RESULTS: Stroke volume was measured in 9 pigs with a pulmonary artery ultrasound flow probe at 5 and 10 cmH2O of PEEP and three volume states (baseline, bleeding, and retransfusion) and compared against stroke volume estimates of four calibrated pulmonary pulse contour algorithms based on pulse pressure or pressure integration. Bland-Altman comparison with correction for multiple measurements and trend analysis were performed. Heart rate and stroke volumes were 104 ± 24 bpm and 30 ± 12 mL, respectively. The stroke volume estimates had a minimal bias: - 0.11 mL (95% CI - 0.55 to 0.33) to 0.32 mL (95% CI - 0.06 to 0.70). The limits of agreement were - 8.0 to 7.8 mL for calibrated pulse pressure to - 10.4 to 11.5 mL for time corrected pressure integration, resulting in a percentage error of 36 to 37%. The calibrated pulse pressure method performed best. Changes in stroke volume were trended very well (concordance rates 73-100%, r2 0.26 to 0.987, for pulse pressure methods and 71-100%, r2 0.236 to 0.977, for integration methods). CONCLUSIONS: Pulmonary artery pulse contour methods reliably detect acute changes in stroke volume with good accuracy and moderate precision and accurately trend short-term changes in cardiac output over time.

Effects of Trendelenburg position and increased airway pressure on hepatic regional blood flow of normal and resected liver.

High portal venous blood flow (Qpv) may contribute to posthepatectomy liver failure. Both Trendelenburg position (TP) and elevated airway pressure (Paw) increase backpressure to venous return and may thereby reduce Qpv. The aim of this study was to evaluate the effects of TP and increased Paw on hepatosplanchnic hemodynamics before and after major liver resection. Arterial and venous blood pressures, Qpv, extrasplanchnic inferior vena cava (Qivc), superior mesenteric (Qsma), hepatic (Qha), and carotid artery blood flows (Qca) were measured in 14 anesthetized and mechanically ventilated pigs in supine and 30° TP during end-expiratory hold at 5 cmH2O positive end-expiratory pressure (PEEP) and during inspiratory hold with Paw of 15, 20, 25, and 30 cmH2O. After major liver resection, the interventions were repeated in seven randomly selected animals. At baseline, TP increased right atrial pressure (Pra) and Qpv but not Qivc or Qsma. With increased Paw in the supine position, Pra increased and all regional blood flows decreased. TP during increasing Paw attenuated the decrease in Qpv, Qsma, and Qivc but not in Qha or Qca. After liver resection, the effects of TP during increasing Paw remained, albeit at higher portal vein pressures. However, TP alone did not increase IVC venous return. Increasing Paw in supine position reduces Qpv and all other regional flows, while the reduction in Qpv is attenuated in TP, suggesting partly preserved liver waterfall or decreased intrahepatic resistance. Liver resection, despite resulting in major intrahepatic blood flow changes, does not fundamentally influence the interaction of increasing Paw and TP on regional perfusion.NEW & NOTEWORTHY In Trendelenburg position (TP), liver blood flow is the only contributor to increased venous return measured in the inferior vena cava (IVC), which attenuates the decreased IVC venous return induced by increasing airway pressure. After liver resection, TP similarly attenuated effects of increasing airway pressure.

The Effects of Vasoconstriction And Volume Expansion on Veno-Arterial ECMO Flow.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is gaining widespread use in the treatment of severe cardiorespiratory failure. Blood volume expansion is commonly used to increase ECMO flow (QECMO), with risk of positive fluid balance and worsening prognosis. We studied the effects of vasoconstriction on recruitment of blood volume as an alternative for increasing QECMO, based on the concepts of venous return. METHODS: In a closed chest, centrally cannulated porcine preparation (n = 9) in ventricular fibrillation and VA-ECMO with vented left atrium, mean systemic filling pressure (MSFP), and venous return driving pressure (VRdP) were determined in Euvolemia, during Vasoconstriction (norepinephrine 0.05, 0.125, and 0.2 µg/kg/min) and after Volume Expansion (3 boluses of 10 mL/kg Ringer's lactate). Maximum achievable QECMO was examined. RESULTS: Vasoconstriction and Volume Expansion both increased maximum achievable QECMO, delivery of oxygen (DO2), and MSFP, but right atrial pressure increased in parallel. VRdP did not change. The vascular elastance curve was shifted to the left by Vasoconstriction, with recruitment of stressed volume. It was shifted to the right by Volume Expansion with direct expansion of stressed volume. Volume Expansion decreased resistance to venous return and pump afterload. CONCLUSIONS: In a circulation completely dependent on ECMO support, maximum achievable flow directly depended on the vascular factors governing venous return-i.e., closing conditions, stressed vascular volume and the elastance and resistive properties of the vasculature. Both treatments increased maximum achievable ECMO flow at stable DO2, via increases in stressed volume by different mechanisms. Vascular resistance and pump afterload decreased with Volume Expansion.