Graded lower body negative pressure induces intraventricular negative pressures and incremental diastolic suction: a pressure-volume study in a porcine model

Abstract

Lower body negative pressure (LBNP) has been a tool to study compensatory mechanisms to central hypovolemia for decades. However, underlying hemodynamic mechanisms were mostly assessed non-invasively and remain unclear. We hypothesized that incremental LBNP reduces diastolic filling and thereby affects left ventricular (LV) diastolic suction (DS). Here, we investigated the impact of graded LBNP at 3 different levels of seal as well as during beta-adrenergic stimulation by invasive pressure-volume (PV) analysis. Eight Landrace pigs were instrumented closed-chest for PV assessment. LBNP was applied at three consecutive locations: I) cranial, 10cm below xiphoid process; II) medial, half-way between cranial and caudal; III) caudal, at the iliac spine. Level III) was repeated under dobutamine infusion. At each level, baseline measurements were followed by application of incremental LBNP of -15, -30 and -45 mmHg. LBNP induced varying degrees of preload-dependent hemodynamic changes, with cranial LBNP inducing more pronounced effects than caudal. According to the Frank-Starling mechanism, graded LBNP progressively reduced LV stroke volume (LV SV) following a decrease in LV end-diastolic volume. Negative intraventricular minimal pressures were observed during dobutamine-infusion as well as higher levels of LBNP. Of note, incremental LV negative pressures were accompanied by increasing DS volumes, derived by extrapolating the volume at zero transmural pressure, the so-called equilibrium volume (V0), related to LV SV. In conclusion, graded preload reduction shifts the PV loop to smaller volumes and end-systolic volume below V0, which induces negative LV pressures and increases LV suction. Accordingly, LBNP induced central hypovolemia is associated with increased DS.

Impact of Increasing Lower Body Negative Pressure and Its Abrupt Release on Left Ventricular Hemodynamics in Anesthetized Pigs

“…LV-EDP and LV-EDV ( Figure 4 E,F) significantly decreased from baseline at step iii (−45 mmHg) irrespective of sealing position, while, once again, significant decrease occurred already at a pressure of −15 mmHg at the cranial position. Overall, dobutamine infusion markedly impacted on LV volume and pressure changes, resulting in lower volumes and negative LV-EDP [ 14 ].…”

“…The experimental setup has been described in detail before [ 12 , 13 , 14 ]. Briefly, all experiments were performed at the Section for Biomedical Research of the Medical University of Graz at identical time of day, location and room temperature.…”

“…The detailed protocol has been described in a recently published sub-study, focusing on the impact of LBNP on diastolic suction [ 14 ]. The LBNP sealing was performed at three different positions, as represented in Figure 2 : I, 10 cm caudal of the xiphoid process; II, halfway between I and III; and III, at the height of the anterior iliac spine, which is the default LBNP sealing position in humans.…”

“…Furthermore, hemodynamic assessment at position III was repeated during beta-adrenergic stimulation. Dobutamine was infused continuously after a single bolus and titrated to double the steady-state maximum LV dP/dt (position IIId), as previously published [ 12 , 13 , 14 ]. We clearly wanted to rule out any additional systemic effect of dobutamine between positions I to III and therefore chose to administer it only during position III, as this is also the position considered most comparable to the one used in protocols in humans.…”

“…Data assessment and analysis were performed as previously described by our study group [ 13 , 14 ]. Briefly, PV-loops and time intervals were analyzed using CircLab Software (custom made by P. Steendijk [ 16 ]).…”