Introduction: Lower body negative pressure (LBNP) has been used to examine compensatory mechanism to central hypovolemia for several decades. LBNP served as a model of hemorrhagic shock or other stressors such as orthostasis or even as a countermeasure for spaceflight induced cephalad fluid shifts. Current evidence of LBNP-induced effects, however, comes from non-invasive studies carried out largely in human participants. In this study we evaluated the effects of graded LBNP, applied at different body positions, as well as during beta-adrenergic stress, on left ventricle diastolic properties using invasive pressure-volume (PV) analysis.
Methods:  7 landrace pigs (68±9kg) were acutely anesthetized and instrumented with a left ventricular (LV) conductance catheter for PV assessment. The protocol consisted of 4 measurement steps. The LBNP chamber was sealed at 3 different body locations in the supine position: i) cranial, 10cm below the xiphoid process; ii) medial, half-way between cranial and caudal; iii) caudal, at the anterior superior iliac spine. Finally, iv) a dobutamine stress test was performed at caudal position. At each step, following baseline measurements, increasing LBNPs of -15, -30 and -45 mmHg were applied. Aortic occlusions were performed to obtain pressure-volume relationships. Measurements were taken when steady-state hemodynamics were attained.
Results and discussion:  LBNP was hemodynamically well tolerated up to -45 mmHg during measurement steps ii) to iv), while at step i) a maximal LBNP of -30 mmHg could be applied without inducing hemodynamic instability. Heart rate did not increase at any protocol step, meaning no reflex tachycardia was observed throughout the study. The graded decrease in LV filling volume led to a drop in mean aortic pressure (mAOP) throughout the protocol steps, while the expected decrease of cardiac output (CO) occurred already at a LBNP of -30mmHg in step i and ii. In step iii and dobutamine (step iv) CO decreased only upon exposure to -45 mmHg LBNP. LV enddiastolic pressure (Ped) and volume (Ved) fell proportionally to the intensity of applied negative pressures. The graded decrease in LV filling was mirrored by a fall in minimal rate of LV pressure decrease (LV-dP/dTmin), which was more pronounced at step i than ii and iii. Interestingly, the lusitropic effect of Dobutamine compensated for the preload loss up to a -30 mmHg LBNP (Figure below). In line with this, LV minimum pressure, representing LV suction, decreased to negative values at increasing LBNPs.  Finally, graded decrease in LV filling did not impact on the EDPVR-derived LV volume at enddiastolic pressure of 10 mmHg (LV VPed10), indicating a stable LV capacitance throughout the protocol.
Conclusions:  LBNP induced varying degrees of preload-dependent hemodynamic changes according to the different body locations at which LBNP was applied, with cranial LBNP inducing more pronounced hemodynamic effects than the caudal one. As the applied LBNP acutely reduced preload, mAOP and CO fell accordingly, while dobutamine infusion partially counterbalanced the preload loss via increased contractility and lusitropy. Impaired LV filling was accompanied by enhanced LV suction, as indicated by negative LV minimum pressures at increasingly applied LBNP, while LV compliance was not affected.