Validation of lower body negative pressure as an experimental model of hemorrhage

Abstract

Lower body negative pressure (LBNP), a model of hemorrhage (Hem), shifts blood to the legs and elicits central hypovolemia. This study compared responses to LBNP and actual Hem in sedated baboons. Arterial pressure, pulse pressure (PP), central venous pressure (CVP), heart rate, stroke volume (SV), and +dP/dt were measured. Hem steps were 6.25%, 12.5%, 18.75%, and 25% of total estimated blood volume. Shed blood was returned, and 4 wk after Hem, the same animals were subjected to four LBNP levels which elicited equivalent changes in PP and CVP observed during Hem. Blood gases, hematocrit (Hct), hemoglobin (Hb), plasma renin activity (PRA), vasopressin (AVP), epinephrine (EPI), and norepinephrine (NE) were measured at baseline and maximum Hem or LBNP. LBNP levels matched with 6.25%, 12.5%, 18.75%, and 25% hemorrhage were -22 ± 6, -41 ± 7, -54 ± 10, and -71 ± 7 mmHg, respectively (mean ± SD). Hemodynamic responses to Hem and LBNP were similar. SV decreased linearly such that 25% Hem and matching LBNP caused a 50% reduction in SV. Hem caused a decrease in Hct, Hb, and central venous oxygen saturation (ScvO2). In contrast, LBNP increased Hct and Hb, while ScvO2 remained unchanged. Hem caused greater elevations in AVP and NE than LBNP, while PRA, EPI, and other hematologic indexes did not differ between studies. These results indicate that while LBNP does not elicit the same effect on blood cell loss as Hem, LBNP mimics the integrative cardiovascular response to Hem, and validates the use of LBNP as an experimental model of central hypovolemia associated with Hem.

The role of cerebral oxygenation and regional cerebral blood flow on tolerance to central hypovolemia

“…While application of LBNP does not mimic all of the responses observed in traumatic hemorrhage (e.g., tissue trauma, pain, and metabolic responses, such as acidosis), this technique allows us to isolate the physiological responses of central hypovolemia without these confounding factors. In addition, although LBNP does not elicit blood cell loss, as seen in actual hemorrhage, it does mimic some of the cardiovascular and cerebral blood flow responses elicited by hemorrhage (17,21,36).…”

“…However, arterial oxygen content should be similar between groups as 1) experiments were conducted in a normoxic testing environment, 2) we assume hemoglobin concentration would increase in both groups on the basis of similar reductions in central blood volume and subsequent fluid extravasation (17,21), and 3) central hypovolemia elicited by LBNP stress does not induce any changes in arterial oxygen saturation or Pa O 2 (21,50).…”

“…Two recent studies reported comparable hemodynamic responses to LBNP and blood loss up to 1,000 ml in humans (21,36) and 25% loss of total blood volume in baboons (17). It is well established that during the initial stages of progressive central hypovolemia, reflex cardiovascular responses are initiated (e.g., tachycardia, peripheral vasoconstriction) (5,6,15,19,24,38), protecting the vital organs from hypoperfusion.…”

Coagulation changes during lower body negative pressure and blood loss in humans

“…LBNP sequesters circulating blood in the lower body, thereby reducing central blood volume and mimicking hemodynamic responses generated during BL (4,15,18). However, it is unclear if markers of coagulation system activation respond similarly during these protocols.…”

“…Lower body negative pressure (LBNP) is a technique that is used as a noninvasive surrogate to study many of the physiological responses to BL (4,15,18). LBNP sequesters circulating blood in the lower body, thereby reducing central blood volume and mimicking hemodynamic responses generated during BL (4,15,18).…”