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.

Keywords: blood loss; blood pressure; cardiac output; central hypovolemia; central venous pressure; stroke volume.

Fig. 1.

Central venous pressure (A) and pulse pressure (B) during baseline and 4 steps of hemorrhage (●) and lower body negative pressure (LBNP; ○) corresponding to 6.25% (n = 14), 12.5% (n = 14), 18.75% (n = 14), and 25% (n = 12) total blood volume loss. Data are expressed as means ± SD. Two-factor repeated-measures ANOVA table P values are shown.

Fig. 2.

Systolic blood pressure (A), heart rate (B), stroke volume (C), cardiac output (D), vascular resistance (E), and +dP/dt (F) during baseline and 4 steps of hemorrhage (●) and LBNP (○) corresponding to 6.25% (n = 14), 12.5% (n = 14), 18.75% (n = 14) and 25% (n = 12) total blood volume loss. Data are expressed as means ± SD. Two-factor repeated-measures ANOVA table P values are shown.

Fig. 3.

Stroke volume expressed as percent change from baseline during 4 steps of hemorrhage (●) and LBNP (○) corresponding to 6.25% (n = 14), 12.5% (n = 14), 18.75% (n = 14) and 25% (n = 12) total blood volume loss. Data are expressed as means ± SD.

Fig. 4.

Hemoglobin (Hgb, A), hematocrit (Hct, B), bicarbonate (HCO₃, C), base excess (BE, D), lactate (E), and central venous oxygen saturation (ScvO₂, F) are shown at baseline of hemorrhage (●, solid lines) and LBNP (○, dashed lines) and at the maximum level of hemorrhage and matching LBNP (MAX). Values are means ± SD; n = 12. *Difference from baseline (P < 0.01). †Difference between hemorrhage and LBNP (P < 0.01).

Fig. 5.

Plasma renin activity (A), vasopressin (B), norepinephrine (C), and epinephrine (D) are shown at baseline of hemorrhage (●, solid lines) and matching LBNP (○, dashed lines), and at the maximum level of hemorrhage and matching LBNP (MAX). Values are means ± SD; n = 12. *Difference from baseline (P < 0.01). †Difference between hemorrhage and LBNP (P < 0.01).

Fig. 6.

Stroke volume expressed as percent change from baseline during 4 steps of hemorrhage in baboons (expressed as ml/kg, ●), the corresponding levels of LBNP in baboons (○), and during previous LBNP experiments in humans (△, n = 117). Data are expressed as means ± SD.

Fig. 7.

Estimates of blood loss in humans (△, ml) corresponding to various levels of LBNP calculated from the results from the current study in baboons (ml/kg, ●). Data are expressed as means ± SD.