Heart Rate Variability during Simulated Hemorrhage with Lower Body Negative Pressure in High and Low Tolerant Subjects

Abstract

Heart rate variability (HRV) decreases during hemorrhage, and has been proposed as a new vital sign to assess cardiovascular stability in trauma patients. The purpose of this study was to determine if any of the HRV metrics could accurately distinguish between individuals with different tolerance to simulated hemorrhage. Specifically, we hypothesized that (1) HRV would be similar in low tolerant (LT) and high tolerant (HT) subjects at presyncope when both groups are on the verge of hemodynamic collapse; and (2) HRV could distinguish LT subjects at presyncope from hemodynamically stable HT subjects (i.e., at a submaximal level of hypovolemia). Lower body negative pressure (LBNP) was used as a model of hemorrhage in healthy human subjects, eliciting central hypovolemia to the point of presyncopal symptoms (onset of hemodynamic collapse). Subjects were classified as LT if presyncopal symptoms occurred during the -15 to -60 mmHg levels of LBNP, and HT if symptoms occurred after LBNP of -60 mmHg. A total of 20 HRV metrics were derived from R-R interval measurements at the time of presyncope, and at one level prior to presyncope (submax) in LT and HT groups. Only four HRV metrics (Long-range Detrended Fluctuation Analysis, Forbidden Words, Poincaré Plot Descriptor Ratio, and Fractal Dimensions by Curve Length) supported both hypotheses. These four HRV metrics were evaluated further for their ability to identify individual LT subjects at presyncope when compared to HT subjects at submax. Variability in individual LT and HT responses was so high that LT responses overlapped with HT responses by 85-97%. The sensitivity of these HRV metrics to distinguish between individual LT from HT subjects was 6-33%, and positive predictive values were 40-73%. These results indicate that while a small number of HRV metrics can accurately distinguish between LT and HT subjects using group mean data, individual HRV values are poor indicators of tolerance to hypovolemia.

Keywords: heart period variability; heart rate variability; hemorrhage; hypovolemia; lower body negative pressure.

Figure 1

Stroke volume (A) and R–R interval (B) during progressive lower body negative pressure (LBNP) in low tolerant subjects (closed circles, solid line) and high tolerant subjects (open circles, dashed line). At baseline, there are 33 low tolerant subjects and 87 high tolerant subjects. The number of subjects at the subsequent time points during LBNP decline as subjects experience presyncopal symptoms at various levels of LBNP. Data are shown as mean ± SE. * Denotes group differences at the same LBNP level (p ≤ 0.05).

Figure 2

Sample R–R interval tracings from one low tolerant subject (lower tracing, open circles) and one high tolerant subject (upper tracing, closed circles) are shown for a 2-min time span during LBNP level of − 60 mmHg.

Figure 3

(A) Long-range detrended fluctuation analysis (DFA long), (B) forbidden words (FW), (C) Poincare plot standard deviations ratio (SD1/SD2), and (D) fractal dimensions by curve length (FD-L) in low tolerant (LT) at presyncope (solid circles, n = 33) and high tolerant (HT) at submax (open circles, n = 87) level of lower body negative pressure (LBNP). Data are shown as box (25th/75th percentiles) and whisker (90th/10th percentiles) plots with median value (black line).