Time course of compensatory physiological responses to central hypovolemia in high-and low-tolerant human subjects

Lusha Xiang, Carmen Hinojosa-Laborde, Kathy L. Ryan, Caroline A. Rickards, Victor A. Convertino

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10 Scopus citations


Lower body negative pressure (LBNP) simulates hemorrhage in human subjects. Most subjects (67%) exhibited high tolerance (HT) to hypovolemia, while the remainder (33%) had low tolerance (LT). To investigate the mechanisms for decompensation to central hypovolemia in HT and LT subjects, we characterized the time course of total peripheral resistance (TPR), heart rate (HR), and muscle sympathetic nerve activity (MSNA) during LBNP to tolerance determined by the onset of decompensation (presyncope, PS). We hypothesized that 1) maximum (Max) TPR, HR, and MSNA would coincide, and 2) PS would result from simultaneous decreases in TPR, HR, and MSNA in LT and HT subjects but occur earlier in LT than in HT subjects. Max TPR was lower and occurred earlier in LT (n = 59) than in HT (n = 113) subjects (LT: 24 ± 1 mmHg·min·1−1 at 756 ± 31 s; HT: 28 ± 1 mmHg·min·1−1 at 1,265 ± 37 s, P < 0.01). Max TPR occurred several minutes before PS. During subsequent decrease in TPR, HR and MSNA continued to increase. Max HR (LT: 111 ± 2 beat/min at 923 ± 27 s; HT: 130 ± 2 beats/min at 1489 ± 23 s, P < 0.01) occurred several seconds before PS. Higher MSNA (P < 0.01) was attained in HT (n = 10; 51 ± 5 bursts/min at max TPR; 54 ± 5 bursts/min at max HR) than LT subjects (n = 4; 41 ± 8 bursts/min at max TPR; 39 ± 8 bursts/min at max HR). The onset of cardiovascular decompensation is a biphasic process in which vasodilation occurs before bradycardia and sympathetic withdrawal. This pattern was similar in LT and HT but occurred earlier in LT subjects. We conclude that sudden bradycardia plays a critical role in the determination of tolerance to central hypovolemia.

Original languageEnglish
Pages (from-to)R408-R416
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number2
StatePublished - 20 Aug 2018


  • Blood pressure
  • Cardiac output
  • Heart rate
  • Hypovolemia
  • Stroke volume
  • Sympathetic activity
  • Tolerance
  • Total peripheral resistance


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