Abstract
Hemorrhage initially triggers a rise in sympathetic nerve activity (SNA) that maintains blood pressure (BP); however, SNA is suppressed following severe blood loss causing hypotension. We hypothesized that adrenergic C1 neurons in the rostral ventrolateral medulla (C1RVLM) drive the increase in SNA during compensated hemorrhage, and a reduction in C1RVLM contributes to hypotension during decompensated hemorrhage. Using fiber photometry, we demonstrate that C1RVLM activity increases during compensated hemorrhage and falls at the onset of decompensated hemorrhage. Using optogenetics combined with direct recordings of SNA, we show that C1RVLM activation mediates the rise in SNA and contributes to BP stability during compensated hemorrhage, whereas a suppression of C1RVLM activity is associated with cardiovascular collapse during decompensated hemorrhage. Notably, re-activating C1RVLM during decompensated hemorrhage restores BP to normal levels. In conclusion, C1 neurons are a nodal point for the sympathetic response to blood loss.
Highlights
Hemorrhage is a leading cause of death following traumatic injuries, accounting for 1.5 million deaths per year worldwide (Lord et al, 2014; Cannon, 2018)
This analysis revealed that fluorescence emitted by GCaMP7s expressed in C1 neurons in the rostral ventrolateral medulla (C1RVLM) is exquisitely sensitivity to hypotension, with the greatest sensitivity of this response occurring over a range of blood pressure (BP) that fall below the resting mean arterial pressure (MAP) (Figure 1I)
The results suggest that a reduction in the activity of C1 neurons contributes to the fall in lumbar sympathetic nerve activity (LSNA), heart rate (HR), and BP that occurs during the decompensated phase
Summary
Hemorrhage is a leading cause of death following traumatic injuries, accounting for 1.5 million deaths per year worldwide (Lord et al, 2014; Cannon, 2018). Elevated HR and TPR during hemorrhage maintain blood pressure (BP) near normal levels despite reduced blood volume, a condition termed compensated hemorrhage (Schadt and Ludbrook, 1991; Evans et al, 2001; Schiller et al, 2017). If hemorrhage is not controlled, further blood loss triggers an abrupt reduction in HR and TPR mediated by a reflex sympathetic withdrawal, causing severe hypotension and often syncope (Evans et al, 2001; Convertino et al, 2021). This condition, termed decompensated hemorrhage, is the prelude to circulatory shock and death and is considered a ‘‘last-ditch’’ effort to increase venous return and reduce cardiac metabolism (Schiller et al, 2017; Cannon, 2018; Convertino et al, 2021). The neural mechanisms responsible for this drastic shift in physiological state (compensated to decompensated) are not well understood
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