Hemodynamic management using norepinephrine improves respiratory and cardiovascular function and spinal cord blood flow during acute cervical spinal cord injury in rats

Cervical spinal cord injury results in severe cardiorespiratory impairments due to interruptions of bulbospinal pathways innervating to phrenic motoneurons and thoracic sympathetic preganglionic neurons. Additionally, the injury substantially impacts spinal cord blood flow, attributed to damage to the spinal vessels and the blood–spinal cord barrier. Current clinical guidelines suggest maintaining the mean arterial pressure between 85–90 mmHg during the acute phase of spinal cord injury; however, there is no preclinical animal evidence to examine the optimal timing and effect of hemodynamic management on respiratory function and spinal microcirculation following injury. Accordingly, the present study aimed to comprehensively investigate the therapeutic efficacy of hemodynamic agent (i.e., norepinephrine) on cardiorespiratory function and spinal cord blood flow during compression vs. decompression phases of acute cervical spinal cord injury. Adult male rats underwent mid-cervical spinal cord compression followed by decompression were received an intravenous infusion of 1) saline (7 ml/kg/hr), 2) norepinephrine (125 μg/kg/hr) during compression, or 3) norepinephrine during decompression. Respiratory and cardiovascular patterns were measured in conjunction with monitoring of spinal cord blood flow utilizing a laser speckle contrast imaging device. There are three major findings in the present study. First, saline infusion during cervical spinal cord compression resulted in a significant reduction in the minute ventilation (45 ± 10% of baseline, p<0.01) and the mean arterial blood pressure (71 ± 10% of baseline, p<0.01), which is accompanied by a hypoperfusion of spinal cord blood flow (62 ± 11% of baseline, p<0.01). Second, infusion of norepinephrine during compression significantly enhanced the minute ventilation (75 ± 21% of baseline, p<0.01) and improved spinal cord blood flow (92 ± 22% of baseline, p<0.01), with mean arterial blood pressure returning to the normal values. The improvement of physiological function could be still maintained even norepinephrine was no longer administrated during decompression phase. Importantly, the ischemia-reperfusion rebound of spinal cord blood flow during the decompression phase was significantly mitigated by infusion of norepinephrine during compression. Third, norepinephrine infusion during decompression was surprisingly unable to improve the minute ventilation despite the mean arterial blood pressure could be maintained at the normal level. Furthermore, the ischemia-reperfusion effect on spinal cord blood flow was significantly exaggerated (136 ± 17% of baseline, p<0.01). These data indicated that norepinephrine exerts differential effects on the cardiorespiratory function and spinal cord blood flow depending on the time point of administration. Our results suggest that infusion of norepinephrine during compression is beneficial for functional improvement, while norepinephrine may aggravate ischemia reperfusion injury when infusing during decompression. This study provides essential pre-clinical evidence underscoring the importance of determining the optimal timepoint of hemodynamic management to achieve the maximal therapeutic efficacy and prevent the potential side effects during acute cervical spinal cord injury. Support for this work was provided by grants from the National Science and Technology Council (NSTC 112-2628-B-110-003-MY3). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.