Therapeutic Efficacy of Hemodynamic Management Using Norepinephrine on Cardiorespiratory Function Following Cervical Spinal Cord Contusion in Rats.

Abstract

Cervical spinal cord injury usually leads to cardiorespiratory dysfunction due to interruptions of the supraspinal pathways innervating the phrenic motoneurons and thoracic sympathetic preganglionic neurons. Although clinical guidelines recommend maintaining the mean arterial pressure within 85-90 mmHg during the first week of injury, there is no pre-clinical evidence from animal models to prove the therapeutic efficacy of hemodynamic management. Accordingly, the present study was designed to investigate the therapeutic efficacy of hemodynamic management in rats with cervical spinal cord contusion. Adult male rats underwent cervical spinal cord contusion and the implantation of osmotic pumps filled with saline or norepinephrine (NE) (125 μg/(kg·h) for 1 week). The cardiorespiratory function of unanesthetized rats was examined using a non-invasive blood pressure analyzer and double-chamber plethysmography. Cervical spinal cord contusion caused a long-term reduction in the mean arterial pressure and tidal volume. This hypotensive response was significantly reversed in contused rats receiving NE (1 day: 88 ± 19 mmHg; 2 weeks: 96 ± 13 mmHg) compared with contused rats receiving saline (1 day: 72 ± 15 mmHg; 2 weeks: 82 ± 10 mmHg). NE also significantly improved the tidal volume 1 day post-injury (contused + NE: 0.7 ± 0.2 mL; contused + saline: 0.5 ± 0.1 mL). Immunofluorescence staining results revealed that injury-induced reductions of noradrenergic and glutamatergic fibers within the thoracic spinal cord were significantly improved by NE. These results provided the evidence demonstrating that hemodynamic management using NE significantly improves cardiorespiratory function by alleviating neural pathway damage after cervical spinal cord contusion.