Autonomic dysreflexia in a rat model spinal cord injury and the effect of pharmacologic agents.

Abstract

The object of this study was to develop a spinal cord injury (SCI) rat model for autonomic dysreflexia (AD), assessing the effect of alpha-adrenergic and calcium channel blockade and to determine the relationship of detrusor-external sphincter dyssynergia (DESD) to the development of AD. A laminectomy was performed in male rats at the T4 or T10 level and a controlled 50 g cm blunt SCI was induced using an impounder. Four weeks after injury, changes in arterial blood pressure and heart rate were monitored while simultaneous cystometry (CMG) and pelvic floor electromography (EMG) were performed in vivo in sham (control) and spinal cord injured rats. The effects of terazosin (0.1 mg/kg), diltiazem (0.5 mg/kg), and oxybutynin chloride (0.1 mg/kg) on hemodynamic changes were assessed independently. Both T4 and T10 SCI rat displayed evidence of DESD (enhanced pelvic floor EMG activity at cystometric capacity) while control rats did not. Only T4 injured rats exhibited evidence of AD, with mean blood pressure elevations from 82.9 +/- 13.6 to 93.9 +/- 11.3 mm Hg (P < 0.01) and a mean heart rate decrease from 332.2 +/- 56.5 to 311.1 +/- 54.5 beats/min (P = 0.02) at cystometric capacity. The intravenous administration of terazosin or diltiazem abolished the AD response during CMG. The administration of oxybutynin exhibited the ability to increase bladder capacity and improve compliance in all 3 groups but did not blunt AD. The rat model of SCI effectively reproduced hemodynamic changes consistent with the AD complex in T4 level SCI but not T10 level SCI animals, despite incomplete lesions. Blockade with either an alpha-1 or a calcium channel antagonist effectively ablated the AD response to bladder distention. Anticholinergic agents had no effect on AD. DESD frequently accompanies autonomic dysreflexia, although the development of AD is not a prerequisite for DESD.

• Authors: D A Rivas, M B Chancellor, B Huang, S K Salzman
• Journal: Neurourology and urodynamics (Neurourol Urodyn) Vol. 14 Issue 2 Pg. 141-52 ( 1995) ISSN: 0733-2467 [Print] United States
• PMID: 7780441 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Antagonists
• Calcium Channel Blockers
• Mandelic Acids
• Parasympatholytics
• Terazosin
• Diltiazem
• oxybutynin
• Prazosin

Topics

• Adrenergic alpha-Antagonists (pharmacology)
• Animals
• Autonomic Nervous System Diseases (complications, physiopathology)
• Calcium Channel Blockers (pharmacology)
• Diltiazem (pharmacology)
• Disease Models, Animal
• Male
• Mandelic Acids
• Parasympatholytics (pharmacology)
• Prazosin (analogs & derivatives, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Spinal Cord Injuries (complications, drug therapy, physiopathology)
• Urinary Bladder, Neurogenic (drug therapy, physiopathology)
• Urodynamics (physiology)