Effect of proximal arterial perfusion pressure on function, spinal cord blood flow, and histopathologic changes after increasing intervals of aortic occlusion in the rat.

BACKGROUND AND PURPOSE

Cross-clamping of the thoracic aorta results in spinal cord ischemia and prominent systemic hypertension. Using a rat model of transient spinal cord ischemia. we examined the effects of manipulation of proximal aortic blood pressure on spinal cord blood flow (SCBF), neurological dysfunction, and changes in spinal histopathology after increasing intervals of aortic occlusion.

METHODS

Aortic occlusion was induced by the inflation of a 2F Fogarty catheter placed into the thoracic aorta in rats anesthetized with halothane (1.5%). A tail artery was cannulated to monitor distal arterial pressure (DAP). To measure SCBF, a laser probe was implanted into the epidural space of the L-2 vertebra. To manipulate proximal arterial pressure (PAP), the left carotid artery was cannulated with a 20-gauge polytetrafluoroethylene catheter to permit blood withdrawal and infusion from a peripheral reservoir during aortic occlusion. In a survey study, spinal cord ischemia was induced in single animals at intervals of 6, 10, 15, 30, or 40 minutes with PAP controlled at 40, 60, 80, and 110 to 120 mm Hg. In a second series, ischemia was induced in groups of animals for 0, 6, 8, 10, and 12 minutes with PAP controlled at 40 mm Hg. After ischemia the animals survived for 2 to 3 days. During this recovery period, neurological functions were evaluated, followed by quantitative histopathology of the spinal cord.

RESULTS

Under normal conditions, cross-clamping yields an acute proximal hypertension (125 to 135 mm Hg), a fall of DAP to 15 to 22 mm Hg, and a decrease in SCBF to 7% to 11% of baseline values. With the use of the external reservoir, proximal hypertension could be abolished and the PAP maintained at target pressures. In these studies a typical syndrome of tactile allodynia, spastic paraplegia, and necrotic changes affecting the central part of the gray matter after 24 to 48 hours of reperfusion was observed at the following combinations of ischemic intervals and PAP values: > 10 minutes/40 mm Hg; > 12 minutes/60 mm Hg; > 16 minutes/80 mm Hg; and > 30 minutes/uncontrolled. Lowering PAP resulted in a corresponding decrease in residual SCBF. Systematic studies at a PAP of 40 mm Hg at occlusion intervals of 6, 8, 10, and 12 minutes revealed that 100% of rats were paraplegic after 10- and 12-minute ischemia, and these rats showed corresponding signs of spinal histopathology.

CONCLUSIONS

The present study shows that systemic intraischemic hypotension (40 mm Hg) significantly potentiates neurological dysfunction after transient aortic occlusion. The mechanism of the observed effect may include elimination of collateral flow during aortic occlusion and/or consequent potentiation of hypoperfusion during reperfusion. These data indicate that PAP during occlusion should be monitored and/or controlled because it is a critical variable in the determination of outcome in this model of spinal cord ischemia.