There is considerable evidence that Ca++ ions play a key role in the pathogenesis of posttraumatic ischemia and ischemic cell death.1,5 For example, ischemic depolarization of cell membranes is associated with an intracellular shift of Ca++ which promotes smooth-muscle contraction and vasospasm, impairs mitochondrial function, and enhances the production of vasoactive prostanoids.20,22,39 Nimodipine, a dihydropyridine calcium channel blocker, has recently been shown to increase posttraumatic SCBF,19 although the effect on recovery of posttraumatic axonal function is not known. Guha, et al.,19 reported that the effect of nimodipine on postinjury SCBF required the concomitant administration of the vasopressor adrenaline to correct posttraumatic hypotension and to prevent further lowering of the mean arterial blood pressure (MABP) by peripheral vasodilatation. However, there is evidence that catecholamines may exacerbate neuronal injury after cord trauma,28,31 hence an alternative method of maintaining the MABP would theoretically enhance the possibility of achieving recovery of axonal function. Recently, Wallace and Tator48 reported that hypervolemic hemodilution with dextran 40 significantly increased MABP and SCBF after SCI in rats; therefore, dextran 40 would appear to be a suitable adjunct to nimodipine. In the present study, the combination of MEP and SSEP recordings and SCBF measurement has been used to examine whether the administration of nimodipine and dextran 40, alone or together, could increase posttraumatic SCBF and improve axonal function in the cord after acute experimental SCI.
Nimodipine and placebo were donated by Miles Pharmaceuticals, Inc. The IBAS II image analysis system was kindly loaned to us by Zeiss Canada, Ltd. Excellent technical assistance was provided by J. Loukides, D. Wilken, and R. Wunderlich.
Wood JHSimeone FAFink EAet al: Hypervolemic hemodilution in experimental focal cerebral ischemia. Elevation of cardiac output, regional cortical blood flow, and ICP after intravascular volume expansion with low molecular weight dextran. J Neurosurg 59:500–5091983J Neurosurg 59:
Rats obtained from Charles River Canada, Inc., St. Constant, Quebec, Canada.
Modified aneurysm clip manufactured by Walsh Manufacturing Co., Ltd., Oakville, Ontario, Canada.
Signal averager, Model 8400, manufactured by Cadwell Laboratories Inc., Kennewick, Washington.
IBAS II image analysis system provided on loan by Zeiss Canada Ltd., Don Mills, Ontario, Canada.
This research was supported by grants from the Medical Research Council of Canada, the Canadian Paraplegic Association, and Miles Pharmaceuticals, Inc.