Background and Objectives Celiac plexus neurolysis, although effective in relieving pain associated with upper abdominal malignancy, occasionally results in paraplegia. Diffusion of the neurolytic agent to arteries supplying the spinal cord has been postulated as a cause, and previous studies with isolated lumbar segmental arteries have demonstrated contraction in response to ethanol and phenol. The mechanism of this contractile effect is unknown, but a role for insular free calcium (Ca²⁺ _i) is suggested by the known involvement of Ca²⁺ _i in both smooth muscle vasoconstriction and toxic cell injury. The authors sought to determine whether nontoxic concentrations of ethanol cause a direct elevation of Ca²⁺ _i in arterial smooth muscle and endothelium.

Methods Primary cultures of human aortic smooth muscle and endothelial cells were studied to determine the direct effect of ethanol independent of interactions with agonists or contractile proteins. Ca²⁺ _i levels were determined in single cells with digitized video fluorescence microscopy, using ratio imaging of the Ca²⁺ _i-sensitive fluorophore fura-2.

Results In aortic smooth muscle cells, initial Ca²⁺ _i was 98 ± 41 nM (n = 59 cells). Histamine (10 μM) as a positive control caused an increase in Ca²⁺ _i, as expected. Ethanol alone, at doses of 2-5% (v/v) also caused a sustained elevation in Ca²⁺ _i of physiologically significant magnitude. Ethanol at doses of 5% or lower did not cause any visibly apparent injury within 30 minutes. In contrast, 10% or higher ethanol doses quickly caused membrane blebbing, a sign of toxic injury, followed by cell death within 20 minutes. Aortic endothelial cells were more resistant to ethanol than smooth muscle cells, in terms of both Ca²⁺ _i elevation and cell death.

Conclusions Ethanol, even at nontoxic concentrations, has a direct effect on aortic smooth muscle Ca²⁺ _i, large enough to be associated with significant vasoconstriction. The findings suggest a possible role for pharmacologic agents that preserve Ca²⁺ _i homeostasis in protecting against neurolysis-induced paraplegia, although additional study is required before clinical application is appropriate.