Procaine, Lidocaine, and Hypothermia Inhibit Calcium Paradox in Glial Cells

Abstract

The purpose of this study was to determine the effects of local anesthetics (lidocaine and procaine) and hypothermic perfusion on Na+/Ca2+ exchanger activity during reperfusion-induced calcium paradox in vitro. Hypothetically, this work provides a mechanism for reperfusion paradox injury in vitro that may relate to a variety of ischemic insults in vivo. Intracellular calcium ([Ca2+]i) in individual cells was measured using a fura-2 photometry system during protocols previously shown to dramatically and persistently increase [Ca2+]i in a manner that replicates certain phases of reperfusion injury in vivo. Our results suggest that short (< 5.0 min) exposure to hypocalcia prompts subsequent, potentially lethal, sodium-dependent calcium entry via the reverse phase of the Na+/Ca2+ exchanger. The local anesthetics lidocaine or procaine are able to block [Ca2+]i increases when added at the time of reperfusion. Furthermore, since [Ca2+]i is normally increased when local anesthetics are added by themselves, the results suggest that local anesthetics promote the forward mode of Na+/Ca2+ exchange (i.e., Na-dependent calcium removal) in addition to reverse Na+/Ca2+ exchanger blockade. Low temperature (18 degrees C) perfusion or reperfusion also affects exchanger dynamics and attenuates calcium entry during such protocols. These experiments further implicate the Na+/Ca2+ exchanger in reperfusion-mediated cell injury and provide potential ways to therapeutically modify such phenomena in vivo.

Differential action of spasmolytic vasodilators on platelet aggregation and endothelial cell‐dependent anti‐aggregation

“…A variety of pharmacological interventions, such as topical lidocaine ( 1–5), papaverine ( 2, 6), prostaglandin E 1 (PGE 1 ) ( 7), calcium (Ca 2+ ) channel blockers ( 1, 6), nitrovasodilators ( 6), and pentobarbital ( 5), has been developed for this purpose through clinical and/or experimental evaluation. Intravenous administration of these drugs is also believed to be beneficial in reducing the risk of no‐reflow phenomenon occurring after reperfusion ( 8–14).…”