Increases in spinal cerebrospinal fluid potassium concentration do not increase isoflurane minimum alveolar concentration in rats

Abstract

Background: Previous studies demonstrated that MAC for isoflurane directly correlates with the concentration of Na(+) in cerebrospinal fluid surrounding the spinal cord, the primary site for mediation of the immobility produced by inhaled anesthetics. If this correlation resulted from increased irritability of the cord, then infusion of increased concentrations of potassium (K(+)) might be predicted to act similarly. However, an absence of effect of K(+) might be interpreted to indicate that K(+) channels do not mediate the immobility produced by inhaled anesthetics whereas Na(+) channels remain as potential mediators. Accordingly, in the present study, we examined the effect of altering intrathecal concentrations of K(+) on MAC.

Methods: In rats prepared with chronic indwelling intrathecal catheters, we infused solutions deficient in K(+) and with an excess of K(+) into the lumbar space and measured MAC for isoflurane 24 h before, during, and 24 h after infusion. Rats similarly prepared were tested for the effect of altered osmolarity on MAC (accomplished by infusion of mannitol) and for the penetration of Na(+) into the cord.

Results: MAC of isoflurane never significantly increased with increasing concentrations of K(+) infused intrathecally. At infused concentrations exceeding 12 times the normal concentration of KCl, i.e., 29 mEq/L, rats moved spontaneously at isoflurane concentrations just below, and sometimes at MAC, but the average MAC in these rats did not exceed their control MAC. At the largest infused concentration (58.1 mEq/L), MAC significantly decreased and did not subsequently return to normal (i.e., such large concentrations produced injury). Infusions of lower concentrations of K(+) had no effect on MAC. Infusion of osmotically equivalent solutions of mannitol did not affect MAC. Na(+) infused intrathecally measurably penetrated the spinal cord.

Conclusions: The results do not support a mediation or modulation of MAC by K(+) channels.

Figure 1

A schematic of the Methods used in the present study.

Figure 2

Intrathecal infusion of K⁺ did not increase isoflurane MAC. MAC0 is the control MAC obtained during intrathecal infusion of normal artificial cerebrospinal fluid (aCSF). MAC1 is the MAC obtained during intrathecal infusion of aCSF containing the indicated concentrations of K⁺. Thus, MAC1/MAC0 indicates the fractional change in MAC produced by the altered K⁺ concentration. The largest concentration infused (58.1 mEq/L) significantly (P < 0.001) decreased MAC, but this decrease also was associated with injury to the cord as reflected in the failure of a subsequently determined MAC (MAC2) to return to normal.

Figure 3

Separate control groups of rats received artificial cerebrospinal fluid (aCSF) containing a normal concentration of K⁺, but various concentrations of mannitol, concentrations that changed osmolarity as much as the studies in which K⁺ had been altered. No significant changes in MAC were associated with changes in osmolarity.

Figure 4

Intrathecal infusion of artificial cerebrospinal fluid (aCSF) containing decreased and increased concentrations of Na⁺, respectively, decreased and increased cord concentrations of Na⁺ (P < 0.002 for the difference in cord concentrations for the infusion of increased versus decreased Na⁺ concentrations) without altering cerebral Na⁺ concentrations (difference not significant. Values are given as the fraction of the average value during infusion of normal aCSF. N = 6 for all groups.