Influence of Calcium Concentration on the Neuromuscular Effects of Vecuronium on the Hemidiaphragm-Phrenic Nerve of Rats

Lee, Soo Il; Ko, Dae Kwon; Lee, Jong Hwan; Hwang, Gi Baeg

Abstract

BACKGROUND
Calcium disturbance may clinically produce diaphragmatic weakness. Extracellular calcium is necessary for diaphragmatic contraction, suggesting that the diaphragm behaves more like cardiac muscle. The effect of extracellular Ca2 concentrations on the relaxation action of vecuronium was studied in rat hemidiaphragm-phrenic nerve preparations.
METHODS
Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (200 300 g). Preparations were bathed in Kreb's solution of (mM): NaCl 118, KCl 5, CaCl2 2.5, NaHCO3 30, KH2PO4 1, MgCl2 1 and glucose 11, then maitained at 37oC when aspirated with a mixture of 95% O2 and 5% CO2. Isometric forces generated in response to 0.1 Hz, 2 Hz for 2 seconds and, 50 Hz for 2 seconds with supramaximal electrical stimulation (0.2 msec, rectangular) to the phrenic nerve, were measured with a force transducer. Single twitch tension and peak tetanic tension were calculated as a percentage of control. TOF fade was calculated as (1-(T4/T1))x100. Each preparation was exposed to the alterations in calcium concentrations of the Kreb's solution (3.75, 3.125, 1.5, 1.25, 0.625, 0.3125 (mM)), and the adequate volume of vecuronium stock solution was added to the tissue bath for desired bath concentration. The effects of calcium and vecuronium were allowed to reach a steady state before measurement of tension parameters was done. Single twitch tensions or peak tetanic tensions, which were measured at each calcium concentration, were compared respectively. EC5, EC25, EC50, EC75, and EC95 of vecuronium for a single twitch tension, TOF fade, and peak tetanic tension at each calcium concentration, were calculated using a sigmoid Emax model. We compared the EC50 of vecuronium according to calcium concentrations. Data was compared by the Kruskal-Wallis test with a post hoc Wilcoxon rank sum test. A p-value of below 0.05 was considered significant.
RESULTS
The range of calcium concentration studied didn't produce differences among single or tetanictensions respectively. The EC50's of vecuronium decreased as calcium concentration decreased.
CONCLUSIONS
The reduction of calcium concentration can augment the action of vecuronium on the diaphragm.