Comparative effects of pancuronium and vecuronium on rat diaphragm and isolated hepatocytes

Abstract

Pancuronium and vecuronium are among the nondcpolarizing neuromuscular blocking drugs currently used in clinical anaesthesia. Previous reports have indicated that pancuronium is a powerful (more powerful than vecuronium) muscle relaxant, in both animal and human species [ 1-31. In addition. it has been shown that pancuronium is more effective than vecuronium in causing lactate dehydrogenase release from rat isolated hepatocytes 14). In the present study, the effects of low and high concentrations of pancuronium and vecuronium on neuromuscular blockade, and o n cell mcmbrane structure, were studied in the rat isolated diaphragm and liver cells, to determine and relate blocking concentrations of these drugs with their cellular effects on different tissues in the same animal.Twelve rats were killed, by a blow to the head, and bled. The tissues were removed and immediately placed in cold Krebs-Henseleit solution for 30 min. The tissues were then set up in organ baths containing Krebs solution plus pancuronium or vecuronium (low or high concentration). The effect of pancuronium and vecuronium on indirectly elicited twitch tensions (at 0.2 Hz) was studied using an organ bath technique. The cellular effects of pancuronium and vecuronium were assessed in terms of damage to cell membranes (lesions) and blood vessels, and inflammatory responses.Incubation with muscle relaxants was for a period of 5 min; histological sections, fixation and staining of tissues were standard [4,5]. The results are shown in Table I .It was concluded that pancuronium was a more powerful muscle relaxant than vecuronium. However, at high blocking concentration, only pancuronium produced cellular lesions, i.e. caused damage to cell membrane and internal structures, in the rat hepatocytes. Table I . Effects of pnncwoniutn and veciironium on muscle twitch tension and on cell mernhruries in the rut diaphragm and liver cel1.s Results are means f S.E.M. ( t i = 12). Statistical significance: *I>< 0.05, **P< 0.0 1. Twitch tension Concentration blockade ("h) Cellular effects on diaphragm or liver cells Pancuronium Low (350 n M ) 72 f 3.1 ** N o significant effect o n cell membrane in the diaphragm and liver. High (35 /AM) 100%~ Produced lesions in cell membrane. Caused hepatic cell necrosis and inflammation. N o effect o n cell membrane in both types o f tissues. Produced slight distortion of cellular organization. N o damage to cell membrane. n o lesions and n o lymphocyte infiltration. blockade 35 f 1.4* 92 f 2.5 Vecuronium Low (320 n M )High (32 /AM)