Acute Late Sepsis Attenuates Effects of a Nondepolarizing Neuromuscular Blocker, Rocuronium, by Facilitation of Endplate Potential and Enhancement of Membrane Excitability In Vitro

Background Sepsis attenuates the muscle-relaxing effects of nondepolarizing neuromuscular blockers. The authors investigated the effects of acute late sepsis on neuromuscular transmission and neuromuscular actions of rocuronium to clarify the mechanisms by which sepsis attenuates the effects of nondepolarizing neuromuscular blockers. Methods Sepsis was induced by cecal ligation and puncture operation. Endplate potentials, acetylcholine potentials, and electrotonic potentials were recorded from the motor endplates of isolated diaphragms from acute late septic and nonseptic rats. Results (1) Sepsis did not influence the effect of rocuronium to decrease endplate potential amplitude, which was increased by sepsis itself; (2) sepsis facilitated the effect of rocuronium to decrease quantal acetylcholine release, which was increased by sepsis itself; (3) sepsis did not influence the effect of rocuronium to decrease acetylcholine sensitivity, which was decreased by sepsis itself; (4) sepsis decreased critical depolarization, and rocuronium did not influence critical depolarization. Conclusions These results indicate that acute late sepsis facilitates endplate potentials and enhances excitability of the muscle membrane, indicated by a decrease of critical depolarization. It is thought that these elicit the sepsis-induced attenuation of the muscle-relaxing effects of rocuronium.

Effect of in vivo fetal infusion of dexamethasone at 0.75 GA on fetal ovine resistance artery responses to ET-1

At 110–111 days gestation, instrumented fetal sheep were administered saline or dexamethasone (2.2 μg · kg−1 · h−1 iv) for 48 h. Measurement of fetal blood pressure showed a greater increase in dexamethasone-treated ( n = 6) compared with control ( n = 5) fetuses (7.3 ± 2.3 vs. 0.6 ± 2.3 mmHg, P < 0.05). Fetuses were delivered by cesarean section, and the femoral muscle and brain were obtained under halothane anesthesia. Femoral and middle cerebral arteries (∼320-μm internal diameter) were evaluated using wire myography. Sensitivity to KCl (2.5–125 mM) and the magnitude of the maximal vasoconstriction to 125 mM K+ were similar in femoral and middle cerebral arteries from dexamethasone-treated vs. control fetuses. Acetylcholine-induced vasorelaxation was similar in femoral arteries from control and dexamethasone-treated fetuses. Middle cerebral arteries did not relax to acetylcholine. Sensitivity to endothelin-1 (ET-1; 0.1 pM-0.1 μM) and magnitude of the ET-1-induced vasoconstriction were greater in femoral arteries from dexamethasone-treated vs. control fetuses ( P < 0.05). Autoradiographical studies with receptor-specific ligands demonstrated increased ETA-receptor binding, the principal receptor subtype, in femoral muscle vessels ( P < 0.001) but decreased ETA-receptor binding in middle cerebral arteries ( P < 0.01) from dexamethasone-treated compared with control fetuses. Relatively little ETB-receptor binding was evident in all tissues examined. We conclude that hyperreactivity to ET-1, due to increased ETA-receptor binding, may be involved in the dexamethasone-induced increase in peripheral vascular resistance in fetal sheep in vivo.

Endothelium-dependent relaxations in canine coronary arteries are enhanced in early heart failure and persist in recovery

In vitro coronary artery responsiveness to noradrenaline, phenylephrine, and BHT-920 together with functional relaxation to acetylcholine was assessed in dogs at the early onset of pacing-induced heart failure (1 week) and in dogs recovered from heart failure (3 weeks paced, followed by 4 weeks discontinued pacing). α-Adrenoceptor stimulation produced contractile responses that were unaltered in early congestive heart failure and recovery. Contractions to noradrenaline and BHT-920 were always less than those produced by phenylephrine. Endothelium-intact arteries demonstrated relaxations in response to noradrenaline and BHT-920, but not phenylephrine. Relaxations to noradrenaline were enhanced 24% in early heart failure and 47% following recovery from heart failure, compared with control. BHT-920 produced relaxations that were augmented 21 and 76% in early heart failure and recovery, respectively. Contractile sensitivity to noradrenaline increased 5-fold in early heart failure and was not different in recovery, compared with control. Contractile sensitivity to BHT-920 and phenylephrine was unaltered throughout. Acetylcholine produced relaxations that were increased 21% in early heart failure and 13% after recovery from congestive heart failure. Furthermore, acetylcholine sensitivity was significantly enhanced in early heart failure and recovery. The current study reveals a progressive adaptation of the coronary endothelium in congestive heart failure, possibly directed towards protection against excessive vasoconstriction due to circulating catecholamines.Key words: endothelium, congestive heart failure, coronary arteries, α-adrenoceptors, noradrenaline, acetylcholine.