Clinical and experimental pharmacology & physiology
-
Clin. Exp. Pharmacol. Physiol. · Oct 2012
Effects of fatty acids on cardioprotection by pre-ischaemic inhibition of the malate-aspartate shuttle.
1. The malate-aspartate shuttle (MAS) is the main pathway for balancing extra- and intramitochondrial glucose metabolism. Pre-ischaemic shutdown of the MAS by aminooxyacetate (AOA) mimics ischaemic preconditioning (IPC) in rat glucose-perfused hearts. ⋯ Postischaemic glucose oxidation was suppressed by FA and did not differ significantly between the different groups. 4. In conclusion, the reduction in IS induced by pre-ischaemic MAS shutdown is not compromised by physiological FA concentrations. Transient MAS shutdown may be involved in IPC, but is not sufficient on its own as the underlying mechanism for IPC.
-
Clin. Exp. Pharmacol. Physiol. · Oct 2012
Adenosine A(2A) receptor antagonists are broad facilitators of antinicotinic neuromuscular blockade monitored either with 2 Hz train-of-four or 50 Hz tetanic stimuli.
1. The 2 Hz train-of-four ratio (TOF(ratio)) is used to monitor the degree of patient curarization. Using a rat phrenic nerve-hemidiaphragm preparation, we showed that antinicotinic agents, such as hexamethonium, d-tubocurarine and pancuronium, but not cisatracurium, decreased contractions produced by physiological nerve activity patterns (50 Hz) more efficiently than those caused by 2 Hz trains. ⋯ ZM 241385 was the only compound tested in this series that facilitated recovery from tetanic fade produced by cisatracurium. 3. The data suggest that distinct antinicotinic relaxants interfere with fine-tuning neuromuscular adaptations to motor nerve stimulation patterns via activation of presynaptic muscarinic and adenosine receptors. These results support the use of A(2A) receptor antagonists together with atropine to facilitate recovery from antinicotinic neuromuscular blockade.