Ischaemic conditioning strategies reduce ischaemia/reperfusion-induced organ injury.

Reperfusion of tissues subjected to prolonged ischaemia results in ischaemic/reperfusion injury. Fortunately, there are strategies that can be applied to attenuate this injury. These include ischaemic pre- and post-conditioning; both have been shown experimentally to reduce ischaemic/reperfusion injury by up to 75%. The molecular mechanisms of ischaemic conditioning involve the activation of surface G-protein-coupled receptors for adenosine, bradykinin, opioids, and cannabinoids. These in turn stimulate growth receptors which then trigger the activation of cytoprotective pathways resulting in a reduction in apoptosis via the mitogen-activated protein kinase/extracellular-signal regulated kinase 1/2 kinase route and a reduction in opening of mitochondrial permeability transition pores (mPTPs) via the phosphatidylinositol 3-kinase pathway. Opening of mPTPs can cause cell death. Recently, activated surface tumour necrosis factor-α receptors have been shown to also contribute to cytoprotection by activating the Janus kinase and the signal transducer and activating factor of transcription-3 pathway. Research into the mechanisms of ischaemic conditioning is still ongoing and hopefully, with the better understanding of this phenomenon, new therapeutic strategies, with possible translation into meaningful clinical trials, will be developed to reduce ischaemic/reperfusion injury.

Comparison of the effects of inhalational anaesthetic agents on sympathetic activity in rabbits.

The effects of inhalational anaesthetic agents on renal sympathetic nerve activity (RSNA) were compared in anaesthetized rabbits. Concentrations of 6% desflurane, 1.2% isoflurane, and 2.4% enflurane increased mean RSNA up to 32, 36 and 44% while higher concentrations, of 12, 2.4 and 3.2% depressed it by 42, 83 and 5%, respectively. For halothane RSNA was unchanged up to 0.8% and decreased by 36% at 1.6% concentration. Nitrous oxide increased RSNA up to 28% at 50% concentration. Maximum reductions in mean arterial pressure (MAP) were 60% for both 2.4% isoflurane and 3.2% enflurane, 50% for 12% desflurane and 1.6% halothane, while 70% nitrous oxide increased MAP by 22%. In conclusion, unlike the entirely depressive effects of halothane, the effects of desflurane, isoflurane and enflurane were biphasic involving excitation at lower concentrations and depression of RSNA and a reduction in MAP at higher concentrations. Nitrous oxide caused increases in both RSNA and MAP.

Vagally mediated sympathoexcitation and central depression by desflurane in rabbits.

The effects of desflurane on renal sympathetic nerve activity (RSNA) were studied in intact or vagotomized anaesthetized rabbits with initial concentrations of 4.5-18%, subsequently equilibrated to end-tidal concentrations from 3%, 6%, 9% and 12% each for 20 min allowing sympathetic activity to stabilize. In intact animals, immediate transient increases in mean sympathetic activity from 27% to 63% were closely related to initial concentrations from 4.5% to 18%. During subsequent equilibration this remained elevated by 25-30% up to 6%, returned to control at 9% and fell by 33% at 12%. Bilateral vagotomy abolished sympathoexcitation apart from small increases in sympathetic activity, for example 14% at 4.5% (P < 0.05). We conclude that increases in inspired desflurane concentrations evoked rapid transient vagally mediated reflex sympathoexcitation with a small extra-vagal contribution. Central depression of sympathetic activity started at 6% and was 33% below baseline at 12%.

Specific actions of halothane, isoflurane, and desflurane on sympathetic activity and A delta and C somatosympathetic reflexes recorded in renal nerves in dogs.

BACKGROUND: This was a study of the relative effects on directly recorded sympathetic activity of desflurane, isoflurane, and halothane. METHODS: Renal sympathetic nerve activity (RSNA) was recorded with bipolar electrodes in renal nerves exposed retroperitoneally in anesthetized (alpha-chloralose), paralyzed (succinylcholine), and artificially ventilated dogs. Somatosympathetic responses were evoked by supramaximal electrical stimulation of radial nerves (0.33 Hz, 30 V, 0.5 ms). Spontaneous and evoked activity were rectified, averaged, and integrated to allow quantitative comparison of the effects of 3-12% desflurane, 0.6-2.4% isoflurane, and 0.4-1.6% halothane. RESULTS: Increasing concentrations of isoflurane progressively depressed mean RSNA, Adelta, and C reflexes by 40% (P < 0.01), 50% (P < 0.01) and 70% (P < 0.001) respectively at 2.4% concentration. Halothane depressed both reflexes equally by approximately 60% (P < 0.01) at 1.6% concentration, without significant depression of spontaneous RSNA. Desflurane increased and subsequently decreased RSNA by 37% (P < 0.02) and 65% (P < 0.001) at concentrations of 6% and 12% respectively, and although somatosympathetic reflexes remained unchanged up to 9%, both were depressed equally by 70% (P < 0.01) at 12% concentration. CONCLUSION: After equilibration, lower concentrations of desflurane remained excitatory, but, like isoflurane, higher concentrations depressed RSNA. The effect of halothane on RSNA was insignificant. Isoflurane depressed C more than Adelta somatosympathetic reflexes, which is uncorrelated with lipid solubility because desflurane and halothane, which have the highest and lowest minimum alveolar concentration, respectively, depressed both equally.

The effect of sevoflurane on spontaneous sympathetic activity, A delta and C somatosympathetic reflexes, and associated hemodynamic changes in dogs.

UNLABELLED: This study examined the effect of sevoflurane on spontaneous renal sympathetic nerve activity (RSNA), A delta- and C-fiber-mediated somatosympathetic reflexes, and hemodynamic changes in anesthetized dogs. RSNA, and A delta and C reflexes evoked by electrical stimulation of the radial nerve were observed in multifiber recordings of efferent activity in renal sympathetic nerves. Sevoflurane was administered at 1%, 2%, 3%, and 4% end-tidal concentrations for periods of 20 min. The mean A delta reflexes decreased by 20%, 39%, and 54% (P < 0.05 to < 0.01), and the C reflexes decreased by 38%, 62%, and 74% (P < 0.05 to < 0.01) at concentrations of 2%, 3%, and 4%, respectively. The relatively greater effect on C reflexes was significant (P < 0.05) and comparable with the effect of mu-opioids. There was no change in mean RSNA, heart rate (HR), and cardiac output (CO) up to 3% sevoflurane, but these decreased by 36%, 24%, and 13% (P < 0.05), respectively, at 4% sevoflurane. Sevoflurane 1%-4% caused a virtually linear reduction in systemic vascular resistance (SVR) from 7% (P < 0.05) to 44% (P < 0.05), together with a reduction in mean arterial pressure (MAP) that was significant for concentrations greater than 2%. The results indicate that sevoflurane causes a greater depression of C compared with A delta reflexes, and that the reduction in MAP was entirely due to a decrease in SVR up to 3%, whereas at 4% sevoflurane, reductions in sympathetic activity, HR, and CO also contributed its depressor effect. IMPLICATIONS: The relatively greater depressant effect of sevoflurane on C compared with A delta nociceptive somatosympathetic reflexes is similar to mu-opioids. The hypotensive effect of sevoflurane was significant at 2% concentration, whereas heart rate, cardiac output and sympathetic activity were reduced only at concentrations greater than 3%.

Dissociation between the effect of nitrous oxide on spontaneous and reflexly evoked sympathetic activity in dogs.

We have examined the effect of nitrous oxide on spontaneous sympathetic activity and A delta- and C-fibre mediated somatosympathetic reflexes in renal nerves, evoked by supramaximal electrical stimulation of radial nerves in anaesthetized, paralysed dogs undergoing mechanical ventilation. In six preparations, nitrous oxide was administered at end-tidal concentrations of 10%, 30%, 50% and 70%, each for 20 min. Spontaneous renal sympathetic activity increased significantly to 147.8% and 151.2% of control values with 50% and 70% nitrous oxide, respectively (P < 0.05), but there were no significant changes in A delta and C reflexes. We conclude that the large increase in spontaneous sympathetic activity was dissociated from somatosympathetic reflexes which remained unchanged at these concentrations of nitrous oxide.

Patient-controlled sedation for cataract surgery using peribulbar block.

Patients undergoing cataract surgery using peribulbar block were allocated randomly to self-administer doses of either midazolam 0.1 mg or propofol 3.3 mg without a lock-out facility; in the control group the syringe was charged with saline, not as a placebo, but to "blind" the surgeon and the nurse observer. For midazolam and propofol, median doses were 2.54 (0.1-6.0) mg and 87.4 (0-145) mg, respectively. Patient-controlled sedation significantly reduced the level of anxiety, with median visual analogue anxiety scores in the midazolam, propofol and saline groups of 5 (0-38) mm, 5 (0-25) mm and 15 (0-92) mm, respectively (P < 0.05). Some patients did not administer the sedative when available while others in the saline group would have benefited from anxiolytic drugs. While both drugs prevented an increase in heart rate, only midazolam prevented an increase in arterial pressure during surgery.