Questioning the cardiocirculatory excitatory effects of opioids under volatile anaesthesia.

BACKGROUND: Opioid-induced hyperalgesia has been demonstrated in awake animals. We observed an increased haemodynamic reactivity in response to noxious stimuli in rats under sevoflurane anaesthesia treated with a very low dose of sufentanil. The aim of this investigation was to determine whether the two phenomena share a common origin: an opioid-induced excitatory reaction. To address this, we administered several drugs with proven efficacy in opioid hyperalgesia to rats presenting with haemodynamic hyper-reactivity. METHODS: The MACbar of sevoflurane was measured in controls and in animals treated with sufentanil 0.005 micro g kg(-1) min(-1) before and after administration of i.v. (0.25, 0.5 mg kg(-1)) and intrathecal (i.t.) (250 micro g) ketamine, i.v. (0.5, 1 mg kg(-1)) and i.t. (30 micro g) MK-801(NMDA antagonist), i.v. (0.1, 0.5 mg kg(-1)) naloxone, i.v. (10 mg kg(-1)) and i.t. (50, 100 micro g) ketorolac or i.t. (100, 150 micro g) meloxicam (COX-2 inhibitor). RESULTS: Sufentanil 0.005 micro g kg(-1) min(-1) significantly increased MACbar (3.2 (sd 0.3) versus 1.9 (0.3) vol%). With the exception of naloxone, all drugs displayed a significant MACbar-sparing effect (>50%) in controls. Naloxone completely prevented haemodynamic hyperactivity. Two patterns of reaction were recorded for the other drugs: either hyper-reactivity was suppressed and the MACbar-sparing effect was maintained (i.t. ketamine, i.t. MK-801, i.t. ketorolac [100 micro g], i.t. meloxicam [150 micro g]) or hyper-reactivity was blocked but MACbar-sparing effect was lost (i.v. ketamine [0.5 mg kg(-1)], i.v. MK-801 [0.5, 1 mg kg(-1)], i.v. ketorolac [10 micro g kg(-1)], i.t. ketorolac [50 micro g], i.t. meloxicam [100 micro g]). CONCLUSIONS: We have demonstrated that low-dose sufentanil-induced haemodynamic hyper-reactivity is an excitatory micro -opiate-related phenomenon. This effect is reversed by drugs effective in treating opiate-induced hyperalgesia.

Effect of methionine on glycolysis in tumor cells: in vivo and in vitro NMR studies.

Inhibition of glycolysis by methionine is a phenomenon previously shown in transformed cells growing in culture. In a recent paper, [Collet V. et al., Q. Magn. Res. Biol. Med. 11, 127-134 (1995)] we investigated this effect in vivo by 13C nuclear magnetic resonance spectroscopy, but the results did not clearly support this hypothesis. In this work, in vivo 13C NMR spectroscopy has been performed on tumors developing in nude mice following the injection of two types of cells established in culture: (1) rat kidney cells transformed by Kirsten murine sarcoma virus, (NRK-K), i.e. the same tumor cell line as that used in the original paper; and (2) a well dedifferentiated human prostate adenocarcinoma cell line (PC3). Furthermore, in vitro experiments were performed with the same tumor cell lines. The effect of methionine on glycolysis was assayed by biochemical monitoring of lactate production in the supernatant of these cells grown in vitro. Lastly, 1H in vitro NMR spectroscopy of the PC3 line performed on perchloric extracts of both supernatants and cells growing in the presence of (1-13C) glucose, allowed simultaneous detection of glucose and lactate as well as estimation of the lactate-specific enrichment. The in vitro experiments confirmed the inhibiting effect of methionine on glycolysis and demonstrated the absence of a significant modification of the pentose phosphate pathway activity by this aminoacid. In contrast, none of the in vivo experimental results were compatible with this phenomenon, which is probably affected by more general physiological events.

An experimental approach for dynamic rat liver observation in vivo and ex vivo by 31P localized MR spectroscopy for follow-up of liver status at different steps of orthotopic transplantation--a feasibility study.

An experimental approach was evaluated to perform a follow-up of rat liver transplantation by 31P spectroscopy. The approach is based on the use of an implanted surface coil attached to the liver and inductively coupled to the receiver/transmitter line by an external coupling loop. Spatial localization to the liver was performed by selective excitation and dephasing of spins in a slice between the implanted and the coupling coil, the slice being positioned on a proton image acquired prior to spectroscopy. Characteristics of the protocol were established on a phantom and in vivo on non-transplanted rat livers indicating good localization and high signal-to-noise ratio. Preliminary results obtained on transplanted livers revealed a relation between evolution of the 31P spectrum and animal survival. As shown in separate experiments, the same technique also enabled easy acquisition of the 31P profile of livers stored at 4 degrees C in University of Wisconsin solution. Therefore, the experimental approach described here opens up the possibility of measuring changes of the 31P profile on the same liver during the whole transplantation procedure, i.e., in the donor, during preservation and after transplantation, and comparing evolution of spectra with transplantation outcome.