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H~GI~ OUTPUT RENAL FAILUltE has been shown to follow the administration of methoxyflurane. 1 The relationship is apparently dose-dependent3 It would appear that some of the products of metabolism of the drug are responsible for the vasopressin resistant diabetes insipidus that has been well-documented to follow general anaesthesia with this agent, aIn particular, the evidence is compelling which links inorganic fluoride, derived from the metabolism of methoxyflurane and the development of renal dysfunction following its administration. 8Previous observations have shown that failure of autoregulation of renal blood flow follows the administration of methoxyflurane. 4 The suggestion was made that such failure may be followed by a change in the intrarenal distribution of blood and that this may influence the handling of the metabolic products of methoxyflurane. This, in turn, might affect the nephrotoxicity of the agent.Although autoregulation maintains total renal blood flow remarkably constant in the face of alterations in systemic blood pressure, 5 nevertheless, the distribution of blood is heterogeneous throughout the renal parenchyma. ~ In ordinary circumstances, the outer cortex receives three-quarters of the total flow of blood to the kidney. The juxtamedullary cortex and the outer medulla receive, in contrast, only about one-fiRh of total renal flow. r It is possible for this distribution to alter radically without any marked or even obvious change in total renal blood flow. On the other hand, alterations in distribution may also accompany changes in total flow.Outer cortical nephrons have shorter tubular systems than those of the deeper and iuxtamedullary nephrons. They are relative salt losers when they are compared with deeper nephrons which tend to conserve salt. In addition, outer cortical nephrons have a particularly rich autonomic innervation of the afferent glomerular arterioles and also have considerably larger quantities of renin associated with the juxtaglomular apparatus than is found elsewhere. 7The precise functions of these arrangements is open to question, but that they are significant is probably indisputable. Either nervous or hormonal mechanisms (or possibly both) may influence autoregnlation of total flow and also the intrarenal distribution of perfusion.

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The effects of dobutamine, a new catecholamine, have been studied during anaesthesia with halothane, halothane and nitrous oxide and alphaprodine. Renal blood flow is increased by dobutamine as are mean arterial pressure and heart rate. The increase in rate is less marked during alphaprodine anaesthesia than when halothane is administered. Dobutamine may prove a useful agent in the management of acute circulatory failure but it is capable of inducing dysrhythmias under the conditions of these experiments.

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