Sodium, ATP, and intracellular pH transients during reversible complete ischemia of dog cerebrum.

Abstract

We tested the hypotheses that with the onset of cerebral ischemia, massive cellular sodium influx does not occur until adenosine triphosphate is fully depleted and that on reperfusion, neuronal sodium efflux does not occur until adenosine triphosphate is fully restored. We examined the temporal relationships among transcellular sodium, energy metabolism, and intracellular pH with sodium and phosphorus magnetic resonance spectroscopy in a new, hemodynamically stable, brain stem-sparing model of reversible, complete cerebral ischemia in eight anesthetized dogs. Inflation of a neck tourniquet after placement of glue at the tip of the basilar artery resulted in decreased blood flow to the cerebrum from 29 ±5 to 0-3 ±0.5 ml/min/100 g. Medullary blood flow was not significantly affected, and arterial blood pressure was unchanged. Sodium signal intensity decreased and did not lag behind the fall in adenosine triphosphate. After 12 minutes of ischemia, reperfusion resulted in a more rapid recovery of sodium intensity (12.4±4.8 minutes) than either adenosine triphosphate (16.5±3.7 minutes) or intracellular pH (38.9±1.8 minutes). Because intracellular sodium has a weaker signal than extracellular sodium, the decreased sodium intensity is interpreted as sodium influx and indicates that sodium influx does not require full depletion of adenosine triphosphate. Rapid recovery of sodium intensity during early reperfusion may represent sodium efflux, although increased plasma volume and sodium uptake from plasma may also contribute. If our interpretation of the sodium signal is correct, delayed recovery of adenosine triphosphate may be due to the utilization of adenosine triphosphate for the restoration of transcellular sodium gradient (Stroke 1991^2:233-241) T he application of magnetic resonance spectroscopy (MRS) to in situ brain allows the time course of ischemically perturbed cerebral bioenergetics as reflected by adenosine triphosphate (ATP), phosphocreatine, and intracellular pH 1 -2 and transcellular sodium gradient 3 to be examined. The potential interactions of brain sodium gradients, intracellular pH, and bioenergetics are many. Maintenance of a normal sodium gradient, necessary for normal neurologic function, is an ATP- Received May 25, 1990; accepted October 17, 1990. dependent process and accounts for 40% of the metabolic demand of the brain as assessed by highdose lidocaine during barbiturate coma. 4 Maintenance of a normal intracellular pH is critical for proper functioning of most enzymatic processes. With the onset of complete ischemia, intracellular pH falls as glucose stores are converted to lactic acid and ATP is hydrolyzed.5 Soon after ATP depletion, extracellular Na + activity decreases. 6 However, Na + influx may precede the sudden decrease in extracellular Na + activity as measured by microelectrodes if this early Na + influx is accompanied by sufficient water to maintain a constant sodium activity. On reperfusion, limited ATP generation may be diverted into restoring ionic gradients instead of main...

Emergency Preservation and Resuscitation with Profound Hypothermia, Oxygen, and Glucose Allows Reliable Neurological Recovery after 3 h of Cardiac Arrest from Rapid Exsanguination in Dogs

“…Different from DHCA, clinical application of EPR in management of ExCA would only be feasible after a normothermic ExCA has occurred. Brain energy reserve is depleted B5 mins after normothermic CA (Shaffner et al, 1999;Eleff et al, 1991). Thus, to postpone energy failure, it may be important for preservation strategies to prevent energy depletion in brain and restore energy levels during induction of hypothermia.…”

Diffusion-weighted imaging studies of cerebral ischemia in gerbils. Potential relevance to energy failure.

“…Hansen 32 has shown that the extracellular potassium concentration ([K + ] e ) changes by only a small amount during the 1-2 minutes following the onset of ischemia or anoxia, but that this is followed by a steep increase in [K + ] c as depolarization ensues. Both Eleff et al 33 and Pekar et al 34 have measured intracellular ATP and sodium by nuclear magnetic resonance (NMR) spectroscopy following complete ischemia. The observations reported by Pekar et al using both phosphorus-31 and multiple quantum-filtered sodium-23 NMR spectroscopy show that upon production of cerebral ischemia there is a delay of approximately 2 minutes before the ATP level begins to fall and that of intracellular sodium begins to increase.…”

“…3338 Eleff et al 33 have suggested that the initial phase after reperfusion consists of energy-driven sodium extrusion (and thus, presumably, accumulation of potassium), such that full ATP recovery is delayed until this process reaches a steady state, and this is then followed by normalization of intracellular pH. The rate of energy recovery following ischemia depends on the duration of ischemia.…”

How can sodium MRI techniques help us understand acute stroke?

“…A similar decrease of 11 ± 8% in sodium signal was detected in a rabbit model in a region which ultimately infarcted, although it was not possible to say whether this measured decrease was in core or penumbra tissue (28) . Further, a 13% decrease in sodium signal was detected in a spectroscopic study of a canine model, but again no discrimination between core and penumbra was possible (44) . Nevertheless, if verified in further studies, this decrease in sodium signal could help identify the presence of penumbra tissue in the acute phase, and hence a PWI-Na mismatch approach may be warranted, or indeed Na-MR imaging alone (27) .…”