Flow Thresholds for Cerebral Energy Disturbance and Na⁺ Pump Failure as Studied by in vivo ³¹P and ²³Na Nuclear Magnetic Resonance Spectroscopy

Abstract

Summary:The relationships among CBF, cerebral en ergy metabolism, Na + pump activity, and electrocortico grams (ECoG) following graded hypotension were studied in 48 gerbils. Energy metabolism and Na+ pump activity were estimated by in vivo 31p and 23Na nuclear magnetic resonance (NMR) spectroscopy, and CBF was determined by [14C]iodoantipyrine methods at the end of the experiments. The CBF measured in normotensive an imals was 0.51 ± 0.07 ml/g brain/min. Following graded hypotension, no 31p spectral change was observed until CBF fell to 0.21-0.27 ml/g brain/min, at which level the intracellular pH began to decrease in association with Address correspondence and reprint requests to Dr. Hiroaki Naritomi at Cerebral Circulation Laboratory, National Cardio vascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565, Japan.Abbreviations used: ECoG, electrocorticogram; NMR, nu clear magnetic resonance; PCr, phosphocreatine; pHi, intracel lular pH; Pi, inorganic phosphate. 16in association with inorganic phosphate (Pi) elevation. At this level, ECoG became isoelectric, although no adeno sine triphosphate (ATP) change yet resulted. At a flow level of 0.12-0.14 ml/g brain/min, ATP began to decrease gradually. At 0.04-0.05 ml/g brain/min, PCr and ATP vir tually disappeared, and the 23Na signal intensity suddenly changed. The present study demonstrated flow thresholds for the development of tissue acidosis, PCr-Pi changes, and ATP reduction. It appears that functional suppression occurs prior to ATP changes, whereas Na + pump failure results after ATP depletion. Key Words: CBF thresholds for cerebral ischemia-Cerebral energy metabolism-Intracellular pH-Na+ pump activity31p and 23Na nuclear magnetic resonance spectroscopy.pump failure differ considerably. The former lies somewhere between 0. 15 and 0.20 mllg brain/min (Sharbrough et aI. , 1973; Trojaborg and Boysen, 1973; Heiss et aI. , 1976; Astrup et aI. , 1977; Bran ston et aI. , 1977), whereas the latter is at approxi mately 0. 06-0. 08 ml/g brain/min (Astrup et aI., 1977; Branston et aI., 1977). The former may repre sent the flow threshold at which mild energy distur bance begins, whereas the latter may represent the threshold for energy exhaustion. However, few studies have yet been undertaken on the flow-en ergy relationship, and the above mentioned as sumptions remain to be confirmed.In vivo nuclear magnetic resonance (NMR) spec troscopy is a potentially useful tool for examining the physiological and biochemical natures of organs noninvasively. With this method, it is possible to estimate not only changes of high-energy phos phate, but also those of intracellular pH (pHi) or

Assessment of Postischemic Cerebral Energy Metabolism in Cat by 31P NMR: The Cumulative Effects of Secondary Hypoxia and Ischemia

“…2), consistent with a finding in gerbil by Naritomi et al (1988), before there was an appreciable decline in the ATP. Thus, in contrast to the previous indirect conclusion of Crockard et al (1987), it seems that EEG activity does not fail be cause energy in the form of ATP is not available.…”

Brain Tissue Concentrations of ATP, Phosphocreatine, Lactate, and Tissue pH in Relation to Reduced Cerebral Blood Flow following Experimental Acute Middle Cerebral Artery Occlusion

“…LCBF/energy metabolism thresholds cannot be assigned precisely because of the large variability of our data. However, our results are in agreement with those recently reported by Crockard et al (1987) and Naritomi et al (1988). Crockard's group combined measurements of LCBF with H 2 clearance in brain regions of gerbils subjected to unilateral or bilateral carotid occlu sion, with measurements of phosphorus metabo lites, intracellular pH, and lactate made by 31p and lH NMR spectroscopy .…”

“…Their study revealed a threshold effect in the metabolism of cerebral tissue with CBF under 20 mllmin/100 g . Naritomi et al (1988) com bined autoradiographic measurements of LCBF with 31p and 2 3Na NMR; they found that PCr and ATP began to decrease at a CBF level of 18-23 and 12-14 mllmin/100 g, respectively.…”

Alterations in Cerebral Blood Flow and Phosphorylated Metabolites in Piglets during and after Partial Ischemia

“…min-' -100 g-' was associated with failure to maintain control levels of cerebral high energy metabolites. This CBF is higher than the critical flow threshold for energy failure in adult animals of other species such as gerbils (13,14). When expressed as a relative reduction in CBF, energy failure in piglets occurs at similar flow decrements as in adult rats (10) and gerbils (14).…”

“…Recently combined CBF and 31P NMR measurements have established that the flow threshold for energy failure is in the range of 12-20 ml . min-' -100 g-I in adult gerbils ( 13,14).…”