Chemical and functional correlates of postischemic renal ATP levels.

Abstract

Renal energy metabolism was investigated before, during, and after ischemic insults of varying durations with in vivo 31P NMR spectroscopy. The postischemic recovery of renal ATP was found to be a biphasic process regardless of the length of the ischemia. This two-stage recovery consisted of a quick initial component immediately upon reflow followed by a slower, more gradual return toward preischemlc levels. To characterize the source of each phase of the recovery, kidneys were extracted with perchloric acid at the end of the different periods of ischemia (before reflow). Concentrations of adenine nucleotides and breakdown products adenosine, inosine, and hypoxanthine were determined by 1H NMR spectroscopy. Excellent correlation was found between the residual nucleotide pool and the magnitude of the initial phase of ATP recovery. Additionally, the renal ATP content after 120 min of reflow was shown to have a strong correlation with subsequent functional recovery. These experiments show that in vivo 31P NMR can provide new and dynamic information concerning the biochemical recovery from ischemia. Furthermore, this data has the potential to predict the eventual functional recovery of the organ.It is well-known that during renal ischemia, ATP levels fall to less than 25% of preischemic values and remain low for the duration of the insult (1-9). After an ischemic episode, the recovery of ATP is incomplete (2-5, 10). Previous studies from our laboratory (8, 9) using in vivo 31P NMR indicated that, after 45 min of bilateral renal artery occlusion, the recovery of cellular ATP is a biphasic process. There is a rapid initial recovery of ATP immediately upon reflow and a slower, more gradual recovery that continues as ATP returns toward its preischemic levels. In addition, these previous studies showed that postischemic augmentation of cellular ATP by the infusion of adenine nucleotides was associated with significant improvement in renal function 24 hr after the initial injury (8,9,11,12).The present study evaluates both of these previous observations by varying the duration of the insult in order to modulate the biochemical and functional severity of the ischemic injury. In this manner, we determined the components of the biphasic recovery of cellular ATP and also the relationship of functional recovery to the renal ATP concentration after 2 hr of reflow. The magnitude of the initial recovery of ATP was found to be a good index of the residual adenine nucleotide pool in the kidney at the end of the ischemic interval. In addition, there is a direct linear correlation between the tissue concentration of ATP following 120 min of recovery and renal function 24 hr later. Moreover, the pattern of recovery of renal ATP during this time period provides an assessment of the net rate of ATP resynthesis.Thus, delineation of the recovery of cellular ATP by in vivo 31P NMR provides new and dynamic information concerning the biochemical and functional recovery from an ischemic renal injury. MATERIALS AND METHODSIn Vivo NMR E...

FK 506 ameliorates the hepatic injury associated with ischemia and reperfusion in rats

“…2). A similar strong association between postischemic hepatic ATP content and subsequent recovery has been demonstrated in other models of hepatic (16) and renal (17) ischemia. The improved survival of the group 3 animals pretreated with FK 24 hr before the initiation of ischemia was reflected also by lower serum levels of AL T (Fig.…”

Renal Cell Injury: Metabolic and Structural Alterations

“…Thus, the third phase of ATP regen- eration is particularly important with respect to the severity of the injury, and the restoration of cellular ATP is critically dependent on the ability of injured cells to effectively use endogenous precursors during reperfusion. These important alterations in adenine nucleotide metabolism have been correlated with the degree of renal functional impairment and structural alterations (7,8,12,13). For example, animals subjected to progressive degrees of renal hypoperfusion develop acute renal failure only when severe ATP depletion occurs (13), and when renal perfusion is altered to the same degree only those animals in which ATP is severely depleted develop evidence of functional impairment (12).…”

“…With the application of in I~I J O nuclear magnetic resonance spectroscopy, it has been possible to further delineate alterations in adenine nucleotide metabolism that occur as a consequence of renal hypoperfusion or ischemia (7,8). Three phases of this relationship have been found to be of particular importance (Fig.…”

Disassociation of Postischemic Recovery of Renal Adenosine Triphosphate and Cellular Integrity

“…These technical improvements included a redesigned and rebuilt coil, use of a cuffed vascular occluder that did not change the load factor or position of the kidney during ischemia, and placement of a femoral artery line to be sure the vascular occlusion was complete and was effectively released. These improvements in NMR technique have now: 1) allowed acquisition of spectra at intervals of 3.5 min instead of 7 min, as previously reported (19); 2) obviated the need for reshimming, inasmuch as the kidney does not move during occlusion or reperfusion; and 3) enhanced sensitivity with improved signal-to-noise ratio. Changes in cellular ATP during the early rapid phase of recovery, the first 30 min of reflow, can now be examined.…”

“…The impact of this improvement in cellular ATP during early reflow and on the long-term recovery from ischemic acute renal failure has been delineated. Our laboratory has shown previously that improvement in cellular energetics is associated with enhanced renal function, amelioration of histomorphologic damage, and sustained recovery of glomerular and tubule function (3,9,19).…”