Biochemical Changes During Acute Physiological Failure in the Rat: Ii. The Behavior of Adenine and Pyridine Nucleotides of the Liver During Shock

Abstract

The acute hypoxia, caused by severe blood loss, gives rise to the rapid breakdown of glycogen in the liver and concurrent increase in the concentration of ATP in the mitochondria. The increase in adenosine triphosphate (ATP) continues until the onset of the reversible phase of shock. The glycogen reserve approaches depletion during the late reversible phase. Simultaneously, the generation of ATP in the mitochondria ceases and the concentration begins to fall. It would appear that at this time the adenylate kinase mechanism in the mitochondrial membrane comes into play to convert the adenosine diphosphate (ADP) into ATP and adenosine monophosphate (AMP). As the condition becomes irreversible the residual ATP and phosphorylated intermediates of the Embden–Meyerhof system undergo rapid hydrolysis with liberation of AMP and inorganic phosphate in the cytoplasm.The concentration of the pyridine nucleotides undergoes no change in any of the liver cell components until the onset of the irreversible phase of failure. Thereafter, these nucleotides undergo a progressive conversion to the reduced form.

Nicotinamide Adenine Dinucleotide (NAD) Content of Liver with Hemorrhagic Shock

“…This stuldy indicates that there is a decrease in the total nicotinamide adenine dinucleotides in liver in shock with a concomitant shift toward the reduced form lowering the NAD+/NADH ratio. The decrease in NAD+ with shock in liver homogenates is in agreement with the findings of Loiselle and Denstedt (1). The experimental shock model employed by Loiselle and Denstedt (1) was, however, quite different from the model employed in this study.…”

“…The decrease in NAD+ with shock in liver homogenates is in agreement with the findings of Loiselle and Denstedt (1). The experimental shock model employed by Loiselle and Denstedt (1) was, however, quite different from the model employed in this study. Whereas we monitored the degree of shock by following mean arterial blood pressure and maintained hypotension by slow reinfusion of varying amounts of shed blood, the above authors merely allowed animals to bleed and determined the stage of shock by observing respiratory alterations.…”

“…Whereas we monitored the degree of shock by following mean arterial blood pressure and maintained hypotension by slow reinfusion of varying amounts of shed blood, the above authors merely allowed animals to bleed and determined the stage of shock by observing respiratory alterations. As nearly as it could be ascertained, the "irreversible shock" stage of Loiselle and Denstedt (1) would be comparable to the beginning of take back of shed blood in our shock model. The results of treatment of animals with blood and Ringer's lactate in this study indicate that the levels of NAD are rapidly restored to normal by replenishlment of circulatory volume.…”

In vivo comparison of cerebral tissue PO2 and cytochrome aa3 reduction-oxidation state in cats during hemorrhagic shock.

“…Alterations such as uncoupling of phosphorylative activity from respiration, inhibition of ATPase enzyme activity, and defective ion transport are evident (3,4). There is a progressive conversion of the pyridine nucleotides to the reduced form in the mitochondria of the livers in rats during shock (10). Structurally, the mitochondria swell, broken membranes are demonstrable, and in the final stages complete disappearance of the inner mitochondrial structure is apparent (11).…”