Nucleotide degradation and functional impairment during cardioplegia: amelioration by inosine.

Abstract

A major objective of myocardial protection is conservation of the adenine nucleotide pool during the ischemic period. At any moment, myocardial ATP content is a function of its rates of synthesis and degradation. Although hypothermic cardioplegia greatly reduces energy use during ischemia, 1' ATP degradation still outstrips production and nucleotide degradation products such as adenosine, inosine and hypoxanthine accumulate in the myocardium. '6 These constitute a purine base pool available for resynthesis of ATP during the postischemic recovery period. Failure to recover normal cardiac function after cardiopulmonary bypass correlates well with the inability to resynthesize normal levels of ATP. 14 7,8 However, this may be a consequence of the loss of ATP precursors rather than

Postoperative Cardiac Support with a Pulsatile Assist Pump: Techniques and Results

“…Equally important is the observation that the profoundly depressed myocardium is capable of regaining sufficient function not only to again support the ciruculation but also to provide the necessary reserve to permit the patient to return to a comfortable life-style. The recovery of myocardial function is thought to be a result of a decrease in compliance due to a loss of the myocardial edema associated with ischemic injury (6) and the rebuilding of depleted adenine nucleotides associated with reversible ischemic injury (7).…”

Role of adenosine in the treatment of myocardial stunning

“…The observation that both regional and global ischemia was associated with a rapid depletion of HEPs, including ATP, suggests that a deficiency of energy supply was the cause of contractile dysfunction following ischemia. The administration of adenosine, inosine, and drugs that increase endogenous adeno-sine levels by inhibiting its degradation, such as erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA), have been shown to accelerate ATP repletion after both regional and global ischemia [53][54][55][56][57]. Infusions of ribose that increase the level of 5-phosphoribosyl-l-pyrophosphate, a major limiting factor for the biosynthesis of adenine nucleotides, or 5 amino-4imidazolcarboxamide riboside (AICAR), which bypasses the initial metabolic processes in the salvage pathways, have also been shown to increase myocardial ATP levels [22,58].…”