Prolonged depletion of ATP and of the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs

Reimer, Keith A.; Hill, M L; Jennings, Robert B.

doi:10.1016/0022-2828(81)90219-4

Cited by 351 publications

(99 citation statements)

References 24 publications

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“…However, a cause-and-effect relationship between low adenine nucleotides and irreversible cellular damage has not been clearly established. One reason for this is that it has not been possible to restore ATP levels rapidly, and to determine whether restoration of ATP results in reversal of cellular damage (Reibel and Rovetto, 1979;Reimer et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Neely¹,

Grotyohann²

1984

Circulation Research

547

162

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SUMMARY. The mechanism of irreversible damage to ischemic myocardium was investigated in the perfused rat heart. The time of transition from reversible to irreversible damage to contractile function was accelerated by accumulation of glycolytic products and increases in extracellular calcium. Both of these effects were largely independent of adenine nucleotide levels in the tissue. With zero coronary flow and 1.25 nut calcium the decrease in ability of the heart to recover ventricular function with reperfusion after 30 minutes of ischemia was directly correlated with accumulation of glycolytic products (as estimated by tissue lactate) during ischemia. The extent of lactate accumulation during ischemia was varied by preperfusing the hearts for 0, 10, or 15 minutes under anoxic, high coronary flow conditions to deplete tissue glycogen prior to ischemia, and by adding lactate back to the perfusate of these hearts during the ischemic period. Recovery of ventricular function was inversely related to tissue lactate during ischemia and varied from 28 to 92%, even though there was little or no change in tissue levels of residual adenosine triphosphate. Increasing extracellular calcium accelerated the time of onset of irreversible damage with little or no change in residual adenosine triphosphate levels. At any given calcium concentration, the time-dependent declines in the ability of the heart to recover ventricular function was also largely independent of adenosine triphosphate levels. These studies suggest a major role of anaerobic glycolytic products (lactate, hydrogen ion, or NADH) in ischemic damage to the heart that is unrelated to loss of tissue adenine nucleotides. With zero or low flow ischemia, this effect may result in irreversible damage to the myocardium before adenine nucleotides are reduced to critically low levels. (Circ Res 55: 816-824, 1984)

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Section: Discussionmentioning

confidence: 99%

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Neely¹,

Grotyohann²

1984

Circulation Research

547

162

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“…Accordingly, local infusion of ATP was used to successfully delay the onset of irreversible ischaemic injury and the role of high energy phosphates in preservation of ischaemic myocardium was highlighted [572]. Delayed resynthesis of ATP following its depletion during myocardial ischaemia was proposed [573] and thus, ATP-MgCl 2 was used for the treatment of ischaemia (see [574][575][576]). Extracellular ATP and adenosine appear to play complementary, protective roles in ischaemic pre-conditioning through P2YR and P1R, respectively [577].…”

Section: Ischaemiamentioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

119

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This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

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“…Myocardial ATP concentration also remains reduced by an average of 22% after 3 days of reperfusion after a 15-minute coronary occlusion, and like cardiac function it returns to normal by 1 week. 1 ' Reimer et al 16 noted that after 4 days of reperfusion following 15 minutes of occlusion of the left circumflex coronary artery of the dog, the ATP concentration of the posterior papillary muscle was still significantly less than the control. Morphologic changes in the myocardium parallel those occurring in function and ATP concentration.…”

mentioning

confidence: 99%

The stunned myocardium: prolonged, postischemic ventricular dysfunction.

Braunwald¹,

Kloner²

1982

Circulation

2,604

643

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SUMMARY Myocardial ischemia has, for many decades, been viewed as an all-or-none process that causes myocardial necrosis when prolonged and severe, but whose effects are transient when it is brief or mild. In view of the evidence that the ischemic process may "hit, run and stun," perhaps our thinking about the consequences of myocardial ischemia should be expanded. According to this formulation, an ischemic insult not of sufficient severity or duration to produce myocardial necrosis may acutely affect myocardial repolarization and cause angina (hit); but these changes wane rapidly (run), when the balance between myocardial oxygen supply and demand has been reestablished. However, the ischemia may interfere with normal myocardial function, biochemical processes and ultrastructure for prolonged periods (stun). The severity and duration of these postischemic changes depend on the length and intensity of the ischemia, as well as on the condition of the myocardium at the onset of the ischemic episode. Furthermore, it is likely that when the myocardium is repeatedly stunned, it may exhibit chronic postischemic left ventricular dysfunction, an ill-defined condition. If prolonged, chronic postischemic left ventricular dysfunction can progress to myocardial scarring and ischemic cardiomyopathy, it may be important to determine how often it can be ameliorated by permanent improvement of myocardial perfusion by surgical treatment.THE EARLIEST recorded investigation on the effects of coronary artery occlusion on the action of the heart was in 1698, when Chirac' ligated a coronary artery in the dog and noted that soon thereafter the heart ceased to beat. Late in the nineteenth century, Porter2 demonstrated that coronary ligation resulted in a reduction in the systolic ventricular pressure and in its rate of rise as well as in an elevation of diastolic ventricular pressure.

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Prolonged depletion of ATP and of the adenine nucleotide pool due to delayed resynthesis of adenine nucleotides following reversible myocardial ischemic injury in dogs

Cited by 351 publications

References 24 publications

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts.

Cardiac purinergic signalling in health and disease

The stunned myocardium: prolonged, postischemic ventricular dysfunction.

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