Cellular physiologists are investigating the mechanisms of contraction cessation in cardiomyocytes in response to ischemic injury. In an animal experiment, the left anterior descending coronary artery is ligated at time 0, and changes in ATP levels within the affected myocardial cells are recorded. At which point on the graph does the affected portion of the myocardium stop contracting?

Question

Cellular physiologists are investigating the mechanisms of contraction cessation in cardiomyocytes in response to ischemic injury.  In an animal experiment, the left anterior descending coronary artery is ligated at time 0, and changes in ATP levels within the affected myocardial cells are recorded.  At which point on the graph does the affected portion of the myocardium stop contracting?

Quizplus · Accepted Answer

11ec160b_3a95_0a77_9249_1309127cfaa4_MD0001_00 The major early biochemical consequence of total myocardial ischemia is cessation of aerobic glycolysis and initiation of anaerobic glycolysis. This transition occurs within seconds and results in inadequate production of high-energy phosphates (eg, ATP and creatine phosphate) and the accumulation of deleterious metabolites, including lactate. Although total ATP levels remain relatively normal during the first few minutes of ischemia, ATP is rapidly depleted from areas of the cell with high metabolic demand, such as the cytosol surrounding the contraction fibers and electrolyte transport pumps. The depletion of ATP in critical cellular areas and the accumulation of toxins result in loss of contractility within about 60 seconds of total myocardial ischemia (Choice A). As ischemia persists, ATP levels within the affected cardiac myocytes continue to fall while lactate levels continue to rise. When ischemia lasts less than 30 minutes, loss of contractile function is reversible. However, on restoration of blood flow, full myocardial contractility is not immediately restored. Instead, there is prolonged dysfunction of the myocardium (myocardial stunning), with contractility gradually returning to normal over the next several hours to days. Increasing durations of ischemia prolong the time that the myocardium remains stunned. Under hypoxic conditions, ATP within cardiomyocytes is degraded to ADP, AMP, and eventually adenosine. Adenosine is able to cross the cell membrane and function as a vasodilator when coronary blood flow is insufficient to meet myocardial demand. However, persistent ischemia can lead to depletion of massive amounts of adenosine. After 30 minutes of total myocardial ischemia, about half of the cellular adenine stores are lost. At this point, failure of cellular homeostasis is inevitable and ischemic injury becomes irreversible (Choice E). Educational objective: Loss of cardiomyocyte contractility occurs within 60 seconds after the onset of total ischemia. When ischemia lasts less than 30 minutes, restoration of blood flow leads to reversible contractile dysfunction (myocardial stunning), with contractility gradually returning to normal over the next several hours to days. However, after about 30 minutes of total ischemia, ischemic injury becomes irreversible.

Cellular Physiologists Are Investigating the Mechanisms of Contraction Cessation in Cardiomyocytes