Basal metabolism does not account for high O₂consumption in stunned myocardium

Abstract

Myocardial O2 consumption (MV˙o 2) in stunned myocardium is relatively high compared with the reduced ventricular function. The mechanism of this “oxygen paradox” could occur at different levels: basal metabolism, excitation-contraction coupling, and energy production. In one previously reported series on 12 isolated, blood-perfused rabbit hearts, left ventricular systolic and diastolic function in stunned myocardium were significantly decreased compared with control, whereas total MV˙o 2 was not. The MV˙o 2 for the unloaded contraction was overproportionately high for the decreased function in stunned myocardium, and contractile efficiency was clearly deteriorated. To assess whether the basal metabolism specifically is elevated in stunned myocardium, a second series ( n =14) with a similar protocol was performed in this study. Basal MV˙o 2 after KCl arrest (0.5 ± 0.3 ml ⋅ min−1 ⋅ 100 g−1) was significantly lower than that measured after KCl arrest (1.2 ± 0.5 ml ⋅ min−1 ⋅ 100 g−1) in an additional series on nonischemic hearts ( n = 8). Our conclusion is that basal MV˙o 2 in stunned myocardium is not elevated. Thus this O2-consuming portion of total MV˙o 2 is not responsible for the inefficiency in stunned myocardium. Instead, a “metabolic stunning” occurs at the level of both excitation-contraction coupling and force development by the contractile apparatus.

Mechanoenergetic inefficiency in the septic left ventricle is due to enhanced oxygen requirements for excitation?contraction coupling

“…Basal MVO 2 in non-ischemic, arrested hearts from different species varies from 2.0 to 3.5 mlÁmin À 1 Á100 g À 1 [13]. These different levels depend on several factors such as time of measurement after cardiac arrest, perfusion pressure, temperature, and type of arrest, conditions that were comparable between the groups in our study.…”

Mitochondria: A mirror into cellular dysfunction in heart disease

“…The metabolic stunning that occurs with I/R injury [27], is suggested to be due to increased ATP requirement for myofilament contraction, [29,30], which may result from altered interactions with the myofibrils in response to myofilament proteins undergoing disease-induced PTM [87][88][89] and/or uncoupling of OxPhos [27]. As a result, the OxPhos pathway of the mitochondria has been the subject of numerous investigations.…”

“…Whilst there is a return to near-normal myocardial O 2 consumption (MVO 2 ) with myocardial stunning, reduced contractile function persists [25,26]. Regarded as the 'oxygen paradox', it has been suggested to be the result of a form of 'metabolic stunning' [27], where the down-regulation of oxidative metabolism is observed in the absence of MVO 2 alterations [28]. This suggests that increased MVO 2 is a consequence of increased ATP requirement for contraction [29,30] and/or uncoupling of OxPhos [27], thereby indicating the importance of the mitochondria in the development of I/R injury.…”

“…Regarded as the 'oxygen paradox', it has been suggested to be the result of a form of 'metabolic stunning' [27], where the down-regulation of oxidative metabolism is observed in the absence of MVO 2 alterations [28]. This suggests that increased MVO 2 is a consequence of increased ATP requirement for contraction [29,30] and/or uncoupling of OxPhos [27], thereby indicating the importance of the mitochondria in the development of I/R injury. With prolonged ischemic injury, the myocardium undergoes ischemia-induced cell death as a consequence of both necrosis and apoptosis [31,32].…”

Advanced Cardiac MR Imaging of Ischemic Heart Disease

“…As described earlier, this decrease in deoxygenated hemoglobin level would contribute to an increase in T2, although the magnitude of this effect has not been determined clinically in the setting of acute myocardial infarction. Stunned myocardium, unlike infarcted myocardium, however, consumes oxygen at the same rate as normal contracting myocardium (82), and the venous deoxygenated hemoglobin concentration would be similar to that of normal myocardium. Stunned tissue and infarcted tissue both show wall motion abnormalities, which are difficult to distinguish.…”