Myocardial Hibernation

Sawyer, Douglas B.; Loscalzo, Joseph

doi:10.1161/01.cir.0000014689.12415.89

Cited by 33 publications

(11 citation statements)

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“…Hibernation is currently considered not only as a simple consequence of an oxygen deficit, but rather as an adaptive response to maintain cardiomyocyte viability in the setting of reduced blood flow (146). In stunning parallel with septic cardiomyopathy, the hibernating myocardium exhibits reduced calcium responsiveness (147), ultrastructural changes including loss of myofibrils (148), loss of mitochondria (149), and apoptosis-induced cell loss (150,151). Moreover, there is evidence that TNF-α and iNOS contribute to myocardial hibernation (152).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, there is evidence that TNF-α and iNOS contribute to myocardial hibernation (152). Interestingly, these changes seem to be dose dependent, with moderate increases leading to reversible myocardial dysfunction, and greater increases resulting in irreversible injury (148). Thus, a crucial question is whether exceeding a certain threshold level of TNF-α, iNOS, or further unidentified mediators triggers the conversion from reversible to irreversible myocardial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Events in the Cardiomyopathy of Sepsis

Flierl

Rittirsch

Huber‐Lang

et al. 2008

Mol Med

109

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Septic cardiomyopathy is a well-described complication of severe sepsis and septic shock. However, the interplay of its underlying mechanisms remains enigmatic. Consequently, we constantly add to our pathophysiological understanding of septic cardiomyopathy. Various cardiosuppressive mediators have been discovered, as have multiple molecular mechanisms (alterations of myocardial calcium homeostasis, mitochondrial dysfunction, and myocardial apoptosis) that may be involved in myocardial dysfunction during sepsis. Finally, the detrimental roles of nitric oxide and peroxynitrite have been unraveled. Here, we describe our present understanding of systemic, supracellular, and cellular molecular mechanisms involved in sepsis-induced myocardial suppression. SYSTEMIC, SUPRACELLULAR MECHANISMS Decreased Coronary Blood FlowOne of the first suggestions was that reduced coronary perfusion in the septic heart might be responsible for a setting of global cardiac ischemia. This hypothesis was soon abandoned after direct measurements of coronary blood flow were obtained, showing no reduced, but rather increased, coronary blood flow (22,23). In later studies, however, increased levels of plasma troponin were observed and correlated with the severity of myocardial depression during sepsis and septic shock (24). Myocardial necrosis could not be observed in patients who died from septic shock (3,25), however, raising the question whether increases in troponin were due to cytokine-induced, transient increases in cardiomyocyte membrane permeability to troponin. To date, this remains to be determined. Alterations of MicrovasculatureThere is now increasing evidence that sepsis and septic shock leads to changes of the myocardial microvasculature. In a canine model of endotoxemia, maldistribution of heterogeneous coronary blood flow has been reported (26). These findings might be caused by endothelial swelling and nonocclusive intravascular fibrin deposits in the microvasculature (27). In parallel, activated cardiomyocytes from septic mice promoted transendothelial migration and activation of circulating neutrophils into the interstitium (28) where these cells may augment the sepsis-induced intracardial inflammation, and contribute to an increased vascular leakage, which has been described to also impair cardiac function and compliance secondary to myocardial edema (29,30). Yet, studies have failed to confirm cellular hypoxia in a murine sepsis model (31). Cardiosuppressing Circulating Proinflammatory MediatorsAnother hypothesis suggested circulating myocardium-depressing factors as the cause of septic cardiomyopathy (32). Parrillo et al. (33) confirmed the existence of a cardiodepressant substance by incubating isolated rat cardiomyocytes with serum obtained from septic shock patients, leading to decreased amplitude and velocity of cardiomyocyte shortening. Levels of cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and the complement anaphylatoxin, C5a, are known to be elevated in the circulation during sepsis an...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular Events in the Cardiomyopathy of Sepsis

Flierl

Rittirsch

Huber‐Lang

et al. 2008

Mol Med

109

View full text Add to dashboard Cite

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“…Such an ischemic "penumbra" may be at risk in the ensuing days of further cell death 16 or triggering conversion to hibernation over a longer period. 17 Previously, the lack of recovery in the region of infarction despite restoration of patency to the IRA has been attributed largely to "reperfusion injury" mediated through myocardial apoptosis, 18 the generation of free radicals, 19 and associated inflammatory response. 20 Our findings extend previous work highlighting impaired microvascular perfusion in AMI despite conventionally successful reperfusion therapy, with a low likelihood of recovery of function in these affected regions.…”

Section: Taylor Et Al Microvascular Reperfusion In Ami 2083mentioning

confidence: 99%

Detection of Acutely Impaired Microvascular Reperfusion After Infarct Angioplasty With Magnetic Resonance Imaging

et al. 2004

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Background-Despite the reopening of the infarct-related artery (IRA) with infarct angioplasty, complete microvascular reperfusion does not always ensue. Methods and Results-We performed cardiovascular MRI (CMR) in 20 acute myocardial infarction (AMI) patients within 24 hours of successful infarct angioplasty and 10 control patients without obstructive coronary artery disease on a clinical 1.5-T CMR scanner. Three-month follow-up CMR in AMI patients evaluated the impact of abnormal reperfusion on recovery of function. Infarction was localized by delayed contrast hyperenhancement and impaired systolic thickening. Microvascular perfusion was assessed at rest by first-pass perfusion CMR after a bolus of gadolinium-DTPA by use of the time to 50% maximum myocardial enhancement. Whereas contrast wash-in was homogeneous in control patients, AMI patients exhibited delays in the hypokinetic region subtended by the IRA compared with remote segments in 19 of 20 patients, with a mean contrast delay of 0.9Ϯ0.1 seconds (95% CI, 0.6 to 1.2 seconds). At follow-up, the mean recovery of systolic thickening was lower in segments with a contrast delay of 2 seconds or more (10Ϯ7% versus 39Ϯ4%, PϽ0.001). A contrast delay Ն2 seconds and infarction Ͼ75% transmurally were independent predictors of impaired left ventricular systolic thickening at 3 months (Pϭ0.002 for severe contrast delay, Pϭ0.048 for Ͼ75% for transmural infarction). Conclusions-CMR detects impaired microvascular reperfusion in AMI patients despite successful infarct angioplasty, which when severe is associated with a lack of recovery of wall motion.

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“…Incomplete occlusion or intermittent reopening, 13 and other factors such as ischemic preconditioning, 14 residual blood flow in the infarct-related artery, 6 or recruitment of collaterals 15,16 may prevent complete necrosis and preserve viable myocardium. Other studies have demonstrated the existence of stunned or hibernating myocardium at the area at risk 17,18 and that hibernating myocardium may recover contractile function and that time window to salvage viable myocardium and ameliorate adverse left ventricular remodeling may be extended to weeks if collateral circulation is present. 19 In fact, our study also showed that patients with preserved collateral circulation showed a strong trend toward a greater myocardial salvage compared with patients with absent collateral circulation.…”

Section: American Heart Journal December 2006mentioning

confidence: 99%