Myocardial Hibernation

Myocardial hibernation is an adaptation caused by chronic or intermittent reduction in coronary flow characterized as reduced regional contractile function that recovers after removal of the artery stenosis. A subacute downregulation of contractile function in response to reduced regional myocardial blood flow can occur, which normalizes regional energy and substrate metabolism but does not persist more than 12-24 h. Chronic hibernation develops in response to episodes of myocardial ischemia and reperfusion, progressing from repetitive stunning with normal blood flow to hibernation with reduced blood flow, reviewed by Heusch.80 

Salient features of the hibernating myocardium are the increase in glucose uptake out of proportion to coronary flow (metabolism/perfusion mismatch)81 and the increase in myocardial glycogen content with ultrastructural characteristics resembling those of the fetal heart.82 

Recording of left ventricular developed pressure (LVDP is defined as ihe difference between systolic and diastolic left ventricular pressure) from Langcndorff perfused heart after stabilization followed by complete flow cessation (zero-flow global ischemia) and flow re-establishment (reperfusion). Note the development of isctiemic contracture (black arrow) and hypcrcontracturc early at the time of reperfusion (white arrow). 

Left ventricular pressure recording of a perfused rat heart model of zero-flow global ischemia and reperfusion. A progressive increase in LVDP occurs at reperfusion. This corresponds to myocardial stunning (data from our laboratory). 

Arrhythmias are observed during the ischemic phase as well as at reperfusion in most of the animal models. In the first 2-10 min of ischemia, a burst of irregular ventricular tachycardia occurs but evolution to ventricular flbrillation is rare. These arrhythmias are mainly of a reentry nature. A second phase of arrhythmias is evident after 20-30 min of ischemia. The percentage of animals that show this delayed phase of arrhythmias is small and the evolution to ventricular flbrillation is more frequent and the animals can die. This phase is associated with a massive release of catecholamines, changes in calcium overload and an increase in extracellular potassium, reviewed by Carmeliet.55 

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Gerber BL, Vanoverschelde JL, Bol A, Michel C, Labar D, Wijns W et al. Myocardial blood flow, glucose uptake, and recruitment of inotropic reserve in chronic left ventricular ischemic dysfunction. Imphcations for the pathophysiology of chronic myocardial hibernation. Circulation 1996 94 651-659... 

G. Heusch, R. Schulz and S.H. Rahimtoola, Myocardial hibernation - a delicate balance, Am. J. Physiol. 288, H984-H999 (2005). 

Qureshi U, Nagueh SF, Afridi I, et al. Dobutamine echocardiography and quantitative rest-redistribution 201T1 tomography in myocardial hibernation. Circulation 1997 95(3) 626-35. 

Heusch G, Schulz R. Myocardial hibernation adaptation to ischaemia. Eur Heart J... 

Residual trapping of metabolic analogues by hibernating myocardium, such as FDG [46-48], "Carbon ("Q acetate [49-52], and "C palmitate [53-55] reflects sufficient integrity of myocytes and their metabolism to allow recovery of myocardial contractile function after revascularization. 

Ross J, Jr. Myocardial perfusion-contraction matching. Implications for coronary heart disease and hibernation. Circulation 1991 83 1076-1083... 

Dilsizian V, Bonow RO. Current diagnostic techniques of assessing myocardial viability in patients with hibernating and stuimed myocardium. Circulation 1993 87 1-20... 

In the context of acute myocardial injury where the maximal restoration of blood flow to the ischemic/hibernating... 

G. Heusch, J. Rose, A. Skyschally, H. Post and R. Schulz, Calcium responsiveness in regional myocardial short-term hibernation and stunning in the in situ porcine heart. Inotropic responses to postextra-systolic potentiation and intracoronary calcium, Circulation 93(8), 1556-66 (1996). 

D.K. Kalra, X. Zhu, M.K. Ramchandani, G. Lawric, M.J. Reardon, D. Lee-Jackson, W.L. Winters, N. Sivasubramanian, D.L. Mann and W.A. Zoghbi, Increased myocardial gene expression of tumor necrosis factor-alpha and nitric oxide synthase-2 a potential mechanism for depressed myocardial function in hibernating myocardium in humans, Circulation 105(13), 1537-1540 (2002). 

R. A. Kloner, K. Przyklenk, S. H. Rahimtoola, E Braunwald, Myocardial stunning and hibernation mechanisms and clinical implication. In Stunning, hibernation and calcium in myocardial ischemia and reperfusion, Opie LH, ed. Kluwcr Academic Publishers, Boston pp 251-280 (1992). 

A persistent defect, that is unchanged and is present on both exercise and rest images indicates MI or scar tissue. Persistent defect or defects can also be caused by chronic severe ischemia (hibernating myocardium). In order to differentiate between severely ischemic, but still viable myocardium, from scar tissue, myocardial viability studies are indicated. 

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