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M EC H A N I S M S O F D I S E AS E

Review Article

Mechanisms of Disease

FR A N K L I N H . EP S T E I N, M . D. , Editor

H

IBERNATING

M

YOCARDIUM

WILLIAM WIJNS, M.D., STEPHEN F. VATNER, M.D., AND PAOLO G. CAMICI, M.D.

From the Cardiovascular Center, Onze Lieve Vrouw Ziekenhuis, Aalst, Belgium (W.W.); the Cardiovascular and Pulmonary Research Institute, Al-legheny University of the Health Sciences, Pittsburgh (S.F.V.); and the Medical Research Council Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, London (P.G.C.). Address reprint re-quests to Dr. Vatner at the Cardiovascular and Pulmonary Research Insti-tute, Allegheny University of the Health Sciences, 320 E. North Ave., Pittsburgh, PA 15212.

©1998, Massachusetts Medical Society.

OR many years, the functional sequelae of chronic coronary artery disease were consid-ered irreversible and amenable only to pallia-tive therapy. For example, a finding of asynergy (the absence of contraction) on the left ventriculogram was thought to indicate the presence of infarcted myocardium or scarring. It is now clear, however, that chronic left ventricular dysfunction (i.e., re-duced contraction or even asynergy) in patients with coronary artery disease is not necessarily irreversible. This new concept is based on two earlier observa-tions. The first was that myocardial dysfunction that was present before the performance of coronary-artery bypass grafting was often reversed after revas-cularization.1-3 This observation was made possible

because surgeons fortuitously disregarded the pre-vailing wisdom and bypassed each graftable vessel, without much consideration of the contractile status of the underlying myocardium, leading to the seren-dipitous finding that even akinetic segments could regain systolic contraction. The second observation was that inotropic stimulation with epinephrine caused transient improvement in regional and global left ventricular dysfunction in patients with coronary artery disease, an effect termed the “epinephrine

ventriculogram” (Fig. 1).4 The improvement in

func-tion, which would not have occurred if the dysfunc-tion had been due to prior myocardial infarcdysfunc-tion and scar formation, indicated the residual viability of my-ocardium subtending areas of hypokinesia (depressed

F

contraction), akinesia (no contraction), or dyskinesia (paradoxical contraction) at rest.

These observations led Diamond et al. to suggest in 1978 that “ischemic noninfarcted myocardium can exist in a state of function hibernation.”5 The

concept of hibernating myocardium, proposed sev-eral years later by Rahimtoola,6,7 has enhanced the

recognition that chronic left ventricular dysfunction may be reversible. Hibernating myocardium is fre-quently detected in patients with ischemic heart fail-ure, and its identification has provided a new ration-ale for coronary revascularization.

This review focuses on the clinical aspects of hi-bernating myocardium and the pathophysiologic mechanisms underlying the condition. The main goal is to stress the clinical importance and prevalence of hibernating myocardium, defined as chronic, revers-ible left ventricular dysfunction due to coronary ar-tery disease. The concept of responsiveness to ino-tropic stimulation is inherent in the definition. There are also certain pathognomonic histologic features of hibernating myocardium. The extent to which blood flow is chronically and severely reduced and the extent to which myocardial stunning (i.e., tran-sient postischemic myocardial dysfunction with rela-tively normal blood flow)8,9 is involved in the

patho-genesis remain controversial and are discussed below.

CLINICAL ASPECTS OF HIBERNATING MYOCARDIUM

Patterns of Left Ventricular Dysfunction

The extent and severity of reversible left ventricu-lar dysfunction vary considerably. The dysfunction may be limited to a discrete portion of the left ven-tricle, with a relatively normal ejection fraction, or may involve global impairment of left ventricular function and heart failure. The severity of functional impairment ranges from hypokinesia to akinesia or dyskinesia, and revascularization of the dysfunction-al regions may result in the recovery of regiondysfunction-al as well as global left ventricular function.10-12

Incidence

Coronary artery disease is the leading cause of morbidity and mortality in developed countries,13

and the extent of left ventricular dysfunction is one of the most important determinants of the progno-sis.14 Advances in medical therapy, particularly the

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transplanta-The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

tion is a successful treatment for heart failure, but it is available only to a small number of patients.15 In

many patients, including those with severe heart fail-ure, coronary revascularization is an alternative ther-apeutic approach if hibernating myocardium can be

demonstrated.15

The prevalence of hibernating myocardium in pa-tients with coronary artery disease can be estimated from the frequency of improvement in regional ab-normalities in wall motion after revascularization. In a prospective study of 252 patients with coronary dis-ease but no electrocardiographic evidence of previous myocardial infarction, who were referred for coronary angiography, evidence of reduced contraction was present in 33 percent of the patients. Eighty-five per-cent of the asynergic myocardial segments that were

revascularized had improved function.16

Up to 50 percent of patients with previous infarc-tion may have areas of hibernating tissue mixed with areas of scar tissue, even in the presence of Q waves on the electrocardiogram.17 The incidence and

de-gree of functional recovery after coronary revascular-ization depend on a number of factors, including the severity of global left ventricular dysfunction preop-eratively, the technique used for myocardial protec-tion during surgery, the presence or absence of per-ioperative myocardial infarction, and the adequacy of revascularization. On the basis of the available da-ta, functional recovery varies widely, occurring in 24

to 82 percent of all dysfunctional segments.18

Identification of Patients with Hibernating Myocardium

Chronic left ventricular dysfunction should be suspected in patients with symptoms of coronary

artery disease who also have dyspnea on exertion, exercise intolerance, or signs of incipient heart fail-ure. If the suspicion is confirmed by noninvasive techniques for assessing regional wall-motion abnor-malities, then possible causes of the dysfunction should be considered.

Hibernating myocardium should be suspected in all patients with coronary artery disease and chronic left ventricular dysfunction of any degree, ranging from regional dysfunction to ischemic cardiomyopa-thy. Other causes of left ventricular dysfunction, whether or not they are associated with coronary ar-tery disease, should be ruled out (Fig. 2). Although left ventricular dysfunction due to hibernating myo-cardium occurs only in patients with coronary artery disease, the presence and severity of left ventricular dysfunction are not necessarily commensurate with the extent and severity of the coronary artery dis-ease. In many patients, perfusion through preexist-ing collateral vessels and newly developed collateral vessels in the coronary circulation can result in the preservation of normal left ventricular function de-spite the presence of coronary artery disease.19

Hibernating myocardium suggests the presence of viable tissue, and this can be determined with the use of imaging techniques that detect either the presence of myocardial tissue that contracts if stim-ulated appropriately or the persistence of metabolic activity within the regions of dysfunctional myocar-dium. Interventions that can transiently force the hi-bernating myocardium to contract include afterload reduction by sublingual administration of nitrates20

and inotropic stimulation by postextrasystolic poten-tiation (i.e., by means of an induced extrasystole21,22) Figure 1. End-Diastolic and End-Systolic Profiles of the Left Ventricle before and after Epinephrine Challenge in a Patient with Coronary Artery Disease and Resting Left Ventricular Dysfunction.

After stimulation with epinephrine, there was improvement in function, particularly in the anteroapical region. The numbers indicate the percentage of axis shortening during systole. The ejection fraction increased from 32 to 54 per-cent. Data are reproduced from Horn et al.4 with the permission of the publisher.

Systole

Diastole Systole

Diastole

24 24 26

18 18

20

11

6

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M EC H A N I S M S O F D I S E AS E

or an infusion of a catecholamine.4 Ventriculography

performed during catheterization is difficult to repeat. Hibernating myocardium, however, can now be detected by stress echocardiography.23-27

Echocardi-ography performed during the infusion of increasing

doses of dobutamine28 is a widely used and accurate

method to detect hibernating myocardium and pre-dict regional and global recovery of function after revascularization. Hibernating myocardium con-tracts in response to a low dose of intravenous

do-butamine (5 to 10 mg per kilogram of body weight

per minute), but its function may deteriorate after the infusion of a high dose of dobutamine (up to 40

mg per kilogram per minute), because the flow re-serve (i.e., the ability of myocardial blood flow to in-crease in response to augmented oxygen

require-ments) is reduced and cannot meet the increased metabolic demand, resulting in ischemia with a fur-ther reduction in contraction. If the presence of is-chemia, as well as hibernating myocardium, can be demonstrated, the likelihood of functional recovery after revascularization increases.28

The use of nuclear imaging techniques to detect hibernating myocardium relies on the demonstra-tion of membrane integrity or residual metabolic activity within the hibernating areas.29 Various

radi-onuclides with different physical and physiologic characteristics can be used for this purpose. Myocar-dial retention of the potassium analogue thallium-201 can be detected by single-photon-emission

com-puted tomography.29,30 Thallium-201 is administered

while the patient is at rest, and images are obtained Figure 2. Algorithm for the Identification of Patients with Hibernating Myocardium.

In addition to the evaluation of the viability of myocardial segments, the final choice of treatment is guided by factors such as coexisting conditions, age, and coronary anatomy. In most cases, medical treatment complements revascularization. CAD denotes coronary artery disease.

Check for

Rule out

Risk factors for atherosclerosis< Regional dysfunction

Confirm left ventricular dysfunction<

Quantitate left ventricular ejection fraction and volumes Acute myocardial ischemia<

Other causes of dysfunction frequently associated with CAD (e.g., alcohol< abuse, mitral regurgitation, arterial hypertension)

Dilated cardiomyopathy< Primary valvular disease< Myocarditis<

Postpartum cardiomyopathy< Hyperthyroidism<

Amyloidosis

Revascularization< Medical treatment

Medical treatment< Heart transplantation

Rule out

CAD present CAD absent

Myocardial viability present Myocardial viability absent Clinical suspicion of left ventricular dysfunction

Noninvasive assessment of left ventricular function

Documentation of CAD by angiography

If revascularization possible

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10 to 20 minutes and 4 hours later. In normal my-ocardium, thallium-201 uptake is initially high but de-creases rapidly within hours. Conversely, in hibernat-ing myocardium, the uptake is initially low but then increases, a phenomenon related to thallium-201 re-distribution.31 When stress–redistribution imaging is

performed, the evaluation of tissue viability requires an additional injection of tracer while the patient is at rest, with subsequent imaging. It is important to determine the severity of the defect in thallium-201 uptake after redistribution. When radioactivity in the dysfunctional area is expressed in relation to the maximal radioactivity in a normally contracting area, an uptake greater than 50 percent of that in the nor-mal area is the best predictor of functional recovery after revascularization.32

Technetium-99m sestamibi, another radionuclide that is only minimally redistributed and is not taken

up by necrotic myocardium,33 has proved useful for

assessing myocardial viability. The prediction of func-tional recovery is based on the semiquantitative anal-ysis of residual sestamibi uptake in dysfunctional segments as compared with remote areas with high uptake. An uptake of 50 to 60 percent is used as the threshold for viable tissue.34

Residual aerobic metabolism, as assessed by the clearance of [11C]acetate, and glucose metabolism, as

assessed by the uptake of [18F]fluorodeoxyglucose,

are common features of noncontracting myocardial segments that are still viable. Residual metabolic activity can be detected with the use of positron-emission tomography.11,35 Once it has been

phos-phorylated by hexokinase, fluorodeoxyglucose is not metabolized further and therefore accumulates in tissue, providing a strong positive signal that can be readily identified. An increased uptake of fluorode-oxyglucose in relation to myocardial perfusion, or flow–metabolism mismatch, is indicative of hiber-nating myocardium, whereas matched defects are in-dicative of scar tissue.11 Preoperative measurements

of regional flow and uptake of fluorodeoxyglucose accurately predict functional recovery after revascu-larization in patients with severely depressed ventric-ular function.11,29

None of the currently available techniques for the identification of myocardial viability can be consid-ered unequivocally superior to the others (Table 1).18

All these techniques have equivalent sensitivity, but the specificity is highest with dobutamine echocar-diography and lowest with thallium-201 studies. Re-cent data suggest that the accuracy of these tech-niques may vary with the severity of left ventricular dysfunction.36 In the absence of a prospective

evalu-ation of cost effectiveness, the initial approach to the preoperative study of patients with coronary artery disease and left ventricular dysfunction can be either stress echocardiography or nuclear imaging with sin-gle-photon-emission or positron-emission

comput-ed tomography, depending on availability and exper-tise. Promising new approaches that are currently under evaluation are metabolic imaging with

single-photon-emission computed tomography,37

myocar-dial contrast echocardiography,38 and magnetic

res-onance imaging.39

Effect of Treatment

Patients with coronary artery disease are often re-ferred for revascularization because of angina, and the success of the procedure is judged according to the extent of improvement in symptoms. In recent years, however, an increasing number of patients with coronary artery disease and evidence of chron-ically dysfunctional but viable myocardium who do not have angina have been treated with revascular-ization. The most striking benefit of this approach is the improvement in the ejection fraction, which is sometimes dramatic and occurs most often in pa-tients with severely depressed ventricular contractil-ity. This improvement is directly related to the num-ber of dysfunctional but viable segments (i.e., the mass of viable tissue).11,37,40 This relation is even

more obvious when the functional response to

exer-*Sensitivity is defined as the number of viable segments of myocardium divided by the number with recovery of function. Specificity is defined as the number of nonviable segments divided by the number without recov-ery of function. Values for sensitivity and specificity are weighted means. There are no significant differences in sensitivity among the techniques. Both thallium-201 tests have significantly less specificity than the other methods; dobutamine echocardiography has greater specificity than the other methods. CI denotes confidence interval, and PET positron-emission tomography. Data are from Bax et al.18

†With stress–redistribution imaging, thallium-201 is administered intra-venously during exercise, and redistribution imaging is performed four hours later, followed by the administration of a second dose of thallium-201 while the patient is at rest.

‡With rest–redistribution imaging, thallium-201 is administered intra-venously while the patient is at rest, with redistribution imaging performed four hours later.

TABLE 1. SENSITIVITYAND SPECIFICITYOF TECHNIQUES TO PREDICT FUNCTIONAL RECOVERYAFTER REVASCULARIZATION

IN PATIENTSWITH LEFT VENTRICULAR DYSFUNCTION DUETO CHRONIC CORONARY ARTERY DISEASE.*

TECHNIQUE SENSITIVITY SPECIFICITY

NO. OF

PATIENTS

NO. OF

STUDIES

% (95% CI)

Technetium-99m sestami-bi imaging

83 (78–87) 69 (63–74) 207 10

Dobutamine echocardi-ography

84 (82–86) 81 (79–84) 448 16

Thallium-201 stress– redistribution imaging†

86 (83–89) 47 (43–51) 209 7

[18F]fluorodeoxyglucose

PET

88 (84–91) 73 (69–74) 327 12

Thallium-201 rest–redis-tribution imaging‡

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M EC H A N I S M S O F D I S E AS E

cise or dobutamine is evaluated after treatment.41

The magnitude of improvement in the symptoms of heart failure and in exercise capacity is proportional to the mass of revascularized myocardium that was demonstrated to be viable preoperatively.42,43

To our knowledge, there have been no prospective studies of the prognostic implications of revascular-izing hibernating myocardium. However, the results of the Coronary Artery Surgery Study, which

com-pared bypass surgery with medical treatment,3

indi-cate that patients with multivessel disease and poor ventricular function benefited the most from surgery in terms of survival, despite a higher rate of periop-erative mortality than that for patients with similar degrees of coronary artery disease and relatively nor-mal left ventricular function. There was no system-atic preoperative testing of myocardial viability, but the survival benefit in the overall cohort of surgical patients probably stemmed largely from the benefit in the subgroup of patients with hibernating myo-cardium. Furthermore, observational studies indi-cate that the results of medical treatment as com-pared with surgical revascularization in patients with chronic left ventricular dysfunction are strongly af-fected by the presence of viable myocardium.44-49

For example, in patients with a mismatch of blood flow and metabolism, as detected by positron-emis-sion tomography, medical treatment is associated with higher rates of morbidity and mortality from cardiac causes.44-47 The finding that mortality is higher in

patients with evidence of hibernating myocardium who do not undergo revascularization supports the concept that revascularization improves the progno-sis in such patients.

HISTOPATHOLOGICAL FEATURES

On the basis of samples obtained at the time of bypass surgery, hibernating myocardium is charac-terized by the following histologic findings: loss of contractile proteins (sarcomeres) in a substantial number of cardiac myocytes without loss of cell vol-ume, glycogen-rich perinuclear zones adjacent to areas with numerous small mitochondria, nuclear changes with heterochromatin distributed evenly over the nucleoplasm, and substantial loss of sarcoplasmic reticulum.50,51 These changes, which are usually

con-fined to islets of subendocardial myocardium, indi-cate cell dedifferentiation as a consequence of a switch from an active contractile state to a stable noncontractile state. Indeed, hibernating cardiac my-ocytes seem to adopt an embryonic phenotype, as shown by the expression of smooth-muscle actin and changes in the expression of cytoskeletal pro-teins such as titin and cardiotin.52 There is a direct

correlation between the severity of the ultrastructur-al changes and the time course of functionultrastructur-al recov-ery.53 However, whether cell dedifferentiation is

re-versible after revascularization or whether cell death

by apoptosis or necrosis eventually occurs is not

known.54,55 It is assumed, but not documented, that

some cellular dedifferentiation will be corrected, since function is recovered.

PATHOPHYSIOLOGIC MECHANISMS

Initial observations supported the concept that hibernating myocardium recovers function soon af-ter revascularization,56,57 but more recent studies

have demonstrated that recovery may be delayed for a period of up to several months.58 Delayed recovery

would be expected if the morphologic changes were severe.53,59 The finding that in some patients

func-tion is regained rapidly whereas in others it is de-layed suggests that the degree of structural alter-ations may vary. Furthermore, it is likely that there are structural differences in different segments of hi-bernating myocardium in the same patient. Alterna-tively, rapid recovery may reflect only transient im-provement in function due to afterload reduction or catecholamine stimulation.56,57

The most controversial issue is whether resting myocardial blood flow is substantially reduced in hi-bernating myocardium. The classic definition, which was not based on quantitative flow measurements, postulated that resting myocardial blood flow was

both chronically and severely reduced.6,7 For

exam-ple, studies using thallium-201 imaging before and after coronary-bypass surgery suggested that the op-eration improved blood flow.30,32 Studies in which

regional myocardial blood flow was quantitated non-invasively by positron-emission tomography, consid-ered the most accurate method of measuring blood flow in humans, have provided evidence that blood flow in hibernating myocardial segments is not creased to an extent that would account for the de-gree of cardiac dysfunction.19,60-68 In one study, for

example, the resting blood flow to hibernating my-ocardium was 0.80 ml per minute per gram of tis-sue, which is 85 percent of the value in subjects with normal left ventricular function.60 Such a small

re-duction in blood flow cannot account for the severe degree of myocardial dysfunction that is characteris-tic of hibernating myocardium. Furthermore, the blood flow to individual segments of the myocardi-um varies widely, ranging from 0.2 to 2.0 ml per minute per gram even in normal subjects.69,70 The

observation of persistent oxidative metabolism also supports the view that perfusion to hibernating seg-ments is nearly normal.19,71 Because myocardial

oxy-gen extraction can increase only by small amounts,

ox-ygen delivery depends on an adequate blood supply.72

The initial hypothesis of reduced blood flow to hibernating myocardium was based mainly on the results of preoperative and postoperative thallium-201 scintigraphy, as noted above.29,30,32 However,

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Figure 3. Regional Ventricular-Wall Thickening during Frequent Episodes of Myocardial Ischemia In-duced by Transient Excitement in a Pig with Coronary Constriction.

The transient excitement induced an imbalance between the supply of and demand for myocardial oxygen in the setting of limited flow reserve and resulted in repetitive instances of myocardial stun-ning, which eventually could not be corrected and led to chronic regional left ventricular dysfunction (hibernating myocardium). Panel A shows systolic wall thickening (as the percent change from control values) distal to the constricted artery in response to repeated reductions in regional function after episodes of excitement for the periods (in seconds) indicated. Two days after the last episode, systolic wall thickening was still reduced by 50 percent. Panel B shows a beat-by-beat analysis of the rate of change in left ventricular pressure over time (dP/dt, an index of myocardial contractility), heart rate, and systolic wall thickening distal to the occluded artery during and after one episode of excitement. Values are expressed as the percent change from base line. The reduction in systolic wall thickening followed the increase in heart rate and left ventricular dP/dt, suggesting that the functional deficit was caused by an imbalance between the supply of and demand for oxygen in response to the hemody-namic changes rather than to a primary reduction in coronary blood flow. Reproduced from Shen and Vatner79 with the permission of the publisher.

165

50

115 135

¡100 100

0

¡50 50

¡20 ¡10 0 10 20 30 40 50 60 70 80 90 100 110

Time (sec) Excitement

dP/dt

% Change

Heart rate Wall thickening

¡120 20

¡60

¡80

¡100 ¡40 0

¡20

0 5 min 10 min 15 min 20 min 25 min 2 hr 48 hr

Time

A

B

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M EC H A N I S M S O F D I S E AS E

normal myocardium, segments of hibernating myo-cardium do not thicken during systole. Because of the limited spatial resolution of nuclear tomography, radioactivity in the hibernating segments is difficult to detect, and an artifactual defect may be seen de-spite maintained flow.73 In addition, the level of

blood flow to normal myocardium is often higher than base-line levels at rest, particularly in patients with a low ejection fraction, in whom compensatory increases in contractility are required to sustain pump function.19,63,68 Finally, images of radionuclide

up-take and retention reflect the concentration of radi-onuclide per gram of tissue in the region of interest. Thus, in the case of a dysfunctional myocardial seg-ment in which half the tissue is viable and half is scarred, with normal blood flow in the viable com-ponent and nearly no blood flow in the fibrotic component, thallium-201 uptake per gram of tissue cannot be higher than 50 percent of the normal val-ue for the entire segment, which may not reflect the blood supply to the viable hibernating myocardium. Most of these limitations can be overcome by quantitative positron-emission tomography.60 Indeed,

in studies of patients with coronary artery disease and chronic left ventricular dysfunction but no pre-vious infarction, resting blood flow to hibernating segments, as measured with positron-emission

to-mography and [13N]ammonia, was normal.19 In

pa-tients with a mixture of hibernating myocardium and scar tissue, flow to the residual hibernating myocardium has been measured with the use of [15O]water.61,64,65,67 Since the uptake of [15O]water in

fibrotic tissue is negligible, it can be used to measure flow per gram of perfusable tissue.60,61 In these

stud-ies as well, flow to the viable myocardium in hiber-nating regions was nearly normal.

What causes chronic myocardial dysfunction, if resting blood flow is not substantially reduced? It is not possible to induce large chronic reductions in blood flow that cause hibernating myocardium in animals, and most data in animals are therefore lim-ited to those arising from a 50 percent reduction in transmural blood flow for less than three hours.74-77

Hibernating myocardium produced in this way functions metabolically and mechanically like that in humans both during the period of reduced blood flow and after blood flow has been restored. The ex-tent to which these results can be extrapolated to the problem of chronic myocardial hibernation is ques-tionable, however, and infarction may occur with longer periods of coronary stenosis. In a study in pigs in which coronary stenosis was maintained for 24 hours, as verified by continuous direct measure-ment of blood flow, infarction did occur.78 In

con-trast, gradual coronary constriction in pigs caused chronic dysfunction, despite the absence of a reduc-tion in blood flow.79,80

If chronically hibernating myocardium is

charac-terized by severely reduced myocardial function and either normal or moderately reduced blood flow, as most of the recent studies in patients suggest, the re-sult is a mismatch between flow and function that is similar to “stunned myocardium.” Defined as post-ischemic myocardial dysfunction with relatively nor-mal blood flow, stunned myocardium was described first in animals8,9 and more recently in patients with

coronary artery disease.81 One can infer from the

documentation of relatively normal blood flow in patients with hibernating myocardium19,64-66 that

hi-bernating myocardium must involve a component of stunned myocardium.

Pigs with gradual coronary stenosis are a useful experimental model of hibernating myocardium be-cause of its chronicity.79,80 These animals have severe

myocardial dysfunction in the zone of the heart that is distal to the stenotic coronary artery. This region of myocardium does not show evidence of necrosis but does have the histologic features of hibernating myocardium, such as increased glycogen deposition

and myolysis.80 Furthermore, the segments of

myo-cardium with depressed function respond positively to a catecholamine challenge.80 Base-line blood flow

to these chronically dysfunctional segments is nor-mal, a finding consistent with the results of clinical studies using positron-emission tomography.19,61-68

Multiple episodes of demand-induced ischemia and consequent myocardial stunning have been observed in pigs with coronary restriction (Fig. 3). The effects of stunning were cumulative; full recovery did not occur, and the myocardium remained functionally depressed. Similarly, exercise-induced ischemia in patients with chronic coronary artery disease can re-sult in myocardial stunning.81

CONCLUSIONS

Hibernating myocardium can be defined as re-versible left ventricular dysfunction due to chronic coronary artery disease that responds positively to inotropic stress. However, a full definition of hiber-nating myocardium must include chronically stunned myocardium as a component. Patients with hiber-nating myocardium have reduced coronary flow re-serve because of coronary artery disease. When the coronary flow reserve is reduced, any stress results in an imbalance between the demand for oxygen and its supply and, consequently, in myocardial ischemia. On recovery, myocardial stunning is manifested, and repeated episodes result in hibernating myocardium. Considering the ubiquity of stress-induced ischemia in patients with coronary artery disease, the clinical prevalence of hibernating myocardium, and its re-sponse to therapeutic intervention, it is important that clinicians recognize and treat this condition.

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Figure

Figure  3.  Regional  Ventricular-Wall  Thickening  during  Frequent  Episodes  of  Myocardial  Ischemia  In-

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