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PubMed1991

Segmental wall motion abnormalities in the absence of clinically documented myocardial infarction: clinical significance and evidence of hibernating myocardium.

To determine the frequency and significance of left ventricular wall motion abnormalities in patients without clinical evidence of myocardial infarction, we reviewed the two-dimensional echocardiograms of 252 patients who had no history or electrocardiographic evidence of myocardial infarction and who subsequently underwent coronary angiography. Seventy-seven patients (31%) had one or more segmental wall motion abnormalities. Sixty-six of the 77 patients (86%) had significant coronary artery disease (greater than or equal to 50% luminal diameter stenosis). Seventy-four percent of the patients with coronary artery disease had multivessel disease. The left ventricle was divided into anterior and posterior regions. In the 66 patients, there were 77 separate regions with wall motion abnormalities (49 hypokinesis, 22 akinesis, 6 dyskinesis), including 60 regions (78%) supplied by coronary vessels with greater than or equal to 70% stenosis. Thirty-two patients underwent coronary artery bypass surgery or percutaneous transluminal coronary angioplasty. Follow-up echocardiograms were obtained in 19 patients who had wall motion abnormalities involving 22 regions. Twenty of the 22 regions were revascularized. Wall motion improved in 17 of 20 regions (85%) and returned to normal in 15 regions (75%). We conclude that segmental wall motion abnormalities may be detected by echocardiography in up to one third of patients evaluated for suspected coronary artery disease without documented myocardial infarction. These abnormalities are associated with a high likelihood of multivessel disease as well as with significant narrowing of the artery supplying the region demonstrating abnormal wall motion. Improvement in segmental wall motion abnormalities after revascularization suggests that these areas represent regions of hibernating myocardium.

Adult↗
PubMed1992

Myocardial hibernation identified by hyperbaric oxygen treatment and echocardiography in postinfarction patients: comparison with exercise thallium scintigraphy.

To evaluate the potential for hyperbaric oxygen (HBO) to produce transient improvement in function in areas of myocardium ischemic at rest (hibernating myocardium), 24 patients were studied within 1 week of acute myocardial infarction. Results were compared with single-photon emission computed tomography (SPECT) thallium-201 exercise scintigraphy. Echocardiography demonstrated improved contraction following HBO in 20 of 62 damaged left ventricular segments in 12 of 24 patients. Thirteen of the 28 segments and 9 of the 14 patients showing reversible ischemia on SPECT imaging showed improvement with HBO. There were eight segments with apparently normal resting contraction that showed a reversible thallium defect. Of 42 segments with fixed contraction abnormalities following HBO, eight had reversible thallium defects, four had normal thallium kinetics, and 30 had fixed thallium defects. Thus hyperbaric oxygen can demonstrate improvement in function in some segments of left ventricle after infarction. There is some overlap with viability as determined by thallium studies, but the two techniques may be complementary in describing myocardial ischemia.

Adult↗
PubMed1992

Reperfusion of hibernating myocardium: contractile function, high-energy phosphate content, and myocyte injury after 3 hours of sublethal ischemia and 3 hours of reperfusion in the canine model.

Hibernating myocardium has been defined as a persistent impairment of contractile function resulting from reduced coronary blood flow that can be partially or completely resolved once coronary perfusion is restored. In fact, recent clinical reports have documented a dramatic improvement in contractile function after relief of chronic sublethal ischemia. To investigate the phenomenon of sublethal ischemia followed by reperfusion, we assessed myocyte morphology, high-energy phosphate content, and regional contractile function in dogs undergoing (1) 3 hours of subtotal coronary artery occlusion (CO) and 3 hours of reflow or (2) 3 hours of total CO followed by reflow, in which myocyte viability was maintained by extensive collateral perfusion during ischemia (total CO/negligible necrosis). Data were compared with findings in a third group of dogs with total CO and low collateral blood flow during ischemia, in which large confluent infarcts developed. Endocardial blood flow averaged 30 +/- 6% (p less than 0.01) and 27 +/- 4% (p less than 0.01) of baseline preocclusion values during ischemia in the groups with subtotal CO and total CO/negligible necrosis, versus 3 +/- 1% of baseline values in dogs with total CO/confluent necrosis. Both the subtotal CO and total CO/negligible necrosis groups exhibited only mild-to-moderate reversible myocyte injury (assessed by electron microscopy) and had essentially no necrosis: infarct size was 1 +/- 1% (p less than 0.01) and 4 +/- 2% (p less than 0.01) of the risk region in the subtotal CO and total CO/negligible necrosis groups, versus 55 +/- 9% of the risk region in the total CO/confluent necrosis group. Furthermore, myocardial high-energy phosphate stores were in part preserved in all dogs that underwent sublethal ischemia: endocardial adenosine triphosphate (ATP) content was 55 +/- 11% (p less than 0.01) and 56 +/- 8% (p less than 0.01) versus 11 +/- 2% of baseline values in the subtotal CO, total CO/negligible necrosis, and total CO/confluent necrosis groups, respectively. At 3 hours post occlusion, segment shortening averaged +21 +/- 10% of baseline values in dogs with subtotal CO, (p less than 0.01 versus both total CO groups), -29 +/- 9% in dogs with total CO/negligible necrosis, and -36 +/- 13% in dogs with total CO/confluent necrosis. Reperfusion after sublethal ischemia produced an acute improvement in contractile function in both the subtotal CO and total CO/negligible necrosis groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1994

Dobutamine echocardiography and resting-redistribution thallium-201 scintigraphy predicts recovery of hibernating myocardium after coronary revascularization.

The value of dobutamine echocardiography and resting thallium-201 scintigraphy to predict reversal of regional left ventricular wall motion dysfunction after revascularization in patients with chronic coronary artery disease was assessed. Improvement in wall motion during dobutamine echocardiography and normal or mildly decreased uptake on thallium-201 scanning are strong predictors of reversible left ventricular dysfunction. Dobutamine echocardiography and resting thallium-201 scanning are simple and safe methods of assessing hibernating myocardium.

Angioplasty, Balloon, Coronary↗
PubMed1995

Rest technetium 99m-sestamibi tomoscintigraphy in hibernating myocardium.

The myocardial uptake of rest-injected technetium 99m sestamibi on single-photon-emission computed tomographic images was assessed in 25 patients. All had an area of myocardial dysfunction that could be related to a coronary artery stenosis. None of the patients had clinical evidence of a myocardial infarction. Three months after revascularization, viability was demonstrated by contrast angiography and center-line analysis in 21 (78%) of the 27 formerly hibernating territories. Among these, none had a transmural defect, and 38% had a normal technetium 99m-sestamibi uptake. The four transmural preoperative defects were located in territories without viability. Eight of the 9 territories that were normal at scintigraphy proved to be viable postoperatively. It is concluded that as long as some residual technetium 99m-sestamibi uptake is present, viable myocardium is also present.

Aged↗
PubMed1989

Studies on the estrus cycle of the ground squirrel (Citellus citellus L.) at experimentally induced hibernation.

Eighty-five ground squirrels (C. citellus L.) were examined immediately after arousal (March-June). It was established that the animals were in estrus at the end of March; in April they were pregnant; in May they were in lactation; and in June they were already at rest, a postlactation period. Fifteen ground squirrels were treated with Hibernal and then placed in a chamber for 30 days at external temperature, 8-12 degrees C. In this case the estrus cycle of hypothermic ground squirrels was not changed. A retarded involution of corpus luteum persisted for a month and cystic follicles appeared in the ovary.

Animals↗
PubMed1996

[Stunned myocardium or hibernating myocardium? Apropos of a case].

The authors relate a case report of unstable angina pectoris accompanied by a well-documented stunned myocardium phenomenon. Stunned and hibernating myocardium resulting from an acute or chronic coronary ischaemia on the myocardium are notions which widely govern revascularisation indications, especially after a myocardial infarction. At present, their detection is based on isotopic methods and stress echocardiography.

Angina, Unstable↗
PubMed2006

Dobutamine stress echocardiography is highly accurate for the prediction of contractile reserve in the early postoperative period, but may underestimate late recovery in contractile reserve after revascularization of the hibernating myocardium.

OBJECTIVE: We sought to investigate the accuracy of dobutamine stress echocardiography to predict the degree and timing of recovery in resting function and contractile reserve (CR) after revascularization of the hibernating myocardium. METHODS: In all, 24 patients with ischemic cardiomyopathy (ejection fraction < 40%) underwent dobutamine stress echocardiography 1 week before and 6 weeks, 3 months, and 6 months after coronary artery bypass grafting. RESULTS: Recovery rates at 6 weeks, 3 months, and 6 months postoperation were 21%, 33%, and 45% (P < .01) for resting function and 55%, 65%, and 74% (P < .01) for CR. Positive and negative predictive values for recovery of resting function and CR at 6 months postrevascularization were 66% vs 97% (P < .001) and 78% vs 48% (P < .001), respectively. Positive and negative predictive values were both high for recovery of CR at 6 weeks postrevascularization (89% and 78%). CONCLUSIONS: Dobutamine stress echocardiography can predict early recovery in CR postrevascularization with an excellent accuracy but may underestimate the degree of late recovery in CR.

Cardiomyopathies↗
PubMed2006

Relevance of apoptosis in influencing recovery of hibernating myocardium.

BACKGROUND: Hibernating myocardium (HM) is viable but dysfunctional myocardium which can recover following revascularization. Myocyte necrosis is virtually absent in HM; however, cellular loss may take place by apoptosis, although this is controversial. AIM: To assess the presence of apoptosis and its relevance in HM. METHODS: During coronary artery by-pass surgery (CABG), 21 patients underwent transmural biopsy in the dysfunctional left anterior descending artery tributary area of the left ventricle (LV), with kinetic recovery at follow-up, thus fulfilling the HM criteria. All patients underwent echocardiographic follow-up at 12 months. All biopsies were evaluated by light microscopy, electron microscopy (EM), and molecular analysis. RESULTS: All biopsies were structurally altered, showing increased fibrosis and myocytes with variable size. Myocyte dedifferentiation was not detected by immunohistochemistry or EM. On stepwise linear regression, 1 year LVEF was predicted by the apoptotic index (beta=-0.973, p=0.002), the normotrophic cell percentage (beta=0.449, p=0.038), and mean fibrosis (beta=-0.412, p=0.51). CONCLUSIONS: Our biopsy study detected a wide range of morphological substrate heterogeneity in HM with degenerative features. We have demonstrated for the first time in humans that myocyte apoptosis is an important phenomenon in HM, negatively influencing LV functional recovery after CABG.

Apoptosis↗
PubMed2004

Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death.

OBJECTIVES: The aim of the present study was to objectify the loss of myocytes and the mechanism by which myocytes die in human hibernating myocardium (HHM). BACKGROUND: Intracellular degeneration, reduced cellular protein synthesis, and the replacement fibrosis contribute to structural disintegration of HHM. METHODS: In 14 patients, HHM was diagnosed by dobutamine echocardiography, radionuclide ventriculography, and thallium-201 scintigraphy. Functional recovery was documented by repeating the preoperative clinical investigations three months after successful coronary artery bypass graft surgery (CABG). During CABG, transmural biopsies were taken from the center of HHM regions and studied by electron microscopy, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) method, reverse transcription-polymerase chain reaction, and Western blotting. Control samples were taken from nondiseased human myocardium. RESULTS: All patients showed significant improvement or normalization of the regional function of HHM. Ubiquitin-related autophagic cell death was evident ultrastructurally by the occurrence of autophagic vacuoles, cellular degeneration, and nuclear disassembly. Ubiquitin-protein complexes were found in 0.03 +/- 0.008% (control: 0%, p < 0.005) of all myocytes. The proteasome 20S subunit/total myocytes were reduced from 63.3 +/- 9.6% in control myocardium to 36.9 +/- 8.4% in HHM. Complement-9, indicating oncosis, was found in only one of 14 biopsies. TUNEL-positive myocytes were 0.002 +/- 0.0003%. Electron microscopy showed apoptotic cells in 3 of 14 samples. However, the bcl-2/bax ratio was significantly reduced. Moreover, caspase-3 messenger ribonucleic acid was 8.5 times upregulated, and caspase-3 was activated. Cell death was absent in controls. CONCLUSIONS: In HHM, ubiquitin-related autophagic cell death and apoptosis cause a loss of myocytes. This plays an important role in progressive tissue damage and causes a reduction of the extent of functional recovery of HHM.

Aged↗
PubMed2006

Patients with hibernating myocardium show altered left ventricular volumes and shape, which revert after revascularization: evidence that dyssynergy might directly induce cardiac remodeling.

OBJECTIVES: The purpose of this study was to investigate whether post-ischemic left ventricular (LV) remodeling might be induced by regional contractile dysfunction per se (i.e., in the absence of transmural necrosis) and whether this phenomenon is potentially reversible after contractile recovery. BACKGROUND: Formation of extensive scar tissue is thought to be chiefly responsible for post-infarction LV remodeling; however, myocardial necrosis also causes loss of contractility. We investigated LV geometry and shape in a setting in which contractile dysfunction occurs in the presence of preserved myocyte viability, and thus it is potentially reversible. METHODS: In 42 patients with chronically dysfunctional myocardium, we evaluated (by two-dimensional echocardiography) LV global and regional function, volumes, and sphericity index (SI), at baseline and 8 +/- 3 months after coronary revascularization. Myocardial viability before revascularization was evaluated by dobutamine echocardiography. RESULTS: At baseline, regional and global function were depressed and LV dilation was present. Revascularization was followed by recovery of ejection fraction (from 33 +/- 6% to 45 +/- 10%, p < 0.0001) and wall motion score index (from 2.29 +/- 0.31 to 1.74 +/- 0.42, p < 0.0001). After revascularization, significant improvement of end-systolic volume index (from 78 +/- 23 ml/m2 to 56 +/- 23 ml/m2, p < 0.0001), end-diastolic volume index (from 118 +/- 26 ml/m2 to 99 +/- 26 ml/m2, p < 0.0001), and SI (from 0.69 +/- 0.14 to 0.52 +/- 0.11, p < 0.0001) was also observed. Improvement in LV volumes and SI were significantly correlated to the number of segments recovering function after revascularization. CONCLUSIONS: Hibernating myocardium is associated with major alterations in LV volumes and shape, which significantly revert after revascularization. Thus, chronic dyssynergy per se is sufficient to induce ischemic LV remodeling in patients.

Aged↗
PubMed2005

QT dispersion is determined by the relative extent of normal, hibernating, and scarred myocardium in patients with chronic ischemic cardiomyopathy. A dobutamine stress echocardiography study before and after surgical revascularization.

INTRODUCTION: The aim of the present study was to evaluate a possible association between QT dispersion (QTd) and the amount of viable and scarred myocardial tissue after revascularization in patients with coronary artery disease and impaired left ventricular (LV) function. METHODS: Twenty-two patients with ischemic LV dysfunction underwent dobutamine stress echocardiography (DSE) before and 6 months after surgical revascularization. Mean corrected QT-interval value and QTd were calculated at baseline and follow-up. Segments consisting of transmural scar were determined as the segments that remained akinetic in all stages of DSE despite reperfusion. Patients were divided into 2 groups according to the number of definitive segments consisting of transmural scar (minor scar group, < or =2 scarred segments; major scar group, >2 scarred segments). RESULTS: QTd was significantly lower in the minor compared with the major scar group at baseline and follow-up (mean [SD], 61 [22] vs 98 [33] milliseconds, P = .008, and 45 [18] vs 68 [21] milliseconds, P = .01, respectively). Segments consisting of transmural scar positively correlated to QTd at baseline (r = 0.53, P = .01) and follow-up (r = 0.62, P = .002). CONCLUSIONS: QTd is positively correlated with the extent of scarred myocardial tissue assessed by DSE. Surgical revascularization results in reduction of QTd in all patients with hibernating myocardium and LV dysfunction.

Cardiomyopathies↗
PubMed1996

Delineation of myocardial stunning and hibernation by positron emission tomography in advanced coronary artery disease.

With positron emission tomography, the resting flow abnormalities underlying reversible left ventricular dysfunction in 17 patients with chronic coronary artery disease were delineated. The level of flow in reversible dysfuncTional segments (i.e., those demonstrating improvement after revascularization) was markedly variable, ranging from 0.32 to 1.25 ml/gm/min. In 20 of these segments, flow was preserved, whereas in 12 segments, flow was reduced, when compared with that in, age-matched controls. Preservation of flow was associated with preservation of myocardial oxygen consumption and no alterations in myocardial substrate use. In contrast, a reduction in flow resulted in a decrease myocardial oxygen consumption and an increase in myocardial glucose use. Thus resting reversible left ventricular dysfunction in patients with chronic coronary artery disease can reflect a diversity of resting flow abnormalities. Moreover, myocardial perfusion at rest is frequently within normal limits, suggesting that the reversible mechanical dysfunction in these patients is attributable to intermittent myocardial stunning and not hibernation.

Adult↗
PubMed2003

Prediction of functional recovery of hibernating myocardium using harmonic power Doppler imaging and dobutamine stress echocardiography in patients with coronary artery disease.

The aim of this study was to compare the accuracy of harmonic power Doppler imaging (HPDI) and dobutamine stress echocardiography (DSE) in predicting recovery of myocardial function after bypass surgery. HPDI using triggering imaging with the administration of Levovist (Shering AG, Berlin, Germany) and DSE were performed in 34 patients (mean age 64 +/- 5 years) with left ventricular dysfunction. A repeat echocardiogram at rest was performed 3 months after revascularization. Of the 408 revascularized dysfunctional segments, 188 (45%) improved on the repeat echocardiogram. HPDI exhibited overall similar sensitivity (88% vs 87%) and accuracy (74% vs 79%) but lower specificity (61% vs 72%, p<0.05) compared with DSE for predicting recovery of myocardial function. Only delayed opacification at the 1:8 triggering point, demonstrated in 62% of viable segments, exhibited higher sensitivity (63%) and positive (58%) and negative (66%) predictive values than early opacification at 1:4 (25%, p<0.001; 35%, p<0.001; and 49%, p<0.001, respectively) in predicting functional recovery. The presence of contrast enhancement within the revascularized area resulted in a significant improvement after revascularization in wall motion score index and ejection fraction compared with areas with residual contrast defect (1.9 +/- 0.3 vs 2.3 +/- 0.3, p<0.01; 36 +/- 6% vs 29 +/- 5%, p<0.01, respectively). Significant correlations were observed between the contrast score index and the follow-up wall motion score index (r = -0.67) and between the contrast score index and the follow-up ejection fraction change (r = 0.65). Triggered HPDI has high sensitivity in detecting hibernating myocardium and can accurately predict the potential for recovery of ischemic left ventricular dysfunction 3 months after revascularization.

Aged↗
PubMed1998

Super-normal 201Tl retention in hibernating myocardium: an ex-vivo study using the failing human heart.

OBJECTIVE: Although the relationship between delayed 201Tl distribution and blood flow in acutely ischemic and infarcted myocardium has been widely explored in the experimental setting, its behaviour in chronically hypoperfused dysfunctioning human myocardium has not yet been evaluated. METHODS: In tissue samples of excised failing hearts taken from ischemic (IHD) patients and idiopathic dilated cardiomyopathy (IDC) controls, we evaluated the relationship between delayed 201Tl retention (4 h redistribution), blood flow (assessed by means of 99mTc-labelled human albumin microspheres injected during transplantation) and biochemically-assessed fibrosis. 201Tl activity was expressed as the percent of the activity in the region with highest flow and the least fibrosis. RESULTS: Fibrosis and 201Tl activity were inversely related (r = -0.62, P = 0.0001). In IDC controls, low flows corresponded to uniformly preserved 201Tl retention. In IHD, 46 segments with flows < or = 0.60 ml.min-1.g-1 and 20 segments with flows > 0.60 ml.min-1.g1 showed matching delayed 201Tl retention and flow values; in the remaining 27, there was a disproportionately high tracer accumulation in comparison with flow (flow/201Tl mismatch). Despite significantly less fibrosis and lower flows, the mismatch segments showed significantly greater. 201Tl activity than the segments with concordantly high tracer retention and flow values. Conversely, at equivalent flow rates, the mismatch regions had less fibrosis than the areas with concordantly depressed 201Tl activity and perfusion. CONCLUSIONS: This super-normal 201Tl retention in hibernating myocardium may indicate a mechanism of cell adaptation to chronic hypoperfusion.

Adult↗
PubMed2001

Hibernation-induction peptide and cell death: [D-Ala2,D-Leu5]enkephalin blocks Bax-related apoptotic processes.

The psychostimulant methamphetamine, both in vivo and in vitro, caused a mitochondrial cytochrome c release, the translocation of Bax from cytosol into mitochondrion, and the oligomerization of Bax. These effects by methamphetamine were blocked by a neuroprotective and hibernation-induction delta opioid peptide [D-Ala2,D-Leu5]enkephalin (DADLE). These results suggest that methamphetamine causes apoptosis by affecting the dynamics of Bax and that the neuroprotective property of DADLE may be due partly to its ability to potently block Bax-related apoptotic processes.

Animals↗
PubMed2003

Cold hibernated elastic memory foams for endovascular interventions.

Cold hibernated elastic memory (CHEM) polyurethane-based foam is a new shape memory polymeric self-deployable structure. Standard cytotoxicity and mutagenicity tests were conducted on CHEM in vitro, to ensure biocompatibility before studying potential medical applications. In vivo, lateral wall aneurysms were constructed on both carotid arteries of eight dogs. Aneurysms were occluded per-operatively with CHEM blocks. In two dogs, CHEM embolization was compared with gelatin sponge fragment embolization. Internal maxillary arteries (Imax) were also occluded with CHEM using a 6F transcatheter technique. Angiography and pathology were used to study the evolution of aneurysms and Imax at 3 and 12 weeks. Imax embolized with CHEM foam remained occluded at 3 weeks. Most aneurysms embolized with CHEM showed a small residual crescent of opacification at initial angiography, but angiographic scores were significantly better at 3 weeks. Thick neointima formation over the CHEM at the neck of aneurysms was demonstrated at pathology. The foamy nature of CHEM favours the ingrowth of cells involved in neointima formation. New devices for endovascular interventions could be designed using CHEM's unique physical properties.

Aneurysm↗