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At least 1,297 records · Page 72Linked to original sources
PubMed2001

Long-term results of coronary artery bypass grafting procedure in the presence of left ventricular dysfunction and hibernating myocardium.

OBJECTIVE: Long-term left ventricular (LV) performance and patient outcome after coronary artery bypass grafting (CABG) procedure in the presence of depressed LV function and hibernating myocardium (HM) have been poorly determined. Therefore, we prospectively evaluated patients undergoing CABG with severe LV dysfunction and HM to elucidate postoperative prognosis. METHODS: We enrolled 120 consecutive patients undergoing CABG with severe LV dysfunction and HM as assessed by dobutamine echocardiography and by rest-redistribution radionuclide (Thallium-201) study. Mean patient age was 60+/-9 years (range 31-77 years). Mean preoperative LVEF was 28%+/-9 (range 10-40%). All patients underwent echocardiographic study to assess LV recovery of function intraoperatively, prior to hospital discharge, at 3 months, at 1 year, and yearly during the follow-up. Univariate and multivariate analysis were performed to to evaluate predictors of postoperative survival. RESULTS: There were 2 hospital (1.6%) and 15 late (12.5%) deaths, mainly for heart failure, leading to an actuarial survival of 80+/-6% and 60+/-9% at 5 and 8 years, respectively. LVEF significantly improved perioperatively (from 28+/-9% to 40+/-2%, P<0.01). Increase in LVEF, however, was gradually offset over the time (EF of 33+/-9%, 32+/-8%, and 30+/-9% at 3 months, and 12 months, and 8 years after surgery, respectively). Furthermore, patients who experienced limited LV functional recovery perioperatively had a more remarkable decline of LVEF thereafter, and suffered from recurrence of heart failure symptoms (freedom from heart failure 82+/-5% and 60+/-8% at 4 and 8 years respectively). Advanced preoperative NYHA Class, and age were independent risks factors for reduced postoperative survival. Preoperative angina and use of arterial conduits apparently did not influence patient morbidity and mortality at long term. CONCLUSION: CABG procedure in the presence of HM enhances LV recovery of function and has a favourable prognosis. Functional benefit of the left ventricle, however, appears to be time-limited, despite remarkable improvement in patient functional capacity. Advanced preoperative heart failure, minimal perioperative improvement of LVEF, and age account for a poor long-term prognosis.

Adult↗
PubMed1996

Myocardial stunning, hibernation, and ischemic preconditioning.

From the present review, it may be concluded that myocardial ischemia results in far more complicated syndromes than previously realized. Although not all aspects of the issues discussed in this review are currently a clinical reality in the daily practice of cardiovascular anesthesiologists, the understanding and application of these concepts are growing rapidly. Indications for revascularization procedures will be adjusted in patients with evidence of hibernating myocardium. In the future, postoperative myocardial dysfunction may be diminished by the prevention of myocardial stunning, for instance by altering the composition of the cardioplegic solution and other interventions. Finally, additional advances may involve reduction of the extent of perioperative myocardial infarctions by application of ischemic preconditioning.

Angina Pectoris↗
PubMed2000

A self-perpetuating vicious cycle of tissue damage in human hibernating myocardium.

Recently, we proposed the hypothesis that a vicious cycle exists in human hibernating myocardium (HM) between the progression of myocyte degeneration and the development of fibrosis. We now investigated the pathomechanism of this cycle in more detail and established a correlation between the severity of the morphological changes and the degree of postoperative functional recovery of HM. HM was diagnosed by dobutamine echocardiography, thallium-201 scintigraphy and radionuclide ventriculography. Functional recovery was present at 3 months after coronary bypass surgery but remained unchanged at 15 months. Forty patients were subdivided into 2 groups: A with complete and B with incomplete recovery. Biopsies taken during surgery and studied by electron microscopy, immunocytochemistry, rt-PCR, and morphometry revealed myocyte degeneration and inflammatory and fibrinogenic changes in a widened interstitial space. We report here for the first time an upregulation of TGF-beta1 evident by a 5-fold increase of fibroblasts and macrophages exhibiting a TGF-beta1 content 3-fold larger than in control, and a > 3-fold increase in TGF-beta1 mRNAby rt-PCR. The number of angiotensin converting enzyme (ACE) containing structures was increased (n/mrm2: control-11.4, A-17.6, B-19.2, control vs. A and B, p < 0.05). Fibrosis was more severe in group B than A or control (%: C-10.1; A-21.2; B-40.6; p < 0.05). Capillary density was significantly reduced (n/mm2: C-1152; A-782; B-579, p < 0.05) and intercapillary distance was widened (microm: C-29.5, A-36.1, B-43.3, p < 0.05). The number of CD 3 (n/mm2: C-5.0; A-9.6; B-9.4, ns) and CD 68 positive cells (n/mm2: C-37.2; A-80.7; B-55.0, C vs. A p < 0.05) was elevated in HM as compared to control indicating an inflammatory reaction. Cut-off points for functional recovery are fibrosis > 32%, capillary density < 660/mm2 and intercapillary distance > 39.0 microm. In HM a self-perpetuating vicious cycle of tissue alterations leads to progressive replacement fibrosis and continuous intracellular degeneration which should be interrupted by early revascularization.

Adult↗
PubMed2002

ET(A) receptor blockade improves post-ischaemic functional recovery in 'hibernating' rat myocardium.

Endothelin-1 (ET-1) is a potent vasoconstrictor, and ET(A) receptors mainly mediate this effect. Elevated plasma levels of ET-1 are observed in patients with coronary heart disease. The release of this peptide from the damaged endothelium may play a role in the initiation and maintenance of myocardial ischaemia. This study examines the ET(A) receptor-mediated role of endogenous ET-1 in post-ischaemic myocardial function after prolonged hypoperfusion in normal non-failing hearts. In an isolated rat heart model for short-term myocardial hibernation, left ventricular functional recovery after 3 h of hypoperfusion (15% of pre-ischaemic flow) followed by 2 h of reperfusion was determined. Under steady-state conditions, coronary flow, left ventricular pressure (LVP) and dP/dt(max) were measured in the isovolumically beating heart. Additionally, the maximal inotropic response (LVP and dP/dt(max)) to calcium stimulation was determined. To study the role of ET(A) receptors under these pathophysiological conditions, one group was treated with the ET(A) antagonist BQ 610 (0.8 micromol/l) during hypoperfusion, and compared with a control group which received a saline infusion during hypoperfusion. Reperfusion for 2 h after 3 h of hypoperfusion resulted in partial functional recovery in both groups. Post-ischaemic recovery was significantly better in the hearts that were treated with the ET(A) antagonist BQ 610 during hypoperfusion (LVP, +19.5% compared with control; dP/dt(max), +13.7% compared with control). The inotropic response to calcium was nearly normalized after ET(A) blockade. Thus the normal non-failing myocardium profits from ET(A) receptor blockade during a prolonged period of hypoperfusion, resulting in significantly better post-ischaemic recovery of myocardial function.

Animals↗
PubMed2000

Sensitivity, specificity, and predictive accuracies of non-invasive tests, singly and in combination, for diagnosis of hibernating myocardium.

OBJECTIVE: To determine the best test(s) for predicting functional recovery of hibernating myocardium after reperfusion. METHODS: A prospective study to compare echocardiographic left ventricular diastolic wall thickness (> or =5 mm), low-dose dobutamine echocardiography and rest-redistribution thallium-201 scintigraphy, alone and in combination, for predicting recovery of left ventricular akinesis after surgical revascularization. RESULTS: Twenty-eight consecutive patients aged 58+/-9 years were studied. Of the 448 left ventricular segments, 263 were akinetic at rest; 230/263 (87%) had wall thickness > or =5 mm, 135 (51%) had a positive response and 175 (66.5%) were graded viable on thallium. Of akinetic segments 61% improved after surgery. Left ventricular score decreased from 2.3+/-0.4 to 1.8+/-0.4 (P<0.01) and ejection fraction increased from 27+/-10 to 37+/-14% (P<0.01). For predicting results at 1 year, diastolic wall thickness had a sensitivity and a predictive accuracy of a negative test of 100% but a specificity of 28% and predictive accuracy of a positive test of 61%. The addition of dobutamine echocardiography or thallium-201 improved the predictive accuracy of a positive test to 76% and 69%, respectively; the addition of both tests was not of greater benefit than that of a single test. CONCLUSIONS: Diastolic wall thickness <5 mm on echocardiography was the best simple and single predictor of non-recovery of left ventricular dysfunction. The addition of dobutamine echocardiography or thallium-201, but not both, was the best solution for predicting recovery of left ventricular dysfunction. In times of limited resources, these findings are important from a clinical point of view.

Adult↗
PubMed2002

Revascularization of hibernating myocardium: rate of metabolic and functional recovery and occurrence of oxidative stress.

BACKGROUND: Left ventricular (LV) dysfunction due to coronary artery disease (CAD) may improve after revascularization in patients with hibernating myocardium (HM). METHODS AND RESULTS: We compared the rate of metabolic (arterial-great cardiac vein differences of lactate, glucose and pyruvate) and functional (intra-operative transesophageal and epicardial echocardiography) recovery and occurrence of oxidative stress (myocardial release of oxidized glutathione (GSSG)) early after surgical revascularization, in patients with CAD, LV dysfunction and HM (n=16) vs those with preserved LV function (n=15). By comparing the two groups, we observed that, after de-clamping, in patients with HM (a) the kinetic of lactate production was converted to extraction (P<0.01 at 1, 5, 10 and 20 min after revascularization), (b) myocardial extraction of pyruvate increased (P<0.01 during the first 5 min after revascularization), (c) GSSG release was less and of shorter duration (P<0.01 at all times), (d) segmental wall motion score improved from 2.4+/-0.3 to 1.7+/-0.5 (P<0.01) as did the thickening of the akinetic territories corresponding to the antero-distal septum and to the distal anterior wall regions (to 36+/-23%, and to 36+/-13%, respectively). There was a correlation between the rate of recovery of metabolic and functional indices. CONCLUSIONS: The contractile and metabolic recovery of HM is more rapid than that of non-HM, and it is not accompanied by oxidative stress.

Blood Glucose↗
PubMedDate not supplied

The pathophysiology of myocardial hibernation: current controversies and future directions.

It is now widely accepted that patients with chronic coronary artery disease can experience prolonged regional ischemic dysfunction that does not necessarily arise from irreversible tissue damage and, to some extent, can be reversed by restoration of blood flow. Recent clinical and experimental data suggest that this form of chronic but reversible left ventricular dysfunction represents a complex, progressive, and dynamic phenomenon. The initial stages of dysfunction are probably caused by chronic stunning. They are characterized by normal resting perfusion but reduced flow reserve, mild myocyte alterations, maintained membrane integrity (allowing the transport of both thallium and glucose), preserved capacity to respond to an inotropic stimulus, and no or little tissue fibrosis. After revascularization, functional recovery will probably be rapid and complete. On the other hand, the more advanced stages of dysfunction likely correspond to chronic hibernation. They usually are associated with reduced rest perfusion; increased tissue fibrosis; more severe myocyte alterations (degeneration[?], apoptosis); and a decreased ability to respond to inotropic stimuli. Nonetheless, membrane function and glucose metabolism may long remain preserved. After revascularization, functional recovery, if any, will probably be quite delayed and mostly incomplete.

Animals↗
PubMed2002

Future strategies of reverse remodeling prevention of hibernation.

A complex interrelationship exists among chronic ischemic left ventricular dysfunction, persistence of myocardial viability and possibility to limit progression of chronic heart failure. Cardiac remodeling is influenced by several factors still under investigation. Hibernation is basically an adaptive mechanism to chronically abnormal coronary blood flow, characterized by metabolic and structural alterations of the cardiac tissue, that are fully recovered upon revascularization. The estimate of the prevalence of myocardial viability in patients with chronic ischemic left ventricular dysfunction is crucial and different figures can be obtained by applying different diagnostic techniques and analyzing different cohorts of patients. In patients with chronic heart failure and substantial areas of myocardial ischemia and viability, revascularization is likely to prolong survival. The amount of viable myocardium needed to be clinically relevant remains to be established: only randomized prospective studies, focusing on both functional improvement and prognosis, will give an evidence-based conclusion. An aggressive and thoughtful surgical approach to patients with ischemic heart failure can yield satisfying long-term results, with survival rates superior to medical management alone, and can constitute a true and valid alternative to heart transplantation.

Heart Failure↗
PubMed1998

Hibernation during hypoxia in cardiomyocytes. Role of mitochondria as the O2 sensor.

During myocardial hibernation, decreases in coronary perfusion elicit inhibition of contraction, suggesting that energy demand is attenuated. We previously found an inhibition of contraction and O2 consumption during hypoxia (3% O2; PO2 = 20 torr for >2 h) in cardiomyocytes, which was reversible after reoxygenation. This study sought to determine whether mitochondria function as cellular O2 sensors mediating this response. Embryonic cardiomyocytes were studied under controlled O2 conditions. Hypoxia produced no acute decrease in mitochondrial potential as assessed using tetramethylrhodamine ethylester (TMRE). Cellular [ATP] was preserved throughout hypoxia, as assessed using the probe Magnesium Green. Thus, ATP synthesis and utilization remained closely coupled. Cells adapted to hypoxia for >2 h exhibited a 4% increase in mitochondrial potential upon reoxygenation, suggesting that a partial inhibition of cytochrome c oxidase had existed. To test whether the oxidase serves as an O2 sensor, azide was administered (1 mM) to simulate the effects of hypoxia by lowering the Vmax of the oxidase. The effects of azide on contraction and mitochondrial potential mimicked the response to hypoxia. We conclude that partial inhibition of cytochrome oxidase during hypoxia allows mitochondria to function as the O2 sensor mediating the decreases in ATP utilization and O2 consumption during hypoxia.

Adenosine Triphosphate↗
PubMed2004

The contribution of hibernation to heart failure.

For many years the functional sequelae of chronic coronary artery disease (CAD) were considered irreversible. Evidence accrued over the past three decades proves that this concept is not necessarily true. Non-randomised studies demonstrated that coronary revascularisation (CR) confers symptomatic and prognostic benefits to patients with CAD and heart failure. Based on available studies, one can assume that the beneficial effect of CR in heart failure derives primarily from recovery of contractile function in 'hibernating myocardium' (HM), i.e., chronically dysfunctional, but viable, myocardium subtended by stenosed coronary arteries which recovers after CR. Cardiac imaging with echocardiography, single photon and positron emission tomography (PET) and magnetic resonance allows the identification of HM. These techniques have comparable predictive values in patients with moderate left ventricular impairment. PET studies have shown that resting myocardial blood flow is preserved in most cases of HM while its main feature is a severe impairment of coronary flow reserve. Thus, the pathophysiology of HM is more complex than initially postulated. Recent evidence that repetitive ischaemia in patients can be cumulative and lead to more severe and prolonged stunning, lends further support to the hypothesis that, at least initially, stunning and HM are two facets of the same coin.

Coronary Artery Disease↗
PubMed2005

Suppressed phospholamban levels differentiate irreversibly dysfunctional from hibernating myocardium in humans.

OBJECTIVES: We studied whether dysfunction of human hibernating (HIB) and irreversibly dysfunctional myocardium (IRDM) are associated with altered levels of the sarcoplasmatic reticulum calcium handling proteins Ca2+-ATPase (SERCA2a) and its inhibitor phospholamban (PLB). DESIGN: In 12 patients myocardial biopsies were taken during bypass surgery and analysed for contents of these proteins. We classified regions as control, HIB, or IRDM based on echocardiographic studies before and 6 months after surgery. RESULTS: SERCA2a content (mean+/-SEM) was similar to control in HIB and IRDM (2.6 +/- 1.7, 3.8 +/- 2.0, and 3.4 +/- 1.9 units/g non-collagen protein (NCP), p = 0.40). PLB content was similar to control in HIB (2.6 +/- 0.4 and 3.5 +/- 0.5 units/microg NCP) but reduced in IRDM (0.9 +/- 0.2 units/microg NCP, p < 0.05). SERCA2a:PLB ratio, an indicator of SERCA2a activity, did not differ between control and HIB (1.2 +/- 0.3 and 1.4 +/- 0.4 units/microg NCP) but was increased in IRDM (5.1 +/- 1.7 units/microg NCP, p < 0.05). CONCLUSIONS: Inappropriate SERCA2a activity due to suppressed PLB levels may represent a maladaptive mechanism in chronic ischemic myocardium being causally linked to irreversibility of left ventricular dysfunction.

Analysis of Variance↗
PubMed1993

Regional wall motion abnormalities in stunned and hibernating myocardium.

The clinical recognition that chronic dysfunctioning myocardial segments may retain viable myocardium has important therapeutic consequences. 'Stunned myocardium' and 'hibernating myocardium' have been proposed to distinguish respectively between post-ischaemic left ventricular dysfunction, a condition which normalizes spontaneously, and persistent wall motion abnormalities due to chronic hypoperfusion. This study examines the possible link between these two conditions.

Animals↗
PubMed1996

Viable cultured neurons in ambient carbon dioxide and hibernation storage for a month.

Neurobasal is a bicarbonate-buffered medium optimized for the growth of embryonic rat hippocampal neurons at pH 7.3 in 5% CO2. Neurons die within hours in this or in other 26 mM bicarbonate buffers when transferred to ambient CO2 (0.2%). Death is associated with a rapid rise in medium pH to 8.1. A new CO2-independent modification of Neurobasal (Hibernate E), when supplemented with B27, can maintain neuron viability for at least 2 days in ambient CO2. This same medium can also be used to store viable brain tissue for up to a month with refrigeration. These advances should facilitate studies of neuron physiology outside the incubator as well as storing and transporting neuronal tissue.

Animals↗
PubMed2001

Enhanced 99Tc(m)-MIBI SPECT detection of hibernating myocardium following the use of sub-lingual nitroglycerine.

The purpose of this study was to assess the feasibility of detecting hibernating myocardium using 99Tc(m)-MIBI SPECT imaging following the use of sublingual glyceryl trinitrate (GTN). Thirty-eight subjects were studied, five asymptomatic and 33 with a history of myocardial ischaemia or myocardial infarction (MI). The study was conducted on two separate days, both at rest, one under controlled basal conditions and the other 20 min following the sublingual administration of GTN. A total of 190 cardiac segments were qualitatively analysed and 72 segments with fixed defects were compared to the study following the use of GTN for evidence of improved radionuclide uptake. Following GTN, 73.6% of fixed segment defects showed no change in uptake, 5.5% showed probable improvement whilst in 20.8% a definite enhanced uptake was demonstrated. In 3.7% of segments, worsening of radionuclide uptake was observed.

Administration, Sublingual↗
PubMed2002

The pathology of hibernating myocardium.

Myocardial hibernation represents a protective mechanism of muscle preservation in the setting of atherosclerotic coronary artery disease. Long-standing myocardial hypoperfusion leads to diminished myocardial contractility that reverses with improved blood flow after revascularization. The morphologic changes in both animal models and humans are described.

Adaptation, Physiological↗
PubMed2005

Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium.

It is unknown whether short-term modulation of substrate supply affects cardiac performance in heart failure patients with chronic ischemic myocardium. The aim of this study was to determine whether modulation of myocardial substrate metabolism with insulin and free fatty acids (FFAs) affects contractile function of chronically stunned (CST) and hibernating (HIB) myocardium at rest and after maximal exercise. We studied eight nondiabetic patients with ejection fraction (EF) 30 +/- 4% (SE) and CST/HIB in 49 +/- 6% of the left ventricle: 36 +/- 6% CST and 13 +/- 2% HIB as determined by 99m Technetium-Sestamibi single photon emission computed tomography (SPECT) and [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Each patient was subjected to a 3-h infusion of 1) saline, 2) insulin-glucose (i.e., euglycemic insulin clamp; high insulin, suppressed FFA), and 3) somatostatin-heparin (suppressed insulin, high FFA). Echocardiographic endpoints were global EF and regional contractile function [maximum velocity (Vmax) and strain rate (epsilon max)] as determined by tissue Doppler imaging at steady state and after maximal exercise. EF was similar at baseline and steady state and increased after exercise to 36 +/- 5% (P < 0.05). Baseline regional Vmax and epsilon max were highest in control, intermediate in CST and HIB, and lowest in infarct regions (P < 0.05). Steady-state EF, Vmax, and epsilon max were not affected by metabolic modulation in any region. After maximal exercise, contractile function increased in control, CST, and HIB (P < 0.05), but not in infarct, regions. Exercise-induced contractile increments were unaffected by metabolic modulation. Metabolic modulation does not influence contractile function in CST and HIB regions. Chronic ischemic myocardium has preserved ability to adapt to extreme, short-term changes in substrate supply at rest and after maximal exercise.

Aged↗
PubMed2001

Role of endogenous opioids in ischemic preconditioning but not in short-term hibernation in pigs.

Endogenous opioids are involved in ischemic preconditioning (IP) in several species. Whether or not opioids are important for IP and short-term myocardial hibernation (STMH) in pigs is currently unknown. In 34 enflurane-anesthetized pigs, the left anterior descending coronary artery was flow constantly perfused. Subendocardial blood flow (Endo), infarct size (IS; percent area at risk), and the free energy change of ATP hydrolysis (DeltaG) were determined. After 90-min severe ischemia and 120-min reperfusion, IS averaged 28.3 +/- 5.4% (means +/- SE) (n = 8; Endo: 0.047 +/- 0.009 ml. min(-1) x g(-1)). IP by 10-min ischemia and 15-min reperfusion reduced IS to 9.9 +/- 3.8% (P < 0.05, n = 8; Endo: 0.044 +/- 0.009 ml. min(-1) x g(-1)). After naloxone (1 mg/kg iv followed by 2 microg x kg(-1) x min(-1)), IS averaged 25.8 +/- 7.0% (n = 6; Endo: 0.039 +/- 0.008 ml x min(-1) x g(-1)) without and 24.7 +/- 4.7% (n = 6; Endo: 0.044 +/- 0.006 ml x min(-1) x g(-1)) with IP. At 5-min moderate ischemia in the presence of naloxone, Endo decreased from 0.90 +/- 0.07 to 0.28 +/- 0.03 ml x min(-1) x g(-1)and DeltaG decreased from -58.6 +/- 1.0 to -52.6 +/- 0.4 kJ/mol. Prolongation of ischemia to 90 min did not alter Endo, but DeltaG recovered toward control values (57.7 +/- 1.1 kJ/mol), and the myocardium remained viable. These responses are identical to those of nonnaloxone-treated pigs. Endogenous opioids are involved in IP but not in STMH in pigs.

Adenosine Triphosphate↗