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PubMed2005

Intracoronary administration of autologous bone marrow mononuclear cells after induction of short ischemia is safe and may improve hibernation and ischemia in patients with ischemic cardiomyopathy.

BACKGROUND: Recent studies suggest that myocardial administration of stem cells improves perfusion and function of ischemic myocardium. The present study evaluated the safety and efficacy of simple intracoronary administration of mononuclear autologous bone marrow (BM) cells in patients with ischemic cardiomyopathy without revascularization option. METHODS AND RESULTS: We enrolled 6 consecutive patients with ischemic cardiomyopathy, who were in New York Heart Association classes III to IV despite optimal medical treatment without revascularization options and who, on dobutamine stress echocardiograph (DSE), were found to have left ventricular ejection fraction < 35% with significant hibernation and ischemia in at least 2 myocardial segments. BM cell suspension was collected, and on the next day, during coronary angiography, mild ischemia was induced by a short balloon inflation in each coronary conduit with a TIMI flow of > or = 2 followed by slow infusion of up to 50 mL of BM cells suspension to each conduit. At baseline and 4 months' follow-up, patients underwent clinical evaluation, Holter monitoring, and DSE. BM infusion was successful in all patients. One patient developed postprocedure hypotension and troponin increase. At 4 months' follow-up New York Heart Association class improved from 3.5 +/- 0.5 to 2.3 +/- 1.0, P = .04, and resting ejection fraction improved from 25% +/- 7% to 28% +/- 8%, P = .055. We observed improvement in resting wall motion score only in the segments with hibernation in baseline DSE (2.3 +/- 0.5 to 2.0 +/- 0.6, P = .03) and improvement in high-dose dobutamine wall motion score, only in segments showing significant ischemia at baseline DSE (2.5 +/- 0.5 to 2.0 +/- 0.6, P = .001). There were no clinical arrhythmias or increased arrhythmia burden by Holter monitoring. CONCLUSIONS: In patients with severe symptomatic ischemic cardiomyopathy, mild induction of ischemia followed by intracoronary infusion of unmanipulated autologous BM is feasible and safe and may improve hibernation and ischemia.

Aged↗
PubMed2006

Placebo or trimetazidine (99m)Tc tetrofosmin myocardial SPECT and low-dose dobutamine echocardiography in hibernating myocardium.

BACKGROUND: Trimetazidine (TMZ) improves (99m)Tc sestamibi uptake in myocardial single photon emission tomography (SPECT). This study compared TMZ (99m)Tc tetrofosmin SPECT and low-dose dobutamine echocardiography (LDDE) as predictors of functional recovery of hibernating myocardium after coronary revascularization. METHODS: Thirty-one patients with prior myocardial infarction and left ventricular dysfunction underwent coronary angiography, LDDE, placebo SPECT and TMZ SPECT. Echocardiographic follow-up was obtained at 2/6 months; the clinical follow-up lasted 2 years. RESULTS: Twenty-three (74.2%) patients (195 dysfunctioning left ventricular segments) were revascularized. TMZ improved (99m)Tc tetrofosmin uptake (p = 0.0001) as well as LVEF at gated SPECT (p = 0.04). At 2-months, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated (LDDE 71.9, 78.7, 71, 79.5; placebo SPECT 66.2, 75.6, 65.4, 76.3; TMZ SPECT 79.2, 67.7, 61.6, 83.3, respectively). The specificity improved in placebo and TMZ SPECT (82.1 and 78.7%) at 6-months follow-up. Two patients (2/23) with hibernating myocardium treated with revascularization and three (3/4) treated medically died a cardiac death (p = 0.0016, log rank 12.89). None (0/4) without viability died during the 2-year follow-up (p = 0.6, log rank 0.28). CONCLUSIONS: The addition of TMZ to (99m)Tc tetrofosmin SPECT improved diagnostic accuracy. The importance of hibernating myocardium revascularization was confirmed.

Adult↗
PubMed2006

Brief sympathetic activation precedes the development of ventricular tachycardia and ventricular fibrillation in hibernating myocardium.

BACKGROUND: Hibernating myocardium develops inhomogeneity in myocardial sympathetic innervation with spontaneous sudden cardiac death (SCD) because of ventricular fibrillation (VF). The triggers and prodromal arrhythmias initiating SCD in this substrate are unknown. METHODS: Swine chronically instrumented with a proximal left anterior descending coronary artery stenosis underwent placement of an implantable telemetry unit capable of continuously recording digitized electrocardiogram and left ventricular pressure signals at 1 kHz in conscious unrestrained animals for periods of up to 5 months. RESULTS: Spontaneous SCD (n = 10) was initiated by a close-coupled premature ventricular contraction followed by ventricular tachycardia (VT) that degenerated into VF during brief sympathetic activation. Peak heart rates were similar in animals that developed SCD vs survivors (250 +/- 12 vs 261 +/- 6 bpm). Electrocardiogram evidence of ischemia preceding VT/VF occurred in only 1 animal, and there was no significant infarction. CONCLUSIONS: Spontaneous VT/VF in hibernating myocardium develops during brief sympathetic activation with only rare evidence of acute ischemia. This supports the notion that the regional remodeling accompanying hibernating myocardium may be a novel substrate for the development of SCD in chronic ischemic heart disease.

Animals↗
PubMed2004

Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium: a comparative study.

OBJECTIVE: Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. METHODS: Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 microg/kg (mid-dose, n = 6, 30 injections/animal), 6 microg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 microg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. RESULTS: In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 +/- 0.04 at 1 month and 0.75 +/- 0.07 at 3 months compared with 0.68 +/- 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 +/- 0.03 at 1 month and 0.72 +/- 0.04 at 3 months compared with 0.67 +/- 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 +/- 0.06 at 1 month and 0.85 +/- 0.05 at 3 months (P <.001) compared with 0.67 +/- 0.04 at baseline. In the high group, myocardial blood flow was 0.81 +/- 0.06 at 1 month and 0.83 +/-.04 at 3 months (P =.03) compared with 0.71 +/- 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. CONCLUSIONS: In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 microg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.

Analysis of Variance↗
PubMed1998

Correlation of myocardial histologic changes in hibernating myocardium with dobutamine stress echocardiographic findings.

OBJECTIVE: The objective of this study was to correlate histologic changes in hibernating myocardium with dobutamine stress echocardiography (DSE). METHODS: Patients (n = 8) with anterior regional wall motion abnormalities in the seven echocardiographic segments representing the territory supplied by a significantly stenosed left anterior descending coronary artery had preoperative DSE performed (yielding 56 segments for analysis). Two transmural biopsy specimens were taken from the anterior wall of the left ventricle during coronary artery bypass grafting. RESULTS: Morphometric histologic analysis of biopsy specimens showed significantly less fibrosis in segments demonstrating inotropic reserve (p < 0.05) and significantly less fibrosis in segments demonstrating improvement in wall motion on echocardiography 3 months after revascularization (p < 0.05). DSE had a sensitivity of 100% and a specificity of 62% for detection of hibernating myocardial segments. Percent fibrosis was inversely correlated with percent nucleated cells (r = 0.66, p < 0.01) and directly correlated with cytoplasmic clearance (r = 0.76, p < 0.01). CONCLUSION: Inotropic response during DSE correlates with histologic evidence of hibernating myocardium.

Cardiotonic Agents↗
PubMed1997

Endogenous protective mechanisms in myocardial ischemia: hibernation and ischemic preconditioning.

Myocardial ischemia, even if it persists for a prolonged period of time, does not inevitably induce irreversible damage. Recent studies have identified 2 phenomena that are characterized by endogenous cardioprotective features, i.e., myocardial hibernation and ischemic preconditioning. Myocardial hibernation is characterized by chronic contractile dysfunction during persistent ischemia. The myocardium remains viable, and function is restored upon reperfusion. Ischemic preconditioning is characterized by delayed development of infarct size when prolonged and severe myocardial ischemia is preceded > or = 1 short-lasting episodes of ischemia and reperfusion. While ischemic preconditioning involves the activation of the adenosine A1 receptor, the bradykinin receptor, and activation of adenosine triphosphate (ATP)-dependent potassium channels, the mechanisms underlying myocardial hibernation are still unclear.

Adaptation, Physiological↗
PubMed2002

Evidence for an active inflammatory process in the hibernating human myocardium.

Myocardial hibernation refers to a state of prolonged impairment of left ventricular function in the presence of coronary artery disease, which may be reversed by revascularization. In this study we present evidence for a local inflammatory reaction in hibernating myocardial segments from patients undergoing coronary revascularization. We obtained transmural myocardial biopsies guided by transesophageal echocardiography from patients with ischemic ventricular dysfunction undergoing bypass surgery. Among the 28 biopsied segments included in the study, 23 showed evidence of systolic dysfunction. The majority of dysfunctional segments (85.7%) were viable ((201)Tl uptake >/= 60%). The samples were stained with markers for mast cells, mature resident macrophages, and the monoclonal antibody Mac387 that labels newly recruited myeloid cells. Dysfunctional segments showed more extensive fibrosis and higher macrophage density than normal segments. Among the 23 dysfunctional segments, 12 recovered function as assessed with echocardiograms 3 months after revascularization. Segments with postoperative functional recovery had comparable macrophage and mast cell density with those showing persistent dysfunction. However, biopsied segments that subsequently recovered function contained significantly higher numbers of newly recruited Mac387-positive leukocytes (18.7 +/- 3.1 cells/mm(2), n = 12 versus 8.6 +/- 0.9 cells/mm(2), n = 11; P = 0.009). In addition, monocyte chemotactic protein-1, a potent mononuclear cell chemoattractant, was predominantly expressed in segments with recovery of function. Myocardial hibernation is associated with an inflammatory response leading to active leukocyte recruitment. Dysfunctional myocardial segments that show an active inflammatory reaction have a greater potential for recovery of function after revascularization. We postulate that revascularization may promote resolution of the ongoing inflammation, preventing further tissue injury and fibrosis.

Aged↗
PubMed1998

Different outcomes of the reperfused myocardium: insights into the comments of stunning and hibernation.

There are several potential outcomes of myocardial ischaemia. When ischaemia is severe and prolonged, irreversible damage occurs and there is no recovery of contractile function. Interventions aimed at reducing mechanical activity and oxygen demand either before ischaemia or during reperfusion have been shown to delay the onset of ischaemic damage and to improve recovery during reperfusion. When myocardial ischaemia is less severe but still prolonged, myocytes may remain viable but exhibit depressed contractile function. Under these conditions, reperfusion restores complete contractile performance. This type of ischaemia leading to a reversible, chronic left ventricular dysfunction has been termed 'hibernating myocardium'. It is important clinically recognize hibernation as reperfusion of hibernating myocardium by angioplasty or heart surgery restores contraction and this correlates with long term survival. A third possible outcome after a short period of myocardial ischaemia is a transient post-ischaemic ventricular dysfunction, a situation termed 'stunned myocardium'.

Chronic Disease↗
PubMed1997

Identification of hibernating myocardium: comparative accuracy of myocardial contrast echocardiography, rest-redistribution thallium-201 tomography and dobutamine echocardiography.

OBJECTIVES: We sought to evaluate the comparative accuracy of myocardial contrast echocardiography (MCE), quantitative rest-redistribution thallium-201 (Tl-201) tomography and low and high dose (up to 40 microg/kg body weight per min) dobutamine echocardiography (DE) in identifying myocardial hibernation. BACKGROUND: Myocardial contrast echocardiography can assess myocardial perfusion and may therefore be useful in predicting myocardial hibernation. However, its accuracy in comparison to myocardial perfusion scintigraphy and to that of high dose DE remains to be investigated. METHODS: Eighteen patients (aged [+/- SD] 57 +/- 10 years) with stable coronary artery disease and ventricular dysfunction underwent the above three modalities before coronary revascularization. Myocardial contrast echocardiography was achieved with intracoronary Albunex. Rest echocardiographic and Tl-201 studies were repeated > or = 6 weeks after revascularization. RESULTS: Of 109 revascularized segments with severe dysfunction, 46 (42%) improved. Left ventricular ejection fraction increased from 38 +/- 14% to 45 +/- 13% at follow-up (p = 0.003). Rest Tl-201 uptake and the ratio of peak contrast intensity of dysfunctional to normal segments with MCE were higher (p < 0.01) in segments that recovered function compared with those that did not. Myocardial contrast echocardiography, thallium scintigraphy and any contractile reserve during DE had a similar sensitivity (89% to 91%) with a lower specificity (43% to 66%) for recovery of function. A biphasic response during DE was the most specific (83%) and the least sensitive (68%) (p < 0.01). The best concordance with MCE was Tl-201 (80%, kappa 0.57). Changes in ejection fraction after revascularization related significantly to the number of viable dysfunctional segments by all modalities (r = 0.54 to 0.65). CONCLUSIONS: In myocardial hibernation, methods evaluating rest perfusion (MCE, Tl-201) or any contractile reserve have a similar high sensitivity but a low specificity for predicting recovery of function. A limited contractile reserve (biphasic response) increases the specificity of DE. Importantly, the three techniques identified all patients who had significant improvement in global ventricular function.

Aged↗
PubMed1997

Proportionate reversible decreases in systolic function and myocardial oxygen consumption after modest reductions in coronary flow: hibernation versus stunning.

OBJECTIVES: This study sought to determine whether modest short-term reductions in coronary flow can produce subsequent proportionate reductions in myocardial function and O2 consumption compatible with myocardial hibernation. BACKGROUND: Acute studies indicate that myocardial energy utilization can be downregulated during moderate flow reduction. Whether this apparently beneficial adjustment persists into the reperfusion period is unsettled because most postischemic contractile dysfunction has been presumed to represent stunned or irreversibly injured myocardium. METHODS: Responses of regional myocardial function and O2 consumption were assessed in chronically instrumented dogs after approximately 50% reductions in flow for 2 h (n = 8) or repeated 2-min total coronary occlusions (n = 6). RESULTS: When unrestricted perfusion was restored after sustained partial occlusions, regional function and O2 consumption stabilized at proportionate, systematically decreased levels ([mean +/- SEM] 80 +/- 3.1% and 81 +/- 5.1% of control values, both p < 0.05) and then returned to control values within 24 h. Similar proportionate reductions occurred after as few as five cycles of brief total occlusion (79 +/- 5.1% and 83 +/- 1.6% of control values, both again p < 0.05); these persisted with additional occlusions and then returned to baseline values within 3 h. The absence of irreversible injury was documented histologically in both series. Sham animals (n = 5) showed no changes in regional function or O2 consumption throughout similar experimental periods. CONCLUSIONS: Moderate decreases in coronary flow or repeated brief coronary occlusions can be followed by proportionate reversible reductions in regional systolic function and O2 consumption compatible with the traditional definition of myocardial hibernation. These findings emphasize the complexity of myocardial responses to flow restriction and call attention to limitations in characterizing reversibly hypocontractile myocardium as simply hibernating or stunned.

Animals↗
PubMed1997

Myocardial cell death and apoptosis in hibernating myocardium.

OBJECTIVES: This study was designed to study apoptosis in hypoperfused hibernating myocardium subtending severe coronary stenosis. BACKGROUND: Apoptosis contributes to myocyte death in acute myocardial infarction. METHODS: A left anterior descending coronary artery stenosis was created in 13 pigs and maintained for 24 h (n = 4), 7 days (n = 5) and 4 weeks (n = 4) to reduce coronary blood flow by a mean of 34% with severe regional myocardial systolic dysfunction, as documented by echocardiography. Apoptosis was detected with an in situ end-labeling method and confirmed by "deoxyribonucleic acid laddering" on agarose-gel electrophoresis. The severity of apoptosis was expressed as the percentage of apoptotic myocyte nuclei and nonapoptotic myocardial nuclei. RESULTS: Myocardial blood flow of the anterior left ventricular wall was reduced from 1.00 +/- 0.18 to 0.66 +/- 0.21 ml/min per g (p < 0.01), with a severe reduction of anterior regional wall thickening from a mean (+/-SD) of 39 +/- 4% to 9 +/- 8% (p < 0.01). There was no myocardial infarction in five pigs and minimal patchy infarction of < or = 6% of the area at risk in eight pigs. Apoptotic myocytes were observed in the hibernating myocardial region in all pigs (4.8 +/- 2.3%). Myocyte apoptosis was patchy in distribution and was found predominantly in the subendocardial myocardium (9.8 +/- 4.6%) and rarely in the subepicardial myocardium (0.32 +/- 0.45%). Apoptosis was found not only around focal fibrosis areas, but also in areas without fibrosis or patchy infarction. Apoptosis was found not only in 24-h hypoperfused myocardium, but also in 4-week hypoperfused myocardium. The severity of myocyte apoptosis correlated significantly with regional coronary blood flow reduction (r = 0.75, p < 0.01). No apoptosis was found in the normal control region. CONCLUSIONS: This study demonstrates that there is ongoing myocyte death through myocyte apoptosis in hypoperfused hibernating myocardium.

Animals↗
PubMed2000

Role of ground trash volatiles in the selection of hibernation sites by boll weevils.

Volatiles play a large role in governing the behavior of boll weevils (Anthonomus grandis Boheman). They are attracted to cotton plants, and the female is sexually attracted to the male. The attracting compounds in both instances are terpenoids. Primarily in the fall of the year, boll weevils seek hibernation sites in leaf trash, where they remain until the following spring or summer. In the present study, essential oils were prepared by steam distillation from several leaf samples known to be prevalent at hibernation sites, and the oils were analyzed by GLC-MS. On the basis of the resulting presumptive identifications by comparison with those of standards, a number of mixtures were formulated and were field tested, as were the essential oils. The field tests failed to support unambiguously the premise that boll weevils select hibernation sites on the basis of leaf odor alone. However, in the presence of the sex pheromone, beta-caryophyllene (P > T = 0.08), or a mixture of three sesquiterpene hydrocarbons (P > T = 0.10), or a mixture of alkyl alcohols (P > T = 0.15) increased captures. The response to formulations of the sex pheromone with beta-caryophyllene may be primarily sexual, based on its presence in female boll weevils.

Animals↗
PubMed1998

Methods of assessment and clinical relevance of myocardial hibernation and stunning. Assessment of myocardial viability.

During the past decade there has been intense clinical interest in the differentiation between scar tissue and postischemic viable myocardium and its relevance to patient treatment and outcome. Frequently used paradigms of myocardial viability are hibernation and stunning which both refer to reversible left-ventricular contraction impairment. Hibernation describes the concomitant reduction of myocardial perfusion and contractility, whereas stunning characterizes contractile impairment persisting for some time after perfusion has been restored. In the clinical setting ischemia, stunning, hibernation, and necrosis may coexist. A variety of imaging techniques encompassing a wide range of physiologic entities such as contractile function, perfusion, membrane integrity and cell metabolism are currently in use to differentiate between these conditions, and they allow an accurate decision making with respect to revascularization procedures or conservative management. This article reviews current concepts and diagnostic methods to assess viable myocardium, and it attempts to address the clinical relevance of revascularization procedures in patients with coronary artery disease harboring dysfunctional but viable myocardium.

Cell Survival↗
PubMed1993

Post-ejection wall thickening as a marker of successful short term hibernation.

OBJECTIVE: Short term hibernating myocardium is characterised by a decrease in contractile function in proportion to the reduced blood flow, the recovery of creatine phosphate despite ongoing ischaemia, a recruitable inotropic reserve, and the absence of necrosis. During acute myocardial ischaemia systolic wall thickening decreases and post-ejection wall thickening develops. The extent of post-ejection thickening during severe ischaemia correlates with the recovery of contractile function during reperfusion. Whether the extent of post-ejection wall thickening can also distinguish short term hibernating myocardium from more severely ischaemic, infarcting myocardium and thus predict the amount of viable tissue was tested in 13 anaesthetised pigs. METHODS: The left anterior descending coronary artery (LAD) was cannulated and perfused at constant flow. After control measurements of regional myocardial blood flow (with radiolabelled microspheres) and wall thickening (sonomicrometry), coronary inflow was reduced to produce a reduction in regional contractile function by 60-100%. After 85 minutes of ischaemia, dobutamine was infused into the LAD for five minutes to determine the extent of inotropic reserve. Transmural biopsies were taken to measure regional myocardial creatine phosphate content and infarct size was determined after two hours of reperfusion by staining with triphenyl tetrazolium chloride. RESULTS: The extent of post-ejection wall thickening after 85-90 minutes of ischaemia correlated with the myocardial creatine phosphate content (r = 0.812, n = 11, p < 0.01) and the extent of the dobutamine recruitable inotropic reserve (r = 0.783, n = 7, p < 0.05). A negative correlation existed between the extent of post-ejection wall thickening and % infarct size (r = -0.699, n = 10, p < 0.05 for the transmural piece of tissue containing the ultrasonic crystals; r = -0.743, n = 10, p < 0.05 for the area of the left ventricle at risk). Finally, post-ejection wall thickening after 85-90 minutes of ischaemia correlated with the recovery of contractile function at 30 minutes reperfusion (r = 0.657, n = 10, p < 0.05). CONCLUSION: The extent of post-ejection wall thickening may indicate the amount of viable tissue after 85-90 minutes of low flow ischaemia. The greater the post-ejection wall thickening, the more myocardium is successfully hibernating.

Animals↗
PubMed2001

Lessons from experimental models of hibernating myocardium.

Chronic animal models of viable dysfunctional myocardium are now available that recapitulate most if not all of the physiological findings in humans with hibernating myocardium. These include chronic reductions in resting perfusion and contractile function, critical limitations in coronary flow reserve and increased uptake of 18F-2-deoxyglucose. These changes occur in the absence of infarction or necrosis and are accompanied by regional reductions in sarcoplasmic reticulum calcium-handling proteins and myocyte loss that arise secondary to apoptosis. Longitudinal studies of viable dysfunctional myocardium indicate that a state of chronic stunning with normal resting flow precedes the development of hibernating myocardium but these are distinct entities within a continuum of chronic adaptations to ischemia. This indicates that reductions in resting flow are the result rather than cause of chronic contractile dysfunction. Thus, the original concept proposing an acute prolonged reduction in flow as the initial stimulus producing hibernating myocardium needs to be revised.

Animals↗
PubMed2001

Clinical importance of stunned and hibernating myocardium.

Myocardial stunning and hibernation are states of potentially reversible myocardial dysfunction, which were first described more than 20 years ago (c.1980). Important advances have now been made in the ability to detect stunned and hibernating myocardium, as well as in the understanding of the impact of these conditions on patient outcomes. We discuss here the clinical importance of stunned and hibernating myocardium for patients with several common cardiac conditions.

Angina Pectoris↗
PubMed1998

Predictive value of dobutamine echocardiography and positron emission tomography in identifying hibernating myocardium in patients with postischaemic heart failure.

OBJECTIVE: To compare the predictive value of dobutamine echocardiography (DE) and positron emission tomography (PET) in identifying reversible chronic left ventricular (LV) dysfunction (hibernating myocardium) in patients with coronary artery disease (CAD) and overt heart failure. PATIENTS: 30 patients (four women) with CAD and heart failure undergoing coronary artery bypass grafting (CABG). METHODS: Myocardial viability was assessed with DE (5 and 10 micrograms/kg/min) and PET with [18F] 2-fluoro-2-deoxy-D-glucose (FDG) under hyperinsulinaemic euglycaemic clamp. Regional (echo) and global LV function (MUGA) were assessed at baseline and six months after CABG. RESULTS: 192 of the 336 (57%) dysfunctional LV segments improved function following CABG (hibernating) and the LV ejection fraction (EF) increased from 23(7) to 32(9)% (p < 0.0001) (in 17 patients > 5%). DE and PET had similar positive predictive values (68% and 66%) in the identification of hibernating myocardium, but DE had a significantly lower negative predictive value than PET (54% v 96%; p < 0.0001). A significant linear correlation was found between the number of PET viable segments and the changes in EF following CABG (r = 0.65; p = 0.0001). Stepwise logistic regression identified the number of PET viable segments as an independent predictor of improvement in EF > 5%, whereas the number of DE viable segments, the baseline LVEF, and wall motion were not. CONCLUSIONS: DE has a higher false negative rate than PET in identifying recoverable LV dysfunction in patients with severe postischaemic heart failure. The amount of PET viable myocardium correlates with the functional outcome following CABG.

Cardiotonic Agents↗
PubMed2004

Activation of p38 MAPK and increased glucose transport in chronic hibernating swine myocardium.

In preconditioned myocardium, activation of the mitogen-activated protein kinase (MAPK) p38 leads to increased glucose uptake via enhanced GLUT-4 translocation. Glucose uptake is also increased in chronic hibernating myocardium, but the role of p38 MAPK and GLUT-4 translocation has not been studied. Nine swine underwent instrumentation of the proximal left anterior descending coronary artery (LAD) with a small, external constrictor. At 3 mo after instrumentation, myocardial glucose uptake by PET imaging was higher in the LAD than in the remote region under basal, fasted conditions (0.08 +/- 0.02 vs. 0.04 +/- 0.01 micromol.min(-1).g(-1), P < 0.05). Compared with the remote region, the LAD region demonstrated increased membrane-bound GLUT-4 relative to total content (61 +/- 04 vs. 45 +/- 06%, P < 0.05), higher glycogen (28.37 +/- 4.41 vs. 19.26 +/- 1.87 mg/g wet wt, P < 0.05), and increased inducible nitric oxide synthase (NOS) activity (1.43 +/- 0.34 vs. 0.51 +/- 0.21 activity/mg protein, P < 0.05). p38 MAPK was 47 +/- 14% higher in the LAD than in the remote region (P < 0.05) and correlated well with the absolute degree of GLUT-4 membrane-bound translocation (r = 0.81, P < 0.01), relative increase in glycogen (r = 0.70, P < 0.05), and total NOS activity (r = 0.68, P < 0.05). In chronic hibernating myocardial tissue, p38 MAPK activation is increased under basal fasted conditions and correlates well with the increased degree of GLUT-4 translocation, glycogen accumulation, and NOS activity. As in preconditioned myocardium, activation of p38 MAPK may play an important role in the metabolic adaptations that characterize chronic hibernating myocardium.

Animals↗