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PubMed1992

An animal model of chronic coronary stenosis resulting in hibernating myocardium.

An experimental animal model of hibernating myocardium is presented. Sixteen animals were initially prepared of which seven were selected for final review. Hearts were instrumented in two separate surgical procedures such that maximum phasic flow velocity in the left anterior descending (LAD) coronary artery was reduced by 50% and followed over 1 wk. Regional shortening declined at 1 wk to 62% of aerobic values (P less than 0.048) and did not improve over 2 h reperfusion. Metabolic determinations, obtained after 1 wk of coronary stenosis and immediately sampled before and after release of the LAD flow constrictor, showed no evidence of acidosis, hypercarbia, or an inability to extract oxygen at the tissue level. Thereafter, during the 2-h reperfusion period, hearts were able to respond to dobutamine (10 micrograms/kg infusion over 1 min) challenge with an appropriate shift in an end-systolic length estimate of contractility. Mitochondrial respiration at the conclusion of the studies in the reperfused bed demonstrated near normal recovery compared with aerobic values. None of the seven hearts showed gross evidence of infarction and only one heart was noted to have a few microfocal changes of healing infarction. Thus a new model of coronary stenosis is presented, which affected substantial reductions in mechanical function consistent with the concepts of hibernating myocardium. These mechanical events were not associated with marked metabolic abnormalities, reflecting advanced ischemia or mitochondrial dysfunction and could be transiently improved with inotropic stimuli. This model may prove beneficial as a tool in understanding mechanistic events underlying the hibernating heart.

Animals↗
PubMed1995

Regional short-term myocardial hibernation in swine does not involve endogenous adenosine or KATP channels.

Short-term hibernating myocardium is characterized by reduced contractile function during persistent ischemia, the recovery of metabolism over time, a recruitable inotropic reserve, and the lack of necrosis. The mechanisms underlying myocardial hibernation are unclear. The present study addressed the role of endogenous adenosine and that of activation of ATP-dependent potassium (KATP) channels. In 22 enflurane-anesthetized swine, coronary inflow was reduced to decrease regional myocardial work (W, measured by sonomicrometry) by 60-70% at 5 min of ischemia; this flow reduction has previously been shown to be compatible with the development of myocardial hibernation. Systemic hemodynamics, W, subendocardial blood flow (measured by microspheres), and the myocardial creatine phosphate content (measured by biopsies, mumol/g wet wt) were measured under control conditions and during 90 min of ischemia, with an intracoronary dobutamine infusion during the last 5 min of ischemia. The impact of endogenous adenosine was eliminated by infusion of intracoronary adenosine deaminase (ADA), and the impact of activation of KATP channels by glibenclamide. Creatine phosphate content recovered in the placebo-treated swine (n = 8, 3.8 +/- 1.9 to 5.8 +/- 2.0 mumol/g wet wt) as well as in swine receiving ADA (n = 7, 4.1 +/- 1.2 to 6.0 +/- 1.7 mumol/g wet wt) or glibenclamide (n = 7, 2.8 +/- 1.3 to 6.7 +/- 1.6 mumol/g wet wt) when ischemia was prolonged from 5 to 85 min. At the end of 90 min of ischemia, W increased during intracoronary dobutamine in all three groups to a comparable extent, and myocardial necrosis was absent in all three groups of swine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1976

Characterization of midbrain component of the trigger for arousal from hibernation.

The ability of the midbrain reticular formation (MRF) to trigger arousal from hibernation and to change body temperature (Tb) during euthermia was tested in golden-mantled ground squirrels (Citellus lateralis). During hibernation (ambient temperature 5-6 degrees C) microinjections of cholinomimetic compounds (acetylcholine and carbachol) triggered full arousal or produced transient increases in Tb in 15 out of 19 tests; MRF microinjections of norepinephrine (NE) and 5-hydroxytryptamine (5-HT), at the same concentrations that produced full arousal when microinjected into the preoptic/anterior hypothalamus (PO/AH) area in previous experiments, has no effect on Tb in 13 out of 16 tests. In experiments on euthermic ground squirrels tested at an ambient temperature of 25 degrees C, MRF microinjections of acetylcholine raised Tb, whereas the monoamines had no significant effects. These results show that cholinoceptive neurons in the MRF can trigger arousal from hibernation and increase Tb during euthermia. The failure of NE and 5-HT to produce any significant effects at the same doses that were reported to be effective in the PO/AH indicates that the functional organization of the MRF portion of the arousal mechanism is different from that reported for the PO/AH.

Acetylcholine↗
PubMed2002

Improvement of collateral perfusion and regional function by implantation of peripheral blood mononuclear cells into ischemic hibernating myocardium.

OBJECTIVE: This study was performed to evaluate the angiogenic effect of implantation of peripheral blood mononuclear cells (PB-MNCs) compared with bone marrow mononuclear cells (BM-MNCs) into ischemic hibernating myocardium. METHODS AND RESULTS: A NOGA electromechanical system was used to map the hibernating region and to inject cells. PB-MNCs and BM-MNCs contained similar levels of vascular endothelial growth factor and basic fibroblast growth factor, whereas contents of angiogenic cytokines (interleukin-1beta and tumor necrosis factor-alpha) were larger in PB-MNCs. Numbers of endothelial progenitors were approximately 500-fold higher in BM-MNCs. In BM-MNC-implanted myocardia of pigs, an increase in systolic function (ejection fraction from 33% to 52%) and regional blood flow (2.1-fold) and a reduction of the ischemic area (from 29% to 8%) were observed. PB-MNC implantation reduced the ischemic area (from 31% to 17%), the extent of which was less than that seen with BM-MNCs. In saline-implanted myocardium, the ischemic area expanded (from 28% to 38%), and systolic function deteriorated. Angiography revealed an increase in collateral vessel formation by PB-MNC or BM-MNC implantation. Capillary numbers were increased 2.6- and 1.7-fold by BM-MNC and PB-MNC implantation, respectively. BM-MNCs but not PB-MNCs were incorporated into neocapillaries. CONCLUSIONS: Catheter-based implantation of PB-MNCs can effectively improve collateral perfusion and regional function in hibernating ischemic myocardium by its ability to mainly supply angiogenic factors and cytokines.

Angiogenesis Inducing Agents↗
PubMed2002

Increased myocardial gene expression of tumor necrosis factor-alpha and nitric oxide synthase-2: a potential mechanism for depressed myocardial function in hibernating myocardium in humans.

BACKGROUND: Whether cardioinhibitory cytokines are elevated in regions of hibernating myocardium and account in part for the depression in resting function is currently not known. Methods and Results- Thirteen patients with stable ischemic ventricular dysfunction scheduled for bypass surgery underwent preoperative dobutamine echocardiography (DE) and intraoperative myocardial biopsies. The numbers of copies of mRNA for the negatively inotropic cytokines tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (NOS2) were quantified by reverse transcription-polymerase chain reaction. In normal segments, myocardial TNF-alpha was barely detectable (1.2+/-0.4 copies per 10(6) copies of beta-actin). A 13.7-fold increase in myocardial TNF-alpha was observed in dysfunctional segments with a biphasic response to DE (contractile reserve and ischemia) and was highest (45.5-fold) in segments with ischemia and without contractile reserve (P<0.001). A similar graded increase was seen for NOS2. Cytokine results were also similar if analysis was performed using recovery of function at 3 months as the index of viability. The change in serum TNF-alpha and nitrite levels from baseline to 3 months after surgery correlated inversely with both the change in ejection fraction and the number of DE viable segments (r=-0.92 to -0.93; P<0.001). CONCLUSIONS: TNF-alpha and NOS2 gene expression is regionally upregulated in hibernating myocardium to a level intermediate between that of normal regions and ischemic regions without contractile reserve. This, along with a decline in serum cytokine levels after revascularization proportional to the extent of myocardial viability, suggests a contributing role for cardioinhibitory cytokines in the observed depression of function seen in hibernating myocardium.

Female↗
PubMed2003

Identification of hibernating myocardium with quantitative intravenous myocardial contrast echocardiography: comparison with dobutamine echocardiography and thallium-201 scintigraphy.

BACKGROUND: There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl(201)) scintigraphy. METHODS AND RESULTS: Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl(201) tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in hibernating myocardium were similar to segments with normal function and higher than dysfunctional myocardium without recovery of function (P<0.001). The best MCE parameter for predicting functional recovery was Peak MCIxbeta, an index of myocardial blood flow (area under the curve, 0.83). MCE parameters were higher in segments with contractile reserve and Tl(201) uptake > or =60% (P<0.05) and identified viable segments without contractile reserve by DE. The sensitivity of Peak MCIxbeta >1.5 dB/s for recovery of function was 90% and was similar to Tl(201) scintigraphy (92%) and any contractile reserve (80%); specificity was higher than for Tl(201) and DE (63%, 45%, and 54%, respectively; P<0.05). CONCLUSIONS: MCE with intravenous contrast identifies myocardial hibernation in humans. Prediction of viable myocardium with MCE is best using quantification of myocardial blood flow and provides improved accuracy compared with DE and Tl(201) scintigraphy.

Aged↗
PubMed1995

Dobutamine echocardiography in myocardial hibernation. Optimal dose and accuracy in predicting recovery of ventricular function after coronary angioplasty.

BACKGROUND: Myocardial hibernation is a condition of chronic left ventricular dysfunction associated with severe coronary artery disease whereby significant recovery of function occurs after revascularization. Identification of hibernating myocardium has important prognostic and therapeutic implications. The presence of contractile reserve as assessed by dobutamine echocardiography may be promising in the detection of hibernation. We designed a prospective study to evaluate the accuracy and optimal dose of dobutamine echocardiography for predicting recovery of ventricular function after angioplasty in patients with stable coronary artery disease and ventricular dysfunction. METHODS AND RESULTS: Twenty patients with stable coronary artery disease and segmental ventricular dysfunction scheduled for coronary angioplasty underwent dobutamine echocardiography before revascularization using incremental doses of 2.5, 5, 7.5, 10, 20, 30, and 40 micrograms/kg per minute every 3 minutes. Digital images of all eight stages were displayed simultaneously (two quad screens side by side) and interpreted using a 16-segment ventricular model and a 6-grade scoring system. Serial resting echocardiograms before, early (< 1 week), and late (> or = 6 weeks) after angioplasty were digitized and randomized in a quad-screen format for the assessment of recovery of function. Wall motion score index in the revascularized regions decreased from 2.86 +/- 0.76 before angioplasty to 2.12 +/- 1.03 late after angioplasty (P < .05). Of 320 ventricular segments, 148 had abnormal wall motion at baseline and 114 were revascularized. Recovery of function (> or = 2 grades) occurred in 25% of revascularized segments early and in 33% late after angioplasty. Of the 34 abnormal segments not revascularized, recovery of function occurred in only 1. During dobutamine echocardiography, abnormal segments exhibited one of four responses: biphasic (improvement at low dose and worsening at high dose) in 28% of segments, sustained improvement (persistent improvement till peak dose) in 18%, worsening in 15%, and no change in 39%. A biphasic response had the highest predictive value (72%) for recovery of function followed by worsening only (35%), while the lowest was seen with a "no-change" or sustained improvement response (13% and 15%). Combining biphasic and worsening responses resulted in a sensitivity of 74% and specificity of 73% for assessment of recovery of individual segments and 90% and 60%, respectively, for functional recovery of individual patients (n = 10). In segments with a biphasic response, the low dose at which improvement in wall motion was most prevalent (84%) was 7.5 micrograms/kg per minute and increased to 94% when the 5 and 7.5 micrograms/kg per minute doses were displayed. The reworsening phase of the biphasic response was usually seen with doses > or = 20 micrograms/kg per minute but was also observed as early as the 7.5 micrograms/kg per minute dose. CONCLUSIONS: The wall motion response during dobutamine echocardiography is useful in the prediction of recovery of ventricular function after revascularization in patients with stable coronary artery disease and ventricular dysfunction. The administration of low as well as high doses of dobutamine is needed for optimal evaluation.

Adult↗
PubMed1996

Only hibernating myocardium invariably shows early recovery after coronary revascularization.

BACKGROUND: The aims of this study were to identify hibernating myocardium (hypocontractile, hypoperfused viable myocardium that regains contractility after revascularization) in the clinical setting and to predict functional outcome in patients with coronary artery disease after coronary revascularization. METHODS AND RESULTS: Preoperative data related to the anterior free wall of the left ventricle were collected in 50 coronary bypass surgery candidates (positron emission tomography [PET], [13N]NH3 for flow, and [18F]FDG for metabolism [MET]; equilibrium-gated nuclear angiography [EGNA] for regional ejection fraction [REF]; and histological data from myocardial biopsies for percentage fibrosis and viable myocytes). Three months after surgery, the patients had follow-up PET and EGNA investigations. A principal-components analysis identified four patient clusters. Cluster 1 (n = 9) had normal viable myocardium. Cluster 2 (n = 18) had viable hypocontractile myocardium (REF, 39 +/- 12%) showing a PET mismatch pattern. Cluster 3 (n = 16) had viable hypocontractile myocardium associated with morphological myocyte injury showing a matched moderate decrease in flow (66 +/- 11%) and MET (70 +/- 11%). Cluster 4 (n = 7) had hypocontractile myocardium with mainly scar tissue (fibrosis, 74 +/- 12%). After surgery, only cluster 2, with hibernating myocardium, showed significant improvement in REF (from 39 +/- 12% to 50 +/- 13%, P < .05). Cluster 3, with sites of morphological myocyte injury, showed no recovery. The stepwise logistic regression showed a combination of low preoperative REF and high MET to be the best predictor of functional recovery (P < .008). CONCLUSIONS: Multivariate analysis identifies hibernating myocardium showing early postrevascularization recovery, as opposed to viable but myolytic myocardium with no early recovery. Postrevascularization recovery can be predicted (combination of low REF and high MET) by noninvasive techniques.

Adult↗
PubMed1998

Positron emission tomography analysis of [1-(11)C] acetate kinetics in short-term hibernating myocardium.

BACKGROUND: Modeling of the time-[1-(11)C]acetate activity curve assumes a constant concentration of labeled tricarboxylic acid cycle intermediates and associated metabolites, such as glutamate and aspartate, which may, however, decrease in short-term hibernating myocardium. METHODS AND RESULTS: In 12 anesthetized pigs, [1-(11)C]acetate was injected as a bolus into the cannulated left anterior descending coronary artery during normoperfusion, inotropic stimulation, and early (5 to 45 minutes) and prolonged ischemia (60 to 90 minutes). Regional myocardial oxygen consumption (MVO2, microliters per minute per gram) was measured, and the absence of necrosis was verified by triphenyl tetrazolium chloride staining. Inotropic stimulation increased MVO2 from 52.5+/-7.4 to 195.4+/-36.2 (mean+/-SD) and the rate constant (kmono, minutes[-1]) of [1-(11)C]acetate clearance from 0.094+/-0.018 to 0.322+/-0.076. During early ischemia, MVO2 and kmono were decreased to 24.3+/-8.5 and 0.061+/-0.011, respectively. Kmono closely correlated to MVO2 during normoperfusion, inotropic stimulation, and early ischemia. In short-term hibernating myocardium, however, at an unchanged MVO2, kmono increased toward control values (0.080+/-0.014). Myocardial glutamate and aspartate concentrations (biopsies) decreased to 47+/-26% and 77+/-18%; the peak count rate decreased to 66+/-22% of its respective control value. After correction for the decreases in glutamate and aspartate or in peak count rate, kmono was again decreased (0.050+/-0.016 or 0.052+/-0.014, respectively), and a close relationship to MVO2 was restored. CONCLUSIONS: Kmono correlates to MVO2 in short-term hibernating myocardium when the decreases in aspartate and glutamate or in peak count rate are considered.

Acetates↗
PubMed2003

Persistent stunning induces myocardial hibernation and protection: flow/function and metabolic mechanisms.

To test the hypothesis that persistent myocardial stunning can lead to hibernating myocardium, 13 pigs were chronically instrumented, and persistent stunning was induced regionally by 6 repetitive episodes of 90-minute coronary stenosis (CS) (30% reduction in baseline coronary blood flow [CBF]) followed by full reperfusion every 12 hours. During the 1st CS, CBF fell from 43+/-2 to 31+/-2 mL/min, and anterior wall thickening (AWT) fell by 54+/-8%, but posterior WT did not change. AWT never recovered fully and remained depressed by 31+/-7% before the 6th CS, reflecting persistent myocardial stunning, but baseline CBF was not changed. Surprisingly, during the 6th CS, AWT did not fall further despite a similar reduction in CBF during CS, as occurred with the 1st episode. Regional Mo2 fell similarly during the 1st and 6th CS. During the 1st CS, plasma glucose uptake increased, whereas free fatty acid (FFA) uptake was reduced. Before the 6th CS, glucose uptake remained elevated, whereas FFA uptake remained reduced. Histology revealed enhanced glycogen deposition, which could be explained by decreased glycogen synthase kinase (GSK)-3beta protein levels and activity. These results indicate that persistent stunning, even in the absence of chronic ischemia, can recapitulate the phenotype of myocardial hibernation. This results in a shift in the flow/function relationship where a 30% decrease in CBF is no longer accompanied by a fall in myocardial function, which could be explained, in part, by a shift in substrate utilization. These hemodynamic/metabolic adjustments could facilitate survival of hibernating myocardium.

Animals↗
PubMed2004

Cellular mechanisms of contractile dysfunction in hibernating myocardium.

Ischemic heart disease is a leading cause of chronic heart failure. Hibernation (ie, a chronic reduction of myocardial contractility distal to a severe coronary stenosis and reversible on revascularization) is an important contributing factor. The underlying cellular mechanisms remain however poorly understood. In young pigs (n=13, ISCH), an acquired coronary stenosis >90% (4 to 6 weeks) resulted in the development of hibernating myocardium. Single cardiac myocytes from the ISCH area were compared with cells from the same area obtained from matched normal pigs (n=12, CTRL). Myocytes from ISCH were larger than from CTRL. In field stimulation, unloaded cell shortening was reduced and slower in ISCH; relaxation was not significantly different. The amplitude of the [Ca2+]i transient was not significantly reduced, but reducing [Ca2+]o for CTRL cells could mimic the properties of ISCH, inducing a significant reduction of contraction, but not of [Ca2+]i. Action potentials were longer in ISCH. With square voltage-clamp pulses of equal duration in ISCH and CTRL, the amplitude of the [Ca2+]i transient was significantly smaller in ISCH, as was the Ca2+ current. Near-maximal activation of the myofilaments resulted in smaller contractions of ISCH than of CTRL cells. There was no evidence for increased degradation of Troponin I. In conclusion, cellular remodeling is a major factor in the contractile dysfunction of the hibernating myocardium. Myocytes are hypertrophied, action potentials are prolonged, and L-type Ca2+ currents and Ca2+ release are decreased. The steep [Ca2+]i dependence of contraction and possibly a reduction of maximal myofilament responsiveness further enhance the contractile deficit.

Actin Cytoskeleton↗
PubMed2005

Resting myocardial blood flow is impaired in hibernating myocardium: a magnetic resonance study of quantitative perfusion assessment.

BACKGROUND: Although impairment in perfusion reserve is well recognized in hibernating myocardium, there is substantial controversy as to whether resting myocardial blood flow (MBF) is reduced in such circumstances. Quantitative first-pass cardiovascular magnetic resonance (CMR) perfusion imaging allows absolute quantification of MBF. We hypothesized that MBF assessed at rest by quantitative CMR perfusion imaging is reduced in hibernating myocardium. METHODS AND RESULTS: Twenty-seven patients with 1 or 2-vessel coronary disease and at least 1 dysfunctional myocardial segment undergoing PCI were studied with preprocedure, early (24 hours), and late (9 months) postprocedure CMR imaging. First-pass perfusion images at rest were acquired in 3 short-axis planes by use of a T1-weighted turboFLASH sequence. In each slice, MBF was determined for 8 myocardial segments in mL . min(-1) . g(-1) by deconvolution of signal intensity curves with an arterial input function measured in the left ventricular blood pool. Cine MRI for assessment of global and segmental function and delayed enhancement MRI for detection of viability were also obtained. All coronary lesions were 80% to 95% stenosis in severity. Over all segments, mean MBF normalized by rate-pressure product ("corrected MBF") was 1.2+/-0.3 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments without significant coronary stenosis and 0.7+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in segments with coronary stenosis before PCI (mixed model controlling for slice and segment z=-23.9, P<0.001). Early after the procedure, the MBF was 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in revascularized segments and 1.3+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) in nondiseased segments (z=-6.1, P<0.001). Late after PCI, the systolic wall thickening and end-diastolic wall thickness both increased significantly more (both P<0.001) in the myocardial segments subtended by severe coronary stenosis (8+/-17% to 40+/-19% and 6.5+/-1.1 to 9.3+/-2 mm, respectively) than in the myocardial segments supplied by nondiseased vessels. Mean MBF in dysfunctional segments with significantly improved contraction after revascularization was 0.8+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) before PCI and 1.2+/-0.2 mL . min(-1) . g(-1) . (mm Hg . bpm/10(4))(-1) after PCI (z=2.0, P=0.04). CONCLUSIONS: CMR perfusion imaging detects impaired resting MBF in hibernating myocardial segments.

Aged↗
PubMedDate not supplied

Hibernated human fetal striatal tissue: successful transplantation in a rat model of Huntington's disease.

The use of fresh human fetal tissue in neural transplantation presents considerable logistical difficulties and limits the clinical applicability of this promising therapy. This study compared the survival of human fetal striatal tissue that had been stored for 24 h in a defined hibernation medium with that of fresh human fetal striatal tissue following xenotransplantation in a rat model of Huntington's disease (HD). Six to 7 weeks postgrafting, there was no significant difference between fresh and hibernated grafts in volume or in various striatal phenotypic markers, although there was a trend towards decreased graft volume. We conclude that short-term hibernation of this tissue is without significant adverse effects on the survival of grafted human fetal striatal tissue. This has important implications for the practical implementation of clinical neural transplant programs in HD.

Acetylcholinesterase↗
PubMed1992

Hibernating myocardium associated with coronary artery dissection and vasospastic angina.

Hibernating myocardium is an uncommon clinical state involving persistently impaired myocardial function. A 61-year-old man was admitted because of vasospastic angina. Coronary angiography revealed coronary artery dissection in the midportion of the right coronary artery, and segmental vasoconstriction was evoked by acetylcholine. In this patient, hibernating myocardium in the dissected region was clearly demonstrated by dipyridamole thallium-201 imaging. This report describes the first documented case of hibernating myocardium associated with coronary artery dissection, and the usefulness of dipyridamole thallium-201 imaging in the assessment of this state. Coronary artery spasm might be relevant to the etiology of coronary artery dissection.

Aortic Dissection↗
PubMedDate not supplied

[Hibernating myocardium: a clinical reality].

Myocardial hibernation is believed to occur in ventricular dyssynergic regions chronically deprived of coronary flow enough to warrant the preservation of contractile function. Pathophysiology of this condition remains largely unclear, mainly because good experimental models for its study are still lacking. Various methods can be clinically employed to detect hibernation in patients with chronic ventricular dysfunction. These methods use the principle of unmasking contractile reserve, or are based on the demonstration of preserved membrane function or myocardium metabolism in the dyssynergic regions. The correct identification of viable hibernating myocardium is crucial in the process of deciding which coronary disease patients would potentially benefit from revascularization procedures.

Humans↗
PubMed2000

Hibernating myocardium, stunning, ischemic preconditioning: clinical relevance.

Hibernation is a chronic condition that can be due to either chronic low perfusion or repetitive stunning. When oxygen demands increase, prolonged periods of ischemia occur, resulting in multiple episodes of stunning. Because hibernation may play a significant role in refractory failure, the diagnosis of hibernation followed by reperfusion can be life saving. Myocardium that has sustained a transient sublethal injury but has the potential for recovery with time is referred to as stunned myocardium. Myocardial stunning is commonly seen after coronary artery bypass surgery: variable periods of myocardial ischemia are sustained during coronary artery bypass graft surgery, and when these patients return to the intensive care unit, their ventricular function is severely impaired because of the prolonged anoxia during bypass. With the support of artificial assist devices, counterpulsation or temporary use of catecholamines, these patients improve and have a favorable prognosis. Similarly, recovery occurs with time in stunning that follows AMI or cardiac transplantation because in either case the heart had been temporarily anoxic. Clinical observations of ischemic preconditioning include the following: (1) first-effort angina or "warm-up phenomenon," i.e., angina with exercise early, but similar or greater effort the rest of the day does not cause any angina and (2) mortality of AMI is lower in patients with a history of angina preceding AMI. Angina 1 to 2 hours before AMI is the most effective time window for ischemic preconditioning. A less potent "second window" is observed when angina occurs during the second to fourth day before AMI. Adenosine possesses marked cardioprotective properties and has been used to pharmacologically induce ischemic preconditioning with some success. Work is still in progress.

Adenosine↗
PubMed2000

Importance of heart rate for acute hibernation in isolated blood-perfused piglet hearts.

BACKGROUND: Hibernating myocardium may benefit from revascularization. There are several experimental models for acute hibernation. In intact hearts low-flow ischemia causes time-dependent metabolic alterations, termed "metabolic adaptation". In isolated heart preparations metabolic responses to low-flow ischemia vary, and signs of metabolic adaptation are not consistently found. In isolated hearts global ischemia may cause bradycardia unless the hearts are paced. We hypothesized that the lack of consistent metabolic adaptation to low-flow ischemia in isolated hearts might be due to bradycardia during ischemia. In this study we investigated the influence of heart rate on metabolism and function in an isolated heart preparation. METHODS: Isolated blood-perfused piglet hearts were subjected to 120 min 10% flow. In groups A (n=9) and B (n=4) hearts were not paced during ischemia, in groups C (n=5) and D (n=5) hearts were paced at pre-ischemic heart rate during ischemia. RESULTS: Without pacing, heart rate declined to approximately 1/3 during ischemia and anaerobic metabolism showed a slight decline over time. With pacing, production of protons, pCO2 and lactate showed a bell-shaped curve which peaked at 20-25 min of ischemia, followed by a subsequent decline towards the end of ischemia (overall p < 0.001 for all). However, reperfusion revealed impaired recovery of function in paced hearts compared to non-paced hearts (53 +/- 7% vs 77 +/- 4%, p < 0.05) concomitant with higher release of creatine kinase (455 +/- 93 IU/100 g vs 106 +/- 13 IU/100 g, p < 0.01). CONCLUSIONS: When heart rate is allowed to decline during low-flow ischemia in isolated piglet hearts, signs of metabolic adaptation are not evident. When hearts are paced during ischemia time-dependent alterations in anaerobic metabolism occur, resembling observations seen in intact beating hearts. However, paced hearts also show indications of increased cellular injury, indicating that in paced hearts the metabolic consequences are mostly due to increased irreversible cell injury. Thus, the model for acute hibernation with 10% flow in isolated blood-perfused piglet hearts are critically dependent on bradycardia during ischemia.

Acute Disease↗
PubMed2002

Myocardial hibernation: a clinician's perspective.

Patients with myocardial hibernation have reversible left ventricular dysfunction after revascularization. Viability testing can identify those patients whose left ventricular dysfunction is primarily due to hibernation rather than scar. Patients with a substantial amount of hibernating myocardium seem to have a better outcome with revascularization than medical therapy. Patients with poor viability do worse after revascularization than patients with good viability.

Algorithms↗