Regional Myocardial Oxygen Consumption Research Articles

Complement- and endothelial activation after out-of-hospital cardiac arrest is associated with poor cerebral outcome

Acetate has a pivotal role in the intermediary metabolism of living cells. Glucose, fatty acids and other carbon sources for oxidation are converted to acetate before entering the mitochondrial tricarboxylic acid cycle. 11C-acetate PET is an established technique in cardiac imaging since decades and allows accurate estimates of both regional myocardial blood flow (MBF) and oxygen consumption (MVO2) to be obtained simultaneously from a single scan of less than 30 min duration. Image acquisition is based on dynamic imaging and analysis requires kinetic modeling approaches for optimal results. These requirements, as well as the need for an on-site cyclotron for carbon-11 production, so far limited the clinical use to advanced PET facilities. In recent years, myocardial 11C-acetate PET has seen a renewed interest in heart failure research into myocardial external efficiency (MEE). MEE is defined as the ratio of the energy associated with external pressure-volume work (cardiac output x systemic blood pressure, converted to Joule) and chemical energy consumed (MVO2 x left ventricular mass (LVM), converted to Joule). Cardiac output and LVM can be measured by echocardiography, magnetic resonance imaging or directly from the 11C-acetate PET scan, and hence provides a fully non-invasive approach to detailing important aspects of the inner workings of the heart. MEE is increasingly used to evaluate new therapies in heart failure and has been validated for that purpose. MEE has a high reproducibility and might potentially also be of use for early diagnosis of heart failure before symptoms develop.This chapter describes scanning parameters with image analysis and summarizes the clinical utility of MBF, MVO2 and MEE measurements obtained from 11C-acetate PET.

Calcium Antagonist Verapamil and Reperfusion Injury of the Heart

An experimental study to examine the effect of verapamil, given into a coronary artery, on reperfusion injury. The study was randomized but not blinded. This study was conducted in the animal laboratory of the Department of Anesthesiology and Critical Care in an academic institution. The study was performed in an anesthetized open-chest pig model. Left anterior coronary artery (LAD) occlusion for 15 minutes followed by 90 minutes of reperfusion. Verapamil or saline was given into the LAD artery either at the time the coronary artery was occluded (ie, during acute severe ischemia or during the reperfusion period). LAD artery blood flow, regional myocardial function, and metabolism were assessed by the end-systolic pressure length relationship, regional systolic shortening, postsystolic shortening, regional myocardial oxygen consumption, and local cardiac vein lactate. Verapamil given during ischemia resulted in a shorter period of regional myocardial stunning when compared with saline or verapamil during reperfusion. The difference in the verapamil strategies (ie, verapamil administered during ischemia versus verapamil during the reperfusion period) can probably be explained by a difference in the effective dose of the drug present in the heart at the time reperfusion started rather than the period of administration per se.

Negative inotropic action of propofol is enhanced in the acute ischemic myocardium of dogs

We investigated the effects of propofol on contractility and oxygen balance in acute ischemic myocardium and compared them with those of normal myocardium using a coronary microembolization model in dogs. In open-chest dogs, the left anterior descending coronary artery (LAD) was perfused through an extracorporeal bypass from the carotid artery. Regional myocardial contractility and myocardial oxygen balance were evaluated along with segment shortening (%SS), regional myocardial oxygen consumption (MVO2), and lactate extraction ratio (LER) of the area perfused by the LAD. Acute ischemia was produced by repeated injection of microspheres into the LAD-perfused area until %SS decreased by 50% of baseline. In normal myocardium, intracoronary infusion of propofol at doses of 1.2 and 2.4 mg x kg(-1) x h(-1) caused slight decreases in %SS to 83% +/- 8% and 80% +/- 10%, respectively. In ischemic myocardium, propofol caused greater decreases in %SS (59% +/- 18% and 35% +/- 20%, respectively). The changes in MVO2 after propofol infusion generally paralleled the changes in %SS, but LER was not changed in either ischemic or normal myocardium. Propofol causes a greater decrease in the contractility of acute ischemic myocardium as compared with normal myocardium in which myocardial oxygen imbalance is not involved as a mechanism.

Global and regional myocardial oxygen consumption and blood flow in severe cardiomyopathy with left bundle branch block

In patients with dilated cardiomyopathy (DCM), left bundle branch block (LBBB) is a common finding. The characteristic feature is an asynchronous septal wall motion and most frequently a delay of the lateral and/or posterior wall segments. With the onset of cardiac resynchronization therapy, there is a focus on the specific pathophysiology of a LBBB. However, quantitative data on regional myocardial oxygen consumption (MVO(2)) and blood flow (MBF) are missing. We studied 31 patients with severe DCM and LBBB (ejection fraction 22.1+/-7.1%) and 14 patients with mild to moderate DCM without LBBB (ejection fraction 46.7+/-7.9%). Global and regional MVO(2) as well as MBF were determined from a dynamic (11)C-acetate positron emission tomography (PET) study. Global MVO(2) and MBF were lower in the DCM group with LBBB than in the control group (P<0.05). Regionally, the LBBB group revealed a higher (P<0.05) MVO(2) and MBF in the lateral wall than in the other walls. The control group did not show significant differences between the myocardial walls and demonstrated a smaller variability of the parameters. DCM patients with LBBB exhibit a more heterogeneous distribution of MVO(2) and MBF among the myocardial walls than DCM patients without LBBB. Due to the LBBB associated electromechanical alterations, the highest regional values of MVO(2) and MBF are found in the lateral wall.

Effect of cardiac resynchronization therapy on global and regional oxygen consumption and myocardial blood flow in patients with non-ischaemic and ischaemic cardiomyopathy

We studied the effects of cardiac resynchronization therapy (CRT) on global and regional myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) in non-ischaemic (NICM) and ischaemic dilated cardiomyopathy (ICM). Thirty-one NICM and 11 ICM patients, all of them acute responders, were investigated. MVO2 and MBF were obtained by 11C-acetate PET before and after 4 months of CRT. In NICM global MVO2 and MBF did not change during CRT, while the rate pressure product (RPP) normalized MVO2 increased (P=0.03). Before CRT regional MVO2 and MBF were highest in the lateral wall and lowest in the septum. Under therapy, MVO2 and MBF decreased in the lateral wall (P=0.045) and increased in the septum (P=0.045) resulting in a more uniform distribution. In ICM, global MVO2, MBF, and RPP did not change under CRT. Regional MVO2 and MBF showed no significant changes but a similar tendency in the lateral and septal wall to that in NICM. CRT induces changes of MVO2 and MBF on a regional level with a more uniform distribution between the myocardial walls and improved ventricular efficiency in NICM. Based on the investigated parameters, CRT appears to be more effective in NICM than in ICM.

Improvement in regional and global myocardial oxygen consumption in resynchronization therapy: A C-11-acetate positron emission tomography study

Improvement in regional and global myocardial oxygen consumption in resynchronization therapy: A C-11-acetate positron emission tomography study

β-adrenergic blockade during severe ischemia

Objective: To examine the effect of acebutolol, a β-adrenergic-receptor blocker, on severe regional myocardial ischemia, specifically the effects on regional myocardial function and metabolism. Design: Randomized study. Setting: Animal laboratory of the Department of Anesthesiology and Critical Care, University of Stellenbosch Medical School. Participants: Anesthetized open-chest pig model (n = 18). Interventions: Regional left ventricular function and metabolism were evaluated. Severe stenosis was applied to the left anterior descending coronary artery. After establishing regional myocardial ischemia, acebutolol was administered intravenously, and results were compared with controls who did not receive acebutolol. Animals were prospectively randomized to 1 of the groups. Measurements and Main Results: Regional myocardial function and metabolism were assessed by end-systolic pressure relationship, regional systolic shortening, postsystolic shortening, regional myocardial oxygen consumption, and lactate dynamics. Coronary blood flow was determined with a Doppler flow probe. Results indicated that acebutolol increased regional myocardial blood flow, and this resulted in less severe regional myocardial ischemia, improved function, and an increase in regional myocardial oxygen consumption. Conclusion: The β-Adrenergic-receptor antagonist was successful in reducing regional myocardial ischemia in this model. This reduction was achieved by an increase in coronary blood flow, which resulted in an improvement in regional mechanical function and an increase in oxygen consumption. Copyright 2002, Elsevier Science (USA). All rights reserved.

Effects of intracoronary calcium chloride on regional oxygen balance and mechanical function in normal and stunned myocardium in dogs

Brief myocardial ischaemia has been demonstrated to result in mechanical and coronary endothelial dysfunction, in which calcium may play a role. We examined whether the mechanical and vascular responses to calcium are altered in postischaemic, reperfused myocardium. Regional myocardial oxygen consumption (MVO2), mechanical function and coronary blood flow (CBF) in response to calcium chloride (0.10, 0.25, 0.50 and 0.75 mg ml(-1) of CBF) directly infused into the left anterior descending (LAD) artery were determined before (normal) and 30 min after a 15-min-period of LAD occlusion (stunned) in an open-chest canine model. Percentage segment shortening (%SS) and percentage postsystolic shortening (%PSS) in the LAD territory were determined using ultrasonic crystals and CBF using a Doppler transducer. Myocardial extraction of oxygen (EO2) and lactate (Elac) was calculated. The infusion of calcium chloride resulted in dose-dependent increases in %SS and MVO2 but did not affect %PSS in normal myocardium. These changes were accompanied by parallel increases in CBF, resulting in no change in EO2. In stunned myocardium, the responses to calcium chloride were not significantly altered, with the exception of a reduction in %PSS. However, ischaemia and reperfusion itself significantly reduced %SS and Elac and increased %PSS. These data suggest that calcium chloride improves regional systolic and diastolic function both in normal and stunned myocardium. Calcium chloride is unlikely to cause direct coronary vasoconstriction or to deteriorate regional mechanical function in postischaemic myocardium.

Preserved myocardial blood flow and oxygen supply-demand balance with active coronary perfusion during simulated off-pump coronary artery bypass grafting.

During off-pump coronary artery bypass surgery, concern remains about the possible myocardial injury associated with the transient occlusion and stabilization of the target vessels. Although intraluminal shunts are used to avoid ischemia during graft anastomosis, blood flow through the shunts can be affected by upstream pressure and inherent resistance, resulting in reduced blood flow during hypotension or severe proximal stenosis. In anesthetized dogs regional myocardial blood flow (microspheres), oxygen consumption, lactate extraction, and systolic shortening (sonomicrometry) were measured in the myocardium served by the left anterior descending coronary artery with native perfusion after interposition of a 2.25-mm shunt (> or = 90% of left anterior descending diameter) and during active coronary perfusion with a constant flow pump. Measurements were made under normotension and hypotension produced by partial caval occlusion to reduce arterial pressure by 50%. Interposition of the shunt reduced blood flow by 67.8%, regional oxygen delivery by 59.8%, and systolic shortening by 45.6% relative to baseline, but lactate extraction (31.0% vs 31.2%) and oxygen supply-consumption (O(2)S/myocardial oxygen consumption ratio, 2.7 +/- 0.5 vs 2.6 +/- 0.5) were comparable with baseline values. Hypotension further decreased these physiologic values and was associated with local lactate production (-67.4% extraction) and decreased O(2)S/myocardial oxygen consumption ratio (1.3 +/- 0.1). Active coronary perfusion was associated with regional blood flow, oxygen delivery, systolic shortening, and lactate extraction comparable with baseline values. In contrast to the shunt, active perfusion maintained myocardial flow, oxygen delivery, and lactate extraction during hypotension and normalized the O(2)S/myocardial oxygen consumption ratio, although systolic shortening decreased as a result of ventricular unloading. Intraluminal shunts may impede oxygen delivery to the target myocardium, which precipitates regional ischemia during transient hypotension. Active coronary perfusion provides adequate oxygen supply independent of systemic blood pressure.

Oxygen wastage of stunned myocardium in vivo is due to an increased oxygen cost of contractility and a decreased myofibrillar efficiency

We investigated whether an increased oxygen cost of contractility and/or a decreased myofibrillar efficiency contribute to oxygen wastage of stunned myocardium. Because Ca(2+)-sensitizers may increase myofibrillar Ca(2+)-sensitivity without increasing cross-bridge cycling, we also investigated whether EMD 60263 restores myofibrillar efficiency and/or the oxygen cost of contractility. Regional fiber stress and strain were calculated from mesomyocardially implanted ultrasound crystals and left ventricular pressure in anesthetized pigs (n=18). Regional myocardial oxygen consumption (MVO(2)) was measured before contractility (end-systolic elastance, E(es)) and total myofibrillar work (stress-strain area, SSA) were determined from stress-strain relationships. Atrial pacing at three heart rates and two doses of dobutamine were used to vary SSA and E(es), respectively. After stunning (two times 10-min ischemia followed by 30-min reperfusion), measurements were repeated following infusion of saline (n=8) or EMD 60263 (1.5 mg.kg(-1) i.v., n=10). Linear regression was performed using: MVO(2)=alpha.SSA+beta.E(es)+gamma.HR(-1) (alpha(-1), myofibrillar efficiency; beta, oxygen cost of contractility; and gamma, basal metabolism/min). Stunning decreased SSA by 57% and E(es) by 64%, without affecting MVO(2), while increasing alpha by 71% and beta by 134%, without affecting gamma. From the wasted oxygen, 72% was used for myofibrillar work and 18% for excitation-contraction coupling. EMD 60263 restored both alpha and beta. Oxygen wastage in stunning is predominantly caused by a decreased myofibrillar efficiency and to a lesser extent by an increased oxygen cost of contractility. Considering that EMD 60263 reversed both causes of oxygen wastage, it is most likely that this drug increases myofibrillar Ca(2+)-sensitivity without increasing myofibrillar cross-bridge cycling.

Comparison of myocardial oxygen consumption using 11C acetate positron emission tomography scanning in a working and non-working heart transplant model.

In acute cardiac rejection, changes in myocardial oxygen consumption occur; non-invasive detection of these metabolic changes would have obvious clinical utility. In the classic cervical, heterotopic, canine, transplant model, the heart is non-working. It has a low myocardial oxygen consumption. Creation of a working model with normal myocardial oxygen consumption would enhance validity of non-human studies. Clearance of 11C acetate was determined by positron emission tomography (PET) scanning and compared with myocardial oxygen consumption in normal and transplanted canine hearts. Donor hearts from mongrel dogs (2.5-3 kg; n=4) were transplanted into the neck of adult beagles (12-15 kg; n=4), no immunosuppression was given. Two non-working hearts were modified to eject only coronary flow via the right ventricle. In two hearts, a novel working model was created with aortic regurgitation to load the left ventricle. Working and non-working hearts underwent PET scanning on post-operative days 2 and 4. Normal dog hearts (n=2) and native hearts of transplanted dogs (n=3) were used to validate the scanning technique. Coronary sinus and aortic oxygen saturation data along with myocardial blood flow (radiolabeled microspheres) confirmed that clearance of 11C acetate in normal and transplanted hearts followed a bi-exponential model. Myocardial oxygen consumption was correlated with the rate constant of 11C acetate rapid phase clearance (r=0.91) in normal and transplanted hearts. The working hearts had increased myocardial oxygen consumption compared to non-working hearts. This study (1) introduces a model of a working heterotopic cardiac transplantation with near-normal oxygen consumption; and (2) demonstrates that regional myocardial oxygen consumption in transplanted hearts can be detected by 11C acetate PET.

An overview of radiotracers in nuclear cardiology

Coronary blood flow is regulated by anatomical, hydraulic, mechanical, and metabolic factors. 1 Myocardial perfusion depends on both the driving pressure gradient and the resistance of the vascular bed. Through autoregulation, the coronary bed maintains myocardial perfusion within a narrow range, despite wide fluctuations in coronary perfusion pressure. 2 Autoregulation of coronary blood flow is driven by changes in regional myocardial metabolism and oxygen consumption. Coronary artery stenosis may induce different alterations of the autoregulation of coronary blood flow, resulting in impairment in myocardial function such as myocardial ischemia, myocardial stunning, myocardial hibernation, and myocardial infarction. Different radiotracers may be used as means of assessing the impairment of myocardial function; the choice of which tracer must be used as a means of identifying this dysfunction should depend primarily on the clinical questions to be answered. Myocardial perfusion single-photon emission computed tomography (SPECT) with thallium-201‐ and technetium-99m‐labeled agents is a well-established modality for the evaluation of patients with suspected or known coronary artery disease (CAD).3-7 Furthermore, different positron emission tomography (PET) perfusion tracers may be used for the quantitative measurement of absolute or relative myocardial blood flow, such as nitrogen-13 ammonia, rubidium82 chloride, and oxygen-15 water. Moreover, considering that myocardial ischemia is associated with alterations in myocardial metabolism, the use of metabolic tracers has emerged as a useful approach in investigating the effects of CAD on myocardial metabolism. The tracers used as a means of assessing cardiac metabolism in patients with heart diseases are labeled fatty acids and fluorine-18 fluorodeoxyglucose (FDG). PERFUSION IMAGING AGENTS WITH SPECT Thallium-201

Regional myocardial oxygen consumption estimated by carbon-11 acetate and positron emission tomography before and after repetitive ischemia.

Preserved myocardial oxygen consumption estimated by carbon 11-acetate and positron emission tomography (PET) in myocardial regions with chronic but reversibly depressed contractile function in patients with ischemic heart disease have been suggested to be caused by repeated short episodes of acute myocardial ischemia. To evaluate this hypothesis myocardial 11C-acetate PET imaging was performed before and after acute repetitive myocardial ischemia. In open chest dogs (n = 8), the left anterior descending coronary artery was occluded 4 times for 5 minutes alternating with 5 minutes of reperfusion. Before and after repetitive coronary occlusions, oxygen 15 water/oxygen 15 carbon monoxide (blood flow), and 11C-acetate (oxygen consumption) PET imaging were performed. Left ventricular regional systolic wall thickening was measured with sonomicrometry. Forty-five minutes after the ischemic episodes, systolic ventricular wall thickening was decreased by 90%, whereas myocardial blood flow was reduced by 21% compared with baseline values (P < .05). Ninety minutes after the ischemic episodes, estimated oxygen consumption was unaltered compared with the baseline level despite a sustained 70% decrease in the regional contractile function (P < .05). Oxygen consumption estimated by 11C-acetate PET imaging is preserved after repeated episodes of acute myocardial ischemia despite a severe impairment of contractile function.

Simultaneous noninvasive determination of regional myocardial perfusion and oxygen content in rabbits: toward direct measurement of myocardial oxygen consumption at MR imaging.

To determine whether myocardial arterial perfusion and oxygen concentration can be quantified simultaneously from the same images by using spin labeling and the blood oxygenation level-dependent (BOLD) effect with fast spin-echo (SE) imaging. A T2-weighted fast SE pulse sequence was written to image isolated, arrested, blood-perfused rabbit hearts (n = 6) at 4.7 T. Perfusion images with intensity in units of milliliters per minute per gram that covered the entire left ventricle with 0.39 x 0.39 x 3.00-mm resolution were obtained in less than 15 minutes with a 32-fold reduction in imaging time from that of a previous study. Estimates of oxygen concentration were made from the same images acquired for calculation of perfusion images. Estimates of regional myocardial oxygen content could be made from the perfusion images; this demonstrated the feasibility of three-dimensional calculation of regional oxygen consumption, which requires concomitant measurement of both oxygen content and flow. Fast SE imaging was shown to be as sensitive to hemoglobin desaturation as standard SE imaging. Perfusion abnormalities and oxygen deficits were easily identified and verified qualitatively with gadopentetate dimeglumine on both perfusion and BOLD images obtained after coronary arterial ligation. T2-weighted fast SE imaging combined with perfusion-sensitive spin labeling can be used to measure myocardial arterial perfusion and oxygen concentration. This provides the groundwork for calculation of regional myocardial oxygen consumption.

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

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. 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. Kmono correlates to MVO2 in short-term hibernating myocardium when the decreases in aspartate and glutamate or in peak count rate are considered.

Dependency of contractile reserve on myocardial blood flow: implications for the assessment of myocardial viability with dobutamine stress echocardiography.

Contractile reserve, improvement in contractile function during inotropic stimulation, is a proposed marker of viable myocardium. This study was designed to address, in patients with left ventricular dysfunction due to chronic coronary artery disease, whether contractile reserve depends on myocardial blood flow. We studied 19 patients, at rest and during dobutamine, with 2D echocardiography for regional mechanical function and PET for regional myocardial blood flow ([(15)O]water) and oxygen consumption ([11C]acetate). Of 166 myocardial segments, 21 had normal systolic function, 56 were dysfunctional but contractile reserve-positive, and 89 were dysfunctional and contractile reserve-negative. Myocardial blood flow at rest was lower in contractile reserve-negative (0.41+/-0.18 mL x g(-1) x min(-1)) than in contractile reserve-positive (0.50+/-0.22 mL x g(-1) x min(-1)) and normal segments (0.55+/-0.20 mL x g(-1) x min(-1), P<.009). After dobutamine infusion, blood flow increased less in contractile reserve-negative (0.63+/-0.38 mL x g(-1) x min(-1)) than in contractile reserve-positive (1.28+/-0.65 mL x g(-1) x min(-1)) and normal segments (1.93+/-0.83 mL x g(-1) x min(-1), P<.0001). Likewise, myocardial oxygen consumption was lower at rest in contractile reserve-negative (clearance rate of [11C]acetate, 0.043+/-0.012 min(-1)) than in contractile reserve-positive (0.048+/-0.01 min(-1)) and normal segments (0.058+/-0.008 min(-1), P<.02). Myocardial oxygen consumption with dobutamine increased less in contractile reserve-negative (0.060+/-0.013 min(-1)) than in contractile reserve-positive (0.077+/-0.016 min(-1)) and normal segments (0.092+/-0.024 min(-1), P<.0001). Of segments defined as viable by PET, 54% were contractile reserve-negative and exhibited lower blood flow with dobutamine (0.72+/-0.36 mL x g(-1) x min(-1)) than with viable, contractile reserve-positive segments (1.29+/-0.70 mL x g(-1) x min(-1), P<.0001). Contractile reserve depends, in part, on the level of myocardial blood flow at rest and during inotropic stimulation.

Preconditioning with Ischaemia Reduces Both Myocardial Oxygen Consumption and Infarct Size in a Graded Pattern

We tested the hypothesis that ischaemic preconditioning reduces pre-ischaemic energy demand and thereby reduces the energy supply–demand mismatch imposed by coronary artery occlusion. Experiments were performed in 52 open chest pigs anaesthetised with sodium pentobarbital. One or two cycles, each of 10 min LAD occlusion followed by 30 min reperfusion, served as the preconditioning stimuli. The degree of protection was evaluated by measuring infarct size (tetrazolium stain) as percentage of area at risk (fluorescent particles) after 45 min LAD occlusion followed by 2 h reperfusion. One preconditioning cycle reduced regional myocardial oxygen consumption (MVO2) by 15±3% (P<0.05), whereas two cycles of preconditioning reduced MVO2by 25±3% (P<0.05vone cycle). This reduction was probably due to reduced energy demand, as both coronary blood flow and arteriovenous oxygen differences decreased, without lactate release or reduction in peak hyperaemic flow response. Energy requirements were most likely also reduced during ischaemia since repayment of flow debt after the second ischaemic period was 33±7% less than after the first ischaemic period (P<0.001). One preconditioning cycle reduced infarct size from 58±3% of area at risk to 40±5% (P<0.05), whereas two cycles of preconditioning reduced infarct size to 15±4% of area at risk (P<0.05vone cycle). We conclude that preconditioning with ischaemia reduces energy consumption in a graded pattern. This effect may contribute to the graded protective effect of ischaemic preconditioning.

Chronic myocardial hibernation in humans. From bedside to bench.

Since the pioneering work of Tennant and Wiggers,1 it has been known that total ischemia leads to a prompt cessation of contraction and eventually results in the appearance of cell damage and irreversible myocardial necrosis. Accordingly, in the minds of many cardiologists, the discovery of an abnormal regional contraction in a patient with coronary artery disease has long been equated with the presence of irreversible myocardial necrosis. With the advent of recanalization therapy, however, evidence progressively accumulated that prolonged regional “ischemic” dysfunction did not always arise from irreversible tissue damage and, to some extent, could be reversed by restoration of blood flow.2 3 4 5 These observations have led to the speculation that chronically hypoperfused myocardium, which is often referred to as “hibernating,”2 3 4 5 6 could maintain viability by simply reducing its metabolic demand to match the decreased supply for as long as myocardial perfusion was inadequate. The chronic impairment of contractile function in this setting has been regarded as a protective mechanism by which the heart spontaneously downgrades its myocardial function, minimizes its energy requirements, and prevents the appearance of irreversible tissue damage.2 4 5 The concept of chronic hibernation thus consists of two parts: a unique clinical observation that bears important implications for the management of patients with chronic coronary artery disease2 3 4 5 6 and a pathophysiological hypothesis, yet to be demonstrated, implying that the chronic dysfunction is due to a chronic reduction of resting MBF.4 5 Other aspects that were not included in the original description, ie, the rapidity of mechanical recovery after successful revascularization7 and the response of dysfunctional myocardium to inotropic stimulation, are now also considered to be integral parts of this condition. The purpose of this discussion is to review some of the …

Local inotropic stimulation by methylene blue does not improve mechanical dysfunction due to myocardial stunning.

We tested the hypothesis that reduction of intramyocardial cyclic guanosine monophosphate (GMP) by methylene blue (MB) would improve mechanical dysfunction in stunned myocardium. Regional stunning was produced in nine open-chest anesthetized dogs by a 12-min left anterior descending coronary artery (LAD) occlusion. MB was infused into the LAD during reperfusion (1 mg/kg per min). Stunning reduced LAD force development, introduced a significant time delay between the onset of force and shortening (delay) and caused significant systolic bulging to occur. Stunning reduced systolic regional work (the integrated product of force and segment shortening during systole), but did not significantly alter regional oxygen consumption or cyclic GMP levels. MB decreased cyclic GMP (1.8 +/- 0.2 to 0.9 +/- 0.1 pmol/g) and increased peak force (36 +/- 5 to 55 +/- 10 g). However, MB increased delay (93.9 +/- 18.4 to 233 +/- 19 ms) and systolic bulging (5.9 +/- 2.1% to 9.3 +/- 2.8%) and further reduced systolic regional work (control; 4204 +/- 933 g x mm/min; stunned: 2191 +/- 542 g x mm/min; MB: 1153 +/- 516 g x mm/min). MB increased regional myocardial oxygen consumption (7.4 +/- 1.0 to 15.6 +/- 2.7 ml O2/min per 100 g). These results suggest that depressed contractility, while present in myocardial stunning, is not the primary cause of mechanical dysfunction.

Thoracic Epidural Anesthesia During Coronary Artery Bypass Surgery

The effects of high thoracic epidural anesthesia (TEA) on cardiac sympathetic nerve activity, myocardial blood flow and metabolism, and central hemodynamics were studied in 20 patients undergoing coronary artery bypass grafting (CABG). In 10 of the patients, TEA (T1-5 block) was used as an adjunct to a standardized fentanyl-nitrous oxide anesthesia. Hemodynamic measurements and blood sampling were performed after induction of anesthesia but prior to skin incision and after sternotomy. Assessment of total and cardiac sympathetic activity was performed by means of the norepinephrine kinetic approach. Prior to surgery, mean arterial pressure (MAP), great cardiac vein flow (GCVF), and regional myocardial oxygen consumption (Reg-MVO2) were lower in the TEA group compared to the control group. During sternotomy there was a pronounced increase in cardiac norepinephrine spillover, MAP, systemic vascular resistance index (SVRI), pulmonary capillary wedge pressure (PCWP), GCVF, and Reg-MVO2 in the control group. These changes were clearly attenuated in the TEA group. None of the patients in the TEA group had metabolic (lactate) or electrocardiographic signs of myocardial ischemia. Three patients in the control group had indices of myocardial ischemia prior to and/or during surgery. We conclude that TEA attenuates the surgically mediated sympathetic stress response to sternotomy, thereby preventing the increase in myocardial oxygen demand in the pre-bypass period without jeopardizing myocardial perfusion.