Myocardial late gadolinium enhancement: a head-to-head comparison of motion-corrected balanced steady-state free precession with segmented turbo fast low angle shot.

AIM: To evaluate the image quality and diagnostic agreement with a head-to-head comparison of late gadolinium enhancement (LGE) images acquired by the motion-corrected (MOCO) balanced steady-state free precession (bSSFP) phase sensitivity inversion recovery (PSIR) and conventional segmented fast low angle shot (FLASH) PSIR methods15,16 in a patient cohort with a wide spectrum of cardiovascular disease. MATERIALS AND METHODS: In 59 consecutive patients, signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs) of the normal myocardium (NM), LGE, and blood pool (BP) were pair-wise compared between the two different sequences. A further semi-qualitative score system (graded 1 -4) was used to compare the overall image quality (OIQ). The diagnostic agreement of the two techniques were evaluated by both transmural severity and absolutely quantitative size of LGE. RESULTS: The SNRs of the NM, LGE, and BP of MOCO bSSFP were 4.8±3.4, 53.6±35.6 and 43.2±29.3, compared with 3.9±3.6 (p=0.126), 27.7±18.5 (p<0.001) and 24.3±13.4 (p<0.001) of FLASH LGE, respectively. The CNRs of LGE to NM, LGE to BP, and BP to NM were 48.3±33.1 versus 23.8±16.7 (p<0.001), 6.5±21.6 versus 3.8±10.8 (p<0.001), and 38.3±27.2 versus 20.3±10.7 (p=0.448), respectively. The OIQ of MOCO bSSFP was higher than that of segmented FLASH (median 4 versus median 3, p<0.001). For quantification of LGE size, there is good agreement and high correlation (r=0.992, p<0.001) between the two methods. CONCLUSIONS: MOCO bSSFP is a feasible, robust sequence for LGE imaging, especially for patients with arrhythmia and those incapable of breath-holding due to severe heart failure.

Myocardial fat overgrowth in Proteus syndrome.

Proteus syndrome (PS) is a rare, mosaic disorder with asymmetric and distorting overgrowth of the skeletal system, skin, and adipose tissues. Cardiac abnormalities are rare in this syndrome and only two prior cases have been reported. Many patients with PS followed at our institution underwent transthoracic echocardiograms for preoperative evaluation or as work-up for associated pulmonary disease. Some were noted to have prominent, focal echodense areas in the myocardium. We further investigated cardiac findings in a cohort of children and adult patients with PS. Patients with abnormal echocardiograms were referred for cardiac magnetic resonance imaging, Holter monitoring, and exercise treadmill testing. Twenty children and adults with PS, age 24 months to 50 years old, underwent transthoracic echocardiograms. Seven patients (35%) had focal bright echodense areas within the myocardium suggesting fatty infiltration. The majority of patients had significant involvement of the interventricular septum. The cardiac characteristics of all patients with fatty infiltration on transthoracic echocardiograms were compared to Proteus patients without these findings. There were no significant differences in chamber sizes, mass, systolic or diastolic function. No increased risk of conduction defects or arrhythmias was found. This study shows that abnormal fat overgrowth is a common finding in the myocardium in patients with Proteus syndrome; however, it is not associated with functional derangements or arrhythmias. Further evaluation of a larger number of Proteus patients is needed in order to determine the frequency and prognosis of cardiac involvement. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Serum vitamin D and parathyroid hormone in relation to cardiac structure and function: the ICELAND-MI substudy of AGES-Reykjavik.

CONTEXT: Emerging evidence suggests that vitamin D and PTH may play a role in the development of cardiac diseases. OBJECTIVE: We investigated whether 25-hydroxyvitamin D (25OHD) and PTH concentrations are cross-sectionally associated with cardiac structure and function using magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: ICELAND-MI is a substudy of the Age, Gene/Environment Susceptibility-Reykjavik Study, an older-aged community-dwelling cohort with oversampling of participants with diabetes (29%) and measurements between 2004 and 2007. Serum 25OHD concentrations were measured using an immunoassay (n = 992). Intact PTH concentrations were measured using a 2-site immunoassay (n = 203). We included 969 participants for this cross-sectional analysis (mean age 76 ± 5.3 years, 51% female). Mean 25OHD was 54.2 ± 25.5 nmol/L and the median PTH was 4.5 pmol/L (range 1.5-18). MAIN OUTCOMES: MRI to measure cardiac structure and function was the main outcome. RESULTS: The lowest 25OHD category (<25 nmol/L) compared with the highest category (≥75 nmol/L) was associated with a smaller left and right atrial area in unadjusted analyses; however, the associations became nonsignificant after adjustment for covariates. The highest PTH quartile compared with the lowest quartile was significantly associated with a 7.3 g (95% confidence interval 0.8, 13.8) greater left ventricular (LV) mass and a 5.1% (-9.1, -1.1) lower LV ejection fraction compared with the lowest PTH quartile in the fully adjusted model. CONCLUSIONS: Serum 25OHD concentrations were not associated with MRI measures in an older white population. Higher PTH concentrations were associated with greater LV mass and lower systolic function and may point to a potential role for PTH as a determinant of cardiac remodeling.

Advances in clinical applications of cardiovascular magnetic resonance imaging.

Cardiovascular magnetic resonance (CMR) is an evolving technology with growing indications within the clinical cardiology setting. This review article summarises the current clinical applications of CMR. The focus is on the use of CMR in the diagnosis of coronary artery disease with summaries of validation literature in CMR viability, myocardial perfusion, and dobutamine CMR. Practical uses of CMR in non-coronary diseases are also discussed.

Extended coverage first-pass perfusion imaging using slice-interleaved TSENSE.

Parallel imaging applied to first-pass, contrast-enhanced cardiac MR can yield greater spatial coverage for a fixed temporal resolution. The method combines rate R=2 acceleration using TSENSE with shot-to-shot interleaving of two slices. The square root R SNR loss is largely compensated for by a longer effective repetition time (TR) and increased flip angle associated with slice interleaving. In this manner, increased spatial coverage is achieved while comparable or better image quality is maintained. Single-heartbeat temporal resolution was accomplished with spatial coverage of eight slices at heart rates up to 71 bpm, six slices up to 95 bpm, and four slices up to 143 bpm. Experiments in normal subjects (N=6) were performed to assess signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values.

Arterial wall MRI characteristics are associated with elevated serum markers of inflammation in humans.

Inflammation contributes to atherosclerosis, but assessment in humans is largely restricted to measurement of markers in blood. We determined whether MRI properties of large arteries were associated with markers of inflammation in serum. Double inversion recovery, fast spin-echo images of the common carotid arteries and infrarenal aorta were obtained at 1.5 T both before and after gadolinium-DTPA (0.1 mmol/kg) in 52 subjects > or =40 years of age, 17 of whom had no risk factors for atherosclerosis and thus served as controls. Twenty-two study participants had increases in wall thickness (14), T2-weighted signal intensity (11), and/or contrast enhancement values (7) that were >2 standard deviations (SDs) from control group mean values. Ten subjects in this group had evidence of focal plaques in the carotids (5) and/or aorta (6). Compared with the remaining 30 subjects, these 22 had significantly higher levels of interleukin-6 (3.53 +/- 2.46 vs. 1.97 +/- 1.37 pg/mL, P = 0.004), C-reactive protein (0.56 +/- 0.98 vs. 0.30 +/- 0.52 mg/dL, P = 0.019), vascular cell adhesion molecule-1 (572 +/- 153 vs. 471 +/- 130 ng/mL, P = 0.012), and intercellular adhesion molecule-1 (244 +/- 80 vs. 202 +/- 45 ng/mL, P = 0.015), and nonsignificant differences in levels of E-selectin (46.1 +/- 18.9 vs. 42.3 +/- 11.3 ng/mL, P = 0.369). Thus, MRI characteristics of the aorta and carotid arteries were associated with elevated serum markers of inflammation, frequently in the absence of definite atheroma. MRI of large arteries may provide a new approach to investigate the contribution of inflammation to atherogenesis.

Gadolinium-enhanced, vessel-tracking, two-dimensional coronary MR angiography: single-dose arterial-phase vs. delayed-phase imaging.

The purposes of our study were to investigate the benefits of using a single dose of an extracellular contrast agent for coronary magnetic resonance angiography (CMRA) and to determine the relative benefits of arterial-phase vs. delayed-phase image acquisition. The right coronary artery was imaged in 10 healthy adults using a breath-hold, two-dimensional fast gradient echo pulse sequence designed for vessel tracking (multiphase, multislice image acquisition). Pre- and postcontrast CMRA was performed. Postcontrast imaging consisted of arterial- and delayed-phase CMRA following a 15 mL bolus (single dose) of contrast media and of delayed-phase imaging following a cumulative 45 mL contrast dose (triple dose). Contrast-enhanced CMRA provided a significantly higher (P < 0.001) signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) than noncontrast CMRA. CNR was highest for single-dose arterial-phase CMRA (13.1 +/- 4.5) and triple-dose delayed-phase CMRA (13.0 +/- 4.8), followed by single-dose delayed-phase CMRA (8.4 +/- 3.5) and noncontrast CMRA (4.2 +/- 1.8). Single-dose arterial-phase CMRA provided the best visualization of the distal right coronary artery and was preferred for blinded physician assessments. We concluded that utilization of a single dose of extracellular contrast media improves CMRA, especially if timed for arterial-phase imaging. J. Magn. Reson. Imaging 2001;13:682-689.

Hypertrophic cardiomyopathy caused by a novel alpha-tropomyosin mutation (V95A) is associated with mild cardiac phenotype, abnormal calcium binding to troponin, abnormal myosin cycling, and poor prognosis.

BACKGROUND: We report hypertrophic cardiomyopathy (HCM) in a Spanish-American family caused by a novel alpha-tropomyosin (TPM1) mutation and examine the pathogenesis of the clinical disease by characterizing functional defects in the purified mutant protein. METHODS AND RESULTS: HCM was linked to the TPM1 gene (logarithm of the odds [LOD] score 3.17). Sequencing and restriction digestion analysis demonstrated a TPM1 mutation V95A that cosegregated with HCM. The mutation has been associated with 13 deaths in 26 affected members (11 sudden deaths and 2 related to heart failure), with a cumulative survival rate of 73+/-10% at the age of 40 years. Left ventricular wall thickness (mean 16+/-6 mm) and disease penetrance (53%) were similar to those for the ss-myosin mutations L908V and G256E previously associated with a benign prognosis. Left ventricular hypertrophy was milder than with the ss-myosin mutation R403Q, but the prognosis was similarly poor. With the use of recombinant tropomyosins, we identified several functional alterations at the protein level. The mutation caused a 40% to 50% increase in calcium affinity in regulated thin filament-myosin subfragment-1 (S1) MgATPase assays, a 20% decrease in MgATPase rates in the presence of saturating calcium, a 5% decrease in unloaded shortening velocity in in vitro motility assays, and no change in cooperative myosin S1 binding to regulated thin filaments. CONCLUSIONS: In contrast to other reported TPM1 mutations, V95A-associated HCM exhibits unusual features of mild phenotype but poor prognosis. Both myosin cycling and calcium binding to troponin are abnormal in the presence of the mutant tropomyosin. The genetic diagnosis afforded by this mutation will be valuable in the management of HCM.

Optimization of fast cardiac imaging using an echo-train readout.

Fast gradient-echo sequences that use an echo-train readout are becoming more widely used, particularly for imaging the heart. An important issue for these sequences involves determining the optimal duration for the echo-train readout. In normal volunteer scans and theoretically the echo-train readout duration was varied from 2.4 to 32.8 msec. Myocardial signal-to-noise ratio (SNR), myocardium-tag signal difference-to-noise ratio (SDNR), flow artifact-to-noise ratio (FNR), and geometric distortion were measured and/or calculated. Our results showed that to obtain high SNR, SDNR, and data acquisition efficiency while minimizing FNR and geometric distortion, the readout duration should be 10-15 msec at 1.5 T.

Magnetic resonance first-pass myocardial perfusion imaging.

Magnetic resonance first-pass perfusion imaging has developed considerably over the past decade. It is possible to acquire 7-8 imaging planes every heartbeat at rest and in two heartbeats during stress using high-performance gradients and hybrid echoplanar methods. T1 weighting can be achieved with volumetric saturation pulses or selective "notch" pulses. First-pass studies can be quantified, but it also is possible to directly visualize myocardial perfusion abnormalities as subendocardial defects with less contrast enhancement than surrounding myocardium. It is feasible to detect stress-induced perfusion abnormalities in patients with coronary artery disease. Magnetic resonance imaging (MRI) perfusion abnormalities associated with myocardial infarction have significantly different characteristics from those seen on nuclear methods such as thallium, where the final appearance of images represents a combination of perfusion, viability, and wall thickness. Infarcted myocardium enhances during the first-pass MRI study unless there is microvascular or epicardial obstruction. Microvascular obstruction after myocardial infarction is easily detected and has adverse prognostic significance. Stress-induced perfusion abnormalities are not synonymous with coronary artery disease, as they can be detected in hypertrophic cardiomyopathy. MRI perfusion methods appear promising as long as physicians interpret the results in accordance of the physiology portrayed in the images.

Real-time three-dimensional echocardiography for measurement of left ventricular volumes.

Left ventricular (LV) volumes are important prognostic indexes in patients with heart disease. Although several methods can evaluate LV volumes, most have important intrinsic limitations. Real-time 3-dimensional echocardiography (RT3D echo) is a novel technique capable of instantaneous acquisition of volumetric images. The purpose of this study was to validate LV volume calculations with RT3D echo and to determine their usefulness in cardiac patients. To this end, 4 normal subjects and 21 cardiac patients underwent magnetic resonance imaging (MRI) and RT3D echo on the same day. A strong correlation was found between LV volumes calculated with MRI and with RT3D echo (r = 0.91; y = 20.1 + 0.71x; SEE 28 ml). LV volumes obtained with MRI were greater than those obtained with RT3D echo (126 +/- 83 vs 110 +/- 65 ml; p = 0.002), probably due to the fact that heart rate during MRI acquisition was lower than that during RT3D echo examination (62 +/- 11 vs 79 +/- 16 beats/min; p = 0.0001). Analysis of intra- and interobserver variability showed strong indexes of agreement in the measurement of LV volumes with RT3D echo. Thus, LV volume measurements with RT3D echo are accurate and reproducible. This technique expands the use of ultrasound for the noninvasive evaluation of cardiac patients and provides a new tool for the investigational study of cardiovascular disease.

Visualization of aortic valve leaflets using black blood MRI.

Although magnetic resonance imaging (MRI) is capable of imaging various physiological parameters associated with the heart valves, it has generally been difficult to visualize the valve leaflets directly. The aortic valve was imaged in 120 patients referred for cardiac MRI to assess myocardial volumes or mass. The average patient age was 37 and ranged from 9 to 75 years. Heart rate ranged from 43 to 100 bpm. Imaging was performed on a 1.5 T scanner equipped with enhanced gradients and a cardiac phased-array coil. A double inversion recovery fast spin-echo sequence was used to acquire short-axis images of the aortic valve in a breath-hold (15 +/- 3 seconds). All three leaflets of the aortic valve were seen in 102 of 120 studies (85%). Two leaflets were detected in another 15 subjects. No leaflets were seen in three individuals. Seven cases of a bicuspid or thickened aortic valves were clearly distinguished from normal valves. The signal-to-noise ratio of aortic leaflets (14 +/- 5) was significantly higher than that of the residual blood signal in the aortic root (7 +/- 4, P < 0.001). MR images showed the aortic valve leaflets in a high fraction of people with suspected normal aortic valves and detected seven cases of abnormal aortic valves. The potential of MRI to study both the anatomic and functional consequences of valvular heart disease warrants further study. J. Magn. Reson. Imaging 1999;10:771-777.

Myocardial oxygenation in vivo: optical spectroscopy of cytoplasmic myoglobin and mitochondrial cytochromes.

The oxygenation state of myoglobin and the redox state of cytochrome c provide information on the PO(2) in the cytosol and mitochondria, respectively. An optical "window" from approximately 540 to 585 nm was found in the pig heart in vivo that permitted the monitoring of myoglobin and cytochrome c without interference from Hb oxygenation or blood volume. Scanning reflectance spectroscopy was performed on the surgically exposed left ventricle of pigs. Difference spectra between control and a total left anterior descending coronary artery occlusion revealed maxima and minima in this spectral region consistent with myoglobin deoxygenation and cytochrome c and b reduction. Comparison of in vivo data with in vitro fractions of the heart, including Hb-free tissue whole heart and homogenates, mitochondria, myoglobin, and pig red blood cells, reveals minimal contributions of Hb in vivo. This conclusion was confirmed by expanding the blood volume of the myocardium and increasing mean Hb O(2) saturation with an intracoronary infusion of adenosine (20 microgram. kg(-1). min(-1)), which had no significant effect on the 540- to 585-nm region. These results also suggested that myoglobin O(2) saturation was not blood flow limited under these conditions in vivo. Work jump studies with phenylephrine also failed to change cytochrome c redox state or myoglobin oxygenation. Computer simulations using recent physical data are consistent with the notion that myoglobin O(2) saturation is >92% under basal conditions and does not change significantly with moderate workloads. These studies show that reflectance spectroscopy can assess myocardial oxygenation in vivo. Myoglobin O(2) saturation is very high and is not labile to moderate changes in cardiac workload in the open-chest pig model. These findings indicate that myoglobin does not contribute significantly to O(2) transport via facilitated diffusion under these conditions.

Visible-light photon migration through myocardium in vivo.

Empirical data between 510 and 590 nm of diffuse reflected light from the pig heart in vivo have shown that myoglobin and cytochrome c absorption peaks with little apparent contribution of red blood cell (RBC) Hb. Monte Carlo simulations of photon migration in tissue were performed to compare the effects of myoglobin and cytochromes with those of blood Hb on photon pathlengths and diffuse reflectance of visible wavelengths (450-600 nm) from the pig heart in vivo. Wavelength dependence of the input parameters, including the transport-corrected scattering coefficients (1.1-1.2 mm(-1)) and the absorption coefficients of blood-free solubilized heart tissue (0.43-1.47 mm(-1)), as well as the absorption coefficients of Hb, were determined by an integrating sphere method and standard spectrophotometry, respectively. The Monte Carlo simulations indicate that in the 510- to 590-nm range the mean path length within the myocardium for diffusely reflected light varies from 1.4 to 1.2 mm, whereas their mean penetration depth within the epicardium is only 330-400 micrometer for blood-free heart tissue. Analysis shows that the blood Hb absorption extrema are only observable between 510 and 590 nm when RBC concentration in tissue is >0.5%. Blood within vessels much larger than capillaries does not contribute significantly to the spectral features, because virtually all light in this spectral range is absorbed during transit through large vessels (>100 micrometer). This analysis suggests that diffuse reflected light in the 510- to 590-nm region will show spectral features uniquely associated with myoglobin and cytochrome c oxygenation states within 400 micrometer of the surface of the heart in situ as long as the capillary RBC concentration remains <0.5%.

Myocardial velocity gradient imaging by phase contrast MRI with application to regional function in myocardial ischemia.

Velocity-encoded phase contrast magnetic resonance imaging (MRI) has the potential to quantify regional myocardial contractile function with a sensitivity to motion comparable to implanted ultrasonic crystals. An MRI sequence and post-processing algorithm were developed to measure myocardial velocity gradients on a 1.5 T MRI scanner. These methods were validated on a rotating phantom and applied to dogs before (n = 11) and during prolonged coronary occlusion (n = 5). In phantom validation studies, the average absolute error corresponded to motion equivalent to 0.03 +/- 0.04 mm (mean +/- SD) during the repetition time of the experiment. Rigid body corrections during post-processing significantly simplified the interpretation of myocardial velocity vectors. In vivo, rigid body motion contributes substantially to the recorded myocardial velocities in systole and diastole and can give the false impression of regional wall motion abnormalities. After rigid body correction, normal systolic and diastolic velocity vectors in short-axis views of the left ventricle were primarily directed toward the center of the left ventricle. Transmural radial strain rate was 2.0 +/- 0.6 sec-1 during systole and -3.6 +/- 1.1 sec-1 during early diastole in normal canine hearts. Ischemic myocardium was easily discriminated from normal left ventricle by velocity-encoded phase contrast MRI both qualitatively and quantitatively (P < 0.01 in systole and P < 0.05 in early diastole). Although the myocardial velocity images have a spatial resolution on the order of a millimeter, the velocity encoding describes the mechanical consequences of focal myocardial ischemia with sensitivity to submillimeter displacement of the pixels. The three-dimensional nature of velocity-encoded MRI is particularly well suited to the study of the complex motion of the heart in vivo.

Segmented k-space fast cardiac imaging using an echo-train readout.

A segmented k-space fast gradient-echo pulse sequence with an echo-train readout (FGRE-ET) was developed for high-quality cine imaging of the heart in reduced scan times. Using segmented FGRE-ET, cine images of the heart can be acquired in as few as 1-5 heart beats and do not display the geometric distortion and flow-related artifacts typically associated with cardiac echoplanar imaging (EPI). Segmented FGRE-ET was compared with conventional segmented FGRE and with conventional multi-phase EPI in normal volunteers. Segmented FGRE-ET was found to have reduced temporal blurring compared with segmented FGRE for cine imaging in 4 heart beats (P<0.05). Also, segmented FGRE-ET did not display geometric distortion characteristic of conventional EPI (P<0.05). Segmented FGRE-ET may be particularly applicable to functional cardiac stress testing because it allows versatile cine imaging in very short breath-holds.

Using cardiac phase to order reconstruction (CAPTOR): a method to improve diastolic images.

A method is proposed to reconstruct multiphase images that accurately depicts the entire cardiac cycle. A segmented, gradient-recalled-echo sequence (FASTCARD) was modified to acquire data continuously. Images were reconstructed retrospectively by selecting views from each heartbeat based on cardiac phase rather than the time elapsed from the QRS complex. Cardiac phase was calculated using a model that compensates for beat-to-beat heart rate changes. Images collected using cardiac phase to order reconstruction (CAPTOR) depict the entire cardiac cycle and lack the temporal gap that is characteristic of prospectively reconstructed sequences. Time-volume curves of the left ventricle capture the contribution of atrial contraction to end-diastolic volume (EDV). Transmitral phase-contrast flow measurements show a second peak inflow (alpha wave) that is absent in the standard sequence. Because atrial contraction contributes to ventricular EDV, images using CAPTOR potentially may provide a more reliable measure of EDV, stroke volume, and ejection fraction than standard techniques.

Maximum oxidative phosphorylation capacity of the mammalian heart.

It is difficult to estimate the maximum in vivo aerobic ATP production rate of the intact heart independent of limitations imposed by blood flow, oxygen delivery, and maximum mechanical power. This value is critical for establishing the kinetic parameters that control oxidative phosphorylation, as well as for providing insights into the limits of myocardial performance. In this study, the maximum ADP-P(i)-driven heart mitochondrial respiratory rate (MV(O2 mito)) was determined with saturating levels of oxygen, substrates, and cofactors at 37 degrees C. These rates were normalized to cytochrome alpha1 alpha3 (cytochrome oxidase; Cyt a) content. To extrapolate this rate to the intact heart, the Cyt a content of the myocardium (nmol Cyt a/g wet wt myocardium) was determined in the same hearts. The maximum ADP-P(i)-driven mitochondrial respiratory rates were 676 +/- 31 and 665 +/- 65 nmol O2 x min(-1) x nmol Cyt a(-1) in the dog and pig, respectively. The Cyt a content in the two species was 43.6 +/- 2.4 and 36.6 +/- 3.1 nmol Cyt a/g wet wt, respectively. With these values, the MV(O2 mito) was calculated to be 29.5 (dog) and 24.3 (pig) micromol O2 x min(-1) x g wet wt myocardium(-1). Comparison with in vivo studies shows that the exercising heart can utilize 80-90% of its maximum oxidative capacity, implying there is little aerobic ATP production reserve in the mammalian heart.

Metabolic adaptation to a gradual reduction in myocardial blood flow.

BACKGROUND: Studies during 20% to 50% reductions in regional coronary blood flow have revealed a number of metabolic and functional adaptations that suggest the heart downregulates energy requirements and contractility in response to ischemia. In contrast to prior studies of sudden changes in coronary blood flow, we tested whether the heart could reduce ATP consumption commensurate with a gradual decrease in coronary blood flow or whether transient metabolic abnormalities are a necessary trigger in this process. METHODS AND RESULTS: From 0 to 35 minutes, mean left anterior descending coronary artery blood flow was reduced by approximately 1% per minute in 10 acutely anesthetized and instrumented swine. Coronary blood flow then was held constant between 35 and 60 minutes at the resulting 35% net blood flow reduction. Although systemic hemodynamics remained stable, a significant decrease in regional left ventricular systolic wall thickening developed (from control value of 45 +/- 11% to 18 +/- 11% at 60 minutes, P < .001) without a sustained decrease in the phosphorylation potential (as assessed by a < 2% decrease in either the transmural or subendocardial phosphocreatine-to-ATP ratio) and with minimal myocardial lactate production (4 +/- 44 mumol.min-1 x 100 g-1). CONCLUSIONS: Metabolic markers of ischemia such as ratio of phosphocreatine to ATP, ATP content, lactate content, and lactate production were blunted during this protocol of gradually worsening ischemia. Thus, contractile abnormalities of mild ischemia can develop with minimal metabolic evidence of ischemia. The downregulation of myocardial energy requirements can almost keep pace with the gradual decline in coronary blood flow.

Metabolic aspects of hibernating myocardium.

Myocardial hibernation describes the clinical entity of a dysfunctional region of myocardium with reduced flow that shows improvement in function after flow is restored. It is postulated that despite the reduced flow, metabolic activity is sufficient to prevent tissue necrosis. Experimental work in animals supports this. A moderate reduction in flow to a region of the left ventricle in pigs initially results in the typical metabolic picture of ischemia: ATP and PCr fall and anaerobic metabolism is present. However, over the next hour, a hypometabolic response occurs that eliminates almost all metabolic findings of ischemia despite ongoing flow reductions. This appears to be an actively and tightly regulated response. The reduction in systolic function is an important part of the hypometabolic state, but cannot fully account for the downregulation of energy use.