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Björn Wieslander,
Katherine C Wu,
Zak Loring,
Linus G Andersson,
Terry F Frank,
Gary Gerstenblith,
Gordon F Tomaselli, Robert G Weiss,
Galen S Wagner,
Martin Ugander,
David G Strauss
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ABSTRACT: INTRODUCTION: Outcome of cardiac resynchronization therapy is severely worsened by myocardial scar at the left ventricular (LV) pacing site. We aimed to describe the diagnostic performance of electrocardiographic (ECG) criteria based on the Selvester QRS scoring system, first in localizing myocardial scar and second in screening for any non-septal scar in patients with strictly defined LBBB. METHODS AND RESULTS: In 39 cardiomyopathy patients with LBBB, 17 with scar, 22 without scar, late gadolinium-enhancement cardiac magnetic resonance images (CMR-LGE) and 12-lead ECGs were analyzed for scar presence in 5 LV wall segments. The ECG criteria with the best diagnostic performance in detecting scar in each segment and in the four non-septal segments together were identified. Criteria for detecting non-septal scar had 75% (95% CI: 51%-90%) sensitivity, 95% (78%-99%) specificity, 92% (67%-99%) positive predictive value and 84% (65%-94%) negative predictive value. For each individual wall segment, 40%-60% sensitivities and 77%-100% specificities were found. CONCLUSIONS: The 12-lead ECG can convey information about scar presence and location in this population of cardiomyopathy patients with LBBB. ECG screening criteria for scar in potential CRT LV pacing sites were identified. Further exploration is required to determine the clinical utility of the 12-lead ECG in combination with other imaging modalities to screen for scar in potential LV pacing sites in CRT candidates.
Journal of electrocardiology 03/2013; · 1.08 Impact Factor
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ABSTRACT: BACKGROUND: Recent meta-analyses suggest that the effectiveness of cardiac devices may differ between genders. Compared to men, women may not benefit as much from implantable defibrillators (ICDs), yet benefit more from cardiac resynchronization therapy (CRT). Myocardial scar burden is associated with increased incidence of appropriate ICD shocks but decreased response to CRT and may explain gender differences in device benefit. OBJECTIVE: To test the hypothesis that the extent of myocardial scar is less in women than men. METHODS: In 235 patients referred for primary prevention ICDs who underwent cardiac magnetic resonance imaging, we compared scar size by gender. Analyses were performed for all patients (ICD cohort) and those receiving biventricular pacemakers (CRT subgroup). RESULTS: In the ICD cohort, women (vs. men) had a higher prevalence of non-ischemic cardiomyopathy (NICM, 64% vs. 39%, p<0.001) which accounted for a smaller overall scar burden (0.5% vs 13%, p<0.01). Likewise, in the CRT subgroup, the higher prevalence of NICM in women (83% vs. 46%, p=0.01) also contributed to a smaller scar size (0 vs 13%, p<0.01). Women also had significantly less scarring of the inferolateral LV wall. CONCLUSIONS: In a cohort of patients undergoing clinically indicated ICD and CRT, women had less myocardial scar than men. This difference was primarily driven by a higher prevalence of NICM in women. These findings may have important implications for the future study of gender disparities in ICD and CRT outcomes.
Heart rhythm: the official journal of the Heart Rhythm Society 01/2013; · 4.56 Impact Factor
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ABSTRACT: Magnetic resonance imaging (MRI) has emerged as a powerful and reliable tool to non-invasively study the cardiovascular system in clinical practice. Because transgenic mouse models have assumed a critical role in cardiovascular research, technological advances in MRI have been extended to mice over the last decade. These have provided critical insights into cardiac and vascular morphology, function, and physiology/pathophysiology in many murine models of heart disease. Further, MR spectroscopy (MRS) has allowed the non-destructive study of myocardial metabolism in both isolated hearts and in intact mice. This article reviews the current techniques and important pathophysiologic insights from the application of MRI/MRS technology to murine models of cardiovascular disease.
AJP Heart and Circulatory Physiology 01/2013; · 3.71 Impact Factor
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ABSTRACT: Our objective is to test the hypothesis that coronary endothelial function (CorEndoFx) does not change with repeated isometric handgrip (IHG) stress in CAD patients or healthy subjects.
Coronary responses to endothelial-dependent stressors are important measures of vascular risk that can change in response to environmental stimuli or pharmacologic interventions. The evaluation of the effect of an acute intervention on endothelial response is only valid if the measurement does not change significantly in the short term under normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two coronary artery endothelial function measurements separated by a ten minute interval in healthy subjects and patients with coronary artery disease (CAD).
Twenty healthy adult subjects and 12 CAD patients were studied on a commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were quantified before and during continuous IHG stress, an endothelial-dependent stressor. The IHG exercise with imaging was repeated after a 10 minute recovery period.
In healthy adults, coronary artery CSA changes and blood-flow increases did not differ between the first and second stresses (mean % change ±SEM, first vs. second stress CSA: 14.8%±3.3% vs. 17.8%±3.6%, p = 0.24; PDFV: 27.5%±4.9% vs. 24.2%±4.5%, p = 0.54; blood-flow: 44.3%±8.3 vs. 44.8%±8.1, p = 0.84). The coronary vasoreactive responses in the CAD patients also did not differ between the first and second stresses (mean % change ±SEM, first stress vs. second stress: CSA: -6.4%±2.0% vs. -5.0%±2.4%, p = 0.22; PDFV: -4.0%±4.6% vs. -4.2%±5.3%, p = 0.83; blood-flow: -9.7%±5.1% vs. -8.7%±6.3%, p = 0.38).
MRI measures of CorEndoFx are unchanged during repeated isometric handgrip exercise tests in CAD patients and healthy adults. These findings demonstrate the repeatability of noninvasive 3T MRI assessment of CorEndoFx and support its use in future studies designed to determine the effects of acute interventions on coronary vasoreactivity.
PLoS ONE 01/2013; 8(3):e58047. · 4.09 Impact Factor
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ABSTRACT: In coronary magnetic resonance angiography, a magnetization-preparation scheme for T(2) -weighting (T(2) Prep) is widely used to enhance contrast between the coronary blood-pool and the myocardium. This prepulse is commonly applied without spatial selection to minimize flow sensitivity, but the nonselective implementation results in a reduced magnetization of the in-flowing blood and a related penalty in signal-to-noise ratio. It is hypothesized that a spatially selective T(2) Prep would leave the magnetization of blood outside the T(2) Prep volume unaffected and thereby lower the signal-to-noise ratio penalty. To test this hypothesis, a spatially selective T(2) Prep was implemented where the user could freely adjust angulation and position of the T(2) Prep slab to avoid covering the ventricular blood-pool and saturating the in-flowing spins. A time gap of 150 ms was further added between the T(2) Prep and other prepulses to allow for in-flow of a larger volume of unsaturated spins. Consistent with numerical simulation, the spatially selective T(2) Prep increased in vivo human coronary artery signal-to-noise ratio (42.3 ± 2.9 vs. 31.4 ± 2.2, n = 22, P < 0.0001) and contrast-to-noise-ratio (18.6 ± 1.5 vs. 13.9 ± 1.2, P = 0.009) as compared to those of the nonselective T(2) Prep. Additionally, a segmental analysis demonstrated that the spatially selective T(2) Prep was most beneficial in proximal and mid segments where the in-flowing blood volume was largest compared to the distal segments. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 08/2012; · 2.96 Impact Factor
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ABSTRACT: Reduced myofibrillar ATP availability during prolonged myocardial ischemia may limit post-ischemic mechanical function. Because creatine kinase (CK) is the prime energy reserve reaction of the heart and because it has been difficult to augment ATP synthesis during and after ischemia, we used mice that overexpress the myofibrillar isoform of creatine kinase (CKM) in cardiac-specific, conditional fashion to test the hypothesis that CKM overexpression increases ATP delivery in ischemic-reperfused hearts and improves functional recovery. Isolated, retrograde-perfused hearts from control and CKM mice were subjected to 25 min of global, no-flow ischemia and 40 min of reperfusion while cardiac function [rate pressure product (RPP)] was monitored. A combination of (31)P-nuclear magnetic resonance experiments at 11.7T and biochemical assays was used to measure the myocardial rate of ATP synthesis via CK (CK flux) and intracellular pH (pH(i)). Baseline CK flux was severalfold higher in CKM hearts (8.1 ± 1.0 vs. 32.9 ± 3.8, mM/s, control vs. CKM; P < 0.001) with no differences in phosphocreatine concentration [PCr] and RPP. End-ischemic pH(i) was higher in CKM hearts than in control hearts (6.04 ± 0.12 vs. 6.37 ± 0.04, control vs. CKM; P < 0.05) with no differences in [PCr] and [ATP] between the two groups. Post-ischemic PCr (66.2 ± 1.3 vs. 99.1 ± 8.0, %preischemic levels; P < 0.01), CK flux (3.2 ± 0.4 vs. 14.0 ± 1.2 mM/s; P < 0.001) and functional recovery (13.7 ± 3.4 vs. 64.9 ± 13.2%preischemic RPP; P < 0.01) were significantly higher and lactate dehydrogenase release was lower in CKM than in control hearts. Thus augmenting cardiac CKM expression attenuates ischemic acidosis, reduces injury, and improves not only high-energy phosphate content and the rate of CK ATP synthesis in postischemic myocardium but also recovery of contractile function.
AJP Heart and Circulatory Physiology 08/2012; 303(7):H844-52. · 3.71 Impact Factor
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Circulation Cardiovascular Imaging 07/2012; 5(4):e53. · 5.94 Impact Factor
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ABSTRACT: Speed and signal-to-noise ratio (SNR) are critical for localized magnetic resonance spectroscopy (MRS) of low-concentration metabolites. Matching voxels to anatomical compartments a priori yields better SNR than the spectra created by summing signals from constituent chemical-shift-imaging (CSI) voxels post-acquisition. Here, a new method of localized Spectroscopy using Linear Algebraic Modeling (SLAM) is presented, that can realize this additional SNR gain. Unlike prior methods, SLAM generates spectra from C signal-generating anatomic compartments utilizing a CSI sequence wherein essentially only the C central k-space phase-encoding gradient steps with highest SNR are retained. After MRI-based compartment segmentation, the spectra are reconstructed by solving a sub-set of linear simultaneous equations from the standard CSI algorithm. SLAM is demonstrated with one-dimensional CSI surface coil phosphorus MRS in phantoms, the human leg and the heart on a 3T clinical scanner. Its SNR performance, accuracy, sensitivity to registration errors and inhomogeneity, are evaluated. Compared to one-dimensional CSI, SLAM yielded quantitatively the same results 4-times faster in 24 cardiac patients and healthy subjects. SLAM is further extended with fractional phase-encoding gradients that optimize SNR and/or minimize both inter- and intra-compartmental contamination. In proactive cardiac phosphorus MRS of six healthy subjects, both SLAM and fractional-SLAM (fSLAM) produced results indistinguishable from CSI while preserving SNR gains of 36-45% in the same scan-time. Both SLAM and fSLAM are simple to implement and reduce the minimum scan-time for CSI, which otherwise limits the translation of higher SNR achievable at higher field strengths to faster scanning.
Journal of Magnetic Resonance 05/2012; 218:66-76. · 2.14 Impact Factor
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ABSTRACT: Coronary endothelial function is abnormal in patients with established coronary artery disease and was recently shown by MRI to relate to the severity of luminal stenosis. Recent advances in MRI now allow the noninvasive assessment of both anatomic and functional (endothelial function) changes that previously required invasive studies. We tested the hypothesis that abnormal coronary endothelial function is related to measures of early atherosclerosis such as increased coronary wall thickness.
Seventeen arteries in 14 healthy adults and 17 arteries in 14 patients with nonobstructive coronary artery disease were studied. To measure endothelial function, coronary MRI was performed before and during isometric handgrip exercise, an endothelial-dependent stressor, and changes in coronary cross-sectional area and flow were measured. Black blood imaging was performed to quantify coronary wall thickness and indices of arterial remodeling. The mean stress-induced change in cross-sectional area was significantly higher in healthy adults (13.5%±12.8%, mean±SD, n=17) than in those with mildly diseased arteries (-2.2%±6.8%, P<0.0001, n=17). Mean coronary wall thickness was lower in healthy subjects (0.9±0.2 mm) than in patients with coronary artery disease (1.4±0.3 mm, P<0.0001). In contrast to healthy subjects, stress-induced changes in cross-sectional area, a measure of coronary endothelial function, correlated inversely with coronary wall thickness in patients with coronary artery disease (r=-0.73, P=0.0008).
There is an inverse relationship between coronary endothelial function and local coronary wall thickness in patients with coronary artery disease but not in healthy adults. These findings demonstrate that local endothelial-dependent functional changes are related to the extent of early anatomic atherosclerosis in mildly diseased arteries. This combined MRI approach enables the anatomic and functional investigation of early coronary disease.
Circulation Cardiovascular Imaging 04/2012; 5(3):341-8. · 5.94 Impact Factor
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ABSTRACT: This study tested the hypothesis that acute administration of the xanthine oxidase (XO) inhibitor allopurinol improves cardiac high-energy phosphate concentrations in human heart failure (HF) and increases the rate of adenosine triphosphate (ATP) synthesis through creatine kinase (CK), the primary myocardial energy reserve.
Studies of patients and animal models implicate impaired myocardial high-energy phosphate availability in HF. The XO reaction is a critical terminal step in ATP and purine degradation and an important source of reactive oxygen species. Thus, XO inhibition is a potentially attractive means to improve energy metabolism in the failing human heart.
We randomized 16 patients with nonischemic cardiomyopathy in a double-blind fashion to allopurinol (300 mg intravenously) or placebo infusion, 4-to-1, the latter for purposes of blinding only. The myocardial concentrations of ATP and creatine phosphate (PCr) and the rate of ATP synthesis through CK (CK flux) were determined by (31)P magnetic resonance spectroscopy.
Allopurinol infusion increased mean cardiac PCr/ATP and PCr concentration by ∼11% (p < 0.02), and mean CK flux by 39% (2.07 ± 1.27 μmol/g/s to 2.87 ± 1.82 μmol/g/s, p < 0.007). Calculated cytosolic adenosine diphosphate concentration decreased, whereas the free energy of ATP hydrolysis (ΔG(∼ATP)) increased with allopurinol. The increased CK flux was disproportionate to substrate changes, indicating increased CK enzyme activity.
Intravenous administration of the XO inhibitor allopurinol acutely improves the relative and absolute concentrations of myocardial high-energy phosphates and ATP flux through CK in the failing human heart, offering direct evidence that myofibrillar CK energy delivery can be pharmaceutically augmented in the failing human heart. (Intravenous Allopurinol in Heart Failure; NCT00181155).
Journal of the American College of Cardiology 02/2012; 59(9):802-8. · 14.16 Impact Factor
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Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:P74. · 3.72 Impact Factor
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Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:P73. · 3.72 Impact Factor
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Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:O52. · 3.72 Impact Factor
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ABSTRACT: Annually, ≈80,000 Americans receive guideline-based primary prevention implantable cardioverter-defibrillators (ICDs), but appropriate firing rates are low. Current selection criteria for ICDs rely on left ventricular ejection fraction, which lacks sensitivity and specificity. Because scar-related myocardial tissue heterogeneity is a substrate for life-threatening arrhythmias, we hypothesized that cardiac magnetic resonance identification of myocardial heterogeneity improves risk stratification through (1) its association with adverse cardiac events independent of clinical factors and biomarker levels and (2) its ability to identify particularly high- and low-risk subgroups.
In 235 patients with chronic ischemic and nonischemic cardiomyopathy with a left ventricular ejection fraction of ≤35% undergoing clinically indicated primary prevention ICD implantation, gadolinium-enhanced cardiac magnetic resonance was prospectively performed to quantify the amount of heterogeneous myocardial tissue (gray zone [GZ]) and dense core scar. Serum high-sensitivity C-reactive protein (hsCRP) and other biomarkers were assayed. The primary end point was appropriate ICD shock for ventricular tachycardia/fibrillation or cardiac death, which occurred in 45 (19%) patients at a 3.6-year median follow-up. On univariable analysis, only diuretics, hsCRP, GZ, and core scar were associated with outcome. After multivariable adjustment, GZ and hsCRP remained independently associated with outcome (P<0.001). Patients in the lowest tertile for both GZ and hsCRP (n=42) were at particularly low risk (0.7% per year event rate), whereas those in the highest tertile for both GZ and hsCRP (n=32) had an event rate of 16.1% per year, P<0.001.
In a cohort of primary prevention ICD candidates, combining a myocardial heterogeneity index with an inflammatory biomarker identified a subgroup with a very low risk for adverse cardiac events, including ventricular arrhythmias. This novel approach warrants further investigation to confirm its value as a clinical risk stratification tool. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00181233.
Circulation Cardiovascular Imaging 01/2012; 5(2):178-86. · 5.94 Impact Factor
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ABSTRACT: Takayasu arteritis (TA) is a rare form of chronic inflammatory granulomatous arteritis of the aorta and its major branches. Late gadolinium enhancement (LGE) with magnetic resonance imaging (MRI) has demonstrated its value for the detection of vessel wall alterations in TA. The aim of this study was to assess LGE of the coronary artery wall in patients with TA compared to patients with stable CAD.
We enrolled 9 patients (8 female, average age 46±13 years) with proven TA. In the CAD group 9 patients participated (8 male, average age 65±10 years). Studies were performed on a commercial 3T whole-body MR imaging system (Achieva; Philips, Best, The Netherlands) using a 3D inversion prepared navigator gated spoiled gradient-echo sequence, which was repeated 34-45 minutes after low-dose gadolinium administration.
No coronary vessel wall enhancement was observed prior to contrast in either group. Post contrast, coronary LGE on IR scans was detected in 28 of 50 segments (56%) seen on T2-Prep scans in TA and in 25 of 57 segments (44%) in CAD patients. LGE quantitative assessment of coronary artery vessel wall CNR post contrast revealed no significant differences between the two groups (CNR in TA: 6.0±2.4 and 7.3±2.5 in CAD; p = 0.474).
Our findings suggest that LGE of the coronary artery wall seems to be common in patients with TA and similarly pronounced as in CAD patients. The observed coronary LGE seems to be rather unspecific, and differentiation between coronary vessel wall fibrosis and inflammation still remains unclear.
PLoS ONE 01/2012; 7(12):e50655. · 4.09 Impact Factor
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ABSTRACT: Magnetic resonance angiography (MRA) provides a noninvasive means to detect the presence, location and severity of atherosclerosis throughout the vascular system. In such studies, and especially those in the coronary arteries, the vessel luminal area is typically measured at multiple cross-sectional locations along the course of the artery. The advent of fast volumetric imaging techniques covering proximal to mid segments of coronary arteries necessitates automatic analysis tools requiring minimal manual interactions to robustly measure cross-sectional area along the three-dimensional track of the arteries in under-sampled and non-isotropic datasets. In this work, we present a modular approach based on level set methods to track the vessel centerline, segment the vessel boundaries, and measure transversal area using two user-selected endpoints in each coronary of interest. Arterial area and vessel length are measured using our method and compared to the standard Soap-Bubble reformatting and analysis tool in in-vivo non-contrast enhanced coronary MRA images.
Proceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on Biomedical Imaging 01/2012;
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Ashish Gupta,
Ashwin Akki,
Yibin Wang,
Michelle K Leppo,
V P Chacko,
D Brian Foster,
Viviane Caceres,
Sa Shi,
Jonathan A Kirk,
Jason Su,
Shenghan Lai,
Nazareno Paolocci,
Charles Steenbergen,
Gary Gerstenblith, Robert G Weiss
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ABSTRACT: ATP is required for normal cardiac contractile function, and it has long been hypothesized that reduced energy delivery contributes to the contractile dysfunction of heart failure (HF). Despite experimental and clinical HF data showing reduced metabolism through cardiac creatine kinase (CK), the major myocardial energy reserve and temporal ATP buffer, a causal relationship between reduced ATP-CK metabolism and contractile dysfunction in HF has never been demonstrated. Here, we generated mice conditionally overexpressing the myofibrillar isoform of CK (CK-M) to test the hypothesis that augmenting impaired CK-related energy metabolism improves contractile function in HF. CK-M overexpression significantly increased ATP flux through CK ex vivo and in vivo but did not alter contractile function in normal mice. It also led to significantly increased contractile function at baseline and during adrenergic stimulation and increased survival after thoracic aortic constriction (TAC) surgery-induced HF. Withdrawal of CK-M overexpression after TAC resulted in a significant decline in contractile function as compared with animals in which CK-M overexpression was maintained. These observations provide direct evidence that the failing heart is "energy starved" as it relates to CK. In addition, these data identify CK as a promising therapeutic target for preventing and treating HF and possibly diseases involving energy-dependent dysfunction in other organs with temporally varying energy demands.
The Journal of clinical investigation 12/2011; 122(1):291-302. · 15.39 Impact Factor
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ABSTRACT: The purpose of this study was to improve the blood-pool signal-to-noise ratio (SNR) and blood-myocardium contrast-to-noise ratio (CNR) of slow-infusion 3-T whole-heart coronary MR angiography (MRA).
In 2D sensitivity encoding (SENSE), the number of acquired k-space lines is reduced, allowing less radiofrequency excitation per cardiac cycle and a longer TR. The former can be exploited for signal enhancement with a higher radiofrequency excitation angle, and the latter leads to noise reduction due to lower data-sampling bandwidth. Both effects contribute to SNR gain in coronary MRA when spatial and temporal resolution and acquisition time remain identical. Numeric simulation was performed to select the optimal 2D SENSE pulse sequence parameters and predict the SNR gain. Eleven patients underwent conventional unenhanced and the proposed 2D SENSE contrast-enhanced coronary MRA acquisition. Blood-pool SNR, blood-myocardium CNR, visible vessel length, vessel sharpness, and number of side branches were evaluated.
Consistent with the numeric simulation, using 2D SENSE in contrast-enhanced coronary MRA resulted in significant improvement in aortic blood-pool SNR (unenhanced vs contrast-enhanced, 37.5 ± 14.7 vs 121.3 ± 44.0; p < 0.05) and CNR (14.4 ± 6.9 vs 101.5 ± 40.8; p < 0.05) in the patient sample. A longer length of left anterior descending coronary artery was visualized, but vessel sharpness, coronary artery coverage, and image quality score were not improved with the proposed approach.
In combination with contrast administration, 2D SENSE was found effective in improving SNR and CNR in 3-T whole-heart coronary MRA. Further investigation of cardiac motion compensation is necessary to exploit the SNR and CNR advantages and to achieve submillimeter spatial resolution.
American Journal of Roentgenology 08/2011; 197(2):374-82. · 2.78 Impact Factor
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Sebastian Kelle,
Allison G Hays,
Glenn A Hirsch,
Gary Gerstenblith,
Julie M Miller,
Angela M Steinberg,
Michael Schär,
John H Texter,
Ernst Wellnhofer, Robert G Weiss,
Matthias Stuber
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ABSTRACT: Coronary vessel distensibility is reduced with atherosclerosis and normal aging, but direct measurements have historically required invasive measurements at cardiac catheterization. Therefore, we sought to assess coronary artery distensibility noninvasively using 3.0 Telsa coronary magnetic resonance imaging (MRI) and to test the hypothesis that this noninvasive technique can detect differences in coronary distensibility between healthy subjects and those with coronary artery disease (CAD). A total of 38 healthy, adult subjects (23 men, mean age 31 ± 10 years) and 21 patients with CAD, diagnosed using x-ray angiography (11 men, mean age 57 ± 6 years) were studied using a commercial whole-body MRI system. In each subject, the proximal segment of a coronary artery was imaged for the cross-sectional area measurements using cine spiral MRI. The distensibility (mm Hg(-1) × 10(3)) was determined as (end-systolic lumen area - end-diastolic lumen area)/(pulse pressure × end-diastolic lumen area). The pulse pressure was calculated as the difference between the systolic and diastolic brachial blood pressure. A total of 34 healthy subjects and 19 patients had adequate image quality for coronary area measurements. Coronary artery distensibility was significantly greater in the healthy subjects than in those with CAD (mean ± SD 2.4 ± 1.7 mm Hg(-1) × 10(3) vs 1.1 ± 1.1 mm Hg(-1) × 10(3), respectively, p = 0.007; median 2.2 vs 0.9 mm Hg(-1) × 10(3)). In a subgroup of 10 patients with CAD, we found a significant correlation between the coronary artery distensibility measurements assessed using MRI and x-ray coronary angiography (R = 0.65, p = 0.003). In a group of 10 healthy subjects, the repeated distensibility measurements demonstrated a significant correlation (R = 0.80, p = 0.006). In conclusion, 3.0-Tesla MRI, a reproducible noninvasive method to assess human coronary artery vessel wall distensibility, is able to detect significant differences in distensibility between healthy subjects and those with CAD.
The American journal of cardiology 05/2011; 108(4):491-7. · 3.58 Impact Factor
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ABSTRACT: The creatine kinase (CK) reaction is central to muscle energetics, buffering ATP levels during periods of intense activity via consumption of phosphocreatine (PCr). PCr is believed to serve as a spatial shuttle of high-energy phosphate between sites of energy production in the mitochondria and sites of energy utilization in the myofibrils via diffusion. Knowledge of the diffusion coefficient of PCr (D(PCr)) is thus critical for modeling and understanding energy transport in the myocyte, but D(PCr) has not been measured in humans. Using localized phosphorus magnetic resonance spectroscopy, we measured D(PCr) in the calf muscle of 11 adults as a function of direction and diffusion time. The results show that the diffusion of PCr is anisotropic, with significantly higher diffusion along the muscle fibers, and that the diffusion of PCr is restricted to a ∼28-μm pathlength assuming a cylindrical model, with an unbounded diffusion coefficient of ∼0.69 × 10(-3) mm(2)/s. This distance is comparable in size to the myofiber radius. On the basis of prior measures of CK reaction kinetics in human muscle, the expected diffusion distance of PCr during its half-life in the CK reaction is ∼66 μm. This distance is much greater than the average distances between mitochondria and myofibrils. Thus these first measurements of PCr diffusion in human muscle in vivo support the view that PCr diffusion is not a factor limiting high-energy phosphate transport between the mitochondria and the myofibrils in healthy resting myocytes.
AJP Cell Physiology 03/2011; 301(1):C234-41. · 3.54 Impact Factor
