Exercise training increases heat shock protein in skeletal muscles of old rats

PURPOSE: The effects of chronic exercise training on the expression of heat shock protein (HSP) in skeletal muscle of senescent animals are unknown. Therefore, the purpose of this study was to investigate the effects of chronic exercise training on skeletal muscle HSP expression in both young and old rats. METHODS: Young adult (3 months) and old (23 months) female Fisher 344 rats were assigned to either a sedentary control or an endurance exercise trained group (N = 6 per group). Exercised animals ran (60 min.d-1, 5 d.wk-1) on a treadmill at approximately 77% VO2peak for 10 wk. After completion of the training program, the soleus (SOL), plantaris (PL), and the red (RG) and white portions (WG) of the gastrocnemius muscles were excised, and citrate synthase (CS) activity and the relative levels of HSP72 were determined. RESULTS: Training resulted in increases (P < 0.05) in VO2peak in both young (67.6 +/- 3.1 vs 86.9 +/- 1.6 mL.kg-1.min-1) and old animals (54.5 +/- 1.8 vs 68.2 +/- 2.2 mL.kg-1.min-1). Training increased CS activity and the relative levels of HSP72 (P < 0.05) in all four skeletal muscles in both young and old animals. Specifically, compared with age-matched sedentary controls, exercise training resulted in increased (P < 0.05) levels of HSP72 in skeletal muscles of both young (SOL + 22%, PL +94%, RG + 44%, WG + 243%) and old animals (SOL +15%, PL +73%, RG +38%, WG +150%). CONCLUSIONS: These findings reveal that the exercise-induced accumulation of HSP72 in skeletal muscle differs between fast and slow muscles. Further, these data indicate that the exercise-induced accumulation of HSP72 in highly oxidative skeletal muscles (SOL and RG) is similar between young and old animals. In contrast, aging is associated with a blunted expression of HSP72 in fast skeletal muscles (PL and WG) in response to chronic exercise.     

Investigation and optimization of parameter accuracy in dynamic contrast-enhanced MRI

PURPOSE: To present a modified pharmacokinetic model for improved parameter accuracy and to investigate the influence of an inaccurate arterial input function (AIF) on dynamic contrast-enhanced (DCE)-MRI parameter estimates of the transfer constant (Ktrans), blood volume (vp), and interstitial volume (ve). MATERIALS AND METHODS: Tissue uptake curves were simulated over a large range of physiological values and analyzed for different AIF measurement errors and temporal resolutions. The AIF measurement was assumed to be inaccurate in the bolus amplitude (rapid sampling) or susceptible to unknown temporal offsets (slow sampling with biexponential decay fit). RESULTS: The modified model adequately reduces errors in parameter estimates arising from transit time effects. An error in the AIF bolus amplitude results in an inversely proportional error in Ktrans and vp; ve remains robust. More consistent error in Ktrans (approximately 20% underestimation) was obtained using a biexponential AIF, at the expense of severely underestimating vp. CONCLUSION: While an accurate, high temporal resolution AIF is essential for estimating vp, a biexponential AIF acquired at low temporal resolution (<20 seconds) provides robust estimates of ve and results in a Ktrans underestimation comparable to that from a 25% error in the initial AIF bolus amplitude.     

Inflammation in carotid atherosclerotic plaque: a dynamic contrast-enhanced MR imaging study

PURPOSE: To prospectively evaluate if there is an association between plaque enhancement at magnetic resonance (MR) imaging and proinflammatory cardiovascular risk factors and plaque content. MATERIALS AND METHODS: This study was performed with informed consent, HIPAA compliance, and institutional review board approval. Contrast agent dynamics within carotid plaques were measured in 30 patients (29 men, one woman; mean age, 67.7 years +/- 10.7 [standard deviation]) who were scheduled to undergo carotid endarterectomy. Measurements were based on kinetic modeling of images obtained at 15-second intervals during which a gadolinium-based contrast agent was injected. The time-varying signal intensities within the plaques were used to estimate the fractional plasma volume (vp) and transfer constant (Ktrans) of contrast material into the extracellular space. Pearson correlation coefficients were computed between blinded MR measurements and histologic measurements of plaque composition, including macrophages, neovasculature, necrotic core, calcification, loose matrix, and dense fibrous tissue. Correlation coefficients or mean differences were computed regarding clinical markers of cardiovascular risk. RESULTS: Analyzable MR images and histologic results were obtained in 27 patients. Measurements of Ktrans correlated with macrophage (r = 0.75, P < .001), neovasculature (r = 0.71, P < .001), and loose matrix (r = 0.50, P = .01) content. Measurements of v(p) correlated with macrophage (r = 0.54, P = .004), neovasculature (r = 0.68, P < .001), and loose matrix (r = 0.42, P = .03) content. For clinical parameters, significant associations were correlated with Ktrans only, with decreased high-density lipoprotein levels (r = -0.66, P < .001) and elevated Ktrans measurements in smokers compared with nonsmokers (mean, 0.134 min(-1) vs 0.074 min(-1), respectively; P = .01). CONCLUSION: The correlations between Ktrans and histologic markers of inflammation suggest that Ktrans is a quantitative and noninvasive marker of plaque inflammation, which is further supported by the correlation of Ktrans with proinflammatory cardiovascular risk factors, decreased high-density lipoprotein levels, and smoking.     

Ovariectomy, hindlimb unweighting, and recovery effects on skeletal muscle in adult rats

INTRODUCTION: The effect of female sex hormones on skeletal muscle is unclear. Reports suggest that female sex hormones have an anabolic effect, have no effect, or are detrimental to skeletal muscle. METHODS: To amplify ovarian hormones' potential effects on skeletal muscle, 6-mo-old virgin intact (sham), ovariectomized (OVX), and ovariectomized plus estrogen (OVX + E2) rats were hindlimb unweighted (HLU) for 4 wk. To investigate estrogen's influence on the recovery process, OVX-HLU, sham-HLU and OVX + E2 HLU rats were cage-recovered for 2 wk following 4 wk of HLU. Changes in muscle mass were determined for the soleus (SOL), extensor digitorum longus (EDL), quadriceps (QUAD), gastrocnemius (GAST), tibialis anterior (TA), plantaris (PLA), and flexor carpi radialis (FCR). Dry weights were determined for GAST and TA. Peak tetanic tension was ascertained in the postural SOL and locomotor PLA. RESULTS: HLU resulted in a significant (p < 0.05) decline in mass of all muscles studied except EDL and FCR. The magnitude of atrophy resulting from suspension was similar between groups including wet and dry muscle mass normalized to bodyweight. Following HLU there were no differences between intact and OVX rats for contractile characteristics. Reloading for 2 wk resulted in recovery of wet muscle mass in intact and OVX + E2 rats for SOL, PLA, GAST, QUAD, and TA and in dry mass for GAST and TA. Reloaded OVX-HLU rats failed to recover wet muscle mass in all but the SOL and failed to recover GAST and TA dry weight. For example, PLA mass values for intact (sham) rats were 350 +/- 33, 284 +/- 41, and 346 +/- 44 mg for the control, HLU, and recovery groups, respectively. PLA values for OVX rats were 378 +/- 29, 316 +/- 30, and 325 +/- 23 mg for the control, HLU, and recovery groups. DISCUSSION: Results suggest that ovarian function influences the recovery of skeletal muscle mass following a period of reduced physical activity.     

Contrast agent-enhanced, free-breathing, three-dimensional coronary magnetic resonance angiography.

For free-breathing, high-resolution, three-dimensional coronary magnetic resonance angiography (MRA), the use of intravascular contrast agents may be helpful for contrast enhancement between coronary blood and myocardium. In six patients, 0.1 mmol/kg of the intravascular contrast agent MS-325/AngioMARK was given intravenously followed by double-oblique, free-breathing, three-dimensional inversion-recovery coronary MRA with real-time navigator gating and motion correction. Contrast-enhanced, three-dimensional coronary MRA images were compared with images obtained with a T2 prepulse (T2Prep) without exogenous contrast. The contrast-enhanced images demonstrated a 69% improvement in the contrast-to-noise ratio (6.6 +/- 1.1 vs. 11.1 +/- 2.5; P < 0.01) compared with the T2Prep approach. By using the intravascular agent, extensive portions (> 80 mm) of the native left and right coronary system could be displayed consistently with sub-millimeter in-plane resolution. The intravascular contrast agent, MS-325/AngioMARK, leads to a considerable enhancement of the blood/muscle contrast for coronary MRA compared with T2Prep techniques. The clinical value of the agent remains to be defined in a larger patient series. J. Magn. Reson. Imaging 1999;10:790-799.     

Intravascular susceptibility agent effects on tissue transverse relaxation rates in vivo.

Since vascular architecture differs among tissues, it was hypothesized that the change in transverse relaxation rate produced by a given tissue concentration of susceptibility contrast agent also varies by tissue. This is relevant to strategies to map regional blood volume by MRI using indicator dilution techniques. R*(2) was measured in rat organs over a range of susceptibility agent concentrations at 1.5 T. Rat red blood cells loaded with dysprosium-DTPA-BMA served as an intravascular susceptibility agent. Tissue samples were frozen in vivo and dysprosium concentrations were independently measured using inductively coupled plasma atomic emission spectroscopy. The slope (k) of R*(2) vs. tissue dysprosium concentration in sec(-1) mM(-1) for myocardium was 97.1 (95% C.I. 77. 0-117.2), liver 122.6 (108.3-136.9), spleen 22.5 (8.8-36.3), kidney 68.1 (58.6-77.6), and skeletal muscle 77.9 (4.1-151.6); k was significantly different (P < 0.05) for all pairings except those with skeletal muscle. Therefore, relative values of tissue blood volume derived from dynamic images of first pass contrast effects may be in error because k is not constant for different conditions.     

Dynamic MRI for imaging tumor microvasculature: comparison of susceptibility and relaxivity techniques in pelvic tumors

PURPOSE: To assess the reproducibility of intrinsic relaxivity and both relaxivity- and susceptibility-based dynamic contrast enhanced (DCE) MRI in pelvic tumors; to correlate kinetic parameters obtained and to assess whether acute antivascular effects are seen in response to cisplatin- or taxane-based chemotherapy. MATERIALS AND METHODS: T1-weighted and T2*-weighted DCE-MRI and basal R2* measurements were performed on three consecutive days in women with gynecological tumors. The third scan was 21.0 (range 17.3-23.5) hours after the first cycle of chemotherapy. Kinetic parameter estimates were obtained and correlated between techniques. Test-retest reproducibility and response to treatment were assessed. RESULTS: Relative blood volume (rBV) and relative blood flow (rBF) correlated strongly with transfer constant (Ktrans), kep, and the initial area under the gadopentetate dimeglumine (Gd-DTPA) concentration-time curve (IAUGC) (all P<0.01). The group 95% confidence interval (CI) for change was -10.8 to +12.1%; +/-5.1%; -9.5 to +10.5%; +/-7.5%; for Ktrans, ve, kep, and IAUGC, respectively, and +/-13.6%, +/-2.4%, +/-11.6%, and +/-11.0%, for rBV, mean transit time (MTT), rBF, and R2*, respectively. There were no significant acute changes in kinetic parameter estimates in response to treatment on group analysis, apart from a small decrease in ve. CONCLUSION: The results confirm the dominant influence of flow on Ktrans in untreated gynecological tumors. There is no evidence of an acute, large magnitude antivascular effect caused by cisplatin- or taxane-based chemotherapy.     

Capillarization in skeletal muscle of rats with cardiac hypertrophy

PURPOSE: Exercise intolerance during chronic heart failure (CHF) is localized mainly in skeletal muscle. A decreased capillarization may impair exchange of oxygen between capillaries and muscle tissue and in this way contribute to exercise intolerance. We assessed changes in capillary supply in plantaris and diaphragm muscles of a rat aorta-caval fistula (ACF) preparation, a volume overload model for CHF. METHODS: An ACF was created under equithesin anesthesia. Plantaris and diaphragm muscles were removed 6 wk postsurgery and examined for myosin heavy chain (MyHC) content and capillary supply. RESULTS: Cardiac hypertrophy was 96% (P < 0.002) after ACF. The Type IIb MyHC content of the plantaris muscles increased (33.9 +/- 3.3 vs 49.8 +/- 3.8%; mean +/- SEM) at the expense of Type IIa MyHC (17.6 +/- 1.8 vs 11.2 +/- 1.7%) in ACF rats (P < 0.05). In the diaphragm, the number of Type I (32.1 +/- 2.3 vs 40.6 +/- 2.7%) and IIb fibers (40.6 +/- 1.9 vs 49.6 +/- 3.6%) increased at the expense of Type IIa fibers (26.8 +/- 2.5 vs 9.4 +/- 0.9%) (P < 0.05). The capillary number per fiber did not change, and this indicated that no capillary loss occurred with ACF. Also, the capillary density was maintained in the diaphragm and plantaris muscles of ACF rats. Furthermore, the coupling between fiber type, size, and metabolic type of surrounding fibers, with the capillary supply to a fiber, was maintained in rats with an ACF. CONCLUSION: The cardiac hypertrophy induced by volume overload seems adequate to prevent atrophy and changes in the microcirculation of limb and diaphragm muscles.     

Cardiac cine MRI: comparison of 1.5 T, non-enhanced 3.0 T and blood pool enhanced 3.0 T imaging

INTRODUCTION: Cardiac cine imaging using balanced steady state free precession sequences (bSSFP) suffers from artefacts at 3.0 T. We compared bSSFP cardiac cine imaging at 1.5 T with gradient echo imaging at 3.0 T with and without a blood pool contrast agent. MATERIALS AND METHODS: Eleven patients referred for cardiac cine imaging underwent imaging at 1.5 T and 3.0 T. At 3.0 T images were acquired before and after administration of 0.03 mmol/kg gadofosveset. Blood pool signal-to-noise ratio (SNR), temporal variations in SNR, ejection fraction and myocardial mass were compared. Subjective image quality was scored on a four-point scale. RESULTS: Blood pool SNR increased with more than 75% at 3.0 T compared to 1.5 T (p<0.001); after contrast administration at 3.0 T SNR increased with 139% (p<0.001). However, variations in blood pool SNR at 3.0 T were nearly three times as high versus those at 1.5 T in the absence of contrast medium (p<0.001); after contrast administration this was reduced to approximately a factor 1.4 (p=0.21). Saturation artefacts led to significant overestimation of ejection fraction in the absence of contrast administration (1.5 T: 44.7+/-3.1 vs. 3.0 T: 50.7+/-4.2 [p=0.04] vs. 3.0 T post contrast: 43.4+/-2.9 [p=0.55]). Subjective image quality was highest for 1.5 T (2.8+/-0.3), and lowest for non-enhanced 3.0 T (1.7+/-0.6; p=0.006). CONCLUSIONS: GRE cardiac cine imaging at 3.0 T after injection of the blood pool agent gadofosveset leads to improved objective and subjective cardiac cine image quality at 3.0 T and to the same conclusions regarding cardiac ejection fraction compared to bSSFP imaging at 1.5 T.     

Cine gradient refocused echo (GRE) imaging of intravascular masses: differentiation between tumor and nontumor thrombus.

Spin echo MR imaging has not permitted reliable differentiation between intraluminal blood clot and tumor thrombus. This study assessed the role of ECG referenced repetitive gradient refocused echo (cine GRE) imaging for the differentiation of intravascular tumor from blood clot. Cine GRE images were reviewed in 23 patients, 11 of whom had intravascular tumor and 12 of whom had intravascular blood clots. Percentage contrast between the lesion and skeletal muscle as the reference tissue was determined from a subjective review of the images and objective signal intensity measurements. Intravascular clots were found to be lower in signal intensity than muscle (mean -55 +/- 29%). Intravascular tumors showed higher signal intensity relative to muscle (mean +17 +/- 9%) with the exception of myxomas (n = 2), which had signal intensity values relative to muscle as low as clots (mean -41 +/- 17%). Three masses in the inferior vena cava were composed of central tumor and peripheral clot; the two components could be differentiated with cine GRE imaging. Cine GRE imaging provides adequate signal intensity differences to visualize intravascular masses and helps to differentiate intravascular clot from tumor thrombus. However, if the tumor contains substantial amounts of iron, then the signal is also low and consequently clot and thrombus may not be distinguishable. This can occur in some atrial myxomas.     

Hyperbaric oxygen increases the contractile function of regenerating rat slow muscles

Human trials of hyperbaric oxygen (HBO) treatment of sports-related muscle injuries are equivocal. Although most human skeletal muscles are composed of mixed muscle fiber types, it is unclear whether HBO affects fiber types differently. PURPOSE: We tested the hypothesis that HBO can enhance the functional properties of regenerating rat soleus muscles that are composed predominantly of slow fibers. METHODS: After intramuscular injection of bupivacaine hydrochloride to induce the degeneration of all fibers within the soleus muscle, treated rats received daily HBO treatment at 3 atmospheres absolute. RESULTS: In untreated rats, injured muscles demonstrated a reduced force-producing capacity (control soleus vs injured soleus, 220.3 +/- 2.5 vs 157.6 +/- 3.3 kN.m(-2) at 25 d postinjury, respectively, P < 0.05) and contained smaller regenerating muscle fibers than uninjured soleus muscles (fiber cross sectional area in control soleus vs injured soleus, 2289 +/- 164 vs 1154 +/- 92 microm 2 at 25 d postinjury, respectively, P < 0.05). The regenerating soleus muscles of HBO-treated rats demonstrated a greater force-producing capacity as a percentage of contralateral control muscles than the regenerating muscles from untreated rats at 14 d postinjury (regenerating HBO-soleus peak tension and untreated soleus peak tension, 42.9 +/- 1.9 and 35.8 +/- 3.9% of contralateral control muscles, respectively, P < 0.05), but no effect of treatment was observed at 25 d postinjury. CONCLUSION: HBO enhanced the contractile properties of regenerating rat soleus muscles after myotoxic injury, but this improvement was not sustained for the duration of the regenerative process. The data indicate that the outcome of HBO treatment of a muscle injury may be influenced by the fiber type composition of the injured muscle.     

Pharmacokinetic modeling of dynamic contrast-enhanced MRI of the hand and wrist in rheumatoid arthritis and the response to anti-tumor necrosis factor-alpha therapy.

Dynamic contrast-enhanced MRI (DCE-MRI) of the hand and wrist was performed in 11 patients with rheumatoid arthritis twice before and once 2 weeks after treatment with anti-tumor necrosis factor (TNF)-alpha therapy. A rapid, T1-weighted 3D spoiled gradient echo (SPGR) sequence was used for the dynamic imaging. T1 estimation was performed using similar images obtained at different flip angles. The relative radiofrequency field was estimated from the known T1 of the periarticular fatty marrow. The arterial input function (AIF) was measured at each examination, and normalized to the expected plasma concentration to reduce partial volume effects. Synovial enhancement was modeled to yield values for Ktrans, ve, and vp. Ktrans and ve showed good reproducibility. There was a significant decrease of about 20% in Ktrans after 2 weeks of treatment. This study demonstrates the potential of DCE-MRI and pharmacokinetic modeling to study early changes in inflammatory activity in rheumatoid arthritis following treatment.     

Attenuation of contraction-induced skeletal muscle injury by bromelain.

The proteolytic enzyme, bromelain, reportedly has therapeutic effects in the treatment of inflammation and soft tissue injuries. We tested the hypothesis that bromelain attenuates skeletal muscle injury induced by lengthening contractions. The left extensor digitorum longus (EDL) muscle of anesthetized hamsters was injured using a motorized foot pedal which repeatedly flexed/extended the foot through a range of 125 degrees. The EDL muscle was electrically stimulated for 400 ms during plantarflexion. Animals were assigned randomly to either a 0-d group (evaluated 3-h post-injury) or to untreated (UT) or bromelain-treated (T) groups, evaluated 3, 7, or 14 d post-injury. Following injury, T received 5 mg.kg-1 b.w. of bromelain, twice daily. Maximum isometric tetanic force (Po) was measured in vitro, then muscles were fixed, sectioned, and examined for evidence of fiber damage. The Po of injured muscles from T were higher than Po of injured muscles from UT at 3 (18.7 +/- 0.4 vs 16.5 +/- N.cm-2 and 14 d (20.5 +/- 0.6 vs 18.2 +/- 0.6 N.cm-2) (P less than 0.05), but not 7 d (19.5 +/-0.7 vs 17.7 +/- 0.8 N.cm-2). The Po of UT injured muscles were significantly lower than Po of contralateral control muscles at all time periods. Po of injured muscles from T were lower than Po from control muscles at 3 and 7 d (P less than 0.05), but not 14 d. The number of intact fibers of 3-d UT injured muscles was lower than the number of intact fibers in control muscles (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fast elevation of the intramyocellular lipid content in the presence of circulating free fatty acids and hyperinsulinemia: a dynamic 1H-MRS study.

The influence of a short-term elevation of free fatty acids (FFAs) on intramyocellular lipids (IMCL) under hyperinsulinemic conditions was monitored in five healthy male subjects in the course of a 5-hr hyperinsulinemic glucose clamp. During the glucose clamp a lipid emulsion (Intralipid 20(R)) and heparin were administered intravenously. IMCL was quantified in the tibialis anterior (TA) and the soleus (SOL) muscle by (1)H-MRS. A rapid elevation of the IMCL pool was found in both muscles (61% in TA and 22% in SOL) in the 5-hr time period. A control hyperinsulinemic glucose clamp in the same study group, repeated without elevation of circulating FFAs, did not lead to significant changes in IMCL for both muscles. The present study shows for the first time that only the combination of high concentrations of FFAs and insulin lead to marked storage of lipids in skeletal muscle cells in humans. Magn Reson Med 45:179-183, 2001.     

NMR of skeletal muscle. Differences in relaxation parameters related to extracellular/intracellular fluid spaces

The relationships between the T1 and T2 relaxation times, tissue water content and extracellular fluid space of two types of skeletal muscle groups were studied in rabbits and rats by means of NMR proton spectroscopy (10 MHz). Although there was no significant difference in the total water content between muscles rich in type I (74.5 +/- .8%; soleus) or type II (75.0 +/- .7%; gastrocnemius) fibers, the respective T1 (521 +/- 25 vs. 486 +/- 16 millisecond; p less than .01) and T2 (39.5 +/- 1.8 vs. 36.5 +/- 1.0 millisecond; p less than .01) relaxation times were consistently prolonged. The longer relaxation times of the soleus as compared with the gastrocnemius muscle were related to a larger extracellular fluid space as measured by (35S) sulfate +34.5%; p less than .01). For this reason, it seems likely selective changes in these spaces will be detectable by NMR proton imaging.     

Comparison of a reference region model with direct measurement of an AIF in the analysis of DCE-MRI data.

Models have been developed for analyzing dynamic contrast-enhanced (DCE)-MRI data that do not require measurements of the arterial input function (AIF). In this study, experimental results obtained from a reference region (RR) analysis are compared with results of an AIF analysis in the same set of five animals (four imaged twice, yielding nine data sets), returning estimates of the volume transfer constant (Ktrans) and the extravascular extracellular volume fraction (ve). Student's t-test values for comparisons of Ktrans and ve between the two models were 0.14 (P=0.88) and 0.85 (P>0.4), respectively (where the high P-values indicate no significant difference between values derived from the two models). Linear regression analysis indicated there was a correlation between Ktrans extracted by the two methods: r2=0.80, P=0.001 (where the low P-value indicates a significant linear correlation). For ve there was no such correlation (r2=0.02). The mean (absolute) percent difference between the models was 22.0% for Ktrans and 28.1% for ve. However, the RR parameter values were much less precise than the AIF method. The mean SDs for Ktrans and ve for the RR analysis were 0.024 min-1 and 0.06, respectively, vs. 0.002 min-1 and 0.03 for AIF analysis.     

Improvement of image quality of non-invasive coronary artery imaging with magnetic resonance by the use of the intravascular contrast agent Clariscan (NC100150 injection) in patients with coronary artery disease

PURPOSE: To assess the feasibility of Clariscan, an intravascular contrast agent, for free breathing, navigator assisted, high resolution, three-dimensional-magnetic resonance coronary angiography (MRCA) in patients, as extracellular contrast agents are unfavorable for the improvement of image quality. MATERIALS AND METHODS: MRCA was performed in 10 patients with known coronary artery disease (CAD) with (1-5 mg Fe/kg body weight) and without contrast agent. RESULTS: Compared to unenhanced images, Clariscan did not improve signal-to-noise (SNR) or contrast-to-noise ratios (CNR) compared to fat or myocardium in the proximal parts of the coronary arteries. However, when analyzing the peripheral parts (>4 cm from origin), CNR(fat) and CNR(myo) improved up to a factor of 1.81 and 5.85, respectively, at a dose of 3 mg Fe/kg body weight, while SNR did not reach statistical significance. The visible length of the coronary arteries was improved from 49 +/- 18 mm to 73 +/- 33 mm. The proximal diameter was reduced from 3.6 +/- 0.8mm to 3.2 +/- 0.8 mm, representing more closely the diameter of 3.1 +/- 0.7 mm measured by quantitative coronary angiography. Of 11 significant stenoses (>50%), eight were identified in the enhanced compared to six in the unenhanced images. CONCLUSION: The use of Clariscan at a dose of 2-3 mg Fe/kg body weight improves image quality of three-dimensional-MRCA, especially in the peripheral segments, and, thus, the diagnostic accuracy for the detection of CAD.     

Delayed contrast agent kinetics in ischemic skeletal muscle

PURPOSE: To detect skeletal muscle ischemia with first-pass gadolinium (Gd) kinetics after exercise. MATERIALS AND METHODS: Eleven subjects with intermittent claudication performed a symptom-limited bilateral plantar flexion exercise in the magnet. Regional ROIs were placed bilaterally in the gastrocnemius and soleus muscles, and a signal intensity (SI) time-curve analysis was performed. Induced ischemia was validated prior to the MRI with the systolic ankle-arm blood pressure index (AAI) measured after a symptom-limited treadmill exercise. RESULTS: Exercise induced ischemic pain in 16 of 22 legs with a significantly reduced AAI (0.31 +/- 0.15). The time to contrast arrival (TCA) was delayed in symptomatic ischemic legs vs. asymptomatic legs (16.3 +/- 6.9 seconds vs. 11.1 +/- 2.7 seconds, P < 0.05). The maximum SI during recovery was higher in the soleus muscle than in the gastrocnemius muscle in ischemic legs (1.55 +/- 0.1 vs. 1.44 +/- 0.1, P < 0.05). Symptomatic regions had a less steep upslope than asymptomatic regions (43 +/- 15 vs. 63 +/- 14, P < 0.001), with a graded upslope response to ischemia. However, a normal upslope was found in 10 of 29 ischemic regions, and some of the regions showed delayed contrast arrival, suggesting a pseudonormal upslope in ischemic regions. CONCLUSION: Exercise-induced ischemia was detected with the use of an SI time-curve analysis. However, disregarding the arterial input function and distribution volume of the tracer may lead to misinterpretation of some ischemic regions.     

Noninvasive evaluation of skeletal muscle oxidative metabolism after heart transplant

PURPOSE: The main aim of the present study was to investigate skeletal muscle oxidative metabolism in heart transplant recipients (HTR) by noninvasive tools. METHODS: Twenty male HTR (age 50.4 +/- 2.6 yr; mean +/- SE) and 17 healthy untrained age-matched controls (CTRL) performed an incremental exercise (IE) and a series of constant-load (CLE) moderate-intensity exercise tests on a cycloergometer. The following variables were determined: heart rate (HR); breath-by-breath pulmonary O2 uptake (VO2); and skeletal muscle (vastus lateralis) oxygenation indices by continuous-wave near-infrared spectroscopy. Changes in concentration of deoxygenated hemoglobin (Hb) and myoglobin (Mb) (Delta[deoxy(Hb + Mb)]), expressed as a fraction of values obtained during a transient limb ischemia, were taken as an index of skeletal muscle O2 extraction. "Peak" values were determined at exhaustion during IE. Kinetics of adjustment of variables were determined during CLE. RESULTS: VO2peak, HRpeak, and Delta[deoxy(Hb + Mb)] peak were significantly lower in HTR than in CTRL (17.1 +/- 0.7 vs 34.0 +/- 1.9 mL.kg(-1).min(-1), 133.8 +/- 3.8 vs 173.0 +/- 4.8 bpm, and 0.42 +/- 0.03 vs 0.58 +/- 0.04, respectively). In HTR, Delta[deoxy(Hb + Mb)] increase at submaximal workloads was steeper than in CTRL, suggesting an impaired O2 delivery to skeletal muscles, whereas the lower Delta[deoxy(Hb + Mb)] peak values suggest an impaired capacity of O2 extraction at peak exercise. VO2 and HR kinetics during CLE were significantly slower in HTR than in CTRL, whereas, unexpectedly, no significant differences were found for Delta[deoxy(Hb+Mb)] kinetics (mean response time: 21.3 +/- 1.1 vs 20.2 +/- 1.2 s). CONCLUSION: The findings confirm the presence of both "central" (cardiovascular) and "peripheral" (at the skeletal muscle level) impairments to oxidative metabolism in HTR. The noninvasiveness of the measurements will allow for serial evaluation of the patients, in the presence and/or absence of rehabilitation programs.     

Contrast-enhanced MRI of brown adipose tissue after pharmacological stimulation.

A non-invasive method for studying the modifications induced in lipid depots by hormonal stimulation could extend knowledge of adipose tissues. We studied the effect of adrenergic stimulation on interscapular brown adipose tissue (IBAT) of rats using contrast-enhanced MRI. Controls and rats pre-treated with adrenaline 40 s before the acquisition of pre-contrast images were used. In the control group, IBAT showed an enhancement of 56 +/- 29%, whereas adrenaline pre-treatment resulted in a significantly higher value (83 +/- 49%, P < 0.05). In the control group, the skeletal muscle of the anterior limb showed an enhancement of 24 +/- 12%, while adrenaline pre-treatment led to a higher value (26 +/- 10%), although the difference was not significant. In the control group, the skeletal muscle adjacent to the IBAT showed an enhancement of 30 +/- 13%, while adrenaline pre-treatment resulted in a non-significantly higher value (33 +/- 10%). In both groups, enhancement values in the muscle adjacent to the IBAT were significantly higher than the values in the muscle of the anterior limb (P < 0.05). This study demonstrates the feasibility of detecting the effect of hormonal stimulation on small fat depots. The demonstration of greater blood flow in the muscles surrounding the IBAT than in the muscles of the anterior limb suggests that the muscles of the back operate in synergy with the IBAT.