Antioxidant effects on hypoxia-induced oxidative stress and apoptosis in rat rotator cuff fibroblasts.

Most cells, highly sensitive to oxygen levels, undergo apoptosis under hypoxia. Therefore, the involvement of hypoxia in rotator cuff tendon degeneration has been proposed. While previous studies have reported that hypoxia induces apoptosis in rotator cuff fibroblasts (RCFs), little research has investigated whether antioxidants have cytoprotective effects against RCF apoptosis. The present study aimed at determining whether the antioxidant N-acetylcysteine (NAC) exerted cytoprotective effects against hypoxia-induced RCF apoptosis. Third-passage rat RCFs were divided into normoxia, NAC, hypoxia and NAC-hypoxia groups. The hypoxia inducer was 1,000 µmol/L cobalt chloride (CoCl2); the antioxidant was 20 mmol/L NAC. Expressions of hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 (HO-1), cell viability, intracellular reactive oxygen species (ROS) production, apoptosis rates as well as expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase-1 (PARP-1), vascular endothelial growth factors-ß (VEGF-ß) and matrix metalloproteinase-2 (MMP-2) were evaluated. Expression of HIF-1α and HO-1 was significantly higher in the hypoxia group than in the normoxia group (p < 0.001). Cell viability was significantly lower in the hypoxia group than in the normoxia group (p < 0.001). Intracellular ROS production, apoptosis rate and expressions of cleaved caspase-3, cleaved PARP-1, VEGF-ß and MMP-2 were significantly higher in the hypoxia group than in the normoxia group (p < 0.001). All these responses were significantly attenuated by pre-treatment with NAC (p ≤ 0.001). ROS were involved in hypoxic RCF apoptosis induced by CoCl2; NAC, an ROS scavenger, inhibited hypoxia-induced RCF apoptosis by inhibiting ROS production.

Hospital survey on patient safety culture in Sarawak General Hospital: A cross sectional study.

INTRODUCTION: Patient safety is defined as 'the prevention of harm caused by errors of commission and omission'. Patient safety culture is one of the important determining factor in safety and quality in healthcare. The purpose of this study is to assess the views and perceptions of health care professionals about patient safety culture in Sarawak General Hospital (SGH). METHODS: A cross-sectional study, using the 'Hospital Survey on Patient Safety Culture (HSOPSC)' questionnaire was carried out in 2018 in SGH. Random sampling was used to select a wide range of staff in SGH. A self-administered questionnaire was distributed to 500 hospital staff consisting of doctors, nurses, pharmacist and other clinical and non-clinical staff, conducted from March to April 2018. A total of 407 respondents successfully completed the questionnaire. Therefore, the final response rate for the survey was 81.4%. This study used SPSS 22.0 for Windows and Hospital Data Entry and Analysis Tool that works with Microsoft Excel developed by United States Agency for Healthcare Research and Quality (AHRQ) to perform statistical analysis on the survey data. RESULTS: Majority of the respondents graded the overall patient safety as acceptable (63.1%) while only 3.4% graded as excellent. The overall patient safety score was 50.1% and most of the scores related to dimensions were lower than the benchmark scores (64.8%). Generally, the mean positive response rate for all the dimensions were lower than composite data of AHRQ, except for "Organizational Learning - Continuous Improvement", which is also the highest positive response rate (80%), higher than AHRQ data (73%). The result showed that SGH has a good opportunity to improve over time as it gains experience and accumulates knowledge. On the other hand, the lowest percentage of positive responses was "Non-punitive response to error" (18%), meaning that most of the staff perceived that they will be punished for medical error. CONCLUSIONS: The level of patient safety culture in SGH is acceptable and most of the scores related to dimensions were lower than benchmark score. SGH as a learning organisation should also address the issues of staffing, improving handoff and transition and develop a non-punitive culture in response to error.

Guidelines for training in cardiovascular magnetic resonance (CMR).

These "Guidelines for training in Cardiovascular Magnetic Resonance" were developed by the Certification Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) and approved by the SCMR Board of Trustees.

Multidisciplinary approach in the management of a complicated crown root fracture.

BACKGROUND: This article describes the management of a complicated crown root fracture. CASE REPORT: A young patient presented with a crown root fracture of the maxillary left central incisor with an oblique subgingival fracture line. A multidisciplinary treatment approach including endodontic treatment, orthodontic extrusion, surgical extraction and intra-alveolar repositioning was used to gain sufficient crown length of the fractured maxillary incisor. The coronally repositioned maxillary left central incisor was stabilised by sutures and a resin wire splint. A resin core was built up followed by fabrication of an all-ceramic crown. Clinical and radiographic follow-up of the maxillary left central incisor after 24 months showed no signs of bone resorption or pathology and good aesthetics and functions were maintained.

Microvascular integrity and the time course of myocardial sodium accumulation after acute infarction.

Loss of membrane permeability caused by ischemia leads to cellular sodium accumulation and myocardial edema. This phenomenon has important implications to left ventricular structure and function in the first hours after myocardial infarction. We hypothesized that during this period of time, after prolonged coronary occlusion and complete reflow, the rate of myocardial sodium accumulation is governed by microvascular integrity. We used 3-dimensional (23)Na MRI to monitor myocardial sodium content changes over time in an in vivo closed-chest canine model (n=13) of myocardial infarction and reperfusion. Infarcts with microvascular obstruction (MO) defined by both radioactive microspheres and contrast-enhanced (1)H MRI showed a slower rate of sodium accumulation as well as lower blood flow at 20 minutes and 6 hours after reperfusion. Conversely, the absence of MO was associated with faster rates of sodium accumulation and greater blood flow restoration. In addition, infarct size by (23)Na MRI correlated best with infarct size by triphenyltetrazolium chloride and contrast-enhanced (1)H MRI at 9 hours after reperfusion. We conclude that in reperfused myocardial infarction, sodium accumulation is dependent on microvascular integrity and is slower in regions of MO compared with those with patent microvasculature. Finally, (23)Na MRI can be a useful tool for monitoring in vivo myocardial sodium content in acute myocardial infarction.

Transmural extent of acute myocardial infarction predicts long-term improvement in contractile function.

BACKGROUND: Previous animal studies have demonstrated that the transmural extent of acute myocardial infarction defined by contrast-enhanced MRI (ceMRI) relates to early restoration of flow and future improvements in contractile function. We tested the hypothesis that ceMRI would have similar predictive value in humans. METHODS AND RESULTS: Twenty-four patients who presented with their first myocardial infarction and were successfully revascularized underwent cine and ceMRI of their heart within 7 days (scan 1) of the peak MB band of creatine kinase. Cine MRI was repeated 8 to 12 weeks later (scan 2). The transmural extent of infarction on scan 1 and wall thickening on both scans were determined using a 72-segment model. A total of 524 of 1571 segments (33%) were dysfunctional on scan 1. Improvement in segmental contractile function on scan 2 was inversely related to the transmural extent of infarction on scan 1 (P=0.001). Improvement in global contractile function, as assessed by ejection fraction and mean wall thickening score, was not predicted by peak creatine kinase-MB (P=0.66) or by total infarct size, as defined by MRI (P=0.70). The best predictor of global improvement was the extent of dysfunctional myocardium that was not infarcted or had infarction comprising <25% of left ventricular wall thickness (P<0.005 for ejection fraction, P<0.001 for mean wall thickening score). CONCLUSION: In patients with acute myocardial infarction, the transmural extent of infarction defined by ceMRI predicts improvement in contractile function.

Early assessment of myocardial salvage by contrast-enhanced magnetic resonance imaging.

BACKGROUND: Myocardial salvage after acute myocardial infarction is defined clinically by early restoration of flow and long-term improvement in contractile function. We hypothesized that contrast-enhanced magnetic resonance imaging (MRI), performed early after myocardial infarction, indexes myocardial salvage. We studied the relationship between the transmural extent of hyperenhancement by contrast-enhanced MRI, restoration of flow, and recovery of function. METHODS AND RESULTS: The left anterior descending coronary artery was occluded in dogs (n=15) for either 45 minutes, 90 minutes, or permanently. Cine and contrast-enhanced MRI were performed 3 days after the procedure; cine MRI was also done 10 and 28 days after the procedure. The transmural extent of hyperenhancement and wall thickening were determined using a 60-segment model. The mean transmural extent of hyperenhancement for the 45-minute occlusion group was 22% of the 90-minute group and 18% of the permanent occlusion group (P:<0.05 for both). The transmural extent of hyperenhancement on day 3 was related to future improvement in both wall thickening score and absolute wall thickening at 10 and 28 days (P:<0.0001 for each). For example, of the 415 segments on day 3 that were dysfunctional and had <25% transmural hyperenhancement, 362 (87%) improved by day 28. Conversely, no segments (0 of 9) with 100% hyperenhancement improved. The transmural extent of hyperenhancement on day 3 was a better predictor of improvement in contractile function than occlusion time (P:<0.0001). CONCLUSIONS: A reduction in the transmural extent of hyperenhancement by contrast-enhanced MRI early after myocardial infarction is associated with an early restoration of flow and future improvement in contractile function.

Visualization of discrete microinfarction after percutaneous coronary intervention associated with mild creatine kinase-MB elevation.

BACKGROUND: Mild elevations in creatine kinase-MB (CK-MB) are common after successful percutaneous coronary interventions and are associated with future adverse cardiac events. The mechanism for CK-MB release remains unclear. A new contrast-enhanced MRI technique allows direct visualization of myonecrosis. METHODS AND RESULTS: Fourteen patients without prior infarction underwent cine and contrast-enhanced MRI after successful coronary stenting; 9 patients had procedure-related CK-MB elevation, and 5 did not (negative controls). The mean age of all patients was 61 years, 36% had diabetes, 43% had multivessel coronary artery disease, and all had a normal ejection fraction. Twelve patients (86%) received an intravenous glycoprotein IIb/IIIa inhibitor; none underwent atherectomy, and all had final TIMI 3 flow. Of the 9 patients with CK-MB elevation, 5 had a minor side branch occlusion during stenting, 2 had transient ECG changes, and none developed Q-waves. The median CK-MB was 21 ng/mL (range, 12 to 93 ng/mL), which is 2.3x the upper limit of normal. Contrast-enhanced MRI demonstrated discrete regions of hyperenhancement within the target vessel perfusion territory in all 9 patients. Only one developed a new wall motion abnormality. The median estimated mass of myonecrosis was 2.0 g (range, 0.7 to 12.2 g), or 1.5% of left ventricular mass (range, 0.4% to 6.0%). Hyperenhancement persisted in 5 of the 6 who underwent a repeat MRI at 3 to 12 months. No control patient had hyperenhancement. CONCLUSIONS: Contrast-enhanced MRI provides an anatomical correlate to biochemical evidence of procedure-related myocardial injury, despite the lack of ECG changes or wall motion abnormalities. Mild elevation of CK-MB after percutaneous coronary intervention is the result of discrete microinfarction.

Limits of detection of regional differences in vasodilated flow in viable myocardium by first-pass magnetic resonance perfusion imaging.

BACKGROUND: Perfusion imaging techniques intended to identify regional limitations in coronary flow reserve in viable myocardium need to identify 2-fold differences in regional flow during coronary vasodilation consistently. This study evaluated the suitability of current first-pass magnetic resonance approaches for evaluating such differences, which are 1 to 2 orders of magnitude less than in myocardial infarction. METHODS AND RESULTS: Graded regional differences in vasodilated flow were produced in chronically instrumented dogs with either left circumflex (LCx) infusion of adenosine or partial LCx occlusion during global coronary vasodilation. First-pass myocardial signal intensity-time curves were obtained after right atrial injection of gadoteridol (0.025 mmol/kg) with an MRI inversion recovery true-FISP sequence. The area under the initial portion of the LCx curve was compared with that of a curve from a remote area of the ventricle. Relative LCx and remote flows were assessed simultaneously with microspheres. The ratio of LCx and remote MRI curve areas and the ratio of LCx and remote microsphere concentrations were highly correlated and linearly related over a 5-fold range of flow differences (y=0.96 x+/-0.07, P<0.0001, r(2)=0.87). The 95% confidence limits for individual MRI measurements were +/-35%. Regional differences of >/=2-fold were consistently apparent in unprocessed MR images. CONCLUSIONS: Clinically relevant regional reductions in vasodilated flow in viable myocardium can be detected with 95% confidence over the range of 1 to 5 times resting flow. This suggests that MRI can identify and quantify limitations in perfusion reserve that are expected to be produced by stenoses of >/=70%.

Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function.

BACKGROUND: Contrast MRI enhancement patterns in several pathophysiologies resulting from ischemic myocardial injury are controversial or have not been investigated. We compared contrast enhancement in acute infarction (AI), after severe but reversible ischemic injury (RII), and in chronic infarction. METHODS AND RESULTS: In dogs, a large coronary artery was occluded to study AI and/or chronic infarction (n = 18), and a second coronary artery was chronically instrumented with a reversible hydraulic occluder and Doppler flowmeter to study RII (n = 8). At 3 days after surgery, cine MRI revealed reduced wall thickening in AI (5+/-6% versus 33+/-6% in normal, P<0.001). In RII, wall thickening before, during, and after inflation of the occluder for 15 minutes was 35+/-5%, 1+/-8%, and 21+/-10% and Doppler flow was 19.8+/-5.3, 0.2+/-0.5, and 56.3+/-17.7 (peak hyperemia) cm/s, respectively, confirming occlusion, transient ischemia, and reperfusion. Gd-DTPA-enhanced MR images acquired 30 minutes after contrast revealed hyperenhancement of AI (294+/-96% of normal, P<0.001) but not of RII (98+/-6% of normal, P = NS). Eight weeks later, the chronically infarcted region again hyperenhanced (253+/-54% of normal, n = 8, P<0.001). High-resolution (0.5 x 0.5 x 0.5 mm) ex vivo MRI demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent of myocyte necrosis with and without reperfusion at 1 day (R = 0.99, P<0.001) and 3 days (R = 0.99, P<0.001) and collagenous scar at 8 weeks (R = 0.97, P<0.001). CONCLUSIONS: In the pathophysiologies investigated, contrast MRI distinguishes between reversible and irreversible ischemic injury independent of wall motion and infarct age.

Relationship of elevated 23Na magnetic resonance image intensity to infarct size after acute reperfused myocardial infarction.

BACKGROUND: Elevated 23Na MR image intensity after acute myocardial infarction has previously been shown to correspond to high tissue [Na+] and loss of myocardial viability. In this study, we explored the potential of in vivo 23Na MRI to assess infarct size and investigated possible mechanisms for elevated 23Na image intensity. METHODS AND RESULTS: Thirteen dogs and 8 rabbits underwent in situ coronary artery occlusion and reperfusion and were imaged by 23Na MRI. For anatomically matched left ventricular short-axis cross sections (n=46), infarct size measured by in vivo 23Na MRI correlated well with triphenyltetrazolium chloride staining (r=0.87, y=0.92x+3.37, P<0.001). Elevated 23Na image intensity was observed in infarcted myocardium (206+/-37% of remote in dogs, P<0.001; 215+/-58% in rabbits, P<0.002) but was not observed after severe but reversible ischemic injury (101+/-11% of baseline, P=NS). High-resolution ex vivo imaging revealed that regions of elevated 23Na image intensity appeared to be identical to those of infarcted regions (r=0.97, y=0.92x+1.52, P<0.001). In infarcted regions, total tissue [Na+] was elevated (89+/-12 versus 37+/-9 mmol/L in control tissue, 156+/-60% increase, P<0.001) and was associated with increased intracellular sodium (254+/-68% of control, P<0.005) and an increased intracellular sodium/potassium ratio (868+/-512% of control, P<0.002). Morphometric analysis demonstrated only a minor increase in extracellular volume (17+/-8% versus 14+/-5%, P<0.05) in the infarcted territory. CONCLUSIONS: Elevated 23Na MR image intensity in vivo measures infarct size after reperfused infarction in both a large and a small animal model. The mechanism of elevated 23Na image intensity is probably intracellular sodium accumulation secondary to loss of myocyte ionic homeostasis.

Contrast-enhanced magnetic resonance imaging of myocardium at risk: distinction between reversible and irreversible injury throughout infarct healing.

OBJECTIVES: We sought to determine the relationship of delayed hyperenhancement by contrast magnetic resonance imaging (MRI) to viable and nonviable myocardium within the region at risk throughout infarct healing. BACKGROUND: The relationship of delayed MRI contrast enhancement patterns to injured but viable myocardium within the ischemic bed at risk has not been established. METHODS: We compared in vivo and ex vivo MRI contrast enhancement to histopathologic tissue sections encompassing the entire left ventricle in dogs (n = 24) subjected to infarction with (n = 12) and without (n = 12) reperfusion at 4 h, 1 day, 3 days, 10 days, 4 weeks and 8 weeks. In vivo MR imaging was performed 30 min after contrast injection. RESULTS: The sizes and shapes of in vivo myocardial regions of elevated image intensity (828+/-132% of remote) were the same as those observed ex vivo (241 slices, r = 0.99, bias = 0.05+/-1.6% of left ventricle [LV]). Comparison of ex vivo MRI to triphenyltetrazolim chloride-stained sections demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent ofinfarction at every stage of healing (510 slices, lowest r = 0.95, largest bias = 1.7+/-2.9% of LV). Conversely, hyperenhanced regions were smaller than the ischemic bed at risk defined by fluorescent microparticles at every stage of healing (239 slices, 35+/-24% of risk region, p<0.001). Image intensities of viable myocardium within the risk region were the same as those of remote, normal myocardium (102+/-9% of remote, p = NS). CONCLUSIONS: Delayed contrast enhancement by MRI distinguishes between viable and nonviable regions within the myocardium at risk throughout infarct healing.

Quantification and time course of microvascular obstruction by contrast-enhanced echocardiography and magnetic resonance imaging following acute myocardial infarction and reperfusion.

OBJECTIVES: We aimed to validate contrast-enhanced echocardiography (CE) in the quantification of microvascular obstruction (MO) against magnetic resonance imaging (MRI) and the histopathologic standards of radioactive microspheres and thioflavin-S staining. We also determined the time course of MO at days 2 and 9 after infarction and reperfusion. BACKGROUND: Postinfarction MO occurs because prolonged ischemia produces microvessel occlusion at the infarct core, preventing adequate reperfusion. Microvascular obstruction expands up to 48 h after reperfusion; the time course beyond 2 days is unknown. Though used to study MO, CE has not been compared with MRI and thioflavin-S, which yield precise visual maps of MO. METHODS: Ten closed-chest dogs underwent 90-min coronary artery occlusion and reperfusion. Both CE and MRI were performed at 2 and 9 days after reperfusion. The MO regions by both methods were quantified as percent left ventricular (% LV) mass. Radioactive microspheres were injected for blood flow determination. Postmortem, the myocardium was stained with thioflavin-S and 2,3,5-triphenyltetrazolium chloride. RESULTS: Expressed as % total LV, MO by MRI matched in size MO by microspheres using a flow threshold of <40% remote (4.96+/-3.52% vs. 5.32+/-3.98%, p=NS). For matched LV cross sections, MO by CE matched in size MO by microspheres using a flow threshold of <60% remote (13.27+/-4.31% vs. 13.5+/-4.94%, p=NS). Both noninvasive techniques correlated well with microspheres (MRI vs. CE, r=0.87 vs. 0.74; p=NS). Microvascular obstruction by CE corresponded spatially to MRI-hypoenhanced regions and thioflavin-negative regions. For matched LV slices at 9 days after reperfusion, MO measured 12.94+/-4.51% by CE, 7.11+/-3.68% by MRI and 9.18+/-4.32% by thioflavin-S. Compared to thioflavin-S, both noninvasive techniques correlated well (CE vs. MRI, r=0.79 vs. 0.91; p=NS). Microvascular obstruction size was unchanged at 2 and 9 days (CE: 13.23+/-4.11% vs. 12.69+/-4.97%; MRI: 5.53+/-4.94% vs. 4.68+/-3.44%; p=NS for both). CONCLUSIONS: Both CE and MRI can quantify MO. Both correlate well with the histopathologic standards. While MRI can detect regions of MO with blood flow <40% of remote, the threshold for MO by CE is <60% remote. The extent of MO is unchanged at 2 and 9 days after reperfusion.

Safety of gadoversetamide in patients with acute and chronic myocardial infarction.

PURPOSE: To assess the safety data from two large, multicenter, phase 2 trials on the use of gadoversetamide (OptiMARK, Tyco Healthcare/Mallinckrodt, St. Louis, MO) as a contrast agent in delayed hyperenhancement magnetic resonance imaging (DE-MRI) in patients with acute and chronic myocardial infarction (MI). MATERIALS AND METHODS: The study population from both trials comprised 577 patients who were randomly assigned to one of four dose groups (0.05, 0.1, 0.2, or 0.3 mmol/kg) before undergoing DE-MRI. Safety evaluations included physical and electrocardiographic (ECG) examinations. Vital signs, laboratory values, adverse events (AE), and serious adverse events (SAE) were monitored before and after contrast administration. RESULTS: Of the 577 patients who received gadoversetamide, 124 (21.5%) reported a total of 164 AEs; most were mild (139 AEs; 84.8%) or moderate (25 AEs; 15.2%). ECG-related changes were the most frequent AE. Site investigators judged only eight AEs as likely related to gadoversetamide and only two of the eight as clinically relevant. Further evaluation suggested neither AE was related to gadoversetamide. Two SAEs were reported, but none was judged related to gadoversetamide by the site investigators. CONCLUSION: Gadoversetamide is safe for use in patients with acute or chronic MI up to a dose of 0.3 mmol/kg.

Evaluation of myocardial viability by MRI.

Distinguishing between viable and non-viable myocardium is an important clinical issue. Several magnetic resonance (MR) techniques to address this issue have been proposed. Spectroscopy of phosphorus-31 and hydrogen-1 from creatine as well as imaging of sodium-23 and potassium-39 reflect information related to cellular metabolism. The spatial and temporal resolutions of these techniques are limited, however, by the small magnitude of the MR signal. Proton imaging techniques include examination of pathologic alterations in MR relaxation times (T1 and T2), wall thickness and thickening, cine MRI combined with low-dose dobutamine, first-pass contrast enhancement patterns, and delayed contrast enhancement patterns. Of the proton imaging approaches, cine MRI combined with low-dose dobutamine is supported by the largest body of clinical evidence supporting the hypothesis that the technique yields useful information regarding myocardial viability. Recent data suggest that delayed contrast enhancement examines the transmural extent of viable myocardium irrespective of contractile function and that this technique should also be considered in a clinical setting.

Theory of high-speed MR imaging of the human heart with the selective line acquisition mode.

Selective line acquisition mode (SLAM) reduces magnetic resonance imaging time by a factor n relative to conventional techniques. Seventeen patients with cardiac disease and three volunteers were examined with SLAM and two-frame interpolation (2FI). SLAM images were sharper than 2FI images and showed well-defined endocardial borders. SLAM is best suited for fast imaging of moving objects, such as the heart, confined to 1/n of the field of view.

Myocardial Gd-DTPA kinetics determine MRI contrast enhancement and reflect the extent and severity of myocardial injury after acute reperfused infarction.

BACKGROUND: Contrast medium-enhanced magnetic resonance images of acute, reperfused infarcts have shown hypoenhanced and hyperenhanced regions in areas of injured myocardium. The precise mechanisms that lead to these altered enhancement patterns are unknown. This study was designed to evaluate possible mechanisms and to relate altered enhancement patterns to myocardial perfusion and viability. METHODS AND RESULTS: Thirteen rabbits underwent in situ coronary artery occlusion and reperfusion followed by isolated perfusion with cardioplegic solution. T1-weighted spin-echo images were acquired continuously during step changes in perfusate Gd-DTPA concentration. Regional blood flow was also measured by use of radioactive microspheres in all rabbits. There were marked differences in Gd-DTPA wash-in and washout time constants (wash-in, 0.8 +/- 0.1, 2.1 +/- 02, and 16.3 +/- 2.4 minutes, P < .001; washout, 1.6 +/- 0.1, 4.8 +/- 0.5, and 31.1 +/- 3.3 minutes, P < .001) in normal, infarct rim, and infarct core regions, respectively, resulting in differential enhancement of these regions. Microsphere flows in the infarct rim and core were 42.9 +/- 4.0% and 12.0 +/- 1.6% of normal myocardium and correlated well with washout time constants (r = .86, y = 0.77x - 0.002, P < .001), suggesting that these time constants index the severity of microvascular damage. In addition, spatial maps of washout time constants were produced. The extent of regions with abnormal time constants correlated well with triphenyltetrazolium chloride-determined infarct size (r = .94, y = 0.95x + 4.17, P < .001). CONCLUSIONS: In contrast-enhanced magnetic resonance images of acute, reperfused rabbit infarcts, differential image intensity is primarily due to regional differences in contrast agent wash-in and washout time constants. These regional differences in time constants also indicate the extent and severity of myocardial injury.

Physiological basis for potassium (39K) magnetic resonance imaging of the heart.

The potassium cation (K+) is fundamentally involved in myocyte metabolism. To explore the potential utility of direct MRI of the most abundant natural isotope of potassium, 39K, we compared 39K magnetic resonance (MR) image intensity with regional myocardial K+ concentrations after irreversible injury. Rabbits were subjected either to 40 minutes of in situ coronary artery occlusion and 1 hour of reperfusion (n=26) or to 24 hours of permanent occlusion (n=4). The hearts were then isolated and imaged by 39K MRI (n=10), or tissue samples were analyzed for regional 39K content by MR spectroscopy (n=9), K+ and Na+ concentrations by atomic emission spectroscopy (inductively coupled plasma atomic emission spectroscopy; n=5), or intracellular K+ content by electron probe x-ray microanalysis (n=6). Three-dimensional 39K MR images of the isolated hearts were acquired in 44 minutes with 3 x 3 x 3-mm resolution. 39K MR image intensity was reduced in infarcted regions (51.7+/-4. 8% of remote; P<0.001). The circumferential extent and location of regions of reduced 39K image intensity were correlated with those of infarcted regions defined histologically (r=0.97 and r=0.98, respectively). Compared with remote regions, tissue analysis revealed that infarcted regions had reduced 39K concentration (by MR spectroscopy, 40.5+/-9.3% of remote; P<0.001), reduced potassium-to-sodium ratio (by inductively coupled plasma atomic emission spectroscopy, 20.7+/-2.1% of remote; P<0.01), and reduced intracellular potassium (by electron probe x-ray microanalysis, K+ peak-to-background ratio 0.95+/-0.32 versus 2.86+/-1.10, respectively; P<0.01). We acquired the first 39K MR images of hearts subjected to infarction. In the pathophysiologies examined, potassium (39K) MR image intensity primarily reflects regional intracellular K+ concentrations.

Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction.

BACKGROUND: A technical advance in contrast-enhanced magnetic resonance imaging (MRI) has significantly improved image quality. We investigated whether healed myocardial infarction can be visualised as hyperenhanced regions with this new technique, and whether assessment of the transmural extent of infarction yields new physiological data. METHODS: 82 MRI examinations were carried out in three groups: patients with healed myocardial infarction; patients with non-ischaemic cardiomyopathy; and healthy volunteers. Patients with healed myocardial infarction were prospectively enrolled after enyzmatically proven necrosis and imaged 3 months (SD 1) or 14 months (7) later. The MRI procedure used a segmented inversion-recovery gradient-echo sequence after gadolinium administration. Findings were compared with those of coronary angiography, electrocardiography, cine MRI, and creatine kinase measurements. FINDINGS: 29 (91%) of 32 patients with infarcts imaged at 3 months (13 non-Q-wave) and all of 19 imaged at 14 months (eight non-Q-wave) showed hyperenhancement. In patients in whom the infarct-related-artery was identified by angiography, 24 of 25 imaged at 3 months and all of 14 imaged at 14 months had hyperenhancement in the appropriate territory. None of the 20 patients with non-ischaemic cardiomyopathy or the 11 healthy volunteers showed hyperenhancement. Irrespective of the presence or absence of Q waves, the majority of patients with hyperenhancement had only non-transmural involvement. Normal left-ventricular contraction was shown in seven patients examined at 3 months and three examined at 14 months, but in these cases hyperenhancement was limited to the subendocardium. INTERPRETATION: The presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction can be accurately determined by contrast-enhanced MRI.

DXplain on the Internet.

DXplain, a computer-based medical education, reference and decision support system has been used by thousands of physicians and medical students on stand-alone systems and over communications networks. For the past two years, we have made DXplain available over the Internet in order to provide DXplain's knowledge and analytical capabilities as a resource to other applications within Massachusetts General Hospital (MGH) and at outside institutions. We describe and provide the user experience with two different protocols through which users can access DXplain through the World Wide Web (WWW). The first allows the user to have direct interaction with all the functionality of DXplain where the MGH server controls the interaction and the mode of presentation. In the second mode, the MGH server provides the DXplain functionality as a series of services, which can be called independently by the user application program.