Cardioprotection by minocycline in a rabbit model of ischemia/reperfusion injury: Detection of cell death by in vivo 111In-GSAO SPECT.

BACKGROUND: Preclinical studies indicate that minocycline protects against myocardial ischemia/reperfusion injury. In these studies, minocycline was administered before ischemia, which can rarely occur in clinical practice. The current study aimed to evaluate cardioprotection by minocycline treatment upon reperfusion. METHODS: Rabbits were subjected to myocardial ischemia/reperfusion injury and received either intravenous minocycline (n = 8) or saline (n = 8) upon reperfusion. Cardiac cell death was assessed by in vivo micro-SPECT/CT after injection of Indium-111-labeled 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (111In-GSAO). Thereafter, hearts were explanted for ex vivo imaging, γ-counting, and histopathological characterization. RESULTS: Myocardial damage was visualized by micro-SPECT/CT imaging. Quantitative GSAO uptake (expressed as percent injected dose per gram, %ID/g) in the area at risk was lower in minocycline-treated animals than that in saline-treated control animals (0.32 ± 0.13% vs 0.48 ± 0.15%, P = 0.04). TUNEL staining confirmed the reduction of cell death in minocycline-treated animals. CONCLUSIONS: This study demonstrates cardioprotection by minocycline in a clinically translatable protocol.

The Return of the Vulnerable Plaque: Optical Coherence Tomography Imaging of a Case of a Late In-Stent Restenotic Chronic Total Occlusion.

Although the use of drug-eluting stents (DES) has dramatically decreased the incidence of in-stent restenosis (ISR), concerns regarding the late manifestations of ISR remain. Optical coherence tomography (OCT) imaging provides unique insights into characteristics and patterns of ISR. We report a case of late DES ISR with unusual heterogeneous intracoronary luminal characteristics suggestive of vulnerable atherosclerotic plaque activity by OCT imaging. This case demonstrates that late ISR after DES may involve more than mere neointimal hyperplasia with lesion-associated craters, septae, and neoatherosclerosis. The use of OCT provides novel insights into the mechanisms and potential biology of the late DES ISR.

Ultrafast optical-ultrasonic system and miniaturized catheter for imaging and characterizing atherosclerotic plaques in vivo.

Atherosclerotic coronary artery disease (CAD) is the number one cause of death worldwide. The majority of CAD-induced deaths are due to the rupture of vulnerable plaques. Accurate assessment of plaques is crucial to optimize treatment and prevent death in patients with CAD. Current diagnostic techniques are often limited by either spatial resolution or penetration depth. Several studies have proved that the combined use of optical and ultrasonic imaging techniques increase diagnostic accuracy of vulnerable plaques. Here, we introduce an ultrafast optical-ultrasonic dual-modality imaging system and flexible miniaturized catheter, which enables the translation of this technology into clinical practice. This system can perform simultaneous optical coherence tomography (OCT)-intravascular ultrasound (IVUS) imaging at 72 frames per second safely in vivo, i.e., visualizing a 72 mm-long artery in 4 seconds. Results obtained in atherosclerotic rabbits in vivo and human coronary artery segments show that this ultrafast technique can rapidly provide volumetric mapping of plaques and clearly identify vulnerable plaques. By providing ultrafast imaging of arteries with high resolution and deep penetration depth simultaneously, this hybrid IVUS-OCT technology opens new and safe opportunities to evaluate in real-time the risk posed by plaques, detect vulnerable plaques, and optimize treatment decisions.

Optimal flushing agents for integrated optical and acoustic imaging systems.

An increasing number of integrated optical and acoustic intravascular imaging systems have been developed and hold great promise for accurately diagnosing vulnerable plaques and guiding atherosclerosis treatment. However, in any intravascular environment, the vascular lumen is filled with blood, a high-scattering source for optical and high-frequency ultrasound signals. Blood must be flushed away to provide clearer images. To our knowledge, no research has been performed to find the ideal flushing agent for combined optical and acoustic imaging techniques. We selected three solutions as potential flushing agents for their image-enhancing effects: mannitol, dextran, and iohexol. Testing of these flushing agents was performed in a closed-loop circulation model and in vivo on rabbits. We found that a high concentration of dextran was the most useful for simultaneous intravascular ultrasound and optical coherence tomography imaging.

Epicardial adipose tissue volume as a marker of coronary artery disease severity in patients with diabetes independent of coronary artery calcium: findings from the CTRAD study.

AIMS: The association between epicardial adipose tissue (EAT) volume and coronary artery disease (CAD) severity was evaluated, independent of traditional risk factors and coronary artery calcium (CAC) scores, in patients with diabetes type 2 (DM-2) using cardiac computed tomography angiography (CTA). METHODS: A multivariate analysis was utilized to assess for an independent association after calculating EAT volume, CAD severity, and calcium scores in 92 patients with DM-II from the CTRAD study. We graded CAD severity as none (normal coronaries), mild-moderate (<70% stenosis), and severe (70% or greater stenosis). RESULTS: A total of 39 (42.3%) asymptomatic patients with diabetes did not have CAD; 30.4% had mild/moderate CAD; and 27.1% had severe CAD. Mean EAT volume was highest in patients with severe CAD (143.14 cm(3)) as compared to mild/moderate CAD (112.7 cm(3)), and no CAD (107.5 cm(3)) (p = 0.003). After adjustment of clinical risk factors, notably, CAC score, multivariate regression analysis showed EAT volume was an independent predictor of CAD severity in this sample (odds ratio 11.2, 95% confidence interval 1.7-73.8, p = 0.01). CONCLUSIONS: Increasing EAT volume in asymptomatic patients with DM-II is associated with presence of severe CAD, independent of BMI and CAC, as well as traditional risk factors.

Comparison of epicardial adipose tissue volume and coronary artery disease severity in asymptomatic adults with versus without diabetes mellitus.

Epicardial adipose tissue (EAT) has been shown to have important effects on the development of coronary artery disease (CAD) through local paracrine influences on the vascular bed. We compared a cohort of asymptomatic patients with type II diabetes mellitus (DM) without known CAD to an age- and gender-matched group of asymptomatic patients without DM from the CTRAD (Cardiac CT's Role in Asymptomatic Patients with DM-II) study in which patients underwent a cardiac computed tomography angiogram, for early detection of CAD. Mean EAT volumes of 118.6 ± 43.0 and 70.0 ± 44.0 cm(3) were found in the DM and non-DM groups, respectively. When stratified by the presence and severity of CAD, it was found that in the DM (p = 0.003) and non-DM groups (p <0.001), there was a statistically significant increase in EAT volume as the patients were found to have increasingly severe CAD. After adjusting for age, race, gender, DM, hypertension, insulin use, body mass index, and coronary artery calcium (CAC) score, the presence of >120 cm(3) of EAT was found to be highly correlated with the presence of significant CAD (adjusted odds ratio 4.47, 95% confidence interval 1.35 to 14.82). We found that not only is EAT volume an independent predictor of CAD but that an increasing volume of EAT predicted increasing severity of CAD even after adjustment for CAC score.

Integrated IVUS-OCT Imaging for Atherosclerotic Plaque Characterization.

For the diagnosis of atherosclerosis, biomedical imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed. The combined use of IVUS and OCT is hypothesized to remarkably increase diagnostic accuracy of vulnerable plaques. We have developed an integrated IVUS-OCT imaging apparatus, which includes the integrated catheter, motor drive unit, and imaging system. The dual-function imaging catheter has the same diameter of current clinical standard. The imaging system is capable for simultaneous IVUS and OCT imaging in real time. Ex vivo and in vivo experiments on rabbits with atherosclerosis were conducted to demonstrate the feasibility and superiority of the integrated intravascular imaging modality.

Role of echocardiography in the treatment of cardiac tamponade.

Accumulation of fluid within the pericardial sac results in elevation of intrapericardial pressure with consequent cardiac compression or tamponade. Cardiac tamponade is a life-threatening condition which requires urgent evacuation of pericardial effusion (PE). Current pericardial evacuation techniques and approaches are varied. Echocardiography provides valuable insights into identifying patients who are suitable candidates and further facilitates pericardiocentesis by improving guidance techniques. Several previous publications have provided excellent reviews of the pathophysiology of cardiac tamponade. We review the clinical presentation and role of echocardiography for diagnosis of tamponade. We focus on medical and surgical approaches for the removal of PE. Moreover, as the clinical and hemodynamic consequences of PE depend on the volume and the rate of accumulation of PE, we review the various scenarios of "small" PE resulting in cardiac tamponade.

Unique morphological variations of transient midventricular syndrome: a case series-review.

Older individuals (especially women) enduring an inciting emotional or physical event are prone to developing left ventricular ballooning syndrome. Ballooning of apical distribution is the most common type. However, a midventricular variant is increasingly reported. As this variant becomes further delineated, we describe a case series in which various morphological patterns of midleft ventricular segments are seen. Each case involves a female patient with a presumptive diagnosis of acute coronary syndrome, who upon further cardiac workup demonstrated normal epicardial coronary blood flow. Subsequent cardiac imaging, including transthoracic echocardiography, revealed unique midventricular dilation and akinesis, with preserved or hypercontractility of the basal and apical segments. However, more unique to this, was the fact that the left ventricular regional wall motion abnormalities were of either "symmetric" ballooning morphology, involving all mid segments of the left ventricle; or more dramatically, "asymmetric" ballooning morphology, which involves abnormal regional motion of only a focal left ventricular wall. Furthermore, we review current literature on midventricular ballooning and propose likely mechanisms and optimal treatment strategies in the face of potential complications of midventricular ballooning syndrome.

Evaluation of non-ST segment elevation acute chest pain syndromes with a novel low-profile continuous imaging ultrasound transducer.

BACKGROUND: This investigation was designed to test the hypothesis that continuous cardiac imaging using an ultrasound transducer developed in our laboratory (ContiScan) is superior to electrocardiogram (ECG) monitoring in the diagnosis of coronary artery disease (CAD) in patients with acute non-ST segment elevation chest pain syndromes. METHODS: Seventy patients with intermediate to high probability of CAD who presented with typical anginal chest pain and no evidence of ST segment elevation on the ECG were studied. The 2.5-MHz transducer is spherical in its distal part mounted in an external housing to permit steering in 360 degrees. The transducer was placed at the left sternal border to image the left ventricular short-axis view and recorded on video tape at baseline, during and after episodes of chest pain. Two ECG leads were continuously monitored. The presence of CAD was confirmed by coronary arteriography or nuclear or echocardiographic stress testing. RESULTS: Twenty-four patients had regional wall motion abnormalities (RWMA) on their initial echo which were unchanged during the period of monitoring. All had evidence of CAD. Twenty-eight patients had transient RWMA. All had evidence of CAD. Eighteen patients had normal wall motion throughout the monitoring period, 14 of these had no evidence of CAD, and four had evidence of CAD. These four patients did not have chest pain during monitoring. The sensitivity, specificity, and accuracy of echocardiographic monitoring for diagnosing non-ST elevation myocardial infarction was 88%, 100%, and 91% respectively. The sensitivity, specificity, and accuracy of the ECG for diagnosis of CAD were 31%, 100%, and 52%, respectively. Echocardiography was superior to ECG (P < 0.001). CONCLUSIONS: The data indicate that continuous cardiac imaging is superior to ECG monitoring for the diagnosis of CAD in patients presenting with acute non-ST segment elevation chest pain syndromes. This technique could be a useful adjunct to ECG monitoring for myocardial ischemia in the acute care setting.

Implications of acute left ventricular remodeling during squatting stress echocardiography.

BACKGROUND: We previously demonstrated that squatting induces left ventricular (LV) wall motion abnormalities (WMA) in areas subtended by stenotic coronary arteries. In addition, it was observed that some subjects developed acute changes in LV shape (acute left ventricular remodeling [ALVRM]) during squatting. OBJECTIVE: This study tested the hypothesis that patients with ALVRM during squatting echocardiography have higher incidences of severe coronary artery disease (CAD). METHODS: Echocardiography was performed in all standard views during standing and squatting. End-systolic frames in the apical four-chamber view were analyzed. RESULTS: The subjects were divided into three groups. Group 1 consisted of 12 subjects who developed squatting-induced ALVRM with apical and distal posterior septal akinesis, dilation of the apex and marked LV shape change at end-systole. Group 2 consisted of 20 subjects with distal posterior septal and apical akinesis without ALVRM, during squatting. Group 3 consisted of 64 subjects who developed WMA in areas other than the apex (n = 49), or normal wall motion (n = 15) during squatting. Coronary angiography in group 1 revealed that 6 subjects had left main coronary artery stenosis (LMCAS ≥ 50%), two had severe three vessel disease (≥ 90% stenosis), and one had 100% left anterior descending coronary artery occlusion. Severe CAD was defined for purpose of this study as the presence of LMCAS, or severe three vessel disease (≥ 90% stenosis). Six subjects in group 2 had LMCAS and none had severe three vessel disease (P < 0.05 vs. group 1 for LMCAS and/or three vessel disease). In group 3, eight had LMCAS and none had severe three vessel disease (P < 0.0001 vs. group 1). CONCLUSION: Patients with ALVRM have severe CAD. Therefore, patients who develop ALVRM during squatting require urgent evaluation for revascularization therapy.

Comparison of squatting stress echocardiography and dobutamine stress echocardiography for the diagnosis of coronary artery disease.

BACKGROUND: Dobutamine stress echocardiography (DSE) is commonly used for the diagnosis for coronary artery disease (CAD). We previously demonstrated that squatting induces wall motion abnormalities (WMA) in areas subtended by stenotic coronary arteries. OBJECTIVE: This study was designed to test the hypothesis that dobutamine and squatting stress echocardiography are equally useful for the diagnosis of CAD. METHODS: We studied 39 patients who were scheduled to have coronary angiography for the evaluation of chest pain. Each patient had squatting stress echocardiography followed by DSE. For squatting stress echocardiography the echocardiogram in standard views was recorded in the standing position. The procedure was repeated during squatting for 2 minutes. Dobutamine echocardiography was performed using standard protocol. The squatting and dobutamine stress echocardiograms were interpreted by an observer blinded to the results of coronary angiography. RESULTS: During squatting, new or worsening WMA developed in 20 patients. Six patients developed WMA in the left anterior descending artery territory, three in circumflex territory, three in the right coronary artery territory, and eight in multiple coronary territories. The sensitivity, specificity, and accuracy of squatting echocardiography for diagnosis of CAD were 95%, 94%, and 94%, respectively. For DSE, the sensitivity, specificity, and accuracy for the diagnosis of CAD were 85%, 94%, and 90%, respectively. There was no significant difference between squatting and dobutamine stress echocardiography for the diagnosis of CAD (P = 0.702). CONCLUSION: These data indicate that squatting and dobutamine echocardiography are equally useful in the diagnosis of CAD. In selected patients, squatting echocardiography may be used in place of dobutamine echocardiography for the diagnosis of CAD.

Detection of wall motion abnormalities during ambulatory echocardiography using a novel ultrasound transducer.

BACKGROUND: This investigation was designed to determine whether transient wall motion abnormalities due to myocardial ischemia induced by walking could be detected by ambulatory echocardiography. METHODS: Two groups were studied. Group 1 consisted of 10 males (mean age 34 years) who had no symptoms of angina. Group 2 consisted of eight selected patients (mean 61 years) with angina and angiographic evidence of coronary artery disease. The 2.5 MHz transducer is spherical in its distal part and mounted in an external housing to permit steering in 360°. The external housing was attached to the chest wall using an adhesive patch. The transducer was placed in the 3rd or 4th intercostal space at the left sternal border to permit imaging of the left ventricle (LV) in its short axis and attached to the chest wall. The transducer was interfaced with an Acuson Cypress echocardiography system which was placed on a mobile cart. To permit portability, the echocardiography system was powered by a capacitor (UPS device). The subjects were asked to walk along the corridor as fast as possible for 10 minutes or until the onset of symptoms while pushing the cart. The short axis of the LV was displayed on a monitor and recorded on optical disks. RESULTS: The heart rate, systolic blood pressure (SBP), and double product of Group 1 at rest were 77 ± 3 beats/min, 119 ± 13 mmHg, and 9,150 ± 868, respectively, and increased to 106 ± 8 beats/min, 129 ± 15 mmHg, and 1,3793 ± 2,176 with walking. The baseline heart rate, SBP, and double product were 71 ± 12 beats/min, 130 ± 14 mmHg, and 8,555 ± 1,928 in Group 2 and increased to 94 ± 14 beats/min, 135 ± 20 mmHg, and 12,480 ± 3,830 with walking. All patients in Group 1 had normal wall motion at rest and during walking. Patients in Group 2 had normal wall motion during rest and new wall motion abnormalities were noted in all subjects during walking (anterior septum and/or anterolateral wall in seven, posterolateral wall in one). The wall motion abnormalities resolved shortly after discontinuation of walking. CONCLUSION: Ambulatory echocardiography permitted the detection of transient wall motion abnormalities in patients with coronary artery disease (CAD). This technique could be potentially useful in evaluating selected patients for myocardial ischemia.

Atherosclerosis in chronic kidney disease: lessons learned from glycation in diabetes.

In diabetes, glycation is a nonenzymatic posttranslational modification resulting from the bonding of a sugar molecule with a protein or lipid followed by oxidation, resulting in the development of advanced glycation end products (AGE). Like glycation, carbamylation is a posttranslational protein modification that is associated with AGE formation. Glycation of extracellular matrix proteins and low-density lipoprotein with subsequent deposition in the vessel wall could contribute to inflammatory response and atheroma formation. It is logical to extrapolate that carbamylation may result in modification of vessel wall proteins similar to glycation, and predispose to atherosclerosis.

Integrated intravascular optical coherence tomography (OCT) - ultrasound (US) catheter for characterization of atherosclerotic plaques in vivo.

A miniature integrated intravascular optical coherence tomography (OCT) - ultrasound (US) catheter for real-time imaging of atherosclerotic plaques has been developed, providing high resolution and deep tissue penetration at the same time. This catheter, with an outer diameter of 1.18mm, is suitable for imaging in human coronary arteries. The first in vivo 3D imaging of atherosclerotic microstructure in a rabbit abdominal aorta obtained by an integrated OCT-US catheter is presented. In addition, in vitro imaging of cadaver coronary arteries were conducted to demonstrate the imaging capabilities of this integrated catheter to classify different atherosclerotic plaque types.

Use of contrast echocardiography to detect displacement of the needle during pericardiocentesis.

Bedside pericardiocentesis is a safe and routinely practiced procedure. We report a case in which echocardiography-guided pericardiocentesis was performed urgently for cardiac tamponade. In this case, there was displacement of the periocardiocentesis needle that was only detected by change in the color of aspirated fluid and confirmed by the use of contrast echocardiography. We prescribe the use of routine echocardiographic monitoring during pericardiocentesis to avoid this type of complication.

The Sirtuin System: The Holy Grail of Resveratrol?

The oxidative stress theory has been associated with atherosclerosis and has prompted a multitude of studies to evaluate the effects of antioxidants on cardiovascular disease prevention. Resveratrol, a relatively new antioxidant has gained considerable curiosity. This polyphenol stilbene identified in grape skin, is believed to be the main component contributing to the anti-atherosclerotic benefits linked to red wine consumption. It has demonstrated the ability to protect endothelial cells from lipid damage, promote vasodilation via modulation of nitric oxide synthesis, and inhibit platelet aggregation and smooth muscle proliferation. Although the complete mechanism of Resveratrol has yet to be fully elucidated, the Sirtuin system, consisting of 7 highly conserved families of regulator genes, are thought to be instrumental in establishing the various health benefits. In this article we assess the current applications, mechanism, pharmacokinetics, bioavailability, and safety profile of the novel antioxidant Resveratrol and provide an in-depth review of the influence of the Sirtuin system on the Resveratrol mechanism of action. We resolve that while early data on Resveratrol are promising, the anti-oxidative and ultimately, anti-atherosclerotic potential depends on further clarification of the intricate and complex relationship between Resveratrol and the Sirtruin system.

Serum level of pigment epithelium-derived factor is a marker of atherosclerosis in humans.

OBJECTIVE: Pigment epithelium-derived factor (PEDF) could play a protective role against atherosclerosis. However, there is no clinical study to examine the relationship between serum level of PEDF and atherosclerosis in humans. METHODS/RESULTS: The study involved 317 consecutive outpatients in Kurume University Hospital (220 male and 97 female) with a mean age of 62.1±9.1. We examined whether serum level of PEDF were independently associated with vascular inflammation evaluated by [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and intima-media thickness (IMT) in carotid artery in humans. Carotid [(18)F]-FDG uptake, an index of vascular inflammation within the atherosclerotic plaques, was measured as standardized uptake value (SUV). Mean serum PEDF level, carotid SUV and IMT values were 13.5±1.1 µg/mL, 1.34±0.19, and 0.71±0.15 mm, respectively. In multiple stepwise regression analysis, estimated glomerular filtration rate (p<0.001), males (p<0.001), homeostasis model assessment of insulin resistance index (p<0.05), heart rate (p<0.05), triglycerides (p<0.05), carotid IMT (p<0.05), waist circumference (p<0.05) and carotid SUV (p<0.05) were independently correlated to PEDF level (R(2)=0.332). CONCLUSION: The present study reveals that serum level of PEDF is independently associated with vascular inflammation and IMT, thus suggesting that PEDF level is a novel biomarker that could reflect atherosclerosis in humans.