Endothelial progenitor cells delivered into the pericardial space incorporate into areas of ischemic myocardium.

OBJECTIVE: Our objective was to determine whether autologous endothelial progenitor cells (EPCs) delivered into the pericardial space will migrate to and incorporate into ischemic myocardium in a porcine model. BACKGROUND: Use of EPCs to enhance neovascularization and preserve myocardial function in ischemic tissue is undergoing intense scrutiny as a potential therapy. Delivery into the pericardial sac may overcome some of the limitations of currently employed cell delivery techniques. METHODS: EPCs were immunopurified from peripheral blood of Yorkshire pigs by selecting for the CD31 surface antigen, and adherent cells were cultured for 3-5 days. After myocardial ischemia was induced in the left anterior descending (LAD) artery, either autologous DiI (1,1'-dioctadecyl-1-3,3,3',3'-tetramethylindocarbocyanine perchlorate)-labeled EPCs (n=10) or serum-free medium (SFM; n=8) was delivered into the pericardial space using a percutaneous transatrial approach. Animals were sacrificed on Day 7 or 21. Echocardiography was performed at baseline, during ischemia, and on Day 7 in six SFM group animals and six EPC group animals. RESULTS: On Day 7, EPCs were identified in the left ventricular (LV) anterior wall or anterior septum in all six EPC-treated animals (cell density of 626 ± 122/mm(2)). On Day 21, EPCs were identified in the LV anterior wall or anterior septum in three of four EPC-treated animals (cell density of 267 ± 167/mm(2)). These cells showed dual staining for DiI and Bandeiraea simplicifolia lectin I (a marker of both native and exogenous endothelial cells). At the Day 7 follow-up, echocardiography demonstrated that fractional shortening in the EPC-treated group was 30.6 ± 3.4, compared with 22.6 ± 2.8 in SFM controls (P=.05). CONCLUSIONS: EPCs can migrate from the pericardial space to incorporate exclusively into areas of ischemic myocardium and may have favorable effects on LV function.

Multiple yellow plaques assessed by angioscopy with quantitative colorimetry in patients with myocardial infarction.

BACKGROUND: Multiple angioscopic yellow plaques are associated with diffuse atherosclerotic plaque, and may be prevalent in patients with myocardial infarction (MI), so in the present study the yellow plaques in the coronary arteries of patients with MI was evaluated using quantitative colorimetry, and compared with those of patients with stable angina (SA). METHODS AND RESULTS: In the recorded angioscopic images of 3 coronary vessels in 29 patients (15 patients with MI, 14 with SA), yellow plaques were determined as visually yellow regions with b* value >0 (yellow color intensity) measured by the quantitative colorimetric method. A total of 90 yellow plaques were identified (b* =19.35+/-8.3, 3.05-45.35). Yellow plaques were significantly more prevalent in 14 (93%) of 15 culprit lesions of MI as compared with 8 (57%) of 14 of SA (p=0.03). In non-culprit segments, yellow plaques were similarly prevalent in 13 (87%) patients with MI and 11 (79%) with SA (p=0.65). Overall, multiple (> or =2) yellow plaques were prevalent in 13 (87%) patients with MI, similar to the 10 (71%) with SA (p=0.38). The number of yellow plaques was significantly higher in patients with MI (3.8+/-1.9) than in those with SA (2.4+/-1.6, p=0.03). CONCLUSION: The present study suggests that patients with MI tend to have diffuse atherosclerotic plaque in their coronary arteries.

Topographic association of angioscopic yellow plaques with coronary atherosclerotic plaque: assessment with quantitative colorimetry in human coronary artery autopsy specimens.

Yellow plaques seen during coronary angioscopy are thought to be the surrogates for superficial intimal lipids in coronary plaque. Given diffuse and heterogeneous nature of atherosclerosis, yellow plaques in coronaries may be seen as several yellow spots on diffuse coronary plaque. We examined the topographic association of yellow plaques with coronary plaque. In 40 non-severely stenotic ex-vivo coronary segments (average length: 52.2 +/- 3.1 mm), yellow plaques were examined by angioscopy with quantitative colorimetry. The segments were cut perpendicular to the long axis of the vessel at 2 mm intervals, and 1045 slides with 5 microm thick tissue for whole segments were prepared. To construct the plaque surface, each tissue slice was considered to be representative of the adjacent 2 mm. The circumference of the lumen and the lumen border of plaque were measured in each slide, and the plaque surface region was constructed. Coronary plaque was in 37 (93%) of 40 segments, and consisted of a single mass [39.9 +/- 3.9 (0-100) mm, 311.3 +/- 47.4 (0.0-1336.2) mm2]. In 30 (75%) segments, multiple (2-9) yellow plaques were detected on a mass of coronary plaque. The number of yellow plaques correlated positively with coronary plaque surface area (r = 0.77, P < 0.0001). Yellow plaques in coronaries detected by angioscopy with quantitative colorimetry, some of them are associated with lipid cores underneath thin fibrous caps, may be used to assess the extent of coronary plaque. Further research using angioscopy could be of value to study the association of high-risk coronaries with acute coronary syndromes.

Intravascular imaging of atherosclerotic human coronaries in a porcine model: a feasibility study.

OBJECTIVES: To perform intravascular imaging of atherosclerotic human coronary conduits in an animal model under conditions of flow and cardiac motion that approximate those encountered in vivo. BACKGROUND: Given the lack of animal models of vulnerable plaque, a model which would allow imaging of human disease and simulate coronary motion and blood flow could advance the development of emerging technologies to detect vulnerable plaques. METHODS: Human coronary segments from adult cadaver hearts were prepared as xenografts. In anesthetized Yorkshire pigs (45-50 kg) the chest was opened and the exposed aorta and right atrium were cannulated and attached in an end-to-end fashion to the human coronary xenograft, forming an aorto-atrial conduit. The xenograft was fixed to the anterior wall of the heart to simulate motion. Angiography and intravascular ultrasound (IVUS) of each graft were performed. RESULTS: Twelve human coronary grafts (10 from right coronary segments) were prepared and implanted successfully in seven animals. All animals tolerated the procedure. The average graft length was 39 +/- 2.3 mm. Blood flow rates distal to the graft were >100 ml/min in nine grafts. IVUS was performed in all 12 grafts and documented expansion of arterial (6.9%) and luminal (9.3%) dimensions during the cardiac cycle (P < 0.001 for both). There was a wide range of coronary atherosclerotic pathology within the grafts, including intimal thickening, fibrocalcific plaque, and deep lipid pools. CONCLUSION: This human-to-porcine coronary xenograft model allows intravascular imaging of human coronary pathology under conditions of blood flow and motion, and may be used to develop technologies aimed at identifying high-risk plaques.

High yellow color intensity by angioscopy with quantitative colorimetry to identify high-risk features in culprit lesions of patients with acute coronary syndromes.

High yellow color intensity (HYCI) regions of atherosclerotic plaque, determined by angioscopy with quantitative colorimetry, are associated with lipid cores underneath thin fibrous caps in ex vivo tissue samples. To determine whether HYCI regions of coronary plaque are associated with disruption or thrombus in living patients, quantitative colorimetry was applied to angioscopy, and the color of culprit lesions was measured in patients with acute coronary syndromes. In 46 patients with acute coronary syndromes (acute myocardial infarction, n = 14; unstable angina pectoris [UAP] with culprit thrombus, n = 16; and UAP without culprit thrombus, n = 16), the recorded angioscopic images of culprit lesions were analyzed using a quantitative colorimetric method based on the L*a*b* color space applied to angioscopy (positive b* = yellow color intensity). HYCI was defined as b* value >23. Plaque disruption was significantly more prevalent in 19 of 24 HYCI regions (79%) than in 9 of 22 non-HYCI regions (41%) (p = 0.007). Culprit HYCI regions were prevalent in patients with myocardial infarction (11 of 14 [79%]), followed by those with UAP with thrombus (9 of 16 [56%]) and UAP without thrombus (4 of 16 [25%]) (p = 0.01 for trend), and were significantly more prevalent in 66% of patients with myocardial infarction and UAP with thrombus compared with 25% of those with UAP without thrombus (p = 0.007). In conclusion, HYCI regions of coronary plaque may be indicative of high-risk lesions vulnerable to thrombosis. Coronary angioscopy with quantitative colorimetry could be used to study the association between high-risk coronary lesions and future cardiovascular events.

Quantitative colorimetry of atherosclerotic plaque using the L*a*b* color space during angioscopy for the detection of lipid cores underneath thin fibrous caps.

OBJECTIVES: Yellow plaques seen during angioscopy are thought to represent lipid cores underneath thin fibrous caps (LCTCs) and may be indicative of vulnerable sites. However, plaque color assessment during angioscopy has been criticized because of its qualitative nature. The purpose of the present study was to test the ability of a quantitative colorimetric system to measure yellow color intensity of atherosclerotic plaques during angioscopy and to characterize the color of LCTCs. METHODS: Using angioscopy and a quantitative colorimetry system based on the L*a*b* color space [L* describes brightness (-100 to +100), b* describes blue to yellow (-100 to +100)], the optimal conditions for measuring plaque color were determined in three flat standard color samples and five artificial plaque models in cylinder porcine carotid arteries. In 88 human tissue samples, the colorimetric characteristics of LCTCs were then evaluated. RESULTS: In in-vitro samples and ex-vivo plaque models, brightness L* between 40 and 80 was determined to be optimal for acquiring b* values, and the variables unique to angioscopy in color perception did not impact b* values after adjusting for brightness L* by manipulating light or distance. In ex-vivo human tissue samples, b* value >/=23 (35.91 +/- 8.13) with L* between 40 and 80 was associated with LCTCs (fibrous caps <100 mum). CONCLUSIONS: Atherosclerotic plaque color can be consistently measured during angioscopy with quantitative colorimetry. High yellow color intensity, determined by this system, was associated with LCTCs. Quantitative colorimetry during angioscopy may be used for detection of LCTCs, which may be markers of vulnerability.

Update on coronary angioscopy: review of a 20-year experience and potential application for detection of vulnerable plaque.

Predicting the occurrence of future acute coronary syndromes remains an important challenge of contemporary cardiology. It is thought that detecting the individual vulnerable plaques in patients can be an important step to preventing myocardial infarction and sudden cardiac death. Coronary angioscopy can provide detailed information of the luminal surface of plaque, such as color, thrombus, or disruption, and is one of a few possibly useful imaging modalities for identifying vulnerable plaques. During its 20-year history, coronary angioscopy has been used as a diagnostic tool or to guide coronary angioplasty, and has contributed to our understanding of the pathophysiology of coronary artery disease. Yellow plaques seen during angioscopy seem to have many characteristics of high risk or vulnerable plaques, most consistent with the thin-cap fibroatheroma. Moreover, differences in yellow color have been reported to reflect differences in the structure or composition of plaques. Development of quantitative methods to assess plaque color and histopathologic correlations in conjunction with prospective natural history studies may lead to advances in vulnerable plaque detection by coronary angioscopy. Although current angioscopic devices are limited by the need to displace the column of blood in order to see the vessel wall, and by the lack of quantitative colorimetric methods, advances in technology may lead to new device versions that could be practical for expanded clinical use.

Angioscopic follow-up study of coronary ruptured plaques in nonculprit lesions.

OBJECTIVES: Changes of ruptured plaques in nonculprit lesions were evaluated using coronary angioscopy. BACKGROUND: The concept of multiple coronary plaque ruptures has been established. However, no detailed follow-up studies of ruptured plaques in nonculprit lesions have yet been reported. METHODS: Forty-eight thrombi in 50 ruptured coronary plaques in nonculprit lesions in 30 patients were identified by angioscopy. The percent diameter stenosis (%DS) at the target plaques on quantitative coronary angiographic analysis and the serum C-reactive protein (CRP) level were measured. RESULTS: The mean angioscopic follow-up period was 13 +/- 9 months. Thirty-five superimposed thrombi still remained at follow-up, and the predominant thrombus color changed from red (56%) at baseline to pinkish-white (83%) at follow-up. The healing rate increased according to the angioscopic follow-up period (23% at 12 months, p = 0.044). The %DS at the healed plaque increased from baseline to follow-up (12.3 +/- 5.8% vs. 22.7 +/- 11.6%, respectively; p = 0.0004). The serum CRP level in patients with healed plaques (n = 10) was lower than that in those without healed plaques (n = 19; 0.07 +/- 0.03 mg/dl vs. 0.15 +/- 0.11 mg/dl, respectively; p = 0.007). CONCLUSIONS: The present study demonstrated that: 1) ruptured plaques in nonculprit lesions tend to heal slowly with a progression of angiographic stenosis; and 2) the serum CRP level might reflect the disease activity of the plaque ruptures.

Elevated troponin T levels and lesion characteristics in non-ST-elevation acute coronary syndromes.

BACKGROUND: Elevated troponin T levels in non-ST-elevation acute coronary syndromes (NSTE-ACS) have been shown to predict an adverse outcome. Furthermore, it has been reported that troponin T could help improve the effectiveness of such new antithrombotic drugs as platelet GPIIb/IIIa antagonists and low-molecular-weight heparins. We hypothesized that such elevated troponin T levels in NSTE-ACS indicate the presence of thrombus at culprit lesions, and this hypothesis was verified through the use of coronary angioscopy. METHODS AND RESULTS: We studied 57 consecutive patients with NSTE-ACS who underwent preinterventional angioscopy. Before catheterization, we obtained blood samples to determine troponin positivity, and the patients were then classified as either troponin-positive or troponin-negative groups (diagnostic threshold, 0.1 ng/mL). Using angioscopy at the culprit lesions, we examined the presence of coronary thrombus, yellow plaque, and complex plaque. Moreover, we compared the preinterventional angiographic parameters (thrombus and complexity of the culprit lesion, and TIMI flow) between the two groups. Twenty-two patients were troponin-positive and 35 patients were troponin-negative. Univariate analyses indicated that the TIMI flow and the incidence of coronary thrombus detected with angioscopy correlate with the elevated troponin T levels. A multivariate logistic regression analysis showed the presence of coronary thrombus detected with angioscopy to be the only independent factor associated with elevated troponin T levels in patients with NSTE-ACS (odds ratio, 22.1; 95% CI, 2.59 to 188.42; P=0.0046). CONCLUSIONS: Using angioscopy, the elevated troponin T levels in NSTE-ACS were confirmed to be strongly associated with the presence of coronary thrombus.

Changes in coronary plaque color and morphology by lipid-lowering therapy with atorvastatin: serial evaluation by coronary angioscopy.

OBJECTIVES: Changes in coronary plaque color and morphology by statin therapy were evaluated using coronary angioscopy. BACKGROUND: Coronary plaque stabilization by statin therapy has not been clarified in humans. METHODS: Thirty-one patients with coronary artery disease were divided into either the comparison group (n = 16) or the atorvastatin group (n = 15). Before treatment and 12 months after, the color and complexity of 145 coronary plaques were determined according to angioscopic findings. The yellow score of the plaque was defined as 0 (white), 1 (light yellow), 2 (yellow), or 3 (dark yellow), and its disrupted score was defined as 0 (smooth surface) or 1 (irregular surface) and as 0 (without thrombus) or 1 (with thrombus). In each patient, the mean yellow score and mean disrupted score were calculated. RESULTS: Mean low-density lipoprotein cholesterol (LDL-C) decreased by 45% in the atorvastatin group, whereas an increase of 9% was seen in the comparison group. The mean yellow score decreased from 2.03 to 1.13 in the atorvastatin group, whereas it increased from 1.67 to 1.99 in the comparison group. There was a good correlation between the change in the mean yellow score and the change in LDL-C levels (r = 0.81, p < 0.0001). The change in the mean yellow score and mean disrupted score differed significantly between the two groups (p = 0.002 and p = 0.03, respectively). CONCLUSIONS: This is the first report clarifying detailed changes in coronary plaque by statin in humans. This study indicated that lipid-lowering therapy changes plaque color and morphology and should then lead to coronary plaque stabilization.

Unique single coronary artery with acute myocardial infarction: observation of the culprit lesion by intravascular ultrasound and coronary angioscopy.

We report an acute myocardial infarction in a patient with a single coronary artery. The right coronary artery arose from the middle portion in the left anterior descending artery through the transverse branch. This type of single coronary artery has not been previously reported. Moreover, this is the first report in which the culprit lesion in a patient with a single coronary artery was observed by intravascular ultrasound and coronary angioscopy. The patient underwent successful coronary stent deployment.

Increased expression of monocyte chemoattractant protein-1 in atherectomy specimens from patients with restenosis after percutaneous transluminal coronary angioplasty.

The plasma concentration of monocyte chemoattractant protein-1 (MCP-1) antigen is higher in patients with restenosis after coronary angioplasty than in those who do not restenose. In this study the MCP-1 expression of coronary atherectomy specimens was investigated by immunohistochemistry. Samples were obtained from 12 patients with restenosis and 15 with de novo lesions by directional coronary atherectomy. MCP-1 immunoreactivity was found in all patients in the restenosis group and in 8 of the de novo group. The frequency of macrophage expression was higher in the restenosis group than in de novo group. These results indicate that local expression of MCP-1 may be associated with the mechanisms of vascular remodeling after coronary angioplasty.

Challenging case of pulse infusion thrombolysis using a unique pump system for a patient with deep vein thrombosis: a case report.

A 69-year-old man presented with chronic deep vein thrombosis due to massive thrombi extending from the inferior vena cava to both femoral veins. He had undergone surgery for prostatic cancer in 1991, and since then he had been taking an artificial estrogen agent. He was successfully treated by pulse infusion thrombolysis using a unique pump system, which we have developed, without complication.