Time course of vascular remodeling, formation of neointima and formation of neoadventitia after angioplasty in a porcine model.

BACKGROUND: Vascular remodeling is the major cause of restenosis after coronary balloon angioplasty but the pathophysiology of this process is not known. OBJECTIVE: To examine the time courses of vascular remodeling, formation of neointima and adventitial changes after coronary angioplasty. DESIGN: An experimental study on pigs using coronary angiography, intravascular ultrasound (IVUS), and histology. METHODS: Deep vessel-wall injury was induced by conventional balloon angioplasty in the circumflex and right coronary arteries, and by retraction of a chain-encircled balloon in the left anterior descending artery. Angiography in all three arteries and IVUS measurements in circumflex and left anterior descending arteries were performed before and after angioplasty, and at follow-up on days 0, 1, 4, 7, 14, 28, and 56 (n = 5 in each group). Serial IVUS measurements were used to determine vascular remodeling. Formation of neointima and neoadventitia was measured by histomorphometry. RESULTS: Angiographically evident loss of lumen and ultrasonographically detectable constrictive remodeling occurred between day 7 and day 28. IVUS measurements showed that late loss of lumen (days 28 and 56) was correlated to vascular remodeling but not to the increase in wall area (neointima plus media). Histomorphometry revealed that neointima was present from day 7 and that amount of neointima increased up to day 28. Area of adventitia increased during the first 4 days and remained unchanged thereafter. Adventitial neovascularization by vasa vasorum was observed from day 4 onward. CONCLUSIONS: Formation of neoadventitia precedes late loss of lumen, constrictive remodeling, and formation of neointima. The time course of vascular remodeling coincides with growth of neointima rather than with changes in the adventitia.

Histopathologic validation of in-vivo angioscopic observation of coronary thrombus after angioplasty in a porcine model.

BACKGROUND: Coronary angioscopy has been reported to be superior to angiography and intravascular ultrasound for detecting intracoronary thrombus. However, in-vivo histopathologic validation of angioscopic detection of intracoronary thrombus had not been performed. OBJECTIVE: To perform histopathologic validation of in-vivo angioscopic detection of coronary thrombus. DESIGN: An experimental, blinded comparison of angioscopy and histopathology. METHODS: Coronary angioscopy was performed from 0 to 14 days after angioplasty in 39 porcine coronary arteries. When thrombus was detected by angioscopy, it was subclassified into white, mixed red-white, or red thrombus according to color. By histopathology the presence of thrombus was determined and subclassified into platelet-rich, mixed platelet-erythrocyte, or erythrocyte-rich thrombus. RESULTS: Angioscopy correctly classified 19 of 21 coronary thrombi (sensitivity 90%) but incorrectly classified nine of 18 arteries without formation of thrombus as having a thrombus (specificity 50%). Positive and negative predictive values were 68 and 82%, respectively. The angioscopic subclassification of thrombus into white, mixed red-white, or red thrombi was not correlated to the corresponding histopathologic morphology (platelet-rich, mixed platelet-erythrocyte, or erythrocyte-rich) of the observed thrombi (chi2 test: P = 0.5). CONCLUSIONS: Angioscopic detection of thrombus in vivo had high sensitivity and negative predictive value but low-to-moderate specificity and positive predictive value. Visual assessment of color of angioscopically detected thrombi seemed not to reflect histopathologic morphology of thrombus according to the definitions used in the present study.

Thrombus organization plays no major role in late neointimal formation after angioplasty in porcine coronary arteries.

Thrombus organization has been suggested to play a major role in late neointimal formation after coronary angioplasty. We sought to describe the time sequence of lesion formation after angioplasty in porcine coronary arteries and to quantify the relation between early thrombosis and late neointimal formation. Deep vessel wall injury was induced by conventional balloon angioplasty in the circumflex (CX) and right coronary (RCA) arteries and by retraction of a chain-encircled balloon in the left anterior descendent artery (LAD). Lesions were assessed by histomorphometry at days 0, 1, 4, 7, 14, 28, and 56 after angioplasty. A response-to-injury index (lesion area/injury length) was determined for each artery. Angioplasty led to rupture/removal of media. Thrombus was present at the exposed adventitia at days 0, 1, and 4. From day 7, neointima was observed on the luminal side of the arterial wall. All thrombus had disappeared at day 28, at which only neointima was observed. Histomorphometry revealed that lesion formation after angioplasty was a gradually increasing process from day 0 to day 28 with no further growth from day 28 to day 56. Maximal thrombus size (day 4, RCA: 0.07+/-0.04 mm, CX: 0.23+/-0.16 mm, LAD: 0.15+/-0.11 mm) was significantly smaller than late neointimal formation (day 28, RCA: 0.68+/-0.18 mm, CX: 0.63+/-0.23 mm, LAD: 0.71+/-0.18 mm) in all three arteries (p < .03). Lesion formation after angioplasty is a gradually increasing process for 4 weeks. Maximal thrombus size is about four times smaller than late neointimal formation. Thus, thrombus organization plays no major role in late neointimal formation.