Increased plasminogen activator inhibitor-1 and apolipoprotein (a) in coronary atherectomy specimens in acute coronary syndromes.

BACKGROUND: Although increased tissue factor expression is known in vulnerable plaques, there is no reported study to compare plaque fibrinolysis in stable and unstable plaques. This study investigates the extent of plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein (a) [apo(a)] in the plaques of different types of coronary artery disease as well as the correlation between these molecules and infiltration of macrophages to plaques. METHODS: Using immunohistochemical staining, we examined PAI-1 expression and apo(a) deposition in coronary atherosclerotic specimens obtained by directional coronary atherectomy from 19 patients with acute myocardial infarction (AMI), 12 with unstable angina pectoris (UAP), and 13 with stable angina pectoris (SAP). The percentages of the total areas of specimens stained with PAI-1 or apo(a) were estimated by an NIH image program. The proportion of macrophages as a percentage of all cells in plaques was calculated as the macrophage density. RESULTS: We found significantly higher percentages of total areas of specimens stained with PAI-1 in AMI (25.5 +/- 8.6%, P < 0.001) and UAP (22.2 +/- 10.4%, P < 0.005) than in SAP (9.5 +/- 5.0%), as well as with apo(a) (AMI; 11.7 +/- 7.1%, P < 0.005, UAP; 11.1 +/- 5.5%, P < 0.01 versus SAP; 3.9 +/- 1.5%). Linear regression analysis of all the samples showed a correlation between PAI-1 or apo(a) and macrophage density (PAI-1: r = 0.75, P < 0.001 and apo(a): r = 0.56, P < 0.001). CONCLUSIONS: Our results suggest a possible contribution of increased PAI-1 and apo(a) in plaques to the pathogenesis of acute coronary syndromes including impaired fibrinolysis.

Expression of cytokine and adhesion molecule mRNA in atherectomy specimens from patients with coronary artery disease.

Coronary arteriosclerosis is an underlying condition in acute myocardial infarction (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP), and is also related to restenosis (RS) following coronary intervention. To investigate the pathogenesis of this condition, a quantitative reverse transcriptase polymerase chain reaction was used to determine relative levels of mRNA for interleukin (IL)-1beta, IL-6, IL-8, transforming growth factor beta (TGF-beta), intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell adhesion molecule (VCAM)-1 using directional coronary atherectomy (DCA) specimens. Eleven patients with AMI, 7 with UAP, 10 with SAP and 6 with RS following a previous coronary intervention underwent DCA. The mRNA intensity for each molecule was expressed by comparing it with that of beta-actin mRNA. The AMI and UAP patients showed high frequencies of mRNA for IL-1beta, IL-8, TGF-beta, and ICAM-1 together with strong intensities of expression, whereas SAP patients showed decreased mRNA expression for these molecules. Increased IL-6 mRNA expression was observed only in AMI samples. Specimens from RS patients revealed an accumulated expression of proinflammatory cytokines, except for IL-6, as well as of TGF-beta. The study suggests that variation in mRNA expression may reflect the pathophysiology of specific types of coronary artery disease, and remodeling following vascular injury.

Angioscopy after laser and balloon coronary angioplasty.

OBJECTIVES: Percutaneous intracoronary angioscopy was used to study the morphologic changes occurring in coronary arteries after balloon or laser angioplasty. BACKGROUND: Angioscopy is thought to provide details of the coronary vessel lumen and the inner wall. METHODS: Coronary lesions were studied in 44 patients with a 4.5F Imagecath angioscope before and after each interventional procedure. Balloon and laser angioplasty were performed in 21 (group I) and 23 patients (group II), respectively. There was no difference in age, gender or angiographic lesion appearance before the procedure between the two groups. RESULTS: Circumferential visualization of the target lesion was successfully completed in 17 group I and 19 group II patients. A larger lumen than that observed at baseline was seen in all 17 group I and in 13 of the 19 group II patients. Tissue remnants were observed in all group I and II patients. Laser irradiation resulted in characteristic sharp-edged craters. Dissection was identified in 2 of 19 patients before versus 9 of 19 patients after balloon angioplasty (p < 0.05) and in 0 of 23 patients before versus 4 of 23 patients after laser angioplasty (p = NS). Subintimal hemorrhage was observed in 3 of 19 patients before versus 11 of 19 patients after balloon angioplasty (p < 0.05) and in 2 of 23 patients before versus 4 of 23 patients after laser angioplasty (p = NS). The frequency of hemorrhage was higher in group I than in group II (11 of 19 vs. 4 of 23, respectively, p < 0.02). CONCLUSIONS: Angioscopy provides valuable information on lesion morphology after coronary interventions. Balloon dilation results in a high rate of dissection and subintimal hemorrhage. Laser angioplasty is able to ablate obstructing tissue and results in a lower rate of subintimal hemorrhage than balloon dilation.

[Coronary vasospastic activity at sites of percutaneous transluminal coronary angioplasty: evaluation using intracoronary acetylcholine administration].

To investigate coronary vasospastic activity after percutaneous transluminal coronary angioplasty (PTCA), we performed intracoronary injection of acetylcholine in 55 patients, mean 3.3 months after successful PTCA. Coronary spasm was defined as transient total or subtotal occlusion of the PTCA sites. Sixty-nine lesions of the 55 patients were examined to determine whether spasm was provoked by incremental doses of acetylcholine. Restenosis was defined as coronary luminal narrowing of > or = 50% after nitroglycerin or isosorbide dinitrate. Twenty of the 55 patients (36%) and 23 of the 69 lesions (33%) had coronary spasm. There was no correlation between the incidence of coronary spasm and the interval from PTCA to the acetylcholine test. The spasm was provoked in 17 lesions of the 50 non-restenotic lesions (34%) and was also provoked in 6 of the 19 restenotic lesions (32%). On the other hand, restenoses occurred in 6 of the 23 spastic lesions (26%) and in 13 of the 43 non-spastic lesions (28%). There was no correlation between the incidence of coronary spasm and the occurrence of restenoses. Twenty-four patients had undergone acetylcholine provocative test before PTCA. Among these 24 patients, 11 had coronary spasm before PTCA, and 7 had coronary spasticity after PTCA. Four patients who had positive evidence of coronary spasm before PTCA did not show negative spasm after PTCA. On the other hand, 3 patients who did not show evidence of coronary spasm showed positive evidence of coronary spasm after PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

[Study of sympathetic nervous function under effort induced ischemia in patients with angina pectoris with I-123 metaiodobenzylguanidine (MIBG) myocardial SPECT images].

I-123 metaiodobenzylguanidine (MIBG) is a norepinephrine analog, which can be used to study the sympathetic nervous function of the heart. With MIBG myocardial SPECT images sympathetic nervous function under effort induced ischemia were studied in 18 patients with significant coronary artery lesions. In 5 patients with effort induced ischemic region in stress T1-201 myocardial images rest MIBG images were collected and then exercise stress test was performed. Patients continued exercising for 3 minutes after onset of symptom. Post-stress MIBG images were collected. Definite ischemic region was noted in stress Tl-201 myocardial images, however no differences were noted between rest and post-stress MIBG images. These results suggested that exercise induced ischemia did not enhance release of uptaken MIBG. In 13 patients with significant coronary artery lesions symptom-limited exercise stress test was performed MIBG and Tl-201 were simultaneously injected at onset of symptom and patients continued exercising for an additional one minute. In 6 cases (46%, 6/13) MIBG defects with Tl-201 uptake were noted. These results showed that exercise induced ischemia depressed net MIBG uptake and that sympathetic nervous function (MIBG images) may be more sensitive to ischemic damage than muscle (Tl-201 images). It is suggested that exercise induced ischemia depressed reuptake of norepinephrine at sympathetic nervous endings. MIBG myocardial SPECT images may be useful for evaluating sympathetic nervous function under ischemia.

[Characteristics of stress Tl-201 myocardial SPECT images in patients with coronary artery lesion of just proximal portion of left anterior descending artery or high lateral branch].

Noninvasive detection of coronary artery lesion of just proximal portion of left anterior descending artery (LAD) is important because of its high morbidity. It is angiographically difficult to distinguish LAD and high lateral branch (HL). Utility of stress Tl-201 myocardial SPECT images for this purpose characteristics of ischemic region induced by coronary artery lesion of just proximal portion of LAD or HL were studied in 15 patients with localized stenosis more than 75% at just proximal portion of LAD and 5 patients with localized stenosis more than 75% at HL. Width of ischemic region at basal plane of SPECT images was determined by circumferential maximum count profile analysis of stress Tl-201 myocardial images. Width of ischemic region induced by coronary artery lesion of just proximal portion of LAD was 168 +/- 34 degrees. Right margin of ischemic region was 20 +/- 6 degrees and in 10 of 15 patients right margin lay between 20 degrees and 60 degrees. Left margin was -146 +/- 40 degrees and 7 patients with left margin more than -150 degrees showed left dominant coronary artery. Width of ischemic region induced by coronary lesion of HL was 64 +/- 10 degrees. Right margin of ischemic region was 78 +/- 10 degrees and left margin was 14 +/- 10 degrees. These results showed the possibility of detecting coronary artery lesion of just proximal portion of LAD and lesion of HL by stress Tl-201 myocardial SPECT images.

[Denervated myocardium detected by I-123 metaiodobenzylguanidine myocardial imaging following successful percutaneous transluminal coronary thrombolysis].

I-123 metaiodobenzylguanidine (MIBG) is taken up by sympathetic nerve endings. Thirteen patients with acute myocardial infarction, in whom reperfusion was achieved with percutaneous transluminal coronary thrombolysis (PTCR), MIBG and Tl-201 (Tl) images 14 days after PTCR which were simultaneously performed were studied. In the late stage, Tl myocardial stress test was also performed to detect ischemia. The extent of myocardial defect was estimated as percent defect. Wall motion was assessed by echocardiography. Ejection fraction (EF) was assessed in the chronic phase using left ventriculography. In nine of the 13 patients, the denerved myocardial regions having the MIBG defects were noted using a Tl uptake. A percent defect noted in MIBG images was 25 +/- 6% and was greater than those (6 +/- 6%,p less than 0.01) in Tl images. During the convalescent phase, the wall motion of the denerved region was restored (2, normal; 4, mild hypokinesis; 3, moderate hypokinesis) and in the chronic phase, EF was well preserved (61 +/- 14%). Ischemic regions noted in stress images coincided with denerved regions. In four patients without the denerved myocardium, EF was 46 +/- 3% (p less than 0.05) and wall motion of defect areas was akinetic. Both EF and myocardial viability were more preserved in cases with denerved region; i.e., PTCR was successfully performed in these cases. It was suggested that the denerved region was the area of severe ischemia during the acute phase and that it was salvaged by PTCR. The sympathetic nerve was damaged by severe ischemia, and depressed sympathetic function persisted long after the recovery of both myocardial perfusion and the wall motion.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nicorandil on coronary spasm.

In patients in whom dynamic coronary obstruction plays a predominant role in the pathogenesis of angina pectoris, dilatation of large coronary arteries and relief of coronary spasm account for the main mechanism of action of antianginal drugs. In this study, the acute vasodilating effects of nicorandil, a newly developed antianginal drug, were assessed in 10 patients who had spontaneous and ergonovine-evoked coronary spasms. The prompt, complete relief of both spontaneous and evoked coronary spasms was obtained in all of 10 patients with nicorandil. The coronary spasmolytic effect of nicorandil in the present series is thus considered to be beneficial to the treatment of coronary spasm.