Incidence of thrombosis in perioperative and non-operative myocardial infarction.

BACKGROUND: The contribution of thrombosis to the aetiology of perioperative myocardial infarction (MI) is uncertain. We used optical coherence tomography (OCT) to determine the presence of thrombus and plaque morphology in patients experiencing a perioperative MI and matched patients experiencing a non-operative MI using OCT. METHODS: We conducted a single-centre, prospective, cohort study. Thirty patients experiencing a perioperative MI and 30 matched patients experiencing a non-operative MI, without ST elevation, underwent OCT to determine the presence of thrombus and culprit lesion plaque morphology. Angiography and OCT were performed a mean of 1.93(1.09) days and 1.53(0.68) days after the onset of perioperative and non-operative MI, respectively. OCT images were evaluated by an independent core laboratory without knowledge of whether the patient had suffered a perioperative or non-operative MI. RESULTS: We identified thrombus at the culprit lesion in four of 30 patients (13.3%) who experienced a perioperative MI and in 20 of 30 patients (66.7%) who experienced a non-operative MI, P<0.01. The only non-culprit lesion with thrombus was in a perioperative MI patient who also had a culprit lesion thrombus. Perioperative and non-operative MI culprit lesions demonstrated fibroatheroma in 18 patients (60.0%) us 20 patients (66.7%), respectively (P=0.52) and thin cap fibroatheroma in one patient (3.3%) us five patients (16.7%), respectively (P=0.11). One perioperative MI patient (3.3%) suffered a cardiac death and no non-operative MI patient died during the 30-day follow-up. CONCLUSIONS: Thrombosis was less common in perioperative than non-operative MI, despite similar underlying plaque morphology.

Randomized Trial of Primary PCI with or without RoutineManual Thrombectomy

During primary percutaneous coronary intervention (PCI), manual thrombectomymay reduce distal embolization and thus improve microvascular perfusion. Smalltrials have suggested that thrombectomy improves surrogate and clinical outcomes,but a larger trial has reported conflicting results.MethodsWe randomly assigned 10,732 patients with ST-segment elevation myocardial infarction(STEMI) undergoing primary PCI to a strategy of routine upfront manualthrombectomy versus PCI alone. The primary outcome was a composite of deathfrom cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, orNew York Heart Association (NYHA) class IV heart failure within 180 days. The keysafety outcome was stroke within 30 days.ResultsThe primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomygroup versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in thethrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.86). Therates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone;hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.34) and the primary outcome plusstent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio,1.00; 95% CI, 0.89 to 1.14; P = 0.95) were also similar. Stroke within 30 days occurredin 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%)in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P = 0.02).ConclusionsIn patients with STEMI who were undergoing primary PCI, routine manual thrombectomy,as compared with PCI alone, did not reduce the risk of cardiovasculardeath, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heartfailure within 180 days but was associated with an increased rate of stroke within30 days. (Funded by Medtronic and the Canadian Institutes of Health Research;TOTAL ClinicalTrials.gov number, NCT01149044.

Identifying women with severe angiographic coronary disease.

OBJECTIVES: To determine sex/gender differences in the distribution of risk factors according to age and identify factors associated with the presence of severe coronary artery disease (CAD). DESIGN: We analysed 23,771 consecutive patients referred for coronary angiography from 2000 to 2006. SUBJECTS: Patients did not have previously diagnosed CAD and were referred for first diagnostic angiography. OUTCOME MEASURES: Patients were classified according to angiographic disease severity. Severe CAD was defined as left main stenosis > or = 50%, three-vessel disease with > or = 70% stenosis or two-vessel disease including proximal left anterior descending stenosis of > or = 70%. Univariate and multivariate logistic regression was used to assess the association between risk factors and angina symptoms with severe CAD. RESULTS: Women were less likely to have severe CAD (22.3% vs. 36.5%) compared with men. Women were also significantly older (69.8 +/- 10.6 vs. 66.3 +/- 10.7 years), had higher rates of diabetes (35.0% vs. 26.6%), hypertension (74.8% vs. 63.3%) and Canadian Cardiovascular Society (CCS) class IV angina symptoms (56.7% vs. 47.8%). Men were more likely to be smokers (56.9% vs. 37.9%). Factors independently associated with severe CAD included age (OR = 1.05; 95% CI 1.05-1.05, P < 0.01), male sex (OR = 2.43; CI 2.26-2.62, P < 0.01), diabetes (OR = 2.00; CI 1.86-2.18, P < 0.01), hyperlipidaemia (OR = 1.50; CI 1.39-1.61, P < 0.01), smoking (OR = 1.10; CI 1.03-1.18, P = 0.06) and CCS class IV symptoms (OR = 1.43; CI 1.34-1.53, P < 0.01). CCS Class IV angina was a stronger predictor of severe CAD amongst women compared with men (women OR = 1.82; CI 1.61-2.04 vs. men OR = 1.28; CI 1.18-1.39, P < 0.01). CONCLUSIONS: Women referred for first diagnostic angiography have lower rates of severe CAD compared with men across all ages. Whilst conventional risk factors, age, sex, diabetes, smoking and hyperlipidaemia are primary determinants of CAD amongst women and men, CCS Class IV angina is more likely to be associated with severe CAD in women than men.

Quality of life at referral predicts outcome of elective coronary artery angiogram.

BACKGROUND: Patients' anxiety and quality of life (HRQL) are affected by waiting for diagnostic tests such as coronary artery angiogram (CATH). It is unknown whether HRQL and psychological status at the time of referral are related to likelihood of coronary artery disease (CAD) as diagnosed by CATH. PURPOSE: The purposes of this study were (1) to determine patients' anxiety and HRQL at the time of referral for elective CATH and (2) to assess the impact of baseline HRQL on likelihood of CAD. METHODS: This was a prospective observational study of 1009 patients referred for elective CATH. Questionnaires were mailed to patients within 2 weeks of referral. Packages contained a general HRQL measure (SF-36), a condition-specific HRQL measure (Seattle Angina Questionnaire) and the State-Trait Anxiety Inventory (STAI). Patients returned the baseline questionnaires in a postage-paid envelope. RESULTS: : Complete data were available for 90.6% of patients (n=914). At baseline, general HRQL was significantly lower than population norms for healthy individuals (p<0.0001), but significantly higher than population norms for patients living with angina (p<0.02). Also at baseline, patients' (n=971) mean state anxiety score on the STAI was 44.3 (SD=13.3), reflecting 'high anxiety'. Logistic regression analysis revealed 3 predictors of angiographically documented CAD: male sex (OR 5.76; CI 3.75-8.84), the SF-36 physical functioning subscale (OR 1.05; CI 1.01-1.07) and older age (OR 2.38; CI 1.48-3.82). CONCLUSION: At the time of referral for elective CATH patients have high levels of anxiety and poor HRQL. It is possible that patient-rated physical HRQL at the time of referral adds to our ability to triage patients according to urgency ratings.

Efficacy of hirudin in reducing cardiovascular events in patients with acute coronary syndrome undergoing early percutaneous coronary intervention.

AIMS: Although hirudin is superior to unfractionated heparin for prevention of death, myocardial infarction, or refractory ischaemia in patients with non-ST-elevation acute coronary syndrome, it is not clear whether hirudin is also of benefit in acute coronary syndrome patients undergoing early percutaneous coronary intervention. METHODS AND RESULTS: In the OASIS 2 trial, 10 141 patients with non-ST-elevation acute coronary syndrome were randomized to 72 h of intravenous hirudin or unfractionated heparin. Percutaneous coronary intervention was performed at the discretion of the investigator. One hundred and seventeen patients underwent percutaneous coronary intervention within the first 72 h ("early percutaneous coronary intervention"). In patients undergoing early percutaneous coronary intervention, hirudin compared with unfractionated heparin was associated with a significantly lower incidence of death or myocardial infarction at 96 h (6.4% vs 21.4%, OR 0.30; 95% CI: 0.10-0.88) and 35 days (6.4% vs 22.9%, OR 0.25; 95% CI: 0.07-0.86). In the unfractionated heparin group, death or myocardial infarction was significantly higher at 35 days in patients undergoing early percutaneous coronary intervention compared with those managed conservatively (22.9% vs 7.3%, OR 3.14, P<0.001) but this early percutaneous coronary intervention-related hazard was not observed in hirudin-treated patients (6.4% vs 6.8%, OR 0.94 P=1.0). A time-dependent covariate for percutaneous coronary intervention was not significant in a Cox regression model, suggesting a similar treatment benefit with hirudin before and after percutaneous coronary intervention. After adjustment for percutaneous coronary intervention propensity, the benefits of hirudin remained significant. There were three major bleeds in patients undergoing early percutaneous coronary intervention, all in patients randomized to hirudin. CONCLUSION: In patients with non-ST-elevation acute coronary syndrome undergoing early percutaneous coronary intervention, a direct thrombin inhibitor such as hirudin may be more effective than heparin in reducing the incidence of ischaemic complications.

Arterial elastase activity after balloon angioplasty and effects of elafin, an elastase inhibitor.

Increased proteolytic activity may be a factor in intimal hyperplasia after balloon angioplasty (BA). The objectives of this study were to assess elastase activity after BA in a rabbit arterial double-injury model and the effects of elastase inhibition. Elastase activity increased immediately after BA, reached an 8-fold peak at 1 week, and declined to baseline levels by 4 weeks. Elastin zymography showed that the elastase activity was associated predominantly with a molecular mass of 25 kDa. Elastase activity was significantly inhibited in vitro by elafin and phenylmethylsulfonyl fluoride, selective inhibitors of serine elastases. A second group of animals was transfected after BA with a plasmid containing the cDNA for either elafin or a control (chloramphenicol acetyltransferase, CAT) construct by using a hemagglutinating virus of Japan-liposome transfection technique. Arterial segments were obtained at 48 hours, 1 week, and 4 weeks to assess transgene expression, arterial wall elastase activity, and intimal cross-sectional area, respectively. Elafin transgene expression was evident at 48 hours and resulted in a significant (80%) inhibition of elastase activity compared with chloramphenicol acetyltransferase-transfected arteries. There was a 43% reduction in intimal cross-sectional area in elafin-transfected arteries (0.28+/-0.22 versus 0.16+/-0.07 mm(2) for CAT-transfected versus elafin-transfected arteries, respectively; P<0.05). These data suggest that an early increase in serine elastase activity after BA contributes to intimal hyperplasia. Serine elastase inhibition may be a potential therapeutic approach to inhibit intimal hyperplasia.

Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study.

BACKGROUND: Despite the use of aspirin, there is still a risk of ischaemic events after percutaneous coronary intervention (PCI). We aimed to find out whether, in addition to aspirin, pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI. METHODS: 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been randomly assigned double-blind treatment with clopidogrel (n=1313) or placebo (n=1345). Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission, and for a median of 10 days overall. After PCI, most patients (>80%) in both groups received open-label thienopyridine for about 4 weeks, after which study drug was restarted for a mean of 8 months. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or urgent target-vessel revascularisation within 30 days of PCI. The main analysis was by intention to treat. FINDINGS: There were no drop-outs. 59 (4.5%) patients in the clopidogrel group had the primary endpoint, compared with 86 (6.4%) in the placebo group (relative risk 0.70 [95% CI 0.50-0.97], p=0.03). Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death, myocardial infarction, or any revascularisation (p=0.03), and of cardiovascular death or myocardial infarction (p=0.047). Overall (including events before and after PCI) there was a 31% reduction cardiovascular death or myocardial infarction (p=0.002). There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group (p=0.001). At follow-up, there was no significant difference in major bleeding between the groups (p=0.64). INTERPRETATION: In patients with acute coronary syndrome receiving aspirin, a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events, compared with placebo.

Bleeding risks with abciximab after full-dose thrombolysis in rescue or urgent angioplasty for acute myocardial infarction.

BACKGROUND: The bleeding risk associated with platelet glycoprotein IIb/IIIa inhibition in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) after full-dose thrombolysis for acute myocardial infarction (AMI) is unclear. We examined the risk and predictors of bleeding complications in patients with AMI who received abciximab during rescue or urgent PTCA after full-dose thrombolytic therapy. METHODS: A multicenter retrospective cohort of 147 consecutive patients who underwent PTCA within 48 hours after full-dose thrombolysis for AMI was studied. Bleeding events (major, minor, nuisance) from the onset of AMI to discharge were compared between those who received abciximab (n = 57) and those who did not (n = 90). RESULTS: Baseline clinical characteristics were similar between the two groups. Despite lower doses of procedural heparin, the incidence of non-coronary artery bypass graft-related major and minor bleeding was higher in the abciximab group than in controls (63% vs 39%, P =.004). Although the risk of major bleeding was 4-fold with abciximab (12% vs 3%, P =.04), only one intracranial and one fatal bleeding event occurred. Multivariable regression identified abciximab therapy as the most powerful independent predictor of combined major and minor bleeding, with a hazard risk ratio of 1.9 (P =.04). CONCLUSIONS: In the setting of rescue or urgent PTCA within 48 hours after full-dose thrombolytic therapy after AMI, major and particularly minor bleeding were frequently encountered. The adjunctive use of abciximab increased these bleeding risks by approximately 2-fold.

Impact of right ventricular involvement on mortality and morbidity in patients with inferior myocardial infarction.

OBJECTIVES: We sought to evaluate the prognostic impact of right ventricular (RV) myocardial involvement in patients with inferior myocardial infarction (MI). BACKGROUND: There is uncertainty regarding the risk of major complications in patients with inferior MI complicated by RV myocardial involvement. Whether these complications are related to RV myocardial involvement itself or simply to the extent of infarction involving the left ventricle (LV) is also unknown. METHODS: We examined the incidence of death and mechanical and electrical complications in patients with (n = 491) and without (n = 638) RV myocardial involvement and in patients with anterior MI (n = 971) in an analysis from the Collaborative Organization for RheothRx Evaluation (CORE) trial. Left ventricular infarct size was assessed by technetium-99m-sestamibi single-photon emission computed tomography and peak creatine kinase, and LV function was assessed by radionuclide angiography. We also performed a meta-analysis in which we pooled the results of our study with previous smaller studies addressing the same question. RESULTS: Six-month mortality was 7.8% in inferior MI compared with 13.2% in anterior MI. Among patients with inferior MI, serious arrhythmias were significantly more common in patients with RV myocardial involvement who also had a trend toward higher mortality, pump failure and mechanical complications. However, this was not associated with a difference in LV infarct size or function. A meta-analysis of six studies (n = 1,198) confirmed that RV myocardial involvement was associated with an increased risk of death (odds ratio [OR] 3.2, 95% confidence interval [CI] 2.4 to 4.1), shock (OR 3.2, 95% CI 2.4 to 3.5), ventricular tachycardia or fibrillation (OR 2.7, 95% CI 2.1 to 3.5) and atrioventricular block (OR 3.4, 95% CI 2.7 to 4.2). CONCLUSIONS: Patients with inferior MI who also have RV myocardial involvement are at increased risk of death, shock and arrhythmias. This increased risk is related to the presence of RV myocardial involvement itself rather than the extent of LV myocardial damage.

Unimicrobial appendicitis due to non-vaccine serotype of streptococcus pneumoniae: Implications for and management and prevention.

The aetiology of appendicitis is usually polymicrobial. We report a rare case of appendicitis caused by Streptococcus pneumoniae as the only causative organism. The case assumes significance because it occurs in the absence of any predisposing factor for invasive pneumococcal infection, it is unimicrobial, it may lead to the misdiagnosis of primary peritonitis due to pneumococcus, and it undermines the efficacy of polyvalent pneumococcal vaccine.

Throat carriage of pneumococci in healthy school children in the Union Territory of Pondicherry.

BACKGROUND & OBJECTIVES: Colonisation of Streptococcus pneumoniae in the throat is common among children the world over. Little is known about the relationship of nasopharyngeal carriage and invasive disease or the way it spreads within the households and close confines. There is a paucity of data on the colonization of Strep. pneumoniae in the throat of healthy children in India. To determine the prevalence of pneumococcal carriage in school children of urban and rural Pondicherry, a study was undertaken. METHODS: Throat swabs of healthy school-going children between 5-10 yr of age were examined for pneumococcal carriage, by standard bacteriological techniques. RESULTS: A prevalence rate of 24.3 per cent was noted. There was no difference in the carriage rate among the rural children when compared to urban children. No age, sex or geographical predilection of pneumococcal carriage was noted. A statistically significant seasonal variation, however, was seen. Carriage rate increased during the colder months and was found to be the highest in the months of March and November. INTERPRETATION & CONCLUSIONS: Strep. pneumoniae circulates in the community among healthy children. Carriage rate is influenced by seasonal variation.

Evaluation of the role of abciximab (Reopro) as a rescue agent during percutaneous coronary interventions: in-hospital and six-month outcomes.

Abciximab is effective for the prevention of complications when administered prior to percutaneous coronary intervention (PCI). The efficacy and safety of abciximab as an unplanned or rescue agent for complications of PCI is unknown. Rescue versus planned use was compared in 186 consecutive patients. Primary or rescue PCI for acute myocardial infarction (MI) and shock were excluded. Rescue abciximab use was undertaken in 101 patients (54.3%) and planned abciximab was used in 85 (45.7%). The rescue abciximab patients had a lower incidence of previous MI, preprocedural thrombus, multivessel, and vein graft intervention. In-hospital endpoints in the rescue versus planned abciximab patients were death (1.0% vs. 1. 2%, P = 1.0), Q-wave MI (2.0% vs. 2.4%, P = 1.0), any MI (14.9% vs. 9.4%, P = 0.3), target vessel revascularization (TVR; 0% vs. 1.2%, P = 1.0), and composite (15.8% vs. 10.6%, P = 0.3). At 6 months, events were death (4.0% vs. 2.3%, P = 0.69), MI (14.9% vs. 9.4%, P = 0.26), TVR (20.8% vs. 4.7%, P = 0.001), and composite (30.7% vs. 15. 3%, P = 0.01). In-hospital complications between the rescue and planned abciximab patients of major bleed (1.0% vs. 1.8%, P = NS), stroke (0% vs. 1.8%, P = NS), and thrombocytopenia (3.0% vs. 1.8%, P = NS) were similar. There was a significantly higher procedural time (99.6 min vs. 86.1 min, P = 0.02), contrast volume (278.8 ml vs. 223. 5 ml, P = 0.04), and heparin use (8984 u vs. 6003 u, P = 0.0006) in the rescue group. In this nonrandomized comparison, rescue abciximab allowed for the safe discharge from hospital in the majority of patients. However, during a 6-month follow-up, more patients treated with rescue abciximab required TVR with either repeat PCI or CABG. Further studies are warranted to evaluate the overall strategy of rescue abciximab use in PCI.

Plasma urokinase antigen and plasminogen activator inhibitor-1 antigen levels predict angiographic coronary restenosis.

BACKGROUND: The fibrinolytic system is intimately involved in several processes that contribute to restenosis, including clot dissolution, cell migration, and tissue remodeling. However, the role of the individual activators (urokinase [uPA] and tissue plasminogen [tPA] activators) and inhibitors (plasminogen activator inhibitor [PAI-1]) of the fibrinolytic system in maintaining patency after coronary artery angioplasty and stenting is unclear. METHODS AND RESULTS: We prospectively studied 159 patients with stable angina who underwent successful elective angioplasty (n=110) or stenting (n=49) of de novo native coronary artery lesions. Plasma samples were drawn at baseline (before angioplasty) and serially after angioplasty (immediately afterward and 6 hours, 24 hours, 3 days, 7 days, 1 month, 3 months, and 6 months afterward). Antigen and activity assays were performed for uPA, tPA, and PAI-1. Follow-up quantitative coronary angiography was performed in 92% of eligible patients. The overall angiographic restenosis rate (diameter stenosis >50%) was 31% (37% in PTCA patients, 17% in stented patients). At all time periods, including baseline, uPA antigen levels were significantly higher and PAI-1 antigen levels were significantly lower in patients with restenosis. Restenosis rates for patients in the upper tertile of baseline uPA antigen levels were 2-fold higher than for those in the lower 2 tertiles (46% versus 24% and 22%, respectively; P<0.004). In a stepwise regression multivariate analysis, obstruction diameter after the procedure and uPA antigen were significant predictors of follow-up diameter stenosis. CONCLUSIONS: Plasma uPA antigen levels and PAI-1 antigen levels identify patients at increased risk for restenosis after percutaneous coronary revascularization.

Bacterial contamination of anterior chamber during IOL surgery.

PURPOSE: To study the nature and frequency of bacterial contamination during cataract surgery. METHODS: The preoperative smears from the conjunctiva and anterior chamber (AC) fluid aspirates during extra-capsular cataract surgery (ECCE) with posterior chamber intraocular lens (PCIOL) implantation in 40 eyes were analysed for aerobic and anaerobic bacteria. Any change in the bacterial strains isolated before and after cataract surgery was also studied. RESULTS: AC fluid aspirates were positive for bacteria in 15 eyes (37.5%). Coagulase-negative Staphylococcus was the most common aerobe (39.4%) and Propionibacterium acnes the most common anaerobe. Of the 15 cases with positive AC fluid cultures, 6 showed an organism in the AC aspirate different from the conjunctival smear. CONCLUSION: Clinically there was no endophthalmitis in any of the eyes. Factors such as preoperative antibiotic use, the antibacterial properties of aqueous, or low inoculum size could explain this. The preoperative conjunctival smear may not be useful in predicting the AC fluid contamination or outcome of cataract surgery.

Failed coronary stent deployment.

BACKGROUND: Coronary stent deployment failure may be more common in clinical practice than generally appreciated. The incidence of failed deployment in routine clinical practice and the clinical sequelae have not been described. This study sought to determine the incidence and consequences of failed coronary stent deployment and to identify clinical and angiographic characteristics associated with deployment failure. METHODS AND RESULTS: A series of 1303 consecutive procedures involving attempted coronary stenting were reviewed retrospectively. Failed stent deployment was defined as failure of the stent to be either delivered to or adequately deployed at the target lesion site. Clinical records and angiograms were reviewed and qualitative coronary angiography was performed for all cases of failed deployment. Deployment was unsuccessful in 108 (8.3%) cases involving 134 stents. Stenting was attempted as a primary procedure in 40%, as bailout in 18%, and for suboptimal angioplasty in 43% of cases. In 87% of cases, attempts were made to withdraw the stent from the coronary artery. Stent retrieval was successful in 45%, peripheral embolization occurred in 38% of patients, and in 4% the stent dislodged in the left main artery. In 35% of cases, additional stent(s) were successfully deployed. Deployment failure was associated with an overall in-hospital adverse outcome in 19% of patients, including 16% urgent coronary artery bypass grafting, 5% nonfatal myocardial infarction, and 3 in-hospital deaths. At 6-month follow-up, 39% of patients had had at least 1 adverse clinical outcome of death, myocardial infarction, or repeat target lesion revascularization. CONCLUSIONS: Failure to deploy stents is a serious and relatively common problem that is associated with significant morbidity and mortality rates. Improved deployment strategies, including new stent designs, are required to improve procedural outcomes.

In vivo collagen turnover following experimental balloon angioplasty injury and the role of matrix metalloproteinases.

Extracellular matrix formation is the major component of the restenosis lesion that develops after balloon angioplasty. Although ex vivo studies have shown that the synthesis of collagen is stimulated early after balloon angioplasty, there is a delay in accumulation in the vessel wall. The objectives of this study were to assess collagen turnover and its possible regulation by matrix metalloproteinases (MMPs) in a double-injury iliac artery rabbit model of restenosis. Rabbits were killed at four time points (immediately and at 1, 4, and 12 weeks) after balloon angioplasty. In vivo collagen synthesis and collagen degradation were measured after a 24-hour incubation with [14C]proline. Arterial extracts were also run on gelatin zymograms to determine MMP (gelatinase) activity. Collagen turnover studies were repeated in a group of 1-week postangioplasty rabbits that were treated with daily subcutaneous injections of either a nonspecific MMP inhibitor, GM6001 (100 mg/kg per day), or placebo. Collagen synthesis and degradation showed similar temporal profiles, with significant increases in the balloon-injured iliac arteries compared with control nondilated contralateral iliac arteries immediately after angioplasty and at 1 and 4 weeks. Peak collagen synthesis and degradation occurred at 1 week and were increased (approximately four and three times control values, respectively). Gelatin zymography was consistent with the biochemical data by showing an increase of a 72-kD gelatinase (MMP-2) in the balloon-injured side immediately after the second injury, peaking at 1 week, and still detectable at 4 and 12 weeks (although at lower levels). In balloon-injured arteries, the MMP inhibitor reduced both collagen synthesis and degradation. Overall, at 1 week after balloon angioplasty, GM6001 resulted in a 33% reduction in collagen content in balloon-injured arteries compared with placebo (750 +/- 143 to 500 +/- 78 micrograms hydroxyproline per segment, P < .004), which was associated with a nonsignificant 25% reduction in intimal area. Our data suggest that degradation of newly synthesized collagen is an important mechanism regulating collagen accumulation and that MMPs have an integral role in collagen turnover after balloon angioplasty.

Excimer laser angioplasty vs. balloon angioplasty in saphenous vein bypass grafts: quantitative angiographic comparison of matched lesions.

Technologies which ablate or debulk tissue may result in better angiographic outcomes by altering the elastic properties of the vessel wall. Accordingly, the procedural outcomes of 88 vein graft lesions treated by either excimer laser angioplasty with adjunct balloon angioplasty (PELCA + PTCA, n = 44) (Spectranetics CVX-300, 1.4-, 1.7-, or 2.0-MM catheters) or balloon angioplasty alone (PTCA, n = 44) were analyzed by quantitative angiography (Cardiac Measurement System). Lesions were individually matched for vessel position, reference diameter (RD), and minimal luminal diameter (MLD). Matching was deemed adequate as the preprocedure MLD (PELCA + PTCA, 1.14 +/- 0.48 mm; PTCA, 1.20 +/- 0.47 mm) and RD (PELCA + PTCA, 3.23 +/- 0.56 mm; PTCA, 3.25 +/- 0.57 mm) were not significantly different. There were also no significant differences between PELCA + PTCA- and PTCA-treated lesions with respect to patient age, graft age, lesion length, symmetry, and plaque area. Balloon diameter at maximal inflation was 2.77 +/- 0.55 mm (PELCA + PTCA group) and 2.84 +/- 0.59 mm (PTCA group), P = NS. Final MLD postprocedure was 2.17 +/- 0.54 mm and 2.19 +/- 0.55 mm for PELCA + PTCA- and PTCA-treated lesions (P = NS), respectively. Vessel stretch [(balloon diameter - MLD pre)/RD], elastic recoil [(balloon diameter - MLD post)/RD], and acute gain [(MLD post - MLD pre)/RD] were calculated and normalized for vessel size (RD). Vessel stretch (PELCA + PTCA, 0.60 +/- 0.22; PTCA, 0.59 +/- 0.24; P = NS), elastic recoil (PELCA + PTCA, 0.28 +/- 0.18; PTCA, 0.26 +/- 0.16), and acute gain (PELCA + PTCA, 0.34 +/- 0.24; PTCA, 0.31 +/- 0.23; P = NS) were not significantly different between the two treatment groups. In a matched population of successfully treated vein graft lesions, PELCA + PTCA did not reduce elastic recoil or improve immediate angiographic outcome, as compared with PTCA alone.

Effect of intracoronary saline infusion on dissection during excimer laser coronary angioplasty: a randomized trial. The Percutaneous Excimer Laser Coronary Angioplasty (PELCA) Investigators.

OBJECTIVES: We sought to evaluate whether intracoronary saline infusion during excimer laser coronary angioplasty decreases the incidence of significant laser-induced coronary artery dissections. BACKGROUND: Despite procedural success rates > 90%, coronary artery dissections occur in 17% to 27% of excimer laser coronary angioplasty procedures. Excimer laser irradiation of blood results in vapor bubble formation and acoustomechanical trauma to the vessel wall. Saline infusion into a coronary artery may minimize blood irradiation and consequent arterial wall damage. METHODS: In this prospective, randomized, controlled study, consecutive patients undergoing excimer laser coronary angioplasty were randomly assigned to conventional laser irradiation in a blood medium or to laser irradiation with blood displacement by intracoronary saline infusion. In the patients randomized to intracoronary saline infusion, prewarmed normal saline was injected through the coronary artery guide catheter at a rate of 1 to 2 ml/s using a power injector. The incidence and severity of dissection after excimer laser ablation were evaluated in a core laboratory by angiographers with no knowledge of treatment assignment. The severity of coronary artery dissection was rated on an ordinal scale of 1 to 5. Dissections of grade 2 or higher were considered significant. RESULTS: The mean (+/- SE) dissection grade after laser angioplasty in patients treated with intracoronary saline infusion was 0.43 +/- 0.13 compared with 0.91 +/- 0.26 in patients undergoing laser angioplasty in a blood medium. The incidence of significant dissection was 7% in saline-treated patients compared with 24% in conventionally treated patients (p < 0.05). No significant complications were associated with saline infusion. CONCLUSIONS: Intracoronary saline infusion should be incorporated into all excimer laser coronary angioplasty procedures.