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R Kornowski

Publications and source records attributed to R Kornowski.

At least 73 records · Page 4Linked to original sources
PubMed1998

Paradoxic decreases in atherosclerotic plaque mass in insulin-treated diabetic patients.

This study assessed the impact of diabetes mellitus on atherosclerotic lesion formation. Seventy insulin-treated diabetics, 150 non-insulin-treated diabetics, and 607 nondiabetics with chronic anginal syndromes and de novo native coronary stenoses were studied using (1) angiography, and (2) intravascular ultrasound (reference and lesion arterial, lumen, and plaque areas; area stenosis [reference-lesion/reference lumen area]; remodeling index [reference-lesion lumen area/lesion-reference plaque area]; and slope of the regression line relating lumen area to plaque burden [plaque/arterial area]). Despite being diabetic for longer and having similar lumen compromise, insulin-treated patients had (1) less reference plaque (8.3 +/- 3.4 vs 10.5 +/- 4.5 mm2, p = 0.0015), (2) less stenosis plaque (13.0 +/- 4.9 vs 16.9 mm2, p <0.0001), (3) smaller reference arterial areas (17.1 +/- 5.4 vs 19.7 +/- 6.2 mm2, p = 0.0063), and (4) smaller stenosis arterial areas (15.3 +/- 4.9 vs 19.5 +/- 6.5 mm2, p <0.0001) than non-insulin-treated diabetics. With use of multivariate linear regression analysis, insulin use was an independent (and negative) predictor of reference plaque and arterial areas (p = 0.0308 and p = 0.0179) and stenosis plaque and arterial areas (p = 0.0117 and p = 0.0066). This was also true when normalized for body surface area. The remodeling index showed that insulin treatment resulted in an exaggerated impact of plaque accumulation on lumen compromise. This was confirmed by the slope of the regression line relating lumen area to plaque burden. Patients with a longer duration of diabetes who were treated with insulin for > or = 1 year had (paradoxically) less reference segment and stenosis plaque accumulation. Possible explanations include impaired adaptive remodeling and/or arterial (and plaque) shrinkage.

Aged↗
PubMed1998

Procedural results and late clinical outcomes after placement of three or more stents in single coronary lesions.

BACKGROUND: Previous reports have suggested higher procedural and long-term complications among patients treated with multiple stents for diffuse lesions and/or long dissections. METHODS AND RESULTS: To evaluate procedural success, major complications, and clinical outcomes (> or = 1 year) in a consecutive series of patients treated with multiple (> or = 3) contiguous stents in single lesions, we evaluated in-hospital and long-term (1-year) clinical outcomes in 117 consecutive patients treated with > or = 3 coronary stents compared with a concurrent series of patients treated with 1 or 2 stents (n=1673) between January 1, 1994, and December 31, 1995. Multiple stents were implanted more often in larger vessels, in the right coronary artery or saphenous vein grafts, and for unfavorable lesion characteristics, including long (>20 mm), calcified, ulcerated, thrombotic, and/or flow-obstructing lesions. Overall procedural success was obtained in 97.4% of patients and was similar whether 1 or 2 versus > or = 3 stents were used. Non-Q-wave MI (CK-MB > or = 5 times normal) was more frequent after > or = 3 stents (22.8% versus 13.4%, P=.005). Target lesion revascularization (TLR) was 14.6% for 1 or 2 stents and 13.3% for > or = 3 stents (P=.70). There was no difference in death (2.2% versus 0.9%, P=.34) or Q-wave MI (1.4% versus 0.9%, P=.64) between the two groups (1 or 2 stents versus > or = 3 stents, respectively), and overall cardiac event-free survival was similar during follow-up (P=.70). CONCLUSIONS: Patients treated with multiple (> or = 3) contiguous stents compared with 1 or 2 stents have (1) similar in-hospital procedural success and major complications despite having more unfavorable lesion characteristics, (2) a higher rate of procedural non-Q-wave MI, and (3) similar TLR and overall major cardiac event rates during 1 year of follow-up.

Aged↗
PubMed1998

Current perspectives on direct myocardial revascularization.

Direct myocardial revascularization (DMR), either surgical or catheter-based, uses lasers to create channels between ischemic myocardium and the left ventricular cavity to improve perfusion and decrease angina. This technique can also be used to deliver drugs to the damaged tissue. Candidates include patients with chronic, severe, refractory angina and those unable to undergo conventional surgical revascularization or angioplasty because remaining conduits or acceptable target vessels are lacking. Although the mechanism of action of DMR is still not known, several theories have been proposed, including stimulated angiogenesis. Late sequelae also remain to be determined. Channel characteristics differ depending on whether they were created by carbon dioxide or holmium/yttrium-aluminum-garnet (Ho: YAG) lasers. Catheter-based DMR obviates thoracotomy and anesthesia and, in systems that can create electromechanical maps, fluoroscopy. Phase I clinical trials are now under way to evaluate catheter-based DMR, with endpoints that include improvement in symptoms of angina, exercise capacity, and radionuclide myocardial perfusion.

Cardiac Catheterization↗
PubMed1998

In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia.

OBJECTIVES: We examined the relative contributions of inflammation and arterial injury to neointimal formation in a porcine coronary overstretch restenosis model. BACKGROUND: Previous studies established that stents cause neointimal proliferation proportional to injury. Although inflammation has been postulated to be a major contributor to restenosis after angioplasty, there is a paucity of data on the relation between inflammation and subsequent neointimal formation. METHODS: Twenty-one pigs underwent balloon injury followed by implantation of oversized, tubular, slotted stents (stent/artery ratio 1.2:1) in the left anterior descending coronary artery. Morphometric analysis of the extent of injury (graded as injury score 0 to 3) and inflammation (graded as inflammation score 0 to 3) 1 month later was assessed and correlated with neointimal formation. RESULTS: An inflammatory reaction was observed in 20 of 21 pigs, and significant positive correlations were found between the degree of arterial injury and the extent of the inflammatory reaction (r = 0.80, p < 0.01) and between the extent of inflammatory reaction and the neointimal thickness (r = 0.75, p < 0.01), neointimal area (r = 0.53, p = 0.01) and percent area stenosis (r = 0.66, p < 0.01) within the stents. Importantly, there were areas with inflammation only in the absence of injury, and vice versa, that were also associated with neointimal hyperplasia. CONCLUSIONS: These data suggest that the inflammatory reaction plays an equally important role as arterial injury in neointimal formation after coronary stenting, and that anti-inflammatory approaches may be of value to reduce in-stent restenosis.

Animals↗
PubMed1998

The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation.

OBJECTIVES: We compared the clinical outcomes following coronary stent implantation in insulin-treated diabetes mellitus (IDDM), non-IDDM patients, and nondiabetic patients. BACKGROUND: Diabetic patients have increased restenosis and late morbidity following balloon angioplasty. The impact of diabetes mellitus (DM), especially IDDM, on in-stent restenosis is not known. METHODS: We studied 954 consecutive patients with native coronary artery lesions treated with elective Palmaz-Schatz stents implantation using conventional coronary angiographic and intravascular ultrasound methodology. Procedural success, major in-hospital complications, and 1-year clinical outcome were compared according to the diabetic status. RESULTS. In-hospital mortality was 2% in IDDM, significantly higher (p <0.02) compared with non-IDDM (0%) and nondiabetics (0.3%). Stent thrombosis did not differ among groups (0.9% in IDDM vs. 0% in non-IDDM and 0% in nondiabetics, p >0.1). During follow-up, target lesion revascularization (TLR) was 28% in IDDM, significantly higher (p <0.05) compared with non-IDDM (17.6%) and nondiabetics (16.3%). Late cardiac event-free survival (including death, myocardial infarction [MI], and any coronary revascularization procedure) was significantly lower (p=0.0004) in IDDM (60%) compared with non-IDDM (70%) and nondiabetic patients (76%). By multivariate analysis, IDDM was an independent predictor for any late cardiac event (OR=2.05, p=0.0002) in general and TLR (odds ratio=2.51, p=0.0001) in particular. CONCLUSIONS. In a large consecutive series of patients treated by elective stent implantation, IDDM patients were at higher risk for in-hospital mortality and subsequent TLR and, as a result, had a significantly lower cardiac event-free survival rate. On the other hand, acute and long-term procedural outcome was found to be similar for non-IDDM compared with nondiabetic patients.

Adult↗
PubMed1998

Angiographic Morphology Following Heparin and Aspirin Therapy in Patients with Acute Coronary Syndromes and Intracoronary Thrombus.

This series included 26 patients with acute myocardial infarction (15 patients) or unstable angina (11 patients), with thrombotic lesions identified by angiography and treated with intravenous heparin (mean 8 +/- 3 days, aPTT 1.5-2.5 times baseline) and aspirin (250 mg/day). A quantitative angiographic analysis was performed, and comparison of the lesion morphology before and after the antithrombotic treatment was conducted, using a computer-based analysis of the lesion contour. On average, minimal lumen diameter increased by 15.6% (1.15 +/- 0.5mm to 1.33 +/- 0.5mm, P = 0.02), percent diameter stenosis decreased by 10.7% (60.0 +/- 18% to 53.6 +/- 19%, P = 0.009), percent area stenosis decreased by 6.5% (80.0 +/- 14% to 74.8 +/- 16%, P = 0.05), and TIMI flow increased by 8% (2.5 +/- 0.9 to 2.7 +/- 0.7, P = 0.02). A significant improvement in the lesion morphology was more often observed in the right coronary artery (n = 9), than the left coronary artery (n = 16). We conclude that heparin and aspirin therapy improves the angiographic morphology and TIMI flow of thrombotic lesions in patients sustaining the acute coronary syndrome. This improvement was primarily found when the lesion was located in the right coronary artery.

Journal Article↗
PubMed1998

Hemodynamic changes determine the efficacy of thrombolysis: results from an in-vitro flow model.

BACKGROUND: The efficacy of thrombolytic therapy might be influenced by changes in the hemodynamic status. The aim of the study was to examine whether changes in perfusion pressure could affect the time to reflow in an in-vitro model. METHODS: The in-vitro flow system comprised flexible plastic tubes that enclosed a blood clot formed in one of the circuit arms. Streptokinase (125,000 U) or saline (control) was injected from a proximal side branch to induce thrombolysis. The protocol comprised four treatments: A, perfusion pressure 150/90 mmHg with streptokinase infusion; B, perfusion pressure 150/90 mmHg with saline; C, perfusion pressure 120/60 mmHg with streptokinase; D, perfusion pressure 120/60 mmHg with saline. Reflow was defined as flow restoration determined by the ultrasonic flowmeter. RESULTS: Successful recanalization was obtained in six of six samples subjected to treatment A (100%), two of seven samples subjected to treatment B (28%), three of five samples subjected to treatment C (60%) and none of six samples subjected to treatment D (0%). Time to reflow was 23 +/- 11 min with treatment A, 76 +/- 24 min with treatment B, 66 +/- 25 min with treatment C, and > 90 min with treatment D. CONCLUSIONS: Our data suggest that the hemodynamic status determines the efficacy of streptokinase-induced thrombolysis, and that spontaneous clot lysis is more likely to occur at greater perfusion pressures. It is conceivable that the hypotensive reaction induced by streptokinase in the clinical setting may adversely affect angiographic patency, compared with that observed with other lytic agents such as tissue-type plasminogen activator.

Blood Pressure↗
PubMed1998

Feasibility and safety of percutaneous laser revascularization using the Biosense system in porcine hearts.

BACKGROUND: Direct myocardial revascularization (DMR) is being explored to improve symptoms in patients with refractory ischemic coronary syndromes. This study assessed the safety and feasibility of percutaneous DMR using the Biosense non-fluoroscopic navigation system (incorporating the holmium : yttrium aluminium garnet laser) in pig hearts. METHODS AND RESULTS: Twenty pigs underwent left ventricular mapping using the Biosense system, followed by percutaneous DMR with a holmium : yttrium aluminium garnet laser at 2 J x 1 pulse, and were sacrificed acutely (n = 5), at 24 h (n = 5), and at 3 weeks (n = 10) after the DMR procedure. The hearts were examined grossly and microscopically. Serial creatine kinase-MB level was measured up to 24 h. There were no procedural complications. Animals received 13 +/- 2 channels in 19 +/- 7 min. The catheter was able to reach all regions, including the septum. There was no increase in creatine kinase-MB level up to 24 h. One animal died within an hour of the procedure. There was one sealed perforation into the subepicardial fat as a result of same site laser activation. Histologic evaluation in the acute and 24 h groups revealed laser channels which were 3.6 +/- 2.2 mm long, 1.5 +/- 0.7 mm wide, with an entry angle of 73 +/- 12 degrees. Channels were filled with platelet thrombi acutely and were surrounded by well-defined rims of thermal coagulation and an 'impact zone' of viable myocardium; at 3 weeks, no channels remained patent and they had been replaced by well-healed granulation tissue. CONCLUSIONS: It is feasible and safe to perform percutaneous DMR with the Biosense system and the channels created with the chosen laser parameters are rapidly sealed with platelet thrombi and at 3 weeks are replaced by well-healed granulation tissue.

Animals↗
PubMed1997

Comparison of men versus women in cross-sectional area luminal narrowing, quantity of plaque, presence of calcium in plaque, and lumen location in coronary arteries by intravascular ultrasound in patients with stable angina pectoris.

Women have an increased mortality after coronary interventions compared with men, which may be partly explained by differences in comorbid clinical conditions. However, whether women also have quantitative differences in coronary atherosclerosis is not known. Preinterventional intravascular ultrasound (IVUS) was used to study de novo, nonostial native coronary lesions in 169 women and 549 men with chronic angina. The external elastic membrane (EEM), lumen, and plaque + media (P + M) areas, plaque burden, plaque eccentricity, and calcium were measured at the target lesion and at a proximal reference site. All cross-sectional IVUS measures were also corrected for body surface area. Results are reported as mean +/- 1 SD. Women had significantly smaller reference site EEM (16.5 +/- 5.3 vs 19.4 +/- 6.3 mm2, p <0.0001), lumen (8.7 +/- 3.0 vs 9.9 +/- 4.0 mm2, p = 0.0020), and P + M areas (7.8 +/- 3.7 vs 9.5 +/- 4.2 mm2, p = 0.0001). Women also had significantly smaller lesion site EEM (16.2 +/- 5.9 vs 18.3 +/- 6.7 mm2, p = 0.0028), lumen (2.4 +/- 1.7 vs 2.9 +/- 2.6 mm2, p = 0.0273), and P + M areas (13.6 +/- 5.7 vs 15.3 +/- 6.4 mm2, p = 0.0112). However, when corrected for BSA, these differences were no longer significant. Women and men also had similar reference and lesion plaque burden, eccentricity, and calcium. Preinterventional IVUS analysis failed to detect any quantitative or qualitative differences in coronary atherosclerosis in men compared with women.

Aged↗
PubMed1997

Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasia. A serial intravascular ultrasound study.

BACKGROUND: The increased risk of restenosis after catheter-based coronary interventions in diabetic patients has not been determined. Intravascular ultrasound (IVUS) has shown that the decrease in arterial area is responsible for most of the late lumen loss in nonstented lesions and that intimal hyperplasia is responsible for all of the late lumen loss in stented lesions. METHODS AND RESULTS: Serial (postintervention and follow-up at 5.6 +/- 3.3 months) IVUS was used to study 251 native coronary lesions in 241 patients; 63 patients had treated diabetes mellitus (oral hypoglycemic drugs or insulin). Interventional procedures included percutaneous transluminal coronary angioplasty, directional or rotational atherectomy, excimer laser angioplasty, or Palmaz-Schatz stents. The external elastic membrane (EEM), stent, and lumen areas were measured. The plaque+media (P+M) area in nonstented lesions was calculated as EEM minus lumen area, and the intimal hyperplasia (IH) area in stented lesions was calculated as stent minus lumen area. The anatomic slice selected for serial analysis had an axial location within the target lesion at the smallest follow-up lumen area. Nonstented lesions in diabetics and nondiabetics had a similar decrease in EEM cross-sectional area (CSA; 1.9 +/- 2.8 versus 1.8 +/- 4.2 mm2; P = .6350). However, nonstented lesions in diabetics had a greater increase in P+M CSA (1.3 +/- 2.8 versus 0.6 +/- 2.5 mm2, P = .0720), and the increase in P+M CSA contributed a greater percentage to the decrease in lumen CSA. In stented lesions, the decrease in lumen CSA (5.2 +/- 2.5 versus 2.0 +/- 2.3 mm2) and the increase in IH CSA (5.0 +/- 2.8 versus 1.8 +/- 2.0 mm2) were greater in diabetics than nondiabetics (P = .0009 and P = .0007, respectively). These findings were even more striking in (nonstented and stented) restenotic lesions. CONCLUSIONS: Serial IVUS analysis showed that the main reason for increased restenosis in diabetes mellitus was exaggerated intimal hyperplasia in both stented and nonstented lesions.

Aged↗
PubMed1997

Comparison of short- and long-term prognosis in patients with anterior wall versus inferior or lateral wall non-Q-wave acute myocardial infarction. Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group.

We evaluated the early and long-term prognosis of patients with a first non-Q-wave acute myocardial infarction (AMI) in relation to infarct site. Among 4,314 patients with a first AMI, 610 (14%) had a non-Q-wave AMI. Of them, 248 patients with anterior wall AMI were compared with 327 patients with inferior/lateral AMI. Baseline clinical characteristics were similar in both groups except for higher mean age in the anterior wall group. In-hospital complications were more common among patients with anterior wall AMI than in the inferior/lateral group. Patients with anterior wall AMI also had higher rates of in-hospital (15%), 1-year (12%), and 5-year (36%) postdischarge mortality compared with the inferior/lateral infarction group (10%, 6%, and 22%, respectively). The 1-year cardiac event rate (recurrent AMI and cardiac death) was significantly higher among the anterior wall AMI group than the inferior/lateral AMI group (14.2% and 4.8% respectively, p = 0.001). After adjustment for age, gender, systemic hypertension, diabetes mellitus, prior angina, and treatment with various medications, an increased risk for 1-year (odds ratio 1.31, 95% confidence interval [CI] 0.62 to 2.78) and 5-year mortality (relative risk 1.29, 95% CI 0.90 to 1.85) was observed, but it did not reach statistical significance. Anterior wall AMI location emerged as a predictor for higher 1-year cardiac event rate (odds ratio 3.15, 95% CI 1.59 to 6.78). These findings suggest that AMI location is an important prognostic variable for risk stratification of patients with a first non-Q-wave AMI.

Aged↗
PubMed1997

Influence of guiding catheter selection on the measurement of coronary flow reserve.

The impact of guiding catheter selection on the measurement of coronary flow reserve was assessed by injecting increasing doses of adenosine through 3 different catheters often used during coronary interventions. When guiding catheters with side holes were used, an approximate doubling of the adenosine dose was required to produce a coronary flow reserve response similar to a 12-micrograms dose of adenosine injected through guiding catheters without side holes.

Adenosine↗
PubMed1997

Delayed development of a pseudoaneurysm in the left circumflex artery following angioplasty and stent placement, treated with intravascular ultrasound-guided stenting.

Three months following satisfactory angioplasty and stent placement, a patient developed restenosis and a pseudoaneurysm of a coronary artery segment proximal to the previously stented area. The restenosis and the pseudoaneurysm were successfully treated with intravascular ultrasound-guided primary stenting. The delay in the appearance of the pseudoaneurysm attests to the chronic nature of the lesion.

Adult↗
PubMed1997

An integrated noninvasive system for monitoring the microcirculatory effects of vasoactive drugs: an experimental study.

BACKGROUND: No information is available on the effects of vasoactive drugs on the microcirculation and on the correlation between their effects on the capillary and the systemic circulation. PURPOSE: To characterize the effects of nitroglycerin (NTG), nitroprusside (NP), and metaraminol infusion on microcirculatory variables using a noninvasive monitoring system. METHODS: Increasing doses of NTG (5-40 microg/kg/min) and NP (5-20 microg/kg/min) were intravenously infused to eight rabbits. The microcirculatory parameters were monitored by a combined noninvasive system which included laser Doppler flowmetry (LDF), photoplethysmograph (PPG), and transcutaneous oxygen tension (tc-PO2). Mean blood pressure (MBP) was measured simultaneously. RESULTS: At maximal rate of NTG infusion, the values of LDF, PPG, tc-PO2, and MBP were 72.2 +/- 23.9, 234.7 +/- 165.6, 103.5 +/- 37.4, and 82.7 +/- 7.4% of baseline, respectively. Following NP infusion the LDF, PPG, tc-PO2, and MBP reached 70.8 +/- 24.1, 190.5 +/- 68.9, 70.0 +/- 14.7, and 75.6 +/- 14.6% of baseline, respectively. The tissue oxygenation was significantly reduced during NP infusion compared to NTG (P < 0.05). The values gradually returned to the baseline 10 min after termination of NP infusion, but not after NTG. After injection of 1 mg metaraminol there was a steep decline in LDF, PPG, and tc-PO2 parallel to a significant increase in MBP. When metaraminol was administered after injection of 0.1 mg phenoxybenzamine, these changes were abolished. CONCLUSIONS: This noninvasive system effectively monitors microcirculatory hemodynamic changes induced by vasoactive drugs. NTG and NP cause similar changes in the systemic and microcirculatory bed, with the exception of peripheral oxygenation, which is reduced only during infusion of NP. The changes in the microcirculatory bed following metaraminol and phenoxybenzamine imply that their effects on the arterioles are mediated by adrenergic alpha-receptors.

Analysis of Variance↗
PubMed1997

Acute and chronic effects of self-expanding nitinol stents in porcine coronary arteries.

BACKGROUND: There is a paucity of experimental data regarding self-expanding stents. This study evaluated the acute and chronic effects of CardioCoil, a self-expanding nitinol coil stent, in porcine coronary arteries. METHODS: Twenty-three self-expanding nitinol stents were implanted without associated balloon angioplasty in normal coronary arteries of 12 pigs, which were serially sacrificed up to 6 months. Angiographic and histologic analyses were performed to evaluate the deployment characteristics, patency rates, neointimal response, and unique features of the self-expanding nature of the CardioCoil stent. RESULTS: All stents were successfully deployed and remained patent acutely. Three undersized stents migrated proximally and there was one episode of subacute thrombosis in an oversized stent. The remaining stents were patent throughout the survival period and neointimal responses were favorable for up to 6 months (all mean neointima < 200 microns up to 6 months). There was evidence of continuing stent expansion over time (stent diameter 2.85 +/- 0.78 mm immediately after deployment and 3.24 +/- 0.97 mm at follow-up) and the majority of stent struts were in the adventitia by 6 months. Re-endothelization occurred starting one week after implantation and was complete by 8 weeks. CONCLUSIONS: This study shows that the CardioCoil self-expanding nitinol coil stent, is associated with favorable deployment characteristics and patency rates, although appropriate sizing is more crucial than with balloon-expandable stents. More importantly, there appears to be a "dissociation' between the deep vessel wall injury by the chronic strut expansion process and the neointimal reaction, unlike balloon-expandable stents.

Alloys↗
PubMed1997

Single-dose intramuscular administration of sustained-release Angiopeptin reduces neointimal hyperplasia in a porcine coronary in-stent restenosis model.

BACKGROUND: In-stent restenosis results primarily from neointimal hyperplasia. In a previous study we showed that continuous subcutaneous Angiopeptin infusion for 1 week significantly reduces neointimal hyperplasia in a porcine coronary overstretch in-stent restenosis model. The present study evaluated the relative efficacy of immediate-release and sustained-release Angiopeptin in the same model. METHODS: Thirty pigs (n = 10 in each group) were randomly assigned to three groups: controls receiving no Angiopeptin (Group 1); a sustained-release treatment group receiving one time intramuscular administration of 20 mg of Angiopeptin (Group 2); and a systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 micrograms/kg total dose) (Group 3). One oversized Palmaz-Schatz stent (mean stent/artery = 1.25) was subsequently implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal per cent diameter stenosis) and histology (maximal neointimal area corrected for injury score). RESULTS: A trend towards a reduction in diameter stenosis was observed by angiography, despite a similar degree of injury (25 +/- 17% in Group 1, 13 +/- 8% in Group 2, and 14 +/- 9% in Group 3; P = 0.072 by ANOVA). Histology demonstrated that both Angiopeptin treatment strategies significantly reduced in-stent neointimal area compared with the control group (1.65 +/- 0.97 mm2 in Group 1 versus 0.93 +/- 0.41 mm2 in Group 2 versus 0.85 +/- 0.28 mm2 in Group 3; P = 0.016 by ANOVA). Measurement of plasma Angiopeptin levels revealed comparable levels in both treatment groups, which persisted for up to 2 weeks. CONCLUSIONS: This study shows that single-dose intramuscular administration of sustained-release Angiopeptin reduces in-stent restenosis as effectively as the prolonged systemic treatment requiring a subcutaneous pump. Thus, a practical, effective, pharmacologic therapy for preventing in-stent restenosis may be available and should be evaluated in patients.

Animals↗
PubMed1997

A randomized animal study evaluating the efficacies of locally delivered heparin and urokinase for reducing in-stent restenosis.

BACKGROUND: In-stent restenosis is primarily due to neointimal hyperplasia. Results from recent nonrandomized studies suggest that local delivery of heparin or urokinase to the site of angioplasty or stenting results in a lower rate of restenosis. OBJECTIVE: To determine whether local delivery of heparin or urokinase reduces in-stent restenosis. METHODS AND RESULTS: Thirty-three pigs were assigned randomly to one of three groups: controls (n = 9) administered local saline infusion, the heparin group (n = 15) administered local heparin (6000 u/10 min), and the urokinase group (n = 9) administered local urokinase (250000 u/10 min), via a local delivery catheter (Dispatch) at the site of subsequent stent implantation. Prior to local delivery, all of the animals were subjected to balloon injury (balloon:artery diameter ratio approximately or = 1.3) to facilitate intramural drug impregnation. After local therapy, one Palmaz-Schatz stent (mean stent: artery diameter ratio approximately or = 1.25) was implanted within the left anterior descending coronary artery. The degree of neointimal hyperplasia was evaluated 4 weeks later by angiography (as the maximal percentage diameter stenosis) and histology (as the maximal neointimal area stenosis). We found no difference in percentage diameter stenosis (46 +/- 18% control, 42 +/- 27% heparin group, and 37 +/- 20% urokinase group, P = 0.7) and corrected neointimal area (1.06 +/- 0.42 mm2 control, 0.94 +/- 0.29 mm2 heparin, and 0.88 +/- 0.26 mm2 urokinase group, P = 0.7) among groups at follow-up. The activated clotting time rose slightly for heparin-treated animals, suggesting that systemic delivery had occurred, whereas fibrinogen levels did not change in urokinase-treated animals. CONCLUSIONS: Local deliveries of heparin and urokinase via the Dispatch catheter, at the chosen dosages, do not reduce in-stent neointimal hyperplasia in this porcine model.

Animals↗