Ultrasound thrombolysis in stent thrombosis.

Recent refinement in stent implantation technique and peri-procedural pharmacological treatment has lowered the incidence of stent thrombosis significantly. Still, all stent thromboses are associated with major adverse events. In previous studies it has been suggested that intravascular ultrasound fibrinolysis is safe and effective. In this report, ultrasound successfully reperfused thrombotically occluded stents. These observations suggest that ultrasound may dissolve occlusive platelet-rich thrombus effectively and safely. Cathet. Cardiovasc. Intervent. 51:332-334, 2000.

Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE trial). Results of the feasibility phase.

BACKGROUND: It has been demonstrated that therapeutic ultrasound effects ultrasound thrombolysis by selectively disrupting the fibrin matrix of the thrombus. This study was conducted to evaluate the clinical feasibility of percutaneous transluminal coronary ultrasound thrombolysis in acute myocardial infarction (AMI). METHODS AND RESULTS: Consecutive patients (n = 15) with evidence of anterior AMI and Thrombolysis in Myocardial Infarction (TIMI) grade 0 or 1 flow in the left anterior descending artery underwent coronary ultrasound thrombolysis. Angiographic follow-up was performed after 10 minutes and 12 to 24 hours. Ultrasound induced successful reperfusion (TIMI grade 3 flow) in 87% of the patients. Adjunct percutaneous transluminal coronary angioplasty (PTCA) after ultrasound thrombolysis produced a final residual stenosis of 20 +/- 12% as determined by quantitative coronary angiographic analysis. There were no adverse angiographic signs or clinical effects during the procedure. There was no change in the degree of flow in any of the patients at the 12- to 24-hour angiograms. During hospitalization, 1 patient had recurrent ischemia on the fifth day after the procedure, and emergent catheterization revealed occlusion at the treatment site. The patient was successfully treated with PTCA. CONCLUSIONS: These results suggest that ultrasound thrombolysis has the potential to be a safe and effective catheter-based therapeutic modality in reperfusion therapy for patients with AMI and other clinical conditions associated with intracoronary thrombosis.

Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years.

OBJECTIVE: To test the hypothesis that subjects who clear chylomicron remnants slowly from plasma may be at higher risk of coronary artery disease than indicated by their fasting plasma lipid concentrations. DESIGN: Case control study over three years. SETTING: An 800 bed general municipal hospital. SUBJECTS: 85 normolipidaemic patients with coronary artery disease selected prospectively and matched with 85 normolipidaemic subjects with normal coronary arteries on angiography. INTERVENTIONS: All subjects were given a vitamin A fat loading test which specifically labels intestinal lipoproteins with retinyl palmitate. MAIN OUTCOME MEASURE: Postprandial lipoprotein metabolism. RESULTS: The area below the chylomicron remnant retinyl palmitate curve was significantly increased in the coronary artery disease group as compared with the controls (mean 23.4 (SD 15.0) v 15.3 (8.9) mumol/l.h; 95% confidence interval of difference 4.37 to 11.82). CONCLUSION: Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease.

Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and accumulation of chylomicrons in circulation.

Heparin is a well-known, widely used anticoagulant drug. In addition to its anticoagulant properties, however, it also has a marked influence on fat metabolism. Postprandial lipoproteins may contribute significantly to the development of coronary heart disease. Therefore, it is important to evaluate the effects of heparin on these lipoproteins. The effect of continuous heparin administration on postprandial lipoprotein metabolism was studied in 11 patients with thromboembolic disease. Results were compared with those in a group of six patients given no heparin. Two vitamin A-fat loading tests were done: the first, 5 days before heparin was started and the second, on the fourth day of continuous heparin drip of 1000 U/h, maintaining PTT levels at twice the baseline. To study the effect of acute heparin, an additional fat loading test was done in five patients on the first day of heparin treatment. Vitamin A, specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). The concentrations of chylomicron (Sf > 1000)- and nonchylomicron (Sf < 100)-retinyl palmitate were measured for 10 h postprandially. Four days of continuous intravenous heparin administration increased the area below the chylomicron RP curve from 11091 +/- 4393 to 17684 +/- 5949 micrograms/l.h (P < 0.003). When measured on the first day of heparin treatment in five patients, the area of the chylomicron fraction was reduced from 16678 +/- 6895 to 10474 +/- 3893 micrograms/l.h (P < 0.05). Postheparin lipoprotein lipase activity was significantly lower on the fourth day of heparin, administration than before treatment: 1.8 +/- 1.1 vs. 4.1 +/- 1.3 mumol/FFA per ml per h, respectively (P < 0.0005). In the six control patients with thromboembolic disease in whom heparin therapy was not indicated, no changes in postprandial lipoprotein levels or in lipolytic activity during hospitalization were found. The study demonstrates that 4 days of heparin administration causes an accumulation of chylomicrons in the circulation, most probably as a result of a marked decrease in serum lipolytic activity.

Octogenarian subjects have low postprandial levels of chylomicron remnants: a possible explanation for protection against atherosclerosis.

Postprandial lipoprotein metabolism may play an important role in the development of atherosclerosis. It is widely believed that in healthy octogenarians, the atherogenic process occurs very slowly. In the present study, postprandial lipoprotein metabolism was examined in 14 octogenarian subjects (mean age, 84 +/- 4.2 years) and 19 younger controls (mean age, 50 +/- 4.8 years) using the vitamin A-fat loading test, in which intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Results indicated that mean peak chylomicron remnant RP levels and the areas below the chylomicron remnant RP curve were significantly lower in the octogenarian group than in the controls (625 +/- 329 vs 1321 +/- 688 micrograms/L and 3740 +/- 1078 vs 6162 +/- 1063 micrograms/L.h, respectively; p < .0001). No differences were found between the two groups in chylomicron RP levels or in lipolytic activity. The study suggests that octogenarians do not exhibit the decrease in chylomicron lipolysis that usually accompanies aging. In addition, these subjects have significantly lower levels of chylomicron remnants in the circulation. Since accumulation of these particles has been implicated in the development of atherogenesis, our findings may indicate a major mechanism of atherosclerosis prevention in healthy octogenarians.

Severe defect in clearing postprandial chylomicron remnants in dialysis patients.

Lipid abnormalities have been suggested as a major cause of the accelerated atherosclerosis and the high incidence of coronary heart disease in chronic renal failure patients. In the present work the postprandial lipoprotein metabolism was studied in chronic dialysis patients with or without fasting hypertriglyceridemia using the vitamin A loading test. This method investigates specifically postprandial lipoprotein metabolism. The determination of vitamin A ester level retinyl palmitate (RP) differentiates the circulating plasma chylomicron and chylomicron remnant fractions from the endogenous VLDL and IDL. Subjects with normal renal function with or without fasting hypertriglyceridemia served as control groups. Dialysis patients have significantly higher level of chylomicron remnants for a more prolonged period of time than controls, irrespective of their fasting triglyceride levels. The area below retinyl palmitate chylomicron remnants curve was 26308 +/- 12422 micrograms/liter.hr in the normolipidemic dialysis patients, significantly higher than (6393 +/- 2098 micrograms/liter.hr; P < 0.0001) in the normolipidemic controls. The retinyl palmitate chylomicron remnants curve of the hypertriglyceridemic dialysis patients was 21021 +/- 4560 micrograms/liter.hr, which was higher than 12969 +/- 2215 micrograms/liter.hr (P < 0.0001) in the hypertriglyceridemic controls. Moreover, the hypertriglyceridemic dialysis patients had an additional defect in the lipolysis metabolic step, that is, accumulation of chylomicrons in circulation. These findings show a severe defect in postprandial lipoprotein metabolism in chronic renal failure patients. The prolonged exposure of the vascular wall to high chylomicron remnant concentrations might be an important pathogenetic factor in the accelerated atherosclerosis seen in chronic dialysis patients.

Vitamin A loading--an indicator of post-prandial lipoprotein clearance in healthy and hypertriglyceridemic subjects.

To study post-prandial lipoprotein metabolism in normolipidemic and hypertriglyceridemic subjects, a vitamin A fat loading test was used. This method specifically labels dietary fat particles with retinyl palmitate (RP). Following RP concentrations, metabolic behavior of chylomicrons and chylomicron remnants were studied. In normal subjects, post-prandial lipoproteins were present for more than 10 h. Total RP increased rapidly between 1 and 4 h, peaked at 6 h and declined rapidly between 6 and 10 h. The chylomicron and chylomicron remnant fractions behaved differently, showing precursor product relationship. The hypertriglyceridemic patients demonstrated a very severe defect in chylomicron clearance. This fraction was 2.8-fold higher than in normal subjects, which was 7,260 vs. 2,600 micrograms/l, respectively. The large magnitude and long duration of post-prandial lipemia in normal and hypertriglyceridemic patients support the hypothesis that these atherogenic particles may play a role in the development of coronary heart disease.