[Coronary restenosis]. / Koronare Restenose.

Coronary restenosis is the answer of the arterial wall to a mechanical violation through balloon angioplasty, bare-metal (BM) stent implantation or rotational atherectomy through repeated narrowing. It has great clinical and prognostic relevance and occurs in approximately 30% of non-coated stents and in 10% of coated coronary stents. The wound healing process that precedes restenosis includes inflammatory reactions, cellular proliferation and remodeling of the arterial wall, where protein synthesis of the extracellular matrix is initiated. The inflammatory reaction activates platelets, leucocytes and monocytes and stimulates smooth muscle cells. The medications on the drug-eluting stents (rapamycin, paclitaxel, sirolimus, evarolimus and zotarolimus) inhibit cell division, are cytotoxic and only these sustainably influence restenosis. Whether they play a role in neoatherosclerosis needs to be determined. The mechanism of restenosis with implantation of drug-eluting stents is heterogeneous and associated with the deposition of T­lymphocytes and fibrin. Risk factors for the development of restenosis include mechanical factors, such as incorrect apposition and expansion of stents, inflammation, diabetes mellitus, genetic factors, bypass operations, stent length and stent diameter. The restenosis rate is lower with drug-eluting stents and must be considered differently between the drug-eluting stents. Drug-eluting stents of the latest generation and drug-coated balloons (DCB) showed the best clinical and angiographic results for in-stent restenosis in randomized trials. The BM and older first-generation drug-eluting stents should be avoided. Further randomized studies are needed.

Characterization of the functional border zone around regionally ischemic myocardium using circumferential flow-function maps.

Previous studies have suggested that there exists a functional border zone in myocardium at the lateral margins of an ischemic area. The functional border zone is normally perfused but is characterized by abnormal contractile function. To define the spatial characteristics of this border zone, circumferential maps of left ventricular function by two-dimensional echocardiography and of coronary flow using radioactive microspheres were generated in 18 dogs at baseline and after circumflex coronary occlusion. Circumferential left ventricular wall thickening was measured in all dogs at 22.5 degrees intervals over 360 degrees. In seven dogs, the pathologic slice corresponding to the two-dimensional echocardiographic image was circumferentially dissected into 16 segments corresponding to 22.5 degrees intervals and a subendocardial myocardial blood flow map was derived. In the other 11 dogs, autoradiography was performed of the pathologic slice corresponding to the two-dimensional echocardiographic image, and the hypoperfusion zone was directly measured. There was no difference between the circumferential extent of hypoperfusion zones by either perfusion measurement technique in the five dogs that had both techniques performed (140 +/- 12 versus 124 +/- 7 degrees, p = NS). The hypofunctional zone by two-dimensional echocardiography was significantly larger than the hypoperfusion zone (174 +/- 4 versus 125 +/- 26 degrees, p less than 0.0005), indicating that a zone of normally perfused but abnormally contracting muscle surrounds the ischemic area. However, this border zone in our model was small, measuring 49 +/- 34 degrees (approximately 8 to 9 mm on either lateral border). This suggests that the functional border zone lateral to ischemic myocardium exists, but is relatively discrete.

Immediate rebound followed by deterioration of regional left ventricular function with coronary reperfusion.

The immediate and early effects of coronary artery reperfusion initiated 1 and 3 hours after coronary artery occlusion were evaluated by two-dimensional echocardiographic measurements of overall and regional left ventricular function. A total of 29 anesthetized open chest dogs underwent one of the following: 1 hour occlusion followed by reperfusion (Group I, n = 9), 3 hour occlusion followed by reperfusion (Group II, n = 12) or 5 hour occlusion without reperfusion (Group III, n = 8). Serial two-dimensional echocardiography was performed at baseline; at 1, 3 and 5 hours of coronary occlusion; within 5 minutes of reperfusion; and at 2 hours of reperfusion. After occlusion, all groups manifested significant (p less than 0.01) increases in left ventricular diastolic and systolic area and decreases in left ventricular area ejection fraction. With coronary reperfusion, there was no improvement in these global variables in Groups I and II. However, immediately after reperfusion, there was improvement in the regional extent of dysfunction (Group I, 138 +/- 35 to 66 +/- 62 degrees, p less than 0.05; Group II, 156 +/- 51 to 85 +/- 77 degrees, p less than 0.05) as well as improvement in the regional degree of dyskinesia (p less than 0.05). These regional improvements were transient and resolved by 2 hours of coronary reperfusion. This immediate rebound of function was not associated with the duration of coronary occlusion, hemodynamic variables or ultimate infarct size. Thus, in the anesthetized open chest dog model, coronary artery reperfusion at 1 or 3 hours produces an immediate but transient improvement in regional systolic myocardial function.

Spontaneous echo contrast caused by platelet and leukocyte aggregates?

BACKGROUND AND PURPOSE: Spontaneous echocardiographic contrast (SEC) is correlated to clinical thromboembolic events. We sought to determine the origin of SEC by utilizing direct analysis of left atrial blood. METHODS: We examined the blood of 13 patients with and 19 without SEC. Blood samples were taken from the femoral vein and artery and from the right and left atria after transseptal puncture. Samples were incubated with fluorescence-labeled antibodies directed against the platelet (CD41a-PE, CD42b-PE, and CD62p-FITC) and leukocyte membrane epitopes (CD45-APC and CD14-FITC). The expressed epitopes were analyzed by dual laser flow cytometry immediately after blood withdrawal. RESULTS: In the peripheral blood of both groups, more activation and aggregation were found in the venous blood than in the arterial blood (CD41a, P=0.007; CD14neutro, P=0.017; and leukocyte-platelet aggregates [LTAg], P=0.002). In patients without SEC, the degree of activation and aggregation of the cardiac samples closely resembled the results of the peripheral samples. The degree of activation and aggregation was significantly higher in the right atrium than in the left atrium (LTAg, P<0.01; leukocyte activation, P<0.01; CD41a, P<0.01; CD62p, P<0.02). In contrast, in patients with SEC the parameters of platelet and leukocyte activation as well as LTAg was significantly higher in the left atrium than in the right atrium of the same patient (all P<0.01). A correlation between the amount of SEC and platelet-monocyte aggregates could be found (r=0.92, P<0.0001). CONCLUSIONS: The hypothesis that platelet aggregates are involved in the pathogenesis of SEC is supported by the fact that platelets in the left atrium of patients with SEC showed more activation.

MIC trial: metoprolol in patients with mild to moderate heart failure: effects on ventricular function and cardiopulmonary exercise testing.

UNLABELLED: Beta-blocker therapy results in a functional benefit in patients with heart failure (CHF) due to idiopathic dilated cardiomyopathy (DCM). This study assessed if similar effects were observed in patients with ischemic heart disease (CAD), NYHA II-III after 6 months of therapy with metoprolol. METHODS AND RESULTS: Fifty-two patients with CHF secondary to DCM (26 patients) and CAD (26 patients) and a left ventricular ejection fraction (EF)<40% were enrolled in the placebo-controlled study. The study medication was titrated over 6 weeks, the mean final dosage was 135 mg/day. Three patients died due to cardiogenic shock, two received placebo and one metoprolol. Eight patients did not complete the study due to non-compliance. Metoprolol significantly reduced heart rate at rest and after submaximal and maximal exercise. Vo(2)-max and Vo(2)-AT as well as the 6-min walk test improved significantly after metoprolol treatment. There was a significant increase in EF at rest (27.3-35. 2%), submaximal (28.5-37.7%) and maximal exercise (28.7-40.9%) in the metoprolol-treated patients. No differences were found between patients with CAD and DCM. We also observed reduced left ventricular volumes. CONCLUSION: The additional therapy with metoprolol improved cardiac function and the cardiopulmonary exercise capacity in patients with CHF.

Noncommunicating intramural hematoma: an indication of developing aortic dissection?

A 60-year-old patient was referred to the hospital for persisting chest pain. The first transesophageal echocardiogram showed localized hematomas without aortic dissection. Several days later the patient suffered complete paraplegia after a second episode of chest pain. The transesophageal echocardiogram now showed a complete aortic dissection. Thus whether intramural hematomas can be regarded as an early sign of impending aortic dissection needs to be investigated.

Left ventricular volume determination using Albunex.

The aim of this study was to assess the ability of intravenous injection of Albunex to improve left ventricular volume determination in patients with various cardiac diseases. It is conceivable that the intravenous injection of microbubbles could improve echocardiographic left ventricular border delineation leading to improved interobserver variability. Echocardiograms were obtained during simultaneous intravenous injection of 0.08 and 0.12 ml/kg Albunex (four-chamber view). Within 6 hours after the recording of the contrast echocardiograms routine left heart angiography was performed. Volumes were measured using the slice method in native and contrast echocardiograms as well as in the angiograms by two independent investigators. The mean differences of angiographic-native echocardiographic and angiographic-contrast echocardiographic volumes (ml) as well as the calculated ejection fraction and their confidence intervals were tabulated and significance was anticipated if the confidence interval did not include zero. Significant changes to angiographic values could be observed concerning end-diastolic, echocardiographic, and contrast echocardiographic volumes at end diastole and end systole, while ejection fractions were similar. Differences between observers were significantly smaller in the contrast echocardiographic images than in the native echocardiographic images. Albunex led to a significantly decreased interobserver variability.

Three-dimensional visualization of coronary arteries in excised hearts.

OBJECTIVE: We sought to image coronary arteries in excised hearts. METHODS: Twelve excised pigs' hearts were imaged in a water bath. The aortic valve was closed surgically. A contrast agent (Echovist) was injected into the aortic root and selectively into single coronary arteries. Three-dimensional (3D) imaging was performed with TomTec Echoscan equipment. Mechanical rotations were performed at 1 degrees intervals. The hearts were visualized by InVivo software. Selective coloring of coronary arteries in 3D data sets was obtained by using color superpositioning, which differentiates information before and after injection of contrast. Distance measurements were performed in conventional 3D echocardiograms of coronary arteries and color-superimposed echocardiograms and compared with those from angiograms and casts. RESULTS: After a learning curve, during which optimal conditions for the visualization of coronary arteries were determined, a quick display of all major parts of the coronary tree was obtained. Distance measurements (n >400) revealed that fundamental contrast echocardiography overestimated angiography by 25% +/- 5% and casts by 28% +/- 6%. However, distances in color-superimposed echocardiograms (flow mode 4) were not significantly different from those obtained from angiograms and casts. In harmonic contrast echocardiograms, color super-positioning gave smaller distances compared with those from fundamental contrast echocardiograms, though they were still significantly larger than the reference diameters. CONCLUSIONS: The 3D imaging of epicardial coronary arteries under ideal conditions in a water bath seems feasible and provides insight into coronary visualization with the use of ultrasonography.

Transthoracic and transesophageal echocardiography to diagnose ventricular septal rupture: importance of right heart infarction.

BACKGROUND: Rapid and accurate diagnosis of ventricular septal rupture (VSR) remains difficult, and the monitoring of hemodynamic deterioration is a prerequisite for the institution of adequate therapy. The timing of surgical repair is a matter of controversy. METHODS: Transthoracic, transesophageal, color Doppler, and contrast echocardiography were evaluated in 17 patients with VSR in whom the diagnosis was confirmed by catheterization, surgery, or necropsy. RESULTS: Routine transthoracic echocardiography visualized VSR in four out of 17 patients and, with additional views, in 12 out of 17 patients. Color Doppler echocardiography identified the rupture in 15 out of 16, and contrast echocardiography in 11 out of 11 patients. VSR was identified using transesophageal echocardiography in six out of nine patients, and using color Doppler and contrast echocardiography in all patients. Eight out of 10 patients who developed right heart myocardial infarction (RMI) died, whereas all patients without RMI survived (P = 0.0070). Similarly, eight out of 10 patients with shock died, whereas all patients without survived (P = 0.0070). Shock occurred more often in patients with RMI (eight out of 10) than in patients without (two out of six). All patients with both RMI and shock died, whereas those without both conditions survived (P = 0.0002). CONCLUSION: Modern echocardiography is the method of choice in the diagnosis of VSR. Right ventricular function should be evaluated in patients with VSR because patients with RMI are at high risk of hemodynamic deterioration, with poor outcome. RMI, visible as abnormal wall motion, was identified better with transesophageal than with transthoracic echocardiography.

Changes of neurohumoral parameters and endothelin-1 in response to exercise in patients with mild to moderate congestive heart failure.

UNLABELLED: Plasma endothelin levels are increased in patients with moderate and severe CHF. Conflicting data exist about the endothelin-1 (ET) level in patients with mild to moderate CHF and the effect of maximal exercise on plasma ET levels. METHODS AND RESULTS: We determined the plasma levels of ET and various neurohumoral parameters in 93 patients with CHF in functional class II and III of the NYHA classification at rest and after maximal bicycle exercise. Baseline ET level was increased compared to an age-matched healthy volunteer group (6.95+/-0.31 vs 3.29+/-0.17 pg/ml, mean+/-S.E.M., P<0.05), without significant differences between NYHA class II and III patients. Maximal exercise did not increase the ET level. In contrast, the neurohumoral parameters were significantly increased with maximal exercise. In conclusion, plasma levels of ET are increased in patients with mild to moderate CHF. However, no further increase in response to exercise was observed. Thus, it is highly unlikely that exercise capacity may be limited by ET-mediated peripheral vasoconstriction.

Visualization of myocardial infarction and subsequent coronary reperfusion with MRI using a dog model.

Twelve anesthetized mongrel dogs underwent left thoracotomy with placement of a removable ligature around the left circumflex coronary artery. Following a 3 to 6 hour delay, ECG-gated spin-echo MRI was performed. The ligature was then removed reperfusing the heart, and after a 10-15 min period, MRI repeated. Finally, post-sacrifice images were obtained, and the hearts chemically stained for infarct evaluation. The MR images were subjectively and quantitatively evaluated for visibility of the endocardial border and of the injured myocardium, and for changes after reperfusion. The injured tissue was variably visible in vivo, the major limitation a result of motion blurring and artifact. The abnormal tissue was easily visible on MRI in 11 animals, and not clearly visible in one. The endocardial border was easily seen in 10 animals. The variation of calculated relaxation times was high for both normal and ischemic/infarcted myocardium in the beating hearts (normal: T1 = 566 +/- 288, T2 = 38 +/- 6; injured myocardium: T1 = 637 +/- 250, T2 = 41 +/- 12) in contrast, relatively stationary skeletal muscle measured in the same images had narrower ranges (T1 = 532 +/- 199, T2 = 28 +/- 2). Changes with reperfusion were seen, but not reliably. The infarcted or ischemic zones were easily visible on post-sacrifice images in all animals imaged. Post-sacrifice relaxation times were T1 = 564 +/- 69 msec, T2 = 39 +/- 3 msec for normal heart muscle, and 725 +/- 114, T2 = 47 +/- 5 for ischemic/infarcted tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunological evaluation of the new stable ultrasound contrast agent LK565: a phase one clinical trial.

BACKGROUND: Ultrasound contrast agents (UCAs) allow the enhancement of vascular definition, thereby providing more diagnostic information. LK565 is a new second-generation UCA based on synthetic polymers of aspartic acid which is eliminated from the blood stream via phagocytosis. LK565 forms very stable air-filled microspheres and is capable of repeated passage through the pulmonary capillary bed after peripheral intravenous injection. This characteristic allows examination of the cardiac function or extracardiac vessel abnormalities up to 15 minutes. METHODS: A phase one clinical study was conducted on 15 healthy volunteers to identify the development of an undesirable immune response. Phagocytosis capacity, TNF-alpha secretion, and MHC class II upregulation of monocytes was monitored, as well as microsphere specific antibody development (IgM, IgG). Furthermore, the kinetics of the activation surface markers CD69, CD25, CD71, and CD11b on leukocytes were analyzed. RESULTS: Due to LK565-metabolism the administration of the UCA led to saturation of phagocytes which was reversible after 24 hrs. Compared to positive controls neither significant TNF-alpha elevation, neither MHC class II and activation surface markers upregulation, nor specific antibody development was detectable. CONCLUSION: The administration of LK565 provides a comfortable duration of signal enhancement, esp. in echocardiography, without causing a major activation cascade or triggering an adaptive immune response. To minimize the risk of undesirable adverse events such as anaphylactoid reactions, immunological studies should be included in clinical trials for new UCAs. The use of LK565 as another new ultrasound contrast agent should be encouraged as a safe means to provide additional diagnostic information.

Left atrial thrombi despite anticoagulant and antiplatelet therapy.

To investigate risk factors for embolization in patients with echocardiographically detected left atrial thrombi and to evaluate thrombus development, we examined 29 patients with transesophageal and transthoracic echocardiography at two points during a follow-up of 18 months. We compared patients with a history of possible arterial embolization (n = 13) with those without (n = 16) in regard to age, gender, left atrial dilatation, localization of the thrombus in the left atrial cavity, spontaneous echo contrast, and atrial fibrillation. Eight patients were treated with aspirin, 20 with phenprocoumon. Only left atrial spontaneous contrast was associated with thromboembolism (10/15 patients with spontaneous contrast experienced arterial embolism; p = 0.038). In six patients arterial embolism occurred after thrombus detection (14% per patient per year). Four of these patients were treated with phenprocoumon, two with aspirin. At reexamination, one thrombus was detected in the patient without anticoagulant treatment and one thrombus was detected in the 8 patients treated with aspirin (13%), compared with ten thrombi detected in the 20 patients (50%) treated with phenprocoumon (p = NS). In 17 patients no thrombus was seen at reexamination. Since only 2 patients had undergone thrombectomy and 3 experienced arterial embolism during follow-up, thrombi disappeared under medical therapy in 12 patients. Patients with left atrial thrombi have a high risk of arterial embolization despite proper anticoagulative or antiplatelet treatment. Embolization occurs significantly more often if spontaneous echo contrast can be visualized. Left atrial thrombi can be reduced in size by the administration of antiplatelet and anticoagulative agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of papillary muscle rupture after acute myocardial infarction by transthoracic and transesophageal echocardiography.

The sensitivity of transthoracic echocardiography to visualize the structural abnormality of papillary muscle rupture (PMR) after acute myocardial infarction can be anticipated to average about 50%; therefore, we evaluated five patients exhibiting the condition with both transthoracic and transesophageal echocardiography. The use of the two imaging techniques resulted in the fact that no instance of PMR was missed. Using transthoracic echocardiography in two patients and transesophageal echocardiography in four, the ruptured papillary muscle was visualized directly. Mitral insufficiency as an indirect sign was observed in all patients. In one patient the papillary muscle rupture developed in a mitral valve previously affected by endocarditis. All patients underwent mitral valve replacement and coronary artery bypass grafting. The diagnosis was confirmed at surgery in all patients. Four patients died in hospital, the fifth 5 months later. We recommended that transesophageal echocardiography be performed in patients with suspected PMR if transthoracic echocardiography does not provide an unequivocal diagnosis.

Serial assessment of circumferential regional left ventricular function following complete coronary occlusion.

The effect of abrupt coronary artery occlusion on regional left ventricular (LV) function is well known, but serial changes in circumferential regional function over the first few hours have not been extensively investigated. Circumflex coronary artery occlusion was produced in nine closed-chest, conscious dogs and changes in LV circumferential function were assessed using two-dimensional echocardiography (2DE) performed in the short-axis projection at the mid-papillary muscle level. End-diastolic and end-systolic frames were manually digitized and regional area ejection fractions at 22.5-degree intervals were calculated using a fixed diastolic center of mass. Endocardial motion abnormality was measured from a circumferential regional ejection fraction map. The extent of wall motion abnormality was measured as that exceeding 95% confidence limits of normal controls; the degree of dyssynergy was measured as the planimetered area of the extent of wall motion abnormality. Following circumflex coronary artery occlusion, a wall motion abnormality was well defined with a minute of occlusion and its circumferential extent measured 146 +/- 16 degrees with 11 +/- 2 cm2 absolute degree of dyssynergy. These parameters did not change over the course of the coronary artery occlusion. We conclude that circumferential regional abnormalities produced by coronary occlusions are well defined early and do not change over the first 3 hours of acute ischemia and infarction.

The effect of inotropic stimulation on normal and ischemic myocardium after coronary occlusion.

During acute myocardial ischemia, there exists a zone of myocardial dysfunction that surrounds the central ischemic area that has been termed the functional border zone. We hypothesized that this nonischemic but dysfunctional myocardium may respond to an inotropic challenge. To address this issue, we studied 11 open-chest dogs during acute left circumflex (LCx) occlusion. Simultaneous two-dimensional echocardiograms and radioactive microsphere injections were used to create circumferential left ventricular flow-function maps at the papillary muscle level. Serial studies were performed at baseline, 15 min after LCx occlusion, and after the infusion of dobutamine during LCx occlusion. After occlusion, wall thickening decreased from 52 +/- 8% (mean +/- SEM) to -5 +/- 5% (p less than .01) in the central ischemic zone. The extent of left ventricular dysfunction measured 170 +/- 11 degrees while the subendocardial hypoperfusion zone was 130 +/- 9 degrees (p less than .05), resulting in a functional border zone of 40 +/- 11 degrees. During the infusion of dobutamine, wall thickening did not change in the central ischemic zone but increased adjacent to the functional border zone (p less than .01) and in the normal zone (p less than .05), reducing the extent of the functional border zone to 19 +/- 16 degrees (p less than .05). After dobutamine, the slope of transition of wall thickening from nonischemic to ischemic zones, measured directly from the left ventricular function map, increased on the free wall border (0.71 +/- 0.11 to 0.95 +/- 0.10, p less than .02) to a greater extent than on the septal border (0.60 +/- 0.08 to 0.73 +/- 0.06, p = .07). We conclude that nonischemic myocardium adjacent to ischemic tissue responds to inotropic challenge, dobutamine produces a significant decrease in the size of the functional border zone, and dynamic changes in wall thickening after inotropic intervention are greater in the functional border zone of the lateral free wall than at the septal border of the ischemic area.

In vitro measurement accuracy of three-dimensional ultrasound.

OBJECTIVES: We sought to validate distance and volume measurements in three-dimensional (3-D) ultrasound images. BACKGROUND: Even with the latest equipment, it is not known how accurate 3-D echocardiographic measurements are. METHODS: Six models were imaged in ethanol solution and two within a tissue phantom using a mechanical rotation device rotating in 1 degrees intervals and a real-time 3-D scanner. Distance and volume measurements (n = 60) were performed in two-dimensional (2-D) and 3-D images using TomTec and InViVo software. RESULTS: Distance measurements had a mean total error between 1.12% and 2.31% for Acuson (2.5 MHZ, 3 MHZ, and 4 MHZ) and Hewlett Parkard (HP) fusion frequencies h and m, HP fusion harmonic B in the axial, and between 3.5% and 4.9% in the lateral dimension. HP Harmonic A and B, Volumetrics (2.5 MHZ), and HP fusion Harmonic A exhibited significantly higher differences to reality with a mean difference between 5.1% and 8.9% in the axial and between 6.2% and 7.9% in the lateral direction. Axial 2-D measurements were not different from real dimensions except Volumetrics model 1. In the lateral axis, all imaging modalities were different from reality except the fusion harmonic modus B. Using the HP fusion frequency h and HP fusion Harmonic B-mode, volume measurements in 3-D images significantly underestimated reality, while Acuson's fundamental frequency 3.5 MHZ was not different from real volumes. CONCLUSION: Three-dimensional visualization using different ultrasound settings results in different accuracy.

Rapid in vitro biocompatibility assay of endovascular stents by flow cytometry using platelet activation and platelet-leukocyte aggregation.

Clinical studies suggest that stent design and surface texture are responsible for differences in biocompatibility of metallic endovascular stents. A simple in vitro experimental setup was established to test stent-induced degree of platelet and leukocyte activation and platelet-leukocyte aggregation by flow cytometry. Heparin-coated tantalum stents and gold-coated and uncoated stainless steel stents were tested. Stents were implanted into silicone tubes and exposed to blood from healthy volunteers. Platelet and leukocyte activation and percentage of leukocyte-platelet aggregates were determined in a whole-blood assay by subsequent staining for activation-associated antigens (CD41a, CD42b, CD62p, and fibrinogen binding) and leukocyte antigens (CD14 and CD45) and flow cytometric analysis. Blood taken directly after venous puncture or exposed to the silicone tube alone was used as negative controls. Positive control was in vitro stimulation with thrombin receptor activating peptide (TRAP-6). Low degree of platelet activation and significant increase in monocyte- and neutrophil-platelet aggregation were observed in blood exposed to stents (P < 0.05). In addition, leukocyte activation was induced as measured by increased CD45 and CD14 expression. Heparin coated stents continuously induced less platelet activation and leukocyte-platelet aggregation than uncoated stainless steel stents of the same length and shorter stents of the same structure. Stent surface coating and texture plays a role in platelet and leukocyte activation and leukocyte-platelet aggregation. Using this simple in vitro assay and whole blood and flow cytometry, it seems possible to differentiate stents by their potency to activate platelets and/or leukocytes. This assay could be applied for improving the biocompatibility of coronary stents.

Contrast echocardiography of the left ventricle an independent predictor of pulmonary artery pressure?

To test the hypothesis that left heart opacification is dependent on pulmonary artery pressure, we analyzed consecutively 12 patients with normal and 8 patients with abnormal pulmonary artery pressure with a new lung capillary stable echo contrast agent. Patients underwent contrast echocardiographic examination within 6 hours before right and left heart catheterization with 200 mg/ml and 400 mg/ml SHU 508A intravenously. The mean pulmonary artery pressure was 15.4 mmHg in the patients with normal pulmonary artery pressures and 46.4 mmHg in the patients with pulmonary hypertension (p < 0.000). Echocardiograms were video-intensitometrically analyzed for intensity maximum (MAX), half-time of video-intensity decay (T1/2), area under the intensity curve (AUC) in the right and left ventricle and transit time from left to right heart (TT). Patients with normal pulmonary artery pressure showed sufficient left heart opacification, in the left ventricle MAX was 37 +/- 15 IU, AUC measured 653 +/- 463 IUxs and T1/2 was 4.4 +/- 2.6 s, while patients with elevated pulmonary artery pressure showed no significant left heart opacification. In the left ventricle MAX was 8 +/- 10 IU (p = 0.006), AUC measured 66 +/- 108 (p = 0.003) and T1/2 was 2.0 +/- 2.0 s (p = 0.041). TT was significantly increased in patients with elevated pulmonary artery pressure (11.8 +/- 4.6 s versus 6.5 +/- 2.8 s in patients with normal pulmonary artery pressure, p = 0.005). Thus, elevated pulmonary pressure has a significant impact on left heart opacification, which may be used for diagnostic purposes.

The influence of Albunex on the pulmonary circulation in patients with pulmonary hypertension or left heart failure.

To determine the safety of the ultrasound contrast agent Albunex, its influence on right and left heart haemodynamics in patients with pulmonary artery hypertension or left heart failure was assessed after intravenous injection. Patients with a left ventricular ejection fraction smaller than 40% or a systolic pulmonary artery pressure greater than 40 mmHg received 0.08 and 0.22 ml.kg-1 Albunex and 10 ml albumin in random order during right heart catheterization and transthoracic echocardiography. Right atrial, systolic and diastolic pulmonary artery and capillary wedge pressures were measured at 3 min and 5 min and cardiac output at 5 min after the intravenous injection of Albunex and control. The mean differences of pre- and postinjection values and their confidence intervals were tabulated and significance was anticipated if the confidence interval did not include 0. Significant changes to pre-injection values could be observed in diastolic pulmonary artery pressure 5 min after the injection of albumin and 0.08 ml.kg-1 Albunex, and in right atrial pressure 5 min after the injection of 0.22 ml.kg-1 Albunex only. Since intermediate opacification of the left ventricle was seen in only four patients with 0.22 ml.kg-1 Albunex, in the patients studied higher doses of Albunex and their safety need to be assessed.