Comparison of ethanol septal reduction therapy with surgical myectomy for the treatment of hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was designed to compare the hemodynamic efficacy of nonsurgical septal reduction therapy (NSRT) by intracoronary ethanol with standard therapy (surgical myectomy) for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Nonsurgical septal reduction therapy has gained interest as a new treatment modality for patients with drug-refractory symptoms of HOCM; however, its benefits in comparison to surgery are unknown. METHODS: Forty-one consecutive NSRT patients at Baylor College of Medicine with one-year follow-up were compared with age- and gradient-matched septal myectomy patients at the Mayo Clinic. All patients had left ventricular outflow obstruction with a resting gradient > or =40 mm Hg and none had concomitant procedures. RESULTS: There were no baseline differences in New York Heart Association class, severity of mitral regurgitation, use of cardiac medications or exercise capacity. One death occurred during NSRT because of dissection of the left anterior descending artery. At one year, all improvements in both groups were similar. After surgical myectomy, more patients were on medications (p < 0.05) and there was a higher incidence of mild aortic regurgitation (p < 0.05). After NSRT, the incidence of pacemaker implantation for complete heart block was higher (22% vs. 2% in surgery; p = 0.02). However, seven of the nine pacemakers in the NSRT group were implanted before a modified ethanol injection technique and the use of contrast echocardiography. CONCLUSIONS: Nonsurgical septal reduction therapy resulted in a significantly higher incidence of complete heart block, but the risk was reduced with contrast echocardiography and slow ethanol injection. Surgical myectomy resulted in a significantly higher incidence of mild aortic regurgitation. Nonsurgical septal reduction therapy, guided by contrast echocardiography, is an effective procedure for treating patients with HOCM. The hemodynamic and functional improvements at one year are similar to those of surgical myectomy.

Use of ICHOR-platelet works to assess platelet function in patients treated with GP IIb/IIIa inhibitors.

Platelet glycoprotein GP IIb/IIIa inhibitors have been recently approved for use in treating patients with acute coronary syndromes and those undergoing PCI. The purpose of this study was to assess the feasibility of using a new device, the ICHOR platelet works, to detect platelet inhibition in patients undergoing PCI and treated with abciximab or tirofiban. The study was conducted at Baylor College of Medicine, Houston, Texas. Thirty patients undergoing PCI and treated with abciximab (n = 10) or tirofiban (n = 20) are included. Blood samples were obtained before, at 30 min, at 4 hr, and at 12 hr after starting the GP IIb/IIIa inhibitors and 2 hr after discontinuation. Baseline studies revealed > 95% platelet aggregability in all patients after exposure to ADP (20 microM). After starting tirofiban, 82%, 83%, and 82% of platelets were inhibited at 30 min, 4 hr, and 12 hr. Platelet inhibition decreased to 43% 2 hr after discontinuation of tirofiban. Similarly, ICHOR platelet works detected 91%, 92%, and 85% platelet inhibition at 30 min, 4 hr, and 12 hr after starting abciximab, respectively. Platelet inhibition decreased to 73% 2 hr after discontinuation. The ICHOR platelet works is a promising, simple, and rapid bedside method that may have clinical utility in assessing platelet inhibition in patients treated with GP IIb/IIIa inhibitors. Cathet Cardiovasc Intervent 2001;53:346-351.

Decreased expression of tumor necrosis factor-alpha and regression of hypertrophy after nonsurgical septal reduction therapy for patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Nonsurgical septal reduction therapy (NSRT) is a novel therapeutic strategy for patients with hypertrophic obstructive cardiomyopathy (HOCM). Although the clinical benefits of this technique appear to be clear, the structural and functional changes that lead to improvements in cardiac function are not completely defined. In these studies, we sought to define the effect of NSRT on myocardial function as well as various markers of hypertrophy including the expression of tumor necrosis factor (TNF)-alpha, a cytokine capable of producing fibrosis, left ventricular hypertrophy (LVH), and cardiomyopathy. METHODS AND RESULTS: We performed endomyocardial biopsies of the RV side of the septum and echocardiograms on 15 HOCM patients at baseline and after successful NSRT. Comparative analysis on paired myocardial samples were performed to determine the effects of NSRT on LVH, end-diastolic volume and chamber stiffness, myocyte size, collagen content, and TNF-alpha levels. At baseline, myocardial TNF-alpha levels were increased in all patients. After NSRT, myocyte size, collagen content, and TNF-alpha were significantly decreased. These changes were accompanied by an increase in left ventricular volumes and a reduction in LVH and chamber stiffness. CONCLUSIONS: We suggest that pressure overload in HOCM patients contributes to the development of hypertrophy. These data provide the initial experimental evidence to suggest that TNF-alpha may play a pathogenetic role in the hypertrophy of pressure overload.

Platelet glycoprotein IIb/IIIa receptor antagonists and coronary artery disease.

The importance of platelets in coronary artery disease has been better elucidated in the past 20 years with the continued understanding of their role in the development of the atherosclerotic lesion and acute coronary syndromes. The most recent therapeutic efforts have focused on blockade of the platelet glycoprotein IIb/IIIa receptor, which represents the final common pathway to platelet aggregation and arterial thrombus formation. This manuscript summarizes platelet function and pathophysiology, currently available glycoprotein IIb/IIIa inhibitors, and the important clinical trials with this new class of drugs.

Regression of left ventricular hypertrophy after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by left ventricular hypertrophy (LVH) in the absence of increased external load. Recently, nonsurgical septal reduction therapy (NSRT) with intracoronary ethanol has been introduced to treat severely symptomatic patients with outflow tract obstruction. Its long-term effects on LV mass, however, are unknown. METHODS AND RESULTS: The LV size, function, and outflow tract gradient of 26 HOCM patients (53+/-15 years old) who underwent NSRT were assessed by echocardiography at baseline and 1 and 2 years after the procedure. LVH was evaluated by wall thickness of individual myocardial segments, planimetered myocardial area, and mass. The outflow gradient decreased from 36+/-6 mm Hg before NSRT to 0+/-3 mm Hg at 2 years (P<0.001), with patients experiencing symptomatic improvement (P<0.05). LV end-diastolic and end-systolic dimensions increased significantly at both 1 and 2 years (P<0.001). All parameters of LVH showed evidence of regression. LV mass decreased (301+/-78 g at baseline, 223+/-5 g at 1 year, and 190+/-58 g at 2 years; P<0.01), with the 2-year reduction in mass related to infarct size and the acute reduction in outflow tract gradient (r=0.48, P<0.05 and r=0.63, P<0.01, respectively). CONCLUSIONS: NSRT results in LV remodeling that is characterized by an increase in LV size and a decrease in the extent of LVH.

Echocardiographic insights into the mechanisms of relief of left ventricular outflow tract obstruction after nonsurgical septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: We sought to evaluate the mechanisms by which nonsurgical septal reduction therapy (NSRT) reduces left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic obstructive cardiomyopathy (HOCM) both acutely and on a long-term basis. BACKGROUND: NSRT reduces LVOT obstruction in patients with HOCM and leads to symptomatic improvement. The mechanisms involved, however, are not well studied. METHODS: An initial group of 30 HOCM patients (age 46 +/- 17, 16 women) who underwent NSRT had echocardiographic studies performed at baseline and six months after the procedure. Measurements included LVOT diameter, end-diastolic distance between the anterior mitral leaflet and interventricular septum, septal base function and the angle between LV systolic flow and the protruding mitral leaflets. In addition, pulse Doppler recordings at a point 2.5 cm apical to the mitral valve were acquired and analyzed for peak and mean ejection velocity, peak acceleration rate and the ratio of acceleration time to ejection time (AT/ET). RESULTS: Significant changes were observed after the procedure, with widening in the LVOT, thinning and akinesis of the septal base, decrease in the angle between LV systolic flow and the protruding mitral leaflets, a decrease in peak acceleration rate and an increase in AT/ET. All of these variables had significant relations with the decrease in LVOT obstruction (r = 0.5 to 0.79, p < 0.01). These correlations were then evaluated in a test group of 15 patients who underwent echocardiographic examinations at baseline, acutely in the catheterization laboratory with ethanol injection and at six weeks post NSRT. Acute changes in peak acceleration rate (r = 0.65) and AT/ET (r = 0.73) related significantly (p < 0.01) to the decrease in LVOT obstruction with ethanol. At six weeks, changes similar to those noted in the initial group were observed in LVOT geometry, the angle between LV systolic flow and the protruding mitral leaflets, peak acceleration rate and AT/ET. In both populations combined, these parameters accounted for 72% to 77% of the variance in gradient reduction. CONCLUSIONS: Changes in LV ejection dynamics and septal base function account in part for the acute relief of LVOT gradient after NSRT. The long-term relief of obstruction is dependent on remodeling of LVOT as well as the changes in LV ejection.

Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up.

OBJECTIVE: The objective of this study is to evaluate the one-year outcome of the first 50 patients who underwent nonsurgical septal reduction for symptomatic hypertrophic obstructive cardiomyopathy at our institution. BACKGROUND: Left ventricular outflow tract obstruction is an important determinant of clinical symptoms in patients with hypertrophic obstructive cardiomyopathy. Nonsurgical septal reduction is a new therapy that has been shown to result in left ventricular outflow tract gradient reduction and resolution of symptoms immediately after the procedure and on midterm follow-up. METHODS: Fifty patients with hypertrophic obstructive cardiomyopathy who underwent nonsurgical septal reduction at our institution and completed 1-year follow-up are described. Complete history, physical examination, two-dimensional echocardiography with Doppler and exercise treadmill testing have been analyzed. RESULTS: The mean age of the study group was 53 +/- 17 years. All patients had refractory symptoms before enrollment. Ninety-four percent had class III or IV New York Heart Association class symptoms at baseline compared to none at 1 year (p < 0.001). The exercise duration increased by 136 s at 1 year (p < 0.021). Only 20% of patients were either receiving beta-blockers or calcium-channel blockers on follow-up. The resting left ventricular outflow tract gradient decreased from 74 +/- 23 mm Hg to 6 +/- 18 mm Hg (p < 0.01) and from 84 +/- 28 mm Hg to 30 +/- 33 mm Hg (p < 0.01) in patients with dobutamine-provoked gradient at one year. These changes are associated with decreased septal thickness and preserved systolic function. CONCLUSION: Nonsurgical septal reduction therapy is an effective therapy for symptomatic patients with hypertrophic obstructive cardiomyopathy with persistence of the favorable outcome up to one year after the procedure.

Changes in left ventricular filling and left atrial function six months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The purpose of this study was to evaluate changes in left ventricular (LV) filling, left atrial (LA) volumes and function six months after nonsurgical septal reduction therapy (NSRT) for hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Patients with HOCM frequently have enlarged left atria, which predisposes them to atrial fibrillation. Nonsurgical septal reduction therapy results in significant reduction in left ventricular outflow tract (LVOT) obstruction and symptomatic improvement. However, its effect on LV passive filling volume, LA volumes and function is not yet known. METHODS: Thirty patients with HOCM underwent treadmill exercise testing as well as 2-dimensional and Doppler echocardiography before and six months after NSRT. Data included clinical status, exercise duration, LVOT gradient, mitral regurgitant (MR) volume, LV pre-A pressure and LA volumes. Left atrial ejection force and kinetic energy (KE) were computed noninvasively and were compared with 12 age-matched, normal subjects. RESULTS: New York Heart Association (NYHA) class was lower and exercise duration was longer (p < 0.05) six months after NSRT. The LVOT gradient, MR volume and LV pre-A pressure were all significantly reduced. HOCM patients had larger atria, which had a higher ejection force and KE, compared with normal subjects (p < 0.01). After NSRT, LV passive filling volume increased (p < 0.01), whereas LA volumes, ejection force and KE decreased (p < 0.01). Reduction in LA maximal volume was positively related to changes in LV pre-A pressure (r = 0.8, p < 0.05) and MR volume (0.4, p < 0.05). Changes in LA ejection force were positively related to changes in LA pre-A volume (r = 0.7, p < 0.01) and KE (r = 0.81, p < 0.01). The increase in exercise duration paralleled the increase in LV passive filling volume (r = 0.85, p < 0.05). CONCLUSIONS: Nonsurgical septal reduction therapy results in an increase in LV passive filling volume and a reduction in LA size, ejection force and KE.

Chimeric 7E3 Fab (ReoPro) decreases detectable CD11b on neutrophils from patients undergoing coronary angioplasty.

OBJECTIVES: The purpose of this study was to monitor the effects of chimeric 7E3 Fab (ReoPro) on leukocyte and platelet activation and interaction during coronary angioplasty. BACKGROUND: Increased expression of CD11b on monocytes and neutrophils promotes their adhesion to endothelial cells, extracellular matrix and smooth muscle cells. Thrombin-activated platelets adhere via P-selectin to monocytes and neutrophils. These cell interactions may affect the outcome of coronary angioplasty. METHODS: During coronary angioplasty, venous blood was obtained for flow cytometric detection of leukocyte CD11b; platelet CD41a, CD61a and CD62P; the percentage of leukocytes with adherent platelets and the intensity of bound platelet fluorescence. RESULTS: Leukocyte CD11b expression increased after angioplasty in control patients (neutrophils 171+/-25 to 255+/-31 mean fluorescence intensity [MFI, mean+/-SEM], n=25, p < 0.0001; monocytes 200+/-40 to 248+/-36 MFI, n=17, p < 0.05) and decreased in the patients selected to receive chimeric 7E3 Fab (neutrophils 146+/-30 to 82+/-22 MFI, n=25, p < 0.0001; monocytes 256+/- 53 to 160+/-38 MFI, n= 17, p < 0.05). Neutrophil CD11b decreased after in vitro incubation of whole blood with chimeric 7E3 Fab (n=5, p=0.01), but fMLP-induced increases in CD11b were not prevented. The CD11b expression was unchanged and increased with fMLP stimulation after in vitro incubation of isolated neutrophils with chimeric 7E3 Fab. Direct-labeled chimeric 7E3 Fab was not detected bound to neutrophils in whole blood or isolated cells using flow cytometric techniques. Adhesion of isolated neutrophils to protein-coated glass was not prevented by in vitro incubation with chimeric 7E3 Fab. Platelet activation increased after angioplasty in control patients (CD62P 8.9+/-0.8 to 12.3+/-1.2 MFI, n=25, p < 0.05; CD41a 382+/-25 to 454+/-26 MFI, n=25, p < 0.05, CD61a 436+/-52 to 529+/-58 MFI, n=11, p < 0.05); it did not increase in the patients selected to receive chimeric 7E3 Fab (CD62P 13.2+/-1.0 to 9.0+/-0.9 MFI, n=25, p < 0.05; CD61a 398+/-32 to 410+/-38 MFI, n=7, p=NS). Leukocytes with adherent platelets tended to increase in the control group of patients and decrease after the procedure in patients selected to receive chimeric 7E3 Fab; individual and procedure-related variability were marked. CONCLUSIONS: Despite standard aspirin and heparin therapy, leukocyte and platelet activation with platelet adherence to leukocytes occurs after coronary angioplasty. Although chimeric 7E3 Fab does not bind to leukocytes directly, it influences CD11b expression in whole blood. Modulation of platelet and leukocyte activation and interaction by chimeric 7E3 Fab may contribute to an improved outcome after coronary angioplasty.

Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy.

BACKGROUND: Conventional Doppler parameters are unreliable for estimating left ventricular (LV) filling pressures in hypertrophic cardiomyopathy (HCM). This study was undertaken to evaluate flow propagation velocity by color M-mode and early diastolic annular velocity (Ea) by tissue Doppler 2 new indices of LV relaxation, combined with mitral E velocity for estimation of filling pressures in HCM. METHODS AND RESULTS: Thirty-five HCM patients (52+/-15 years) underwent LV catheterization simultaneously with 2-dimensional and Doppler echocardiography. Pulsed Doppler echocardiography of mitral and pulmonary venous flows was obtained along with flow propagation velocity and Ea. LV preA pressure had weak or no relations with mitral, pulmonary venous velocities and atrial volumes. In contrast, preA pressure related strongly to E velocity/flow propagation velocity (r=0.67; SEE=4) and E/Ea (r=0.76; SEE=3.4). In 17 patients with repeat measurements, preA pressure changes were well detected by measuring E velocity/flow propagation velocity (r=0.68; P=0.01) or E/Ea (r=0.8; P<0.001). PreA pressure estimation with these 2 methods was tested prospectively in 17 additional HCM patients with good results (E velocity/flow propagation velocity, r=0.76; E/Ea, r=0.82). CONCLUSIONS: LV filling pressures can be estimated with reasonable accuracy in HCM patients by measuring E velocity/flow propagation velocity or E/Ea. These ratios also track changes in filling pressures.

Changes in left ventricular diastolic function 6 months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy.

BACKGROUND: Nonsurgical septal reduction therapy (NSRT) decreases left ventricular outflow tract (LVOT) gradient and improves symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM). NSRT effects on LV/left ventricular diastolic function are currently unknown. METHODS AND RESULTS: HOCM patients (n=29) had Doppler echocardiography at baseline and 6 months after NSRT to evaluate changes in LV volume, pre-A-wave pressure, early diastolic mitral annulus velocity (Ea) by tissue Doppler, and tau. At 6 months, a significant reduction in LVOT gradient (from 53.6+/-15 to 6+/-5 mm Hg; P<0.001) was accompanied by improvement in exercise duration (from 284+/-147 to 408+/-178 seconds; P=0.04) and New York Health Association class (from III to I; P<0.001). Pre-A pressure (18+/-6 to 14+/-5 mm Hg; P<0.01) and tau (62+/-8 to 51+/-8 ms; P<0.01) decreased, whereas Ea (5.8+/-1.8 to 8+/-1.8 cml/s; P<0.01) and LV end-diastolic volume (117+/-16 to 130+/-22 mL; P<0.01) increased. CONCLUSIONS: NSRT improves LV relaxation and compliance, which contributes to the symptomatic relief seen at 6 months.

Echocardiography-guided ethanol septal reduction for hypertrophic obstructive cardiomyopathy.

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is frequently responsible for symptoms in hypertrophic obstructive cardiomyopathy (HOCM). Medical therapy is often not sufficient to control these symptoms, and surgical myotomy-myomectomy is required. METHODS AND RESULTS: We enrolled 33 symptomatic patients with HOCM and obstruction (>/=40 mm Hg gradient at rest or >/=60 mm Hg dobutamine-provoked). By contrast echocardiography, the bulging septum was localized and infarcted by injection of 2 to 5 mL of absolute ethanol into the septal artery(ies) supplying the hypertrophied area. Baseline echocardiograms with Doppler, myocardial perfusion tomograms, and treadmill exercise or pharmacological testing were compared with those at 6 weeks and 6 months. The mean rise in creatine kinase was 1964+/-796 U. All patients experienced symptomatic relief; NYHA class decreased from 3. 0+/-0.5 to 0.9+/-0.6 (P<0.001). Exercise time increased from 286+/-193 to 421+/-181 seconds (P=0.03). The resting and dobutamine-provoked gradient decreased from 49+/-33 and 96+/-34 mm Hg to 9+/-19 (P<0.001) and 24+/-31 mm Hg (P<0.001), respectively. Echocardiograms repeated at 6 weeks after the procedure showed a 28% reduction in septal thickness and 17% reduction in left ventricular mass. Myocardial perfusion imaging showed a "septal amputation pattern," with scarring in the upper and middle septal areas. Complete heart block developed in 11 patients, who then required permanent pacemaker implantation. CONCLUSIONS: Echocardiography-guided ethanol septal reduction in patients with HOCM is a safe, minimally invasive procedure that provides symptomatic relief with improved hemodynamic and left ventricular parameters.

Role of myocardial contrast echocardiography during nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was undertaken to evaluate the ability of myocardial contrast echocardiography (MCE) to guide the targeted delivery of ethanol during nonsurgical septal reduction therapy (NSRT) and to assess the relation between the MCE risk area and infarct size determined by enzymatic and radionuclide methods. BACKGROUND: NSRT with intracoronary ethanol is a new promising treatment for patients with hypertrophic obstructive cardiomyopathy (HOCM). Proper localization and quantification of the septal infarct before ethanol injection are highly desirable. MCE can provide accurate delineation of the vascular territory of the coronary arteries. METHODS: Twenty-nine patients with HOCM and maximal medical therapy underwent NSRT. The left ventricular outflow tract (LVOT) gradient by Doppler echocardiography at baseline was 53 +/- 16 mm Hg (mean +/- SD). Before NSRT, MCE was performed in all patients with intracoronary sonicated albumin (Albunex). Diluted sonicated albumin (Albunex) was selectively injected into the septal perforator arteries during simultaneous transthoracic imaging. Immediately after MCE, ethanol was injected into the same vessel. Plasma total creatine kinase (CK), total CK-MB fraction and CK-MB fraction subforms were measured at baseline and serially for 36 h. RESULTS: LVOT gradient decreased to 12 +/- 6 mm Hg (p < 0.001) after NSRT. Accurate mapping of the vascular beds of the septal perforators was successfully attained in all patients by MCE. Furthermore, the MCE risk area correlated well with peak CK (r = 0.79, p < 0.001). Six weeks after NSRT, 23 patients underwent myocardial perfusion studies performed with single-photon emission computed tomography (SPECT). Mean SPECT septal perfusion defect size involved 9.5 +/- 6% of the left ventricle and correlated well with MCE area (r = 0.7), with no statistically significant difference between the risk area estimated by MCE and that by SPECT. CONCLUSIONS: Estimation of the size of the septal vascular territory with MCE is accurate, safe and feasible in essentially all patients during NSRT. MCE can delineate the perfusion bed of the septal perforators and can predict the infarct size that follows ethanol injection.

Diagnosis of coronary artery disease by exercise thallium-201 tomography in patients with a right ventricular pacemaker.

OBJECTIVES: We sought to study the accuracy of exercise perfusion scintigraphy in patients with an implanted apical right ventricular pacemaker. BACKGROUND: The specificity of exercise perfusion scintigraphy is decreased in patients with a left bundle branch block. Patients with a permanent ventricular pacemaker have a similar conduction abnormality that may also potentially result in similar false positive perfusion defects. METHODS: One hundred five patients with a right ventricular pacemaker underwent exercise thallium-201 tomography and coronary angiography within 7 days of each other. Patients with a previous myocardial infarction were excluded. RESULTS: Patients were classified into four groups according to the agreement or disagreement between the thallium tomographic and coronary angiographic results. Only 8% of patients with normal results by both techniques were continuously paced during exercise, compared with 78% of patients with normal angiographic results but abnormal scintigraphic results. The mean defect size was 12% in the latter group. Most of the false positive defects were localized to the inferoposterior (71%), apical (50%) and inferoseptal (28%) walls. CONCLUSIONS: Patients who are paced in the right ventricular apex and who continue to be paced throughout exercise have a high incidence of false positive thallium-201 single-photon emission computed tomographic defects.

Leukocyte activation with platelet adhesion after coronary angioplasty: a mechanism for recurrent disease?

OBJECTIVES: The purpose of this pilot study was to determine whether leukocyte activation occurs, whether leukocyte-platelet complexes develop and whether there is any association between these findings and clinical outcome after coronary angioplasty. BACKGROUND: Increased expression of CD11b on monocytes and neutrophils promotes their adhesion to endothelial cells, extracellular matrix and smooth muscle cells. Thrombin-activated platelets adhere to monocytes and neutrophils through P-selectin. These cell complexes may affect the inflammatory process and, thus, the outcome of coronary angioplasty. METHODS: During elective single-vessel coronary angioplasty in 11 men, samples were obtained for flow cytometric detection of CD11b, as well as the percent of leukocytes with adherent platelets and the intensity of bound platelet fluorescence (number of platelets/leukocyte). RESULTS: After angioplasty, there was an increase in CD11b (monocytes: p = 0.001, neutrophils: p = 0.02) and leukocytes with adherent platelets (p = 0.02). During follow-up, five patients remained in stable condition and six had subsequent clinical events: restenosis and progression of disease requiring coronary artery bypass grafting (n = 3), myocardial infarction involving the dilated artery (n = 1) and unstable angina (n = 2). Values for leukocyte CD11b expression, the percent of leukocytes with adherent platelets and the intensity of bound platelet fluorescence were higher both before and after angioplasty in the six patients experiencing clinical events. CONCLUSIONS: Despite standard aspirin and heparin therapy, leukocyte activation with platelet adherence occurs after coronary angioplasty. The magnitude of leukocyte activation and platelet adherence appears to be higher in patients experiencing late clinical events.

Exercise thallium-201 single photon emission computed tomography for evaluation of coronary artery bypass graft patency.

Thallium-201 single photon emission computed tomography (SPECT) is superior to planar imaging for localizing native coronary stenoses, but has not yet been studied for assessing graft patency late after coronary artery bypass graft surgery (CABG). Accordingly, we studied 50 patients (40 males), aged 58 +/- 9 years (mean +/- SD), who presented for evaluation of angina (30 patients), atypical chest pain (20 patients), and other symptoms (9 patients), late after CABG (51 +/- 47 months). Patients with prior myocardial infarction were excluded. The mean ejection fraction was 58 +/- 17%. All patients underwent coronary angiography within 3 weeks of symptom-limited exercise thallium-201 SPECT. There were 119 grafts, of which 48 had > 50% stenosis by angiography. Thallium-201 SPECT detected 40 of these 48 (83%) stenosed grafts. The sensitivity of thallium-201 SPECT for detecting any graft stenosis was higher than that of the exercise electrocardiogram in patients with typical recurrent angina (84% vs 24%, p < 0.0001), as well as in those with atypical symptoms (70% vs 50%, p = 0.0039). The sensitivity of thallium-201 SPECT for correctly localizing the graft stenosis site was 82% for the left anterior descending, 92% for the right coronary, and 75% for the circumflex coronary artery. In conclusion, exercise thallium-201 SPECT is an excellent method to detect and localize graft stenosis late after CABG; it is far superior to the exercise electrocardiogram alone, both in patients with and without typical recurrent angina.

Sodium-dependent retention of prostaglandins in rat ileum.

An intestinal perfusion technique is reported to study the steady-state ileal mucosal retention of labeled prostaglandins E1, E2, and F2 alpha in rats. Ileal homogenates were analyzed for [3H]prostaglandin E1, [14C]prostaglandin E2, and [14C]prostaglandin F2 alpha after intestinal segments were perfused with Krebs improved Ringer buffers containing sodium or depleted from sodium and replaced with choline, and buffers containing 1 mM ouabain, 2 mM amiloride, or 50 nM tetrodotoxin. Prostaglandin ileal mucosal uptake was also studied after iv injection of tetrodotoxin (20 micrograms/kg body weight). Prostaglandin concentration-dependent transport studies support passive uptake mechanisms for prostaglandin E1 and E2. Physiological concentrations of sodium increased labeled prostaglandins E1, E2, and F2 alpha ileal mucosal uptake and decreased n-octanol-buffer partition coefficients. Unlike sodium, potassium showed no effect on labeled prostaglandin ileal transport. Ouabain, amiloride, and tetrodotoxin in the perfusates did not significantly alter prostaglandin mucosal uptake. However, injecting tetrodotoxin into rats caused a drastic increase of prostaglandin uptake through the ileal mucosa. Therefore, the role of sodium on labeled prostaglandin E1, E2, and F2 alpha ileal mucosal transport can be postulated to be controlled by either one or both of the following mechanisms: a pH-partition passive transport mechanism, and/or a sodium channel-dependent pathway whereby prostaglandin permeation possibly proceeds via a sodium-prostaglandin ion-pair mechanism which is controlled by a gating phenomenon.