Adjunctive abciximab improves outcomes during recanalization of totally occluded saphenous vein grafts using transluminal extraction atherectomy.

Degenerative disease of aortocoronary saphenous vein grafts is a major cause of late morbidity and mortality in patients after coronary bypass surgery. We previously described a technique for recanalization of totally occluded grafts using extraction atherectomy (TEC) as a primary modality. While success was comparable to overnight urokinase, distal embolization, no-reflow, and non-Q myocardial infarction were common. Recently, abciximab has been used adjunctively in angioplasty and stenting with a reduced incidence of periprocedural complications. In order to determine whether abciximab can reduce the incidence of distal embolization, no-reflow, and myocardial infarction during TEC in totally occluded saphenous vein grafts, we compared patients treated with adjunctive abciximab with control subjects not receiving the drug. Male patients with previous coronary bypass surgery, class III-IV angina, and totally occluded saphenous vein grafts serving a vascular territory with ischemia not approachable by standard catheter-based techniques underwent TEC with or without adjunctive abciximab. Recanalization of the graft was achieved in 8/10 (80%) of subjects without abciximab, but complete success was achieved in only 5/10 (50%). In contrast, all procedures in the abciximab group were completely successful, without embolization or no-reflow. Our results suggest that TEC with adjunctive abciximab may be a highly effective approach for management of totally occluded saphenous vein grafts.

One-year follow-up of recanalization of totally occluded aortocoronary saphenous vein grafts using transluminal extraction atherectomy.

Recanalization of totally occluded aortocoronary saphenous vein grafts with extraction atherectomy was successful in 80% of patients. Whereas all patients with unsuccessful procedures were dead at 1 year, 75% of those with successful procedures are alive and free of events.

Predictors of coronary arterial remodeling patterns in patients with myocardial ischemia.

Preangioplasty intravascular ultrasound in 81 patients showed that adaptive remodeling occurred in 35% and constrictive remodeling in 34%. Multivariate analysis showed that smoking and fibrocalcific plaques were associated with constrictive remodeling, whereas small vessel size and hypercholesterolemia were associated with adaptive remodeling.

Congestive heart failure: increased cardiac and extracardiac atrial natriuretic peptide gene expression.

OBJECTIVES: The present investigation was designed to determine if atrial natriuretic peptide (ANP) gene expression increases in extracardiac as well as within the heart in congestive heart failure. METHODS: Congestive heart failure (CHF) was induced by producing cardiac hypertrophy secondary to an aortocaval fistula in Sprague-Dawley rats. To characterize this model, control and CHF rats had cardiac catheterizations and transthoracic echocardiography. ANP messenger RNA was measured by RNAase protection analysis in atria, ventricles, liver, colon, and stomach of CHF and sham rats and quantitated by 2-D scanning. The product of ANP gene expression was determined in each of these tissues with high performance-gel permeation chromatography. To help determine if increased degradation of atrial natriuretic peptides occur in congestive heart failure, the circulating concentrations and the excretion of the atrial natriuretic peptides into urine were measured by specific radioimmunoassays. RESULTS: ANP steady-state mRNA increased 4.2 +/- 0.05 and 4.3 +/- 0.06-fold, respectively, in the antrum of the stomach and within the heart ventricle of CHF rats compared with age-matched sham rats. ANP gene expression was present but not increased in atria, liver, and gastrointestinal tract of the CHF rats. High-performance gel permeation chromatography revealed that the product of this ANP gene expression within the stomach and heart ventricle in CHF animals was the ANP prohormone. There was not any decrease in the metabolism of these peptides by the kidney in CHF. CONCLUSIONS: ANP steady-state mRNA increases in extracardiac (i.e., stomach antrum) tissue as well as in the ventricle of the heart in CHF. The product of the ANP gene expression, i.e., the ANP prohormone is the same in the extracardiac tissues as within the heart. Whether the increased extracardiac ANP steady-state mRNA and its resultant increased atrial natriuretic peptides helps prevent bowel wall edema in CHF needs to be elucidated.

Extraction atherectomy for the recanalization of totally occluded aortocoronary saphenous vein grafts.

This report describes the successful treatment of totally occluded aortocoronary saphenous vein grafts with percutaneous transluminal extraction atherectomy (TEC) in three patients with severe angina and high reoperative surgical risk. The method presented here may provide an alternative to overnight urokinase infusion or repeat surgery in high risk patients.

Patent ductus arteriosus presenting in old age.

This report describes an unusual case of patent ductus arteriosus, presenting in old age. The patient is the oldest living female with patient ductus reported thus far in the medical literature. She initially presented with chest pressure and dyspnea, and subsequently developed subacute bacterial endocarditis and typical angina pectoris with ECG changes, but with normal coronary anatomy.

Acquired coronary angiogenesis after myocardial infarction.

Acquired coronary artery microvascular fistulas have been reported in only a few patients after myocardial infarction. We describe 1 patient in whom serial coronary angiography demonstrated the development of coronary angiogenesis at the site of an old myocardial infarction. The area of neovascularity was associated with a large apical left ventricular thrombus. This finding suggests that growth-promoting mitogens are present in myocardium and thrombus and that angiogenesis occurs in some patients following myocardial infarction.

Evaluation of coronary flow reserve using myocardial contrast echocardiography in humans.

To evaluate the applicability of myocardial contrast echocardiography for the assessment of coronary blood flow reserve, 21 consecutive patients undergoing coronary angiography were studied. Only patients with a single left anterior descending lesion or normal coronary angiogram were included. Intracoronary injections of sonicated albumin were performed before and after the administration of intracoronary papaverine. Good quality studies at baseline and after the administration of papaverine were obtained in 14 of 21 patients. Ten patients had a significant (greater than 75%) single left anterior descending lesion and four had normal or insignificant lesions (70% or less stenosis) in the left anterior descending coronary artery. Time-intensity curves for the left anterior descending coronary artery region of interest were generated and then the peak contrast intensity (PCI), washout half-time (T1/2) and the area under the curve (AUC) were calculated. The post-papaverine increases in PCI and in the AUC, compared to baseline, were 55 +/- 22% and 102 +/- 14% in the four patients with 70% or less left anterior descending diameter stenosis serving as a control group and 3 +/- 25% and 40 +/- 10%, respectively, in the 10 patients with significant left anterior descending coronary artery disease (mean +/- 1 SD, P less than 0.01). In patients with normal coronary arteriography T1/2 increased after intracoronary injection of papaverine. In patients with severe lesions, either an increase or a decrease in T1/2 was observed. Significant left anterior descending coronary artery stenosis associated with impaired coronary blood flow reserve can be detected by failure of myocardial contrast echocardiographic parameters to increase after injection of papaverine. Mild and transient side effects were noted in three patients.

Both cell surface and internalized beta-adrenoceptors are reduced in the failing myocardium.

To study myocardial beta-adrenoceptor internalization in heart failure, we measured beta-adrenoceptor density in the particulate, light vesicle and supernatant fractions of ventricular tissue of dogs with experimental right ventricular failure and sham-operated dogs. Tissue was fractionated by centrifugation, and beta-adrenoceptors were measured by [125I]iodocyanopindolol binding. Compared to sham-operated controls, beta-adrenoceptors were reduced in all fractions of right ventricular tissue from heart failure animals. Thus, the decreased surface (particulate fraction) receptors observed cannot be explained by internalization alone, and must be associated with altered receptor synthesis or degradation.

Chronic beta-adrenoceptor blockade prevents the development of beta-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs.

BACKGROUND: The reductions of myocardial beta-adrenergic receptor density and responsiveness to catecholamines in congestive heart failure are associated with excessive sympathetic stimulation. The purpose of this study was to determine whether the myocardial changes could be prevented by beta-receptor blockade. METHODS AND RESULTS: We administered the oral beta-receptor blocking agent nadolol (40 mg/day) to dogs during an early stage of experimental right heart failure and to sham-operated dogs for 5 weeks. Animals receiving no nadolol were studied concurrently. Nadolol treatment did not prevent right ventricular hypertrophy or elevated concentrations of plasma norepinephrine that occurred in right heart failure, nor did it affect the decrease in myocardial norepinephrine content and norepinephrine uptake activity, suggesting that the hemodynamic stress imposed on the right ventricle of dogs with right heart failure was similar regardless of the presence or absence of beta-receptor blockade. Resting heart rate, right atrial pressure, aortic pressure, cardiac output, right ventricular dP/dt, and left ventricular dP/dt and dP/dt/P measured 5 days after discontinuation of nadolol did not differ significantly from those without nadolol treatment in either right heart failure or sham-operated animals. Sham-operated dogs also showed no changes in myocardial beta-receptor or adenylate cyclase activity after nadolol treatment. However, nadolol treatment prevented the reduction of myocardial beta-receptor density and attenuated the decrease in the cardiac beta-adrenergic sensitivity that occurred in right heart failure. CONCLUSIONS: Excessive sympathetic stimulation may play an important role in the development of beta-receptor downregulation and beta-adrenergic subsensitivity in right heart failure.

Acute hemodynamic effects of pinacidil in hypertensive patients with and without propranolol pretreatment.

To study the systemic and regional hemodynamic effects of the new antihypertensive agent pinacidil, the authors administered intravenously two doses of pinacidil (0.1 mg/kg) to patients with hypertension after 3 days of randomized, double-blind pretreatment with either propranolol or placebo. Pinacidil administration decreased systemic arterial pressure and total peripheral vascular resistance in both groups of patients. It also decreased pulmonary artery wedge pressure, and increased cardiac output, heart rate, and plasma norepinephrine levels; the changes in cardiac output and heart rate were attenuated by propranolol pretreatment. In addition, propranolol-pretreated patients responded to pinacidil with a decrease in forearm blood flow. In contrast, pinacidil administration exerted no significant effects on right atrial pressure, stroke volume, or mean pulmonary arterial pressure alone or in combination with propranolol. The results show that pinacidil is a potent arterial dilator but has little effect on the venomotor tone in patients with hypertension.

Comparison of phenylephrine bolus and infusion methods in baroreflex measurements.

Phenylephrine (PE) bolus and infusion methods have both been used to measure baroreflex sensitivity in humans. To determine whether the two methods produce the same values of baroreceptor sensitivity, we administered intravenous PE by both bolus injection and graded infusion methods to 17 normal subjects. Baroreflex sensitivity was determined from the slope of the linear relationship between the cardiac cycle length (R-R interval) and systolic arterial pressure. Both methods produced similar peak increases in arterial pressure and reproducible results of baroreflex sensitivity in the same subjects, but baroreflex slopes measured by the infusion method (9.9 +/- 0.7 ms/mmHg) were significantly lower than those measured by the bolus method (22.5 +/- 1.8 ms/mmHg, P less than 0.0001). Pretreatment with atropine abolished the heart rate response to PE given by both methods, whereas plasma catecholamines were affected by neither method of PE administration. Naloxone pretreatment exaggerated the pressor response to PE and increased plasma beta-endorphin response to PE infusion but had no effect on baroreflex sensitivity. Thus our results indicate that 1) activation of the baroreflex by the PE bolus and infusion methods, although reproducible, is not equivalent, 2) baroreflex-induced heart rate response to a gradual increase in pressure is less than that seen with a rapid rise, 3) in both methods, heart rate response is mediated by the vagus nerves, and 4) neither the sympathetic nervous system nor the endogenous opiate system has a significant role in mediating the baroreflex control of heart rate to a hypertensive stimulus in normal subjects.

Decreased adrenergic neuronal uptake activity in experimental right heart failure. A chamber-specific contributor to beta-adrenoceptor downregulation.

The reduction of myocardial beta-adrenoceptor density in congestive heart failure has been thought to be caused by agonist-induced homologous desensitization. However, recent evidence suggests that excessive adrenergic stimulation may not produce myocardial beta-receptor downregulation unless there is an additional defect in the local norepinephrine (NE) uptake mechanism. To investigate the association between beta-adrenoceptor regulation and NE uptake activity, we carried out studies in 30 dogs with right heart failure (RHF) produced by tricuspid avulsion and progressive pulmonary artery constriction and 23 sham-operated control dogs. We determined NE uptake activity by measuring accumulation of [3H]NE in tissue slices, NE uptake-1 carrier density by [3H]mazindol binding and beta-adrenoceptor density by [3H]dihydroalprenolol binding. Compared with sham-operated dogs, RHF dogs showed a 26% decrease in beta-adrenoceptor density, a 51% reduction in NE uptake activity, and a 57% decrease in NE uptake-1 carrier density in their right ventricles. In addition, right ventricle beta-receptor density correlated significantly with NE uptake activity and NE uptake-1 carrier density. In contrast, neither NE uptake activity nor beta-receptor density in the left ventricle and renal cortex was affected by RHF. Thus, the failing myocardium is associated with an organ- and chamber-specific subnormal neuronal NE uptake. This chamber-specific loss of NE uptake-1 carrier could effectively reduce local NE clearance, and represent a local factor that predisposes the failing ventricle to beta-adrenoceptor downregulation.