Citations

BACKGROUND Endothelin is an endothelium-derived peptide that produces sustained contraction of arterial and venous smooth muscle in vitro. Several studies have established endothelin as a systemic, renal, and coronary vasoconstrictor in vivo at pharmacological concentrations. Such concentrations of endothelin were antinatriuretic in association with activation of the renin-angiotensin-aldosterone system. Recent studies have demonstrated that endothelin is present in the plasma and that its plasma concentrations are increased in various pathological states associated with systemic and renal vasoconstriction. To date, it remains unclear if such increases in circulating endothelin are associated with biological activity. Thus, the objective of this study was to determine the biological action of endothelin on cardiorenal and endocrine function through administration of exogenous endothelin, which achieves plasma concentrations that have been reported in various pathophysiological conditions. METHODS AND RESULTS Experiments were conducted in two groups of anesthetized dogs. In group 1, endothelin-1 was infused intravenously at 2.5 ng/kg/ml (n = 6), which produced a doubling of circulating concentrations. Group 2 (n = 8) received saline vehicle to serve as a time control. The current studies demonstrate that a twofold increase in plasma endothelin concentrations did not affect mean blood pressure or coronary blood flow. Heart rate and cardiac output decreased in association with increased renal and systemic vascular resistances and antinatriuresis. CONCLUSIONS The present studies demonstrate that endothelin at pathophysiological plasma concentrations produced by exogenous endothelin has biological action. These studies support a functional role for endogenous endothelin as a potentially pathophysiological vasoconstrictor peptide hormone in the regulation of cardiovascular, renal, and endocrine function.

BACKGROUND Patients who have chest pain without electrocardiographic ST elevation are not candidates for thrombolytic therapy in most clinical trials. This study examined the value of technetium-99m-Sestamibi tomographic imaging to assess myocardial perfusion in patients during chest pain without ST elevation. METHODS AND RESULTS Tc-99m-Sestamibi was injected in 14 patients who had chest pain without ST elevation, who subsequently developed enzymatic evidence of myocardial infarction within 24 hours. Tomographic imaging was performed 1-6 hours after injection. Thirteen of 14 patients showed significant perfusion defects indicative of acute myocardial infarction consistent with absent perfusion (20 +/- 15% of the left ventricle; range, 2-53%); one patient had normal images. Because of the absence of definitive electrocardiographic changes, only five patients received reperfusion therapy within 6 hours of the onset of chest pain. Regional wall motion abnormalities were present in nine of nine patients undergoing contrast ventriculography and correlated with the location of the Tc-99m-Sestamibi perfusion defect. At the time of subsequent coronary angiography, total arterial occlusion was present in 11 of the 14 patients. The infarct-related artery could be identified in 13 of the 14 patients. In six of these 13 patients, the left circumflex was the infarct-related artery. CONCLUSIONS Patients who have chest pain without electrocardiographic ST elevation may have arterial occlusion and significant myocardium at risk. Tc-99m-Sestamibi imaging may be of benefit in identifying these patients early so that they can be considered for acute reperfusion therapy.

BACKGROUND We have previously characterized the left ventricular diastolic filling abnormalities in cardiac amyloidosis by Doppler methods. The various filling patterns were shown to be related to the degree of cardiac amyloid infiltration. The purpose of this study was to determine the value of Doppler diastolic filling variables for assessing prognosis in cardiac amyloidosis. METHODS AND RESULTS We performed pulsed-wave Doppler studies of the left ventricular inflow and obtained clinical follow-up data in 63 consecutive patients with biopsy-proven systemic amyloidosis. All patients had typical echocardiographic features of cardiac involvement. The patients were subdivided into two groups according to deceleration time: Group 1 (33 patients) had a deceleration time of 150 msec or less, indicative of restrictive physiology, and group 2 (30 patients) had a deceleration time of more than 150 msec. Of the 63 patients, 32 (51%) died during a mean follow-up period of 18 +/- 12 months. Of these deaths, 25 (78%) were cardiac deaths, and 19 of the 25 patients (76%) were from group 1. The 1-year probability of survival in group 1 was significantly less than that in group 2 (49% versus 92%, p less than 0.001). Bivariate analysis revealed that the combination of the Doppler variables of shortened deceleration time and increased early diastolic filling velocity to atrial filling velocity ratio were stronger predictors of cardiac death than were the two-dimensional echocardiographic variables of mean left ventricular wall thickness and fractional shortening. CONCLUSIONS Doppler-derived left ventricular diastolic filling variables are important predictors of survival in cardiac amyloidosis.

The use of roentgen videometry as a means of studying regional left ventricular wall dynamics and performance was evaluated in 32 patients undergoing coronary arteriography. Nine patients had normal coronary arteriograms and hemodynamic findings (group 1), 8 patients had generalized decrease in left ventricular contraction and abnormal hemodynamic findings (group 2), and 15 patients with coronary artery disease had regional wall dynamics abnormalities (group 3). Sixty-per-second determinations of wall thickness were performed in selected sites of the left ventricle. Measurements performed included end-diastolic wall thickness (EDTw), mean and peak rates of systolic wall thickening (m and p dTw/dt), and fractional systolic increase in wall thickness (ΔTw/EDTw). In patients with uniformly performing ventricles (groups 1 and 2), these parameters correlated well with other parameters of ventricular function. Best distinction between the "normal" group (group 1) and the "abnormal" group (group 2) was achieved when the rates of thickening (m and p dTw/dt) were utilized ( P < 0.001). In patients of group 3, three types of abnormal regional wall dynamics could be determined and quantified objectively: hypokinesia (decreased p dTw/dt), akinesia (p dTw/dt = 0), and dyskinesia (p dTw/dt < 0). The severity of the abnormality of the wall dynamics correlated well with the presence or absence of a previous infarction on the electrocardiogram, and the anatomic location was strongly correlated with the distribution and severity of coronary artery lesions within a given ventricle.

Two patients with corrected transposition of the great arteries and ventricular rotation are described. The ventricular rotations encountered were about the longitudinal and the anteroposterior axes, respectively. The ventricular rotation affected the plane of the ventricular septum, the inflow and outflow tracts of the ventricles, and the interrelationship of the great arteries. Surgical closure of an associated ventricular septal defect was not without its problems.

Twenty-two patients had ventricular septal rupture complicating acute myocardial infarction. Sixteen of the 22 patients underwent surgical repair. The clinical findings, catheterization data, and operative results suggest that closure of the rupture should be delayed when possible from three to six weeks after the infarction to allow firm fibrous healing of the region. When surgery is thus delayed, the operative risks are smaller and the long-term results are good.

Six years have passed since the first successful surgical correction of truncus arteriosus. A review of our experience enables some conclusions regarding the operation. Patients with mild or moderate truncal valve incompetence do not need truncal valve replacement. Patients with severe truncal valve incompetence require valve replacement, which is associated with a significantly increased surgical mortality. The surgical mortality is not increased in hemodynamically favorable patients who have only one pulmonary artery. However, these patients are especially likely to have early development of severe pulmonary vascular disease. The surgical mortality for the patient with uncomplicated disease and two pulmonary arteries, with pulmonary resistance of less than 8.0 units m 2 , is 10%. In patients with pulmonary resistance between 8.0 and 12 units m 2 , the mortality is approximately three times greater. Patients with pulmonary resistances greater than 12.0 units m 2 are probably inoperable. Different hemodynamic criteria must be applied in assessing the operability of patients with a single pulmonary artery. A systemic arterial oxygen saturation less than 85% in a patient with two pulmonary arteries and without pulmonary artery stenosis or a pulmonary artery band usually indicates inoperability. Elective operation usually is deferred until a patient is four years old, but if the patient's clinical condition warrants, the procedure can be done at any time after the age of one year, with a good chance of success. Follow-up on most operated patients has been encouraging.

From 1957 through 1971, 18 patients whose ages ranged from 10 months to 18 years underwent surgical correction of tetralogy of Fallot with absent pulmonary valve. All patients had associated pulmonary arterial aneurysms; in two the left pulmonary artery also was absent. Right middle lobectomy had been performed previously on one patient for lobar emphysema; seven other patients had recurrent pulmonary infections. The ventricular septal defect was closed with a patch in 12 patients and by direct suture in 6. Concomitant infundibular resection was done in all. In four the narrow pulmonary valve annulus was enlarged with an outflow patch, and multiple radial incisions were made in the valve annulus in seven others. The pulmonary arterial aneurysms were not resected in any patients. There were three hopsital deaths (17%) and two late deaths. Complete heart block developed intraoperatively in three patients, all operated on prior to 1963, contributing to the early death of one patient and to the late deaths of the other two. In a follow-up of all 13 survivors at 8 months to 15 years (median 6 years), results were excellent and equal to those of patients who have undergone repair of tetralogy of Fallot with pulmonary valve.

Fifty patients underwent correction of one or two valvular lesions with concomitant insertion of one to three aortocoronary vein bypass grafts. Hospital mortality was 14% and late mortality was 10%. Factors influencing operative mortality were: (1) mitral valve replacement after myocardial infarction; (2) complete obstruction of a coronary artery preoperatively; (3) high left ventricular end-diastolic pressure at rest preoperatively in patients with mitral valve disease; and (4) use of a single aortocoronary graft in the presence of multiple-vessel disease. For patients with significant associated valvular and coronary artery disease, combined correction yields results that appear sufficiently encouraging, judged by mortality and follow-up, to warrant its continued use in selected cases.