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Biomedical subjects

A S Jaffe

Publications and source records attributed to A S Jaffe.

At least 73 records · Page 4Linked to original sources
PubMed1992

Use of intravenous diltiazem in patients with acute coronary artery disease.

The use of calcium antagonists for the treatment of patients with unstable angina and acute myocardial infarction has been a promising area of both basic and clinical research. Despite consistently beneficial effects experimentally, the clinical extrapolation of these results has been less than ideal, especially in patients with evolving myocardial infarction. Calcium antagonists have in some instances failed to manifest benefit and at times have been shown to have negative effects. One reason for this could be the use of oral or sublingual preparations, which result in variable absorption, variable volumes of distribution, and variable clearance. For this reason, an intravenous preparation of one of the calcium antagonists, diltiazem, may be more beneficial. Such a preparation has been developed and its safety confirmed in patients without cardiovascular disease and in patients with acute infarction. Substantial benefit has been documented in patients with stable angina and during noncardiac surgery. Preliminary data in patients with unstable angina suggest that the drug is effective, although studies comparing intravenous diltiazem with other agents or with the oral preparation of diltiazem have not yet been reported. Experimental data in animals with acute infarction have demonstrated that administration of intravenous diltiazem after occlusion, but prior to reperfusion, elicits a marked increase in the degree of myocardial salvage induced by thrombolysis. This appears to be due to the inhibition of lipid peroxidation rather than alterations in coronary perfusion. Thus, it appears that the intravenous preparation may permit the more effective use of diltiazem in patients with acute coronary artery disease.

Angina, Unstable↗
PubMed1992

Importance of left ventricular function and systolic ventricular interaction to right ventricular performance during acute right heart ischemia.

To determine whether modulation of systolic ventricular interaction influences right ventricular performance during right heart ischemia, the effects of septal ischemia and inotropic stimulation were studied in 15 dogs in an open chest preparation. Right coronary branch occlusions led to right ventricular dilation and free wall dyskinesia, reversed septal curvature and reduced left ventricular diastolic volume. In systole, the septum thickened but bulged paradoxically into the right ventricle generating an active but depressed right ventricular systolic pressure (28.9 +/- 5.5 to 22.1 +/- 4.5 mm Hg), with associated decreases in right ventricular stroke work (5.66 +/- 0.94 to 1.92 +/- 0.53 g.m/m2) and left ventricular systolic pressure (123 +/- 11 to 80 +/- 10 mm Hg). Septal ischemia induced systolic septal thinning, left ventricular dilation and decreased left ventricular systolic pressure (80 +/- 10 to 55 +/- 10 mm Hg) and stroke work. Although the extent of paradoxic septal displacement increased, there were further decrements in right ventricular systolic pressure (22.1 +/- 4.5 to 18.7 +/- 4.3 mm Hg) and stroke work (1.92 +/- 0.53 to 0.7 +/- 0.2 g.m/m2). Dopamine infusion augmented left ventricular free wall contraction and increased left ventricular systolic pressure (55 +/- 10 to 172 +/- 17 mm Hg) and stroke work. Although systolic septal thinning persisted, the extent of paradoxic septal displacement increased strikingly and, despite continued right ventricular free wall dyskinesia, right ventricular systolic pressure increased (18.7 +/- 4.3 to 39.6 +/- 6.2 mm Hg) as did right ventricular stroke work (0.7 +/- 0.2 to 7 +/- 1.6 g.m/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Psychosocial adjustment of patients arriving early at the emergency department after acute myocardial infarction.

The psychosocial functioning of patients arriving at the emergency department with an acute myocardial infarction early enough to be candidates for treatment with thrombolytic agents was compared with that of those arriving later. Patients who arrived within 3 hours were significantly more anxious when assessed 1 week after admission and had a consistently worse pattern of psychosocial adjustment 3 months after hospital discharge than did those who arrived later. The implications of these findings for efforts to improve early arrival at the emergency department, as well as for medical and psychosocial outcomes after acute myocardial infarction, were considered.

Adult↗
PubMed1992

Nature and time course of generation of isoforms of creatine kinase, MB fraction in vivo.

OBJECTIVES: This study was designed to characterize the nature and time course of carboxy-terminal lysine cleavages from the tissue isoform of MB creatine kinase (CK) in vivo. BACKGROUND: Rapid conversion of the tissue isoform of MM CK to two additional circulating isoforms with one or both carboxy-terminal lysines cleaved facilitates early detection of new tissue isoform release after acute myocardial infarction and coronary recanalization. Characterization of changes in plasma MB CK isoform profiles, potentially enhancing specificity even further, has been hindered by difficulties in separating the isoform products and elucidation of carboxy-terminal lysine cleavages underlying their formation. METHODS: Isoform species with carboxy-terminal lysine present on B-monomers were separated from those from which lysine had been cleaved by anion exchange chromatography. Carboxy-terminal lysine on M-monomers was assayed with the use of a monospecific antibody. RESULTS: MB CK in four pooled plasma samples from among 77 normal subjects exhibited carboxy-terminal lysine on 48 +/- 21% (mean +/- SEM) of B-monomers and 82 +/- 12% of M-monomers. Within the 1st 16 h after the onset of acute myocardial infarction, virtually all M- and B-monomers exhibited carboxy-terminal lysine, indicating release into plasma and the lack of rapid cleavage of lysine from the tissue isoform. After 20 to 30 h, 43 +/- 9% (three pools from 19 patients) of B-monomers and 95 +/- 10% of M-monomers exhibited lysine at the carboxyl terminus. After 40 to 50 h, 13 +/- 13% (four pools from 34 patients) of B-monomers and 46 +/- 19% of M-monomers still retained carboxy-terminal lysine. CONCLUSIONS: In contrast to MM CK, the tissue isoform of MB CK undergoes slow cleavage of lysine from both monomers in vivo. Sequential cleavage of lysine first from the carboxyl terminus of B-monomers and subsequently from M-monomers is consistent with generation of at least two additional isoforms. Development of assays capable of resolving all of the isoforms of MB CK that can occur in vivo might increase sensitivity for early detection of new tissue isoform release associated with acute myocardial infarction and coronary recanalization compared with currently available assays that resolve only two species.

Chromatography, Ion Exchange↗
PubMed1992

Activation of prothrombin accompanying thrombolysis with recombinant tissue-type plasminogen activator.

Increases in thrombin activity in patients given fibrinolytic agents for acute myocardial infarction have been shown to be important in limiting the ultimate success of coronary thrombolysis. The present study was designed to determine whether increases in thrombin activity reflect, in part, activation of prothrombin accompanying thrombolysis. Plasma concentrations of prothrombin fragment 1.2, a polypeptide released when prothrombin is activated by factor Xa, were measured in 22 patients with acute myocardial infarction before and after treatment with 100 mg of recombinant tissue-type plasminogen activator (rt-PA). Concentrations of prothrombin fragment 1.2 increased from 0.83 +/- 1.1 nM (mean +/- SD) before rt-PA infusion to 1.5 +/- 1.5 nM 2 h after initiation of the infusion (p less than 0.05). After a 5,000-U intravenous dose of heparin given at the end of the infusion of rt-PA, concentrations of prothrombin fragment 1.2 decreased from 1.8 +/- 1.5 to 1.1 +/- 0.9 nM (n = 20, p less than 0.05), although values were still increased compared with concentrations before rt-PA. These results indicate that thrombin activity increases in patients given rt-PA at least in part because of activation of the coagulation system leading to activation of prothrombin. Thus, inhibition of the reactions involving coagulant proteins that lead to activation of prothrombin may be of value as conjunctive treatment to potentiate the efficacy of pharmacologic thrombolysis.

Blood Coagulation↗
PubMed1992

Elevations of CK-MB following pulmonary embolism. A manifestation of occult right ventricular infarction.

To determine the frequency and etiology of elevations of CK-MB in patients with pulmonary emboli, we studied 52 patients with well-documented emboli and the absence of known ischemic heart disease or ECG changes suggestive of acute infarction. All patients were evaluated with serial CK-MB determinations at 8-h intervals. All patients with elevations of CK-MB had noninvasive cardiac evaluations. Four (7.7 percent) of the 52 patients had a rising and falling pattern of CK-MB that satisfied enzyme criteria of acute infarction. Three of these four also manifested classic echocardiographic features of right ventricular infarction. None of the four had evidence of left ventricular regional wall motion abnormalities or dysfunction. Of the 48 patients without elevations of CK-MB, only two had segmental right ventricular dysfunction. These findings suggest that pulmonary emboli can induce right ventricular infarction in some (7.7 percent) patients even when patients with a history of coronary artery disease and/or ECG changes of infarction are excluded. Conversely, the diagnosis of pulmonary embolism should be considered in patients when right ventricular infarction is diagnosed.

Adult↗
PubMed1991

Right atrial ischemia exacerbates hemodynamic compromise associated with experimental right ventricular dysfunction.

To determine the importance of right atrial function with acute right ventricular dysfunction, sequential right ventricular and right atrial ischemia were induced in 15 dogs. Right ventricular ischemia resulted in right ventricular free wall dyskinesia, right ventricular dilation by ultrasound, elevated right ventricular filling pressure and paradoxic septal motion. There were decrements in right ventricular systolic pressure (28.9 +/- 5.5 to 25.5 +/- 4.6 mm Hg) (p less than 0.05 for these and all subsequent values) and stroke work (5.66 +/- 0.94 to 2.66 +/- 0.62 g.m/m2), resulting in reductions in left ventricular preload, systolic pressure (123 +/- 11 to 97 +/- 12 mm Hg) and stroke volume (24.2 +/- 4.3 to 19.1 +/- 5.2 ml). Right atrial contractility was augmented, as indicated by increases in peak A wave amplitude (ratio of peak A wave to mean right atrial pressure 1.22 +/- 0.02 to 1.46 +/- 0.3) and right atrial stroke work (0.11 +/- 0.02 to 0.25 +/- 0.05 g.m/m2). Right atrial ischemia depressed right atrial contraction, as indicated by decreased A wave amplitude (ratio of peak A wave to mean right atrial pressure 1.46 +/- 0.3 to 1.04 +/- 0.2) and stroke work (0.25 +/- 0.05 to 0.04 +/- 0.01 g.m/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Relation between ST segment shifts during ischemia and thrombin activity in patients with unstable angina.

This study was designed to determine in patients with unstable angina whether specific electrocardiographic abnormalities associated with ischemia, the presence of coronary lesions consistent with thrombosis on angiography or the presence of recurrent ischemia reflects increases in thrombin activity as manifested by increased plasma concentrations of fibrinopeptide A. The concentration of fibrinopeptide A in plasma was increased to 6.7 +/- 3.1 nM for the group as a whole (n = 29). Increases were greater in the 17 patients who exhibited reversible ST segment shifts (10.2 +/- 5.2 nM) than in the 12 patients exhibiting reversible T wave abnormalities alone (1.6 +/- 0.2 nM) (p less than 0.01). Nine of the 17 patients with reversible ST segment shifts who underwent coronary angiography had lesions with morphologic characteristics consistent with atherosclerotic plaque complicated by thrombosis compared with only 2 of 9 patients with T wave changes only (p less than 0.05). Plasma concentrations of fibrinopeptide A were markedly elevated in 7 of the 11 patients in whom complex lesions were noted on angiographic examination. Thus, the occurrence of reversible ST segment shifts identifies a group of patients with unstable angina in whom ongoing thrombosis is likely and who may be particularly likely to benefit from antithrombotic therapy.

Angina, Unstable↗
PubMed1990

Dependence of plasmin-mediated degradation of platelet adhesive receptors on temperature and Ca2+.

The effects of activation of plasminogen by streptokinase and tissue-type-plasminogen activator on platelet activation and the membrane glycoproteins (GPs) that mediate platelet adhesion and aggregation are not yet fully defined. To clarify effects on platelets during activation of plasminogen in vitro, we used monoclonal antibodies (MoAbs), flow cytometry, and platelets surface-labeled with 125I to characterize changes in receptors for fibrinogen (GPIIb-IIIa), von Willebrand factor (GPIb), and collagen (GPIa-IIa). Activation of plasminogen in plasma with pharmacologic concentrations of plasminogen activators did not degrade GPIIb-IIIa or GPIb, and caused only a modest decrease in GPIa. In washed platelets GPIIb-IIIa was extensively degraded by plasmin at 37 degrees C in the absence of exogenous Ca2+, conditions that destabilize the IIb-IIIa complex. Degradation of GPIb in washed platelets displayed a similar although less-marked dependence on temperature and the absence of Ca2+. The binding of activation-specific MoAbs did not increase during activation of plasminogen in plasma. We conclude that during pharmacologic fibrinolysis, reported inhibition of platelet function in plasma is not due to degradation of platelet-adhesive receptors. In addition, platelet activation observed during thrombolytic therapy does not appear to be a direct consequence of plasminogen activation.

Antibodies, Monoclonal↗
PubMed1990

Prognostic significance of mitral regurgitation in acute myocardial infarction. The MILIS Study Group.

To define the frequency, natural history and clinical correlates of the murmur of mitral regurgitation (MR) detected after myocardial infarction, clinical data from 849 patients with documented acute myocardial infarction were analyzed. A murmur suggestive of MR was present on admission in 76 patients (9%). Patients with MR on admission were older and more apt to be female and nonwhite. They also had a significantly greater frequency of prior infarction and signs and symptoms of congestive heart failure. There was no difference in the location (anterior or inferior) of infarction. Patients with MR on admission had a 36% mortality compared to 16% for those who developed MR later in the hospitalization and 15% for those without MR by auscultation (p less than 0.001). Correction for differences in baseline variables indicated that the presence of MR on admission did not contribute independently to mortality. Thus, the murmur of MR derives its prognostic significance from integration of multiple clinical, radiographic and electrocardiographic characteristics.

Female↗
PubMed1990

Normal left ventricular performance in children with X-linked hypophosphatemic rickets: a Doppler echocardiography study.

To determine if chronic hypophosphatemia causes myocardial dysfunction, we explored one model for this metabolic derangement by prospectively investigating 11 patients (aged 5-18 years) with X-linked hypophosphatemic rickets (XLH) by M-mode, two-dimensional, and Doppler echocardiography. Inorganic phosphate and calcitriol (1,25-dihydroxyvitamin D3) treatment was withheld 72 h prior to study. None of the patients had cardiovascular symptoms. Fasting serum inorganic phosphate concentrations were subnormal in all: 2.6 +/- 0.5 mg/dl (SD). Serum total and ionized calcium, magnesium, sodium, potassium, and creatine kinase myocardial fraction (CK-MB) levels were unremarkable. Electrocardiograms revealed early repolarization abnormalities in 3 of the 11 patients: 1 had significant QT prolongation (corrected for heart rate), and 2 had T wave abnormalities. Exaggerated U waves occurred in 4 subjects. Resting echocardiograms were normal in 9 patients. In 1 subject there was mitral valve prolapse, and 1 patient possibly had an atrial septal defect (these findings were considered unrelated to hypophosphatemia). All M-mode measurements were normal. The two-dimensionally derived end-diastolic and end-systolic left ventricular volumes were 60.3 +/- 18.0 and 20.5 +/- 6.9 ml, respectively. Left ventricular ejection fraction was 66.1 +/- 4.7%, and the cardiac index by Doppler study was 4.1 +/- 0.8 liters/min per m2 (both values were within normal limits). Although the precise pathogenesis of XLH is unknown and our findings suggest that some electrocardiographic abnormalities may be common in this disorder, we found no evidence for left ventricular dysfunction in this human model of clinically significant long-standing hypophosphatemia.

Adolescent↗
PubMed1990

Major depression, panic disorder, and mitral valve prolapse in patients who complain of chest pain.

PURPOSE: Patients with chest pain but without angiographic evidence of significant atherosclerotic coronary artery disease (CAD) are often found to have other medical or psychiatric disorders, including mitral valve prolapse, panic disorder (PD), and major depressive disorder (MDD). The purpose of this study was to determine the degree of comorbidity between MDD/PD and mitral valve prolapse in a group of patients with non-CAD chest pain. PATIENTS AND METHODS: Patients referred for cardiac catheterization and coronary angiography for suspected CAD who were 70 years of age or younger and without other significant medical illnesses or cardiac complications were eligible for study. The first 100 patients who agreed to a psychiatric diagnostic interview were recruited. RESULTS: Forty-eight of the 100 patients were found to be without significant CAD. Forty-two percent of these patients, compared to 19% of the patients with significant CAD, were found to have either MDD, PD, or both. Eighty percent of the patients without CAD who had mitral valve prolapse also had either MDD or PD (p less than 0.006). CONCLUSIONS: The finding that mitral valve prolapse was significantly associated with MDD/PD has implications for the diagnosis and treatment of patients with non-CAD chest pain, and may explain why these patients complain of symptoms.

Cardiac Catheterization↗
PubMed1990

Determinants of hemodynamic compromise with severe right ventricular infarction.

To elucidate determinants of hemodynamic compromise in patients with acute right ventricular (RV) infarction, we studied 16 patients with hemodynamically severe RV infarction by right heart catheterization and two-dimensional ultrasound. Severe RV systolic dysfunction, evident by ultrasound in all patients as RV dilatation and depressed RV free wall motion, was associated with a broad sluggish RV waveform, diminished peak RV systolic pressure (27.6 +/- 4.5 mm Hg), and depressed RV stroke work (4.6 +/- 2.4 g.m/m2). Paradoxical septal motion was consistently noted. In some cases, the septum bulged into the right ventricle in a pistonlike fashion and appeared to mediate systolic ventricular interaction through which left ventricular septal contraction contributed to RV pressure generation. RV diastolic dysfunction was indicated by elevated RV end-diastolic pressures (13.7 +/- 2.7 mm Hg), RV "dip and plateau," equalization of diastolic filling pressures, and reversal of diastolic septal curvature toward the volume-deprived left ventricle. A prominent right atrial (RA) X and blunted Y descent, indicative of impairment of RV filling throughout diastole, were confirmed in all patients by their relation to RV systolic events. Patients manifested one of two distinct RA waveform morphologies differentiated by A wave amplitude and associated with disparate clinical courses. In eight patients, an RA W pattern was evident, characterized by augmented A waves; eight others manifested an M pattern constituted by depressed A waves. Compared with those with an M pattern, patients with a W pattern had higher peak RV pressures (29.6 +/- 3.8 versus 25.5 +/- 4.3 mm Hg, p less than 0.05), better cardiac output (3.4 +/- 0.3 versus 2.9 +/- 0.7 l/min, p less than 0.05), more favorable response to volume and inotropes, and less frequently required emergency revascularization for refractory shock (none versus five for those with an M pattern). Patients with a W pattern were more severely compromised if atrioventricular dyssynchrony developed and were more dramatically improved by restoration of physiological rhythm. Angiography in patients with depressed A waves demonstrated more proximal coronary obstruction leading to ischemic compromise of RA function, whereas in those with augmented A waves, the culprit lesion was proximal to the RV but distal to the RA branches. These results indicate that hemodynamic compromise in patients with RV infarction is exacerbated by decreased preload reserve that is dependent on atrial systole. The amplitude of the RA A wave, an indication of the status of RA function, is an important determinant of RV performance and hemodynamic compromise.

Blood Pressure↗
PubMed1990

Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension.

Although the mechanisms involved in the pathophysiology of primary pulmonary hypertension have not yet been delineated, thrombosis has been implicated. This study was designed to determine whether thrombin activity as reflected by plasma concentrations of fibrinopeptide A (FPA), a marker of the action of thrombin on fibrinogen, is increased in patients with primary pulmonary hypertension. To evaluate fibrinolytic activity, we measured plasma concentrations of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and cross-linked fibrin degradation products. We studied 31 patients with primary pulmonary hypertension. Plasma FPA concentrations measured by radioimmunoassay, were elevated to 87.4 +/- 36.9 ng/ml (mean +/- SEM). Fifteen minutes after administration of heparin (5,000 U), FPA concentrations decreased to 6.8 +/- 1.4 ng/ml (p less than 0.001 compared with preheparin levels). In 21 of 30 patients (70%), FPA concentrations after heparin administration were less than half the preheparin levels, a response consistent with inhibition of thrombin by heparin and the short half-life of FPA. Despite evidence for marked thrombin activity, plasma concentrations of cross-linked fibrin degradation products were normal in all but four patients. Plasminogen activator inhibitor-1 activity was elevated in 19 of the 27 patients in whom it was measured, potentially limiting the fibrinolytic response. The elevations of FPA indicate that thrombin activity is increased in vivo in patients with primary pulmonary hypertension. Thus, sequential assays of plasma markers of thrombosis and fibrinolysis in vivo may help identify those patients who may benefit from treatment with anticoagulants.

Fibrin Fibrinogen Degradation Products↗
PubMed1990

Validity of enzyme-linked immunosorbent assays of cross-linked fibrin degradation products as a measure of clot lysis.

Concentrations of cross-linked fibrin degradation products (XL-FDPs) in plasma, measured by enzyme-linked immunosorbent assays (ELISAs) based on monoclonal antibodies (MAbs) raised against fragment D-dimer of cross-linked fibrin, increase when patients are given fibrinolytic agents. Whether XL-FDPs derive from circulating cross-linked fibrin polymers in plasma, compared with clot-associated fibrin, has been questioned because increases in XL-FDP are measured by some assays after fibrinolysis in vitro in the absence of clot. We characterized the source of XL-FDP immunoreactivity in plasma of patients with acute myocardial infarction and ischemic heart disease and the response to plasminogen activation in vitro induced by pharmacological concentrations of tissue-type plasminogen activator (t-PA) and streptokinase. XL-FDPs were measured with two different ELISA. One, "pan-specific tag ELISA," was based on a capture MAb specific for XL-FDP and a tag MAb that recognizes an epitope exposed in the fragment D region of both fibrin and fibrinogen, whereas the other, "fibrin-specific tag ELISA," was based on a capture and tag MAbs both specific for fibrin. After plasminogen activation was induced in vitro in plasma from patients with myocardial infarction, increased concentrations of XL-FDP were measured by the pan-specific tag ELISA; however, concentrations measured with the fibrin-specific tag ELISA were not increased. To determine the mechanism for this discrepancy, plasma was subjected to immunoadsorption with a MAb specific for fragment D-dimer before and after in vitro activation of the fibrinolytic system and immunoblotting with a fragment D-dimer-specific MAb and with the pan-specific MAb. Increased concentrations of fragment D-dimer, as well as fibrinogen fragment D at high concentrations, were recognized by the specific MAb. Non-cross-linked fragments were also shown by immunoblotting with the pan-specific MAb to coprecipitate with cross-linked fibrin fragments. This suggested the increased concentrations of XL-FDP measured by the pan-specific tag ELISA after in vitro activation of the fibrinolytic system were due to detection of non-cross-linked fibrinogen fragments. However, fibrin fragment D-dimer concentrations were found to increase in plasma of 15 patients given t-PA for acute myocardial infarction. We conclude fragment D-dimer in plasma of patients during thrombolysis does not originate from circulating soluble cross-linked fibrin but rather is a marker of solid-phase fibrin dissolution, which may be quantitated with assays based on capture and tag antibodies that do not detect fibrinogen or its degradation products.

Antibodies, Monoclonal↗