Biomedical subjects
Publications and source records attributed to A S Jaffe.
The recognition that thrombolytic therapy may be beneficial for coronary thrombolysis has led to an increased use of plasminogen activators in critically ill patients, sometimes with inadequate monitoring. This review delineates the components of the fibrinolytic system, describes mechanisms of fibrinolysis, and presents practical guidelines for monitoring the use of activators of the system.
Platelet factor IV and beta-thromboglobulin are protein constituents of platelet granules. Elevated levels of these proteins in plasma have been used as sensitive indicators of platelet degranulation. Clearance of platelet factor IV is much faster than that of beta-thromboglobulin after release of the proteins in vivo. Although increases of platelet factor IV have been observed in patients with infarction, the implication that they reflect pathogenetic phenomena such as coronary thrombosis has not been assessed explicitly. Accordingly, plasma samples obtained serially from 52 patients with acute myocardial infarction under rigorous conditions verified to minimize platelet degranulation in vitro were evaluated prospectively. Correlative studies were performed to detect left ventricular mural thrombus, and coronary thrombosis was assessed independently in selected patients with indium-111 platelet scintigraphy. Platelet factor IV was normal at the time of admission in patients with infarction, averaging 6.3 +/- 3.3 ng/ml, similar to values in 44 other patients with chest pain without subsequent infarction (5.7 +/- 2.7 ng/ml) and in 25 normal subjects (4.3 +/- 1.6 ng/ml). Platelet factor IV generally did not increase during hospitalization in patients with infarction despite recurrent chest pain, development of left ventricular thrombus or documented recurrent infarction. However, platelet factor IV increased consistently after invasive procedures, accounting for 104 of the total of 110 increases due to platelet activation in vivo as reflected by persistence of elevated levels of beta-thromboglobulin. Thus, platelet factor IV values generally remain normal despite acute myocardial infarction. Rare increases that occur reflect platelet degranulation in vitro due to sampling artifact or perturbations of platelets in vivo due to invasive procedures.(ABSTRACT TRUNCATED AT 250 WORDS)
Although pulmonary artery (PA) catheterization is frequently employed in the management of critically ill patients, there is little documentation that the information obtained alters patient management. This study evaluated prospectively this question in 103 PA catheterizations. Before catheterization, physicians were asked to predict the range of several hemodynamic variables, the presumed diagnosis, and their plan for therapy. After catheterization, each chart was reviewed. The hemodynamics at the time of catheterization and therapy within 8 h of catheterization were noted. Pulmonary artery occlusive (wedge) pressure (WP) was correctly predicted 30% of the time. Cardiac output, systemic vascular resistance (SVR), and right atrial pressure (RAP) were correctly predicted approximately 50% of the time. There was no significant difference in the ability to predict hemodynamics of subgroups with either hypotension or impaired oxygenation. After catheterization, planned therapy was altered in 58% of the cases. Unanticipated therapy was added in 30% of the cases. This study documents the difficulty of predicting accurately hemodynamics based solely on clinical evaluation. Thus, the information obtained by catheterization often leads to alterations in the therapeutic plan. We suggest that PA catheterization is both indicated and useful in the management of critically ill patients.
To assess the effects on the heart itself of coronary thrombolysis induced with either tissue-type plasminogen activator (t-PA) or streptokinase (SK), we performed positron emission tomography with 11C-palmitate in 19 patients with initial transmural myocardial infarction immediately after admission and again within 48 to 72 hr after intracoronary administration of t-PA (n = 2) or SK (n = 17). Clots were persistent in eight patients treated with SK despite an average dose of 336,000 IU, sufficient to markedly deplete fibrinogen. In the absence of lysis, favorable tomographic changes did not occur. In contrast, in each of the 11 patients in whom lysis was induced (two with t-PA and nine with SK) myocardial accumulation of 11C-palmitate improved by an average of 29% in late compared with early studies (p less than .001). Results were comparable in patients with anterior and those with inferior infarction. Thus clot lysis induced with either t-PA or SK led to improved regional myocardial metabolism.
Enzymatic estimates of myocardial infarct size based on plasma levels of MB creatine kinase (MB-CK) were compared with anatomic infarct size in 49 human hearts obtained at autopsy. The patients studied had been enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS) study program within 18 hr of the onset of acute infarction and were treated at one of five participating hospitals. Infarct size was estimated from serial measurements of plasma MB-CK made at the core laboratory for CK analysis. Hearts obtained at autopsy were studied independently by the core pathology laboratory without knowledge of the MB-CK levels or clinical results. Data from the two laboratories were compared at the data coordinating center. Of 49 hearts, 12 were excluded either because anatomic infarct size could not be established or because the infarct occurring at the time of enrollment in the MILIS study could not be distinguished with certainty from other infarcts. Of the remaining 37 hearts, peak MB-CK level was available in 36, but samples sufficient for estimation of infarct size were available in only 25. The overall correlation coefficient (Spearman) was .87 for these 25 hearts, indicating that enzymatic estimates of infarct size correlate closely with anatomic measurements. The results indicate that CK estimates of myocardial infarct size represent a valid clinical end point for assessing myocardial infarct size, and the effect of therapy thereon, in groups of treated and control patients.
The incidence, clinical presentation, and treatment of complications of acute myocardial infarction are presented. Complications discussed include left ventricular failure, cardiogenic shock, cardiorrhexis, conduction defects, and pericarditis.
Previous reports have suggested that creatine kinase isoenzymes are elevated in patients with chronic renal failure and thus are less useful in the evaluation of chest pain in such patients. Our data in 88 patients with chronic renal failure receiving maintenance dialysis confirm this observation for total plasma creatine kinase. However, elevations in MB and BB creatine kinase, although statistically significant, were biologically unimpressive (5.9 +/- 0.05 [SEM] IU/L compared with 4.8 +/- 0.04 IU/L for MB creatine kinase [p less than 0.02], and 5.5 +/- 0.08 ng/ml compared with 3.2 +/- 0.05 ng/ml for BB creatine kinase [p less than 0.0002] ), and were unlikely to cause diagnostic confusion. In 92% of patients with chronic renal failure, plasma MB creatine kinase activity was within the normal range (less than 13 IU/L). Eight percent of patients manifested abnormal MB creatine kinase values; the highest was 20 IU/L. The glass bead method for measuring MB creatine kinase was used to avoid the potential confusion induced by non-creatine kinase-mediated fluorescence, which occurs in the region of MB and BB creatine kinase on electrophoresis. The infrequent and modest increases in plasma MB creatine kinase observed in patients with chronic renal failure should be appreciated, but it should not cause diagnostic confusion, because acute myocardial infarction usually results in more substantial elevations of MB creatine kinase.
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Glyceryl trinitrate was previously said to be contraindicated in patients with acute myocardial infarction. Its intravenous administration during acute infarction, however, was associated with a beneficial effect as determined by ST segment mapping. Most recently in a selected group of patients with acute infarction and abnormal haemodynamics, intravenous glyceryl trinitrate was shown to reduce infarct size estimated by enzymes. The present study was performed to verify the safety of intravenous glyceryl trinitrate in patients with infarction under conventional clinical conditions without invasive monitoring and to determine its effect on infarct size in a prospective randomised trial involving 85 patients with infarction (43 treated and 42 control). Treated patients received glyceryl trinitrate within 10 hours of the onset of symptoms (mean 6.0 hours), and the dose was titrated to preset limits for changes in heart rate and blood pressure. In patients with inferior infarction, infarct size estimated by enzymes in the treated was only 12.2 +/- 1.8 versus 19.1 +/- 3.6 CK gram equivalents per metre squared in the placebo group. A similar but statistically insignificant trend was observed for subendocardial infarction but no difference was observed for anterior infarction. Ventricular arrhythmias determined from 24 hour tapes were more frequent in treated patients though this was not statistically significant. Lignocaine requirements in treated and control (1692 +/- 250 vs 1512 +/- 232 mg/24 h) were similar, as were the requirements for morphine (11.4 +/- 1.8 vs 12.2 +/- 2.2 mg/24 h). Results indicate that intravenous glyceryl trinitrate can be administered safely during evolving infarction without invasive monitoring and reduces infarct size in patients with inferior infarction.
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To evaluate whether abnormal production of type III collagen, the characteristic biochemical feature of patients with the type IV Ehlers-Danlos syndrome, consistently predisposes to mitral valve prolapse, we evaluated the family of a proband with classic type IV Ehlers-Danlos syndrome. Production of type III collagen was assessed with the use of cultured skin fibroblasts. Mitral valve prolapse was detected by M-mode and two-dimensional echocardiography. Biochemical abnormalities in the production of type III collagen and echocardiographic findings of mitral valve prolapse were completely concordant. All patients with abnormal production of type III collagen had mitral valve prolapse and all subjects with normal production of type III collagen had entirely normal echocardiograms. Six of the eight patients with abnormal production of type III collagen had subtle cutaneous abnormalities. The consistent association of abnormal production of type III collagen and mitral valve prolapse in this family suggests that this abnormality of collagen may give rise to mitral valve prolapse.
In consideration of the results of experimental studies indicating that nifedipine, a vasodilating calcium antagonist with little inotropic or electrophysiological effects, increases coronary flow to both normal and ischemic zones potentially rendering protection of ischemic myocardium as well as the results of clinical studies in patients with angina pectoris, this pilot study was carried out in patients with acute myocardial infarction to evaluate the clinical, hemodynamic and electrophysiological responses. Nifedipine was administered sublingually in a dosage of 10 mg initially, after an interval of 1 to 1.5 hours and thereafter to maintain the pressure at the level prevailing after three hours. As compared with a control group, the frequency of ventricular dysrhythmia as well as the frequency of complex dysrhythmias in the 17 treated patients were similar (mean 313 vs. 325 PVCs/24 hours; and 5.9 vs. 3.6 episodes respectively in treated and controls). No patient developed evidence of second or third degree AV block. Systemic vascular resistance fell from 1661 to 1283 dyne . s . cm-5 and cardiac index increased from 3.2 to 3.59 l/min/m2 at one hour. Arterial pressure decreased from 146/93 to 131/88 mm Hg. Pulmonary artery pressure remained unchanged in five patients and decreased by more than 3 mm Hg in four. Thus, in patients with acute myocardial infarction nifedipine decreases systemic resistance and, provided preload is not substantially reduced, increases cardiac output. Neither an exacerbation of chest pain nor an increase in ventricular dysrhythmia was observed. Extensive clinical investigation will be needed to definitively characterize effects of nifedipine on infarct size, coronary flow and prognosis of patients with acute myocardial infarction.
There is controversy concerning the specificity of myocardial infarct imaging with technetium-99m pyrophosphate due to the high frequency of false positive images, especially in patients with unstable angina. In this study technetium-99m pyrophosphate images were compared with frequent determinations of plasma creatine kinase, MB isoenzyme (MB CK) activity in 116 patients admitted with the diagnosis of unstable angina. It was hypothesized that frequent measurement of MB CK activity, a sensitive and specific marker for myocardial necrosis, using sensitive assay techniques would detect small amounts of myocardial necrosis which might have been unrecognized by conventional clinical methods. The scintigraphic results and isoenzyme determinations agreed in 88 percent of patients; both tests were normal in 69 percent and both were abnormal, indicating acute myocardial infarcation, in 19 percent of patients. In the remaining 14 patients (12 percent), the scans were abnormal, but MB CK activity was normal. In five of these patients (4 percent), abnormal scintigrams presumably reflected persistent scan positivity after previous myocardial infarction. Only the remaining nine patients (8 percent) could be classified as having unexplained false positive scans, a frequency substantially less than that reported by other investigators who based the diagnosis of myocardial infarction on conventional clinical criteria. These results suggest that abnormal technetium-99m pyrophosphate images in patients with unstable angina generally indicate myocardial necrosis.
To assess the effects of intravenously administered acebutolol (1-20 mg every 4 hours for 24 hours) on cardiac rhythm and performance, we studied 72 patients with evolving myocardial infarction. Twenty-five patients were treated with acebutolol beginning 6 hours after the first increase in the level of plasma creatine kinase. Enzymatically estimated infarct size was compared with that of 25 controls matched for predicted infarct size. Observed infarct sizes were not significantly different in the 2 groups (37 +/- 5 and 30 +/- 5 CK-gram equivalents, respectively). Mean heart rate, diastolic blood pressure, and cardiac output declined from control values during treatment with acebutolol, but remained within the normal range. Mean pulmonary artery pressure and pulmonary artery occlusive pressure were unchanged. In a group of 22 treated patients matched with 22 control subjects for frequency of ventricular extrasystoles, acebutolol effected a prompt reduction in frequencies of ventricular extrasystoles and repetitive arrhythmias, whereas values were not significantly changed in controls during the corresponding intervals. Accordingly, acebutolol may be a useful antiarrhythmic agent in selected patients with acute myocardial infarction with adversely altering haemodynamic stability or enzymatically estimated infarct size.
Attempts to incorporate the monitoring of central pressures and pacing into one catheter have heretofore been unsuccessful. Recently, a new catheter for monitoring central hemodynamic pressures, which has a right ventricular port (Chandler pacing port), has been devised, which has been reported to allow for simultaneous acquisition of hemodynamic data and reliable pacemaker function as well. To assess the reliability of this catheter, we studied ten consecutive Swan-Ganz catheterizations utilizing this new catheter system. In all instances, hemodynamic monitoring was established without difficulty. In three instances, because of right heart enlargement, fluoroscopy was necessary to position the pacing probe at the right ventricular apex. In all ten instances, a threshold of less than 2.5 mV was obtained. Isolated PVCs and nonsustained ventricular tachycardia were common during insertion. After initial placement, the threshold for sensing and pacing was assessed every 6 hr. Malfunction occurred in three patients. In all, repositioning was accomplished without marked difficulty; in one it required fluoroscopy. In three instances, the Swan-Ganz pacing catheter system malfunctioned. These data are similar to data utilizing other modalities of temporary pacing and suggest that this catheter may be capable of providing hemodynamic monitoring and pacing from a single percutaneous procedure.
The development of an intravenous form of nitroglycerin has further enhanced the role of nitrates in the therapy of cardiovascular disorders. This new preparation permits prompt initiation of therapy and rapid attainment of high systemic levels; because of its short half-life, rapid dose titration is both feasible and safe. The antianginal effects of intravenous nitroglycerin are useful in the treatment of coronary vasospasm and unstable angina pectoris. Its hemodynamic effects are of benefit in the therapy of congestive heart failure and in the control of peri-operative hypertension. Recent data suggest that, with appropriate monitoring, intravenous nitroglycerin can be safely administered to patients with evolving myocardial infarction to reduce the extent of myocardial damage.