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Biomedical subjects

D A Tate

Publications and source records attributed to D A Tate.

At least 19 recordsLinked to original sources

Sites of interleukin-6 release in patients with acute coronary syndromes and in patients with congestive heart failure.

This study examines the source of elevated interleukin-6 (IL-6) levels in patients with acute coronary syndrome (ACS) and congestive heart failure (CHF). IL-6 is elevated in the peripheral blood of patients with ACS and CHF, but it is not known if this proinflammatory cytokine is from a cardiac or extracardiac source. Blood samples were obtained from the femoral artery, femoral vein, left main coronary artery, and coronary sinus in 57 patients during cardiac catheterization. IL-6 levels from 12 patients with ACS and 12 patients with CHF were compared with the IL-6 levels in 33 patients who had neither of these clinical conditions. Median IL-6 levels in the peripheral and coronary circulation were a minimum fivefold higher in patients with ACS or CHF relative to control patients. An elevated transcardiac IL-6 gradient (coronary sinus-left main level) was present in patients with ACS (median 5.2; 25th and 75th percentiles 3.9 and 29.3 pg/ml, respectively) compared with control patients (median 0, -0.7 and 0.5 pg/ml; p < 0.001), but not in patients with CHF (median 0.4, -0.7 and 3.5 pg/ml; p = NS). Elevated IL-6 levels in patients with ACS derive from a cardiac source, presumably from "inflamed" coronary plaques and areas of myocardial necrosis, whereas elevated levels in patients with CHF are most likely the result of extracardiac production.

Adult↗

Effect of sex, hemodynamics, body size, and other clinical variables on the corrected thrombolysis in myocardial infarction frame count used as an assessment of coronary blood flow.

BACKGROUND: Compared with the conventional Thrombolysis In Myocardial Infarction (TIMI) flow grade system, the corrected TIMI frame count (CTFC) quantifies coronary blood flow in a more reproducible fashion. The purpose of this study was to determine if the CTFC is affected by sex, body size, hemodynamics, or other selected clinical variables. METHODS AND RESULTS: CTFC was measured in 534 coronary arteries from 200 consecutive patients referred for coronary angiography. CTFC in each artery was related to patient variables (sex, age, race, and body surface area), clinical variables (cardiac rhythm, medication use, diabetes, hypertension, hypercholesterolemia, smoking, and left ventricular hypertrophy), angiographic variables (wall motion abnormality in each coronary artery distribution, left ventricular ejection fraction, percent stenosis in the artery, and presence of collaterals), and hemodynamic variables (aortic systolic and diastolic blood pressure and left ventricular end-diastolic pressure). By multivariate analysis, CTFC in all arteries was significantly associated with aortic systolic and diastolic pressures and body surface area. In addition, there were significant associations between CTFC and age and sex in some but not all arteries. Although significant, the absolute change in CTFC associated with these variables was small. CONCLUSIONS: CTFC provides a quantitative assessment of coronary blood flow that varies only a small amount in association with body size, systemic arterial pressure, age, and sex.

Age Factors↗

Subacute ventricular free-wall rupture presenting as tamponade without frank hemopericardium.

Ventricular free-wall rupture is a well-known catastrophic complication of acute myocardial infarction. A significant number of patients present in a subacute fashion and can be successfully treated with surgery if diagnosed promptly. We present a case of subacute free-wall rupture that occurred after an undiagnosed myocardial infarction. The findings at pericardiocentesis were unusual in that the fluid was sanguinous but not frank hemopericardium. This patient represents the first known reported case to present without frank hemopericardium who survived and was successfully treated surgically. The absence of frank hemopericardium should not exclude the diagnosis of free-wall rupture.

Cardiac Catheterization↗

Assessment of platelet activation by coronary sinus blood sampling during balloon angioplasty and directional coronary atherectomy.

Three markers of platelet activation (platelet-derived microparticles, fibrinogen binding and expression of P-selectin) were assessed by flow cytometry during diagnostic coronary angiography and therapeutic coronary interventions. In 24 patients undergoing diagnostic angiography, blood was collected to determine if our sampling techniques or coronary angiography caused platelet activation. Changes during diagnostic angiography were used to establish baseline values and interpret changes during coronary interventions. In 21 patients, blood samples were obtained at 5 time points during percutaneous transluminal coronary angioplasty (PTCA) (n = 17) or directional coronary atherectomy (DCA) (n = 4). During coronary interventions, mean values for the percentage of platelets expressing P-selectin or binding fibrinogen increased, but with considerable variation among patients. Individual responses for platelet activation markers in each patient were characterized using a twofold increase to indicate elevation related to the intervention. Patients were classified as having complicated or uncomplicated procedures based on the presence of acute closure, dissection, or thrombus observed by angiography. There were no differences in the percentage of elevated markers between patients with uncomplicated (12.5%) and complicated (19%) PTCA procedures. However, patients treated with DCA had more elevated markers (38%) than those treated with PTCA (15%) (p = 0.04). Our data suggest that the extent of platelet activation in individual patients cannot be predicted by common angiographic findings or complications. More markers of platelet activation were present after DCA and may reflect a greater degree of vascular trauma associated with this procedure.

Angioplasty, Balloon, Coronary↗

Absence of human herpesvirus 8 genomes in coronary atherosclerosis in immunocompetent patients.

Human herpevirus 8 (HHV8) has been localized to the endothelial and spindle cells of KS, suggesting a role for HHV8 in atherosclerosis. None of the 38 coronary atherectomy specimens contained HHV8 with both sensitive nested PCR assays, making it unlikely that persistent viral infection with HHV8 plays a role in coronary atherogenesis in the general population of the United States.

Base Sequence↗

Randomized trial of recombinant platelet factor 4 versus protamine for the reversal of heparin anticoagulation in humans.

BACKGROUND: Protamine reverses heparin anticoagulation, but it can have important side effects. We compared the safety and effectiveness of intravenous recombinant platelet factor 4 (rPF4) as an alternative to protamine in a randomized blinded trial. METHODS AND RESULTS: In 81 patients having diagnostic cardiac catheterization, baseline hemodynamics were measured after a 5000-U bolus of heparin. Repeat measurements were obtained at the end of the procedure, and the anticoagulation status was determined by an activated coagulation time (ACT) and activated partial thromboplastin time (aPTT). Patients then received either protamine (50 mg IV over 10 minutes) or rPF4 (1.0 mg/kg IV over 2 minutes) in a blinded fashion. Serial measurements of hemodynamic and clotting functions were performed 5, 10, 20, and 30 minutes after drug administration. Follow-up measurements and clinical assessments were made at 1, 4, 6, and 24 hours later and after 7 days. Before drug administration, ACTs, aPTTs, and hemodynamics were similar among the groups. After drug infusion, there was no difference in ACT between the protamine and rPF4 patients. At 20 and 30 minutes after drug infusion, ACT and aPTT were slightly higher in those receiving rPF4, but these changes were small and of no clinical significance. There were no clinically meaningful differences in any of the hemodynamic variables between the groups, and there were no serious side effects in any patient. CONCLUSIONS: At the dose used in this study, rPF4 was well tolerated and reversed the anticoagulant effect of heparin. These data support its continued evaluation as an alternative to protamine after cardiac surgery.

Adult↗

Variable influence of heparin and contrast agents on platelet function as assessed by the in vitro bleeding time.

Both heparin and contrast agents have anticoagulant effects which are well-documented but their effects on platelets are not well-characterized. The purpose of the present study was to evaluate the sequential effects of heparin and then a contrast agent on platelet function during an angiographic procedure. Blood samples from 54 patients were obtained at baseline, after a 5000 unit bolus of heparin and after administration of a contrast agent (iohexol, n = 30: diatrizoate, n = 24) during angiography. The in vitro bleeding time (IVBT) was determined on nonanticoagulated whole blood using a hollow fiber device under physiological flow conditions. Mean IVBT at baseline was 3.6 +/- 2.7 minutes and increased to 17.0 +/- 12.3 minutes after heparin (p < 0.01). After heparin, 44.5% of the patients still had a normal IVBT (< 9.0 minutes), 11% of the patients had a moderately increased IVBT and the remaining patients had a large increase in their IVBT. When contrast was given (167 +/- 52 mls) following heparin, mean IVBT was higher in those who received diatrizoate (23.3 +/- 9.4 minutes) compared with iohexol (15.0 +/- 10.9 minutes, p < 0.05). However, 15 patients (28%) continued to have a normal IVBT after contrast and of these 80% had received iohexol.

Aged↗

Reversal of heparin anticoagulation by recombinant platelet factor 4 in humans.

BACKGROUND: Protamine is used to reverse the anticoagulant effects of heparin, but it can have important side effects. Platelet factor 4 (PF4) is a protein found in platelet alpha granules that binds to and thereby neutralizes heparin. We evaluated the safety and effectiveness of intravenous recombinant PF4 to neutralize heparin anticoagulation after cardiac catheterization in a phase 1, open-label trial. METHODS AND RESULTS: The study group consisted of 18 patients having diagnostic cardiac catheterization. Heparin (5000 U) was given after vascular access was obtained. In the first 12 patients, additional heparin was given at the conclusion of the procedure so that all patients had activated coagulation times > 300 seconds before rPF4 was given. Three patients each received 0.5, 1.0, 2.5, or 5.0 mg/kg rPF4 over a period of 3 minutes at the conclusion of the catheterization procedure. In 6 additional patients, extra heparin was not given at the conclusion of the procedure, and 1.0 mg/kg rPF4 was given. Hemodynamic measurements, cardiac output, and serial blood tests were performed 5, 10, 20, and 30 minutes after rPF4 and then into the next 24 hours. There were no serious side effects in any patient, despite transient rPF4 levels as high as 14,870 ng/mL in the patients receiving 5.0 mg/kg. One patient receiving 2.5 mg/kg had a slight transient rise in liver enzymes possibly related to the rPF4. There were no important hemodynamic effects of rPF4 administration at any dose used. Doses of 2.5 and 5.0 mg/kg were uniformly effective in reversing the anticoagulant effect of heparin. At lower doses, rPF4 neutralized the effects of heparin in most but not all patients. Pharmacokinetic analysis suggested a monophasic and one-compartment clearance of the PF4-heparin complex. No neutralizing factors to rPF4 were detected in the samples collected 7 days after dosing. CONCLUSIONS: rPF4, in doses ranging from 0.5 to 5.0 mg/kg over 3 minutes, had no serious side effects. Given in sufficient amounts, rPF4 can completely and rapidly reverse the anticoagulant effects of heparin.

Cardiac Catheterization↗

Impairment of fibrinolysis by streptokinase, urokinase and recombinant tissue-type plasminogen activator in the presence of radiographic contrast agents.

OBJECTIVES: The purpose of this study was to determine whether an adverse interaction exists between radiographic contrast agents and thrombolytic drugs. BACKGROUND: Coronary thrombosis may occur in the setting of unstable angina and after coronary angioplasty. However, the use of thrombolytic drugs in the setting of unstable angina has not been beneficial and, in one large trial of angioplasty in patients with unstable angina, was associated with an increased incidence of ischemic complications and abrupt closure. The reasons for these results are not clear. Coronary arteriography was performed in many of these trials, and it is known that fibrin structure and assembly are altered by radiographic contrast agents. METHODS: Blood samples were obtained from patients before (n = 25) and after (n = 20) angiography using iohexol. Blood samples obtained before angiography were tested for response to streptokinase (10 and 100 IU/ml), urokinase (100, 200 and 500 IU/ml) and recombinant tissue-type plasminogen activator (rt-PA) (100 and 1,000 IU/ml) and the results measured. Iohexol, diatrizoate or ioxaglate (4% by volume) was added to separate aliquots of the baseline sample, and the test was repeated. Blood samples obtained after angiography were tested in a similar manner. RESULTS: The onset of lysis at baseline by rt-PA at 1,000 IU/ml occurred at 72 +/- 8.2 s (mean +/- SD) and was markedly delayed in the presence of diatrizoate (527 +/- 181.7 s, p < 0.001) or iohexol (460 +/- 197.0 s, p < 0.001) but not ioxaglate. At 100 IU/ml, there was no lysis detected with rt-PA after the addition of any contrast agent. The addition of a contrast agent caused similar delays in the onset of lysis by urokinase and streptokinase; similar to rt-PA, the effect was smaller at higher concentrations of drug. In vivo blood samples obtained from the patient after angiography showed delays in the onset of lysis by rt-PA and urokinase but not streptokinase. CONCLUSIONS: These data demonstrate that radiographic contrast agents impede fibrinolysis. This previously undescribed interaction was demonstrated using an in vitro test system, but these findings may have clinical relevance when thrombolytic drugs are used at the time of angiography.

Contrast Media↗

Differences in clot lysis among patients demonstrated in vitro with three thrombolytic agents (tissue-type plasminogen activator, streptokinase and urokinase).

This study compares the ability of 3 thrombolytic drugs to promote clot lysis using a new in vitro testing procedure. Whole blood samples from 132 patients were tested using 5 different concentrations of tissue-type plasminogen activator (t-PA), streptokinase (SK) and urokinase. A mixture of blood and thrombolytic drug was placed on a dry-reagent test card containing reptilase, buffers and paramagnetic particles where clot formation occurred. Analysis of the motion of the clot-embedded paramagnetic particles caused by an oscillating magnetic field was used to define the lysis onset time. The slope of the linear regression plot of lysis onset time versus 1/[drug concentration] defined the kinetic rate constant (k) for each drug in each patient. Higher values of k indicated greater resistance to in vitro clot lysis. In the patients studied, there was a large range of k values for t-PA and SK (coefficient of variation 143 and 137%, respectively) but a smaller range of k for urokinase (coefficient of variation 32%). The coefficients of variation for t-PA and SK observed in the study group were five- to 10-fold greater than the coefficients of variation determined for replicate test measurements. Resistance to all SK concentrations tested was found in 9% of the patients. In vitro sensitivity to thrombolysis was compared among the drugs by correlating the derived k values. These comparisons indicated no relation for any of the drugs; many patients had a relatively low k value for 1 drug, while having a relatively high k value for a different drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests↗

Effect of an anterior wall motion abnormality on the results of single-plane and biplane left ventriculography.

Although the biplane area-length method would be optimal for all left ventriculograms, 2 contrast injections are needed in laboratories with single-plane imaging equipment. The purpose of this study was to develop practical guidelines to identify the need for biplane left ventriculography in laboratories with single-plane equipment. From a retrospective analysis of 91 consecutive biplane ventriculograms (group 1), guidelines were identified that predicted when the ejection fraction calculated by the biplane method would differ significantly from the single-plane value. These guidelines were derived from information immediately available to the operator in the laboratory at the time of the procedure. Patients in group 1 were divided into 3 subgroups: biplane exceeding single-plane ejection fraction by greater than or equal to 0.05 (n = 20); single-plane exceeding biplane ejection fraction by greater than or equal to 0.05 (n = 14); and ejection fractions within +/- 0.04 by the 2 methods (n = 57). By multivariate analysis, the only predictor of a higher ejection fraction calculated by the biplane method was an anterior wall motion abnormality. This finding was tested prospectively in a separate group of 60 patients (group 2). Left ventriculograms in group 2 patients were stratified before analysis by the presence or absence of an anterior wall motion abnormality. In patients with anterior wall motion abnormalities, the biplane ejection fraction was greater than the single-plane value by 0.05 +/- 0.04 (range -0.03 to +0.15). In contrast, this difference in patients without anterior wall motion abnormalities was -0.01 +/- 0.04 (range -0.09 to +0.06; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

Effect of heparin on coronary arterial patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction.

Infarct artery patency rates at 90 minutes after coronary thrombolysis using recombinant tissue-type plasminogen activator (rt-PA) with and without concurrent heparin anticoagulation have been shown to be comparable. The contribution of heparin to efficacy and safety after thrombolysis with rt-PA is unknown. In this pilot study, 84 patients were treated within 6 hours of onset of acute myocardial infarction (mean of 2.7 hours) with the standard dose of 100 mg of rt-PA over 3 hours. Forty-two patients were randomized to receive additionally immediate intravenous heparin anticoagulation (5,000 U of intravenous bolus followed by 1,000 U/hour titrated to a partial thromboplastin time of 1.5 to 2.0 times control) while 42 patients received rt-PA alone. Coronary angiography performed on day 3 (48 to 72 hours, mean 57) after rt-PA therapy revealed infarct artery patency rates of 71 and 43% in anticoagulated and control patients, respectively (p = 0.015). Recurrent ischemia or infarction, or both, occurred in 3 (7.1%) anticoagulated patients and 5 (11.9%) control patients (difference not significant). Mild, moderate and severe bleeding occurred in 52, 10 and 2% of the group receiving anticoagulation, respectively, and 34, 2 and 0% of patients in the control group, respectively (p = 0.006). These data indicate that after rt-PA therapy of acute myocardial infarction, heparin therapy is associated with substantially higher coronary patency rates 3 days after thrombolysis but is accompanied by an increased incidence of minor bleeding complications.

Coronary Angiography↗

Limitations of the metabolic rate meter for measuring oxygen consumption and cardiac output.

Over the past few years, a metabolic rate meter has been introduced for easy measurement of oxygen consumption. However, its accuracy is unproved. In 40 patients (26 men, 14 women, ages 34 to 73 years), cardiac output was measured simultaneously by thermodilution and the Fick method using the metabolic rate meter to quantitate oxygen consumption. In comparison with thermodilution, the results using the Fick method were low (5.26 +/- 1.18 vs 4.14 +/- 0.99 liters/min, respectively, p less than 0.01). In 18 patients cardiac output also was measured by the Fick method using a Douglas bag to quantitate oxygen consumption. In these patients, oxygen consumption measured with the metabolic rate meter was lower than that obtained using the Douglas bag (168 +/- 25 vs 216 +/- 42 ml/min, respectively, p less than 0.01). With the Douglas bag, the Fick and thermodilution cardiac output measurements were similar (4.68 +/- 1.08 vs 4.87 +/- 0.86 liters/min, respectively, difference not significant), and they differed by less than or equal to 10% in 15 patients. In contrast, with the metabolic rate meter, the results of thermodilution were higher than those with the Fick method (4.84 +/- 0.95 vs 3.60 +/- 0.71 liters/min, respectively, p less than 0.01), and differed by less than or equal to 10% in only 1 patient (p less than 0.01). Thus, the values for oxygen consumption and cardiac output obtained with the metabolic rate meter are lower than actual values. This device is less accurate than the Douglas bag.

Adult↗