bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator. Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II-A trial.
Authors: Rogers W J , Baim D S , Gore J M , Brown B G , Roberts R , Williams D O , Chesebro J H , Babb J D , Sheehan F H , Wackers F J
Published: June 2011

To assess the value and timing of percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction (AMI), 586 patients in the Thrombolysis in Myocardial Infarction Study Phase II-A were randomized among three treatment strategies, one using immediate coronary arteriography followed by PTCA if appropriate (immediate invasive strategy group, n = 195), a second that deferred angiography and PTCA for 18-48 hours (delayed invasive strategy group, n = 194), and a third, more conservative, approach in which PTCA was used only if ischemia occurred spontaneously or at the time of predischarge exercise testing (conservative strategy group, n = 197). Predischarge contrast left ventricular ejection fraction, the primary study end point, was similar among the patients in all three treatment groups and averaged 49.3%. The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001). Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01). Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001). At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%), although the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001). Thus, because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy.
Physiological early diastolic intraventricular pressure gradient is lost during acute myocardial ischemia.
Authors: Courtois M , Kovács S J , Ludbrook P A
Published: June 2011

A consistent pattern of intraventricular regional pressure gradients exists under physiological conditions during the rapid filling phase of diastole in the normal dog left ventricle. We hypothesized that this pressure gradient pattern is caused, in part, by early diastolic recoil of the left ventricular walls in conjunction with release of elastic potential energy stored during systole, generating suction and thus contributing to diastolic filling. If so, any condition that interferes with normal regional systolic function might be expected to modify the pattern of the normal early diastolic intraventricular pressure gradients. Accordingly, the present study was designed to determine whether acutely induced regional systolic left ventricular mechanical dysfunction is accompanied by changes in the pattern of the early diastolic intraventricular pressure gradients. Acute myocardial ischemia was induced by balloon occlusion of the left anterior descending coronary artery (LAD) in nine anesthetized closed-chest dogs. The maximum early diastolic intraventricular pressure gradient (MIVP) was measured between the mid-left ventricle and apex with a dual-sensor micromanometer (3-cm spacing between the sensors) before and 20 minutes after LAD occlusion. Ejection fraction (EF) and number of dyskinetic chords (DChords) were measured from left ventricular contrast ventriculograms. Twenty minutes after LAD occlusion, the nine dogs evidenced significant changes in EF (56 +/- 10% to 37 +/- 8%), DChords (0 +/- 0 to 17 +/- 16 chords), left ventricular minimum pressure (-1.7 +/- 0.5 to 0.0 +/- 1.5 mm Hg), left ventricular end-diastolic pressure (4.2 +/- 1.2 to 5.9 +/- 2.2 mm Hg), and heart rate (90 +/- 17 to 103 +/- 18 beats/min).(ABSTRACT TRUNCATED AT 250 WORDS)
Intracardiac, intravascular, two-dimensional, high-frequency ultrasound imaging of pulmonary artery and its branches in humans and animals.
Authors: Pandian N G , Weintraub A , Kreis A , Schwartz S L , Konstam M A , Salem D N
Published: June 2011

Intravascular ultrasound imaging is a promising new method for assessing vascular morphology. We evaluated the capability of intravascular ultrasound to quantify pulmonary artery (PA) morphology in vitro and explored the feasibility of in vivo PA imaging in animals and humans. In the in vitro study of 15 PA segments, we used a 20-MHz prototype ultrasound catheter. Intravascular ultrasound (y) provided crisp images of PA segments and demonstrated excellent correlations with anatomic measurements (x) in the estimation of luminal area (y = 0.89x + 2.95, r = 0.99, p less than 0.001), luminal diameter (n = 30, y = 0.79x + 0.96, r = 0.92, p less than 0.001), and vessel wall thickness (n = 60, y = 0.65x + 0.33, r = 0.85, p less than 0.001). We subsequently introduced the probe into the PA of 10 dogs and were able to obtain real-time, two-dimensional images of the main PA, its major branches, and farther smaller branches as far as the wedge level. To evaluate the in vivo feasibility of PA imaging in conscious humans, we used a commercially available, 20-MHz intravascular ultrasound (IVUS) catheter in 22 subjects through a femoral or jugular venous sheath at the end of standard diagnostic cardiac catheterization. In 20 subjects, we acquired dynamic, high-resolution, cross-sectional images of the proximal and distal PA. Changes in shape and decreasing luminal area could be clearly recognized as the IVUS catheter reached branching points and as it passed more distally. There were no complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Understanding the coronary circulation through studies at the microvascular level.
Authors: Marcus M L , Chilian W M , Kanatsuka H , Dellsperger K C , Eastham C L , Lamping K G
Published: June 2011

Studies of the coronary circulation have divided vascular resistances into three large components: large vessels, small resistance vessels, and veins. Studies of the epicardial microcirculation in the beating heart using stroboscopic illumination have suggested that resistance is more precisely controlled in different segments of the circulation. Measurements of coronary pressure in different sized arteries and arterioles have indicated that under normal conditions, 45-50% of total coronary vascular resistance resides in vessels larger than 100 microns. This distribution of vascular resistance can be altered in a nonuniform manner by a variety of physiological (autoregulation, increases in myocardial oxygen consumption, sympathetic stimulation) and pharmacological stimuli (norepinephrine, papaverine, dipyridamole, serotonin, vasopressin, nitroglycerin, adenosine, and endothelin). Studies of exchange of macromolecules in the microcirculation using fluorescent-labeled dextrans have also identified the size of the small pore (35-50 A) in coronary microvessels that can be altered by myocardial ischemia. Studies of the coronary microcirculation have demonstrated that the control of vascular resistance is extremely complex, and mechanisms responsible for these heterogeneous responses need further examination.
Acceleration of recombinant tissue-type plasminogen activator-induced thrombolysis and prevention of reocclusion by the combination of heparin and the Arg-Gly-Asp-containing peptide bitistatin in a canine model of coronary thrombosis.
Authors: Shebuski R J , Stabilito I J , Sitko G R , Polokoff M H
Published: June 2011

The effect of tissue-type plasminogen activator (t-PA) alone or in combination with heparin, the Arg-Gly-Asp-containing peptide bitistatin, or both heparin and bitistatin was evaluated on thrombolysis time and acute reocclusion in a canine model of coronary thrombosis. Thrombus formation was elicited by electrolytic injury with a needle electrode to the endothelial surface of the circumflex coronary artery in the open-chest, anesthetized dog in the presence of a flow-limiting critical stenosis. Thirty minutes after spontaneous coronary artery occlusion, t-PA (1 mg/kg i.v. over 90 minutes) was administered. Group 1 was given t-PA alone; reperfusion occurred at 78.2 +/- 5.6 minutes with a reperfusion incidence of 60% (6/10). Group 2 received t-PA plus heparin (100 units/kg plus 50 units/kg/hr); reperfusion occurred at 61.9 +/- 9.1 minutes with a reperfusion incidence of 90% (9/10). Group 3 received t-PA plus heparin plus bitistatin (30 micrograms/kg plus 3 micrograms/kg/min); reperfusion occurred at 47.3 +/- 7.6 minutes (p less than 0.05 versus group 1) with a reperfusion incidence of 90% (9/10). Group 4 received t-PA plus bitistatin, and reperfusion occurred at 51.8 +/- 8.5 minutes; however, the reperfusion incidence was only 60% (6/10). In groups 1, 2, and 4, acute reocclusion occurred in more than 80% of the reperfused dogs, whereas in group 3 reocclusion occurred in 22% (2/9) of the reperfused dogs (p less than 0.05 versus group 1). The dose of heparin used in this study increased activated partial thromboplastin times 1.5-2.0-fold over control.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular prostacyclin is increased in patients ingesting omega-3 polyunsaturated fatty acids before coronary artery bypass graft surgery.
Authors: DeCaterina R , Giannessi D , Mazzone A , Bernini W , Lazzerini G , Maffei S , Cerri M , Salvatore L , Weksler B
Published: June 2011

Interest in the antithrombotic potential of diets enriched with fish oil-derived polyunsaturated fatty acids (omega-3 PUFAs) prompted us to examine how these fatty acids, when taken preoperatively, affect hemostasis, plasma lipid levels, and production of prostacyclin (PGI2) by vascular tissues in atherosclerotic patients undergoing coronary artery bypass graft surgery. Fifteen patients with angiographically proven coronary artery disease received 3 g/day eicosapentaenoic acid and 1.3 g/day docosahexaenoic acid as capsules of purified fish oil for 28 days before surgery. Platelet aggregation induced by low concentrations of ADP, collagen, and epinephrine decreased (p less than 0.05) and serum thromboxane B2 decreased 36% (p less than 0.01) from baseline values. Bleeding times increased 40% (p less than 0.01) from baseline. Serum triglycerides decreased 50% (p less than 0.05) without a change in total serum cholesterol. Spontaneous production of PGI2 measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), its stable hydrolytic product, by saphenous vein and aortic and atrial tissues obtained at surgery was greater in tissues from patients receiving omega-3 PUFA supplements than in tissues from matched controls (13.8 +/- 2.2 versus 8.6, 21.0 +/- 3.1 versus 11.5 +/- 2.1, and 166 +/- 13 versus 102 +/- 15 ng/g, respectively, all p less than 0.05). Arachidonate-stimulated production of PGI2, as indicated by increased levels of 6-keto-PGF1 alpha, was increased. Despite changes in platelet function, bleeding time, and vascular PGI2, the perioperative blood loss was not increased in subjects receiving fish oil supplements. Thus, omega-3 PUFAs at moderate dosages may exert antithrombotic effects by increasing prostacyclin production by vessel walls as well as by direct inhibition of platelet activity.
Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography.
Authors: Schwaiger M , Kalff V , Rosenspire K , Haka M S , Molina E , Hutchins G D , Deeb M , Wolfe E , Wieland D M
Published: June 2011

The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial [11C]hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, [11C]hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart.
Effect of beta-adrenergic blockade on myocardial function and energetics in congestive heart failure. Improvements in hemodynamic, contractile, and diastolic performance with bucindolol.
Authors: Eichhorn E J , Bedotto J B , Malloy C R , Hatfield B A , Deitchman D , Brown M , Willard J E , Grayburn P A
Published: June 2011

The hemodynamic effects of beta-adrenergic blockade with bucindolol, a nonselective beta-antagonist with mild vasodilatory properties, were studied in patients with congestive heart failure. Fifteen patients (New York Heart Association class I-IV) underwent cardiac catheterization before and after 3 months of oral therapy with bucindolol. The left ventricular ejection fraction increased from 0.23 +/- 0.12 to 0.29 +/- 0.14 (p = 0.007), and end-systolic elastance, a relatively load-independent determinant of contractility, increased from 0.60 +/- 0.40 to 1.11 +/- 0.45 mm Hg/ml (p = 0.0049). Both left ventricular stroke work index (34 +/- 13 to 47 +/- 19 g-m/m2, p = 0.0059) and minute work (5.5 +/- 2.2 to 7.0 +/- 2.6 kg-m/min, p = 0.0096) increased despite reductions in left ventricular end-diastolic pressure (19 +/- 8 to 15 +/- 5 mm Hg, p = 0.021). There was an upward shift in the peak + dP/dtmax-end-diastolic volume relation (p = 0.0005). These data demonstrate improvements in myocardial contractility after beta-adrenergic blockade with bucindolol. At a matched paced heart rate of 98 +/- 15 min-1, the time constant of left ventricular isovolumic relaxation was significantly reduced by bucindolol therapy (92 +/- 17 versus 73 +/- 11 msec, p = 0.0013), and the relation of the time constant to end-systolic pressure was shifted downward (p = 0.014) with therapy. The slope of the logarithm left ventricular end-diastolic pressure-end-diastolic volume relation was unchanged (p = 0.51) after bucindolol. These data suggest that chronic beta-adrenergic blockade with bucindolol improves diastolic relaxation but does not alter myocardial chamber stiffness. Myocardial oxygen extraction, consumption, and efficiency were unchanged despite improvement in contractile function and mechanical work. Thus, in patients with congestive heart failure, chronic beta-adrenergic blockade with bucindolol significantly improves myocardial contractility and minute work, yet it does not do so at the expense of myocardial oxygen consumption. Additionally, bucindolol improves myocardial relaxation but does not affect chamber stiffness.
Technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile and thallium-201 extraction, washout, and retention at varying coronary flow rates in rabbit heart.
Authors: Marshall R C , Leidholdt E M , Zhang D Y , Barnett C A
Published: June 2011

Technetium-99m hexakis 2-methoxy-2-isobutyl isonitrile (Tc-MIBI) and thallium-201 extraction, washout, and retention were investigated and compared in 20 isolated, isovolumic, retrograde blood-perfused rabbit hearts at flow rates ranging from 0.5 to 3.5 ml/g wet wt min-1 in the absence of tracer recirculation. Mean Tc-MIBI peak instantaneous extraction was lower (0.55 +/- 0.10, p less than 0.001) and more affected by flow rate (p less than 0.05) than 201Tl peak instantaneous extraction (0.83 +/- 0.06). In contrast, the rate of 201Tl washout was significantly faster (p less than 0.05) and initially more dependent on perfusion rate (p less than 0.05) than Tc-MIBI washout. Reflecting its higher peak instantaneous extraction, 201Tl retention was 55-79% higher immediately after isotope injection (p less than 0.001) than Tc-MIBI retention, and relative changes in maximal 201Tl net uptake correlated better (p less than 0.05) with relative flow changes than maximal Tc-MIBI net uptake. However, due to its faster washout rate, the superiority of thallium over Tc-MIBI as a perfusion indicator was lost within 10 minutes of tracer injection under the present single-pass experimental conditions. These data were interpreted to indicate that 1) Tc-MIBI is not as well extracted and has a slower washout rate than 201Tl; 2) varying the coronary flow rate has significant but divergent effects on the extraction, washout, and retention of Tc-MIBI and 201Tl; and 3) the present results support continued evaluation of Tc-MIBI as a possible perfusion indicator.
Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials.
Authors: Coplen S E , Antman E M , Berlin J A , Hewitt P , Chalmers T C
Published: June 2011

Because individual studies evaluating the role of quinidine in the maintenance of sinus rhythm after cardioversion from chronic atrial fibrillation have involved relatively few patients, a meta-analysis of randomized control trials was performed. Six trials published between 1970 and 1984 were selected by two blinded reviewers based on study design and statistical analysis. Data from these six trials involving 808 patients were pooled after testing for homogeneity of treatment effects across trials. Life table estimates of the percent of patients still in sinus rhythm at 3, 6, and 12 months after cardioversion were constructed for quinidine and control groups. The proportion of patients remaining in sinus rhythm in the quinidine group was 69%, 58%, and 50% at 3, 6, and 12 months postcardioversion respectively. The proportion of patients remaining in sinus rhythm in the control group was 45%, 33%, and 25% at the same time intervals. The pooled rate difference, or difference in proportion of patients in sinus rhythm between quinidine and control groups, was 24%, 23%, and 24% at 3, 6, and 12 months of follow-up (p less than 0.001 at all time intervals). The unadjusted total mortality rate in the quinidine-treated patients was 2.9% and in the control group was 0.8%. The odds of dying in the quinidine-treated group were approximately three times that of the control group ("typical" odds ratio = 2.98, p less than 0.05). Thus, quinidine treatment is more effective than no antiarrhythmic therapy in suppressing recurrences of atrial fibrillation but appears to be associated with increased total mortality.
Validity of enzyme-linked immunosorbent assays of cross-linked fibrin degradation products as a measure of clot lysis.
Authors: Eisenberg P R , Jaffe A S , Stump D C , Collen D , Bovill E G
Published: June 2011

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.
Recent progress in understanding apolipoprotein B.
Authors: Young S G
Published: June 2011

For the past 5 years, investigators from many different laboratories have contributed to a greatly increased understanding of two very important lipid-carrying proteins in plasma--apo B-100 and apo B-48. Apo B-100, an extremely large protein composed of 4,536 amino acids, is synthesized by the liver and is crucial for the assembly of triglyceride-rich VLDL particles. Apo B-100 is virtually the only protein of LDL, a cholesteryl ester-enriched class of lipoproteins that are metabolic products of VLDL. The apo B-100 of LDL serves as a ligand for the LDL receptor-mediated uptake of LDL particles by the liver and extrahepatic tissues. The LDL receptor-binding region of apo B-100 is located in the carboxyterminal portion of the molecule, whereas its lipid-binding regions appear to be broadly dispersed throughout its length. Apo B-48 contains the amino-terminal 2,152 amino acids of apo B-100 and is produced by the intestine as a result of editing of a single nucleotide of the apo B mRNA, which changes the codon specifying apo B-100 amino acid 2,153 to a premature stop codon. Apo B-48 has an obligatory structural role in the formation of chylomicrons; therefore, its synthesis is essential for absorption of dietary fats and fat-soluble vitamins. Both apo B-48 and apo B-100 are encoded on chromosome 2 by a single gene that contains 29 exons and 28 introns. An elevated level of apo B-100 in the plasma is a potent risk factor for developing premature atherosclerotic disease. In the past 3 years, many different apo B gene mutations that affect the concentrations of both apo B and cholesterol in the plasma have been characterized. A missense mutation in the codon for apo B-100 amino aid 3,500 is associated with hypercholesterolemia. This mutation results in poor binding of apo B-100 to the LDL receptor, thereby causing the cholesteryl ester-enriched LDL particles to accumulate in the plasma. This disorder is called familial defective apo B-100, and it is probably a cause of premature atherosclerotic disease. Familial hypobetalipoproteinemia is a condition associated with abnormally low levels of apo B and cholesterol; affected individuals may actually have a reduced risk of atherosclerotic disease.(ABSTRACT TRUNCATED AT 400 WORDS)
Ten-year follow-up of quality of life in patients randomized to receive medical therapy or coronary artery bypass graft surgery. The Coronary Artery Surgery Study (CASS)
Authors: Rogers W J , Coggin C J , Gersh B J , Fisher L D , Myers W O , Oberman A , Sheffield L T
Published: June 2011

Quality of life indexes were assessed in 780 patients 10 years after randomization to medical therapy (n = 390) or coronary artery bypass graft surgery (n = 390) in the Coronary Artery Surgery Study. At 10 years, mortality was 21.8% in the medical group and 19.2% in the surgical group (p = NS), and 144 (37%) of the medical group had undergone surgery because of increasing chest pain. At study entry, 22% of medical and surgical patients were angina free; at 1 and 5 years after entry, the frequency of asymptomatic patients was 66% and 63% in the surgical group and 30% and 38% in the medical group. However, by 10 years after entry, the proportion of patients free of angina had fallen to 47% in the surgical group and to 42% in the medical group. Activity limitation and use of beta-blockers and long-acting nitrates were less in the surgical than the medical group at 1 and 5 years after entry but little different from the medical group at 10 years after entry. Throughout follow-up, recreational status, employment status, frequency of heart failure, use of other medications, and hospitalization frequency were similar between the two groups. Thus, indexes of quality of life such as angina relief, increased activity, and reduction in use of antianginal medications initially appear superior in patients with stable manifestations of ischemic heart disease assigned to surgery, but by 10 years after entry, these advantages are much less apparent. Although the observed similarities of the medically and surgically assigned groups at 10 years reflect return of symptoms in the surgical group to some extent, a more important explanation is the performance of late surgery in a large proportion of the medically assigned patients, rendering them asymptomatic.
Thrombolytic and pharmacokinetic properties of a conjugate of recombinant single-chain urokinase-type plasminogen activator with a monoclonal antibody specific for cross-linked fibrin in a baboon venous thrombosis model.
Authors: Collen D , Dewerchin M , Rapold H J , Lijnen H R , Stassen J M
Published: June 2011

Chemical conjugates between recombinant single-chain urokinase-type plasminogen activator (rscu-PA) and a murine monoclonal antibody directed against fragment D-dimer of cross-linked human fibrin (MA-15C5), rscu-PA/MA-15C5, and between rscu-PA and a control monoclonal antibody (MA-1C8), rscu-PA/MA-1C8, were produced by cross-linking with N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). In an in vitro system composed of a [125 I]fibrin-labeled baboon plasma clot immersed in autologous citrated plasma, dose- and time-dependent lysis was obtained with a ratio of the potencies of free and conjugated rscu-PA similar to that in human plasma: 50% lysis in 2 hours required 4.3 micrograms/ml rscu-PA, 1.0 microgram/ml urokinase-type plasminogen activator (u-PA) equivalent rscu-PA/MA-15C5, or 15 micrograms/ml u-PA equivalent rscu-PA/MA-1C8. The thrombolytic and pharmacokinetic properties of rscu-PA and of rscu-PA/MA-15C5 were compared in baboons with a 0.8-1.0 ml [125 I]fibrin-labeled autologous blood clot produced in a femoral vein. Continuous intravenous infusion of these compounds during a 2-hour period resulted in dose- and time-dependent lysis. The thrombolytic potency of rscu-PA/MA-15C5 was 3.0 +/- 0.5 times higher (50% lysis with 0.3 +/- 0.02 mg u-PA equivalent/kg body wt) than that of rscu-PA measured by ex vivo isotope recovery from the femoral vein segment (p less than 0.001) and was 2.7 +/- 0.5 times higher (50% lysis with 0.35 +/- 0.02 mg/kg rscu-PA/MA-15C5) by external radioisotope counting (p less than 0.001). A dose of 0.5 mg/kg of rscu-PA/MA-1C8 was much less active than rscu-PA. After the end of the infusion, u-PA-related antigen disappeared from plasma in a biphasic manner with an initial half-time of 2.7 +/- 0.5 for rscu-PA, 24 +/- 1.2 for rscu-PA/MA-15C5, and 21 +/- 0.5 minutes for rscu-PA/MA-1C8 with corresponding plasma clearances of 340 +/- 40, 20 +/- 3, and 24 +/- 2 ml/min, respectively. In conclusion, the increased thrombolytic potency of rscu-PA/MA-15C5 is the result of a reduction of the thrombolytic potency due to coupling of rscu-PA to the antibody molecule, which is counter-balanced by an enhancement of the thrombolytic potency due to fibrin targeting by the specific idiotype.
Pathophysiological insights into the cardiomyopathy of Chagas' disease.
Authors: Morris S A , Tanowitz H B , Wittner M , Bilezikian J P
Published: June 2011

The evidence gained from both human and animal studies of chronic chagasic cardiomyopathy suggests that the disease occurs as a consequence of several discrete and progressive pathophysiological processes occurring after infection, the ultimate expression of which depends on a host of unidentified factors. Collectively, the infection-associated events compromise microvasculature function and result in hypoperfusion, with consequences indistinguishable from those observed in other, nonparasitological cardiomyopathic diseases secondary to hypoperfusion. Therefore, chronic chagasic cardiomyopathy may share similar pathophysiological abnormalities with other chronic congestive cardiomyopathic states.
Strength-duration and probability of success curves for defibrillation with biphasic waveforms.
Authors: Feeser S A , Tang A S , Kavanagh K M , Rollins D L , Smith W M , Wolf P D , Ideker R E
Published: June 2011

Certain biphasic waveforms require less energy to defibrillate than do monophasic pulses of equal duration, although the mechanisms of this increased effectiveness remain unclear. This study used strength-duration and percent success curves for defibrillation with monophasic and biphasic truncated exponential waveforms to explore these mechanisms. In part 1, defibrillation thresholds were determined for both high- and low-tilt waveforms. The monophasic pulses tested ranged in duration from 1.0 to 20.0 msec, and the biphasic waveforms had first phases of either 3.5 or 7.0 msec and second phases ranging from 1.0 to 20.0 msec. In part 2, defibrillation percent success curves were constructed for 6.0 msec/6.0 msec biphasic waveforms with a constant phase-one amplitude and with phase-two amplitudes of approximately 21%, 62%, 94%, and 141% of phase one. This study shows that if the first phase of a biphasic waveform is held constant and the second phase is increased in either duration or amplitude, defibrillation efficacy first improves, then declines, and then again improves. For pulse durations of at least 14 msec, the second-phase defibrillation threshold voltage of a high-tilt biphasic waveform is higher than that of a monophasic pulse equal in duration to the biphasic second phase (p less than 0.05), indicating that the previously proposed hypothesis of stimulation by the second phase is not the sole mechanism of biphasic defibrillation. These facts indicate the importance of the degree of tilt for the defibrillation efficacy of biphasic waveforms and suggest at least two mechanisms exist for defibrillation with these waveforms, one that is more effective for smaller second phases and another that becomes more effective as the second phase is increased.
Protection from cerebral ischemia by a new imidazole derivative (Y-9179) and pentobarbital. A comparative study in chronic middle cerebral artery occlusion in cats.
Authors: Tamura A , Asano T , Sano K , Tsumagari T , Nakajima A
Published: June 2011

For the purpose of investigating the protective action against cerebral ischemia by a new imidazole derivative (Y-9179) and pentobarbital, regional cerebral ischemia was produced in 53 cats by permanent occlusion of the middle cerebral artery (MCA) via the transorbital approach. In 20 cats, the clips were applied at the origin of the right MCA whereas in the remaining 33 they were applied laterally. The administration of Y-9179 (6.25 and 12.5 mg/kg/day), pentobarbital (25 mg/kg/day) and saline was started 30 min after MCA occlusion and continued for 3 days. The cats were observed for 7 days and then sacrificed. Since there was a remarkable difference in mortality between the medial (65%) and the lateral occlusion groups (15%), the evaluation of drug effects was based only on the results obtained with the lateral occlusion group. The brains were sliced at 4 fixed coronal planes, in which the ratios of the infarcted area in the 2 hemispheres were obtained by planimetry. A statistically significant decrease in the infarction rate was found both in Y-9179 and pentobarbital-treated groups compared to the control group. Since the CNS depressant action of Y-9179 is far less potent than that of pentobarbital, the present results indicate the potential usefulness of Y-9179 in the management of strokes.
Failure of thiopental to modify global anoxic injury.
Authors: Snyder B D , Ramirez-Lassepas M , Sukhum P , Fryd D , Sung J H
Published: June 2011

To corroborate thiopental protection from cerebral anoxia after cardiopulmonary arrest, 23 sedated, curarized, adult dogs were asphyxiated by plugging the endotracheal tube. Cardiopulmonary resuscitation (CPR) was started 7 minutes after electrocortical silence. Twelve animals received no other treatment (controls), 10 regained consciousness and spontaneous respirations, but remained decerebrate, blind, unable to drink or feed. Two dogs returned to a normal neurologic state. Ten dogs were treated with thiopental after CPR, 7 received 15 mg/kg the first minute, followed by 23 mg/kg over 1 hour; 3 received 60 mg/kg in the first 3 minutes, followed by 30 mg/kg over 1 hour. Except for 1 dog in the low-dose group that recovered neurologically, thiopental-treated dogs showed no neurological or survival improvement over the controls.
Hypertension and acute focal cerebral ischemia. Infarction and edema after occlusion of a middle cerebral artery in cats.
Authors: Hayakawa T , Waltz A G , Jacobson R L
Published: June 2011

Hypertension was produced in 8 cats by nephrectomy and wrapping the opposite kidney. Subsequent occlusion of one middle cerebral artery caused ischemic infarcts that were larger than those of 8 normotensive cats. The larger infarcts may have been caused by increases of ischemic cerebral edema resulting from changes in the cerebral endothelial barrier induced by hypertension. In addition to increasing the likelihood of strokes, hypertension in humans may predispose toward larger cerebral infarcts.
Cerebral blood flow immediately following brief circulatory stasis.
Authors: Fischer E G , Ames A , Lorenzo A V
Published: June 2011

Cerebral blood flow was studied in rabbits immediately following complete circulatory stasis of varying duration. Systemic arterial pressure was measured continuously. The postischemic circulation was examined both by an infusion of carbon black and, in separate experiments, by injection of 14C-antipyrine into the blood. We examined the relationship between the duration of stasis, the postischemic arterial pressure, and the amount of cerebral reperfusion. As stasis increased from 5 to 30 min the pressure required to achieve reperfusion of the entire brain rose from 20 to 100 torr. Following even temporary exposure to arterial pressures above 110 torr all areas of the brain were generally reperfused. Blood flow in reperfused brain varied directly with arterial pressure, indicating failure of autoregulation. At normal (preischemic) arterial pressure, postischemic cortical flow was twice the normal rate. The data indicate that the pressure required to initiate flow in ischemic brain increases as the duration of stasis is lengthened and that once flow occurs there will be a significant hyperperfusion unless systemic arterial pressure is lowered to the low normal or hypotensive range.
Brain blood flow and metabolism after global ischemia and post-insult thiopental therapy in monkeys.
Authors: Kofke W A , Nemoto E M , Hossmann K A , Taylor F , Kessler P D , Stezoski S W
Published: June 2011

We measured total and regional cerebral blood flow (CBF, rCBF) and cerebral metabolic rate (CMR) of oxygen (O2), glucose (G), and lactate (L) levels for 4 h after 16 min global brain ischemia in rhesus monkeys with and without post-insult thiopental therapy. Eleven monkeys weighing 4-5 kg anesthetized with 1 percent halothane, 66 percent nitrous oxide and 33 percent oxygen, were subjected to 16 min global brain ischemia by a combination of trimethaphan hypotension (to a mean arterial pressure of 50 torr) and a high pressure (1500 torr) neck tourniquet. Post-ischemia, 7 monkeys were untreated (controls) and 4 received thiopental 90 mg/kg infused intravenously over 60 min, beginning at 5 min post-ischemia. Total CBF and rCBF were measured by continuous monitoring of cerebral venous (torcula) and parietal-occipital (external scintillation) 133Xe activity, respectively, after intra-innominate artery injection of 500 micronCi 133Xe in saline. In control monkeys, hyperemia in rCBF, but not in total CBF was observed at 6-7 min post-ischemia, whereas both total CBF and rCBF increased in thiopental treated monkeys. The hyperemia in thiopental treated monkeys coincided with an increase in CMRG without a proportional increase in CMRO2 or lactate levels. Indeed, CMRO2 was depressed in the first 30 min post-ischemia. At 30 min post-ischemia, CMRO2 rose to twofold greater than pre-ischemia in control monkeys, but only to pre-ischemic levels in thiopental treated monkeys. The data suggest that thiopental therapy improves distribution of brain blood flow and brain glucose uptake early post-ischemia and depresses CMRO2 later post-ischemia.
Effects of hemorrhagic hypotension on the cerebral circulation. III. Neuropathology.
Authors: Graham D I , Fitch W , MacKenzie E T , Harper A M
Published: June 2011

A neuropathological examination was made of 15 cats anesthetized with alpha-chloralose, subjected to a stepwise reduction in mean arterial pressure by graded hemorrhagic hypotension. Five animals were sacrificed by perfusion-fixation at a mean arterial pressure of 75 mm Hg, 5 at a mean pressure of 35 mm Hg and 5 at 25 mm Hg. Ischemic brain damage was seen in only 5 animals, one sacrificed at a mean arterial pressure of 35 mm Hg and 4 at a pressure of 25 mm Hg. It was maximal in the selectively vulnerable areas and included the boundary zones between the major arteries of the cerebral hemispheres, the Ammon's horn and the thalamus.
Factors related to stroke incidence in Hawaii Japanese men. The Honolulu Heart Study.
Authors: Kagan A , Popper J S , Rhoads G G
Published: June 2011

As part of an ongoing longitudinal study of coronary heart disease and stroke among Japanese men in Hawaii, 8,006 men of Japanese ancestry living on the island of Oahu and aged 45-68 at entry examination have been followed by reexamination and surveillance. One hundred and eleven were found to have evidence of prior stroke at the time of the initial examination. During a six-year follow up period of the remaining 7,895 men, 94 developed definite thromboembolic stroke, 33 definite intracranial hemorrhage, and 6 developed stroke of unknown type. The principal risk factors for thromboembolic stroke were: elevated blood pressure, glucose intolerance, age, and electrocardiography evidence of left ventricular hypertrophy or strain. Attributes associated with increased risk of intracranial hemorrhage were elevated blood pressure, electrocardiographic evidence of left ventricular hypertrophy or strain, and alcohol intake. Serum cholesterol level was negatively associated with risk of intracranial hemorrhage.
Positron imaging of cerebral blood flow during continuous inhalation of C15O2.
Authors: Ackerman R H , Subramanyam R , Correia J A , Alpert N M , Taveras J M
Published: June 2011

This investigation tests the hypothesis that the normal cerebral image obtained non-invasively during continuous inhalation of C15O2 is related to cerebral blood flow. Trace amounts of CO2 labeled with the positron-emitting radionuclide 15O were administered to 4 normal subjects at normo- and hypocapnia and to 2 of these subjects at hypercapnia. Hypocapnia typically caused a marked decrease in cerebral 15O activity, and hypercapnia a small increase in activity. The relative difference in the change in count rate in response to hypo- and hypercapnia is what one would expect if the activity represented bloow flow, according to a mathematical model which assumes the 15O label enters the brain as water of perfusion. The findings in this study suggest that the normal cerebral image obtained during continuous inhalation of C15O2 is related to cerebral blood flow, but in a non-linear fashion, and that the technique would be more sensitive to ischemic events than to hyperemic phenomena.
Migrainous cerebral infarction: a tomographic study of cerebral blood flow and oxygen extraction fraction with the oxygen-15 inhalation technique.
Authors: Bousser M G , Baron J C , Iba-Zizen M T , Comar D , Cabanis E , Castaigne P
Published: June 2011

A patient with migraine who had a permanent visual field defect was studied by angiography and CT scan. He also had a tomographic study of cerebral blood flow (CBF) and oxygen extraction fraction (EO2) using the non-invasive continuous oxygen-15 (15O) inhalation technique. Angiography was normal. CT scan revealed an area of decreased density with contrast enhancement suggestive of a recent infarct in the left occipital lobe. The 15O inhalation technique showed a decrease in CBF and EO2, typical of recent infarcts, in the corresponding area, an increase in CBF with normal EO2 in the left temporal lobe, and a decrease in CBF with increased EO2 in the right occipital cortex. These findings illustrate the unusual nature and extent of the ischemic process underlying migrainous cerebral infarction.
Computed tomography in patients presenting with lacunar syndromes.
Authors: Nelson R F , Pullicino P , Kendall B E , Marshall J
Published: June 2011

Of 312 stroke patients who had a CT scan, 37 had presented clinically with a lacunar syndrome. In 18 of the 37, lacunar sized infarcts were demonstrated on the scan, 13 had normal scans and in 6 large infarcts were found. Of these 6.5 and a pure motor hemiplegia and one a pure sensory stroke. Clinical evidence and angiography revealed a potential and treatable source of emboli in both the lacunar sized and the large infarcts. Two conclusions are drawn: a clinical lacunar syndrome may be associated with large infarct; demonstration of a lacunar infarct on CT scan does not exclude the need for angiography in appropriate cases to discover a possible source of emboli.
Production of various models of cerebral infarction in the dog by means of occlusion of intracranial trunk arteries.
Authors: Suzuki J , Yoshimoto T , Tnanka S , Sakamoto T
Published: June 2011

Using the dog, which has been believed unsuitable for research on brain infarction because of an extensive collateral cerebral circulation, we have succeeded in producing at will ischemic foci, as determined from post-occlusion carbon perfusion, in the thalamus, cerebral mantle or entire cerebral hemisphere. This has been achieved by occlusion of various combinations of cerebral vessels at the base of the brain. A unilateral temporal approach has been used in identifying and occluding all of the bilateral trunk arteries. The following models of cerebral infarction have been made: 1) unilateral or bilateral complete cerebral hemisphere infarction, 2) unilateral or bilateral cerebral mantle infarction, 3) unilateral or bilateral thalamic infarction, 4) unilateral hemispheric and contralateral cerebral mantle infarction, 5) unilateral cerebral mantle and contralateral thalamic infarction, and 6) unilateral complete cerebral hemisphere and contralateral cerebral mantle infarction. These models of infarction in the dog can be produced with a high degree of success, and the amount of infarction can be controlled by the duration of vessel occlusion. The pathophysiology of brain infarction and brain edema following recirculation can be hemodynamically, electroencephalographically and biochemically studied using these models of cerebral infarction.
Cerebral hemodynamic response to mental activation in normo- and hypercapnia.
Authors: Maximilian V A , Prohovnik I , Risberg J
Published: June 2011

Changes of regional cerebral blood flow from rest to mental activation by a visually presented spatial reasoning test were measured during normo- and hypercapnia in 10 healthy subjects. Hypercapnia, elicited by inhalation of 6% CO2, resulted in similar flow increases in all 32 cortical regions measured. Increases of flow during testing were seen in post-central regions of the brain whether the resting level was augmented by hypercapnia or not. The results show that an elevated local functional level in the cortex causes an automatic local vasodilatory response which is totally independent of the basal level of perfusion and availability of metabolic substrates.
Intracranial embolization via external carotid artery: report of a case with angiographic documentation.
Authors: Countee R W , Vijayanathan T
Published: June 2011

This report describes our experiences with a patient who developed delayed recurrent retinal and hemispheric ischemia distal to an old internal carotid artery occlusion in the neck. Fundoscopy and sequential cerebral arteriography documented that recurrent ischemic symptoms in this individual were the result of embolic fragments arising from the "stump" of the occluded internal carotid artery and from a diseased external carotid artery. These emboli traversed the external carotid artery and its orbital and intracranial anastomotic connections to reach the symptomatic eye and hemisphere. Ischemic symptoms in this patient were effectively terminated with anticoagulant therapy. We believe that this patient graphically documents that post-occlusion microembolism via the external carotid artery does indeed occur, and probably accounts for post-occlusion recurrent ischemic attacks more frequently than is currently appreciated. Recognition of this phenomenon is of importance because of its significant therapeutic implications. In these situations treatment modalities which terminate embolic phenomena would appear to have a more rational basis than do surgical procedures designed primarily to augment collateral blood flow to the symptomatic organ(s).