Changes of endothelin-1 and atrial natriuretic peptide during dobutamine stress echocardiography

The aim of this study was to test the hypothesis that plasma endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) concentrations in patients with ischemic heart disease are related either to myocardial ischemia or left ventricular (LV) dysfunction during dobutamine stress echocardiography. Plasma concentrations of ET-1 and ANP were measured in three patient groups. Group I (n = 21) patients had normal stress echocardiography and a resting LV ejection fraction (LVEF) of 40% or more. Group II (n = 32) had positive stress echocardiography and a resting LVEF of more than 40%. Group III (n = 18) had positive stress echocardiography with a resting LVEF of less than 40%. All three groups were subjected to thallium 201 scintigraphy and coronary angiography studies. The resting LV end-diastolic pressure was significantly higher in groups II and III than in Group I. The LVEF decreased significantly in group III compared to groups I and II. In the resting state, groups II and III had higher ET-1 concentrations than Group I (p = 0.021 and p = 0.039, respectively). The plasma ANP concentration was higher in group III than in groups I and II (p = 0.005 and p = 0.054, respectively). During peak dobutamine infusion, the ET-1 concentration dropped 8.7% from the baseline in group I, 10.2% in group II, and 10.5% in group III. The ANP concentrations were increased in all three groups but only the increase in Group II reached statistical significance. In conclusion, in patients with suspected ischemic heart disease, the concentrations of ET-1 and ANP may predict significant anatomic and functional coronary artery disease. However, ET-1 does not play a pathophysiologic role during an ischemic attack.     

Diagnostic concordance of telecytology and conventional cytology for evaluating breast aspirates

We examined the effect of a humanized anti-glycoprotein IIb/IIIa monoclonal antibody, YM337, on thrombolysis with tissue-type plasminogen activator in a copper coil-induced coronary thrombosis model in rhesus monkeys. Fifty minutes after the formation of an occlusive thrombus, a test drug was administered by either i.v. bolus injection followed by continuous infusion (YM337, 0.25 mg/kg + 1.5 microg/kg/min) or i.v. bolus injection (aspirin, 17 mg/kg). Sixty minutes after induction of the occlusive thrombus, thrombolysis was initiated with tPA at a total dose of 0.5 mg/kg intravenously administered over 60 min, with 10% given as an initial bolus. The median time to reperfusion was significantly shortened by YM337 [saline, 60 min (n = 5); aspirin, 45 min (n = 5); YM337, 30 min (n = 5)]. The incidence of reocclusion was significantly decreased by YM337 (saline, 4/4; aspirin, 5/5; YM337, 1/5), and the median time to reocclusion was significantly prolonged by YM337 [saline, 30 min (n = 4); aspirin, 30 min (n = 5); YM337, 180 min (n = 5)]. YM337 significantly reduced the thrombus protein content at the end of experiment. ADP-induced platelet aggregation was completely inhibited by YM337. These results suggest that YM337 may be of clinical value as an adjunctive agent in thrombolytic therapy for patients with acute myocardial infarction.     

Endothelin receptor subtypes and their functional relevance in human small coronary arteries

1. The potent constrictor peptide endothelin (ET) has been implicated in various cardiovascular disorders including myocardial infarction and atherosclerosis. We have investigated the nature of ET receptor subtypes present on human small coronary arteries. 2. Small coronary arteries were mounted in a wire-myograph for in vitro pharmacology. To investigate the ET receptor subtypes present in different segments of the coronary vascular tree, arteries were grouped according to internal diameter. Responses in arteries with small internal diameters (mean 316.7+/-7.9 microm; Group B) were compared to those in larger arteries (mean 586.2+/-23.1 microm; Group A). 3. ET-1 consistently and potently contracted arteries from Group A and B, with EC50 values of 1.7 (0.9-3.2) nM (n=15) and 2.3 (1.4-4.2) nM (n=14), respectively. No correlation was observed between ET-1 potency and internal diameter. The response to ET-1 was potently antagonized by the selective ET(A) receptor antagonist PD156707 in both Group A and Group B, yielding pA2 values of 8.60+/-0.12 (n=4-6) and 8.38+/-0.17 (n=4-6), respectively. Slopes from Schild regression were not significantly different from unity. 4. In contrast to ET-1, individual responses to ET-3 were variable. While all arteries from Group A responded to ET-3 (EC50 approximately 69 (23-210) nM) (n=12), no response was obtained in 5 of the 14 tested in Group B. Of those responding, many failed to reach a maximum at concentrations up to 1 microM. ET-1 was more potent than ET-3 in all arteries tested. A biphasic ET-3 response was observed in 8 arteries suggesting that a small ET(B) population was also present in some patients. The selective ET(B) receptor agonist sarafotoxin S6c had little or no effect up to 10 nM (n=4-6). 5. Responses to ET-1 and ET-3 were unaffected by removal of the endothelium in arteries from both groups suggesting a lack of functional, relaxant ET(B) receptors on endothelial cells (n=5). 6. Using autoradiography, specific high density binding of the non-selective, ET(A)/ET(B) ligand [125I]-ET-1 and selective ET(A) ligand [125I]-PD151242 was detected on the vascular smooth muscle layer of small intramyocardial coronary arteries (n=5). In contrast, little or no binding of the selective ET(B) receptor ligand [125I]-BQ3020 was observed (n=5). Similarly, [125I]-ET-1 binding to vascular smooth muscle was absent in the presence of the selective ET(A) receptor antagonist PD156707. 7. We conclude that human small epi- and intramyocardial coronary arteries express predominantly ET(A) receptors and it is these receptors which mediate ET-induced contractions. A constrictor ET(B) receptor population may exist in some patients. However, these receptors may have a limited role as contractions to ET-1 can be blocked fully by the selective ET(A) receptor antagonist PD156707.     

Angiographic evidence of hemorrhagic myocardial infarction after intracoronary thrombolysis with streptokinase

The reperfusion of acutely ischemic myocardium by intracoronary streptokinase thrombolysis is an exciting new therapy for acute myocardial infarction (MI). It appears that successful thrombolysis and reperfusion in the first few hours after acute coronary occlusion may salvage myocardium and possibly improve prognosis. A potential adverse effect of reperfusion is the production of hemorrhage in the area of myocardial necrosis. We report on a patient with prompt, successful coronary thrombolysis by streptokinase infusion who showed angiographic evidence of a hemorrhagic MI.     

Platelet GPIIb/IIIa receptor inhibition by SC-49992 prevents thrombosis and rethrombosis in the canine carotid artery

OBJECTIVE: Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptors represent the final common pathway for aggregation. GPIIb/IIIa inhibition with antibodies or RGD peptides prevents arterial thrombosis. The present study examined the ability of SC-49992 (SC), a GPIIb/IIIa receptor antagonist, to prevent thrombosis in a canine model of carotid artery thrombosis. METHODS: Both carotid arteries of anaesthetised dogs were instrumented with Doppler probes. A 300 microA current was applied to the intimal surface of the right carotid artery via an intraluminal electrode; time to occlusive thrombus formation was noted. SC (30 and 60 micrograms/.kg-1 x min-1, intravenously) or saline was infused for 240 min. The procedure for thrombus formation was repeated after 60 min of drug infusion for the left carotid artery. RESULTS: SC did not alter heart rate or blood pressure. Frequency of occlusive thrombus formation was reduced or prevented in a dose dependent manner (control = 100%, n = 12; SC 30 micrograms = 50%, n = 6; SC 60 micrograms = 0%, n = 6; p < 0.05). SC resulted in a reduction in thrombus weight (p < 0.05) v control. Ex vivo platelet aggregation to ADP and arachidonic acid was inhibited. Platelet reactivity remained inhibited 60 min after cessation of SC infusion. In a second group of animals, a carotid artery thrombus was formed and lysed with administration of anisoylated plasminogen streptokinase activator complex (0.05 U.kg-1). SC (60 micrograms.kg-1 x min-1, intravenously, n = 6) or saline (n = 6) was infused for 240 min. In dogs receiving saline there was an 83% rate of rethrombosis; none of the SC treated animals had reocclusion after recanalisation (p < 0.05). CONCLUSIONS: SC-49992 inhibits ex vivo platelet aggregation, prevents occlusive thrombus formation in a canine model of arterial thrombosis, and prevents rethrombosis after thrombolysis. The data are consistent with results obtained with murine monoclonal antibodies directed against the platelet GPIIb/IIIa receptor.     

Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE trial). Results of the feasibility phase

BACKGROUND: It has been demonstrated that therapeutic ultrasound effects ultrasound thrombolysis by selectively disrupting the fibrin matrix of the thrombus. This study was conducted to evaluate the clinical feasibility of percutaneous transluminal coronary ultrasound thrombolysis in acute myocardial infarction (AMI). METHODS AND RESULTS: Consecutive patients (n = 15) with evidence of anterior AMI and Thrombolysis in Myocardial Infarction (TIMI) grade 0 or 1 flow in the left anterior descending artery underwent coronary ultrasound thrombolysis. Angiographic follow-up was performed after 10 minutes and 12 to 24 hours. Ultrasound induced successful reperfusion (TIMI grade 3 flow) in 87% of the patients. Adjunct percutaneous transluminal coronary angioplasty (PTCA) after ultrasound thrombolysis produced a final residual stenosis of 20 +/- 12% as determined by quantitative coronary angiographic analysis. There were no adverse angiographic signs or clinical effects during the procedure. There was no change in the degree of flow in any of the patients at the 12- to 24-hour angiograms. During hospitalization, 1 patient had recurrent ischemia on the fifth day after the procedure, and emergent catheterization revealed occlusion at the treatment site. The patient was successfully treated with PTCA. CONCLUSIONS: These results suggest that ultrasound thrombolysis has the potential to be a safe and effective catheter-based therapeutic modality in reperfusion therapy for patients with AMI and other clinical conditions associated with intracoronary thrombosis.     

Recombinant lys-plasminogen given before, but not after, recombinant tissue-type plasminogen activator markedly improves coronary thrombolysis in dogs: relationship of thrombolytic efficacy with parameters of fibrinolysis

Recombinant tissue-type plasminogen activator (rt-PA) administration rapidly restores blood flow in thrombosed coronary arteries, but coronary arteries often reocclude after initial thrombolysis. This occurs because of the short half-life of rt-PA and rapid increase in plasminogen activator inhibitor (PAI-1) and alpha2-antiplasmin levels in plasma. We hypothesized that administration of lys-plasminogen, which binds to fibrin with 10 times greater affinity and results in a loose fibrin structure (as compared with native glu-plasminogen), before rt-PA would enhance the thrombolytic efficacy of rt-PA and modulate parameters of fibrinolysis. To examine this hypothesis, dogs with electrically induced stable thrombus in the left anterior descending coronary artery (LAD) were treated with saline (group A, n = 9) or lys-plasminogen (group B, 2 mg/kg, n = 5), followed 10 min later by rt-PA (1 mg/kg in 20 min). Four other dogs with occlusive LAD thrombus were first given rt-PA, followed by lys-plasminogen (2 mg/kg) 50 min later (group C). Lys-plasminogen given before rt-PA restored flow in all dogs in 14 +/- 4 min (vs. 22 +/- 9 min in group A, p < 0.05), continuing > 2 h (vs. 41 +/- 15 min in group A, p < 0.02). Lys-plasminogen given after rt-PA did not potentiate the effect of rt-PA. Plasma t-PA antigen concentrations were highest in group B dogs at 2 h after rt-PA infusion. PAI-1 and alpha2-antiplasmin plasma levels were suppressed in all dogs receiving lys-plasminogen whether it was given before or after rt-PA. Therefore, lys-plasminogen given before rt-PA markedly potentiates the effect of rt-PA and alters the parameters of fibrinolysis. In contrast, lys-plasminogen given after rt-PA does not influence the thrombolytic effect of rt-PA, whereas it suppresses PAI-1 and alpha2-antiplasmin levels in plasma. This study also suggests that binding of plasminogen to the clot is more important than the plasma levels of PAI-1 and alpha2-antiplasmin.     

Effects of endothelin-3 on water and sodium excretion during extracellular volume expansion

The aim of the present study was to elucidate the role of an IV dose of endothelin-3 (ET-3) (5 ng Kg-1 min-1) on mean arterial pressure (MAP), on diuresis and natriuresis in control and in volume expanded anesthetized rats. A systemic infusion of ET-3 in normal rats (Group I) increased MAP and produced a trend of increasing diuresis, without changes in natriuresis. A 10% body weight expansion (Group II) increased diuresis and natriuresis without changes in MAP. The simultaneous infusion of ET-3 and expansion with saline (Group III) resulted in an increase in MAP, an enhanced diuretic response, and a natriuresis of similar magnitude to that observed in Group II. These results suggest that the diuresis produced by a low dose of exogenous ET-3 in control rats, is independent of sodium excretion. Furthermore, the enhanced diuresis caused by ET-3 during expansion is greater than the addition of ET-3 and expansion effects, suggesting that new mechanisms are triggered in order to maintain volume and salt homeostasis in this state.     

Inhibition of arterial thrombosis by recombinant annexin V in a rabbit carotid artery injury model

BACKGROUND: The procoagulant effect of anionic phospholipid may play a major role in the development of arterial thrombosis. METHODS AND RESULTS: Annexin V, a calcium-dependent anionic-phospholipid-binding protein, was expressed and isolated from Escherichia coli and its antithrombotic effect examined in a rabbit carotid artery thrombosis model. A partially occlusive thrombus was formed in the left carotid artery by application of electric current to produce an approximately 50% occlusion of the lumen. After the current was discontinued, flow ceased completely within 42+/-12 minutes (n=6) because of continuing platelet/fibrin thrombus formation. When annexin V was given at doses of 2.8 to 16.6 microg x kg(-1) x min(-1) for a period of 180 minutes, starting at the time the current was stopped, there was a dose-dependent inhibition of thrombus formation. At a dose of 5.6 microg x kg(-1) x min(-1), blood flow remained patent throughout the infusion and for an additional 60 minutes after the infusion was stopped. In addition, there was a decrease in thrombus weight (16+/-7.4 versus 2.0+/-1.0 g), (125)I-fibrin deposition (approximately 45% reduction, P<.001), and (111)In-labeled platelet accumulation (approximately 43% reduction, P<.001). Prior mixing of annexin V with phosphatidylserine micelles abolished the antithrombotic effect of annexin V, whereas mixing with phosphatidylcholine micelles had no effect. The antithrombotic effect of annexin V was not associated with bleeding tendency, as judged by the amount of blood absorbed in a gauze pad placed in a surgical incision extending to the muscle tissue and by the standard template bleeding time. CONCLUSIONS: These observations support a potentially important role for anionic phospholipid exposure in platelets in arterial thrombosis, and inhibition of this activity could be a novel target for therapy in coronary thrombosis and stroke and after angioplasty.     

Erwin Payr, Hans von Haberer, Ernst Jeger--a set of 3 stars in the universe of vascular surgery]

BACKGROUND: Previous studies have demonstrated the prognostic value of radionuclide ventriculography at rest and exercise in patients post myocardial infarction (MI). The number of studies in patients treated with modern reperfusion techniques, including thrombolysis or primary angioplasty, however, is limited. HYPOTHESIS: The aim of this study was to evaluate the prognostic significance of predischarge radionuclide ventriculography at rest and exercise in patients with acute MI treated with thrombolysis or primary angioplasty. METHODS: A total of 272 consecutive patients with acute MI who were randomized to thrombolysis or primary coronary angioplasty underwent predischarge resting and exercise radionuclide ventriculography. Left ventricular ejection fraction at rest, decrease in ejection fraction during exercise > 5 units below the resting value, angina pectoris, ST-segment depression, and exercise test ineligibility were related to subsequent cardiac events (cardiac death, nonfatal reinfarction) during follow-up. RESULTS: During a mean follow-up of 30 +/- 10 months, cardiac death occurred in 11 (4%) patients and nonfatal reinfarction in 14 (5%) patients. Resting left ventricular ejection fraction was the major risk factor for cardiac death. In patients with an ejection fraction < 40%, cardiac death occurred in 16% compared with 2% in those with an ejection fraction > or = 40% (p = 0.0004). In addition, cardiac death tended to be higher in patients ineligible than in those eligible for exercise testing (11 vs. 3%, p = 0.08). None of the other exercise variables (decrease in ejection fraction during exercise > 5 units below the resting value, angina pectoris or ST-segment depression) were predictive for cardiac death. When all exercise test variables in each patient were combined and expressed as a risk score, a low risk (n = 185) and a higher risk (n = 87) group of patients could be identified, with cardiac death occurring in 1 and 10%, respectively. As the predictive accuracy of a negative test was high, radionuclide ventriculography was of particular value in identifying patients at low risk for cardiac death. Radionuclide ventriculography was not able to predict recurrent nonfatal MI. CONCLUSION: In patients with MI treated with thrombolysis or primary angioplasty, radionuclide ventriculography may be helpful in identifying patients at low risk for subsequent cardiac death. In this respect, left ventricular ejection fraction at rest was the major determinant. Variables reflecting residual myocardial ischemia were of limited prognostic value. Identification of a large number of patients at low risk allows selective use of medical resources during follow-up in this subgroup and has significant implications for the cost effectiveness of reperfusion therapies.     

Value of T-wave direction with lead III ST-segment depression in acute anterior wall myocardial infarction: electrocardiographic prediction of a "wrapped" left anterior descending artery

BACKGROUND: Lead III ST-segment depression during acute anterior wall myocardial infarction (AMI) has been attributed to reciprocal changes. However, the value of the T-wave direction (positive or negative) in predicting the site of obstruction and type of the left anterior descending (LAD) artery is not clear and has not been studied before. HYPOTHESIS: The aim of the study was to assess retrospectively the correlation between two patterns of lead III ST-segment depression, and type of LAD artery and its level of obstruction during first AMI. METHODS: The study group consisted of 48 consecutive patients, admitted to the coronary care unit for first AMI, who showed ST-segment elevation in lead a VL and ST-segment depression in lead III on admission 12-lead electrocardiogram. The patients were divided by T-wave direction into Group 1 (n = 31), negative T wave, and Group 2 (n = 17), positive T wave. The coronary angiogram was evaluated for type of LAD ("wrapped", i.e., surrounding the apex or not), site of obstruction (pre- or postdiagonal branch), and other significant coronary artery obstructions. RESULTS: Mean lead III ST-segment depression was 1.99 +/- 1.32 mm in Group 1 and 1.13 +/- 0.74 mm in Group 2 (p = 0.004); mean ST-segment elevation in a VL was 1.35 +/- 0.84 mm and 1.23 +/- 0.5 mm, respectively (p = 0.5). A wrapped LAD was found in 12 patients (38.7%) in Group 1 and in 13 in Group 2 (76.4%) (p = 0.02). The sensitivity of lead III ST-segment depression with positive T wave to predict a wrapped LAD was 52%, and the specificity was 82% with a positive predictive value of 76%. On angiography, 25 patients (80%) in Group 1 and 13 (76%) in Group 2 had prediagonal occlusion of the LAD (p = 0.77). No significant difference between groups was found for right and circumflex coronary artery involvement or incidence of multivessel disease. CONCLUSIONS: The presence of lead III ST-segment depression with positive T wave associated with ST-segment elevation in a VL in the early course of AMI can serve as an early electrocardiographic marker of prediagonal occlusion of a "wrapped" LAD.     

Therapeutic time window for the 21-aminosteroid, U-74389G, in global cerebral ischemia

A novel 21-aminosteroid (U-74389G), a new potent antioxidant, was evaluated for its protective effect on transient global cerebral ischemia. Ischemia was induced by 20 minutes of four-vessel occlusion in adult male Wistar rats. Injection of 21-aminosteroid (U-74389G, 5 mg/kg intraperitoneally injected) was repeated three times. The second injection was performed 30 minutes after the first injection, and the third injection was performed 210 minutes after that. Experimental animals were divided into five groups according to the time drug administration was initiated. Group I (n = 8) began vehicle administration 30 minutes before occlusion. Group II (n = 9) started 21-aminosteroid administration 30 minutes before occlusion. Drug administration in Group III (n = 9) began at the time of reperfusion, in Group IV (n = 8), 30 minutes after reperfusion, and in Group V (n = 6), 60 minutes after reperfusion. Animals in the control group (n = 5) underwent sham operations. One week after ischemia, the number of viable pyramidal neurons was counted in the hippocampal CA1 subfield. The results were as follows: the number of living neurons in Group I was 18.8 +/- 8.7; in Group II, was 44.7 +/- 9.5; in Group III, was 46.4 +/- 9.4; in Group IV, was 40.3 +/- 6.6; in Group V, was 10.2 +/- 2.5; and in the control group was 131 +/- 3.3. Groups II, III, and IV demonstrated significantly higher numbers of living neurons compared with Group I (P < 0.05). The present study revealed that U-74389G attenuated delayed neuronal death in global cerebral ischemia when it was administered before or soon after the ischemic episode.     

Selective inhibition of factor Xa is more efficient than factor VIIa-tissue factor complex blockade at facilitating coronary thrombolysis in the canine model

OBJECTIVES: We determined the effect of adjunctive inhibition of the extrinsic coagulation pathway by factor VIIa-tissue factor complex inhibitors, DEGR VIIa and tissue factor pathway inhibitor (TFPI), and the selective factor Xa inhibitor, tick anticoagulant peptide (TAP), after thrombolytic therapy with tissue-type plasminogen activator (t-PA) in a canine model of electrically induced coronary thrombosis. BACKGROUND: Ongoing thrombin generation is considered an important component of the heightened thrombin activity associated with thrombolytic therapy and may be responsible for reperfusion failure and reocclusion. METHODS: Forty-two dogs with electrically induced coronary thrombus undergoing thrombolysis with t-PA (1 mg/kg over 20 min) were randomly assigned to one of the following adjunctive regimens: TAP (30 micrograms/kg body weight per min for 90 min, n = 10); TFPI (100 to 150 micrograms/kg per min for 90 min, n = 10); DEGR VIIa (1- to 2-mg/kg bolus, n = 10) and saline control (n = 12). The dogs were observed for 120 min after thrombolysis for reocclusion. RESULTS: All three active study agents accelerated the time to reperfusion by an average of 12 min (all p < 0.05). Duration of reflow was greatest with TAP (117 +/- 8 min, p < 0.05 compared with saline control), whereas DEGR VIIa and TFPI did not prolong the duration of reflow. Reocclusion rates were similar among control, DEGR VIIa and TFPI groups (70%, 78% and 67%, respectively). Tick anticoagulant peptide reduced the occurrence of reocclusion (0%, p < 0.05 compared with saline control). CONCLUSIONS: In this experimental model, during systematic blockade of various extrinsic coagulation pathway proteins, we demonstrated that whereas acceleration of thrombolysis occurs with factor VIIa-tissue factor complex inhibition, optimal enhancement of thrombolysis was achieved through specific factor Xa blockade.     

Increased immunoreactive endothelin-1 in human transplant coronary artery disease

BACKGROUND: The pathogenesis of transplant coronary artery disease (TCAD) is unknown, but it is thought to derive from an interaction between immune and nonimmune factors, leading to smooth muscle cell proliferation and accumulation in the expanded neointima. Endothelin-1 (ET-1), a potent vasoconstrictor with mitogenic properties for vascular smooth muscle cells, has recently been demonstrated in native vessel atherosclerosis. The present study used immunohistochemistry to investigate the role of ET-1 in TCAD. METHODS AND RESULTS: ET-1 immunoreactivity and cellular localization were assessed in human coronary arteries with TCAD (n = 13) and in normal coronary arteries (n = 10) with single- and double-label immunohistochemistry. The intensity of immunostaining was determined by a semiquantitative method. Diffuse and intense ET-1 immunoreactivity was found in 11 of 13 patients with TCAD (85%), mainly in myointimal cells and, in lesser amounts, in macrophages and endothelial cells. In contrast, normal coronary arteries had only faint immunostaining localized to the endothelial layer. Mean semiquantitative grade was significantly higher in TCAD than in normal arteries (1.8 versus 0.7; P < .05). ET-1 was more frequently present in lipid-rich, atheromatous lesions than in lipid-poor, proliferative ones. Intimal neovessels consistently immunostained for ET-1. CONCLUSIONS: Immunoreactivity for ET-1 is significantly increased in TCAD, possibly as a result of stimulatory cytokines and growth factors that are upregulated in the posttransplant state. The results suggest a role for this mitogenic peptide in the pathogenesis of graft arteriosclerosis.     

School performance at nine years of age in very premature and very low birth weight infants: perinatal risk factors and predictors at five years of age. Collaborative Project on Preterm and Small for Gestational Age (POPS) Infants in The Netherlands

Continuous measurement of blood flow velocity during interventional procedures has the potential to provide an early warning of coronary flow instability, which can lead to abrupt closure or other adverse events before angiography. The magnitude and fluctuations of the average velocity over time (trend) was studied by using a 0.018-inch Doppler-tipped angioplasty guide wire in 32 patients after coronary angiography (n = 20), atherectomy (n = 2), urgent stent (n = 6), urgent vein graft thrombolysis (n = 4), or acute myocardial infarction (n = 2). The patients (mean age 60 +/- 11 years) had postprocedural in-laboratory flow monitoring for a mean of 19 +/- 11 (range 8 to 36) minutes. The coronary artery monitored was the left anterior descending in 13, circumflex in 6, right coronary artery in 9, and saphenous vein graft in 4. Seven patients had flow-related events during continuous flow velocity monitoring before serial angiographic study. These events included coronary vasospasm (abrupt flow acceleration), vasovagal flow cessation, cyclical flow variations resulting from accumulation of intraluminal thrombus, and rapid decline of flow velocity. The last two patterns were associated with abrupt vessel closure during angioplasty. Continuous flow velocity monitoring is easily incorporated into routine interventional procedures and provides an early indication of unstable flow and the potential for abrupt vessel closure and other adverse events.     

Histopathologic features in atherectomy samples obtained from patient with unstable angina, stable angina and restenosis. Directional Atherectomy Lombardi Group

BACKGROUND: The present study was aimed at investigating the pathologic features of directional coronary atherectomy (DCA) samples obtained from 194 patients (14 females) with stable (n = 68) and unstable (n = 95) angina, and with restenosis (n = 27). METHODS: DCA samples were obtained from culprit lesions, using the Simpson technique. Unstable angina was classified according to E. Braunwald criteria. Stable angina was grouped according to the presence or absence of a prior myocardial infarction (MI). DCA samples were fixed, processed, serially cut and stained with hematoxilin-eosin and with Movat pentachrome stain. RESULTS: The major pathologic findings were thrombosis, inflammation of the superficial plaque layers, and neointimal hyperplasia which often coexisted within a same sample. Their frequencies, in that order, were distributed in the differing groups of patients as follows: 21% (n = 9), 29.2% (n = 12) and 51% (n = 21) of the 41 cases with stable angina without prior MI. 40.7% (n = 11), 40.7% (n = 11), and 51.8% (n = 14) of the 27 cases with stable angina with prior MI. 25% (n = 4), 56.2% (n = 9) and 68.7% (n = 11), of the 16 cases with BI unstable angina. 35.3% (n = 14), 55.8% (n = 19) and 44% (n = 15), of the 34 cases with BII unstable angina. 44.4% (n = 4), 33.3% (n = 3) and 33.3% (n = 3), of the 9 cases with BIII unstable angina. 48.2% (n = 14), 48.2% (n = 14) and 51.8% (n = 15), of the 29 cases with CII unstable angina at 35.8 days after MI. 60% (n = 3), 60% (n = 3) and 40% (n = 2), of the 5 cases with CIII unstable angina at 8.3 days after MI. 26% (n = 7), 48% (n = 13) and 85.1% (n = 23), of the 27 cases with restenosis. According to above observation, the frequency of coronary thrombosis increases with the increase of the severity of myocardial ischemia. However, thrombosis is not found in most unstable angina without prior MI (63% of BI-II-III unstable angina cases do not have thrombus). In addition, thrombus is not a specific finding of unstable angina, given its occurrence, although in a much lower percentage of cases, in stable angina and in restenosis. CONCLUSIONS: Present data show that different ischemic and plaque lesions. This observation questions on the pathogenetic role of thrombus in unstable angina and calls for further investigations on inflammation and neointimal hyperplasia, as well as on the the reciprocal relation between these findings which are often combined within a same lesion.     

Regional wall motion changes with dobutamine as a pharmacological stress test during cardiac catheterization in patients with significant coronary artery disease

BACKGROUND: Preliminary study to test the feasibility of pharmacological stress testing during cardiac catheterization, thus combining anatomical and functional information. PATIENTS AND METHODS: 21 consecutive patients with known or suspected coronary artery disease, referred for diagnostic catheterization. Biplane ventriculography was performed before and during dobutamine infusion. The patients were subdivided into 3 groups: Group I (n = 11, 52%) with at least one territory supplied by a significantly stenosed coronary artery and showing normal resting regional wall motion. Group II (n = 6, 29%) patients in whom the affected vessel(s) supplied exclusively a territory with regional wall motion abnormalities at rest. Group III (n = 4, 19%) had no significant coronary artery disease and served as control. RESULTS: In group I, 9/11 (82%) patients and in group II, 3/6 (50%) patients showed either ischemia or viability reactions or both after dobutamine stress. Overall, substantial functional information was gathered in 12/17 patients (71%). Control patients showed no worsening of regional wall motion under dobutamine. Neither global left ventricular ejection fraction nor left ventricular end diastolic pressure were as accurate in detecting ischemia as regional wall motion analysis. In patients who had only ischemia and no viability reaction as judged by regional wall motion analysis, ejection fraction fell significantly in 4/6 (67%) patients; end diastolic pressure on the other hand rose significantly in 3/6 (50%). CONCLUSIONS: Dobutamine stress testing performed during cardiac catheterization is convenient, feasible and safe and yields clinically useful information in a high percentage (71%) of patients with significant coronary artery disease. Further experience is needed to evaluate the sensitivity, specificity and predictive value of this new approach.     

8-epi PGF2 alpha generation during coronary reperfusion. A potential quantitative marker of oxidant stress in vivo

BACKGROUND: Myocardial reperfusion is believed to be associated with free radical injury. However, indexes of oxidative stress in vivo have been limited by their poor specificity and sensitivity. Isoprostanes are stable products of arachidonic acid formed in a nonenzymatic, free radical-catalyzed manner. We have developed a sensitive and specific assay for one of these compounds, 8-epi prostaglandin (PG) F2 alpha. METHODS AND RESULTS: To address its utility as an index of oxidative stress during coronary reperfusion, we measured urinary levels by gas chromatography/mass spectrometry in a canine model of coronary thrombolysis, in patients with acute myocardial infarction treated with thrombolytic therapy, and in patients after elective coronary artery bypass surgery. Urinary 8-epi PGF2 alpha was unchanged after circumflex artery occlusion in a canine model of coronary thrombolysis (n = 13; 437.2 +/- 56.4 versus 432.7 +/- 55.2 pmol/mmol creatinine) but increased significantly (P < .05) immediately after reperfusion (553.8 +/- 64.7 pmol/mmol). Urinary levels were increased (P < .001) in patients (n = 12) with acute myocardial infarction given lytic therapy (265.8 +/- 40.8 pmol/mmol) compared with age-matched control subjects (n = 20; 91.5 +/- 11.8 pmol/mmol) and patients with stable coronary disease (n = 20; 95.7 +/- 6.3 pmol/mmol). Preoperative levels rose from 113.2 +/- 11.8 to 248.2 +/- 86.3 pmol/mmol at 30 minutes into revascularization to 332.2 +/- 82.6 pmol/mmol by 15 minutes after global myocardial reperfusion (P < .05) and dropped to 181.2 +/- 50.4 pmol/mmol at 30 minutes and 120.2 +/- 9.9 pmol/mmol at 24 hours after bypass surgery (n = 5). Corresponding changes in spin adduct formation, found with electron paramagnetic resonance, were noted in 2 patients. CONCLUSIONS: These data support the hypothesis that free radical generation occurs during myocardial reperfusion. Measurement of isoprostane production may serve as a noninvasive index of oxidative stress.     

Thrombolysis following myocardial infarct. European Secondary Prevention Study

For evaluation of the management of patients with acute myocardial infarction, all cases of ten Zurich hospitals (278, 184 men and 94 women) in the period from 1 January to 31 March 1993 were analyzed retrospectively. 223 patients were released from hospital, 55 died. A follow-up was done 6 months after the patient's discharge by means of a questionnaires to the family doctor (return rate: 65.9%). 48.5% of patients were referred to hospital within the first 6 h. after onset of symptoms, 64% within the first 12 h. 28% (n = 76) of the patients received a thrombolytic therapy, of which 91% (n = 69) got streptokinase and 9% (n = 7) got tissue plasminogen activator. In 81% of the cases the thrombolytic therapy was done within the first hour in hospital, in accumulated 97% of the cases within two hours. In the age group under 65 years (39% of the patients, n = 109), 48 patients received thrombolysis (odds ratio [OR] = 1.0). In the age group between 65 and 74 years (24.5 % of the patients, n = 68), 19 patients received thrombolysis (OR: 0.49; 95% CI: 0.42-0.99; p < 0.05), and in the age group over 74 years (36.5% of the patients, n = 101), 9 patients were received thrombolysis (OR: 0.12; 95% CI: 0.05-0.28; p < 0.0001). 31% of the patients (n = 46) received a coronary angiography, 15% (n = 22) had coronary angioplasty, and 11% (n = 1) received coronary bypass surgery. There is evidence that there should be more importance attached to early hospitalization, if acute myocardial infarction is suspected. Thereby age alone should be considered as a contraindication for thrombolytic therapy. The issue of assumed underuse of thrombolytic therapy should be investigated all over Switzerland.     

Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation is dependent on donor age but not gender

OBJECTIVE: To describe the clinical features of patients with occlusive disease of the proximal (V1) segment of the vertebral artery. DESIGN AND PATIENTS: Patients with either occlusion or high-grade stenosis involving the V1 segment were chosen for study from the New England Medical Center Posterior Circulation Registry. The registry is a consecutive series of patients with signs and symptoms of posterior circulation ischemia seen at the New England Medical Center, Boston, Mass, during a 10-year period. Clinical features, radiographic findings, and patient outcome were reviewed. RESULTS: Of the 407 patients in the registry, 80 (20%) had V1 segment lesions. Patients could be classified into 5 groups: (1) V1 disease and coexistent severe intracranial occlusive disease of the posterior circulation (n=22); (2) V1 disease with evidence of artery-to-artery embolism (n=19); (3) suspected V1 disease with artery-to-artery embolism, but with other potential causes of stroke or less certain vascular diagnosis (n=20); (4) V1 disease associated with hemodynamic transient ischemic attacks (n=13); and (5) proximal vertebral arterial dissection (n=6). Hypertension, cigarette smoking, and coronary artery disease were common risk factors. Clinical features, location of infarct, and outcome differed between groups and reflected the presumed mechanisms of stroke. CONCLUSIONS: Occlusive disease involving the V1 segment of the vertebral artery is common in patients with posterior circulation ischemia, but is often associated with other potential mechanisms of stroke. However, in a series of patients seen at a tertiary referral center, occlusive disease of the V1 segment was the primary mechanism of ischemia in 9% of patients.