Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment.

Activated neutrophils releasing proteolytic enzymes and oxygen free radicals have been implicated in extending myocardial injury after myocardial infarction. Neutrophil elastase was used as a marker of neutrophil activation and the non-peroxide diene conjugate of linoleic acid was used as an indicator of free radical activity in 32 patients after acute myocardial infarction; 17 were treated by intravenous thrombolysis. Patients with acute myocardial infarction had higher plasma concentrations of neutrophil elastase and the non-peroxide diene conjugated isomer of linoleic acid than normal volunteers or patients with stable ischaemic heart disease. Patients treated by thrombolysis had an early peak of neutrophil elastase at eight hours while those who had not been treated by thrombolysis showed a later peak 40 hours after infarction. The plasma concentration of non-peroxide conjugated diene of linoleic acid was highest 16 hours after the infarction irrespective of treatment by thrombolysis. Quantitative imaging with single photon emission tomography showed decreased uptake of indium-111 labelled neutrophils in the infarcted myocardium (as judged from technetium-99m pyrophosphate) in those who had received thrombolysis, suggesting a decreased inflammatory response. The results indicate increased neutrophil activation and free radical production after myocardial infarction; they also suggest that thrombolysis does not amplify the inflammatory response and may indeed suppress it.     

Thrombolytic treatment in acute myocardial infarction: neutrophil activation, peripheral leucocyte responses, and myocardial injury.

OBJECTIVE--To examine early leucocyte responses and neutrophil activation in acute myocardial infarction treated by streptokinase and to relate the findings to coronary recanalisation and indices of myocardial damage in order to provide further information about the role of neutrophils in the evolution of injury. DESIGN--Group analysis of paired blood samples, obtained before streptokinase treatment and one hour after it, and of three indirect measures of myocardial injury: left ventricular ejection fraction, QRS score, and peak creatine kinase. SETTING--The coronary care unit of a district general hospital. PATIENTS--39 patients with acute myocardial infarction who underwent paired blood sampling (before streptokinase and one hour after streptokinase) and cardiac catheterisation 5 (3-8) days later. END POINTS--Changes in peripheral white cell and neutrophil counts and plasma elastase one hour after streptokinase infusion. Comparison of these variables in patients with and without patency of the infarct related coronary artery. Correlations between these variables and indirect measures of myocardial injury. RESULTS--Neutrophil activation, as reflected by plasma elastase, increased sharply one hour after streptokinase. Total white cell and neutrophil counts also increased. Changes tended to be more pronounced in patients with patency of the infarct related artery, though the trend was not statistically significant. Neutrophil activation before streptokinase was unrelated to indirect indices of myocardial injury but only one hour after streptokinase a weak negative correlation with left ventricular ejection fraction had developed. Peripheral neutrophil responses showed a similar relation to ejection fraction and also correlated with peak creatine kinase and QRS score. CONCLUSIONS--Thrombolytic treatment in acute myocardial infarction is associated with an abrupt reactive neutrophil response which provides an early measure of injury. It is also associated with neutrophil activation, probably in response to coronary recanalisation and myocardial reperfusion. Activated neutrophils are recognised as mediators of reperfusion injury in experimental infarction and the data in the present study provide preliminary evidence of a similar pathogenic role in the clinical setting.     

Thrombolytic treatment in acute myocardial infarction: neutrophil activation, peripheral leucocyte responses, and myocardial injury.

OBJECTIVE--To examine early leucocyte responses and neutrophil activation in acute myocardial infarction treated by streptokinase and to relate the findings to coronary recanalisation and indices of myocardial damage in order to provide further information about the role of neutrophils in the evolution of injury. DESIGN--Group analysis of paired blood samples, obtained before streptokinase treatment and one hour after it, and of three indirect measures of myocardial injury: left ventricular ejection fraction, QRS score, and peak creatine kinase. SETTING--The coronary care unit of a district general hospital. PATIENTS--39 patients with acute myocardial infarction who underwent paired blood sampling (before streptokinase and one hour after streptokinase) and cardiac catheterisation 5 (3-8) days later. END POINTS--Changes in peripheral white cell and neutrophil counts and plasma elastase one hour after streptokinase infusion. Comparison of these variables in patients with and without patency of the infarct related coronary artery. Correlations between these variables and indirect measures of myocardial injury. RESULTS--Neutrophil activation, as reflected by plasma elastase, increased sharply one hour after streptokinase. Total white cell and neutrophil counts also increased. Changes tended to be more pronounced in patients with patency of the infarct related artery, though the trend was not statistically significant. Neutrophil activation before streptokinase was unrelated to indirect indices of myocardial injury but only one hour after streptokinase a weak negative correlation with left ventricular ejection fraction had developed. Peripheral neutrophil responses showed a similar relation to ejection fraction and also correlated with peak creatine kinase and QRS score. CONCLUSIONS--Thrombolytic treatment in acute myocardial infarction is associated with an abrupt reactive neutrophil response which provides an early measure of injury. It is also associated with neutrophil activation, probably in response to coronary recanalisation and myocardial reperfusion. Activated neutrophils are recognised as mediators of reperfusion injury in experimental infarction and the data in the present study provide preliminary evidence of a similar pathogenic role in the clinical setting.     

Effect of cardiopulmonary bypass on circulating concentrations of leucocyte elastase and free radical activity

Circulating concentrations of leucocyte elastase and free radical activity were measured in 11 adults undergoing cardiopulmonary bypass. In all patients the bypass procedure was associated with pronounced changes in plasma elastase concentrations, and peak enzyme concentrations correlated closely with the duration of bypass (r = 0.91, p less than 0.001). Serial measurement of octadeca-9, 11-dienoic acid, a non-peroxide marker of free radical activity, showed significant changes only in the plasma free fatty acid fraction, suggesting a direct relation to the action of heparin rather than to the bypass procedure as such. These studies support the hypothesis that neutrophil activation plays a central role in the organ dysfunction that may complicate cardiopulmonary bypass and suggest that elastase release rather than free radical generation may be the appropriate marker of the event.     

Fibrin (ogen)-derived peptide B beta 30-43 is a sensitive marker of activated neutrophils during fibrinolytic-treated acute myocardial infarction in man.

Neutrophils, elastase, the specifically elastase-derived fibrin split product, B beta 30-43, and C-reactive protein were determined in 30 consecutive patients with acute myocardial infarction. At admission to the coronary care unit 4.2 +/- 0.8 hours after the onset of symptoms, all elements were increased above the reference levels, while compared with convalescent levels, only neutrophils and B beta 30-43 were increased. After the streptokinase treatment, neutrophils, elastase, and B beta 30-43 increased abruptly and peaked (p less than 0.0001) within 1.5 hours. Plasma creatine kinase MB and C-reactive protein reached their peak levels after about 12 and 24 hours, respectively. Peak indices of neutrophils and creatine kinase correlated (r = 0.60, p less than 0.0006). Compared with the age-matched reference range, the convalescent level of B beta 30-43 was increased (p less than 0.0001). Of the tested elements suggestive of neutrophil activation, B beta 30-43 showed signs of being the most sensitive. In keeping with animal studies, neutrophils are activated early during the course of acute myocardial infarction and their activation seems to become accelerated by fibrinolytic treatment. Neutrophils may remain activated in the convalescent phase.     

Platelet function and conjugated diene concentrations in diabetic and non-diabetic survivors of acute myocardial infarction.

STUDY OBJECTIVE--The aim was to compare platelet function in diabetic and non-diabetic survivors of acute myocardial infarction and to relate it to an index of free radical activity in these patients. DESIGN--In vivo and in vitro indices of platelet function and diene conjugate molar ratios were measured in diabetic and non-diabetic infarct survivors on admission to hospital and sequentially for 72 h. PATIENTS--The patients were 17 diabetics (age 61.9 years, range 32-74) and 12 non-diabetics (60.8 years, range 39-75) admitted to hospital with acute myocardial infarction confirmed according to WHO criteria. MEASUREMENTS AND MAIN RESULTS--Agonist induced platelet aggregation, beta thromboglobulin levels, and linoleic acid 18:2(9,11)/18:2(9,12) molar ratios did not differ between diabetic and non-diabetic patients on admission. Concentrations of adrenaline producing 50% maximum platelet aggregation (EC50) in whole blood on admission were lower than non-infarct controls in both patient groups. The EC50 values in platelet rich plasma in both groups fell during the 72 h following admission (increases in platelet sensitivity). beta Thromboglobulin concentrations fell following admission in the diabetic group. Diene conjugate molar ratios were higher at 12 h and 24 h compared to admission in diabetic patients. Increases in diene conjugate ratios between admission and 24 h correlated with peak aspartate transaminase levels in both patient groups. No correlations were observed between platelet aggregation, beta thromboglobulin levels, or diene conjugate molar ratios. CONCLUSIONS--During 72 h following myocardial infarction there is a reduction in platelet activation in vivo and an increase in platelet sensitivity to exogenous agonists in vitro. Free radical generated isomers of linoleic acid increase in relation to infarct size, but are unrelated to platelet function. There were no differences in platelet function between diabetic and non-diabetic subjects.     

Transient release of lipid peroxidation products as a non-invasive marker of successful reperfusion after thrombolysis for myocardial infarction.

OBJECTIVES--To evaluate an increase in plasma concentration of thiobarbituric acid reactive substances as a non-invasive biochemical test of reperfusion after thrombolysis and to investigate the relation between the inflammatory response after acute myocardial infarction and the production of the substances. METHODS--Venous samples were taken from 19 patients receiving thrombolysis for acute myocardial infarction before the start of therapy and every hour afterwards up to 5 hours and then at 24 and 48 hours and the concentration of thiobarbituric acid reactive substances measured. These substances are markers of lipid peroxidation induced by free oxygen radicals. Early reperfusion was judged by regression of ST elevation and late coronary artery patency from the results of coronary angiography 24-72 hours after thrombolysis. RESULTS--The concentration of thiobarbituric acid reactive substances increased in only 6 out of 14 patients with signs of early reperfusion. In patients with late coronary artery patency the corresponding number was 6 out of 15. However, a significant increase in the concentration of thiobarbituric acid reactive substances was found for the whole group 24 and 48 hours after treatment. The change in concentration in serum correlated significantly with that of C reactive protein--an acute phase reactant (r = 0.62, P < 0.01)--but not to the serum activities of markers of infarct size such as creatine kinase B and lactate dehydrogenase. CONCLUSIONS--The fluorimetric assay used in this study to measure the concentration of thiobarbituric acid reactive substances seems to be an insensitive method of detecting reperfusion after thrombolysis for myocardial infarction. The increase in concentrations found 24 and 48 hours after treatment correlated with C reactive protein concentrations but not with those of markers of infarct size.     

Neutrophil function in ischemic heart disease

Neutrophils contribute to the healing of and scar formation in myocardium after ischemic injury. Many recent studies indicate that neutrophils may be involved in the genesis and propagation of myocardial ischemia. To characterize neutrophil function in ischemic heart disease, neutrophil chemotaxis, leukotriene B4 (LTB4) generation, and elastase release in plasma were measured in 20 patients with stable angina, 17 patients with unstable angina or acute myocardial infarction (AMI), and 20 age-matched control subjects. Neutrophils from patients with stable angina exhibited markedly increased chemotactic activity and LTB4 generation as compared with the age-matched control subjects (p less than 0.01). Neutrophils of nine of 17 patients with unstable angina or AMI clumped spontaneously ex vivo and exhibited marked pseudopod formation and granule extrusion on electron microscopy. Subsequent chemotactic activity and LTB4 generation by neutrophils from these patients was less than in patients with stable angina, suggesting previous in vivo activation. Plasma levels of peptide B beta, a product of fibrin degradation by human neutrophil elastase, were approximately 15-fold higher (p less than 0.001) in patients with unstable angina or AMI (588 +/- 171 pmol/l, mean +/- SEM) compared with those in patients with stable angina (37 +/- 25 pmol/l) or control subjects (40 +/- 22 pmol/l), confirming intense in vivo neutrophil activation. Our study shows enhanced neutrophil function in patients with ischemic heart disease. The increased neutrophil chemotactic activity and LTB4 generation may be markers of stable angina pectoris. Intense neutrophil activation in unstable angina or AMI, as manifested by morphologic changes in neutrophils and elastase release, may relate to ongoing in vivo cellular activation.     

Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog

Accumulation of polymorphonuclear neutrophils during the acute inflammatory response may exacerbate tissue injury through the release of activated oxygen products or proteolytic enzymes or both. To assess the role of neutrophils in acute myocardial infarction, circulating neutrophil levels in dogs were reduced by 77 +/- 2% (mean +/- SEM) by administering rabbit antiserum to dog neutrophils. Acute myocardial infarction was induced in open-chest anesthetized dogs by 90 minutes of left circumflex coronary artery occlusion followed by 6 hours of reperfusion. Dogs treated with neutrophil antiserum (n = 8) developed myocardial infarcts that were an average of 43% smaller than infarcts in dogs treated with nonimmune rabbit serum (n = 7) (27.0 +/- 4.5% vs 47.1% +/- 7.5% of the area at risk, p less than 0.05). In a saline-treated control group (n = 8), infarct size was 48.0 +/- 4.7% of the area at risk, a value not significantly different from that of the nonimmune serum group but significantly greater than that in the neutrophil antiserum dogs (p less than 0.05). There were no major hemodynamic differences between groups. Histopathologic examination revealed that infarcted myocardium from dogs given saline or treated with nonimmune serum had a substantial neutrophilic infiltrate, which was virtually absent in infarcted tissue from dogs treated with neutrophil antiserum. These observations suggest that neutrophil accumulation in response to myocardial ischemia may be responsible for a substantial portion of the irreversible myocardial injury resulting from temporary coronary artery occlusion.     

Role of free radicals and neutrophils in canine myocardial reperfusion injury: myocardial salvage by a novel free radical scavenger, 2-octadecylascorbic acid

To define the role of oxygen free radicals and neutrophil involvement in evolving myocardial reperfusion injury, we evaluated the effect of 2-octadecylascorbic acid (CV-3611), a novel free radical scavenger, on neutrophil function and the extent of myocardial damage resulting from 90 min of ischaemia followed by 5 h of reperfusion in an experimental model of myocardial infarction. Dogs were randomly assigned to receive CV-3611 (5 mg.kg-1.[5 min]-1, intravenously) just before the onset of reperfusion. Infarct size, as a percent of area at risk, was reduced by 60% in CV-3611 treated group as compared with control, at 16.7(SEM 3.1)% v 41.5(4.5)%, p less than 0.01. Administration of CV-3611 markedly reduced function of neutrophils isolated from peripheral circulation during reperfusion ex vivo as estimated by free radical generation (ferricytochrome c reduction and luminol enhanced chemiluminescence), chemotactic activity, and aggregation induced by A23187. Under these conditions, the enhancement in neutrophil infiltration and free radical generation (luminol enhanced chemiluminescence) in myocardium within area at risk, especially in the border zone between viable and irreversible injured myocardium, was markedly reduced. Haemodynamic profiles were similar between control and CV-3611 treated group. These results suggest that activated neutrophils, especially their generation of oxygen free radicals, contribute to reperfusion induced myocardial injury.     

Pleiotropic effects of neutrophils on myocyte apoptosis and left ventricular remodeling during early volume overload

Most of the available evidence on the role of neutrophils on pathological cardiac remodeling has been pertained after acute myocardial infarction. However, whether neutrophils directly contribute to the pathogenesis of cardiac remodeling after events other than acute myocardial infarction remains unknown. Here we show that acute eccentric hypertrophy induced by aorto-caval fistula (ACF) in the rats induced an increase in the inflammatory response characterized by activation of the STAT pathway and increased infiltration of neutrophils in the myocardium. This early inflammation was associated with a decrease in interstitial collagen accumulation and an increase in myocyte apoptosis. Neutrophil infiltration blockade attenuated MMP activation, ECM degradation, and myocyte apoptosis induced by ACF at 24 hours and attenuated the development of eccentric hypertrophy induced by ACF at 2 and 3 weeks, suggesting a causal relationship between neutrophils and the ACF-induced cardiac remodeling. In contrast, sustained neutrophil depletion over 4 weeks resulted in adverse cardiac remodeling with further increase in cardiac dilatation and macrophage infiltration, but with no change in myocyte apoptosis level. These data support a functional role for neutrophils in MMP activation, ECM degradation, and myocyte apoptosis during eccentric cardiac hypertrophy and underscore the adverse effects of chronic anti-neutrophil therapy on cardiac remodeling induced by early volume overload.     

Thrombin Generation in Patients with Acute Myocardial Infarction Treated with Front-Loaded rt-PA and Recombinant Hirudin (HBW 023)

Thrombin contributes to the pathogenesis of acute myocardial infarction and reocclusion after thrombolysis. Thrombolytic therapy is known to induce a paradoxic increase in thrombin generation. Specific thrombin inhibition enhances thrombolytic therapy in experimental models. The aim of this study was to determine thrombin generation in patients with acute myocardial infarction treated with rt-PA and conjunctive therapy with the specific thrombin inhibitor, recombinant hirudin. Thrombin generation was determined in 17 patients with acute myocardial infarction treated with front-loaded rt-PA (100 mg/90 min) and conjunctive therapy with recombinant hirudin (HBW 023 bolus 0.4 mg/kg, infusion of 0.15 mg/kg/h) over 48 hours. Mean free hirudin plasma levels of 1320–1545 ng/mL produced a stable anticoagulation with mean aPTT values between 63 and 81 seconds throughout the treatment period. Thrombin generation increased during thrombolysis, indicated by a transient elevation of prothrombin fragment 1.2 levels, which were 3.0 nmol/L at baseline, 11.1 nmol/L after 30 minutes, 8.3 nmol/L after 60 minutes, 3.1 nmol/L after 12 hours, and 1.5 nmol/L after 24 hours, respectively. In contrast, thrombin-antithrombin III complex levels during and after thrombolysis did not exceed the baseline level of 21.8 ug/L. Thrombin-hirudin complex levels increased constantly during the 48-hour treatment period from 3.1 ug/L at baseline to 64.2 ug/L. All patients had an open infarct vessel (TIMI 2/3 potency) after 36–48 hours. Thrombolysis with rt-PA is associated with a significant increase in thrombin generation, which is not blocked by r-hirudin, whereas circulating thrombin seems to be effectively inhibited by r-hirudin.     

Plasma glucose on admission to hospital as a metabolic index of the severity of acute myocardial infarction

A pilot study was carried out in 22 non-diabetic patients admitted to hospital within 12 hours of acute myocardial infarction to assess the plasma glucose level on admission as an index of infarct size, morbidity and prognosis. Blood free fatty acid, insulin and potassium concentrations were also measured. Mean enzymatically measured infarct size index was three times larger (p less than 0.005) and the incidence of large infarcts was significantly greater (p less than 0.05) in patients with high (greater than 7.5 mMol/L) than in patients with low (less than 7.5 mMol/L) admission glucose concentrations. Patients in the former group also had higher mean peak free fatty acid concentrations (p less than 0.05). Patients who died within six months of their first infarcts had higher initial glucose values than those who survived longer. Plasma glucose concentrations measured within 12 hours of the onset of symptoms of acute myocardial infarction can be used to differentiate those with large from those with small infarcts in non-diabetic patients.     

Transient ST-elevation myocardial infarction: clinical course with intense medical therapy and early invasive approach, and comparison with persistent ST-elevation myocardial infarction

Patients presenting with ST-elevation myocardial infarction (STEMI), whose symptoms and electrocardiographic changes completely resolve upon admission and before the administration of reperfusion therapy, pose a therapeutic dilemma. The optimal management of this syndrome, termed here as transient STEMI (TSTEMI), has not yet been fully determined. We describe 69 prospectively recorded patients with TSTEMI, of which 63 patients (56.7 +/- 11 years, 48 men) were available for long-term follow-up out of 1244 consecutive patients with acute myocardial infarction (5%). Patients with TSTEMI treated with intravenous isosorbide dinitrate, aspirin, and clopidogrel, and/or with glycoprotein IIb/IIIa inhibitors were compared with a control group of matched patients with STEMI without resolution, who were treated conventionally. The time interval from symptom onset to presentation at the emergency department of patients with TSTEMI was 1.7 +/- 1.3 hours, and to first recording of ST elevations, 1.5 +/- 1.4 hours. Symptoms and electrocardiographic changes fully resolved 1.2 +/- 0.8 hours later, 1 hour after aspirin and nitrate administration. Coronary angiography, performed 36 +/- 39 hours (median, 24 hours) from admission, demonstrated no obstructive lesion or single-vessel obstructive disease in 43 patients (70%). Primary coronary intervention was performed in 48 patients (77%), and 8 patients (13%) were referred to surgery. Left ventricular ejection fraction was within normal limits, and peak creatine kinase was mildly elevated. Patients with TSTEMI had less extensive coronary artery disease (P < .038), better thrombolysis in myocardial infarction flow on angiography (P < .01), lower peak creatine kinase level (P < .001), higher left ventricular ejection fraction (P < .0001), and lower likelihood to sustain a second additional coronary event after index admission (P = .024) than patients with STEMI. Transient STEMI was associated with less myocardial damage, less extensive coronary artery disease, higher thrombolysis in myocardial infarction flow grade in culprit artery, and better cardiac function. These data suggest that immediate intense medical therapy with an early invasive approach is an appropriate therapy in patients with TSTEMI.     

Effect of the collateral circulation on myocardial salvage in patients with acute myocardial infarction]

The effects of the extent of coronary collateral circulations, the duration of myocardial ischemia and recanalization of infarct-related vessels on left ventricular function were evaluated in 43 patients with acute anteroseptal myocardial infarction. All patients had complete occlusions of their proximal left anterior descending coronary arteries and were treated with intra-coronary thrombolytic therapy within 8 hours after the onset of their chest pain. The 43 patients were categorized in 4 groups based on the extent of their coronary collaterals in the early period of myocardial infarction and the results of thrombolysis. Group A consisted of 11 patients with well-developed collaterals who had successful thrombolysis. Group B was comprised of 14 patients with poorly developed or no collaterals, and successful thrombolysis. In group C, there were 9 patients with well-developed collaterals and unsuccessful thrombolysis. In group D, there were 9 patients who had poorly or not developed collaterals, and all had unsuccessful thrombolysis. Four weeks after the intervention, ejection fraction (EF) and regional wall motion (RWM) were calculated from the data of the left ventricular angiograms. There was no significant difference in patients' age, sex, nor in peak serum creatine kinase among the 4 groups or the duration of myocardial ischemia between groups A and B. Patients with successful thrombolysis (groups A and B) had significantly higher EF and preserved RWM of infarct areas compared to patients with unsuccessful thrombolysis (groups C and D, p less than 0.05). Thirteen patients with early reperfusion (within 4 hours after the onset of chest pain) had significantly higher EF and better RWM than did 12 patients with late reperfusion and 18 patients with unsuccessful thrombolysis (p less than 0.01). However, there was no significant correlation between the duration of myocardial ischemia and RWM of the infarct areas among 25 patients who had successful thrombolysis (r = -0.3, NS). Patients in group A had higher EF and better RWM of infarct areas than did patients in groups B, C and D (p less than 0.01). In addition, 3 patients with well-developed collaterals had good RWM despite late reperfusion which occurred more than 4 hours after the onset of symptoms. These results suggest that the extent of coronary collaterals during the early period of myocardial infarction and the time delay from the onset of symptoms to the initiation of thrombolytic therapy are important factors for the salvage of left ventricular function in patients with myocardial infarction.     

The acute inflammatory response to myocardial infarction: imaging with indium-111 labelled autologous neutrophils

The uptake of indium-111 labelled neutrophils was examined in 30 patients with acute myocardial infarction by planar imaging and single photon emission computed tomography. The time from venepuncture to reinjection of the autologous labelled neutrophils was less than 2.5 hours and imaging was carried out 24 hours later. Twenty three patients had a positive uptake of neutrophils in the myocardium and imaging was improved by single photon emission computed tomography. There was a significant difference between the intervals from the onset of chest pain to injection of labelled neutrophils between patients with positive and negative images; early reinjection was more likely to produce a positive image. Indeed, all nine patients reinjected within 18 hours of the onset of symptoms had positive images. The results suggest that the stimulus for activation and migration of neutrophils is transient; this is an important factor if neutrophil release products play a role in cell damage after coronary occlusion.     

The acute inflammatory response to myocardial infarction: imaging with indium-111 labelled autologous neutrophils.

The uptake of indium-111 labelled neutrophils was examined in 30 patients with acute myocardial infarction by planar imaging and single photon emission computed tomography. The time from venepuncture to reinjection of the autologous labelled neutrophils was less than 2.5 hours and imaging was carried out 24 hours later. Twenty three patients had a positive uptake of neutrophils in the myocardium and imaging was improved by single photon emission computed tomography. There was a significant difference between the intervals from the onset of chest pain to injection of labelled neutrophils between patients with positive and negative images; early reinjection was more likely to produce a positive image. Indeed, all nine patients reinjected within 18 hours of the onset of symptoms had positive images. The results suggest that the stimulus for activation and migration of neutrophils is transient; this is an important factor if neutrophil release products play a role in cell damage after coronary occlusion.     

Evidence of increased platelet activation after thrombolysis in patients with acute myocardial infarction.

OBJECTIVE--To assess platelet activation after thrombolysis in patients with acute myocardial infarction. DESIGN--Platelet function was assessed by measurement of the in vivo synthesis of thromboxane by gas chromatography-mass spectrometry of thromboxane's major urinary metabolite, 2,3-dinor-thromboxane-B2. SETTING--Coronary care unit of Huddinge University Hospital. SUBJECTS--30 patients with acute myocardial infarction given either streptokinase 1.5 million units intravenously over one hour + 500 mg aspirin (n = 10), 500 mg aspirin (n = 10), or neither thrombolysis nor aspirin (n = 10). RESULTS--Patients treated by thrombolysis had a 20-fold increase in thromboxane formation during thrombolysis compared with control patients not treated by thrombolysis (p = 0.0001). Until two days after thrombolysis thromboxane production in patients treated with streptokinase did not decrease to a value comparable with patients treated with aspirin but not given thrombolysis. CONCLUSION--Thromboxane production increased considerably during thrombolysis, possibly reflecting greatly enhanced platelet activation. The slow decrease in thromboxane formation after treatment with aspirin suggests that the efficacy of thrombolysis might be improved by more efficient antiplatelet treatment.     

Plasma atrial natriuretic peptide in patients with acute myocardial infarction: effects of streptokinase

Plasma concentrations of immunoreactive atrial natriuretic peptide (mean (SEM] were measured in 135 patients admitted to two coronary care units with myocardial infarction, ischaemic chest pain, or non-ischaemic chest pain. Concentrations were significantly higher in patients with acute myocardial infarction not treated with systemic thrombolysis (60.4 (14.3) pg/ml) than in patients with non-ischaemic chest pain (21.1 (4.3) pg/ml). Patients with ischaemic chest pain had intermediate values (39.3 (7.1) pg/ml). Patients with acute myocardial infarction treated with intravenous streptokinase had normal concentrations of plasma atrial natriuretic peptide (20.2 (3.6) pg/mg), which were significantly lower than those in patients with myocardial infarction not given streptokinase. These changes could not be explained by factors such as age, pre-existing hypertension, renal dysfunction, or cardiac failure, nor treatment other than streptokinase. Raised plasma concentrations of atrial natriuretic peptide in acute myocardial infarction may be a homoeostatic response acting to reduce atrial pressures by natriuresis, diuresis, and venodilatation. The lower concentrations of atrial natriuretic peptide in patients with acute myocardial infarction treated with streptokinase may reflect a short term beneficial haemodynamic effect of streptokinase.     

Plasma atrial natriuretic peptide in patients with acute myocardial infarction: effects of streptokinase.

Plasma concentrations of immunoreactive atrial natriuretic peptide (mean (SEM] were measured in 135 patients admitted to two coronary care units with myocardial infarction, ischaemic chest pain, or non-ischaemic chest pain. Concentrations were significantly higher in patients with acute myocardial infarction not treated with systemic thrombolysis (60.4 (14.3) pg/ml) than in patients with non-ischaemic chest pain (21.1 (4.3) pg/ml). Patients with ischaemic chest pain had intermediate values (39.3 (7.1) pg/ml). Patients with acute myocardial infarction treated with intravenous streptokinase had normal concentrations of plasma atrial natriuretic peptide (20.2 (3.6) pg/mg), which were significantly lower than those in patients with myocardial infarction not given streptokinase. These changes could not be explained by factors such as age, pre-existing hypertension, renal dysfunction, or cardiac failure, nor treatment other than streptokinase. Raised plasma concentrations of atrial natriuretic peptide in acute myocardial infarction may be a homoeostatic response acting to reduce atrial pressures by natriuresis, diuresis, and venodilatation. The lower concentrations of atrial natriuretic peptide in patients with acute myocardial infarction treated with streptokinase may reflect a short term beneficial haemodynamic effect of streptokinase.