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Biomedical subjects

G Montalescot

Publications and source records attributed to G Montalescot.

At least 19 recordsLinked to original sources
PubMed1995

Fibrinogen after coronary angioplasty as a risk factor for restenosis.

BACKGROUND: Fibrinogen is a risk factor for cardiovascular disease and is related to the severity of coronary atherosclerosis. Its role in restenosis after coronary angioplasty remains unknown. Although platelets and thrombosis contribute to the pathogenesis of restenosis, few clinical data are available concerning the relations between restenosis and proteins of the coagulation and fibrinolytic systems. METHODS AND RESULTS: In 107 consecutive patients undergoing coronary angioplasty, we measured plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, and fibrinogen before and immediately after angioplasty and at a 6-month follow-up. The individual changes of intraluminal diameter were measured by quantitative coronary angiography, and patients were classified according to four definitions of restenosis: (1) a final stenosis > 50%, (2) a loss of minimal luminal diameter during the follow-up period greater than the measurement variability in our laboratory (> 0.52 mm), (3) a loss of at least 50% of the gain in luminal diameter achieved by angioplasty, and (4) the combination of definitions 1 and 2. The relations between coagulation variables and each definition of restenosis were assessed univariately; then with the clinical variables included, the relations were analyzed multivariately. Angiographic follow-up was obtained in 92% of patients with a primary success of angioplasty. Global restenosis rates were 38%, 43%, 48%, and 30% for definitions 1 through 4, respectively. Plasma levels of t-PA antigen and PAI-1 antigen were not associated with any of the four definitions of restenosis. Multivariate analysis demonstrated that von Willebrand factor measured immediately after angioplasty predicted restenosis according to definitions 2 and 3. Fibrinogen measured within 6 months of follow-up was significantly increased in all restenosis groups of the four definitions. Patients with a fibrinogen concentration > 3.5 g/L at follow-up had higher restenosis rates than patients with a concentration < 3.5 g/L: 55% versus 22% (P = .001), 68% versus 31% (P = .002), 63% versus 37% (P = .01), and 74% versus 26% (P = .002) for definitions 1 through 4, respectively. The loss index was lower (P = .003) and the net gain higher (P = .03) in patients with a fibrinogen level < 3.5 g/L. There was a significant correlation between fibrinogen level and angiographic loss index (r = .41; P < .0001). Multivariate analysis confirmed that the fibrinogen level predicted restenosis with all definitions. CONCLUSIONS: An independent relation exists between von Willebrand factor measured immediately after angioplasty and restenosis defined by the degree of intraluminal renarrowing. An elevated fibrinogen level during follow-up is a strong biochemical predictor of restenosis. Therefore, fibrinogen should be considered at least as an independent marker of restenosis and perhaps as a common risk factor for both spontaneous coronary atherosclerosis and postangioplasty restenosis, which is an accelerated form of atherosclerosis.

Angioplasty, Balloon, Coronary↗
PubMed1995

[Use of aspirin in coronary disease].

The beneficial effect of aspirin in different situations of coronary artery disease has been clearly demonstrated, but prescription remains empirical due to the lack of phase II trials and the incompletely understood mechanism of action. Since the ISIS-2 study was published in 1988, aspirin is indicated in the acute phase of myocardial infarction as mortality can be reduced by 20% and the rate of reocclusions reduced. The beneficial effect of aspirin in unstable angina has also been demonstrated with a reduction of more than 50% in the combined incidence of mortality and myocardial infarction. Stable angina is an ideal application for low-dose aspirin with an improvement in combined incidence of myocardial infarction and sudden death of 34%. The question of dose remains open. When prescribed for primary or secondary prevention, aspirin should be given at low-doses (50-100 mg/d) in a long-term regimen. The dose should be examined differently for treatment of acute thrombotic events including infarction and unstable angina. Doses above 250 mg/d with an initial dose of 500 mg to 1 g are recommended followed by a relay with 50 to 100 mg/d. Irreversible dose-dependent inhibition of platelet cyclooxygenase by aspirin is nearly total for a single dose of 100 mg. The effect is cumulative for smaller doses and since the anucleated platelets cannot resynthesize the enzyme only new platelet can recover enzymatic activity. The duration of the effect thus is a function of normal platelet turn-over (8 days). Currently, aspirin is indicated in all coronary artery patients and should be discussed for "potential" patients i.e. as primary prevention in healthy subjects at risk of coronary artery disease although the threshold of risk requiring prescription remains to be clearly determined.

Angina Pectoris↗
PubMed1995

[Coronary restenosis: the cardiologist facing problems of definitions].

Many angiographic definitions have been proposed to define restenosis after coronary angioplasty. The utility of each remains poorly defined. The aims of this study were: a) to analyse groups of patients defined by each of three criteria: > 50% stenosis (definition 1), loss > or = 50% of initial gain in diameter (definition 2), loss > or = 0.52 mm of minimal luminal diameter based on the variability of the angiographic measurement (definition 3) and, b) to compare the immediate attitude of the interventional cardiologist with the deferred quantitative angiographic analysis. The angiographic follow-up included 89 patients. The angiographic restenosis rate was 37% (definition 1), 48% (definition 2) and 43% (definition 3). Restenosis as defined by criterion 1 was associated with the greatest degree of postangioplasty residual stenosis (p = 0.02) whereas, with criteria 2 and 3, it was associated with less severe residual stenosis (p = 0.03 and p = 0.007). Definition 2 and 3 are the most similar and definitions 1 and 3 the most complementary. The sensitivity, specificity positive and negative predictive values for recurrence of angina with respect to angiographic restenosis (definition 1) were respectively 63.6%, 77.8%, 63.6%, and 77.8% and are not significantly improved by associated analysis of exercise testing. Discordances between the decision of the interventional cardiologist and the results of quantitative angiography (definition 1) were noted in 12.4% of the stenosis studied, there measuring 44 to 64%. The judgement of the cathetiser of these intermediary stenoses was essentially influenced by the recurrence of angina during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1994

Endothelin-1 in patients with coronary heart disease undergoing cardiac catheterization.

OBJECTIVES: This study examined the possible association between endothelin and coronary atherosclerosis and evaluated the synthesis and release of endothelin in the presence of various stimuli that occur during cardiac catheterization. BACKGROUND: Circulating endothelin has been reported to be increased in diffuse atherosclerosis and acute myocardial infarction. However, the relation between coronary artery disease and endothelin release remains unclear. METHODS: We measured the plasma and urinary concentrations of endothelin immunoreactivity in 45 patients and 10 healthy control subjects. RESULTS: In group IA (n = 9), simultaneous blood sampling in the coronary sinus and femoral artery during coronary angioplasty of the left anterior descending coronary artery demonstrated no immediate changes in plasma immunoreactive endothelin-1 (ir-ET-1) levels. In 11 patients in group IB undergoing coronary angioplasty of a major artery, we did not detect changes in peripheral plasma concentrations of ir-ET-1 within 24 h, but urinary ir-ET-1 levels increased from 9.2 +/- 2.3 to 18.6 +/- 4.9 pg/mg of creatinine a few hours after coronary angioplasty (mean +/- SEM, p < 0.05). This increase in urinary endothelin excretion persisted 24 h later. Group II patients (n = 12) had coronary angiography without coronary angioplasty. Levels of both plasma and urinary ir-ET-1 did not change during the 24-h follow-up period. There was no relation between the severity of coronary atherosclerosis and the plasma or urinary concentrations of ir-ET-1. Systolic aortic pressure correlated with basal urinary excretion of endothelin (r = 0.54, p = 0.03, n = 15). In group III (n = 13), levels of ir-ET-1 in patients undergoing right heart catheterization without angiography did not differ from those in the control group. CONCLUSIONS: The presence or the severity, or both, of coronary atherosclerosis is not associated with a detectable increase in endothelin release. The diagnostic procedures of catheterization do not modify endothelin concentrations in plasma and urine. Vascular stretch or injury, or both, during coronary angioplasty increases urinary ir-ET-1 levels a few hours after the procedure. This increase persists for at least 24 h but is not detectable by brief sampling of peripheral or coronary sinus blood.

Angioplasty, Balloon, Coronary↗
PubMed1994

Eicosanoid biosynthesis in patients with stable angina: beneficial effects of very low dose aspirin.

OBJECTIVE: We assessed the production of eicosanoids and the effects of very low dose aspirin in patients with stable angina under basal conditions and during rapid atrial pacing. BACKGROUND: Platelet activation occurs in acute ischemic syndromes but is still controversial in stable angina. Very low dose aspirin is known to be platelet selective and can be used to test the hypothesis of the platelet origin of increased thromboxane production in stable angina. METHODS: Urinary excretion of eicosanoids was measured in 42 patients, including 24 patients with and 18 patients without coronary artery disease. The effects of 50 mg/day of aspirin were measured at rest and during pacing-induced ischemia in 10 patients with stable angina and were compared with a similar group of patients not treated by aspirin. RESULTS: Excretion of 11-dehydro-thromboxane B2 was 2.6 times higher in patients with stable angina than in healthy subjects (mean [+/- SEM] 74.8 +/- 13.0 [24 patients] vs. 29.0 +/- 5.4 [18 patients] ng/mmol of creatinine, p < 0.01). Urinary prostacyclin metabolite levels did not differ between the two groups. Treatment for 8 days with 50 mg/day of aspirin inhibited platelet cyclooxygenase, as reflected by the 97% reduction of in vitro serum thromboxane production. This aspirin regimen normalized the level of urinary thromboxane metabolites in patients with angina (17.3 +/- 3.4 ng/mmol of creatinine [10 patients], p < 0.001 from baseline level before treatment) and did not change prostacyclin metabolite levels. Atrial pacing in patients with angina not treated with aspirin caused lactate and thromboxane release into the coronary sinus. In patients with very low dose aspirin therapy, pacing did not cause thromboxane release despite inducing myocardial ischemia. However, fractional lactate extraction decreased less sharply in patients with than without aspirin therapy. CONCLUSIONS: Thromboxane production is greatly increased in patients with stable angina. Very low dose aspirin administered to these patients reduces thromboxane synthesis to normal levels, preserves prostacyclin biosynthesis and prevents acute thromboxane release into the coronary circulation during pacing-induced ischemia. Our data suggest that platelets (not monocytes/macrophages) are activated in stable angina to produce thromboxane.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

[Postinfarction hibernating myocardium].

The detection of hibernating myocardium after infarction is important because it justifies the discussion concerning the revascularisation of infarcted zones irrigated by occluded or severely stenosed vessels, but with an adequate collateral circulation to allow hibernation. The detection of hibernating myocardium is particularly important in patients without the classical indications for revascularisation, such as residual spontaneous ischaemia or ischaemia provoked by exercise or pharmacological stress testing. All techniques currently in use tend to overestimate the size of the necrosed, fibrous scar, compared with the amount of viable myocardium. Improved regional myocardial function after revascularisation is the most convincing proof of hibernating myocardium but it can only be obtained retrospectively. The detection of a reserve of contractility in the necrosed territory by an inotropic stimulus is well adapted to the demonstration of stunned myocardium but this method has not been proved in hibernating myocardium. Thallium scintigraphy is certainly useful in the prospective diagnosis of hibernating myocardium but the protocol of examination should be adapted to this specific problem. There is little available data concerning the evaluation of hibernating myocardium by positron emission tomography: the technical advantages of this method in assessing myocardial viability should enable a more accurate evaluation of post-infarction hibernating myocardium. Adequate revascularisation of necrosed territories depends on a deeper understanding and more precise prospective assessment of postinfarction hibernating myocardium.

Humans↗
PubMed1994

[Should all cases of aortic valve stenosis be surgically treated?].

Aortic stenosis is a condition in which progression accelerates with the onset of warning symptoms such as angina pectoris, syncope and heart failure. Surgery must be scheduled as quickly as possible in all such symptomatic patients, even in the presence of concomitant coronary disease, or of left ventricular failure. Aortic valve surgery is possible in the elderly, with a higher operative risk, but with the benefit of a symptomatic improvement identical to that seen in younger individuals, and a prolongation of life expectancy. Surgery is often considered in asymptomatic patients because of the fear of sudden death. In actual fact, sudden death not preceded by other symptoms is rare and the aim of surveillance must be to identify high-risk patients to whom surgery may be offered: poor exercise tolerance in a cautiously administered exercise test, abnormal ventricular function by echocardiography, or the existence of arrhythmias, which are also a severity factor, whether atrial or ventricular. The number of completely asymptomatic cases among patients with tight aortic stenosis is relatively slight, having been evaluated at 5%. It is in these asymptomatic patients, when they are young, that it is possible to delay surgery until the onset of a first symptom.

Age Factors↗
PubMed1993

Coronary artery vasomotion in cardiac transplant patients with normal coronary angiograms.

In 18 consecutive transplant patients with normal coronary angiograms and without calcium blocker therapy, and in 20 controls, we measured the diameters of the left anterior descending artery using quantitative coronary angiography. Measurements were effected on the frames recorded 5 min or more after intravenous administration of 0.4 mg methylergometrine, and 2 min after subsequent 2 mg bolus intracoronary isosorbide dinitrate administration. The arterial vasodilatory capacity was defined as the ratio of the difference of the largest and smallest arterial diameters and the smallest diameter. We observed normal vasoconstriction of the different coronary arterial segments. Coronary arterial diameter decrease from basal state was about 8% and was more pronounced at the distal segments of the left anterior descending artery. There was no difference of vasodilatory capacity between transplant patients and controls for the proximal and middle portion of the left anterior descending artery, while the difference was highly significant for the distal portion. In eight patients, the decrease of the vasodilatory capacity was beyond the lower limit of the normal range of values. The significance of those quantitative angiographic abnormalities is still unproven. They could be due to early vasomotor capacity blunting after transplantation and to late structural alterations of distal coronary vessels in cardiac transplant patients.

Adult↗
PubMed1993

Elevated total plasma homocysteine, a risk factor for thrombosis. Relation to coagulation and fibrinolytic parameters.

Homocystinuria is a rare inherited metabolic disease. Arterial and venous thromboembolic events represent frequent and life-threatening complications in homocystinuric patients. It has been suggested that mild homocysteinemia could be a risk factor for vascular disease. We have therefore measured total plasma homocysteine (HCy) concentrations by radioisotopic assay in 50 subjects with venous or arterial thrombosis and studied the relationship between HCy, coagulation and fibrinolytic parameters. Values were considered abnormal if they were higher than 2.7 standard deviations (SD) above the mean, i.e., 14.1 mmol/l. Thus, eighteen of the 50 patients with thrombosis were classified in the hyperhomocysteinemia group. Nine of these subjects had only this isolated risk factor. No correlations were found between HCy and antithrombin III, protein C, protein S and plasminogen levels, or plasma plasminogen activator inhibitor activity. Nevertheless, the correlation between tissue-plasminogen activator antigen and total plasma HCy was significant (r = 0.61, p < 0.001). Increased homocysteinemia seems to be a risk factor for thrombotic events especially knowing that HCy presents a direct cytotoxic effect. Vitamin therapy, already used in homozygote homocystinuric patients, might be beneficial in the prevention of thromboembolic disease in heterozygous patients.

Adolescent↗
PubMed1993

Imaging the ovine heparin-protamine interaction with 111In-protamine.

Protamine reversal of heparin anticoagulation occasionally induces the release of thromboxane into plasma with catastrophic pulmonary hypertension. To examine the site of neutralization, we labeled protamine sulfate with 111In and compared activity scans after administration of labeled protamine in unheparinized and heparin-anticoagulated sheep. Protamine administration in sheep without prior heparinization did not cause thromboxane release, pulmonary hypertension, or significant leukopenia, and 111In-protamine was rapidly cleared from the lungs (half time 0.48 +/- 0.08 min). Neutralization of heparin anticoagulation by labeled protamine produced elevated plasma thromboxane, pulmonary vasoconstriction, leukopenia, and prolonged pulmonary clearance of 111In-protamine (half time 3.32 +/- 0.43 min). In rats, protamine reversal of heparin anticoagulation did not induce either thromboxane synthesis or pulmonary hypertension, and 111In-protamine cleared rapidly from the lungs. Thus the ovine heparin-protamine reaction produces concomitant pulmonary sequestration of heparin-protamine complexes, thromboxane release, and pulmonary vasoconstriction; this did not occur in the rat. The lung specificity of the reaction and interspecies differences suggest that ovine pulmonary intravascular macrophages may be activated by heparin-protamine complexes to release thromboxane and provoke acute pulmonary vasoconstriction.

Animals↗
PubMed1993

[Effects of ultrasound energy on femoral artery occlusion. Angiographic and angioscopic results].

Ultrasonic energy has been shown to be able to disrupt atherosclerotic plaques and thrombi. The authors used an ultrasonic angioplastic technique developed by the group in 10 patients with a femoral arterial occlusion. The ultrasonic angioplasty was attempted before surgical bypass using a 130 cm long titanium guide wire with a 0.8 mm diameter and a round distal tip measuring 2 or 2.5 mm. Angiographic and angioscopic examinations were performed before and after the procedure in 9 patients. It was not possible to perform the angioplasty in 1 patient. Angioscopy showed that the proximal part of the occlusion consisted of atheromatous material in 3 cases and of thrombus in 6 cases. Angiography showed complete restoration of flow in 4 cases; distal flow was very slow in 4 cases and no distal run-off was observed in 1 case. Angioscopy showed residual stenosis at the site of entry in only 1 case. In 3 cases, the artery had no significant residual stenosis. In the other 5 patients residual stenosis was present and angioscopy showed persistence of strands of fibrin and small thrombi. These results show that ultrasonic angioplasty was capable of recanalising an occlusion in 9 out of 10 patients with partial or total disruption of thrombi. At the present stage of development of this system, balloon angioplasty would be an essential complement in most cases in order to obtain normal flow without significant residual stenosis. The manoeuverability of the guide wire and the relatively small size of the round distal tip explain why not all the thrombi could be treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[Effects of ultrasonic energy on blood clots in vitro].

Ultrasound may be used to dissolve arterial and venous thrombi. Its effects depends on the mode of ultrasonic vibration and on the length of the guide wire. The authors studied the in vitro effects of an ultrasonic angioplasty device coupled with a 130 cm long titanium flexible guide wire. The system comprises an automatic scanning function to determine the optimal frequency of resonance and works in the continuous mode of emission. Sixteen thrombi were studied of which 8 were acellular and 8 whole blood. In each group, 4 were treated in association with streptokinase and 4 by ultrasound alone. The ages of the thrombi in each subgroup were 1, 3, 7 and 15 days. All the thrombi were dissolved in 6 minutes or less (3'15" +/- 1'35") at an average optimal frequency of resonance of 19,444 Hz. Ninety six per cent of the debris had a diameter less than 10 microns. Less than 1% of the debris had a diameter larger than 100 microns. These large particles were observed in cellular thrombi and were almost completely absent in dissolved acellular thrombi. They were very fragile. The dissolution of the thrombi was not accelerated by the association of streptokinase. The ultrasonic energy did not induce D-dimer production and its action was probably due to cavitation. Ultrasonic energy could provide an alternative treatment for thrombotic vascular occlusion provided that more flexible guide wires could be designed.

Humans↗
PubMed1993

[Neurohormonal profile in aortic valve stenosis].

The authors studied the responses of the main systems of sympathetic and hormonal regulation in valvular aortic stenosis, a special model of dissociation between arterial pressure and left ventricular function. The series comprised 14 patients with an average age of 70 +/- 9 years without diuretic therapy presenting with pure calcific aortic stenosis without other valvular or coronary disease. All were in sinus rhythm; 5 were taking an angiotensin converting enzyme inhibitor. Plasma concentrations of endothelin 1, atrial natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, plasma renin activity (PRA), angiotensin II and aldosterone were measured in resting, fasting patients, by blood samplings from a peripheral vein immediately before cardiac catheterisation. The results were compared with the severity of the aortic stenosis (aortic valve area greater or less than 0.7 cm2), the ratio of left ventricular work/myocardial mass (greater or less than 0.6) and treatment (with or without ACE inhibitors). Catecholamine levels were much higher in severe aortic stenosis (noradrenaline: 579 +/- 66 pg/ml when valve surface area > 0.7 cm2 versus 900 +/- 92 pg/ml when valve surface area < 0.7 cm2; p < 0.01). Endothelin -1 and AVP concentrations were normal. Whereas PRA was normal, aldosterone levels were increased in patients without treatment by ACE inhibitors. This treatment did not, however, normalise the noradrenaline levels. The increase in ANF concentration was large when left ventricular work decreased with respect to myocardial mass (190.8 +/- 42.3 pg/ml if W/M was decreased versus 82.7 +/- 15.4 pg/ml when W/M was normal): this could be related to the degree of left ventricular hypertrophy.

Aged↗
PubMed1992

Systemic embolism as a complication of percutaneous mitral valvuloplasty.

Systemic embolism is a potential and severe complication of percutaneous mitral valve dilatation. In our series of 80 cases, the incidence of systemic embolism was 3.75% (3 cases). Two cases occurred during the procedure itself. The cause of embolism was different in each case: cruoric thrombus formation occurred in 2 cases during or after dilatation, and was attributable to inappropriate heparinization, and catheter and guidewire thrombogenicity. In both cases heparin administration was delayed or given at a lower dosage. In the third case, calcific embolism occurred several days after valve dilatation. We think that the embolic calcified fragment was detached from the mitral leaflet at the time of or after balloon inflation. In these 3 cases, intraatrial thrombus mobilization was not the mechanism of systemic embolism. In 2 cases, transesophageal echocardiography had been performed before dilatation and excluded the presence of an atrial thrombus the day before the procedure. It is concluded that, together with mobilisation of left atrial thrombi, which can be adequately detected by transesophageal echocardiography, catheter-induced thrombi represent a significant cause of embolic complications and must be prevented by giving full-dose heparin during the total duration of the procedure. Calcific embolism may also occur, and may become more frequent if mitral valve balloon dilatation is proposed to a larger number of patients with valvular and subvalvular calcifications.

Aged↗
PubMed1992

Lack of platelet-activating factor release during reversible myocardial ischaemia.

Platelet-activating factor (PAF) is involved in experimental models of myocardial ischaemia, and PAF infusion can cause thromboxane release. Thromboxane is produced during brief episodes of reversible myocardial ischaemia in patients with coronary heart disease. To learn whether PAF synthesis is associated with thromboxane production in mild myocardial ischaemia, we performed rapid atrial pacing in four patients with angina pectoris which caused chest pain, ST segment depression (delta ST = -1.8 +/- 0.2 mm) and lactate excretion in the coronary sinus (percent lactate extraction decreased from 20 +/- 6% to -15 +/- 9%). Thromboxane B2 was produced causing a positive transmyocardial gradient (from 88 +/- 154 pg.ml-1 baseline to 1770 +/- 1407 pg.ml-1 at the peak) but there was no PAF release into coronary sinus blood. In four other patients we determined whether more pronounced ischaemia could be associated with PAF synthesis. Coronary sinus blood was sampled before and during balloon occlusion of a major coronary artery: PAF was not detected in coronary sinus, whereas percent lactate extraction decreased from 24 +/- 6% to -63 +/- 22% (n = 4). We conclude that PAF plays a minor role in short episodes of reversible ischaemia and does not participate in thromboxane production.

Angina Pectoris↗
PubMed1992

Diagnosis of pulmonary embolism by transoesophageal echocardiography.

A 68-year-old woman was admitted for major dyspnoea. A transoesophageal echocardiogram was performed after the occurrence of acute circulatory shock. During the examination, the patient was under mechanical ventilation. We found a thrombus that had almost occluded the right pulmonary artery and which was later confirmed by selective angiography. Despite treatment, the patient died 2 days later; autopsy confirmed the thrombus in the right pulmonary artery.

Aged↗
PubMed1992

Role of platelet-activating factor in the ovine heparin-protamine reaction.

Platelet-activating factor (PAF) infusion into sheep, as well as protamine reversal of heparin anticoagulation, causes thromboxane release into plasma, pulmonary hypertension, hypoxemia, and leukopenia. We investigated the possible role of PAF in the heparin-protamine reaction. Intravenous protamine was administered to neutralize heparin anticoagulation in five awake sheep and caused an increase of mean pulmonary arterial pressure from 16.6 +/- 1 (SE) mmHg at base-line to 47 +/- 9 mmHg at 1 min after protamine injection (P < 0.01) because of a 4.5-fold increase of pulmonary vascular resistance. This neutralization reaction induced a 25% reduction of circulating leukocyte count and arterial PO2. Undetectable blood levels of PAF were measured by bioassay and high-performance liquid chromatography during these heparin-protamine reactions. Infusion of BN 52021 (20 mg/kg), a PAF receptor antagonist, before rechallenging the same sheep with heparin and then protamine did not reduce the level of peak pulmonary hypertension or the degree of hypoxemia and leukopenia. We conclude that the leukopenia and thromboxane-mediated pulmonary vasoconstriction occurring after rapid intravascular formation of heparin-protamine complexes in sheep are not due to the release of PAF.

Animals↗