Hemodynamic, platelet and clinical responses to prostacyclin in unstable angina pectoris

The hemodynamic and platelet effects of prostacyclin (PGI2) were investigated in 27 patients with unstable angina (14 treated patients; 13 control subjects) given a 72-hour infusion (5 ng/kg/min) or placebo. This randomized study was double-blind and conducted as a substudy of a multicenter trial testing the clinical efficacy of PGI2. The clinical and angiographic features were identical in the 2 groups. Blood pressure and heart rate were not modified significantly by PGI2. A recurrence of angina during infusion occurred in 8 treated patients (57.1%) and in 8 control subjects (61.5%). Two patients receiving PGI2 and none in the control group developed a myocardial infarction. Levels of 6-keto-prostaglandin F1 alpha, a stable metabolite of PGI2, increased from baseline values (less than 20 pg/ml) to 605 +/- 41 pg/ml during infusion. Levels of fibrinopeptide A, beta-thromboglobulin, platelet factor 4, thromboxane B2 and the platelet aggregates ratio in blood were similar between the 2 groups before, during and after PGI2 infusion. Prostacyclin reduced ex vivo platelet aggregation to adenosine diphosphate and thromboxane B2 generation by approximately 50% during the infusion period with return of aggregation to baseline and platelet thromboxane B2 production to above baseline after the discontinuation of PGI2. Thus, despite favorable effects of PGI2 upon platelet aggregation and systemic hemodynamics, the prostanoid failed to improve the clinical evolution of unstable angina.     

Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model

We wanted to test the hypothesis that NO generation by L-arginine (LA) infusion will be beneficial in increasing blood flow to all organs to counteract the process of global ischemia during cardiopulmonary bypass (CPB) and to reduce platelet emboli by platelet inhibition. The effect of LA infusion on NO formation, vasodilation, and reduction of thromboembolic burden in organs and tissues after CPB was quantified with In-111-labeled autologous platelets in two major groups: 180 minutes CPB (CPB) and 90 minutes CPB plus 90 minutes reperfusion (RP). Platelets labeled with In-111 tropolone (650–780 Ci) were administered 24 hours before CPB and LA infusion (bolus, 10 mg/kg and infusion at 2 mg/kg/min, 21 pigs for 180 minutes CPB) in 8 groups of 30 Yorkshire pigs (30–35 kg, 6 pigs; LA 2 mg/kg/min, 3 pigs; sham-thoracotomy control, 6 pigs; unoperated control, 6 pigs). Two groups of 9 pigs (control CPB, 6 pigs; LA 2 mg/ kg/min, 3 pigs) underwent 90 minutes of CPB and 90 minutes of reperfusion. All pigs were heparinized (ACT >400 seconds); CPB was instituted with a roller pump, an oxygenator (OX: Bentley Univox, 1.8 m²), and an arterial filter (AF: 0.25 m², Bentley) at a blood flow of 2.5–3.5 1/min. Radioactive thrombi in OX and AF and emboli in viscera, brain, and connective tissues were imaged with a gamma camera and were finally measured with an ion chamber and a gamma counter. The percent of injected platelets (mean ± SD) in the organs and tissues of all pigs was calculated. Cerebral emboli were mapped in 25 regions of both hemispheres of pig brain. Flow cytometry with antibodies to CD61 (GPIIIa) and CD62P (GMP-140: control) of porcine platelets was carried out with blood samples taken before, during, and after CPB. Coronary bypass with LA infusion decreased the amount of adherent thrombi in OX and AF (p < 0.07). The embolic burden in brain and lung also decreased. Regional cerebral mapping of In-111 platelets showed reduced emboli in almost all regions, including the medulla, hippocampus, and posterior cerebral cortex in both LA-treated groups. Flow cytometry of blood samples demonstrated the shift of equilibria from single platelet to platelet-aggregate-microparticle during CPB and steady-state level after the first 5–10 minutes of initiation of CPB. The L-arginine infusion reduced thrombi and emboli during CPB in the pig model.     

Clinical study of prostacyclin in extracorporeal circulation. Effects on hemodynamics and coagulation

The effects of prostacycline (PGI2), the most powerful known platelet antiaggregant on platelet count and function during cardiopulmonary bypass, were assessed in a double blind study. One group of 13 patients received 2,5 mg/Kg of Heparin with an infusion of 25 ng/Kg/min of prostacycline instituted 15 minutes before the Heparin, continued at the beginning of cardiopulmonary bypass at a dose of 50 ng/Kg/min and terminated at the end of bypass. A second group of 15 patients were studied by the same protocol with a placebo infusion. The platelet count was significantly higher at the end of cardiopulmonary bypass in the Prostacycline group. Platelet aggregation was reduced by comparison with the control group from the beginning of Prostacycline infusion. The active thrombin time was significantly longer in the Prostacycline group. However, blood loss did not differ significantly between the two groups although it was less in the study group. The platelet count and function during cardiopulmonary bypass with Prostacycline was therefore increased and resulted in a reduction in Heparin consumption.     

Elevated levels of circulating platelet aggregates and beta-thromboglobulin in scleroderma

Levels of circulating platelet aggregates and plasma beta-thromboglobulin reflect the degree of platelet activation in vascular injury and repair. Both values were evaluated in 38 patients with scleroderma and 18 control subjects matched for age, sex, and race. Circulating platelet aggregates (expressed as percentage of total platelet count) were 7.2 +/- 5.5% (mean +/- SD) in the control group and 31.2 +/- 13% in the scleroderma group (p less than 0.0005). Beta-thromboglobulin levels in the control groups were 20 +/- 10 ng/mL and 72.7 +/- 50 ng/mL in the group with scleroderma (p less than 0.0005). A positive correlation was found between the two values (r = 0.6, p less than 0.0005). Significant reductions in circulating platelet aggregates and beta-thromboglobulin levels were achieved in 10 patients by dipyridamole and aspirin therapy. These results show in-vivo activation of platelets in scleroderma with release of platelet granule constituents. Antiplatelet therapy in adequate doses returned both values to normal; however, its long-term effect on scleroderma is not yet known.     

Intravenous infusion of prostacyclin sodium in man: clinical effects and influence on platelet adenosine diphosphate sensitivity and adenosine 3':5'-cyclic monophosphate levels

Clinical tolerance, inhibition of platelet aggregation and intracellular platelet adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were evaluated in normal volunteers given i.v. infusions of prostacyclin sodium at rates up to 15 ng/kg/min. Short-term infusions (30 and 60 minutes) were tolerated at rates up to 10.0 ng/kg/min; higher rates produced headaches, anxiety, nausea and vomiting. Six-hour and 24-hour infusions were tolerated at rates up to only 4.0 ng/kg/min. Twenty-four hour infusions at 4 ng/kg/min produced a consistent 4-7 microM shift to the right in the platelet ADP dose-response curve; this platelet inhibitory activity did not diminish during the infusion. Prostacyclin sodium infusion elevated intracellular cyclic AMP levels, the increases corresponding to the onset of measurable inhibition of ADP-induced aggregation, although the magnitude of the increase did not necessarily reflect the degree of inhibition. Increased template bleeding times were seen with a greater than 10-microM shift in the ADP dose-response curve. We conclude that although prostacyclin sodium has a narrow safety margin, the drug does produce platelet inhibition at infusion rates generally tolerated by healthy volunteers.     

The effects of high-dose heparin on inflammatory and coagulation parameters following cardiopulmonary bypass.

Systemic inflammation and the activation of the coagulation system following cardiopulmonary bypass (CPB) may contribute to postoperative complications. In vitro studies have demonstrated that heparin possesses anti-inflammatory properties. To ascertain the relative benefits of high versus low heparin doses, we studied the impact of varying heparin doses on the inflammatory response and coagulation system during and following CPB. Forty patients scheduled for elective coronary artery bypass surgery requiring CPB were randomized to either a low dose (300 U/kg) (Group L) or a high dose of unfractionated heparin (600 U/kg) (Group H). To evaluate the inflammatory response, proinflammatory cytokines [tumor necrosis factor-alpha and interleukin-6 (IL-6)] were measured at four different times: before CPB (T0), 30 min after the institution of CPB (T1), 30 min after cross-clamp release (T2), and 4 h after the end of CPB (T3). Thrombin-antithrombin complex, platelet factor 4 and anti-activated factor X heparin concentrations were also measured. Patients in Group H received greater heparin (44.934 U versus 27.741 U, P<0.001) and protamine (P=0.003) doses. Postoperative blood loss and blood products transfusions were not significantly different in the groups. At T1, mean heparin plasma concentration was higher in Group H (P<0.001). IL-6 was significantly lower in Group H compared with Group L (P=0.01) only at T1. Using a mixed-effects statistical model, tumor necrosis factor-alpha and IL-6 levels were comparable regardless of the heparin dose. Thrombin-antithrombin complex levels were lower in Group H (P=0.04) and platelet factor 4 levels were significantly lower in Group H at T2 (P=0.04). Higher heparin doses were associated with higher heparin concentrations during CPB. A high heparin dose achieved a better preservation of the coagulation system with less thrombin formation and platelet activation. The heparin dose had small influence on proinflammatory cytokines release.     

A prospective study of the clinical benefits of prostacyclin in 554 cardiopulmonary bypass procedures

Abnormal bleeding after cardiopulmonary bypass (CPB) may result from incomplete neutralization of heparin, increased fibrinolytic activity, consumption of coagulation factors, or from a reduction in the number of circulating platelets together with impairment of platelet function. Although researchers have reason to believe that hemostasis after CPB could be improved with prostacyclin (PGI(2)), a potent inhibitor of platelet aggregation, the drug's clear-cut benefits in this respect have not yet been confirmed. After conducting an initial study concerning the fate of platelets during CPB, in which we determined that PGI(2) had a protective effect, we investigated the effects of PGI(2) infusion during CPB on postoperative blood loss in 554 open-heart surgery patients, 200 of whom underwent valve replacement, 200 of whom had coronary artery bypass grafting (CABG), and 154 of whom underwent repeat valve replacement or CABG. The patients were divided into 2 groups: 277 patients (the study group) received both heparin and PGI(2) during CPB, whereas the remaining 277 patients (the control group) were given heparin alone. Of the patients who underwent surgery for the first time, those treated with PGI(2) had a reduced mean blood loss (p < 0.05 only in CABG patients) in comparison with those who received heparin alone. Of the patients who underwent redo operations, those who received PGI(2) had a nonsignificant tendency toward reduced blood loss. The mean difference in blood loss between the study group and the control group had no clinical relevance, however, because it was less than the smallest practical unit of measurement (i.e., 1 unit of blood).     

Prevention of acquired transient defect in platelet plug formation by infused prostacyclin

Cardiopulmonary bypass in baboons produced transient severe platelet dysfunction (bleeding times prolonged to 27.8 +/- 1.4 min compared with 3.9 +/- 0.7 baseline) that was associated with a parallel release of platelet alpha-granule proteins into plasma (platelet factor 4 and beta- thromboglobulin levels of 28.8 +/- 9.3 and 20.0 +/- 1.8 ng/ml, respectively) and their clearance into urine with a reciprocal depletion from circulating platelets. In contrast, platelet-dense granules did not undergo significant release. The bleeding times normalized rapidly following bypass (8.5 +/- 1.4 min at 1 hr). The infusion of prostacyclin (PGI2) into the bubble oxygenator during bypass (40--80 ng/kg/min) prevented the prolongation in bleeding time (p less than 0.01 compared with untreated control values) but did not block the release of alpha-granule proteins. Dosages outside this range were associated with prolonged bleeding times. These results show that transient platelet dysfunction occurring during cardiopulmonary bypass represents activation of platelets independent of alpha or dense granule release and is blocked by potent short-acting inhibition of platelet function using PGI2 infused into the oxygenator apparatus at optimal therapeutic doses.     

Toxicity of Plasma from Hemodialysis Patients Treated with Heparin or Prostacyclin

Abstract Hemodialysis was performed in 6 uremic patients with either a bolus dose of 5 000 IU heparin or prostacyclin at a constant infusion rate of 5 ng/kg/min. Clinical data, plasma triglycerides (TG), free fatty acids (FFA), platelet aggregation, white blood cell count and plasma toxicity were measured prior to and during both procedures. No serious sideeffects were recorded. Heparin induced a fall in plasma TG, a rise in FFA and increased plasma toxicity. Prostacyclin infusion had no effect on these parameters. During both tests a marked drop in white blood cell count was found 15 min after the start of hemodialysis. During heparin dialysis no clotting was observed in the extracorporeal circuit. During prostacyclin dialysis clotting was observed at the venous line in three cases     

Antithrombotic and vasodilating effects of OP-41483, a prostacyclin derivative

Anti-platelet and vasodilating actions of OP-41483, a derivative of prostacyclin, were studied experimentally and clinically. The ADP-induced human platelet aggregation was significantly inhibited in vitro, the rate being 59% with a dose of 3 micrograms/ml, 75% with 6 micrograms/ml and over 90% with 18 micrograms/ml or more. A significant reduction in deposition of platelet and mural thrombi on the chemically injured luminal surface of the canine femoral vein was observed by treatment with topical administration of the solution (10 micrograms/ml) and/or intravenous infusion (10 ng/kg/min). The blood flow rate of the normal canine femoral artery and the anterior or posterior tibial artery of patients with peripheral arterial occlusive disease at the ankle was moderately increased in cases of intravenous infusion of the compound at a rate of 10 ng/kg/min.     

Cardiopulmonary bypass induces release of soluble CD40 ligand

BACKGROUND: Cardiopulmonary bypass (CPB) is known to induce platelet activation, thrombosis, thrombocytopenia, and a systemic inflammatory response. It is known that CD40 ligand (CD40L) exists in platelets, that a soluble form of this protein (sCD40L) is released on platelet activation, that platelets are the primary source of sCD40L in blood, and that sCD40L is involved in thrombosis and inflammation. The present study was designed to determine whether sCD40L is released during CPB. Methods and Results- Blood was obtained from patients undergoing CPB-requiring surgery and analyzed for sCD40L, interleukin-6, and platelet factor 4 and beta-thromboglobulin (markers of platelet activation). Platelets were also isolated and analyzed for their levels of CD40L. Plasma levels of sCD40L increased >1.7-fold (from 0.29 to 0.51 ng/mL, P=0.001) within 1 hour on CPB and increased further to 3.7-fold (to 1.08 ng/mL, P=0.03) 2 hours after the procedure. Half of the released sCD40L was cleared in 2 hours, which allowed the sCD40L to return to approximately baseline levels 8 hours after the procedure. The platelet content of CD40L was decreased by 40% (2.675 to 1.64 ng/10(8) platelets, P=0.001) 1 hour after initiation of CPB and was similar to that observed for platelet factor 4 and beta-thromboglobulin. Interleukin-6, a marker of inflammation, also increased during CPB. CONCLUSIONS: The present study demonstrates that CPB causes an increase in the concentration of plasma sCD40L. The corresponding decrease in platelet CD40L suggests that this prothrombotic and proinflammatory protein was derived primarily from platelets and may contribute to the thrombotic and inflammatory complications associated with CPB.     

A new stable prostacyclin analogue OP41483 (15-cyclopentyl-omega-pentanor-5(E)-carbacyclin)

Effects of a new stable prostacyclin analogue OP41483 (15-cyclopentyl-omega-pentanor-5(E)-carbacyclin) on platelet aggregation, plasma thromboxane B2 levels, hemodynamic parameters, and clinical safety were studied. Normal volunteers received intravenous infusions of OP41483 at doses of 2.5 (n = 3), 5.0 (n = 3), 10 (n = 3), and 20 (n = 5) ng/kg/min for one hour. During infusion, ADP (adenosine diphosphate)-induced platelet aggregation decreased significantly, and blood pressure decreased slightly, but plasma thromboxane B2 levels did not change significantly. The intravenous infusion of OP41483 at the dose of 10 ng/kg/min for one hour over three successive days was performed. During the each infusion, platelet aggregation and mean blood pressure decreased significantly.     

A Double Blind Study of Prostacyclin in Cardiopulmonary Bypass Surgery

In a double-blind placebo-controlled trial of 48 patients requiring open heart surgery, prostacyclin (PGI2) was infused in a dose of 20 ng/kg/min throughout cardiopulmonary bypass. When compared with the placebo group, the patients given active PGI2 were found to have significantly higher platelet counts from 30 min after commencement of bypass and in the immediate post-operative period, and to have significantly less elevation of the platelet secretory proteins, beta thromboglobulin and platelet factor 4 during bypass. The mean weight increase in the arterial line filters was significantly greater in the placebo-treated patients than in the PGI2 group. It is suggested that infused PGI2 decreases platelet activation during cardiopulmonary bypass and that further studies are required to establish its clinical value in this situation.     

Prostacyclin versus citrate in continuous haemodiafiltration: an observational study in patients with high risk of bleeding

BACKGROUND: The efficacy and safety of prostacyclin (PGI2) and citrate (ACD) anticoagulation were observed and compared during continuous haemodiafiltration. METHODS: Mechanically ventilated patients received either the PGI2 analogue epoprostenol (group A, n = 17) in escalating doses of 4.5-10.0 ng.kg(-1).min(-1) in combination with heparin (6 IU.kg(-1).h(-1)) or 2.2% ACD (group B, n = 15). Blood flow was set to match the circuit-filling volume per unit time equal to the intravascular half-life of PGI2. RESULTS: Median filter lifetimes were 26 h (interquartile range 16-37) in group A (39 filters) and 36.5 h (interquartile range 23-50) in group B (56 filters; p < 0.01). In group A, 4 patients (23.5%, p < 0.05) had the dose reduced due to hypotension. The final mean dose of PGI2 was 8.7 +/- 2.4 ng.kg(-1).min(-1). Four patients in group A (23.5%, p < 0.05) were switched to ACD due to a decrease in platelet count. No bleeding episodes, decrease in platelet count or adverse haemodynamic effects were encountered in group B. The cost of epoprostenol plus low dose heparin (EUR 204.73 +/- 53.04) was significantly higher than the cost of ACD-based anticoagulation (EUR 93.92 +/- 45.2, p < 0.05). CONCLUSION: ACD offers longer filter survival, has no impact on platelet count and is less expensive. Increasing the dose of PGI2 up to the average of 8.7 ng.kg(-1).min(-1) did not increase the haemodynamic side effects.     

Can clonidine,enoximone, and enalaprilat help to protect the myocardium against ischaemia in cardiac surgery?

OBJECTIVE: To evaluate whether clonidine, enoximone, and enalaprilat reduce ischaemia-related myocardial cell damage in cardiac surgery. DESIGN: Prospective randomised controlled trial. SETTING: Clinical investigation in a cardiac anaesthesia department of a university hospital. PATIENTS: 88 consecutive patients undergoing coronary artery bypass surgery. INTERVENTIONS: After induction of anaesthesia patients continuously received the alpha 2 agonist clonidine (group 1, n = 22), the phosphodiesterase (PDE) III inhibitor enoximone (group 2, n = 22), the angiotensin converting enzyme (ACE) inhibitor enalaprilat (group 3, n = 22), or saline solution as placebo (control group, n = 22). The infusion was stopped immediately before the start of cardiopulmonary bypass. MAIN OUTCOME MEASURES: The ST segment was analysed and the activity of creatine kinase isoenzyme MB (CKMB), cardiac troponin T (TnT), and the BB isoenzyme of glycogen phosphorylase (GPBB) were measured before the start of infusion (baseline), after weaning from cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB, and on the morning of the first and third postoperative days. RESULTS: Biometric data and time of cross-clamping were not significantly different in the four groups. Changes in the ST segment indicating ischaemia were least common in the enalaprilat group (P < 0.05). Postoperatively, CKMB activity was significantly higher in the clonidine and the control groups. Both new markers of myocardial cell damage increased more after CPB and postoperatively in the control patients (TnT peak: (mean (SD)) 3.99 (0.35) microgram/1; GPBB peak: 82 (15) ng/ml) and the clonidine-treated group (TnT peak: 3.80 (0.3) microgram/1; GPBB peak: 85 (14) ng/ml). Enalaprilat-treated patients showed the smallest overall changes in standard (CKMB) and new serological markers of myocardial ischaemia (TnT peak: 0.71 (0.1) microgram/1; GPBB peak: 44 (14) ng/ml). CONCLUSIONS: In patients treated with enalaprilat before CPB, both new, more sensitive markers of ischaemic myocardial tissue damage increased significantly less than in an untreated control group. Those treated with enoximone also had lower plasma concentration of TnT and GPBB than the control group, whereas clonidine did not reduce the concentration of these markers of myocardial ischaemia. Pharmacological interventions, such as the continuous infusion of the ACE inhibitor enalaprilat, before start of CPB may help to protect the heart against ischaemia/reperfusion injury.     

Experimental inhibition of protamine cardiotoxicity by prostacyclin

Twelve animals (26+/-5 kg) were subjected to the study. In this experimental study, the authors used prostacyclin to inhibit the toxic metabolite release during protamine administration. Animals were divided into two equal groups. Six animals received prostacyclin (the prostacyclin group), and the other six animals did not receive any additional treatment (the control group). All cardiac output and biochemical measurements were evaluated at baseline; before cardiopulmonary bypass; and at 5, 30, and 60 minutes after protamine administration. The measured cardiac index showed that the hearts treated with prostacyclin had satisfactory preservation of left ventricular function. Metabolic and biochemical data showed that the tumor necrosis factor level was raised significantly in the control group (20.75+/-2.2 in the control group and 13.75+/-2.5 pg/mL in the prostacyclin group). Also, E and P selectin levels were elevated in the control group, but this change was less marked in the prostacyclin group. In addition, the intracellular adhesion molecule-1 (ICAM-1) level was significantly higher in the control group than in the prostacyclin group (9.26+/-2.13 in the control group and 5.13+/-1.66 ng/mL in the prostacyclin group). The authors observed that prostacyclin inhibited the toxic mediator release during heparin reversal with protamine. This inhibition is one way of protecting the myocardium reserves from protamine cardiotoxicity.     

Rituximab in a risk‐adapted treatment strategy gives excellent therapeutic results in nodular lymphocyte‐predominant Hodgkin lymphoma

Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB). As an alternative to protamine, a recombinant inactive antithrombin (riAT) was designed as an antidote to heparin and was previously shown to be as potent as protamine in‐vitro. In the present study, riAT was assessed for its ability to neutralize heparin after CPB in a rat model. After 60 min of CPB under heparin, rats received 5 mg/kg protamine, 37.5 mg/kg riAT or phosphate buffered saline (PBS) as placebo. Residual anticoagulant activity was assessed using the activated partial thromboplastin time assay before, and 10–30 min after reversion. Haemodynamic monitoring was performed and plasma histamine concentration was also measured. In this model, riAT appeared to be as efficient as protamine in neutralizing heparin. Ten minutes after injection, riAT and protamine both decreased heparin activity, to 1.8 ± 1.3 and 4.5 ± 1.4 u/ml, respectively (23.1 ± 5.1 u/ml in placebo group). Furthermore, evolution of mean carotid arterial pressure, heart rate and plasma histamine levels was comparable in rats treated with PBS or riAT, while protamine exhibited haemodynamic side effects and increased histamine plasma concentration. Thus, riAT could represent an advantage over protamine in CPB because it efficiently reverses heparin activity without negative effects on haemodynamic parameters and plasma histamine level.     

The effect of unfractionated and low-molecular-weight heparin on the release of prostacyclin from the arterial wall

Heparin is widely used as an antithrombotic agent, but one reported complication is thrombocytopenia associated with platelet aggregation. The mechanism is not fully clear but heparin interference in the prostaglandin production has been proposed. To investigate if heparin interacts with the production of prostacyclin from the vessel wall, and if low-molecular-weight heparin differs from unfractionated heparin in this respect, excised rabbit aortas were studied in a perfusion model. The vessels were perfused ex vivo for 5 x 15 min and in the last period arachidonic acid was added. Unfragmented heparin (500 IU/kg body weight) or low-molecular-weight heparin (LMWH) (500 antifactor Xa units/kg body weight) were given either 15 min before harvesting the vessels or added directly to the perfusate. The stable degradation product for prostacyclin, 6-keto-PGF1 alpha was not altered by addition of these agents. It is concluded that heparin and LMWH per se do not interact with the prostacyclin system in normal rabbit aortas in the doses studied.     

大剂量乌司他丁在兔常温体外循环中对血小板的影响

目的观察兔常温体外循环（CPB）前应用大剂量乌司他丁对血小板数量和功能的影响。材料和方法20只大耳白兔随机分成2组：乌司他丁组（U组，n=10）和对照组（C组，n=10）。U组在CPB前给予乌司他丁10×10^4U／kg，C组给予等量生理盐水，CPB30min，流量为180—300ml／min，肛温维持在36．5～37．5℃。分别记录CPB前、停机、停机后1h、2h和3h的血流动力学指标，测定血小板计数、血小板粘附率（PAR）和血小板膜糖蛋白GPⅠb、GPⅡb、GPⅢa的分子数。结果CPB后各时间点两组血小板计数较CPB前显著减少（P〈0．01），同时间点两组间无统计学差异（P〉0．05）。CPB后两组PAR较CPB前显著下降（P〈0．01），同时间点C组PAR下降较U组更明显（P〈0．05）。CPB后两组GpⅠb、GpⅡb、GpⅢa分子数较CPB前显著减少（P〈0．01），停机后逐步恢复，同时间点C组较U组更明显（P〈0．05）。结论CPB后血小板数目减少，膜糖蛋白分子数降低，粘附能力下降。CPB前应用大剂量乌司他丁可减少CPB中血小板膜糖蛋白受体的分解，保护血小板功能。     

The interaction of platelets with aortic subendothelium: inhibition of adhesion and secretion by prostaglandin I2

We have studied the effect of prostaglandin I2 on platelet turnover, attachment to the subendothelium, and secretion following balloon deendothelialization of the rabbit aorta. Survival of 51Cr-labeled platelets in the balloon-injured animals remained normal. Thirty minutes after injury, there were 4.52 X 10(6) platelets/sq cm attached to the aortic surface, which was 87% covered by platelets. Although plasma platelet factor 4, as measured by radioimmunoassay, did not rise above the normal level of 6.8 +/- 2.6 ng/ml (mean +/- SEM) during the first hour after balloon injury, platelet factor 4 antigen was detected within the vessel wall by direct immunofluorescence within 30 min of injury. An infusion of 650-850 ng/kg/min prostaglandin I2 completely inhibited platelet aggregation and reduced surface coverage by 84% and platelet attachment by 63%. Animals given 50-100 ng/kg/min prostaglandin I2, which only partially inhibited platelet aggregation, had 70% of the aortic surface covered by platelets. Platelet factor 4 antigen was also detected within the aortic wall. Platelet attachment was normal in animals that had been given 850 ng/kg/min prostaglandin I2 prior to balloon injury but sacrificed after the infusion was stopped and ex vivo platelet aggregation had returned to normal.