Pulmonary Microembolism Research Articles

Preoperative blood donation program and postoperative Low Molecular Weight Heparine (LMWH) prophylaxis in patients undergoing radical prostatectomy

The need and timing of perioperative heparin prophylaxis is matter of debate. The aim of our work is to review the incidence of venous thromboembolism (VTE) after radical retro pubic prostatectomy (RRP) in patients undergoing preoperative blood donation, compressive stockings, haemodilution, surgical prevention of lymphocoele and postoperative low molecular weight heparin therapy as prophylaxis for thrombotic events. This is a retrospective analysis considering a series of 500 RRP performed between 1999 and 2006 by the same Surgeon (MG) at the Urological Unit, Desio, Hospital, Milan, Italy. All the patients were enrolled in an auto transfusion program and were subjected to autologous blood donation. Low molecular weight heparin (.04 ml of Calcic Nadroparin 3800 UI s.c. daily) was administrated within 24 hours following surgery until the 11th post-operative. Age, PSA, basal, preoperative and postoperative haemoglobin values were assessed in each patient. The incidence of venous thromboembolism was calculated taking into consideration occurrences of both pulmonary embolism and deep venous thrombosis. In this retrospective analysis we did not observe any major event including intra- or peri-operative deaths. There was one occurrence of pulmonary microembolism and one sural phlebitis that were treated with prolonged heparin and dicumarol therapy. Two significant haemorrhagic events occurred in the postoperative period requiring surgical revision. These data suggest that low weight heparin prophylaxis starting with 24 hours following radical prostatectomy, associated with preoperative blood donation, intra-operative haemodilution, compression stockings, surgical care to avoid lymphocoele and early mobilization in preventing venous thromboembolism.

Pulmonary capillary embolism caused by cryptococcemia in a hemodialysis patient

In this report, we describe a patient who contracted fatal cryptococcosis after the induction of hemodialysis. A 76-year-old man was hospitalized to initiate hemodialysis. On admission, clinical findings showed no signs of any infections, and hemodialysis was inducted favorably. On the 6th hospital day he suddenly had a dyspnea and died from acute respiratory failure having a dyspnea for only 6 h. By microscopic examination at autopsy, we detected microemboli in the pulmonary capillary arteries caused by Cryptococcus and that the embolic source was a multiple-abscessed spleen. To the best of our knowledge, this is the first reported case of pulmonary capillary microembolism caused by cryptococcemia.

ConfirmedMycoplasma pneumoniaeEndocarditis

Confirmed<i>Mycoplasma pneumoniae</i>Endocarditis

“Glue lung”: pulmonary micro-embolism caused by the glue used during interventional radiology

A boy with a complex Galen’s vein arterovenous malformation was developing multiple endovascular embolisations every 3 months from birth. A treatment was scheduled at 15 months of age. During the...

A sudden death with lung embolism after inadvertent infusion of zinc oxide shake lotion

A 74-year old woman in postoperative treatment after a colonic surgery died immediately after perfusion of about 1.5 mL of a white emulsion which was believed to contain 1% propofol via cardiac catheter into the right atrium. It was strongly suspected that a syringe with a zinc oxide shake lotion (consisting of 20% ZnO, 20% talc, 25% glycerol and 35% water) which was intended for external treatment had been mistaken for the propofol syringe. During autopsy, an anatomic cause of death could not be found. In order to exclude an intoxication and to determine the significance of the perfusion fluid in this context, toxicological and histological investigations were performed. Propofol and other drugs applied to the patient were found in therapeutic or sub-therapeutic range. However, in comparison to a control case, the zinc concentrations determined by AAS were about 200 times higher in lung tissue, 10 times higher in heart blood and 3–4 times higher in kidney and liver tissue. No increase was seen in venous blood. Histology showed a strong embolism of the lung tissue with birefingent sharp-edged crystals, which were identified as the talcum, and an amorphous component (ZnO). The same embolism was seen to a medium extent also in the brain sections and to a low extent in heart, liver, pancreas and kidney. Pulmonary embolism by talcum and zinc oxide was established as the cause of death which occurred by syringe swap due to insufficient security precautions in the drug administration. The results are discussed in context of pulmonary microembolism cases frequently described for drug addicts after injection of crashed talcum containing tablets.

Experimental pulmonary microembolism: effects on hemodynamics, lung mechanics and histopathology

Experimental pulmonary microembolism: effects on hemodynamics, lung mechanics and histopathology

Sudden death with clinically undiagnosed pulmonary hypertension

Four cases of sudden unexpected death associated with pulmonary hypertension are described. In all cases, the presence of pulmonary hypertension had not been clinically detected. In each case, the underlying etiology of the pulmonary hypertension was different with one case each of occult adult congenital heart disease, pulmonary sarcoidosis, pulmonary tumour microembolism from gastric adenocarcinoma, and familial primary pulmonary hypertension. These cases indicate that the forensic pathologist must be aware of occult pulmonary hypertension as a cause of sudden unexpected death in a variety of age groups.

Diffuse Pulmonary Alveolar Hemorrhage and Interstitial Pneumonitis after Subcutaneous Injection of Atelocollagen for Cosmetic Purpose: Two Case Reports

Atelocollagen have been used recently in skin and other soft tissue defect regions more than silicone fluid because of the low incidence of an immune reaction and complications. Several cases of acute pneumonitis after a subcutaneous injection of silicone have been reported. The symptoms were dyspnea, fever, chest pain and hemoptysis. Previous reports have explained the pathophysiology of acute pneumonitis to a pulmonary microembolism and cellular inflammation. We experienced two cases of an acute interstitial pneumonitis and pulmonary hemorrhage after a subcutaneous injection of atelocollagen. They were all healthy young women and complained of dyspnea, fever and blood tinged sputum. The chest radiography and computerized tomography showed a bilateral ground glass opacity in both lung fields. One case recovered completely with conservative treatment but the clinical course of the other case was aggravated to the degree that invasive positive pressure ventilation therapy was required. We report a rare case of a diffuse pulmonary alveolar hemorrhage and an interstitial pneumonitis after the subcutaneous injection of atelocollagen for cosmetic purposes.

Effects of oxygen and nitric oxide inhalation in a porcine model of recurrent microembolism

Inhalation of nitric oxide (iNO) has been proposed for the treatment of acute pulmonary embolism. The present study evaluates the effects of oxygen (O2) and nitric oxide inhalation in a porcine model of sustained pulmonary hypertension induced by recurrent pulmonary microembolism. Twelve pigs were embolized under general anesthesia with 300-microm microspheres intravenously three times over a period of seven weeks. Five pigs served as untreated controls. Hemodynamic and gas exchange responses to 100% oxygen and 40 ppm NO inhalation, and their combination (O2+iNO) were measured seven days after the last embolization. Recurrent microembolism caused sustained pulmonary hypertension (pulmonary vascular resistance index; PVRI 408 +/- 57 dyn x s x cm(-5) x m(-2)) as compared to the control group (PVRI 143 +/- 20 dyn x s x cm(-5) m(-2); P<0.05). PVRI was significantly reduced by O2, iNO, and O2+iNO inhalation by 29 +/- 3, 28 +/- 4, and 32 +/- 3%, respectively. We conclude that both O2 and iNO are selective pulmonary vasodilators in a porcine model of sustained pulmonary hypertension following recurrent pulmonary microembolism and, therefore, may be useful in the treatment not only in the acute phase of pulmonary embolism but also later in the time course of the disease.

Urokinase mediates fibrinolysis in the pulmonary microvasculature

The role of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in fibrinolysis remains unsettled. The contribution of uPA may depend on the vascular location, the physical properties of the clot, and its impact on tissue function. To study the contribution of urokinase within the pulmonary microvasculature, a model of pulmonary microembolism in the mouse was developed. Iodine 125 (125I)–labeled fibrin microparticles injected intravenously through the tail vein lodged preferentially in the lung, distributing homogeneously throughout the lobes. Clearance of125I-microemboli in wild type mice was rapid and essentially complete by 5 hours. In contrast, uPA−/− and tissue-type plasminogen activator tPA−/− mice, but not uPAR−/− mice, showed a marked impairment in pulmonary fibrinolysis throughout the experimental period. The phenotype in the uPA−/− mouse was rescued completely by infusion of single chain uPA (scuPA). The increment in clot lysis was 4-fold greater in uPA−/− mice infused with the same concentration of scuPA complexed with soluble recombinant uPAR. These data indicate that uPA contributes to endogenous fibrinolysis in the pulmonary vasculature to the same extent as tPA in this model system. Binding of scuPA to its receptor promotes fibrinolytic activity in vivo as well as in vitro. The physical properties of fibrin clots, including size, age, and cellular composition, as well as heterogeneity in endothelial cell function, may modify the participation of uPA in endogenous fibrinolysis.

Urokinase mediates fibrinolysis in the pulmonary microvasculature

AbstractThe role of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in fibrinolysis remains unsettled. The contribution of uPA may depend on the vascular location, the physical properties of the clot, and its impact on tissue function. To study the contribution of urokinase within the pulmonary microvasculature, a model of pulmonary microembolism in the mouse was developed. Iodine 125 (125I)–labeled fibrin microparticles injected intravenously through the tail vein lodged preferentially in the lung, distributing homogeneously throughout the lobes. Clearance of125I-microemboli in wild type mice was rapid and essentially complete by 5 hours. In contrast, uPA−/− and tissue-type plasminogen activator tPA−/− mice, but not uPAR−/− mice, showed a marked impairment in pulmonary fibrinolysis throughout the experimental period. The phenotype in the uPA−/− mouse was rescued completely by infusion of single chain uPA (scuPA). The increment in clot lysis was 4-fold greater in uPA−/− mice infused with the same concentration of scuPA complexed with soluble recombinant uPAR. These data indicate that uPA contributes to endogenous fibrinolysis in the pulmonary vasculature to the same extent as tPA in this model system. Binding of scuPA to its receptor promotes fibrinolytic activity in vivo as well as in vitro. The physical properties of fibrin clots, including size, age, and cellular composition, as well as heterogeneity in endothelial cell function, may modify the participation of uPA in endogenous fibrinolysis.

Ventilation heterogeneity does not change following pulmonary microembolism.

By using the multiple-breath helium washout technique, ventilation heterogeneity (VH) after embolic injury in the lung can be quantitatively partitioned into the conductive and acinar components. Total VH, represented by the normalized slope of the phase III alveolar plateau, Sn(III (total)), was studied for 120 min in three groups of anesthetized and paralyzed mongrel dogs. Group 1 (n = 3) received only normal saline and served as controls. Group 2 (n = 4) received repeated infusions of polystyrene beads (250 microm) into the right atrium at 10, 40, 80, and 120 min. Group 3 (n = 3) was similarly treated, except that the embolic beads used were 1,000 microm in diameter. The data show that, despite repeated embolic injury by polystyrene beads of different diameters, there was no significant increase in total VH. The acinar component of Sn(III), which represents VH in the distal airways, accounts for over 90% of the total VH. The conductive component of Sn(III), which represents VH between larger conductive airways, remains relatively constant and a minor component. We conclude that pulmonary microembolism does not result in significant redistribution of ventilation.

Small-Dose Inhaled Nitric Oxide Attenuates Hemodynamic Changes After Pulmonary Air Embolism in Dogs

Inhaled nitric oxide (NO) has been used to treat pulmonary hypertension.Experimental studies have suggested therapeutic effects of NO after pulmonary microembolism. We evaluated the protective effects of NO in dogs during a pulmonary air embolism (PAE). NO (3 ppm) was administered to six anesthetized mongrel dogs (NO group) but not to the seven dogs in the control group. After 20 min, each dog received a venous air injection of 2.5 mL/kg. Hemodynamic evaluation was performed, and blood samples were drawn for blood gas analysis before and after NO inhalation and 5-60 min after the PAE. Both arterial blood pressure and cardiac output were decreased in the control group for >15 min after PAE, whereas NO-treated animals showed only transient hypotension. NO attenuated the pulmonary hypertension after PAE, as demonstrated by small (P < 0.05) increases in pulmonary artery pressure and pulmonary vascular resistance index in NO-treated animals (90% and 135%, respectively) compared with the controls (196% and 282%, respectively). These hemodynamic effects of NO were associated with higher mixed venous O2 tensions and saturations in the NO group compared with the controls. We conclude that small-dose NO (3 ppm) attenuated the hemodynamic changes induced by PAE in dogs. This protective effect of NO on hemodynamics is not accompanied by improvement in pulmonary oxygenation in this setting. Implications: In this study, we evaluated the protective effects of inhaled nitric oxide in a pulmonary air embolism setting. Nitric oxide attenuated the hemodynamic changes induced by pulmonary air embolism without improving pulmonary oxygenation. (Anesth Analg 1999;88:1025-9)

Small-dose inhaled nitric oxide attenuates hemodynamic changes after pulmonary air embolism in dogs.

Inhaled nitric oxide (NO) has been used to treat pulmonary hypertension. Experimental studies have suggested therapeutic effects of NO after pulmonary microembolism. We evaluated the protective effects of NO in dogs during a pulmonary air embolism (PAE). NO (3 ppm) was administered to six anesthetized mongrel dogs (NO group) but not to the seven dogs in the control group. After 20 min, each dog received a venous air injection of 2.5 mL/kg. Hemodynamic evaluation was performed, and blood samples were drawn for blood gas analysis before and after NO inhalation and 5-60 min after the PAE. Both arterial blood pressure and cardiac output were decreased in the control group for >15 min after PAE, whereas NO-treated animals showed only transient hypotension. NO attenuated the pulmonary hypertension after PAE, as demonstrated by small (P < 0.05) increases in pulmonary artery pressure and pulmonary vascular resistance index in NO-treated animals (90% and 135%, respectively) compared with the controls (196% and 282%, respectively). These hemodynamic effects of NO were associated with higher mixed venous O2 tensions and saturations in the NO group compared with the controls. We conclude that small-dose NO (3 ppm) attenuated the hemodynamic changes induced by PAE in dogs. This protective effect of NO on hemodynamics is not accompanied by improvement in pulmonary oxygenation in this setting. In this study, we evaluated the protective effects of inhaled nitric oxide in a pulmonary air embolism setting. Nitric oxide attenuated the hemodynamic changes induced by pulmonary air embolism without improving pulmonary oxygenation.

Precipitate formed by thiopentone and vecuronium causes pulmonary embolism.

To examine the effects of a bolus injection of the precipitate formed by thiopentone and vecuronium on the pharmacokinetic behaviour of thiopentone, cardiopulmonary physiology, and lung histology. Of 16 female rabbits (2.9 to 3.1 kg), eight were injected with a precipitate formed by a mixture of 5 mg.kg-1 thiopentone and 0.67 mg.kg-1 vecuronium via the external jugular vein. Eight control rabbits were injected with 5 mg.kg-1 thiopentone alone. Plasma thiopentone concentration, systolic arterial pressure and PaO2 were measured for 60 min after injection. Histological changes in the lungs were evaluated at one and 60 min. Maximum blood thiopentone concentration in the precipitate group was lower than in the control group (12.9 +/- 4.5 vs 17.0 +/- 1.6 micrograms.ml, P < 0.05), although the half-life of thiopentone in the precipitate group was longer (32.3 +/- 8.5 vs 21.7 +/- 8.2 min, P < 0.05) and the area under the time concentration curve was similar between the two groups. However, the mean residence time was 28% longer in the precipitate group than in controls (P < 0.05). The PaO2 was lower in the precipitate group than in controls one minute after injection (431 +/- 27 vs 464 +/- 18 mmHg, P < 0.05) but not subsequently. Histologically, crystals (30-150 microns in diameter) obstructed small arteries in the lungs at one minute but not at 60 min after injection. Intravenous injection of precipitate causes pulmonary microembolism, with a small transient decrease in PaO2.

Coronary constriction and consequent cardiodepression in pulmonary embolism are mediated by pulmonary big endothelin and enhanced in early endothelial dysfunction.

Myocardial ischemia plays a central role in the development of right ventricular failure after acute pulmonary embolism. This study investigates whether pulmonary mediators act specifically on coronary tone and cardiac contractile function in acute pulmonary microembolization and whether such effects are altered in the case of early systemic atherosclerosis. We employ a novel model of serial perfusion in which an isolated rabbit heart is perfused with the effluent of the same animal's isolated lung. Controlled experiment using isolated organs. Experimental laboratory. Male New Zealand White rabbits (controls). Age-matched, male Watanabe rabbits (hypercholesterolemic, development of accelerated atherosclerosis). Seven isolated control and seven isolated Watanabe hearts were perfused with the saline effluent of the same animal's isolated lung. After the assessment of the baseline data, the lungs were gradually embolized with glass beads measuring 100 microm in diameter to induce an increase in mean pulmonary arterial pressure from 6 to 8 mm Hg, at baseline, up to 25 mm Hg. Pulmonary embolization to 25 mm Hg evoked a coronary constriction, measured as coronary flow decrease to 89 +/- 7% of the baseline value in controls. In the Watanabe group, coronary constriction was significantly enhanced, compared with controls, with coronary flow decreasing to 76 +/- 6% of the baseline value. In both groups, coronary constriction was followed by a deterioration in cardiac contractile performance. This cardiodepression was significantly deeper in Watanabe hearts with respect to both maximum ventricular pressures and maximum rates of pressure development and decline. Coronary constriction and cardiodepression were prevented by coronary infusion of the nonselective endothelin antagonist PD-145065, the endothelinA antagonists A-127722 and BQ-123, and the endothelin-converting enzyme inhibitor phosphoramidon. Concentration of big endothelin in pulmonary effluent increased from 5.6 +/- 0.3 pmol/L in controls and 5.6 +/- 0.2 pmol/L in the Watanabe group, at baseline, to 8.8 +/- 0.4 pmol/L in controls and 8.9 +/- 0.4 pmol/L in the Watanabe group, at 25 mm Hg pulmonary arterial pressure. Endothelin was not detectable at any time during the experiment in pulmonary effluent. The coronary gradient, calculated as a difference in concentration between coronary and pulmonary effluent, was negative for big endothelin and positive for endothelin in both groups. We have demonstrated that an increase in pulmonary release of big endothelin occurs during lung embolism, which, in turn, results in coronary constriction and consequent cardiodepression. This action of big endothelin is based on its local coronary conversion into endothelin. In addition, coronary endothelial dysfunction, attributed to early systemic atherosclerosis, was shown to represent a specific risk factor in these events.

Cladribine for Untreated or Early Low-Grade Non-Hodgkin's Lymphoma

Patients and methods: Forty-four patients, with low-grade non-Hodgkin's lymphoma (LG-NHL) were included in a phase II study between June 1993 and May 1995 and treated with cladribine (CdA) 0.12 mg/kg as a 2 h i.v. infusion daily × 5, repeated after 28 days for up to 6 courses. Thirty-four patients were previously untreated and 10 had progressive disease after initial response to limited chlorambucil treatment. Five patients had also received involved field radiotherapy. Eight patients had mantle cell lymphomas, 22 follicle centre lymphomas, 5 lymphoplasmacytoid lymphomas, 4 small cell lymphocytic lymphomas, 4 marginal zone B-cell lymphomas and 1 had unclassified low-grade NHL.The response rate was 64%, with 11 (25%) CR and 17 (39%) PR while 5 (11%) patients progressed during treatment. The response rate was similar in previously treated and untreated patients. The median number of CdA courses delivered was 3 (1-6) in non-responding patients and 6 (2-6) in responders. Median survival from inclusion was not reached with a median follow-up of 40 months. The median time to progression was 7 mo for all patients, 25+ mo for CR and 16 mo for PR patients. Toxicity was sometimes severe with 2 treatment related deaths, one infectious related and one due to a mucocutaneous syndrome and pulmonary microembolism. In addition, 5 grade 3 or 4 infectious episodes were seen. Seven patients experienced grade 3 or 4 thrombocytopenia and 20 had grade 3 or 4 neutropenia. We conclude that the majority of patients with low-grade non-Hodgkin's lymphoma respond to CdA but that the adverse effects may be severe.

Inhaled Nitric Oxide Selectively Decreases Pulmonary Artery Pressure and Pulmonary Vascular Resistance Following Acute Massive Pulmonary Microembolism in Piglets

Acute massive pulmonary embolism increases pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR), which may lead to early right ventricular failure and subsequent cardiocirculatory deterioration. Inhaled nitric oxide (NO) selectively dilates pulmonary vessels in vivo. Thus, inhaled NO may be useful in preventing cardiocirculatory deterioration following pulmonary embolism. We investigated the effects of inhaled NO in the acute phase of massive pulmonary microembolism in 10 anesthetized and mechanically ventilated piglets (body weight, 18 +/- 2 kg). Microspheres of 300-microns diameter were injected i.v. in an amount sufficient to initially increase mean PAP to 45 mm Hg. Forty-five minutes after pulmonary embolization, the pretreatment control values were recorded. Thereafter, the piglets inhaled 40 ppm NO, and subsequently 80 ppm NO. When 40 ppm NO was inhaled, there was a significant decrease in systolic PAP (-10.3%; 44.5 +/- 2.2 to 39.9 +/- 2.4 mm Hg; p < 0.05) and mean PAP (-9.4%; 32.9 +/- 1.3 to 29.8 +/- 1.3 mm Hg; p < 0.05). PVR was changed by -13.6% (p = 0.07). Administration of 80 ppm NO resulted in a significant decrease in systolic PAP (-12.6%; to 38.9 +/- 1.9 mm Hg; p < 0.05), mean PAP (-11.9%; to 29.0 +/- 1.4 mm Hg; p < 0.05), and PVR (-19.4%; p < 0.05) compared with pretreatment values. Discontinuation of NO inhalation was associated with an immediate return to pretreatment values. Systemic hemodynamics and the arterial and mixed venous oxygen concentrations remained unchanged. We conclude that inhaled NO following acute massive pulmonary microembolism selectively decreases PAP and PVR without influencing systemic hemodynamics in piglets.

Effects of inhaled prostacyclin as compared with inhaled nitric oxide in a canine model of pulmonary microembolism and oleic acid edema

Recently, it has been shown that the inhalation of nitric oxide (NO) and of prostacyclin (PGI2) elicits selective pulmonary vasodilation in a canine model of pulmonary hypertension induced by hypoxic pulmonary vasoconstriction. The present study was designed to investigate whether inhaled NO or PGI2-aerosol, respectively, is also effective in decreasing pulmonary artery pressure in a canine model of acute pulmonary microembolism and oleic acid edema. Prospective, randomized, cross-over design. University animal research laboratory. Eight anesthetized, mechanically ventilated dogs (28 +/- 1 kg). Acute pulmonary microembolization (PME) was induced using glass microbeads (mean diameter: 100 microns) and 0.01 mL/kg of oleic acid. Subsequently, inhaled PGI2 (concentration: 10 micrograms/mL) or NO (50 ppm), respectively, was randomly administered for 15 minutes each and then withdrawn. Central hemodynamics (heart rate [HR], cardiac output [CO], stroke volume [SV], mean arterial pressure [MAP], systemic vascular resistance [SVR], mean pulmonary artery pressure [PAP], pulmonary vascular resistance [PVR]) and gas exchange (PaO2/FIO2 ratio, intrapulmonary shunt [Qs/Qt], alveolar-arterial oxygen difference, [AaDO2]) were assessed. Measurements were performed at control, after PME, and during administration of PGI2 and NO, respectively. PME induced a significant increase (p < 0.001) of MAP (+9%), PAP (+68%), and PVR (+163%), whereas HR, CO, and SV remained unchanged and lung function deteriorated. Inhalation of NO slightly decreased PAP (-10%; p < 0.05) and PVR (-26%; p < 0.01) and improved AaDO2 and PaO2/FIO2. In contrast, inhalation of PGI2 had no consistent effect on pulmonary vascular tone or gas exchange. The data demonstrate that inhaled NO may elicit selective pulmonary vasodilation and improve gas exchange in a canine model of pulmonary microembolism and respiratory insufficiency. However, the degree of these effects was relatively small. The aerosolization of PGI2 under conditions of positive-pressure ventilation did not exert a significant vasodilatory effect on pulmonary vessels and did not improve pulmonary gas exchange in this model.

The effect of xylazine on plasma thromboxane B2 concentration in sheep.

alpha 2-adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep. It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet aggregation were to follow platelet activation in response to the administration of alpha 2 agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B2 concentrations before and after the intravenous administration of the alpha 2-agonist drug xylazine at a dose of 0.1 mg/kg. It was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride (0.125 mg/kg), an alpha 2-adrenoceptor antagonist.