Biomedical subjects

T Pernerstorfer

Publications and source records attributed to T Pernerstorfer.

At least 19 recordsLinked to original sources

PubMed2000

Lepirudin blunts endotoxin-induced coagulation activation.

During sepsis, lipopolysaccharide (LPS) triggers the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation resulting in massive thrombin generation and fibrin polymerization. Recently, animal studies demonstrated that hirudin reduced fibrin deposition in liver and kidney and decreased mortality in LPS-induced DIC. Accordingly, the effects of recombinant hirudin (lepirudin) was compared with those caused by placebo on LPS-induced coagulation in humans. Twenty-four healthy male subjects participated in this randomized, double-blind, placebo-controlled, parallel group study. Volunteers received 2 ng/kg LPS intravenously, followed by a bolus-primed continuous infusion of placebo or lepirudin (Refludan, bolus: 0.1 mg/kg, infusion: 0.1 mg/kg/h for 5 hours) to achieve a 2-fold prolongation of the activated partial thromboplastin time (aPTT). LPS infusion enhanced thrombin activity as evidenced by a 20-fold increase of thrombin-antithrombin complexes (TAT), a 6-fold increase of polymerized soluble fibrin, termed thrombus precursor protein (TpP), and a 4-fold increase in D-dimer. In the lepirudin group, TAT increased only 5-fold, TpP increased by only 50%, and D-dimer only slightly exceeded baseline values (P <.01 versus placebo). Concomitantly, lepirudin also blunted thrombin generation evidenced by an attenuated rise in prothrombin fragment levels (F(1 + 2), P <. 01 versus placebo) and blunted the expression of tissue factor on circulating monocytes. This experimental model proved the anticoagulatory potency of lepirudin in LPS-induced coagulation activation. Results from this trial provide a rationale for a randomized clinical trial on the efficacy of lepirudin in DIC. (Blood. 2000;95:1729-1734)

Adult↗

PubMed2000

Partial inhibition of nitric oxide synthase primes the stimulated pathway of vWF-secretion in man.

Increased release of von Willebrand factor (vWF) has been linked to the pathogenesis of atherosclerosis. For this complex disease, impairment of endothelium-derived, nitric oxide production and impaired vascular relaxation has also been reported. Since endothelially produced nitric oxide (NO) is known to inhibit secretion of the Weibel-Palade bodies in animals, we hypothesized that NO could mitigate vWF secretion. In a randomized, placebo controlled cross-over trial, eight male volunteers received N-monomethyl-L-arginine (LNMMA) to block endothelial NO production or placebo, and vWF release was stimulated by infusing desmopressin in three cumulative doses (0.05, 0.15, 0.4 microg/kg) in both periods. At a threshold dose of 0.l5 microg/kg desmopressin, concomitant partial blockade of NO production resulted in 20% higher levels of vWF (P<0.04). However, maximal vWF release after 0.4 microg/kg desmopressin was unaffected by L-NMMA (Delta7% between periods, P=0.88). These data show the dampening effect of NO production on vWF release in response to threshold concentrations of secretagogues. This may in part explain the higher vWF levels in cardiovascular diseases associated with impaired endothelial NO generation.

Adult↗

PubMed2000

Inhaled nitric oxide reduces pulmonary vascular resistance more than prostaglandin E(1) during heart transplantation.

UNLABELLED: Heart transplantation in patients with increased pulmonary vascular resistance is often associated with postbypass right heart failure. We therefore compared the abilities of prostaglandin E(1) (PGE(1)) and inhaled nitric oxide to reduce pulmonary vascular resistance during heart transplantation. Patients undergoing orthotopic heart transplantation for congestive heart failure were randomly assigned to either a PGE(1) infusion at a rate of 8 ng. kg. (-1)min(-1) starting 10 min before weaning from cardiopulmonary bypass (CPB) (n = 34) or inhalation of 4 ppm nitric oxide starting just before weaning from CPB (n = 34). Both treatments were increased stepwise, if necessary, and were stopped 6 h postoperatively. Hemodynamic values were recorded after the induction of anesthesia, 10 and 30 min after weaning from CPB, and 1 h and 6 h postoperatively. Immediately after weaning from CPB, pulmonary vascular resistance was nearly halved in the nitric oxide group but reduced by only 10% in the PGE(1) group. Pulmonary artery pressure was decreased approximately 30% during nitric oxide inhalation, but only approximately 16% during the PGE(1) infusion. Six hours after surgery, pulmonary vascular resistance and pulmonary artery pressure were similar in the two groups. The ratio between pulmonary vascular resistance and systemic vascular resistance was significantly less in the nitric oxide patients at all postbypass times. In contrast, the pulmonary-to-systemic vascular resistance ratio increased approximately 30% in the patients given PGE(1). Cardiac output, heart rate, mean arterial pressure, right atrial pressure, and pulmonary wedge pressure did not differ between the groups. Weaning from CPB was successful in all patients assigned to nitric oxide inhalation; in contrast, weaning failed in six patients assigned to PGE(1) (P = 0.03). IMPLICATIONS: Nitric oxide inhalation selectively reduces pulmonary vascular resistance and pulmonary artery pressure immediately after heart transplantation which facilitates weaning from cardiopulmonary bypass.

Administration, Inhalation↗

PubMed2000

Surgery and intensive care procedures affect the target site distribution of piperacillin.

OBJECTIVE: Therapeutic failure of antibiotic therapy has been ascribed to pharmacokinetic alterations in compromised patient populations. The present study, therefore, aimed at examining the influences of cardiac surgery and intensive care procedures on the postoperative target site distribution of piperacillin. For this purpose, the penetration of piperacillin to the interstitial space fluid, the relevant target site for most bacterial infections, was compared between patients after aortic valve replacement and healthy volunteers. DESIGN: Comparative study in two study populations. SETTING: The intensive care unit and research ward of a university hospital. PATIENTS: The study population included six otherwise healthy patients scheduled to undergo aortic valve replacement and a control group of six healthy male volunteers. INTERVENTIONS: After the administration of a single i.v. infusion of 4.0 g piperacillin, free piperacillin concentrations were measured in the interstitium of skeletal muscle and subcutaneous tissue by in vivo microdialysis and in venous serum. Piperacillin concentrations were assayed with reversed phase high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Interstitial piperacillin concentrations in muscle and subcutaneous adipose tissue were significantly lower in patients compared with volunteers with the area under the curve for the interstitium/area under the curve for serum concentration ratios ranging from 0.25 to 0.27 and from 0.43 to 1.22 in patients and volunteers, respectively (p < .05 between groups). The terminal elimination half-life was markedly prolonged in patients, leading to a concomitant increase in t > minimal inhibitory concentration (MIC) values, the relevant surrogate for therapeutic success of therapy with beta-lactam antibiotics, for strains with MIC50 <4 microg/mL. For strains with MIC50 >20 microl/mL, however, inadequate target site concentrations were attained in the patient population. CONCLUSIONS: During the postoperative and intensive care periods, target site concentrations of piperacillin are markedly altered and decreased. This may also be true for other antibiotic agents and may have clinical implications in that current dosing guidelines may result in inadequate target site concentrations for high-MIC strains. Conceivably, this could lead to therapeutic failure in some patients.

Adult↗

PubMed1999

[Difference between gastric mucosal pCO2 and arterio-intramucosal pCO2 during orthotopic liver transplantation].

Tonometry is a clinically accepted method to monitor blood flow of the splanchnic region, which is of particular interest in orthotopic liver transplantation (OLT). We investigated the hemodynamic changes and the tonometrically registered perioperative course of the difference between gastric mucosal pCO2 (prCO2) and arterial mucosal CO2 (CO2 gap) in 23 patients undergoing OLT without veno-venous bypass. Gastric mucosal pH (pHi) was additionally calculated. Despite significant changes in systemic hemodynamics during the anhepatic stage and after reperfusion and a significant drop in pHi during anhepacy, the difference between prCO2 and CO2 was constant. These contrasting findings of tonometry, i.e. solely a drop in pHi is, in our opinion, a consequence of the poor metabolic capacity of the liver in the perioperative OLT period, which influenced the calculation of the pHi with the Henderson-Hasselbalch equation. We conclude that, due to methodical problems, calculated pHi is not a reliable indicator of splanchnic blood flow and oxygenation during OLT. We therefore suggest that the prCO2 and the CO2 gap be used to monitor the splanchnic region. These parameters, obtained perioperatively, do not indicate a further reduction in splanchnic oxygenation despite profound changes in systemic hemodynamics during OLT without veno-venous bypass.

Adult↗

PubMed1999

Local anaesthesia versus general anaesthesia for cardioverter-defibrillator implantation.

AIMS: Cardioverter-defibrillators are conventionally implanted under general anaesthesia. However, implantation under conscious sedation is being increasingly used. It has been shown that cardioverter-defibrillators can be implanted in a more pacemaker-like approach: under local anaesthesia for the surgical procedure, and with mild sedation for defibrillation threshold testing only. The aim of the present study was to compare local and general anaesthesia in defibrillation threshold testing and implantation of cardioverter-defibrillators. METHODS AND RESULTS: Forty patients were assigned to two groups: in the first 20 consecutive patients the cardioverter-defibrillator was implanted under general anaesthesia (GA), and in the subsequent 20 patients under local anaesthesia (LA). There was no significant difference between the two groups in regard of age, body weight, underlying disease, left ventricular ejection fraction, and NYHA classification. The defibrillation threshold was 13.7 +/- 5.5 J under local anaesthesia versus 10.7 +/- 4.7 J under general anaesthesia (n.s.). For defibrillation threshold testing 7.9 +/- 3.6 shocks had to be applied in patients under general anaesthesia versus 6.2 +/- 1.3 shocks under local anaesthesia (n.s.). Mean heart rate, arterial oxygen saturation and mean arterial blood pressure remained stable throughout defibrillation threshold testing, irrespective of the type of anaesthesia used. The duration of the surgical procedure was 62 +/- 16 min under GA and 60 +/- 14 min under LA (n.s.), however, the entire implantation procedure was significantly longer in patients under general anaesthesia than in those under local anaesthesia (124 +/- 24 min and 97 +/- 22 min, respectively, p < 0.005). There were no complications in either group and the procedure was well tolerated. With the use of local anaesthesia the cost of anaesthesia were reduced by 72%. CONCLUSION: Local anaesthesia in combination with mild sedation is as safe and well tolerated as general anaesthesia in cardioverter-defibrillator implantation. Lidocaine used for local anaesthesia does not adversely affect the defibrillation threshold. Device implantation in a pacemaker-like approach results in a significant reduction in total procedure time and costs, and facilitates scheduling of the procedure.

Anesthesia, General↗

PubMed1999

Acetaminophen has greater antipyretic efficacy than aspirin in endotoxemia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the antipyretic efficacy of aspirin and acetaminophen (INN, paracetamol) in 30 male volunteers with the use of endotoxin (lipopolysaccharide) to elicit a standardized febrile response. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in parallel groups. Subjects received an intravenous endotoxin bolus of 4 ng/kg after premedication with either placebo, 1000 mg aspirin, or 1000 mg acetaminophen by mouth. RESULTS: Peak body temperatures were 38.5 degrees C +/- 0.2 degrees C in the placebo group, 37.6 degrees C +/- 0.2 degrees C in the acetaminophen group (P = .001 versus placebo), and 38.6 degrees C +/- 0.2 degrees C in the subjects treated with aspirin (P = .001 versus acetaminophen; P = .570 versus placebo) at 4 hours after lipopolysaccharide infusion. Subjective symptom scores for chills and perception of fever were higher in the placebo group than in the acetaminophen group (chills, 2.5 +/- 0.3 versus 1.0 +/- 0.2, P = .009 and fever, 2.5 +/- 0.2 versus 2.0 +/- 0.2, P = .021). Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 levels rose by several orders of magnitude (P < .001 versus baseline in all groups), without significant intergroup differences. CONCLUSIONS: Acetaminophen was the superior antipyretic drug in endotoxemia compared with aspirin. Treatment with acetaminophen ameliorates subjective symptoms induced by endotoxemia without compromising the humoral response of a subject to endotoxin. This observation has clinical interest and may also help to improve the lipopolysaccharide model, which can be used to test anti-inflammatory and anticoagulatory drugs.

Acetaminophen↗

PubMed1999

Splanchnic circulation is maintained during passive hyperventilation in orthotopic liver recipients.

BACKGROUND: Mechanical hyperventilation is an established treatment to reduce brain edema and intracranial pressure in patients with encephalopathia caused by acute liver failure. Hyperventilation and ensuing hypocarbia may also affect central and systemic circulation and thereby influence graft performance in patients following orthotopic liver transplantation (OLT). METHODS: We measured the effects of normocapnia and hypocapnia on systemic hemodynamics, gastric tonometry, as a marker of splanchnic oxygenation, and the indocyanine green kinetic, as a global marker of graft function, in humans post OLT. RESULTS: Hyperventilation was performed to a PaCO2 of 4.2 +/- 0.4 kPa (31 +/- 3.4 mm Hg) for about 1 h in 14 liver transplant recipients. Systemic hemodynamics as well as indices of splanchnic oxygenation and indocyanine green kinetics remained statistically unchanged. CONCLUSION: We did not observe any statistically significant circulatory effects or changes in indocyanine green kinetics in liver transplant recipients in the immediate OLT postoperative period caused by short-term mechanical hyperventilation.

Blood Pressure↗

PubMed1999

Heparin lowers plasma levels of activated factor VII.

Based on heparin's antithrombin and anti-FXa activity and its in vitro inhibition of activated factor VII (FVIIa) activity, we hypothesized that unfractionated heparin (UFH) may decrease plasma levels of FVIIa in humans. Therefore, 10 healthy young male volunteers received an intravenous UFH infusion over 24 h. Heparin decreased FVIIa levels by 30% (95% CI 14-47%) at 12 h, which was sustained until 24 h. In contrast, neither the substrate pool (i.e. total factor VII) as measured by FVII antigen nor FVII activity were affected by UFH. These results may improve our understanding of the regulation of FVIIa levels and heparin's mode of action.

Adult↗

PubMed1999

Effects of nitric oxide on platelet activation during plateletpheresis and in vivo tracking of biotinylated platelets in humans.

BACKGROUND: The use of platelet transfusions has risen considerably over the last few years, which leads to the collection and transfusion of a greater number of donor plateletpheresis units. Plateletpheresis activates platelets in platelet concentrates, which determines the degree of the storage lesion subsequently observed. STUDY DESIGN AND METHODS: As nitric oxide (NO) is a potent inhibitor of platelet aggregation and activation, a placebo-controlled crossover trial was performed in healthy young male volunteers to determine whether the NO-donating compound, sodium nitroprusside (SNP), decreases platelet activation during apheresis and whether activated (p-selectin+) platelets circulate in vivo after transfusion. The study also investigated whether nonradioactive biotin labeling of apheresis platelets is feasible for the study of platelet recovery after transfusion in humans. RESULTS: Platelet activation increased after plateletpheresis in the platelet components, but SNP did not inhibit platelet activation during apheresis, as measured by the percentage of p-selectin expression and the secretion of soluble p-selectin and RANTES. Only a minor increase in p-selectin+ platelets was seen in peripheral blood at 60 minutes after transfusion of the platelets, a rise that was considerably less than that calculated in p-selectin+ platelets if they all were recovered as activated platelets after transfusion. Biotin-labeled platelets averaged 1.5 percent at 10 minutes after transfusion and increased slowly to 2.6 and 3.4 percent after 60 minutes and 24 hours, respectively (p<0.05). CONCLUSION: SNP does not decrease platelet activation during apheresis and subsequent storage, and only a minor proportion of activated (p-selectin+) platelets circulate after transfusion in men. Moreover, biotin labeling of PCs can safely be used in humans for the study of platelet recovery after transfusion, and measuring recovery at 1 hour may lead to an underestimation of the true recovery when activated platelets are transfused.

Biotinylation↗

PubMed1999

Systemic blood pressure and cerebral blood flow velocity during carotid surgery.

BACKGROUND: To evaluate the effect of mean arterial blood pressure (MAP) on cerebral perfusion during carotid surgery, we investigated blood flow velocity in the middle cerebral (Vs,mca) using transcranial Doppler ultrasonography (TCD). METHODS: During carotid crossclamping, treatment included either phenylephrine-induced hypertension without shunting (Group XC; n = 11) or insertion of a shunt (Group S; n = 12). RESULTS: Increasing MAP in Group XC before crossclamping (81 + /-13 mmHg to 107 +/- 12 mmHg) caused an increase of Vs,mca (59 +/- 17 cm/s to 75 +/- 20 cm/s; p < 0.001). During crossclamping without a shunt, Vs,mca was not dependent on MAP, and was reduced (mean 47 +/- 24 cm/s) in relation to preclamp values. In Group S, Vs,mca was always dependent on MAP and the preclamp velocity was maintained (before shunt: 75 +/- 26 cm/sec; during shunt: 79 +/- 30 cm/sec). CONCLUSIONS: Although we found an impaired cerebral autoregulation, Vs,mca was independent of MAP during carotid crossclamping. Thus, TCD measurements have to be interpreted with caution during crossclamping, and the effect of induced hypertension has to be confirmed with more invasive measures of cerebral blood flow.

Aged↗

PubMed1999

Inhalation of nitric oxide as a life-saving therapy in a patient after pulmonary embolectomy.

We describe a 54-yr-old man with cardiogenic shock caused by acute right heart failure after pulmonary embolectomy. Inhalation of nitric oxide led to immediate improvement in respiratory and haemodynamic variables. Inhaled nitric oxide can be used to reduce acute right heart failure until conventional therapy can provide successful haemodynamic stability.

Administration, Inhalation↗

PubMed1999

Endotoxin-induced activation of the coagulation cascade in humans: effect of acetylsalicylic acid and acetaminophen.

During Gram-negative septic shock, lipopolysaccharide (LPS, endotoxin) induces tissue factor (TF) expression. TF expression is mediated by nuclear factor kappaB and amplified by activated platelets. TF forms a highly procoagulant complex with activated coagulation factor VII (FVIIa). Hence, we hypothesized that aspirin, which inhibits LPS-induced, nuclear factor kappaB-dependent TF expression in vitro and platelet activation in vivo, may suppress LPS-induced coagulation in humans. Therefore, we studied the effects of aspirin on systemic coagulation activation in the established and controlled setting of the human LPS model. Thirty healthy volunteers were challenged with LPS (4 ng/kg IV) after intake of either placebo or aspirin (1000 mg). Acetaminophen (1000 mg) was given to a third group to control for potential effects of antipyresis. Neither aspirin nor acetaminophen inhibited LPS-induced coagulation. However, LPS increased the percentage of circulating TF(+) monocytes by 2-fold. This increase was associated with a decrease in FVIIa levels, which reached a minimum of 50% 24 hours after LPS infusion. Furthermore, LPS-induced thrombin generation increased plasma levels of circulating polymerized, but not cross-linked, fibrin (ie, thrombus precursor protein), whereas levels of soluble fibrin were unaffected. In summary, a single 1000-mg dose of aspirin did not decrease LPS-induced coagulation. However, our study showed, for the first time, that LPS increases TF(+) monocytes, substantially decreases FVIIa levels, and enhances plasma levels of thrombus precursor protein, which may be a useful marker of fibrin formation in humans.

Acetaminophen↗

PubMed1999

Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin.

Gram-negative septic shock is mediated in part by endotoxin (lipopolysaccharide; LPS), and animal models have shown that blockade of even single adhesion molecules considerably improves survival. Thus interference with the adhesion cascade may provide a useful therapeutic approach in human sepsis. Young healthy men (n = 30) each received a bolus of 4 ng/kg LPS intravenously to study the effects of endotoxemia on adhesion processes in humans and to identify potential targets for pharmacologic intervention. One third of subjects received pretreatment with 1,000 mg aspirin and 1,000 mg paracetamol to study potential antiinflammatory effects of aspirin or effects of antipyresis. Circulating neutrophils dropped by -80% at 67 min after LPS, monocytes by -96% at 90 min, and lymphocytes by -85% at 240 min. L-selectin expression decreased, particularly on monocytes. Circulating (c)E-selectin levels increased by 820%, von Willebrand factor-Ag (vWF), soluble thrombomodulin, circulating (c)P-selectin, circulating intercellular adhesion molecule-1 (cICAM-1), and circulating vascular cell adhesion molecule-1 (cVCAM-1) by a mean of 65 to 98% (p < 0.001 for all), but cL-selectin by only 15%. Urinary excretion of soluble adhesion molecules was negligible. Aspirin had no influence on the LPS-induced changes of adhesion parameters, but paracetamol blunted the relative increase in vWF while having no effects on the other parameters measured. The consistent, profound, and early upregulation of cE-selectin during endotoxemia indicates that cE-selectin may be a better surrogate marker to monitor the activation status of endothelial cells in systemic inflammation than the other markers measured. Although aspirin did not have any antiinflammatory effects in this model, paracetamol lowered the relative increase in vWF.

Acetaminophen↗

PubMed1999

Effects of endotoxemia on thrombopoiesis in men.

BACKGROUND: Febrile conditions are often associated with increased platelet turnover and refractoriness to platelet transfusions, although several pyrogenic cytokines enhance thrombopoiesis. This study aimed to characterize the effects of experimental human endotoxemia on platelet turnover and thrombopoiesis. METHODS: Endotoxin (4 ng/kg) was infused into 30 healthy men to study the regulation of thrombopoiesis in systemic human inflammation. Platelet counts, plasma thrombopoietin (TPO) and glycocalicin levels, and reticulated platelets (RP) were measured to evaluate the effect of acute endotoxemia on thrombopoiesis. Ten subjects received pretreatment with 1000 mg aspirin po. to evaluate possible effects of aspirin on platelet turnover, and ten subjects received paracetamol to control for effects of antipyresis. RESULTS: Platelet counts dropped by about 15% (p <0.001) one hour after LPS infusion, began to recover at 24 h, and exceeded baseline values by 81% (CI: 5-12; p <0.001 ) at 7 days after LPS iv. Reticulated platelet counts increased from 1.62% (CI: 1.24-2.0) to a maximum of 2.39% (CI: 1.81-2.98; p = 0.003) at 6 h. TPO levels increased from baseline values of 10 A.U/ml (CI: 8.8-11.2) to 15.5 A.U/ml (CI: 13.6-17.3) at 24 h (p <0.001), whereas plasma glycocalicin was not changed (p >0.05). The number of circulating platelet-neutrophil aggregates increased more than 100% at 6 h (p <0.001). Neither aspirin nor paracetamol affected changes in any of the parameters measured. CONCLUSION: Low grade endotoxemia induces a rapid fall of platelet counts, which is followed by an early increase in reticulated platelets and TPO levels but not of glycocalicin levels. Finally peripheral platelet counts increase several days after LPS infusion.

Adult↗

PubMed1998

Jugular venous bulb oxygen saturation depends on blood pressure during cardiopulmonary bypass.

BACKGROUND: Central nervous system dysfunction after cardiopulmonary bypass is frequent and can be caused by inadequate cerebral perfusion and oxygenation. METHODS: To test the effectiveness of cerebral autoregulation during cardiopulmonary bypass, we induced changes in the cerebral perfusion pressure by administering phenylephrine during moderate (29 degrees C) hypothermia. Using the Fick principle, we calculated relative changes in cerebral blood flow from changes in the jugular venous bulb oxygen saturation. RESULTS: Increasing the cerebral perfusion pressure (from 47 +/- 8.2 to 93 +/- 16 mm Hg) induced increases in the jugular venous bulb oxygen saturation by 4.9% and a calculated increase in the cerebral blood flow by 19.9%, strongly suggesting impaired cerebral autoregulation. CONCLUSIONS: Because cerebral autoregulation is impaired during cardiopulmonary bypass, phenylephrine is effective in increasing the cerebral blood flow and may contribute to the prevention of postoperative neurologic dysfunction, especially in patients who have a low jugular venous bulb oxygen saturation.

Blood Pressure↗

PubMed1998

Effects of histamine and nitric oxide synthase inhibition on plasma levels of von Willebrand factor antigen.

Endothelial cells release von Willebrand factor (vWf) either constitutively or by a regulated pathway. Based on various studies in vitro, we hypothesized that the stimulatory action of histamine on vWf release could also be induced in vivo and that it may be inhibited by endogenous production of nitric oxide (NO). Nine healthy subjects received placebo or one of two dosages of a primed constant infusion of the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) in a randomized, double-blind, three-way crossover trial. Histamine was coinfused for 15 minutes at 0.16 microg/kg/min after 30 minutes of pretreatment with either placebo or L-NMMA. Thirty minutes after either the low or the high L-NMMA dose was started, which caused, respectively, a 40% decrease and a 60% decrease in exhaled end expiratory NO level (p = 0.008), there was no increase in von Willebrand factor antigen (vWf-Ag) level (p > 0.05). Histamine caused an 11% (95% confidence interval (CI): 0.4% to 22%; p = 0.011) increase in vWf-Ag level at 125 minutes. After pretreatment with the low and the high L-NMMA doses, vWf-Ag level increased by 18% (Cl: 5% to 31%; p = 0.011) and by 29% (CI: 15% to 42%; p = 0.008), respectively. At 125 minutes, vWf-Ag level was significantly higher after either L-NMMA pretreatment when compared with the results after histamine alone (p < 0.05). In conclusion, the infusion of histamine increased vWf-Ag level, and the inhibition of NO-synthase enhanced this effect, whereas it did not by itself elevate vWf-Ag level. Thus endogenously produced NO may dampen the regulated pathway of vWf secretion; it will be interesting to investigate whether endogenous NO production also inhibits vWf release caused by other stimulators.

Antigens↗

PubMed1998

Effects of nitroglycerin and sodium nitroprusside on endexpiratory concentrations of nitric oxide in healthy humans.

The cellular origin of nitric oxide (NO) in exhaled air of healthy humans is unknown. It is currently not known, whether changes in NO concentrations that originate from pulmonary vessels, can be detected as changes in exhaled NO. Thus, we have studied the effects of increased intravascular NO generation on endexpiratory NO-levels. Twenty-four young healthy volunteers received nitroglycerin (GTN), sodium nitroprusside (SNP) or placebo i.v. in a randomized, double blind cross-over trial. Diastolic blood pressure decreased from 59 mmHg (95% confidence interval: 56-62) during placebo to 48 mmHg (CI: 45-51) and to 48 mmHg (CI: 45-50) after infusions of GTN and SNP, respectively. Heart rate increased from 69 (CI: 65-73) during placebo to 78 (CI: 72-84) and to 84 (CI: 77-92) after infusions of GTN and SNP, respectively (p<0.01 for all comparisons). However, no increase in exhaled NO was detected: endexpiratory NO-concentrations averaged 6.1 ppb (CI: 4.9-7.4), 5.7 ppb (CI: 4.4-7.0) and 6.4 ppb (CI: 5.3-7.6) under placebo, GTN and SNP infusions, respectively (Friedman ANOVA p=0.328). NO release from within the pulmonary vasculature does not significantly contribute to endexpiratory NO concentrations in non-intubated healthy humans suggesting that such NO measurements quantify NO production mainly from non-vascular pulmonary cells.

Adult↗