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J Motsch

Publications and source records attributed to J Motsch.

At least 37 records · Page 2Linked to original sources

Colour Doppler imaging of the interspinous and epidural space.

BACKGROUND AND OBJECTIVE: In recent studies, ultrasonic diagnostic imaging has proved useful in the screening of the trajectory of the epidural needle. With regard to possible side-effects of spinal and epidural anaesthesia caused by vessel injury, we aimed to evaluate the usability of Colour Doppler imaging for the depiction of interspinous vessels in prepuncture examination. METHODS: Ultrasonic examination of the L3/4 interspace area was performed in 20 volunteers. Using a 4-MHz and a 7-MHz probe with B-mode and Colour Doppler imaging, respectively, we compared four settings for the quality of vessel depiction in the puncture area. Overall resolution was evaluated according to the distinction of landmarks. Vascular structures were identified by pulsation (B-mode) or blood flow (Doppler). RESULTS: Colour Doppler imaging of the L3/4 interspace was unachievable using the 7-MHz transducer. Vessel detection was possible in 50% of the B-mode images and in all of the 4-MHz Doppler images. Vessels were perceptible from a diameter of 0.5 mm. Veins were the predominantly visible structures. Overall vessel visibility was best using 4-MHz Colour Doppler. CONCLUSIONS: Prepuncture Doppler imaging can provide the epiduralist with information regarding the position of vessels in the needle trajectory. This might help to reduce complications in regional anaesthesia.

Adult↗

Psychomotor recovery in very old patients after total intravenous or balanced anaesthesia for cataract surgery.

We compared psychomotor recovery after total intravenous anaesthesia (TIVA) with remifentanil/propofol and balanced anaesthesia (BAL) with etomidate/fentanyl/isoflurane in 40 patients, ASA I-III, aged > or =80 yr undergoing elective cataract surgery. Recovery times were recorded and psychomotor recovery was assessed according to simple reaction time, critical flicker fusion frequency (CFF) and short-term memory 30 min, 2 h and 1 day after surgery. Physical characteristics of patients in the two groups (19 in the TIVA group and 21 in the BAL group) were comparable. The TIVA group recovered significantly more quickly. Both groups showed a poorer psychomotor performance 30 min after surgery than at baseline assessment, but simple reaction time and short-term memory were close to baseline values 2 h after surgery. Only performance in the CFF test remained below baseline at this point. No deficits in psychomotor performance were noted on the first day after surgery. We conclude that there is only a minor deficit in psychomotor function in elderly patients 2 h after cataract surgery under general anaesthesia and that psychomotor function recovers completely by 24 h after surgery.

Aged↗

The lumbar epidural space in pregnancy: visualization by ultrasonography.

Epidural anaesthesia is an important analgesia technique for obstetric delivery. During pregnancy, however, obesity and oedema frequently obscure anatomical landmarks. Using ultrasonography, we investigated the influence of these changes on spinal and epidural anatomy. We examined 53 pregnant women who were to receive epidural block for vaginal delivery or Caesarean section. The first ultrasound imaging was performed immediately before epidural puncture; the follow-up scan was done 9 months later. The ultrasound scan of the spinal column was performed at the L3/4 interspace in transverse and longitudinal planes, using a Sonoace 6000 ultrasonograph (Kretz, Marl, Germany) equipped with a 5.0-MHz curved array probe. We measured two distances from the skin to the epidural space: the minimum (perpendicular) and the maximum (oblique) needle trajectory. The quality of ultrasonic depiction was analysed by a numerical scoring system. An average weight reduction of 12.5 kg had occurred by the follow-up examination. During pregnancy, the optimum puncture site available on the skin for epidural space cannulation was smaller, the soft-tissue channel between the spinal processes was narrower, and the skin-epidural space distance was greater. The epidural space was narrower and deformed by the tissue changes. The visibility of the ligamentum flavum, of the dura mater and of the epidural space decreased significantly during pregnancy. Nevertheless, ultrasonography offered useful pre-puncture information. Thus far, palpation has been the only available technique to facilitate epidural puncture. Ultrasound imaging enabled us to assess the structures to be perforated. We anticipate that this technique will become valuable clinically.

Adult↗

Right ventricular upregulation of the Ca(2+) binding protein S100A1 in chronic pulmonary hypertension.

The Ca(2+) binding protein S100A1 increases the Ca(2+) release from the sarcoplasmatic reticulum by interacting with the ryanodine receptor. In order to understand whether this effect might be operative in the early course of hypertrophy, when myocardium is able to meet increased workload, we investigated the expression of S100A1 in a model of moderate right ventricular hypertrophy. The pulmonary arteries of nine pigs were embolised three times with Sephadex G-50. After 70 days, all pigs showed a moderate pulmonary hypertension. Right ventricular tissue of embolised animals showed a significant increase of connective tissue and enlargement of myocyte diameters. In controls, we found a differential expression of S100A1 with significantly lower S100A1 protein levels in right ventricular compared to left ventricular tissue. In pulmonary hypertension, S100A1 expression increased significantly in hypertrophied right ventricles while it was unchanged in left ventricular tissue. No change was observed in the expression of SERCA2a and phospholamban. Our data show, for the first time, that moderate pressure overload results in an upregulation of S100A1. This may reflect an adaptive response of myocardial Ca(2+) homeostasis to a higher workload.

Adaptation, Physiological↗

[First continuous nerve monitoring in thyroid gland surgery].

UNLABELLED: A new "all in one" sensing device was developed for continuous transtracheal intraoperative monitoring and in situ detection of the recurrent laryngeal nerve (RLN) during thyroid surgery. PATIENTS AND METHODS: The new system is based on a double-balloon endotracheal tube with integrated atraumatic stimulating and tracing electrodes. The recurrent laryngeal nerve is stimulated transtracheally and compound action potentials are recorded from the laryngeal muscles. Fifty-five patients were introduced into a phase-one clinical trial. Thirty-five patients with primary thyroid operations, 20 patients with reoperations, 10 of whom had neck dissections. All patients were evaluated laryngoscopically and phoniatrically by an ENT specialist before and after surgery. RESULTS: Compound muscle action potentials were recorded continuously during the whole operation and responded sensitively to tension and pressure to the nerve. There were no accidental permanent RLN palsies. CONCLUSION: The new system offers five advantages: (1) it is atraumatic; (2) it is easy to use; (3) it can monitor continuously with an audio feedback to the surgeon; (4) it works outside the operation field; and (5) it is highly sensitive, even indicating reversible irritation to the nerve.

Adult↗

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Administration, Inhalation↗

Assessment of sex hormone-binding globulin and osteocalcin in patients undergoing coronary artery bypass graft surgery.

OBJECTIVE: To determine sex hormone-binding globulin (SHBG) and osteocalcin (OC) levels in patients undergoing coronary artery bypass graft surgery to clarify the status of peripheral thyroid metabolism and to correlate SHBG and OC with thyroid hormones and adverse postoperative events. DESIGN: Prospective study. SETTING: University medical center. PARTICIPANTS: Fifty randomly selected patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: On the morning of surgery before induction of anesthesia; 30 minutes after cross-clamping of the aorta; 2 hours and 6 hours after aortic cross-clamp removal; and on the first, second, third, and seventh postoperative mornings, blood samples were drawn and analyzed for OC, SHBG, triiodothyronine (tT3), free T3 (fT3), thyroxine (tT4), free T4 (fT4), thyroid-stimulating hormone, and thyroid-binding globulin. Adverse postoperative events were recorded. MEASUREMENTS AND MAIN RESULTS: Mean tT3 and fT3 decreased on average by 35% and 18% but remained within the normal range perioperatively. Similarly, mean SHBG and OC remained within the normal range. More than half of the patients investigated (60%) had OC concentrations below the normal range. Patients with pathologically decreased tT3 (n = 6) and tT4 (n = 16) intraoperatively and postoperatively had SHBG and OC concentrations similar to those in patients with normal tT3 and tT4 levels. Patients with postoperative complications had significantly lower OC levels preoperatively and on the first postoperative morning than those with an uneventful postoperative recovery. CONCLUSION: Despite significant intraoperative and postoperative decreases in levels of thyroid hormones, low T3 syndrome was rare in this patient population. Unchanged concentrations of SHBG and OC in patients with pathologically decreased tT3 or tT4 suggest normal local thyroid exposure at the tissue sites in these patients. OC may act as a predictor for postoperative outcome.

Adult↗

Rocuronium potency and recovery characteristics during steady-state desflurane, sevoflurane, isoflurane or propofol anaesthesia.

We have studied the potency and recovery characteristics of rocuronium during 1.25 MAC of isoflurane, desflurane, sevoflurane or propofol anaesthesia in 84 patients using electromyography. Potency was determined by a cumulative bolus technique. The mean ED50 of rocuronium was 169 (SD 41), 126 (32), 121 (28) and 136 (25) micrograms kg-1 during propofol, isoflurane, sevoflurane and desflurane anaesthesia, respectively (ns), and ED90 values were 358 (62), 288 (29), 289 (28) and 250 (28) micrograms kg-1, respectively. The reduction in ED90 was statistically significant for all three inhalation anaesthetics (P < 0.05) compared with propofol. After 120 min, the cumulative infusion rate of rocuronium to obtain twitch depression of 90-95% was 9.0 (1.9), 6.3 (1.6), 6.1 (2.0) and 6.1 (1.1) micrograms kg-1 min-1 during propofol, isoflurane, sevoflurane and desflurane anaesthesia, respectively (P < 0.01). Recovery index was 22 (13), 27 (10), 28 (13) and 26 (14) min under propofol, isoflurane, sevoflurane and desflurane anaesthesia, respectively (ns). There were no significant differences between the three potent inhalation anaesthetics in relation to potency, infusion requirements or recovery characteristics of rocuronium.

Adult↗

A dose-ranging study of rapacuronium in pediatric patients.

BACKGROUND: The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. METHODS: Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. RESULTS: Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. CONCLUSIONS: Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.

Age Factors↗

Inhaled nitric oxide does not enhance lipid peroxidation in patients with acute respiratory distress syndrome.

OBJECTIVE: To investigate whether inhaled nitric oxide (NO) enhances pulmonary lipid peroxidation as indicated by arterial blood levels of malondialdehyde, hexanal, and pentanal in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Twenty-five patients with ARDS, as defined by the American-European Consensus Conference, and a PaO2/FIO2 < or = 170 mm Hg were enrolled in the study. Four healthy subjects were studied as controls. INTERVENTIONS: On enrollment of the patients in the study, a dose-response test with increasing concentrations of inhaled NO (0, 2, 10, 40, 0 ppm) was performed. Patients who showed an increase of >20% in PaO2 were designated as responders and all others as nonresponders. In responders, this dose-response test was followed by 24 hrs of continuous treatment with inhaled NO at the best NO concentration determined during the dose-response test, whereas nonresponders received standard care. For healthy volunteers, the dose-response test took the form of spontaneous breathing of the same NO concentrations. MEASUREMENTS AND MAIN RESULTS: Eighteen patients (72%) showed an increase of >20% in PaO2 during the dose-response test. This significant improvement in arterial oxygenation in responders led to a significant reduction in FIO2 (responders, 0.73 +/- 0.05 vs. nonresponders, 0.89 +/- 0.05) after 24 hrs of therapy. On enrollment, arterial blood concentrations of malondialdehyde, hexanal, and pentanal were significantly higher than those of healthy volunteers. In addition, arterial concentrations of hexanal and pentanal exceeded mixed venous levels two- to ten-fold. Inhalation of NO did not significantly alter these blood concentrations either during the dose response test or during 24 hrs of therapy. CONCLUSIONS: In patients with ARDS, malondialdehyde, hexanal, and pentanal were significantly elevated, indicating lipid peroxidation. Lipid peroxidation was not further affected by inhalation of NO.

Administration, Inhalation↗

Randomized, placebo-controlled, blinded and cross-matched study on the antiplatelet effect of inhaled nitric oxide in healthy volunteers.

The platelet inhibitory effect of 0-40 ppm inhaled nitric oxide (NO) was investigated in healthy men and women. In both groups, ADP-and collagen-induced platelet aggregation was significantly inhibited 20 (T20) and 40 min (T40) after the beginning of inhalation of 5, 10, and 40 ppm. Moreover, in both men and women, the in vitro bleeding time was significantly prolonged at T20 and T40 during inhalation of 40 ppm. Inhalation of NO also inhibited P-selectin expression at 5, 10, and 40 ppm and fibrinogen binding to the GPIIb/IIIa-receptor at 40 ppm. In conclusion, in healthy volunteers, the platelet inhibitory effect of inhaled NO was not dose-related, since it was significant at 5 and 10 ppm but did not increase during the administration of higher NO concentrations. In addition, gender-related differences were only observed in ADP-induced platelet aggregation at 10 ppm and in bleeding time prolongation at 40 ppm.

Adenosine Diphosphate↗

Global cerebral ischemia due to cardiocirculatory arrest in mice causes neuronal degeneration and early induction of transcription factor genes in the hippocampus.

To analyze the role of specific genes and proteins in neuronal signaling cascades following global cerebral ischemia, it would be useful to have a reproducible model of global cerebral ischemia in mice that potentially allows the investigation of mice with specific genomic mutations. We first report on the development of a model of reversible cardiocirculatory arrest in mice and the consequences of such an insult to neuronal degeneration and expression of immediate early genes (IEG) in the hippocampus. Cardiocirculatory arrest of 5 min duration was induced via ventricular fibrillation in mechanically ventilated NMRI mice. After successful cardiopulmonary resuscitation (CPR), animals were allowed to reperfuse spontaneously for 3 h (n=7) and 7 days (n=7). TUNEL staining revealed a selective degeneration of a subset of neurons in the hippocampal CA1 sector at 7 days. About 30% of all TUNEL-positive nuclei showed condensed chromatin and apoptotic bodies. Immunohistochemical studies of IEG expression performed at 3 h exhibited a marked induction of c-Fos, c-Jun, and Krox-24 protein in all sectors of the hippocampus, peaking in vulnerable CA1 pyramidal neurons and in dentate gyrus. In contrast, sham-operated animals (n=3) did not reveal neuronal degeneration or increased IEG expression in the hippocampus when compared with untreated control animals (n=3). In conclusion, we present a new model of global cerebral ischemia and reperfusion in mice with the use of complete cardiocirculatory arrest and subsequent CPR. Following 5 min of ischemia, a subset of CA1 pyramidal neurons was TUNEL-positive at 7 days. The expression of IEG was observed in all sectors of the hippocampus, including selectively vulnerable CA1 pyramidal neurons. This appears to be a good model which should be useful in evaluating the role of various genes in transgenic and knockout mice following global ischemia.

Animals↗

[In Process Citation]

The increasing number of high-risk patients and the limited number of intensive care beds and shrinking hospital budgets make it necessary to review perioperative management processes. Analyzing the data of the Heidelberg Anesthesia documentation system revealed improvement strategies in operating room management. The coordination of all groups involved is optimized by an operating room management group. This independent group plans and coordinates the operating room procedures, together with emergency cases according to personal, room and specific needs. Establishment of a holding area and a postoperative anesthesia care unit next to central operating units will significantly improve the perioperative organization processes. Redistribution of personnel enables intermediate care units to be opened, which provide additional intensive care bed capacity.

Journal Article↗

Selective vasodilation by nitric oxide inhalation during sustained pulmonary hypertension following recurrent microembolism in pigs.

PURPOSE: This study establishes a new model of sustained pulmonary hypertension induced by recurrent microembolism in pigs and evaluates the effects of nitric oxide (NO) inhalation in this model. MATERIALS AND METHODS: Fourteen pigs were embolized under general anesthesia with 300-microm microspheres intravenously three times over a period of 7 weeks. Four pigs served as untreated controls. Hemodynamic and gas exchange measurements were performed on days 1 and 7 after the last embolization. RESULTS: Recurrent microembolism caused sustained pulmonary hypertension (mean pulmonary artery pressure [MPAP] 26 +/- 2 and 18 +/- 1 mm Hg on days 1 and 7, respectively) compared with the control group (MPAP 13 +/- 1 mm Hg each for days 1 and 7; P < .05, respectively). Right heart hypertrophy was present at autopsy as indicated by an increase in minimal myocyte diameter. Inhaled NO (5 and 40 parts per million [ppm]) was administered on days 1 and 7. On both days, inhaled NO significantly reduced MPAP and pulmonary vascular resistance without affecting systemic hemodynamics. There were no differences in responses to 5 and 40 ppm inhaled NO. CONCLUSION: We conclude that recurrent microembolization in pigs provides a reliable model of sustained pulmonary hypertension. In this model inhaled NO is a selective pulmonary vasodilator, indicating that active vasoconstriction significantly contributes to sustained pulmonary hypertension after recurrent microembolism.

Analysis of Variance↗

Ropivacaine epidural anesthesia and analgesia versus general anesthesia and intravenous patient-controlled analgesia with morphine in the perioperative management of hip replacement. Ropivacaine Hip Replacement Multicenter Study Group.

UNLABELLED: The aim of our study was to compare epidural anesthesia and analgesia (EDA) with ropivacaine versus general anesthesia followed by IV patient-controlled analgesia with morphine (GA/PCA) after hip replacement regarding pain, side effects, and discharge from the postanesthesia care unit. After ethics committee approval, randomization, and informed consent, 90 patients were enrolled. In Group EDA, epidural anesthesia (ropivacaine 10 mg/mL, 15-25 mL) was followed by an epidural infusion (2 mg/mL, 4-6 mL/h for 24 h, plus top-up doses of 6-10 mL for 48 h). GA/PCA patients received general anesthesia (isoflurane/N2O/fentanyl) followed by IV patient-controlled analgesia with morphine postoperatively. Pain was assessed by using visual analog scales (0-100 mm) at rest and during physiotherapy. Pain at rest was less in the EDA (n = 43) group than in the GA/PCA (n = 45) group (at 10 h: 11.8+/-12.9 vs. 28.4+/-17.1 [P< 0.001]; at 24 h: 14.3+/-11.7 vs. 24.0+/-17 [P<0.01]; in 48 h: 14.3+/-9.3 vs. 21.1+/-17.4 [P = 0.1]). Whereas EDA patients were deemed ready for discharge from the postanesthesia care unit earlier than GA/PCA patients (5.6+/-8.9 vs. 39.7+/-41.5 min), the actual discharge time was comparable. The median time for first passage of flatus was shorter in the EDA group than in the GA/PCA group (26 vs. 47 h). Nausea and vomiting were more common in the GA/PCA group than in the EDA group (16% vs. 28% and 11% vs. 22%, respectively), whereas hypotension (11% vs. 4%) and bradycardia (14% vs. 2%) were less frequent. Under the conditions of the present study, EDA with ropivacaine provided pain control after hip replacement superior to that provided by IV patient-controlled analgesia with morphine, particularly during the first 24 h. Both approaches to pain management were equally safe. IMPLICATIONS: Compared with general anesthesia and postoperative IV patient-controlled analgesia with morphine, epidural anesthesia and analgesia with the new local anesthetic ropivacaine enables patients to be discharged sooner from a postanesthesia care unit and provides superior pain relief during the first 24 h after hip replacement.

Amides↗

Long term outcome after out-of-hospital cardiac arrest with physician staffed emergency medical services: the Utstein style applied to a midsized urban/suburban area.

OBJECTIVE: To test the effect of a physician staffed advanced cardiac life support (ALS) system on patient outcome following out-of-hospital cardiac arrest. DESIGN: Observational study. SETTING: Two tier basic life support (BLS) and physician staffed ALS services in the midsized urban/suburban area of Heidelberg, Germany. PATIENTS: All patients suffering out-of-hospital cardiac arrest of cardiac aetiology between January 1992 and December 1994 and who were covered by ALS services. INTERVENTIONS: Physician staffed ALS services. MAIN OUTCOME MEASURES: Return of spontaneous circulation, hospital discharge, and one year survival, according to the Utstein style. RESULTS: Of 330 000 inhabitants, 755 suffered from cardiac arrest covered by the Heidelberg ALS services. In 512 patients, cardiopulmonary resuscitation had been initiated. Of 338 patients with cardiac aetiology, return of spontaneous circulation was achieved in 164 patients (49%), 48 (14%) were discharged alive, and 40 (12%) were alive one year later; most of these patients showed good neurological outcome. Thus, 4.85 patients with cardiac aetiology were saved by the ALS services and discharged alive per 100 000 inhabitants a year. Ventricular fibrillation or tachycardia was detected in 106 patients (31%), other cardiac rhythms in 40 (12%), and asystole in 192 (57%). Hospital discharge rates (and one year survival) in these subgroups were 34.0% (29.2%), 12.5% (7.5%), and 3.6% (3.1%), respectively. Discharge rates increased if cardiac arrest was witnessed (bystander, 20.0%; BLS/ALS personnel, 21.4%; non-witnessed arrest, 3.3%; p < 0.01), and if the time period between the alarm and the arrival of the ALS unit was four minutes or less (</= 4 minutes, 30.6%; 4-8 minutes, 10.4%; > 8 minutes, 8. 1%; p < 0.001). In 69 patients with bystander witnessed cardiac arrest with ventricular fibrillation, the discharge rate was 37.7%; 21 patients were alive after one year. CONCLUSIONS: A two tier BLS and physician staffed ALS system is associated with good long term outcome of patients suffering from out-of-hospital cardiac arrest of cardiac aetiology in a midsized urban/suburban area. Further studies, however, are required to assess whether having a physician in the ALS unit is an independent determinant for improved long term outcome.

Aged↗

Inhaled nitric oxide inhibits human platelet aggregation, P-selectin expression, and fibrinogen binding in vitro and in vivo.

BACKGROUND: Recent data suggest that inhaled NO can inhibit platelet aggregation. This study investigates whether inhaled NO affects the expression level and avidity of platelet membrane receptors that mediate platelet adhesion and aggregation. METHODS AND RESULTS: In 30 healthy volunteers, platelet-rich plasma was incubated with an air/5% CO2 mixture containing 0, 100, 450, and 884 ppm inhaled NO. ADP- and collagen-induced platelet aggregation, the membrane expression of P-selectin, and the binding of fibrinogen to the platelet glycoprotein (GP) IIb/IIIa receptor were determined before (t0) and during the 240 minutes of incubation. In addition, eight patients suffering from severe adult respiratory distress syndrome (ARDS) were investigated before and 120 minutes after the beginning of administration of 10 ppm inhaled NO. In vitro, NO led to a dose-dependent inhibition of both ADP-induced (3+/-3% at 884 ppm versus 70+/-6% at 0 ppm after 240 minutes; P<.001) and collagen-induced (13+/-5% versus 62+/-5%; P<.01) platelet aggregation. Furthermore, P-selectin expression (36+/-7% of t0 value; P<.01) and fibrinogen binding (33+/-11%; P<.01) were inhibited. In patients with ARDS, after two who did not respond to NO inhalation with an improvement in oxygenation had been excluded, an increase in plasma cGMP, prolongation of in vitro bleeding time, and inhibition of platelet aggregation and P-selectin expression were observed, and fibrinogen binding was also inhibited (19+/-7% versus 30+/-8%; P<.05). CONCLUSIONS: NO-dependent inhibition of platelet aggregation may be caused by a decrease in fibrinogen binding to the platelet GP IIb/IIIa receptor.

Administration, Inhalation↗