Learning curve and functional outcomes after laser enucleation of the prostate for benign prostate hyperplasia according to surgeon's caseload.

PURPOSE: To evaluate the impact of surgical caseload on safety, efficacy, and functional outcomes of laser enucleation of the prostate (LEP) applying a structured mentoring program. METHODS: Patient characteristics, perioperative data, and functional outcomes were analyzed descriptively. Linear and logistic regression models analyzed the effect of caseload on complications, functional outcomes and operative speed. Within the structured mentoring program a senior surgeon was present for the first 24 procedures completely, for partial steps in procedures 25-49, and as needed thereafter. RESULTS: A total of 677 patients from our prospective institutional database (2017-2022) were included for analysis. Of these, 84 (12%), 75 (11%), 82 (12%), 106 (16%), and 330 patients (49%) were operated by surgeons at (A) < 25, (B) 25-49, (C) 50-99, (D) 100-199, and (E) ≥ 200 procedures. Preoperative characteristics were balanced (all p > 0.05) except for prostate volume, which increased with caseload. There was no significant difference in change of IPSS, Quality of life, ICIQ, pad usage, peak urine flow, residual urine, and major complications (Group A: 8.3 to E: 7.6%, p = 0.2) depending on the caseload. Caseload was not associated (Odds ratio: 0.7-1.4, p > 0.2) with major complications in the multivariable logistic regression model. Only operating time was significantly shorter with increasing caseload in the multivariable analysis (111-55 min, beta 23.9-62.9, p < 0.001). CONCLUSION: With a structured mentoring program, the safety and efficacy of LEP can be ensured even during the learning curve with very good outcome quality. Only the operating time decreases significantly with increasing experience of the surgeon.

[Perioperative blood pressure management : What is the optimal pressure?] / Perioperatives Blutdruckmanagement : Was ist der optimale Druck?

BACKGROUND: Measurement of blood pressure is part of standard monitoring procedures in anesthesia, in addition to the other vital parameters of heart frequency and peripheral oxygen saturation. In recent years the relevance of the duration and extent of perioperative episodes of hypotension for the occurrence of postoperative complications or even increased mortality have become the focus of scientific investigations. OBJECTIVE: The aim of this review is to briefly recapitulate the physiological aspects of blood pressure and to describe the pathophysiology and risk factors of perioperative hypotension. It describes which potential organ damage can be caused by hypotension and discusses which perioperative blood pressure values are acceptable without harming the patient. METHODS: Review and analysis of the currently available literature. RESULTS: Perioperative hypotension is defined by either absolute systolic arterial pressure (SAP) or mean arterial pressure (MAP) thresholds and by relative blood pressure declines from an individual preoperative baseline value. For the definition of absolute and relative thresholds it needs to be considered that the ultimate target is an adequate perfusion pressure (and not the MAP) and that the preinduction blood pressure is a poor reflection of the patients' normal blood pressure profile. Risk factors for an intraoperative drop in blood pressure are advanced age, higher American Society of Anesthesiologists (ASA) status, low blood pressure prior to induction of anesthesia, the premedication, e.g. angiotensin-converting enzyme (ACE) inhibitors, the anesthesia technique (combination of general and epidural anesthesia) and emergency surgery. The lowest tolerable intraoperative blood pressure should be defined according to the individual patient's preoperative blood pressure and risk profile. Individual thresholds should be determined for the severity and duration of intraoperative hypotension. Empirically, MAP values <65 mm Hg and relative pressure declines of >20-30% are often recommended as thresholds. Below critical blood pressure values the risk of postoperative organ damage (myocardium, kidneys and central nervous system) and mortality increases with longer duration of hypotension. Older people and high-risk patients (e.g. patients in vascular surgery) have a poorer and shorter tolerance of low blood pressure. Postoperative organ complications can be minimized by maintenance of an adequate intraoperative blood pressure CONCLUSION: Anesthesiologists should avoid extensive and prolonged hypotension by timely interventions in order to improve the postoperative outcome of patients.

Drosophila KASH-domain protein Klarsicht regulates microtubule stability and integrin receptor localization during collective cell migration.

During collective migration of the Drosophila embryonic salivary gland, cells rearrange to form a tube of a distinct shape and size. Here, we report a novel role for the Drosophila Klarsicht-Anc-Syne Homology (KASH) domain protein Klarsicht (Klar) in the regulation of microtubule (MT) stability and integrin receptor localization during salivary gland migration. In wild-type salivary glands, MTs became progressively stabilized as gland migration progressed. In embryos specifically lacking the KASH domain containing isoforms of Klar, salivary gland cells failed to rearrange and migrate, and these defects were accompanied by decreased MT stability and altered integrin receptor localization. In muscles and photoreceptors, KASH isoforms of Klar work together with Klaroid (Koi), a SUN domain protein, to position nuclei; however, loss of Koi had no effect on salivary gland migration, suggesting that Klar controls gland migration through novel interactors. The disrupted cell rearrangement and integrin localization observed in klar mutants could be mimicked by overexpressing Spastin (Spas), a MT severing protein, in otherwise wild-type salivary glands. In turn, promoting MT stability by reducing spas gene dosage in klar mutant embryos rescued the integrin localization, cell rearrangement and gland migration defects. Klar genetically interacts with the Rho1 small GTPase in salivary gland migration and is required for the subcellular localization of Rho1. We also show that Klar binds tubulin directly in vitro. Our studies provide the first evidence that a KASH-domain protein regulates the MT cytoskeleton and integrin localization during collective cell migration.

[Pediatric anesthesia for proton radiotherapy : medicine remote from the medical centre]. / Kinderanästhesie zur protonenbestrahlung : medizin fernab der klinik.

Anesthesia care for infants and young children for proton beam radiotherapy demands great technical and vocational skills from the anesthesia team and also a high degree of competence in soft skills. The anesthesia team should be experienced and regularly trained in pediatric anesthesia, especially as the children are often in a reduced general condition. The infrastructure should be established according to the current standards in anesthesiology. Monitoring of vital data, thorax excursions and inadvertent movements of the remotely positioned and sedated patient need to be under constant technical and optical surveillance. Propofol is an ideal hypnotic for the sedation of children under spontaneous breathing for proton beam radiation therapy. It is well tolerated even when given on a daily basis over several weeks. A close cooperation between the pediatric oncologist, radiation oncologist and anesthetist is important in order to manage additional medical problems in an optimal way. The special needs of oncology patients must be taken into consideration when planning anesthesia care.

[Movember health care initiative 2019: prostate cancer screening at the University Hospital Frankfurt]. / Urologische Prostatakrebsvorsorge im Rahmen der Movember-Gesundheitsinitiative 2019 am Universitätsklinikum Frankfurt.

BACKGROUND: Men die earlier than women in Germany. Men also have impaired access to cancer screening compared to women. OBJECTIVES: Our Movember campaign 2019 at University Hospital Frankfurt (UKF) aimed at improving health care awareness in the context of prostate cancer checkup. MATERIALS AND METHODS: In November 2019, every male employee of the UKF with a minimum age of 45 yrs (or 40 yrs with a first degree relative with prostate cancer) was offered a free prostate cancer checkup. This checkup contained digital rectal examination (DRE), transrectal ultrasound and PSA (prostata-specific antigen) testing. RESULTS: Overall, 121/840 employees (14.4%) participated in the Movember campaign. A first degree relative with prostate cancer was reported in overall by 14% of the participants (n = 17). At least one prior prostate cancer check up had 33%. A total of 2.5% (n = 3) had one prior negative prostate biopsy. Median age was 54 yrs (interquartile range 50-58). Median PSA level was 0.9 ng/ml and median free-PSA 0.3 ng/ml. A suspicious DRE was found in 5% (n = 6). After stratification according to age (≤ 50 yrs vs. > 50 yrs), participants over 50 yrs had a significantly higher PSA level (1.0 ng/ml vs. 0.7 ng/ml, p < 0.01) and had more frequently at least one prior prostate cancer checkup in the past (42.0 vs. 12.1%, p < 0.01). All suspicious DREs were in the cohort > 50 yrs. Overall, 32.2% (n = 39) had at least a suspicious checkup. A total of 3.3% (n = 4) had suspicious PSA levels. 17.4% (n = 21) of the participants had a suspicious PSA ratio (< 20%) only. During follow-up, 6 prostate biopsies were performed, with the detection of one case of intermediate-risk prostate cancer (Gleason 3 + 4, pT3a, pPn1, pNx, R0). CONCLUSION: Overall, 121 employees participated in our Movember Prostate cancer checkup campaign with measurement of the PSA level. Suspicious results were recorded in 32.2%. One employee was diagnosed and successfully treated with an intermediate-risk prostate cancer.

Dynein-mediated cargo transport in vivo. A switch controls travel distance.

Cytoplasmic dynein is a microtubule-based motor with diverse cellular roles. Here, we use mutations in the dynein heavy chain gene to impair the motor's function, and employ biophysical measurements to demonstrate that cytoplasmic dynein is responsible for the minus end motion of bidirectionally moving lipid droplets in early Drosophila embryos. This analysis yields an estimate for the force that a single cytoplasmic dynein exerts in vivo (1.1 pN). It also allows us to quantitate dynein-mediated cargo motion in vivo, providing a framework for investigating how dynein's activity is controlled. We identify three distinct travel states whose general features also characterize plus end motion. These states are preserved in different developmental stages. We had previously provided evidence that for each travel direction, single droplets are moved by multiple motors of the same type (Welte et al. 1998). Droplet travel distances (runs) are much shorter than expected for multiple motors based on in vitro estimates of cytoplasmic dynein processivity. Therefore, we propose the existence of a process that ends runs before the motors fall off the microtubules. We find that this process acts with a constant probability per unit distance, and is typically coupled to a switch in travel direction. A process with similar properties governs plus end motion, and its regulation controls the net direction of transport.

[Erythrocyte transfusion: update of the guidelines "therapy with blood components and plasma derivatives"]. / Erythrozytentransfusion : Update zu den Leitlinien "Therapie mit Blutkomponenten und Plasmaderivaten"

The new version of the guidelines, which have now been renamed Cross-sectional guidelines on therapy with blood components and plasma derivatives, is distinguished by focusing on key recommendations. In each section clear recommendations for the selection and indications for the use of each blood product are presented and these recommendations are classified with respect to their strength and evidence level. The most important recommendations in section 1 "Erythrocyte concentrates", which is especially important for the faculty of anesthesiology, will be presented in this article with special reference to the data on which the recommendations are based.

Lipid droplet motility and organelle contacts.

Lipid droplets (LDs) are fat storage organelles integral to energy homeostasis and a wide range of cellular processes. LDs physically and functionally interact with many partner organelles, including the ER, mitochondria, lysosomes, and peroxisomes. Recent findings suggest that the dynamics of LD inter-organelle contacts is in part controlled by LD intracellular motility. LDs can be transported directly by motor proteins along either actin filaments or microtubules, via Kinesin-1, Cytoplasmic Dynein, and type V Myosins. LDs can also be propelled indirectly, by hitchhiking on other organelles, cytoplasmic flows, and potentially actin polymerization. Although the anchors that attach motors to LDs remain elusive, other regulators of LD motility have been identified, ranging from modification of the tracks to motor co-factors to members of the perilipin family of LD proteins. Manipulating these regulatory pathways provides a tool to probe whether altered motility affects organelle contacts and has revealed that LD motility can promote interactions with numerous partners, with profound consequences for metabolism. LD motility can cause dramatic redistribution of LDs between a clustered and a dispersed state, resulting in altered organelle contacts and LD turnover. We propose that LD motility can thus promote switches in the metabolic state of a cell. Finally, LD motility is also important for LD allocation during cell division. In a number of animal embryos, uneven allocation results in a large difference in LD content in distinct daughter cells, suggesting cell-type specific LD needs.

What predicts the outcome in patients with intestinal ischemia? A single center experience.

BACKGROUND: Acute mesenteric ischemia (AMI) is associated with a mortality of 60-80%. Early diagnosis and rapid treatment have a decisive influence on therapy. The aim of this study was to evaluate the prognostic value of AMI markers on mortality, in order to better anticipate the clinical course and to initiate therapeutic steps at an early stage. STUDY DESIGN: An analysis from our prospective database of 302 consecutive patients with AMI who were treated surgically in the Department of General Surgery between February 2003 and October 2014 was performed. Uni- and multivariate analysis of risk factors for mortality have been performed in the total cohort and in two subgroups according to their stay in intensive care unit (ICU) at the time of AMI diagnosis. RESULTS: Of the 302 patients with AMI, 115 were in ICU at the time of diagnosis. Totally, 203 patients underwent computed tomography scan (CT-scan) of the abdomen for diagnosis and 68% of them showed specific signs of AMI. A total of 63 (21%) embolectomies were performed during the surgical procedure. The post-operative mortality rate was 68% (204 patients). Among survivors, 85 (87%) patients developed a short bowel syndrome in the post-operative course. Multivariate analysis showed a significant association between mortality and preoperative lactate>3mmol/L, C-reactive protein>100mg/L and ICU stay at the time of AMI diagnosis. CONCLUSION: Mortality of patients with AMI remains high. Elevated lactate, elevated C-reactive protein and ICU stay are factors associated with increased mortality. Their presence in a patient with suspicion of AMI should trigger a multidisciplinary management in emergency.

Evaluation of the MDACC clinical classification system for pancreatic cancer patients in an European multicenter cohort.

BACKGROUND: The MDACC group recommends to extend the current borderline classification for pancreatic cancer into three groups: type A patients with resectable/borderline tumor anatomy, type B with resectable/borderline resectable tumor anatomy and clinical findings suspicious for extrapancreatic disease and type C with borderline resectable and marginal performance status/severe pre-existing comorbidity profile or age>80. This study intents to evaluate the proposed borderline classification system in a multicenter patient cohort without neoadjuvant treatment. METHODS: Evaluation was based on a multicenter database of pancreatic cancer patients undergoing surgery from 2005 to 2016 (n = 1020). Complications were classified based on the Clavien-Dindo classification. χ2-test, Kaplan-Meier estimator and Cox regression hazard model were used for statistical analysis. RESULTS: Most patients (55.1%) were assigned as type A patients, followed by type C (35.8%) and type B patients (9.1%). Neither the complication rate, nor the mortality rate revealed a correlation to any subgroup. Type B patients had a significant worse progression free (p < 0.001) and overall survival (p = 0.005). Type B classification was identified as an independent prognostic marker for progression free survival (p = 0.005, HR 1.47). CONCLUSION: The evaluation of the proposed classification in a cohort without neoadjuvant treatment did not justify an additional medical borderline subgroup. A new subgroup based on prognostic borderline patients might be the main target group for neoadjuvant protocols in future.

A new method for manipulating transgenes: engineering heat tolerance in a complex, multicellular organism.

BACKGROUND: Heat-shock proteins (hsps) are thought to protect cells against stresses, especially due to elevated temperatures. But while genetic manipulation of hsp gene expression can protect microorganisms and cultured metazoan cells against lethal stress, this has so far not been demonstrated in multicellular organisms. Testing whether expression of an hsp transgene contributes to increased stress tolerance is complicated by a general problem of transgene analysis: if the transgene cannot be targeted to a precise site in the genome, newly observed phenotypes may be due to either the action of the transgene or mutations caused by the transgene insertion. RESULTS: To study the relationship between heat tolerance and hsp expression in Drosophila melanogaster, we have developed a novel method for transgene analysis, based upon the site-specific FLP recombinase. The method employs site-specific sister chromatid exchange to create an allelic series of transgene insertions that share the same integration site, but differ in transgene copy number. Phenotypic differences between members of this series can be confidently attributed to the transgenes. Using such an allelic series and a novel thermotolerance assay for Drosophila embryos, we investigated the role of the 70 kD heat-shock protein, Hsp 70, in thermotolerance. At early embryonic stages, Hsp70 accumulation was rate-limiting for thermotolerance, and elevated Hsp70 expression increased survival at extreme temperatures. CONCLUSION: Our results provide an improved method for analyzing transgenes and demonstrate that, in Drosophila, Hsp70 is a critical thermotolerance factor. They show, moreover, that manipulating the expression of a single hsp can be sufficient to improve the stress tolerance of a complex multicellular organism.

Noninvasive measurement of regional cerebral blood flow by near-infrared spectroscopy and indocyanine green.

Clinicians lack a practical method for measuring CBF rapidly, repeatedly, and noninvasively at the bedside. A new noninvasive technique for estimation of cerebral hemodynamics by use of near-infrared spectroscopy (NIRS) and an intravenously infused tracer dye is proposed. Kinetics of the infrared tracer indocyanine green were monitored on the intact skull in pigs. According to an algorithm derived from fluorescein flowmetry, a relative blood flow index (BFI) was calculated. Data obtained were compared with cerebral and galeal blood flow values assessed by radioactive microspheres under baseline conditions and during hemorrhagic shock and resuscitation. Blood flow index correlated significantly (rs = 0.814, P < 0.001) with cortical blood flow but not with galeal blood flow (rs = 0.258). However, limits of agreement between BFI and CBF are rather wide (+/- 38.2 +/- 6.4 mL 100 g-1 min-1) and require further studies. Data presented demonstrate that detection of tracer kinetics in the cerebrovasculature by NIRS may serve as valuable tool for the noninvasive estimation of regional CBF. Indocyanine green dilution curves monitored noninvasively on the intact skull by NIRS reflect dye passage through the cerebral, not extracerebral, circulation.

Effect of hypertonic saline/dextran on post-stenotic myocardial perfusion, metabolism, and function during resuscitation from hemorrhagic shock in anesthetized pigs.

Resuscitation using small volumes of hypertonic saline solutions normalizes cardiac output without fully restoring arterial pressure. This study compared the efficacy of either 7.2% saline/10% dextran 60 (HSDex) or the identical sodium load of normal saline (NS) to improve regional myocardial blood flow (MBF), contractile function, and oxygen metabolism in the presence of a critical coronary stenosis. Fourteen anesthetized, open-chest pigs (25 +/- 3.6 kg) were instrumented to assess left anterior descending coronary artery (LAD) flow, post-stenotic oxygen, and lactate metabolism, regional myocardial segment shortening (SS, sonomicrometry), and MBF (radioactive microspheres). After implementation of a critical LAD-stenosis, shock was induced by hemorrhage (mean arterial pressure (MAP) 45-50 mmHg for 75 min). Resuscitation was started by infusion (2 min) of either HSDex (n = 7,10% of blood loss) or NS (n = 7, 80% of blood loss); 30 min later 6% dextran 60 (10% of blood loss) was administered in both groups. The LAD-stenosis did not affect myocardial metabolism, SS, or MBF at rest. After hemorrhage, MBF remained unchanged from baseline in non-stenotic but decreased by 53% in post-stenotic myocardium (p < .05). The endo-epicardial flow ratio fell below 1.0 in both areas. SS decreased by 10-15% only in post-stenotic myocardium (p < .05). Resuscitation with both HSDex and NS restored cardiac index (CI) but not MAP. MBF increased above baseline values with either solution in non-stenotic while it remained at shock levels in post-stenotic myocardium, where ischemia persisted as evidenced by lactate production and depressed SS. Neither in non-stenotic nor in post-stenotic myocardium was the epi-endocardial flow ratio normalized upon resuscitation with HSDex or NS. We conclude that in the presence of a flow-limiting coronary stenosis, initial fluid resuscitation with both HSDex and the identical sodium load of NS failed to restore perfusion pressure, redistributed MBF in favor of normally perfused myocardium, and did not reverse ischemia in post-stenotic myocardium.

Effect of profound normovolemic hypotension and moderate hypothermia on circulating cytokines and adhesion molecules.

Hypotension caused by hypovolemic, hemorrhagic shock induces disturbances in the immune system that may contribute to an increased susceptibility to sepsis. The effect of chemically induced hypotension on circulating cytokines and adhesion molecules has not been investigated yet. In 21 patients scheduled for resection of malignant choroidal melanoma of the eye the perioperative serum levels of the cytokines IL-1beta, IL-6, IL-10, TNF-alpha, and the adhesion molecules sE-Selectin and sICAM-1 were investigated. Moderate hypothermia of 32 degrees C was induced in all patients. In 14 patients profound hypotension (mean arterial blood pressure 35-40 mmHg, hypotension group) was induced by enalapril and nitroglycerin for a mean duration of 71 min. In 7 patients the tumor was not resectable, and hypotension was not induced (controls). We did not detect significant differences in serum levels of cytokines or sE-Selectin perioperatively in patients with profound hypotension compared with controls. In both groups IL-6 serum levels increased significantly and reached a maximum after rewarming (17 +/- 6 and 16 +/- 5 pg/dL, respectively, P < 0.001). IL-1beta, IL-10, and TNF-alpha did not change perioperatively in both groups. On the first postoperative day sICAM-1 serum levels were significantly increased in both groups (mean increase of 96 and 54 ng/mL, respectively, P < 0.01 and P < 0.05). We conclude from this study that profound normovolemic arterial hypotension does not seem to have effects on serum levels of circulating IL-1beta, IL-6, IL-10, TNF-alpha, and sE-Selectin. Perioperative moderate hypothermia may be the reason for the postoperative increase in sICAM-1 levels independent of the blood pressure.

Eight hours' inhalation of prostacyclin (PGI2) in healthy lambs: effects on tracheal, bronchial, and alveolar morphology.

OBJECTIVE: To study potential toxic effects of long-term (8 h) inhaled prostacyclin (PGI2) on respiratory tract tissues. DESIGN: In a prospective, randomized order, either PGI2 (n =7) or normal saline (n = 7) was aerosolized during a time period of 8 h in healthy lambs. SETTING: Institute for Surgical Research of the Ludwig-Maximilians University of Munich. ANIMALS: 14 health, anesthetized, ventilated lambs. INTERVENTIONS: All animals were endotracheally intubated followed by tracheotomy. PGI2 solution or normal saline was administered with a jet nebulizer (delivery rate 4-10 ml/h; mass median diameter of aerosol particles 3.1 microns). MEASUREMENTS AND RESULTS: Histomorphological changes after 8-h inhalation of PGI2 solution were compared to those after 8-h inhalation of normal saline. Tracheal and bronchoalveolar tissues were examined by light and electron microscopy in order to assess tissue damage induced by inhaled PGI2. Pathological changes were ranked by a blinded observer following a graduation system ranging from "absence of pathological changes" to "maximal pathological changes". Abnormalities were restricted to the trachea (focal flattening of the epithelium, loss of cilia, slight inflammatory cell infiltration) and alveolar tissue (focal alveolar septal thickening with slight inflammatory cell infiltration), but no statistically significant differences between the PGI2 and control groups were encountered. CONCLUSION: Our findings indicate the absence of PGI2 aerosol-related respiratory tissue damage after 8-h inhalation of PGI2.

Hirudin versus heparin for anticoagulation in continuous renal replacement therapy.

OBJECTIVE: To compare the efficacy and safety of hirudin and heparin for anticoagulation during continuous renal replacement therapy (CRRT) in critically ill patients. DESIGN: Prospective, randomized controlled pilot study. SETTING: Single centre; interdisciplinary intensive care unit at a university hospital. PATIENTS: Seventeen patients receiving CRRT. INTERVENTIONS: Patients were randomly allocated to two groups. Heparin group (nine patients): continuous administration of 250 IU/h heparin; dose was adjusted in 125 IU/h steps with a targeted activated clotting time (ACT) of 180-210 s. Hirudin group (eight patients): continuous infusion of 10 micrograms/kg/h hirudin, dose was adjusted in 2 micrograms/kg/h steps with a targeted ecarin clotting time (ECT) of 80-100 s. Observation time was 96 h. MEASUREMENTS AND MAIN RESULTS: Measured filter run patency and haemofiltration efficacy did not significantly differ between the two groups. Three bleeding complications were observed in the hirudin group, none in the heparin group (P < 0.01). At the onset of bleeding, which occurred 60 or more hours after the start of therapy, only one patient was still under continuous hirudin administration but levels were either in therapeutic range or below. CONCLUSIONS: Hirudin can be used efficiently for anticoagulation in CRRT. Late bleeding complications may have been caused by possible hirudin accumulation, but this was not evident from hirudin plasma and ECT levels. Since bleeding complications were observed only in the presence of documented coagulation disorders, not only adequate drug monitoring but also the plasmatic and cellular coagulation status of the patient should be taken into consideration for adjusting hirudin dosage.

Inhalation of prostacyclin (PGI2) for 8 hours does not produce signs of acute pulmonary toxicity in healthy lambs.

OBJECTIVE: To study the potential side effects and toxicity of inhaling prostacyclin (PGI2) aerosol for 8 h. DESIGN: In a prospective, randomized study 14 healthy lambs received either PGI2 (n = 7) or 0.9% NaCl (n = 7) as an aerosol for 8 h. SETTING: Institute for Surgical Research of the Ludwig-Maximilians-University of Munich. INTERVENTIONS: All animals were studied under general anesthesia in a prone position. They were first intubated endotracheally and later tracheotomized. PGI2 solution (median dose 28 ng/kg per min) or 0.9% NaCl was administered with a jet nebulizer (delivery rate 4-10 ml/h; mass median diameter of aerosol particles 3.1 microns). Bronchoalveolar lavage was performed before and after the inhalation period to collect epithelial lining fluid of alveoli. MEASUREMENTS AND RESULTS: Hemodynamic and respiratory parameters, systemic resorption (plasma levels of 6-keto-prostaglandin-F 1 alpha), in vitro bleeding time, collagen-induced platelet aggregation and global biochemical and cellular composition of the epithelial lining fluid were examined in order to assess the side effects and signs of acute pulmonary toxicity induced by inhaled PGI2. No statistically significant differences were found between the PGI2 and the control groups for any of the parameters examined. CONCLUSION: Inhalation of PGI2 (28 ng/kg per min) over a period of 8 h in healthy lambs does not produce major side effects or acute pulmonary toxicity.

Myocardial blood flow heterogeneity in shock and small-volume resuscitation in pigs with coronary stenosis.

Myocardial blood flow heterogeneity in shock and small-volume resuscitation in pigs with coronary stenosis. J. Appl. Physiol. 83(6): 1832-1841, 1997.-We analyzed the effects of shock and small-volume resuscitation in the presence of coronary stenosis on fractal dimension (D) and spatial correlation (SC) of regional myocardial perfusion. Hemorrhagic shock was induced and maintained for 1 h. Pigs were resuscitated with hypertonic saline-dextran 60 [HSDex, 10% of shed blood volume (SBV)] or normal saline (NS; 80% of SBV). Therapy was continued after 30 min with dextran (10% SBV). At baseline, D was 1.39 +/- 0.06 (mean +/- SE; HSDex group) and 1.34 +/- 0.04 (NS group). SC was 0.26 +/- 0.07 (HSDex) and 0.26 +/- 0.04 (NS). Left anterior descending coronary artery stenosis changed neither D nor SC. Shock significantly reduced D (i.e., homogenized perfusion): 1.26 +/- 0.06 (HSDex) and 1.23 +/- 0.05 (NS). SC was increased: 0.41 +/- 0.1 (HSDex) and 0.48 +/- 0.07 (NS). Fluid therapy with HSDex further decreased D to 1.22 +/- 0.05, whereas NS did not change D. SC was increased by both HSDex (0.56 +/- 0.1) and NS (0.53 +/- 0.06). At 1 h after resuscitation, SC was constant in both groups, and D was reduced only in the NS group (1.18 +/- 0.02). We conclude that hemorrhagic shock homogenized regional myocardial perfusion in coronary stenosis and that fluid therapy failed to restore this.

Inhaled sodium nitroprusside. Non-selective reduction of thromboxane analogue-induced pulmonary vasoconstriction in healthy sheep.

Both inhaled nitric oxide (NO) and inhaled prostacyclin have been shown to selectively decrease pulmonary hypertension of various origin. The aim of the present study was to assess the potential of the NO donor sodium nitroprusside (SNP) to elicit selective pulmonary vasodilation. SNP spontaneously liberates nitric oxide in the presence of reducing substances like cysteine or glutathione, ubiquitous in many different tissues. Inhaled as an aerosol in 3 healthy lambs presenting pulmonary hypertension induced by infusion of a thromboxane analogue, low concentrations of SNP (0.02-0.6 mg/ml) revealed no effect at all. In contrast, high concentrations of SNP (1.0-20.0 mg/ml) lowered pulmonary artery pressure in conjunction with systemic arterial hypotension, suggesting systemic resorption of SNP with subsequent release of its nitroso-group. Selective pulmonary vasodilation was never observed. In conclusion, the present results do not support a selective effect of inhaled SNP in the pulmonary circulation.

Biochemical and cellular composition of alveolar epithelial lining fluid in anesthetized healthy lambs.

Pulmonary toxicity of inhaled materials is often evaluated by (repetitive) assessment of the composition of bronchoalveolar lavage (BAL) fluid or of epithelial lining fluid (ELF) in sheep and lambs. Knowledge of the typical constituents of these fluids obtained from healthy animals is essential for identification of pathologic changes. Few studies have dealt with normal constituents of BAL fluid or ELF in sheep and lamb. The comparability of these studies, however, is limited for reasons concerning the choice of model and BAL technique. The biochemical and cellular composition of alveolar ELF obtained by a standardized BAL procedure was examined in 15 pento-barbital anesthetized 4 months old Merino lambs unexposed to inhaled substances. ELF volume was calculated by using the urea dilution method. We found 20.3 x 10(5) leucocytes per ml ELF, 87.5% of which were alveolar macrophages. Basophils and neutrophils were practically absent while 5% of the counted cells were lymphocytes. 76% of recovered cells were viable. The ELF contained 7 mg/ml total protein; enzyme activities of LDH and AP were 1692 U/l and 145 U/l, respectively.