Pulmonary vein contracts in response to hypoxia

1993 ◽  
Vol 265 (1) ◽  
pp. L87-L92 ◽  
Author(s):  
Y. Zhao ◽  
C. S. Packer ◽  
R. A. Rhoades
Keyword(s):  
Smooth Muscle ◽  
Regional Blood Flow ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Phase 1 ◽  
Pulmonary Veins ◽  
Arterial Phase ◽  
Channel Blockers ◽  
Phase 2 ◽  
Hypoxic Response ◽  
Sustained Contraction

Hypoxic pulmonary vasoconstriction (HPV) is an important regulatory mechanism in matching regional blood flow and ventilation. The HPV response has been well documented on the arterial side, but the response of pulmonary veins to hypoxia has received little attention. The purpose of the present study was to determine whether isolated rat pulmonary veins contract in response to decreased PO2 and, if so, to compare the venous response with that of the pulmonary artery. Rat pulmonary venous and arterial rings were attached to force transducers and precontracted with either a submaximal dose of KCl or norepinephrine under normoxic conditions and then made hypoxic. The pulmonary venous hypoxic response consisted of a single sustained contraction, whereas the arterial response to hypoxia was biphasic, consisting of an initial rapid contraction and then a slowly developed but sustained contraction. The venous hypoxic contraction was significantly greater in magnitude than either phase 1 or phase 2 of the arterial response. Endothelium denudation did not affect the venous hypoxic response. However, the venous hypoxic response was dependent on the level of precontractile tone and also appeared to be dependent on the specific contractile agonist. Unlike the isolated arterial phase 1 hypoxic response (but similar to the arterial phase 2 response) the pulmonary venous hypoxic contraction was inhibited in Ca(2+)-free media or by Ca2+ channel blockers. In summary, pulmonary venous smooth muscle contracts to a relatively greater degree in response to severe hypoxia than does pulmonary arterial smooth muscle. The venous hypoxic response is endothelium independent, as is phase 2 of the arterial response.(ABSTRACT TRUNCATED AT 250 WORDS)

Biphasic contractile response of pulmonary artery to hypoxia

1991 ◽  
Vol 261 (2) ◽  
pp. L156-L163 ◽  
Author(s):  
R. E. Bennie ◽  
C. S. Packer ◽  
D. R. Powell ◽  
N. Jin ◽  
R. A. Rhoades
Keyword(s):  
Pulmonary Artery ◽  
Contractile Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Phase 1 ◽  
Phase 2 ◽  
Hypoxic Response ◽  
Sustained Contraction ◽  
First Response ◽  
Complete Relaxation ◽  
Pulmonary Arterial

Isolated perfused lungs exposed to low O2 exhibit a hypoxic pulmonary vasoconstriction response that is transient in nature. The purpose of this study was to determine whether the isolated pulmonary artery behaves similarly in response to hypoxia. Rat pulmonary arterial rings were placed in tissue baths (37 degrees C, air-5% CO2, pH = 7.4) and attached to force transducers. Maximum contractile responses (Po) to high K+ were elicited. After washout, arterial rings were submaximally contracted and made hypoxic (PO2 = 33.7 +/- 1.3, pH = 7.38 +/- 0.01). Aortic rings were used to obtain comparative data. The isolated pulmonary arterial hypoxic response was biphasic, displaying an initial rapid contraction of short duration (phase 1) then, before complete relaxation of this first response, a second slow but sustained contraction occurred (phase 2). Aortic rings did not exhibit a biphasic response, but showed only an initial short contraction followed by complete relaxation. The contractile response of the pulmonary artery was diminished when the endothelium was rendered nonfunctional. However, the phase 2 response was not endothelium dependent. Neither inhibitors of the lipoxygenase or cyclooxygenase pathways nor scavengers of extracellular reactive oxygen species had any effect on the biphasic hypoxic response. Pulmonary arterial hypoxic contractions were blunted when glucose was absent and appear to be dependent on glycolytic ATP. Results of this study show that hypoxia causes a biphasic contractile response of pulmonary arterial muscle and that two different mechanisms appear to be involved, since the transient phase 1 response is endothelium dependent, whereas the sustained contraction of phase 2 is endothelium independent.

Hypoxic release of calcium from the sarcoplasmic reticulum of pulmonary artery smooth muscle

2001 ◽  
Vol 281 (2) ◽  
pp. L318-L325 ◽  
Author(s):  
Michelle Dipp ◽  
Piers C. G. Nye ◽  
A. Mark Evans
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Phase 1 ◽  
Transient Phase ◽  
Phase 2 ◽  
Hypoxic Response ◽  
Pulmonary Vessels ◽  
Intracellular Ca ◽  
Pulmonary Artery Smooth Muscle ◽  
Phase Phase

The hypoxic constriction of isolated pulmonary vessels is composed of an initial transient phase ( phase 1) followed by a slowly developing increase in tone ( phase 2). We investigated the roles of the endothelium and of intracellular Ca2+ stores in both preconstricted and unpreconstricted intrapulmonary rabbit arteries when challenged with hypoxia (Po 2 16–21 Torr). Removing the endothelium did not affect phase 1, but phase 2 appeared as a steady plateau. Removing extracellular Ca2+ had essentially the same effect as removing the endothelium. Depletion of sarcoplasmic reticulum Ca2+stores with caffeine and ryanodine abolished the hypoxic response. Omitting preconstriction reduced the amplitude of the hypoxic response but did not qualitatively affect any of the above responses. We conclude that hypoxia releases intracellular Ca2+ from ryanodine-sensitive stores by a mechanism intrinsic to pulmonary vascular smooth muscle without the need for Ca2+ influx across the plasmalemma or an endothelial factor. Our results also suggest that extracellular Ca2+ is required for the release of an endothelium-derived vasoconstrictor.

Inhibition of hypoxic pulmonary vasoconstriction by dipyridamole is not platelet mediated

1977 ◽  
Vol 55 (3) ◽  
pp. 448-451 ◽  
Author(s):  
Johannes Mlczoch ◽  
E. Kenneth Weir ◽  
Robert F. Grover
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Drug Treatment ◽  
Direct Effect ◽  
Platelet Function ◽  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxic Response ◽  
Virtual Absence ◽  
Pulmonary Vasoconstriction

Dipyridamole, which is known to alter platelet function, has also been shown to reduce hypoxic pulmonary vasoconstriction. This latter effect could result from dipyridamole either acting on a platelet-mediated system, or acting directly on pulmonary vascular smooth muscle. To investigate these two possibilities, normal dogs were compared with dogs rendered thrombocytopenic by a platelet antiserum. Compared with the hypoxic pressor response before drug treatment, the hypoxic response following dipyridamole was only 32% as great in the normal dogs and only 38% as great in the thrombocytopenic dogs. Thus, dipyridamole was no less effective in reducing the hypoxic pressor response in the virtual absence of platelets. This supports a direct effect of dipyridamole on pulmonary vascular smooth muscle, which could be mediated by an increase in adenosine levels.

Rationalization and internalization

2001 ◽  
Vol 60 (4) ◽  
pp. 215-230 ◽  
Author(s):  
Jean-Léon Beauvois
Keyword(s):  
Phase 1 ◽  
Facilitatory Effect ◽  
Phase 2 ◽  
Causal Explanations ◽  
Reduction Effect ◽  
Dissonance Reduction

After having been told they were free to accept or refuse, pupils aged 6–7 and 10–11 (tested individually) were led to agree to taste a soup that looked disgusting (phase 1: initial counter-motivational obligation). Before tasting the soup, they had to state what they thought about it. A week later, they were asked whether they wanted to try out some new needles that had supposedly been invented to make vaccinations less painful. Agreement or refusal to try was noted, along with the size of the needle chosen in case of agreement (phase 2: act generalization). The main findings included (1) a strong dissonance reduction effect in phase 1, especially for the younger children (rationalization), (2) a generalization effect in phase 2 (foot-in-the-door effect), and (3) a facilitatory effect on generalization of internal causal explanations about the initial agreement. The results are discussed in relation to the distinction between rationalization and internalization.

PENERAPAN MODEL QUANTUM LEARNING UNTUK MENINGKATKAN HASIL BELAJAR AUTOCAD SISWA KELAS X TEKNIK PEMESINAN SMK NEGERI 1 STABAT

2013 ◽  
Vol 5 (1) ◽  
Author(s):  
Abdul Hasan Saragih
Keyword(s):  
Positive Response ◽  
Phase 1 ◽  
First Grade ◽  
Learning Model ◽  
Second Phase ◽  
Phase 2 ◽  
Phase 3 ◽  
The Third ◽  
Third Phase ◽  
Quantum Learning

This classroom research was conducted on the autocad instructions to the first grade of mechinary class of SMK Negeri 1 Stabat aiming at : (1) improving the student’ archievementon autocad instructional to the student of mechinary architecture class of SMK Negeri 1 Stabat, (2) applying Quantum Learning Model to the students of mechinary class of SMK Negeri 1 Stabat, arising the positive response to autocad subject by applying Quantum Learning Model of the students of mechinary class of SMK Negeri 1 Stabat. The result shows that (1) by applying quantum learning model, the students’ achievement improves significantly. The improvement ofthe achievement of the 34 students is very satisfactory; on the first phase, 27 students passed (70.59%), 10 students failed (29.41%). On the second phase 27 students (79.41%) passed and 7 students (20.59%) failed. On the third phase 30 students (88.24%) passed and 4 students (11.76%) failed. The application of quantum learning model in SMK Negeri 1 Stabat proved satisfying. This was visible from the activeness of the students from phase 1 to 3. The activeness average of the students was 74.31% on phase 1,81.35% on phase 2, and 83.63% on phase 3. (3) The application of the quantum learning model on teaching autocad was very positively welcome by the students of mechinary class of SMK Negeri 1 Stabat. On phase 1 the improvement was 81.53% . It improved to 86.15% on phase 3. Therefore, The improvement ofstudent’ response can be categorized good.

In situ deteriorating patient simulation in general practice

2020 ◽  
Vol 70 (suppl 1) ◽  
pp. bjgp20X711425
Author(s):  
Joanna Lawrence ◽  
Petronelle Eastwick-Field ◽  
Anne Maloney ◽  
Helen Higham
Keyword(s):  
Life Support ◽  
Early Recognition ◽  
Phase 1 ◽  
Patient Simulation ◽  
Medical Emergency ◽  
Phase 2 ◽  
Action Plans ◽  
Integrated Simulation ◽  
Deteriorating Patient

BackgroundGP practices have limited access to medical emergency training and basic life support is often taught out of context as a skills-based event.AimTo develop and evaluate a whole team integrated simulation-based education, to enhance learning, change behaviours and provide safer care.MethodPhase 1: 10 practices piloted a 3-hour programme delivering 40 minutes BLS and AED skills and 2-hour deteriorating patient simulation. Three scenarios where developed: adult chest pain, child anaphylaxis and baby bronchiolitis. An adult simulation patient and relative were used and a child and baby manikin. Two facilitators trained in coaching and debriefing used the 3D debriefing model. Phase 2: 12 new practices undertook identical training derived from Phase 1, with pre- and post-course questionnaires. Teams were scored on: team working, communication, early recognition and systematic approach. The team developed action plans derived from their learning to inform future response. Ten of the 12 practices from Phase 2 received an emergency drill within 6 months of the original session. Three to four members of the whole team integrated training, attended the drill, but were unaware of the nature of the scenario before. Scoring was repeated and action plans were revisited to determine behaviour changes.ResultsEvery emergency drill demonstrated improved scoring in skills and behaviour.ConclusionA combination of: in situ GP simulation, appropriately qualified facilitators in simulation and debriefing, and action plans developed by the whole team suggests safer care for patients experiencing a medical emergency.

Clinical Drug Development for the Treatment of Pulmonary Arterial Hypertension: Collaboration With the Pharmaceutical Industry and Regulatory Agencies

2010 ◽  
Vol 9 (4) ◽  
pp. 214-219
Author(s):  
Robyn J. Barst
Keyword(s):  
Clinical Trials ◽  
Pulmonary Arterial Hypertension ◽  
Drug Development ◽  
Phase 1 ◽  
Preclinical Studies ◽  
Phase 2 ◽  
Phase 3 ◽  
Preclinical Testing ◽  
New Drug ◽  
Pulmonary Arterial

Drug development is the entire process of introducing a new drug to the market. It involves drug discovery, screening, preclinical testing, an Investigational New Drug (IND) application in the US or a Clinical Trial Application (CTA) in the EU, phase 1–3 clinical trials, a New Drug Application (NDA), Food and Drug Administration (FDA) review and approval, and postapproval studies required for continuing safety evaluation. Preclinical testing assesses safety and biologic activity, phase 1 determines safety and dosage, phase 2 evaluates efficacy and side effects, and phase 3 confirms efficacy and monitors adverse effects in a larger number of patients. Postapproval studies provide additional postmarketing data. On average, it takes 15 years from preclinical studies to regulatory approval by the FDA: about 3.5–6.5 years for preclinical, 1–1.5 years for phase 1, 2 years for phase 2, 3–3.5 years for phase 3, and 1.5–2.5 years for filing the NDA and completing the FDA review process. Of approximately 5000 compounds evaluated in preclinical studies, about 5 compounds enter clinical trials, and 1 compound is approved (Tufts Center for the Study of Drug Development, 2011). Most drug development programs include approximately 35–40 phase 1 studies, 15 phase 2 studies, and 3–5 pivotal trials with more than 5000 patients enrolled. Thus, to produce safe and effective drugs in a regulated environment is a highly complex process. Against this backdrop, what is the best way to develop drugs for pulmonary arterial hypertension (PAH), an orphan disease often rapidly fatal within several years of diagnosis and in which spontaneous regression does not occur?

scholarly journals A phase 1 and randomized controlled phase 2 trial of the safety and efficacy of the combination of gemcitabine and docetaxel with ontuxizumab (MORAb‐004) in metastatic soft‐tissue sarcomas

Cancer ◽  
2019 ◽  
Vol 125 (14) ◽  
pp. 2445-2454 ◽  
Author(s):  
Robin L. Jones ◽  
Sant P. Chawla ◽  
Steven Attia ◽  
Patrick Schöffski ◽  
Hans Gelderblom ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase 1 ◽  
Soft Tissue Sarcomas ◽  
Phase 2 ◽  
Safety And Efficacy ◽  
Randomized Controlled ◽  
Phase 2 Trial

scholarly journals Quantitative Checklist for Autism in Toddlers (Q-CHAT). A population screening study with follow-up: the case for multiple time-point screening for autism

2021 ◽  
Vol 5 (1) ◽  
pp. e000700
Author(s):  
Carrie Allison ◽  
Fiona E Matthews ◽  
Liliana Ruta ◽  
Greg Pasco ◽  
Renee Soufer ◽  
...  
Keyword(s):  
Phase 1 ◽  
Autism Spectrum ◽  
Population Screening ◽  
Diagnostic Assessment ◽  
Test Accuracy ◽  
Multiple Time ◽  
Phase 2 ◽  
Time Points ◽  
Screening Study

ObjectiveThis is a prospective population screening study for autism in toddlers aged 18–30 months old using the Quantitative Checklist for Autism in Toddlers (Q-CHAT), with follow-up at age 4.DesignObservational study.SettingLuton, Bedfordshire and Cambridgeshire in the UK.Participants13 070 toddlers registered on the Child Health Surveillance Database between March 2008 and April 2009, with follow-up at age 4; 3770 (29%) were screened for autism at 18–30 months using the Q-CHAT and the Childhood Autism Spectrum Test (CAST) at follow-up at age 4.InterventionsA stratified sample across the Q-CHAT score distribution was invited for diagnostic assessment (phase 1). The 4-year follow-up included the CAST and the Checklist for Referral (CFR). All with CAST ≥15, phase 1 diagnostic assessment or with developmental concerns on the CFR were invited for diagnostic assessment (phase 2). Standardised diagnostic assessment at both time-points was conducted to establish the test accuracy of the Q-CHAT.Main outcome measuresConsensus diagnostic outcome at phase 1 and phase 2.ResultsAt phase 1, 3770 Q-CHATs were returned (29% response) and 121 undertook diagnostic assessment, of whom 11 met the criteria for autism. All 11 screened positive on the Q-CHAT. The positive predictive value (PPV) at a cut-point of 39 was 17% (95% CI 8% to 31%). At phase 2, 2005 of 3472 CASTs and CFRs were returned (58% response). 159 underwent diagnostic assessment, including 82 assessed in phase 1. All children meeting the criteria for autism identified via the Q-CHAT at phase 1 also met the criteria at phase 2. The PPV was 28% (95% CI 15% to 46%) after phase 1 and phase 2.ConclusionsThe Q-CHAT can be used at 18–30 months to identify autism and enable accelerated referral for diagnostic assessment. The low PPV suggests that for every true positive there would, however, be ~4–5 false positives. At follow-up, new cases were identified, illustrating the need for continued surveillance and rescreening at multiple time-points using developmentally sensitive instruments. Not all children who later receive a diagnosis of autism are detectable during the toddler period.

scholarly journals Evaluation of health system readiness and coverage of intermittent preventive treatment of malaria in infants (IPTi) in Kambia district to inform national scale-up in Sierra Leone

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Maria Lahuerta ◽  
Roberta Sutton ◽  
Anthony Mansaray ◽  
Oliver Eleeza ◽  
Brigette Gleason ◽  
...  
Keyword(s):  
Sierra Leone ◽  
Phase 1 ◽  
Scale Up ◽  
Intermittent Preventive Treatment ◽  
Vaccine Dose ◽  
Preventive Treatment ◽  
Household Survey ◽  
Register Data ◽  
Phase 2 ◽  
Pentavalent Vaccine

Abstract Background Intermittent preventive treatment of malaria in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a proven strategy to protect infants against malaria. Sierra Leone is the first country to implement IPTi nationwide. IPTi implementation was evaluated in Kambia, one of two initial pilot districts, to assess quality and coverage of IPTi services. Methods This mixed-methods evaluation had two phases, conducted 3 (phase 1) and 15–17 months (phase 2) after IPTi implementation. Methods included: assessments of 18 health facilities (HF), including register data abstraction (phases 1 and 2); a knowledge, attitudes and practices survey with 20 health workers (HWs) in phase 1; second-generation sequencing of SP resistance markers (pre-IPTi and phase 2); and a cluster-sample household survey among caregivers of children aged 3–15 months (phase 2). IPTi and vaccination coverage from the household survey were calculated from child health cards and maternal recall and weighted for the complex sampling design. Interrupted time series analysis using a Poisson regression model was used to assess changes in malaria cases at HF before and after IPTi implementation. Results Most HWs (19/20) interviewed had been trained on IPTi; 16/19 reported feeling well prepared to administer it. Nearly all HFs (17/18 in phase 1; 18/18 in phase 2) had SP for IPTi in stock. The proportion of parasite alleles with dhps K540E mutations increased but remained below the 50% WHO-recommended threshold for IPTi (4.1% pre-IPTi [95%CI 2–7%]; 11% post-IPTi [95%CI 8–15%], p < 0.01). From the household survey, 299/459 (67.4%) children ≥ 10 weeks old received the first dose of IPTi (versus 80.4% for second pentavalent vaccine, given simultaneously); 274/444 (62.5%) children ≥ 14 weeks old received the second IPTi dose (versus 65.4% for third pentavalent vaccine); and 83/217 (36.4%) children ≥ 9 months old received the third IPTi dose (versus 52.2% for first measles vaccine dose). HF register data indicated no change in confirmed malaria cases among infants after IPTi implementation. Conclusions Kambia district was able to scale up IPTi swiftly and provide necessary health systems support. The gaps between IPTi and childhood vaccine coverage need to be further investigated and addressed to optimize the success of the national IPTi programme.

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