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1.
Int J Lang Commun Disord ; 59(1): 340-353, 2024.
Article in English | MEDLINE | ID: mdl-37715545

ABSTRACT

BACKGROUND: Collaborative practice between therapists and parents is a key element of family-centred care and is essential if we want to address family priorities and needs in interventions. However, collaborative practice is challenging for speech and language therapists (SLTs) and parents. To facilitate collaboration, collaborative practices need to be implemented into speech and language therapy for young children with developmental language disorders (DLD) and their families. Actual change and implementation of collaboration in practice will be successful only when it corresponds with patients' needs, in our case the needs of parents of young children with DLD. AIMS: To explore parents' needs in their collaboration with SLTs during therapy for their young child with DLD. METHODS & PROCEDURES: Parents of children with (a risk of) DLD in the age of 2-6 years were eligible for participation. We recruited parents via SLTs. Twelve parents of children with DLD participated in semi-structured interviews about their needs in collaboration with SLTs. We used a phenomenological approach focusing on parents' lived experiences. We transcribed the interviews verbatim. All interviews were read/listened to and discussed by our parent panel, multiple researchers and the interviewer. Two researchers independently analysed the data using the reflective thematic analysis of Braun and Clarke. OUTCOMES & RESULTS: The analysis of the interviews resulted in six themes: (1) knowing what to expect, (2) knowing how to contribute, (3) feeling capable of supporting the child, (4) trusting the therapist, (5) alignment with parents and children's needs, preferences and priorities and (6) time and space for asking questions and sharing information. CONCLUSIONS & IMPLICATIONS: Parents want SLTs to invest time in collaborating with them. Parents need SLTs to empower them to become a collaborative partner and enable them to support their child in daily life. Parents need knowledge about the therapy process and diagnosis and skills in how to support their child's language development. Also, they need emotional support to feel secure enough to support their child, to ask questions to therapists and to bring up their own thoughts and opinions in therapy. Parents' needs are in line with collaborative working as described in literature, which underlines the importance of implementing collaborative working in speech and language therapy for young children with DLD. WHAT THIS PAPER ADDS: What is already known on the subject Several reviews have explored parents' perspectives on speech and language therapy. Results reveal parents' experiences with speech and language therapy in general, and parents' perspectives on specific topics such as shared decision-making and parents/therapists roles in therapy. What this study adds This study adds insights into parents' needs to ensure collaboration with speech and language therapists (SLTs). Parents of young children with developmental language disorders (DLD) need SLTs to invest time to create optimal collaboration. It is important for parents to have enough knowledge about DLD and the SLT process, skills and confidence in how to support their child and opportunities to share thoughts and questions with SLTs. Our results underline the importance of parents being empowered by SLTs to become a collaborative partner. What are the clinical implications of this work? When children are referred to speech and language therapy, parents often venture into an unknown journey. They need support from SLTs to become a collaborative partner in speech and language therapy. Parents need SLTs to invest time in sharing knowledge, skills and power and align therapy to parents' and child's needs, preferences, priorities and expectations.


Subject(s)
Language Development Disorders , Language Therapy , Child , Humans , Child, Preschool , Language Therapy/methods , Speech , Speech Therapy/methods , Parents/psychology , Language Development Disorders/therapy , Language Development Disorders/psychology
2.
Child Care Health Dev ; 50(1): e13167, 2024 01.
Article in English | MEDLINE | ID: mdl-37724049

ABSTRACT

BACKGROUND: Collaboration between therapists and parents of children with developmental disabilities is a key element of family-centred care. In practice, collaboration appears to be challenging for both parents and therapists. This systematic review aims to make explicit how therapists can optimise their collaboration with parents of young children with developmental disabilities, according to the perspectives of parents and therapists. METHODS: A systematic review was conducted using the following databases: Medline (PubMed), CINAHL (OVID) and PsychINFO (OVID). Those papers were selected, which focused on collaboration using a two-way interaction between therapists and parents, exploring the perspectives of therapists and/or parents of children between 2 and 6 years. Papers needed to be published in English or Dutch between 1998 and July 2021. Included papers were synthesised using a qualitative analysis approach by two researchers independently. Results sections were analysed line-by-line, and codes were formulated and discussed by all authors. Codes were aggregated, resulting in a synthesis of specific collaboration strategies in combined strategy clusters. RESULTS: The search generated 3439 records. In total, 24 papers were selected. Data synthesis resulted in an overview of specific strategies organised into five clusters: (1) continuously invest time in your collaboration with parents, (2) be aware of your important role in the collaboration with parents, (3) tailor your approach, (4) get to know the family and (5) empower parents to become a collaborative partner. CONCLUSIONS: This systematic review resulted in an overview of concrete strategies for therapists to use in their collaboration with parents of children with developmental disabilities. The strategies formulated enable therapists to consciously decide how to optimise their collaboration with each individual parent. Making these strategies explicit facilitates change of practice from therapist-led and child-centred towards family-centred care.


Subject(s)
Disabled Children , Parents , Humans , Child, Preschool , Allied Health Personnel , Palliative Care , Awareness
3.
Epidemiol Infect ; 151: e179, 2023 09 19.
Article in English | MEDLINE | ID: mdl-37724460

ABSTRACT

This study determined long-term health outcomes (≥10 years) of Q-fever fatigue syndrome (QFS). Long-term complaints, health-related quality of life (HRQL), health status, energy level, fatigue, post-exertional malaise, anxiety, and depression were assessed. Outcomes and determinants were studied for the total sample and compared among age subgroups: young (<40years), middle-aged (≥40-<65years), and older (≥65years) patients. 368 QFS patients were included. Participants reported a median number of 12.0 long-term complaints. Their HRQL (median EQ-5D-5L index: 0.63) and health status (median EQ-VAS: 50.0) were low, their level of fatigue was high, and many experienced post-exertional malaise complaints (98.9%). Young and middle-aged patients reported worse health outcomes compared with older patients, with both groups reporting a significantly worse health status, higher fatigue levels and anxiety, and more post-exertional malaise complaints and middle-aged patients having a lower HRQL and a higher depression risk. Multivariate regression analyses confirmed that older age is associated with better outcomes, except for the number of health complaints. QFS has thus a considerable impact on patients' health more than 10 years after infection. Young and middle-aged patients experience more long-term health consequences compared with older patients. Tailored health care is recommended to provide optimalcare for each QFS patient.


Subject(s)
Fatigue Syndrome, Chronic , Q Fever , Adult , Humans , Middle Aged , Fatigue/etiology , Fatigue/complications , Fatigue Syndrome, Chronic/epidemiology , Outcome Assessment, Health Care , Q Fever/complications , Q Fever/epidemiology , Quality of Life , Aged
4.
BMC Health Serv Res ; 23(1): 319, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37004033

ABSTRACT

BACKGROUND: Q-fever is a zoonotic disease that can lead to illness, disability and death. This study aimed to provide insight into the perspectives of healthcare workers (HCWs) on prerequisites, barriers and opportunities in care for Q-fever patients. METHODS: A two-round online Delphi study was conducted among 94 Dutch HCWs involved in care for Q-fever patients. The questionnaires contained questions on prerequisites for high quality, barriers and facilitators in care, knowledge of Q-fever, and optimization of care. For multiple choice, ranking and Likert scale questions, frequencies were reported, while for rating and numerical questions, the median and interquartile range (IQR) were reported. RESULTS: The panel rated the care for Q-fever patients at a median score of 6/10 (IQR = 2). Sufficient knowledge of Q-fever among HCWs (36%), financial compensation of care (30%) and recognition of the disease by HCWs (26%) were considered the most important prerequisites for high quality care. A lack of knowledge was identified as the most important barrier (76%) and continuing medical education as the primary method for improving HCWs' knowledge (76%). HCWs rated their own knowledge at a median score of 8/10 (IQR = 1) and the general knowledge of other HCWs at a 5/10 (IQR = 2). According to HCWs, a median of eight healthcare providers (IQR = 4) should be involved in the care for Q-fever fatigue syndrome (QFS) and a median of seven (IQR = 5) in chronic Q-fever care. CONCLUSIONS: Ten years after the Dutch Q-fever epidemic, HCWs indicate that the long-term care for Q-fever patients leaves much room for improvement. Facilitation of reported prerequisites for high quality care, improved knowledge among HCWs, clearly defined roles and responsibilities, and guidance on how to support patients could possibly improve quality of care. These prerequisites may also improve care for patients with persisting symptoms due to other infectious diseases, such as COVID-19.


Subject(s)
COVID-19 , Q Fever , Humans , COVID-19/epidemiology , Delphi Technique , Health Personnel , Q Fever/therapy , Q Fever/diagnosis , Fatigue
5.
Front Epidemiol ; 3: 1144707, 2023.
Article in English | MEDLINE | ID: mdl-38455946

ABSTRACT

Background: A subset of patients experience persisting symptoms after an acute COVID-19 infection, referred to as "post COVID-19 condition". This cross-sectional study aimed to compare symptoms, health-related quality of life (HRQoL), fatigue, mental well-being, and determinants of diminished HRQoL, between patients with post COVID-19 condition categorized by time since acute infection. Methods: We performed an online survey and analyzed responses of 10,194 adult respondents with a confirmed or suspected COVID-19 infection, who experienced persisting symptoms ≥3 months after the initial infection. The most debilitating symptoms and health outcomes were studied separately for respondents 3-6, 7-9, 10-12, 13-18, 19-24, and >24 months after acute infection. Results: At each time period, fatigue, sensory-processing problems, and concentration problems were the most debilitating symptoms reported by respondents, although the proportion of respondents who reported these symptoms differed significantly between time periods. Respondents 3-6 months post-acute infection had the lowest HRQoL (median EQ-5D utility score: 0.59), the highest fatigue level (median score: 110.0) and the highest proportion with a likely depressive disorder (32.4%), whereas respondents 13-18 months post-infection had the highest HRQoL (0.65), the lowest fatigue level (106.0), and the second lowest proportion with a likely depressive disorder (25.0%) (p = 0.000-0.007). Compared to those 13-18 and 19-24 months post-infection, respondents >24 months post-infection had a slightly lower HRQoL (0.60), lower fatigue level (108.0), and lower proportion with a likely depressive disorder (29.2%), although only the differences in HRQoL were statistically significant (p = 0.001-0.010). Younger age, female gender, lower level of education, not having paid work before COVID-19, comorbidity, and not being vaccinated, seemed to be associated with lower HRQoL. Conclusion: Regardless of time since infection, respondents considered fatigue, sensory processing problems and concentration problems the most debilitating symptoms. They experienced a low HRQoL and severe fatigue, even more than two years after acute COVID-19 infection. Respondents 3-6 months post-infection had the worst health outcomes, whereas respondents 13-18 months post-infection had the best outcomes, indicating that, at least for a subgroup of patients, health status may improve over time.

6.
Qual Life Res ; 31(7): 2083-2092, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35091984

ABSTRACT

PURPOSE: Measuring health-related quality of life (HRQoL) with the EQ-5D-5L might lack sensitivity for disease-specific health complaints. This cross-sectional study analyzed whether fatigue and cognitive problems are captured by the EQ-5D-5L in a Q-fever patient population with persistent fatigue/cognitive problems, and whether addition of fatigue/cognition improved the explained variance for HRQoL. METHODS: A Dutch sample of Q-fever patients filled out the EQ-5D-5L and EQ VAS, the fatigue subscale of the Checklist Individual Strength, and a cognition dimension in the EQ-5D-5L format. The extent to which fatigue and cognition were captured by the EQ-5D-5L was determined based on distributional effects, head-to-head comparisons, Spearman rank correlation coefficients, and regression analyses. Explanatory power was determined of the EQ-5D-5L for the EQ VAS with and without a fatigue and cognition dimension. RESULTS: Out of 432 respondents, 373(86%) reported severe fatigue, 387(90%) cognitive problems. EQ-5D-5L utility and EQ VAS scores of respondents reporting severe fatigue/cognitive problems were significantly lower. Fatigue was strongly correlated with EQ-5D-5L dimensions usual activities and pain/discomfort (r = 0.602 and r = 0.510) and moderately with other EQ-5D-5L dimensions (r = 0.305-0.476). Cognition was strongly correlated with usual activities (r = 0.554) and moderately with other dimensions (r = 0.291-0.451). Adding fatigue to the EQ-5D-5L increased explanatory power for the EQ VAS with 6%. CONCLUSION: Fatigue and cognitive problems in Q-fever patients were partially captured by the EQ-5D-5L dimensions. The addition of fatigue to the EQ-5D-5L slightly improved explained variance for the EQ VAS. This potentially also accounts for patients who experience sequelae of other infectious diseases, such as COVID-19.


Subject(s)
COVID-19 , Quality of Life , Cognition , Cross-Sectional Studies , Fatigue , Health Status , Humans , Quality of Life/psychology , Surveys and Questionnaires
7.
J Psychosom Res ; 139: 110258, 2020 12.
Article in English | MEDLINE | ID: mdl-33069049

ABSTRACT

OBJECTIVE: To assess health symptoms, health-related quality of life, participation, and health care satisfaction in Q-fever patients up to 10 years after infection. METHODS: Cross-sectional questionnaire survey in the Netherlands. Data on health symptoms, fatigue (CIS), health-related quality of life (EQ-5D), social/work participation, health care providers and health care satisfaction were collected in patients with chronic Q-fever (CQ), Q-fever fatigue syndrome (QFS), and patients who experience QFS-like disease without a post-infection diagnosis (QLD). RESULTS: A vast majority of the 478 Q-fever patients (response rate 54.3%) face several health problems 10 years after infection. Fatigue was the most prevalent symptom in all groups (91.2%). The median EQ-5D index value differed significantly between the three diagnostic groups (CQ: 0.67; QFS: 0.55; QLD:0.70; p < 0.001). Approximately 50% of all patients had serious problems with work and physical activities, and more than 25% experienced difficulties with leisure time, household and social contacts. Also, more than one third stopped working permanently. Furthermore, GP's, internists, and physical therapists were the most often consulted health care providers. Patients gave low ratings for the overall quality of care for Q-fever, with 75% scoring a 5.0 or lower on a 10-point scale. CONCLUSION: Long-term health consequences are considerable for Q-fever patients, especially for those with QFS. The majority of the patients was unsatisfied with the quality of care for Q-fever. Awareness of the long-term impact of zoonotic diseases like Q-fever is needed to offer optimal health care for these patients.


Subject(s)
Q Fever/complications , Quality of Life/psychology , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Personal Satisfaction , Surveys and Questionnaires , Time Factors
8.
J Cardiovasc Pharmacol ; 50(1): 56-60, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17666916

ABSTRACT

Both hypertension and congestive heart failure are characterized by a reduced vasodilatory capacity. In both conditions, the impairment of endothelial function is mainly the result of a reduced nitric oxide availability. The highly beta1-selective third-generation adrenoceptor blocker nebivolol displays additional endothelium-dependent vasodilating actions in humans as well as in animal models. In this study, we investigated whether these vasodilating properties of nebivolol are preserved in conditions with endothelial dysfunction. The vasodilatory effects of nebivolol were compared with those of the muscarinic agonist methacholine in isolated aortic rings obtained from spontaneous hypertensive rats and rabbits with experimental heart failure. The methacholine-induced responses were attenuated in aortic rings from both spontaneous hypertensive rats and congestive heart failture rabbits (42+/-6% and 25+/-3% vs. 89+/-3% and 54+/-7% for controls, respectively; P<0.05, n=6-13), indicating an endothelial dysfunction in these preparations. In contrast, nebivolol-induced vasorelaxation remained unaffected in both preparations when compared to control preparations (40+/-12% and 43+/-6% vs. 52+/-8% and 50+/-13% for controls, respectively; P>0.05, n=6-13). These results implicate that the favorable hemodynamic profile of nebivolol may be preserved in patients with hypertension or congestive heart failure despite an impaired endothelial function.


Subject(s)
Benzopyrans/pharmacology , Ethanolamines/pharmacology , Heart Failure/drug therapy , Hypertension/drug therapy , Vasodilator Agents/pharmacology , Animals , Aorta, Thoracic , Disease Models, Animal , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Heart Failure/physiopathology , Hypertension/physiopathology , Male , Methacholine Chloride/pharmacology , Muscarinic Agonists/pharmacology , Nebivolol , Rabbits , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Vasodilation/drug effects
9.
Curr Drug Saf ; 1(1): 73-85, 2006 Jan.
Article in English | MEDLINE | ID: mdl-18690917

ABSTRACT

Inhibitors of serotonin (5-HT) and/or noradrenaline (NA) reuptake have been developed for pharmacological treatment of major depressive disorder. Insights in the role of 5-HT and NA in the neurological control of the lower urinary tract have also led to their application in common urological conditions such as stress urinary incontinence (SUI), nocturnal enuresis and ejaculatory disorders. The European approval of the 5-HT and NA reuptake inhibitor (SNRI) duloxetine for treatment of SUI underlines the importance of a new approach in SUI, but has also given rise to questions about the safety of antidepressants in urology. This paper reviews the safety of 5-HT and NA reuptake inhibitors in their on- and off-label use in urology. A systematic Medline search was performed for randomised controlled trials, meta-analyses and practice guidelines dealing with antidepressants in urology. The safety profiles of the drugs in the urological population were compared with data from psychiatric populations. Tricyclic antidepressants are associated with serious cardiovascular side effects. In addition, anticholinergic and antihistaminic side effects are common. Although recently questions have been raised regarding the cardiovascular safety profile of venlafaxine, most selective 5-HT reuptake inhibitors and SNRI have not been associated with serious cardiovascular effects. Their most common side effect is nausea. However, nausea tends to be mild and, importantly, transient. Patient counselling about side effects and up-titrating doses may be useful strategies for minimising discomfort and withdrawals.


Subject(s)
Adrenergic Uptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/adverse effects , Urologic Diseases/drug therapy , Adrenergic Uptake Inhibitors/therapeutic use , Antidepressive Agents/adverse effects , Antidepressive Agents/therapeutic use , Cyclohexanols/adverse effects , Cyclohexanols/therapeutic use , Duloxetine Hydrochloride , Humans , Meta-Analysis as Topic , Norepinephrine/antagonists & inhibitors , Randomized Controlled Trials as Topic , Selective Serotonin Reuptake Inhibitors/therapeutic use , Thiophenes/adverse effects , Thiophenes/therapeutic use , Venlafaxine Hydrochloride
10.
J Cardiovasc Pharmacol ; 43(1): 148-53, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14668581

ABSTRACT

The beta-blocker nebivolol is a racemic mixture of D- and L- enantiomers that displays negative inotropic as well as direct vasorelaxant activity. In addition, it has been proposed that nebivolol exerts endothelium-protective effects caused by its antioxidant properties. In the present study we investigated the effect of D-, L-, and d/l-nebivolol on reactive oxygen species (ROS)-induced endothelial damage and compared it with carvedilol and metoprolol. Isolated rat aortic rings were exposed to ROS by electrolysis of the organ bath medium. Before and after electrolysis, endothelial function was measured by preconstricting the vessels with phenylephrine followed by the addition of methacholine. Carvedilol and nebivolol protected against ROS-induced endothelial damage, whereas metoprolol did not. The protective effect of nebivolol proved not to be stereoselective. Furthermore, we attempted to determine whether nebivolol acts a scavenger itself or whether another mechanism is involved. By means of HPLC measurements it was shown that nebivolol concentrations were decreased after exposure to electrolysis-induced ROS, thus indicating that nebivolol is degraded by its reaction with ROS. Functional experiments, in the rat aorta, demonstrated that exposure of nebivolol to ROS also affects its vasodilator activity. In conclusion, the present study demonstrates that nebivolol alleviates ROS-induced impairment of endothelium-dependent vasorelaxation. This protective effect is very likely the result of a direct ROS-scavenging action by the nebivolol molecule itself.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Benzopyrans/pharmacology , Ethanolamines/pharmacology , Muscle, Smooth, Vascular/drug effects , Oxidative Stress/drug effects , Animals , Aorta , Chromatography, High Pressure Liquid , Male , Nebivolol , Rats , Rats, Inbred WKY , Reactive Oxygen Species
11.
J Cardiovasc Pharmacol ; 43(1): 154-9, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14668582

ABSTRACT

In recent years it has been shown that angiotensin II (Ang II) stimulates formation of reactive oxygen species (ROS), presumably by activation of NAD(P)H oxidase. This ROS formation has been primarily associated with cellular growth regulation by Ang II. The objective of the present study was to investigate whether these ROS contribute to Ang II-induced vasoconstriction. Experiments were performed in isolated rat thoracic aorta. Concentration response curves were constructed for Ang II in the absence and presence of the NAD(P)H oxidase inhibitor DPI, and ROS scavengers catalase and EUK-8. Inhibition of NAD(P)H oxidase as well as scavenging of ROS, decreased the contractile response to Ang II. Administration of NADPH, a substrate for NAD(P)H oxidase, produced vasoconstriction that proved to be sensitive for DPI, catalase, and EUK-8. Exposure of the vessels to exogenous ROS, induced by electrolysis of the organ bath medium, also resulted in a contractile response that was decreased by ROS scavenging. The results suggest that ROS play a role in Ang II-induced vasoconstriction via the activation of NAD(P)H oxidase.


Subject(s)
Angiotensin II/pharmacology , Muscle, Smooth, Vascular/drug effects , Reactive Oxygen Species/metabolism , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Animals , Aorta, Thoracic , Catalase/metabolism , Male , Mitogen-Activated Protein Kinases/metabolism , Muscle, Smooth, Vascular/enzymology , Rats , Rats, Wistar
12.
J Cardiovasc Pharmacol ; 42(2): 232-6, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12883327

ABSTRACT

Nebivolol is a highly selective beta(1) adrenoceptor blocker with additional vasodilating properties. Although it has been shown that the nebivolol-induced vasorelaxation is nitric oxide (NO) and cGMP dependent, the receptor that mediates these actions remains controversial, and serotonergic as well as beta-adrenergic pathways may be involved. Therefore, functional experiments investigating the receptor involved in nebivolol-induced vasorelaxation were performed in the rat aorta. Isolated aortic rings were exposed to cumulative concentrations of nebivolol. Nebivolol concentrations of 3 micromol/L and higher caused vasorelaxation, which was inhibited by the presence of the NO synthase inhibitor l-NNA (100 micromol/L), or by mechanical removal of the endothelium. Exposure of the vessel rings to the selective 5-HT(1A) antagonist NAN-190 (1 micromol/L) or the 5-HT(1/2) antagonist methysergide (1 micromol/L) did not influence nebivolol-induced vasorelaxation. Similarly, the incubation with the beta(2)-adrenoceptor antagonist butoxamine (50 micromol/L) did not prevent vasorelaxation. The selective beta(3)-adrenoceptor antagonist S-(-)-cyanopindolol (1 micromol/L), however, significantly counteracted the nebivolol-induced vasorelaxation. Furthermore, exposure of the aortic rings to cumulative concentrations of the beta(3) selective adrenoceptor agonist BRL37344 caused, like nebivolol, NO-dependent vasorelaxation that was antagonized by S-(-)-cyanopindolol. The results suggest that nebivolol-induced NO-dependent vasorelaxation is, at least in part, caused by a beta(3)-adrenoceptor agonistic effect.


Subject(s)
Benzopyrans/pharmacology , Ethanolamines/pharmacology , Muscle, Smooth, Vascular/drug effects , Receptors, Adrenergic, beta-3/drug effects , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Animals , Drug Interactions , Male , Nebivolol , Rats , Rats, Inbred WKY , Vasoconstrictor Agents/pharmacology
13.
Fundam Clin Pharmacol ; 16(6): 485-94, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12685507

ABSTRACT

The relaxing properties of vasodilator drugs in vitro may depend on the characteristics of the contractile state of the vessel investigated. Rat-isolated thoracic aortas were exposed to different types of pre-contraction. The following vasoconstrictor agents were used: phenylephrine (PhE), a selective alpha1-adrenoceptor agonist; St 587, a partial alpha1-adrenoceptor stimulant; U46619 (U-46). a thromboxane A2 agonist: and potassium ions causing receptor-independent depolarization of the membrane. After pre-contraction, various differential vasodilator drugs were investigated: methacholine (MCh, endothelium dependent), sodium nitroprusside (SNP, NO donor), forskolin (FSK, adenylyl cyclase stimulant) and nifedipine, a Ca2+-antagonist (selective L-type calcium antagonist). The vasodilator activity of these compounds was quantified by their vasodilator potency value (pD2) and efficacy (Emax) obtained from their concentration-response curves. PhE (0.1, 0.3, 3 microM) caused isometric responses of 4.8 +/- 0.3, 6.5 +/- 0.3 and 7.8 +/- 0.5 mN, respectively. An increase of the PhE concentration from 0.1 to 3 microM did not influence the response to FSK while it reduced the pD2 of SNP (8.6 +/- 0.1 to 7.35 +/- 0.1). Under these conditions, only the Emax of MCh was reduced (96.3 +/- 4.3% to 43.3 +/- 6.9%). U46 (0.18, 0.3, 1 microM) increased the contractile force by 7.4 +/- 0.4, 8.8 +/- 0.3 and 10.4 +/- 0.3 mN, respectively. Increasing the concentration of U-46 from 0.18 to 1 microM affected only the efficacy of SNP (84 +/- 4.4% to 17 +/- 8.8%) and MCh (64.5 +/- 12.3% to 0.0 +/- 9.2%) and reduced the potency of FSK (7.91 +/- 0.26 to 7.15 +/- 0.10). The concentration of K+-ions from 25 to 30 and 40 mM increased the contractile force by 4.0 +/- 0.4, 7.0 +/- 0.5 and 10.8 +/- 0.4 mN, respectively. The increase in [K+] caused a potency decrease of FSK (7.1 +/- 0.0 to 5.8 +/- 0.0) whereas both efficacy and potency were reduced for SNP (95.6 +/- 1.8% to 65.8 +/- 1.9% and 8.7 +/- 0.1 to 7.2 +/- 0.1) and MCh (55.4 +/- 3.5% to 24.5 +/- 0.8% and 7.4 +/- 0.3 to 6.1 +/- 0.4). Inhibiting of the endothelial NO production by L-NAME 100 microM resulted after pre-contraction with PhE and potassium in comparable differences in properties for SNP. Pre-contraction with St 587 1, 3, 10 and 30 microM shows comparable results after nifedepine relaxation. The present experiments clearly demonstrate that the characteristics of the applied pre-contraction strongly, but differentially influence both the potency and efficacy of various vasodilator drugs in vitro. Accordingly, in vitro characterization of vasodilator drugs should be performed under a carefully standardized protocol of pre-contraction.


Subject(s)
Aorta, Thoracic/drug effects , Vasoconstriction/drug effects , Vasodilator Agents/pharmacology , Animals , Aorta, Thoracic/physiology , Dose-Response Relationship, Drug , Endothelium, Vascular/physiology , In Vitro Techniques , Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , Rats , Rats, Wistar , Vasoconstrictor Agents/pharmacology
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