RESUMEN
Intrapericardial (IP) administration of certain cardioactive agents allows investigation of local pharmacological actions on the heart and may carry potential benefit to influence myocardial function. The cardioprotective adenosine (ADO) and inosine (INO) may be the most representative candidates. Elimination and cardiovascular effects of IP and intravenously (IV) applied ADO and INO were compared on anesthetized dogs. Their pericardial and systemic concentrations were measured after consecutive administration of increasing ADO and INO doses. In the case of IP administration at the end of the incubation period, pericardial concentrations of adenine nucleosides significantly exceeded the control values. However, the IV applied ADO and INO were rapidly metabolized in the systemic plasma. As characteristic hemodynamic effects, small but sustained decrease in heart rate (IP ADO) and increase in myocardial contractility (IP INO) were observed. During IV administration, ADO and INO exerted remarkable effects on all hemodynamic variables, which then gradually disappeared in 15 minutes. In summary, the elimination of ADO and INO was significantly slower in the pericardial fluid than in the plasma. Considering the balanced cardiac actions and lack of strong systemic hemodynamic effects, IP administration of adenine nucleosides may suggest a promising approach in the local treatment of the diseased heart.
Asunto(s)
Adenosina/farmacología , Cardiotónicos/farmacología , Hemodinámica/efectos de los fármacos , Inosina/farmacología , Pericardio/metabolismo , Adenosina/administración & dosificación , Adenosina/sangre , Adenosina/farmacocinética , Animales , Presión Sanguínea/efectos de los fármacos , Líquidos Corporales/metabolismo , Cardiotónicos/administración & dosificación , Cardiotónicos/sangre , Cardiotónicos/farmacocinética , Perros , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intravenosas , Inosina/administración & dosificación , Inosina/sangre , Inosina/farmacocinética , Masculino , Tasa de Depuración Metabólica , Contracción Miocárdica/efectos de los fármacos , Pericardio/efectos de los fármacosRESUMEN
BACKGROUND: Measurement of pH in exhaled breath condensate (EBC) may represent a novel method for investigating airway pathology. OBJECTIVES: The aim of this longitudinal study was to assess the variability of EBC pH in stable lung transplant recipients (LTR). METHODS: During routine clinical visits 74 EBC pH measurements were performed in 17 LTR. EBC pH was also measured in 19 healthy volunteers on four separate occasions. EBC pH was determined at standard CO2 partial pressure by a blood gas analyzer. RESULTS: Mean EBC pH in clinically stable LTR and in controls was similar (6.38 +/- 0.09 vs. 6.44 +/- 0.16; p = nonsignificant). Coefficient of variation for pH in LTR and controls was 2.1 and 2.3%, respectively. The limits of agreement for between-visit variability determined by the Bland-Altman test in LTR and healthy volunteers were also comparable (-0.29 and 0.46 vs. -0.53 and 0.44). CONCLUSIONS: Our data suggest that the variability of EBC pH in stable LTR is relatively small, and it is similar to that in healthy nontransplant subjects.
Asunto(s)
Pruebas Respiratorias , Trasplante de Pulmón , Adulto , Biomarcadores/análisis , Broncoscopía , Fibrosis Quística/cirugía , Femenino , Humanos , Concentración de Iones de Hidrógeno , Hipertensión Pulmonar/cirugía , Masculino , Reproducibilidad de los Resultados , Pruebas de Función Respiratoria , Manejo de EspecímenesRESUMEN
The adenine nucleosides, adenosine (ADO) and inosine (INO), and the endothelin-1 (ET-1) play an important role in the regulation of coronary and myocardial functions. The pericardial fluid accumulates these regulatory agents and reflects well their levels in the myocardial interstitium. This offers a possibility to examine the local adenine nucleoside-endothelin interactions in heart tissue. We have previously demonstrated that increased levels of intrapericardial (i.p.) ET-1 enhanced significantly the adenine nucleoside concentrations of the pericardial fluid samples. In this study the effects of i.p.-administered ADO and INO were investigated on the pericardial concentrations of ET-1 in the in situ dog heart. The ET-1 concentrations were determined (enzymelinked immunosorbent assay) in the samples obtained from the pericardial fluid and from the arterial plasma before and after i.p. administration of increasing doses of ADO (10, 100 and 1000 muM, n = 8) and INO (1, 10 and 100 mM, n = 8). Standard hemodynamic variables were recorded continuously. We found that i.p. ADO and INO induced dose-dependent increases of pericardial ET-1 levels after a 15-minute incubation period in pericardial (ET-1max,ADO, +121 +/- 26%, P < 0.02; and ET-1max,INO, +84 +/- 27%, P < 0.05) but not in the plasma samples. The i.p. nucleosides elicited slight but characteristic alterations in the heart rate and ventricular contractility (dP/dt). The results suggest that the pericardial adenine nucleosides interact with the myocardial ET-1 and this effect may be provoked from, and can also be detected in, the pericardium.
Asunto(s)
Adenosina/metabolismo , Endotelina-1/metabolismo , Inosina/metabolismo , Miocardio/metabolismo , Pericardio/metabolismo , Adenosina/administración & dosificación , Animales , Perros , Endotelina-1/sangre , Femenino , Frecuencia Cardíaca , Inosina/administración & dosificación , Masculino , Contracción Miocárdica , Regulación hacia Arriba , Presión VentricularRESUMEN
The pericardial fluid may accumulate endogenous regulatory agents, such as catecholamines, endothelin or adenine nucleosides. However, very little information is available on the cardiovascular effects of intrapericardial (i.p.) catecholamines and their interaction with the endogenous endothelins and adenine nucleosides. The cardiovascular effects of increasing doses of i.p.- administered dopamine boluses (0.06-8 micromol/kg, n = 8) were studied in the in situ canine heart: systemic blood pressure, heart rate and left ventricular dP/dt were recorded, and pericardial infusate samples were obtained to measure the changes in endothelin-1 (ET-1), adenosine and inosine levels (enzyme-linked immunosorbent assay and high-performance liquid chromatography methods, respectively). The responses to i.p. dopamine were compared with the effects of i.p. norepinephrine boluses (0.004-0.5 micromol/kg, n = 8). Dopamine elicited dose-dependent increases of heart rate (P < 0.01), and the highest dose of dopamine resulted in significant elevation in dP/dt and blood pressure (P < 0.01) with a nearly twofold increase of i.p. ET-1 (from 14.3 +/- 0.1 pg/mL to 26.1 +/- 0.1 pg/mL, P < 0.02) and a more than threefold augmentation of i.p. adenosine (from 2.9 +/- 0.5 microM to 11.1 +/- 3.0 microM, P < 0.05), but not of inosine levels. Similar responses were obtained with i.p. norepinephrine. The results confirm that i.p. catecholamines exert significant hemodynamic effects and modulate ET-1 and adenosine release from the heart. However, the pattern of catecholamine actions initiated from the pericardium may characteristically differ from that of intravascular ones.
Asunto(s)
Adenosina/metabolismo , Dopamina/metabolismo , Endotelina-1/metabolismo , Hemodinámica , Inosina/metabolismo , Norepinefrina/metabolismo , Pericardio/metabolismo , Animales , Presión Sanguínea , Perros , Dopamina/administración & dosificación , Frecuencia Cardíaca , Inyecciones Intravenosas , Norepinefrina/administración & dosificación , Regulación hacia Arriba , Función Ventricular Izquierda , Presión VentricularRESUMEN
Increased intrapericardial levels of endothelin-1 (ET-1) induce myocardial ischemia and concomitant release of the purine metabolites adenosine (ADO), inosine (INO) and hypoxanthine (HXA) into the pericardial fluid. However, the potential modulatory role of nitrogen monoxide in compensating the ET-1-induced ischemic stress is not fully elucidated. The pericardial elevations of purine metabolite concentrations in the pericardial fluid after ET-1 administration (150 pmol/kg intrapericardially) were measured in the in situ dog heart with (n = 6) or without (n = 5) systemic nitrogen monoxide synthase blockade (30 mg/kg (G)-nitro-L-arginine methyl ester, followed by 6 mg/min intravenously). After control sampling, three consecutive pericardial infusate samples (ET1, ET2, ET3) were obtained for purine metabolite determinations (high-performance liquid chromatography-ultraviolet). It was found that intrapericardial ET-1 elevated the pericardial purine metabolite concentrations significantly in both groups. No significant differences were detected between the control and (G)-nitro-L-arginine methyl ester-treated groups in ischemic changes of pericardial ADOmax (+3.27 +/- 1.13 microM versus +1.84 +/- 0.56 microM), INOmax (+15.21 +/- 2.3 microM versus +12.09 +/- 4.04 microM) and HXAmax (+16.34 +/- 2.98 microM versus +17.09 +/- 5.22 microM) levels and in the maximal ST elevations (0.43 +/- 0.05 mV versus 0.61 +/- 0.08 mV). The hemodynamic variables did not change with ET-1 administration. In conclusion, systemic nitrogen monoxide synthase blockade does not aggravate the ET-1-induced acute myocardial ischemia and the release of purine metabolites, suggesting that endogenous nitrogen monoxide is not a supplementary factor to purine metabolites in this type of coronary adaptive responses.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Isquemia Miocárdica/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Pericardio/enzimología , Purinas/metabolismo , Adaptación Fisiológica , Adenosina/metabolismo , Animales , Modelos Animales de Enfermedad , Perros , Endotelina-1 , Hemodinámica/efectos de los fármacos , Hipoxantina/metabolismo , Inosina/metabolismo , Isquemia Miocárdica/inducido químicamente , Isquemia Miocárdica/fisiopatología , Óxido Nítrico Sintasa/metabolismoRESUMEN
In the middle of the nineties a new, non-invasive method for investigation of the lung aroused the interest of many researchers: the exhaled breath condensate. It shows the extent of the interest that in the last five years more than 80 original articles have been published in this theme. Many substances are found in the expired breath which are detectable in the liquid that we obtain by cooling (= condensing) the exhaled breath. The advantages of this method are that it is non-invasive, convenient, it could be performed with mechanically ventilated patients as well as with children. The most studied substance is the hydrogen-peroxide, which is the marker of oxidative stress, and its level in condensate is elevated in numerous inflammatory diseases. 8-isoprostane was also studied a lot, which is another marker of oxidative stress. Numerous substances could be even measured in condensate, so the decay-product of nitric-oxide (nitrite, nitrate, nitrotyrosine), further nitrosothiol, adenosine, ammonia, different ions, leukotrienes, cytokines; recently even other feature of condensate is examined, such as its pH. The different mediators could help us to know better the diseases, support the diagnosis, follow the treatment or the disease. In this study the authors attempt to present the most important knowledge till now.
Asunto(s)
Pruebas Respiratorias/métodos , Dinoprost/análogos & derivados , Enfermedades Respiratorias/diagnóstico , Enfermedades Respiratorias/metabolismo , Asma/diagnóstico , Asma/metabolismo , Biomarcadores/análisis , Bronquiectasia/diagnóstico , Bronquiectasia/metabolismo , Fibrosis Quística/diagnóstico , Fibrosis Quística/metabolismo , F2-Isoprostanos/análisis , Humanos , Peróxido de Hidrógeno/análisis , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/metabolismo , Fumar/metabolismoRESUMEN
Analysis of exhaled breath condensate is a method for noninvasive assessment of the lung. Condensate can be collected with a nose clip (subjects inhale and exhale via the mouth) or without it (subjects inhale via the nose and exhale via the mouth), but the mode of inhalation may influence condensate volume and mediator levels. We compared condensate volume and adenosine, ammonia, and thromboxane B2 levels in young healthy volunteers (n = 25) in samples collected for 10 minutes from subjects with or without a nose clip. Patients with allergic rhinitis (n = 8) were also studied to assess the effect of upper airway inflammation on mediator levels. Adenosine, ammonia, and thromboxane B2 levels were determined by HPLC, spectrophotometry, and radioimmunoassay, respectively. Volume of condensate was significantly higher without nose clip than that with nose clip (mean +/- SD, 2321 +/- 736 microl and 1746 +/- 400 microl, respectively; p = 0.0001). We found no significant difference in any mediator levels between these two collection modes in healthy volunteers, but adenosine showed a tendency to differ between oral and nasal inhalation in patients with allergic rhinitis. Our data indicate that whereas a greater volume of condensate can be obtained when subjects inhale through their noses, the mode of inhalation does not influence mediator levels in young healthy volunteers, but may affect these levels in patients with allergic rhinitis.
Asunto(s)
Adenosina/análisis , Amoníaco/análisis , Pruebas Respiratorias/métodos , Mediadores de Inflamación/análisis , Inhalación , Boca , Nariz , Rinitis Alérgica Perenne/diagnóstico , Rinitis Alérgica Perenne/fisiopatología , Manejo de Especímenes/métodos , Tromboxano B2/análisis , Adulto , Sesgo , Pruebas Respiratorias/instrumentación , Estudios de Casos y Controles , Constricción , Femenino , Volumen Espiratorio Forzado , Humanos , Modelos Lineales , Masculino , Manejo de Especímenes/instrumentación , Manejo de Especímenes/normas , Volumen de Ventilación Pulmonar , Factores de Tiempo , Capacidad VitalRESUMEN
It has been shown that the adenosine concentration in the pericardial fluid of the normal heart is higher by one order of magnitude than that of the venous plasma. A further increase in the pericardial adenosine concentration was also demonstrated in myocardial ischaemia or hypoxia. It was proposed that pericardial nucleoside levels may represent the interstitial concentrations of the adenine nucleosides. An experimental model was designed to determine the intrapericardial concentrations of adenosine, inosine and hypoxanthine during coronary spasm provoked by intracoronary administration of endothelin-1 (ET-1; 0.08+/-0.02 nmol/g of myocardial tissue). In the in situ dog heart (n=10), adenosine, inosine and hypoxanthine concentrations were determined by HPLC in fluid samples collected from the closed pericardial sac before and after ET-1 administration, and from the systemic arterial blood. Systemic blood pressure, heart rate and standard ECG were registered continuously. We found that the nucleoside concentrations in the infusate samples increased significantly during coronary spasm [adenosine, 1.49+/-0.44 compared with 0.37+/-0.07 microM (P<0.05); inosine, 27.43+/-11.51 compared with 0.47+/-0.11 microM (P<0.05); hypoxanthine, 21.17+/-6.49 compared with 4.91+/-1.24 microM (P<0.05)], while a significant decrease in blood pressure and an elevation in ECG ST segments were observed. The levels of the purine metabolites did not change in the systemic blood. The data indicate that changes in adenine nucleoside levels measured in pericardial infusate samples reflect activation of coronary metabolic adaptation in this model of spastic ischaemia, and that pericardial nucleoside levels may characterize alterations in interstitial adenine nucleoside concentrations.
Asunto(s)
Adenosina/análisis , Vasoespasmo Coronario/metabolismo , Endotelina-1/farmacología , Pericardio/química , Vasoconstrictores/farmacología , Animales , Perros , Hipoxantina/análisis , Inosina/análisis , Modelos Animales , Isquemia Miocárdica/metabolismo , Pericardio/metabolismoRESUMEN
Pericardial fluid accumulates the cardioprotective purine metabolites, as well as the endogenous vasoconstrictor agent endothelin-1 (ET-1). The aim of the present study was to characterize the pericardial concentrations of the purine metabolites adenosine, inosine and hypoxanthine before and after intrapericardial administration of ET-1 to the in situ heart. The closed pericardial sac of anaesthetized dogs (n=9) was cannulated for ET-1 administration and for obtaining native pericardial fluid and control pericardial infusate samples (C1 and C2), as well as consecutive pericardial infusate samples (samples I, II and III) obtained 15 min after intrapericardial administration of 150 pmol/kg ET-1. In an additional five dogs, using the same protocol, ventricular epicardial and endocardial monophasic action potential recordings were performed to assess local ischaemic electrophysiological changes. Significant elevations of pericardial purine metabolite concentrations (measured by HPLC) were found in sample II compared with sample C2: adenosine, 4.5+/-1.7 compared with 0.5+/-0.1 microM (P<0.05); inosine, 18.3+/-2.8 compared with 0.9+/-0.2 microM (P<0.001); hypoxanthine, 38.1+/-8.0 compared with 13.4+/-2.6 microM (P<0.01). Systemic blood pressure, left ventricular pressure and contractility, and systemic plasma levels of the purine metabolites remained unchanged during the ET-1 effect, while significant ECG ST elevations (ST(max) 0.68+/-0.01 mV; P<0.001) were observed. In the five dogs analysed electrophysiologically, the left ventricular epicardial monophasic action potential duration and upstroke velocity decreased significantly at time point II compared with C2, while the endocardial monophasic action potential duration and upstroke velocity did not show ischaemia-related changes. The results suggest that intrapericardial administration of ET-1 induces subepicardial ischaemia, with parallel activation of coronary metabolic adaptive and cardiac self-protective mechanisms in the epimyocardial layer of the heart.
Asunto(s)
Endotelina-1/metabolismo , Pericardio/metabolismo , Purinas/metabolismo , Potenciales de Acción , Adenosina/análisis , Adenosina/sangre , Animales , Líquidos Corporales/metabolismo , Perros , Endotelina-1/farmacología , Pericardio/fisiopatología , Purinas/análisis , Vasoconstrictores/farmacologíaRESUMEN
We investigated whether the level of plasma adenosine (ADO) changed during exercise and whether this could be related to exercise-induced bronchoconstriction. Baseline levels of ADO did not differ, but exercise resulted in higher ADO in patients with asthma than in healthy subjects (86 +/- 35 vs 59 +/- 16 nmol/L; P <.001). In patients with asthma, the increase in ADO was related to decreases in FEV(1) (r (2) = 0.475; P <.05) and SaO(2) (r (2) = 0.693; P <.05). These data suggest that adenosine might be involved in the development of exercise-induced bronchoconstriction.