RESUMO
The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons1. The atmospheric concentration of trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s2. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased3,4. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown3. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010.
RESUMO
In the 30 years since the original description of ischaemic preconditioning, understanding of the pathophysiology of ischaemia/reperfusion injury and concepts of cardioprotection have been revolutionised. In the same period of time, management of patients with coronary artery disease has also been transformed: coronary artery and valve surgery are now deemed routine with generally excellent outcomes, and the management of acute coronary syndromes has seen decade on decade reductions in cardiovascular mortality. Nonetheless, despite these improvements, cardiovascular disease and ischaemic heart disease in particular, remain the leading cause of death and a significant cause of long-term morbidity (with a concomitant increase in the incidence of heart failure) worldwide. The need for effective cardioprotective strategies has never been so pressing. However, despite unequivocal evidence of the existence of ischaemia/reperfusion in animal models providing a robust rationale for study in man, recent phase 3 clinical trials studying a variety of cardioprotective strategies in cardiac surgery and acute ST-elevation myocardial infarction have provided mixed results. The investigators meeting at the Hatter Cardiovascular Institute workshop describe the challenge of translating strong pre-clinical data into effective clinical intervention strategies in patients in whom effective medical therapy is already altering the pathophysiology of ischaemia/reperfusion injury-and lay out a clearly defined framework for future basic and clinical research to improve the chances of successful translation of strong pre-clinical interventions in man.
Assuntos
Traumatismo por Reperfusão Miocárdica , Pesquisa Translacional Biomédica , Animais , Humanos , Precondicionamento Isquêmico Miocárdico/métodos , Precondicionamento Isquêmico Miocárdico/tendênciasRESUMO
Exercise protects against myocardial ischemia-reperfusion (I-R) injury but the mechanism remains unclear. Protection can be transferred from a remotely preconditioned human donor to an isolated perfused rabbit heart using a dialysate of plasma. We hypothesized that physical exercise preconditioning also confers cardioprotection through a humorally mediated effector dependent on opioid receptor activation. Thirteen male volunteers performed vigorous exercise (four 2-minute bouts of high-intensity exercise) and 1 week later they underwent remote ischemic preconditioning (four cycles of 5 min upper limb ischemia and reperfusion). Dialysates were prepared from blood collected before (control) and after the two interventions. Isolated rabbit hearts were perfused with the dialysates without and with co-administration of naloxone (opioid receptor antagonist) prior to 40 min regional ischemia and 2 h reperfusion. Exercise and remote ischemic preconditioning (rIPC) reduced infarct size from 60 ± 5 to 35 ± 5 % and from 57 ± 7 to 27 ± 3 % of the area at risk, respectively (p < 0.05 and < 0.01). Furthermore, post-ischemic left ventricular developed pressure was improved compared with controls (p = 0.08 for exercise and p = 0.04 for rIPC). Co-perfusion with naloxone abrogated the protective effects of exercise and remote ischemic preconditioned dialysates. In conclusion, high-intensity exercise preconditioning elicits cardioprotection through a humorally mediated dependent on opioid receptor activation, similar to rIPC.
Assuntos
Transfusão de Sangue , Exercício Físico , Precondicionamento Isquêmico/métodos , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Comunicação Parácrina , Extremidade Superior/irrigação sanguínea , Adolescente , Adulto , Animais , Hemodinâmica , Humanos , Técnicas In Vitro , Ácido Láctico/metabolismo , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Comunicação Parácrina/efeitos dos fármacos , Coelhos , Fatores de Tempo , Função Ventricular Esquerda , Pressão Ventricular , Adulto JovemRESUMO
The force-frequency relationship (FFR) reflects alterations in intracellular calcium cycling during changing heart rate (HR). Tachycardia-induced heart failure is associated with depletion of intracellular calcium. We hypothesized (1) that the relative resistance to tachycardia-induced heart failure seen in neonatal pigs is related to differences in calcium cycling, resulting in different FFR responses and (2) that pretreatment with digoxin to increase intracellular calcium would modifies these changes. LV +dP/dt was measured during incremental right atrial pacing in 16 neonatal and 14 adult pigs. FFR was measured as the change in +dP/dt as HR was increased. Animals were randomized to control or intravenous bolus digoxin (n = 8 neonate pigs in the 0.05 mg/kg group and n = 7 adult pigs in the 0.025 mg/kg group) and paced for 90 min at 25 bpm greater than the rate of peak +dP/dt. Repeat FFR was then obtained. The postpacing FFR in neonatal control pigs shifted rightward, with peak force occurring 30 bpm greater than baseline (P < 0.03). There was no vertical shift; thus, force at 150 bpm decreased (P < 0.03) and force at 300 beats/min increased (P < 0.08). In adult control pigs, FFR shifted downward (P < 0.01), with decreased force generation at all HRs. In both neonates and adult pigs, digoxin increased +dP/dt at all HRs; however, in neonate pigs digoxin decreased the contractile reserve by abrogation of the rightward shift of FFR. An adaptive response to tachycardia in the neonate pig leads to improved force generation at greater HRs. Conversely, the response of the mature pig heart is maladaptive with decreased force generation. Pretreatment with digoxin modifies these responses.
Assuntos
Animais Recém-Nascidos , Frequência Cardíaca/fisiologia , Contração Miocárdica/fisiologia , Taquicardia/fisiopatologia , Fatores Etários , Animais , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/fisiologia , Estimulação Cardíaca Artificial , Cardiotônicos/farmacologia , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Digoxina/farmacologia , Eletrocardiografia/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Modelos Teóricos , Contração Miocárdica/efeitos dos fármacos , Retículo Sarcoplasmático/efeitos dos fármacos , Retículo Sarcoplasmático/fisiologia , Suínos , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologiaAssuntos
Ecocardiografia Transesofagiana , Cardiopatias/diagnóstico por imagem , Hematoma/diagnóstico por imagem , Complicações Intraoperatórias/diagnóstico por imagem , Oxigenação por Membrana Extracorpórea , Defeitos dos Septos Cardíacos/cirurgia , Humanos , Recém-Nascido , Masculino , Veias Pulmonares/anormalidades , Veias Pulmonares/cirurgiaRESUMO
AIM: Intermittent limb ischaemia prior to cardiac ischaemia is a cardioprotective stimulus. This study was to investigate whether this peripheral stimulus had any effects on basal coronary blood flow and resistance, and to explore its potential mechanisms by studying the effect of femoral nerve transection and Katp blockade by glibenclamide. METHODS: Remote ischaemic preconditioning (rIPC) was induced by four 5-min cycles of lower limb ischaemia. Coronary resistance was measured using standard formulae and coronary blood flow in the left anterior descending artery (LAD) by a flow probe. In experiment 1, coronary ischaemia was induced by inflation of a cuff placed around the mid-LAD, and inflated until cessation of flow. Left ventricular (LV) function was assessed using dp/dt and Tau at 1 and 30 min of ischaemia. Experiment 1: 20 pigs were randomized to control (n = 6), rIPC (n = 7) or femoral nerve transection + rIPC (n = 7) groups. The femoral nerve was transected before the rIPC protocol. All data were collected at fixed heart rates of 120 bpm. Coronary resistance was decreased and flow was increased significantly by the rIPC stimulus (P = 0.003, P = 0.016, paired t-test), and these changes were preserved after femoral nerve transection. Experiment 2: 19 pigs were randomized to control (n = 5), rIPC (n = 8) or glibenclamide-treated rIPC (n = 6) groups. Data were collected at baseline, and during incremental pacing between 120 and 180 bpm. RESULTS: Experiment 1: Coronary resistance was decreased and flow was increased significantly by rIPC stimulus (P = 0.003, P = 0.016, paired t-test), and these changes were preserved after femoral nerve transaction. rIPC was associated with superior LV function (dp/dt(max)) at 30 min, compared with controls and the rIPC + femoral nerve transaction group. Experiment 2: Coronary resistance was significantly lower, and LAD flow was significantly higher in rIPC group (P < 0.0001, P = 0.0008, two-way anova). These effects were reversed in the glibenclamide group. CONCLUSION: The rIPC stimulus leads to reduced coronary resistance and increased flow. This effect, while modified by glibenclamide appears to be a generic effect of remote ischaemia rather than a direct preconditioning effect.
Assuntos
Circulação Coronária/fisiologia , Precondicionamento Isquêmico/métodos , Resistência Vascular/fisiologia , Animais , Antiarrítmicos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/fisiologia , Nervo Femoral/cirurgia , Glibureto/farmacologia , Membro Posterior , Masculino , Modelos Animais , Suínos , Resistência Vascular/efeitos dos fármacos , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: Brain death is associated with profound disturbances of systemic and myocardial oxygen transport, but little is known regarding the acute response of systemic oxygen consumption (VO(2)). METHODS: Brain death was induced in 6 pigs (30.6 +/- 3.0 kg) by balloon inflation into the cranial cavity. VO(2) was continuously measured by respiratory mass spectrometry. Blood pressures and gases were measured from the aorta, superior vena cava, and coronary sinus, with arterial epinephrine and norepinephrine, prior to brain death, at 1, 10, and 90 minutes after brain death. Cardiac output (CO), systemic vascular resistance (SVR), oxygen delivery (DO(2)), oxygen extraction (EO(2)), and myocardial oxygen (mEO(2)) and lactate extractions (mE(1ac)) were calculated. Left ventricular contractility was assessed by micromanometer tipped catheters. RESULTS: VO(2) increased from 4.8 +/- 0.9 to 6.3 +/- 0.9 mL/min/kg 1 minute after brain death (P < .001), and subsequently decreased to below baseline at 90 minutes (P < .001). Left ventricular contractility, CO, and DO(2) increased 1 minute after brain death (P < .001), followed by a rapid decrease to baseline within 10 minutes (P < .001). SVR and EO(2) decreased after brain death (P < .01) and remained low. Lactate remained unchanged. mE(1ac) decreased after brain death despite a decrease in mEO(2) (P < .01), and returned to baseline at 90 minutes. CONCLUSIONS: The initial surge in VO(2) after brain death is offset by the greater increase in DO(2), thus tissue perfusion remains adequate. The lower than baseline VO(2) and SVR at the end of the study period may indicate general metabolic and hemodynamic compromise. The information regarding the profound metabolic alterations imposed by brain death may have implications for management of brain death donors.
Assuntos
Morte Encefálica/fisiopatologia , Miocárdio/metabolismo , Consumo de Oxigênio , Animais , Transporte Biológico , Gasometria , Pressão Sanguínea , Modelos Animais de Doenças , Frequência Cardíaca , SuínosRESUMO
Remote ischemic preconditioning reduces myocardial infarction (MI) in animal models. We tested the hypothesis that the systemic protection thus induced is effective when ischemic preconditioning is administered during ischemia (PerC) and before reperfusion and examined the role of the K(+)-dependent ATP (K(ATP)) channel. Twenty 20-kg pigs were randomized (10 in each group) to 40 min of left anterior descending coronary artery occlusion with 120 min of reperfusion. PerC consisted of four 5-min cycles of lower limb ischemia by tourniquet during left anterior descending coronary artery occlusion. Left ventricular (LV) function was assessed by a conductance catheter and extent of infarction by tetrazolium staining. The extent of MI was significantly reduced by PerC (60.4 +/- 14.3 vs. 38.3 +/- 15.4%, P = 0.004) and associated with improved functional indexes. The increase in the time constant of diastolic relaxation was significantly attenuated by PerC compared with control in ischemia and reperfusion (P = 0.01 and 0.04, respectively). At 120 min of reperfusion, preload-recruitable stroke work declined 38 +/- 6% and 3 +/- 5% in control and PerC, respectively (P = 0.001). The force-frequency relation was significantly depressed at 120 min of reperfusion in both groups, but optimal heart rate was significantly lower in the control group (P = 0.04). There were fewer malignant arrhythmias with PerC during reperfusion (P = 0.02). These protective effects of PerC were abolished by glibenclamide. Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a K(ATP) channel-dependent mechanism. Understanding this process may have important therapeutic implications for a range of ischemia-reperfusion syndromes.
Assuntos
Isquemia/fisiopatologia , Precondicionamento Isquêmico Miocárdico , Infarto do Miocárdio/patologia , Infarto do Miocárdio/prevenção & controle , Canais de Potássio/fisiologia , Trifosfato de Adenosina/fisiologia , Animais , Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Temperatura Corporal , Cardioversão Elétrica , Extremidades/irrigação sanguínea , Glibureto/farmacologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Sus scrofa , Torniquetes , Função Ventricular Esquerda , Pressão VentricularRESUMO
OBJECTIVES: To test the hypothesis that remote ischaemic preconditioning (rIPC) reduces injury after cardiopulmonary bypass (CPB). DESIGN: Randomised study with an experimental model of CPB (3 h CPB with 2 h of cardioplegic arrest). Twelve 15 kg pigs were randomly assigned to control or rIPC before CPB and followed up for 6 h. INTERVENTION: rIPC was induced by four 5 min cycles of lower limb ischaemia before CPB. MAIN OUTCOME MEASURES: Troponin I, glial protein S-100B, lactate concentrations, load-independent indices (conductance catheter) of systolic and diastolic function, and pulmonary resistance and compliance were measured before and for 6 h after CPB. RESULTS: Troponin I increased after CPB in both groups but during reperfusion the rIPC group had lower concentrations than controls (mean area under the curve -57.3 (SEM 7.3) v 89.0 (11.6) ng.h/ml, p = 0.02). Lactate increased after CPB in both groups but during reperfusion the control group had significantly more prolonged hyperlactataemia (p = 0.04). S-100B did not differ between groups. Indices of ventricular function did not differ. There was a tendency to improved lung compliance (p = 0.07), and pulmonary resistance changed less in the rIPC than in the control group during reperfusion (p = 0.02). Subsequently, peak inspiratory pressure was lower (p = 0.001). CONCLUSION: rIPC significantly attenuated clinically relevant markers of myocardial and pulmonary injury after CPB. Transient limb ischaemia as an rIPC stimulus has potentially important clinical applications.
Assuntos
Ponte Cardiopulmonar/efeitos adversos , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/cirurgia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Débito Cardíaco/fisiologia , Ácido Láctico/metabolismo , Pulmão/fisiologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Fatores de Crescimento Neural/metabolismo , Distribuição Aleatória , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/metabolismo , Suínos , Troponina I/metabolismo , Resistência VascularRESUMO
OBJECTIVES: To evaluate the clinical utility of near-infrared spectroscopic (NIRS) monitoring of cerebral (ScO2) and splanchnic (SsO2) oxygen saturations for estimation of systemic oxygen transport after the Norwood procedure. METHODS: ScO2 and SsO2 were measured with NIRS cerebral and thoracolumbar probes (in humans). Respiratory mass spectrometry was used to measure systemic oxygen consumption (O2). Arterial (SaO2), superior vena caval (SvO2) and pulmonary venous oxygen saturations were measured at 2 to 4 h intervals to derive pulmonary (Qp) and systemic blood flow (Qs), systemic oxygen delivery (DO2) and oxygen extraction ratio (ERO2). Mixed linear regression was used to test correlations. A study of 7 pigs after cardiopulmonary bypass (study 1) was followed by a study of 11 children after the Norwood procedure (study 2). RESULTS: Study 1. ScO2 moderately correlated with SvO2, mean arterial pressure, Qs, DO2 and ERO2 (slope 0.30, 0.64. 2.30, 0.017 and -32.5, p < 0.0001) but not with SaO2, arterial oxygen pressure (PaO2), haemoglobin and O2. Study 2. ScO2 correlated well with SvO2, SaO2, PaO2 and mean arterial pressure (slope 0.43, 0.61, 0.99 and 0.52, p < 0.0001) but not with haemoglobin (slope 0.24, p > 0.05). ScO2 correlated weakly with O2 (slope -0.07, p = 0.05) and moderately with Qs, DO2 and ERO2 (slope 3.2, 0.03, -33.2, p < 0.0001). SsO2 showed similar but weaker correlations. CONCLUSIONS: ScO2 and SsO2 may reflect the influence of haemodynamic variables and oxygen transport after the Norwood procedure. However, the interpretation of NIRS data, in terms of both absolute values and trends, is difficult to rely on clinically.
Assuntos
Química Encefálica/fisiologia , Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas/cirurgia , Oxigênio/sangue , Baço/química , Animais , Feminino , Cardiopatias Congênitas/fisiopatologia , Hemodinâmica , Humanos , Masculino , Oximetria , Oxigênio/metabolismo , Consumo de Oxigênio/fisiologia , Pressão Parcial , Período Pós-Operatório , Espectroscopia de Luz Próxima ao Infravermelho , Baço/irrigação sanguínea , SuínosRESUMO
The PUMA (Pollution of the Urban Midlands Atmosphere) Consortium project involved intensive measurement campaigns in the Summer of 1999 and Winter of 1999/2000, respectively, in which a wide variety of air pollutants were measured in the UK West Midlands conurbation including detailed speciation of VOCs and major component analysis of aerosol. Measurements of the OH and HO2 free radicals by the FAGE technique demonstrated that winter concentrations of OH were approximately half of those measured during the summer despite a factor of 15 reduction in production through the photolysis of ozone. Detailed box modelling of the fast reaction chemistry revealed the decomposition of Criegee intermediates formed from ozone-alkene reactions to be responsible for the majority of the formation of hydroxyl in both the summer and winter campaigns, in contrast to earlier rural measurements in which ozone photolysis was predominant. The main sinks for hydroxyl are reactions with NO2, alkenes and oxygenates. Concentrations of the more stable hydrocarbons were found to be relatively invariant across the conurbation, but the impacts of photochemistry were evident through analyses of formaldehyde which showed the majority to be photochemical in origin as opposed to emitted from road traffic. Measurements on the upwind and downwind boundaries of the conurbation revealed substantial enhancements in NOx as a result of emissions within the conurbation, especially during westerly winds which carried relatively clean air. Using calcium as a tracer for crustal particles, it proved possible to reconstruct aerosol mass from the major chemical components with a fairly high degree of success. The organic to elemental carbon ratios showed a far greater influence of photochemistry in summer than winter, presumably resulting mainly from the greater availability of biogenic precursors during the summer campaign. Two urban airshed models were developed and applied to the conurbation, one Eulerian, the other Lagrangian. Both were able to give a good simulation of concentrations of both primary and secondary pollutants at urban background locations.
Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Modelos Teóricos , Acetona/análise , Aerossóis/análise , Monóxido de Carbono/análise , Monitoramento Ambiental , Formaldeído/análise , Radicais Livres/análise , Hidrocarbonetos/análise , Óxidos de Nitrogênio/análise , Ozônio/análise , Tamanho da Partícula , Ácido Peracético/análogos & derivados , Ácido Peracético/análise , Fotoquímica , Reprodutibilidade dos Testes , Reino UnidoRESUMO
Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.
Assuntos
Testes Respiratórios/métodos , Pneumopatias/metabolismo , Biomarcadores/metabolismo , Humanos , Pneumopatias/diagnóstico , Estresse Oxidativo/fisiologia , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To describe the first clinical application of a novel tissue Doppler derived index of contractility, isovolumic acceleration (IVA), in the assessment of the ventricular myocardial force-frequency relation (FFR) in the univentricular heart (UVH). DESIGN: Prospective study. SETTING: Tertiary referral centre. INTERVENTIONS: Non-invasive assessment of the myocardial FFR by tissue Doppler echocardiography during atrial pacing. RESULTS: IVA was used to measure the FFR of the systemic ventricle in patients with structurally normal hearts and in patients with UVHs. Basal IVA of the normal hearts (mean (SD) 1.9 (0.3) m/s2) was significantly greater than that of UVHs in patients with a dominant right ventricle (RV) (1.0 (0.3) m/s2) or left ventricle (LV) (0.8 (0.7) m/s2; p < 0.05 for both). Neither the absolute nor percentage change from basal to peak values of IVA with pacing differed between the three groups. Peak force developed by the normal LV was significantly greater than that of the UVH, dominant LV group but not different from that of the UVH, dominant RV group. CONCLUSION: Contractility at basal heart rate is depressed in patients with UVH compared with the normal LV. Analysis of ventricular FFRs exposes further differences in myocardial contractility. There is no evidence that contractile function of the dominant RV is inferior to that of the dominant LV over a physiological range of heart rates.
Assuntos
Ecocardiografia Doppler , Cardiopatias Congênitas/fisiopatologia , Adolescente , Estimulação Cardíaca Artificial , Criança , Cardiopatias Congênitas/diagnóstico por imagem , Frequência Cardíaca/fisiologia , Ventrículos do Coração/anormalidades , Humanos , Contração Miocárdica/fisiologia , Marca-Passo Artificial , Estudos Prospectivos , Volume SistólicoRESUMO
Chronic cough is a common and distressing symptom. A novel algorithm has been developed for the management of chronic cough, in which an assessment of clinical probability of disease determines the need to proceed to investigation. In this study, the performance of this algorithm in clinical practice was prospectively evaluated. A total of 131 consecutively referred patients (86 females) whose principal presenting symptom was a cough of duration >8 weeks were studied. Their age (median (range)) was 60 (16-88) yrs and cough duration 5.9 (0.2-65) yrs. A cause of cough was established in 93% of cases. The most frequent diagnoses were asthma (24% of cases), gastro-oesophageal disease (22%), post-viral cough (8%), bronchiectasis (8%) and interstitial lung disease (8%). Primary pulmonary disease was significantly more likely in patients with a productive cough and in patients with an abnormal chest radiograph. Only a small proportion (<8%) of patients had multiple causes of cough. The probability of treatment started on the basis of a high clinical suspicion of either asthma, gastro-oesophageal disease or rhinitis being successful was 74%. Overall, 26% of the patients were managed successfully without the need for any form of investigation other than chest radiography and spirometry. Use of the algorithm resulted in identification of the cause of cough and successful treatment in the large majority of cases. It is concluded that this protocol has the potential to improve management by providing a structured approach, reducing the number of investigations performed, and minimising unnecessary delays in treatment.
Assuntos
Algoritmos , Tosse/diagnóstico , Tosse/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncoscopia , Doença Crônica , Tosse/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Probabilidade , Estudos Prospectivos , Testes de Função Respiratória , Fatores de Risco , EspirometriaRESUMO
BACKGROUND: It has been proposed that the pH of airway lining fluid may regulate the fractional exhaled concentration of nitric oxide (Fe(NO)) in respiratory disease. METHODS: Fe(NO), exhaled breath condensate (EBC) pH, and EBC concentrations of nitrite plus nitrate (NO2/NO3) were compared in 12 subjects with stable asthma, 18 with stable cystic fibrosis (CF), and 15 healthy control subjects. Eight of the CF patients were studied on a separate occasion at the start of a pulmonary exacerbation. RESULTS: Fe(NO) was significantly greater in asthmatic subjects than in control subjects (mean 35 v 9 ppb, p<0.001). EBC pH, however, was similar in the asthmatic and control groups (median 5.82 v 6.08, p=0.23). Levels of NO2/NO3 were on average higher in EBC samples from asthmatic subjects, but the difference was not significant. In patients with stable CF both the Fe(NO) (mean 4 ppb, p<0.001) and EBC pH (median 5.77, p=0.003) were lower than in the control group. Levels of EBC NO2/NO3 (median 29.9 microM; p=0.002) in patients with stable CF, in contrast, were significantly higher than in control subjects. During CF exacerbations, EBC pH was further reduced (median 5.30, p=0.017) but Fe(NO) and NO2/NO3 were unchanged. CONCLUSIONS: These findings demonstrate a dissociation between EBC pH and Fe(NO) in inflammatory airways disease.
Assuntos
Asma/metabolismo , Fibrose Cística/metabolismo , Óxido Nítrico/metabolismo , Adulto , Testes Respiratórios/métodos , Estudos de Casos e Controles , Expiração , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Masculino , Óxido Nítrico/análise , Mucosa Respiratória/metabolismo , Testes CutâneosRESUMO
BACKGROUND: Evaluation of right ventricular (RV) function in patients with pulmonary regurgitation (PR) after tetralogy repair remains challenging because of abnormal RV loading conditions. METHODS AND RESULTS: We examined 124 patients, aged 21+/-11.4 years, who had tetralogy repair at 3.7+/-3.5 years. By Doppler echocardiography, 33 patients had mild, 22 moderate, and 69 severe PR; 55 had significant tricuspid regurgitation (TR). Myocardial velocities, myocardial acceleration during isovolumic contraction (IVA), strain, and strain rate were measured at RV and LV base. Tricuspid valve annulus was measured in a 4-chamber view. QRS, QT, and JT intervals and their dispersions were measured from 12-lead electrocardiogram. IVA in the RV was lower in all patients compared with controls (0.8+/-0.4 versus 1.8+/-0.5, P<0.0001) and correlated with the severity of PR (r=-0.43, P<0.0001), whereas myocardial velocities, and strain/strain rate did not. LV IVA correlated with PR (r=-0.32, P<0.001) and with RV IVA (r=0.28, P<0.003). Patients with severe PR had a higher incidence of TR (r=0.69, P<0.0001) and lower RV IVA (1.0+/-0.4 versus 0.6+/-0.3, P<0.0001), a larger tricuspid valve ring diameter (P<0.0001), and prolonged electrical depolarization (P<0.001). Age at surgery or examination did not correlate with PR and with RV function assessed by IVA. In the RV, IVA correlated inversely with QRS duration (P<0.01). CONCLUSIONS: Although load-dependent myocardial velocities and strain are not influenced by the severity of PR and presence of significant TR, IVA demonstrates reduced contractile function in relation to the degree of PR and may be an early, sensitive index for selecting patients for valve replacement.
Assuntos
Ecocardiografia Doppler em Cores , Contração Miocárdica , Complicações Pós-Operatórias/fisiopatologia , Insuficiência da Valva Pulmonar/complicações , Tetralogia de Fallot/cirurgia , Disfunção Ventricular Direita/etiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos Transversais , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pressão , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/fisiopatologia , Sístole , Resultado do Tratamento , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/fisiopatologia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/fisiopatologiaRESUMO
BACKGROUND: Fetal tachycardia often leads to cardiac failure, which in experimental settings can be prevented by direct fetal glucose-insulin administration. In this study, we hypothesize that similar effects can be obtained indirectly by inducing maternal hyperglycemia. METHODS AND RESULTS: Systolic and diastolic indices (dP/dt(max) and tau) of left ventricular function were measured by use of high-fidelity catheters during 180 minutes of aggressive atrial pacing ( approximately 300 bpm) in 12 preterm porcine fetuses. In 6 fetuses, maternal hyperglycemia (15 mmol/L) was induced for the last 120 minutes of pacing. The remaining fetuses served as controls. Glucose, insulin, and free fatty acid levels were determined, as was fetal myocardial glycogen content. Maternal glucose infusion led to significant fetal hyperglycemia and hyperinsulinemia but did not change the inherently low fetal levels of free fatty acids. There were no differences between groups with regard to dP/dt(max) (1025+/-226 and 1037+/-207 mm Hg, P=NS) and tau (20.6+/-2.0 and 21.4+/-1.6 ms, P=NS) at baseline (100%). During the 180 minutes of pacing, systolic function (dP/dt(max)) and diastolic function (tau) deteriorated more in the control group than in the hyperglycemic group (P<0.001 for both). At 180 minutes, dP/dt(max) was 62+/-18% of baseline in controls and 85+/-11% in hyperglycemic fetuses (P=0.03), and tau was 117+/-12% and 98+/-4%, respectively (P=0.004). CONCLUSIONS: Induced maternal hyperglycemia improves fetal cardiac function during fetal tachycardia and suggests a possible additional therapeutic option to improve the function of the failing fetal heart before or during antiarrhythmic therapy. The findings may be relevant in fetal heart failure in general.