RESUMO
A key limitation in assessing the therapeutic impact of non-pharmacological approaches to treating hypertension is the method of reporting outcomes. Reducing the medications required to achieve the same blood pressure may be reported separately to a reduction in the blood pressure without change in medication, and thus lessen the reported beneficial impact of treatment. This study aims to derive a novel scoring system to gauge the therapeutic impact of non-drug treatment of hypertension by utilising a combination of excessive blood pressure and the number of anti-hypertensives into a combined score-the hypertensive index (HTi). The hypertensive index was empirically derived based on the systolic blood pressure and number of antihypertensive drugs, and applied retrospectively to a cohort undergoing intervention for renovascular hypertension. Subgroup and receiver operating characteristic analyses were used to compare the HTi to traditional methods of reporting outcomes. Following intervention (99 patients), 46% had improvement in both medication load and blood pressure, 29% had benefit in blood pressure without reduction in medication load, 15% had reduction in medication load without significant change in blood pressure and 9% showed no benefit in either parameter. The HTi was superior in detecting benefit from intervention compared with measuring blood pressure or medication load alone (AUC 0.94 vs 0.85;0.84). The hypertensive index may be a more sensitive marker of treatment effect than assessing blood pressure measurements alone. The use of such scoring systems in future trial design may allow more accurate reporting of the effects of interventions for hypertension.
Assuntos
Hipertensão Renovascular , Hipertensão , Humanos , Estudos Retrospectivos , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Anti-Hipertensivos/uso terapêuticoRESUMO
Renal artery angioplasty for renovascular hypertension is a controversial subject with considerable data but few certainties. This article is a summary of the Grand Round on Renovascular Hypertension held at the British Hypertension Society Annual Conference in September 2006.
Assuntos
Hipertensão Renovascular/cirurgia , Obstrução da Artéria Renal/cirurgia , Adulto , Angioplastia , Aterosclerose/cirurgia , Humanos , Hipertensão Renovascular/diagnóstico , Hipertensão Renovascular/fisiopatologia , Rim/fisiopatologia , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/fisiopatologiaRESUMO
In human essential hypertension (EH), endothelium-dependent relaxation can occur independent of nitric oxide (NO) and prostacyclin (PGI(2)). Recent in vivo data suggest that rapid compensatory upregulation of endothelial cytochrome P450 epoxygenase 2C9 occurs to preserve vasorelaxation under conditions of decreased NO bioavailability. As one of the vascular actions of CYP2C9 is to modulate small and intermediate conductance endothelial calcium-activated potassium channels (SK(Ca) and IK(Ca)), we examined whether endothelium-dependent relaxation is sensitive to inhibitors of these channels (apamin and charybdotoxin) in resistance-sized vessels from human with EH. Subcutaneous gluteal biopsies were performed on 12 humans with EH and 12 matched control subjects. Resistance arteries were dissected and relaxation responses to carbachol were assessed ex vivo using wire myography in the presence of: (i) N(G)-nitro-L-arginine (L-NOARG)/indomethacin; and (ii) apamin/charybdotoxin. Maximal carbachol relaxation was impaired in EH vs control subjects. No differences in responses were observed with the endothelium-independent agonist, S-nitroso-N-acetyl-penicillamine. Relaxation to carbachol was attenuated following incubation with L-NOARG/indomethacin in vessels from control subjects (P<0.01 analysis of variance (ANOVA)), but not in vessels from patients with EH. The reverse pattern was seen following apamin/charybdotoxin with carbachol relaxation attenuated only in EH vessels (P<0.001 ANOVA). Endothelium-dependent relaxation is resistant to endothelial nitric oxide synthase inhibition but sensitive to blockade of calcium-activated potassium channels in human EH. Studies with more specific inhibitors are required to determine whether this response is mediated by endothelial potassium channel subtypes (SK(Ca) and IK(Ca)).
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Hipertensão/metabolismo , Óxido Nítrico/metabolismo , Canais de Potássio Cálcio-Ativados/metabolismo , Adulto , Idoso , Análise de Variância , Apamina/farmacologia , Biópsia , Nádegas , Carbacol/farmacologia , Estudos de Casos e Controles , Charibdotoxina/farmacologia , Humanos , Indometacina/farmacologia , Masculino , Pessoa de Meia-Idade , Nitroarginina/farmacologia , Norepinefrina/farmacologiaRESUMO
The mechanical responses (active and resting tension, dP/dt, TPT) and ionic exchange characteristics (Ca(++), K(+), Na(+)) which follow upon a variation in temperature, rate, and [K(+)](o) were studied in the rabbit papillary muscle and arterially perfused rabbit interventricular setpum. Abrupt changes in temperature provided a means of separating the contributions of rate of development (intensity) of active state and duration of active state to total active tension development (approximated by isometric tension). Threefold changes in duration of active state with proportional changes in active tension can be induced without evidence for alteration of Ca(++), K(+), or Na(+) exchange. Abrupt cooling produced a moderate ( approximately 15%) increase of dP/dt which suggests an augmentation of active state intensity. Evidence is presented to suggest that this increase of dP/dt is based upon an increase in membrane Ca(++) concentration which occurs secondary to inhibition of active Na(+) transport. The alterations in ionic exchange and active state produced by variation of temperature are discussed in terms of a five-component control system.
RESUMO
In contrast to the large volume of data supporting the dependence of cardiac excitability and phasic contractility on external Na, Van der Kloot and Rubin (1962) and Singh (1962) have reported the persistence of both electrical and phasic mechanical activity in frog atrial and ventricular preparations soaked in isotonic sucrose solutions. The acute ionic dependence of excitability and contractility in small frog atrial trabeculae has been investigated with the conclusion that excitability and phasic contractions may continue for extended periods of time in sucrose media if the extracellular ionic concentrations remain above 2% of normal. This behavior is attributed to the slow exchange properties of the cell surfaces of the frog cardiac trabeculae and the antagonistic effects of Na, K, and Ca ions on both membrane excitability and fiber contractility.
Assuntos
Cálcio/farmacologia , Membrana Celular/fisiologia , Coração/fisiologia , Íons/farmacologia , Contração Muscular , Potássio/farmacologia , Sódio/farmacologia , Animais , Anuros , Função Atrial , Eletrofisiologia , Técnicas In Vitro , PerfusãoRESUMO
The mechanical responses (active and resting tension, dP/dt, TPT) and ionic exchange characteristics (Ca(++), K(+), Na(+)) which follow upon a variation in temperature, rate, and [K(+)](0) were studied in the rabbit papillary muscle and arterially perfused rabbit interventricular setpum. Abrupt changes in temperature provided a means of separating the contributions of rate of development (intensity) of active state and duration of active state to total active tension development (approximated by isometric tension). Threefold changes in duration of active state with proportional changes in active tension can be induced without evidence for alteration of Ca(++), K(+), or Na(+) exchange. Abrupt cooling produced a moderate ( approximately 15%) increase of dP/dt which suggests an augmentation of active state intensity. Evidence is presented to suggest that this increase of dP/dt is based upon an increase in membrane Ca(++) concentration which occurs secondary to inhibition of active Na(+) transport. The alterations in ionic exchange and active state produced by variation of temperature are discussed in terms of a five-component control system.
Assuntos
Troca Iônica , Contração Muscular/fisiologia , Músculos Papilares/fisiologia , Temperatura , Animais , Cálcio/metabolismo , Isótopos de Cálcio/metabolismo , Estimulação Elétrica , Septos Cardíacos/fisiologia , Potenciais da Membrana , Potássio/metabolismo , Coelhos , Sódio/metabolismo , Sacarose/metabolismo , Função VentricularRESUMO
If a hypertensive patient with renal artery stenosis (RAS) is to benefit from percutaneous transluminal renal angioplasty (PTRA) in terms of a sustained improvement in blood pressure control, one may postulate a demonstrable reduction in renal blood flow (RBF) to that kidney, reversible by PTRA. In a population of 32 hypertensive patients, RAS was present in 23 of 62 kidneys. Eleven of the 32 patients underwent renal revascularization, of whom 6 showed improvement in blood pressure control at 6 mo, i.e., had renovascular hypertension (RVH). There was no correlation between RBF and angiographic appearances of the renal artery. Furthermore, there was no significant difference between RBF in the stenosed kidneys of the patients with RVH compared with the stenosed kidneys of patients without RVH. Individual kidney RBF was 22% (s.d. 11) higher 1-3 wk after PTRA but the increase did not correlate with clinical outcome. Angiotensin converting enzyme (ACE) inhibition increased RBF by 25% (s.d. 25) of baseline flow before PTRA but the increase did not correlate with clinical outcome. Measurement of RBF is of limited value for the prediction of the long-term blood pressure response following PTRA.
Assuntos
Hipertensão Renovascular/diagnóstico por imagem , Circulação Renal/fisiologia , Pentetato de Tecnécio Tc 99m , Angiografia Digital , Angioplastia com Balão , Humanos , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/fisiopatologia , Renografia por Radioisótopo , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/terapiaRESUMO
Conditioned medium was collected from vascular smooth-muscle cells grown in culture to determine if these cells synthesize vasoactive substances. The medium caused a short-acting endothelium-independent constriction of rat aorta, followed by a prolonged, endothelium-dependent relaxation. This relaxation was mediated through the release of endothelium-derived relaxing factor (EDRF) as it was abolished by the addition of methylene blue (5 x 10(-6) M), haemoglobin (10(-6) M) or methyl arginine, but was not affected by indomethacin (10(-5) M). Smooth-muscle medium stimulated the production of EDRF from both rat and rabbit thoracic aortic rings as well as from cultured bovine pulmonary artery endothelial cells. The prolonged stimulation of EDRF by smooth-muscle medium was not mimicked by known physiological stimuli to EDRF release; EDRF-stimulating activity was not affected when smooth-muscle cells were grown in the presence of indomethacin (10(-5) M), although serum in the medium was required. The EDRF-stimulating substance(s) in the smooth-muscle medium was heat stable and associated with a high molecular mass (30,000 greater than Mr greater than 3500) water-soluble species that is as yet unidentified.
Assuntos
Endotélio Vascular/fisiologia , Músculo Liso Vascular/fisiologia , Óxido Nítrico/metabolismo , Animais , Aorta/citologia , Aorta/efeitos dos fármacos , Aorta/fisiologia , Células Cultivadas , Endotélio Vascular/citologia , Técnicas In Vitro , Indometacina/farmacologia , Cinética , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Fenilefrina/farmacologia , Coelhos , Ratos , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
Septic shock is a major cause of hospital deaths despite modern intensive therapy. Profound hypotension is caused by a collapse of regulatory mechanisms. Recent advances have established that bacterial products and the host inflammatory response together generate uncontrolled production of nitric oxide throughout the vasculature, accounting for this vasodilatation. Progressive heart failure is a further manifestation of established septic shock. Emerging research suggests that overproduction of nitric oxide within the myocardium likewise leads to loss of normal myocardial function. The possibility exists that exciting future therapies will be able to selectively inhibit the overproduction of nitric oxide and aid recovery from this frequently lethal condition.
Assuntos
Insuficiência Cardíaca/metabolismo , Óxido Nítrico/fisiologia , Choque Séptico/metabolismo , Animais , Insuficiência Cardíaca/etiologia , Humanos , Contração Miocárdica , Miocárdio/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/antagonistas & inibidores , Choque Séptico/complicações , Choque Séptico/tratamento farmacológicoRESUMO
OBJECTIVE: This study aimed to investigate antimicrobial treatment of an infected cochlear implant, undertaken in an attempt to salvage the infected device. METHODS: We used the broth microdilution method to assess the susceptibility of meticillin-sensitive Staphylococcus aureus isolate, cultured from an infected cochlear implant, to common antimicrobial agents as well as to novel agents such as tea tree oil. To better simulate in vivo conditions, where bacteria grow as microcolonies encased in glycocalyx, the bactericidal activity of selected antimicrobial agents against the isolate growing in biofilm were also compared. RESULTS: When grown planktonically, the S aureus isolate was susceptible to 17 of the 18 antimicrobials tested. However, when grown in biofilm, it was resistant to all conventional antimicrobials. In contrast, 5 per cent tea tree oil completely eradicated the biofilm following exposure for 1 hour. CONCLUSION: Treatment of infected cochlear implants with novel agents such as tea tree oil could significantly improve salvage outcome.