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1.
Resuscitation ; 84(8): 1150-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23454260

RESUMO

BACKGROUND: Cardiac arrest is an important cause of mortality. Cardiopulmonary resuscitation (CPR) improves survival, however, delivery of effective CPR can be challenging and combining effective chest compressions with ventilation, while avoiding over-ventilation is difficult. We hypothesized that ventilation with a pneumatically powered, automatic ventilator (Oxylator(®)) can provide adequate ventilation in a model of cardiac arrest and improve the consistency of ventilations during CPR. METHODS/RESULTS: Twelve pigs (∼40 kg, either sex) underwent 3 episodes each of cardiac arrest and resuscitation consisting of 30s of untreated ventricular fibrillation, followed by 5 min of CPR, defibrillation, and ∼30 min of recovery. During CPR in each episode, pigs were ventilated in 1 of 3 ways in random balanced order: manual ventilation using AMBU bag (12 breaths/min), low pressure Oxylator(®) (maximum airway pressure 15 cm H2O with 20 L/min constant flow in automatic mode [Ox15/20]), or high pressure Oxylator(®) (maximum airway pressure 20 cm H2O with 30 L/min constant flow in automatic mode [Ox20/30]). During CPR, both Ox15/20 and Ox20/30 resulted in higher levels of positive end expiratory pressure than manual ventilation. Ox15/20 ventilation also resulted in higher arterial pCO2 than manual ventilation. Ox20/30 ventilation yielded higher arterial pO2 and a lower arterial-alveolar gradient than manual ventilation. All pigs were successfully defibrillated, and no measured haemodynamic variables were different between the groups. CONCLUSION: Ventilation with an automatic ventilation device during CPR is feasible and provides adequate ventilation and comparable haemodynamics when compared to manual bag ventilation.


Assuntos
Reanimação Cardiopulmonar/métodos , Cardioversão Elétrica/efeitos adversos , Parada Cardíaca , Ventiladores Mecânicos/normas , Fibrilação Ventricular/complicações , Animais , Gasometria/métodos , Modelos Animais de Doenças , Parada Cardíaca/sangue , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , Parada Cardíaca/terapia , Hemodinâmica , Modelos Cardiovasculares , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Suínos , Fatores de Tempo , Resultado do Tratamento
2.
Am J Cardiol ; 109(10): 1504-9, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22385756

RESUMO

Pulmonary arterial hypertension (PAH) is a disorder in which pulmonary arterial remodeling and vasoconstriction progressively lead to right heart failure (HF), exercise intolerance, and high mortality. Beta-blockers have been shown to decrease mortality in left-sided HF, but their efficacy in isolated right HF associated with PAH is uncertain. Patients with PAH may have cardiac co-morbidities for which ß-blocker therapy is indicated, and the relative risk benefit of this therapy remains to be proved. This is a prospective cohort study of 94 consecutive patients with PAH divided into 2 groups with and without ß-blocker use at baseline. Rate of all-cause mortality, PAH-related hospitalization, change in 6-minute walk test, right ventricular structure and function measured by echocardiography, and hemodynamics measured by right heart catheterization were determined between subjects with and without ß-blocker use. Beta-blocker use was common (28%) in this cohort. After a median follow-up of 20 months, changes in pulmonary hemodynamics and right ventricular size and function were similar between groups. There were no statistically significant differences in adverse events including PAH-related hospitalization or all-cause mortality (p = 0.19), presence of right HF by last visit (p = 0.75), or change in last 6-minute walk distance (p = 0.92). In conclusion, ß-blocker use is not uncommon in a select group of patients with PAH and cardiac co-morbidities and did not appear to exert detrimental effects in clinical, functional, and hemodynamic outcomes. Further randomized data are needed to evaluate the potential benefits and risks of ß-blocker use in patients with PAH.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Hipertensão Pulmonar/tratamento farmacológico , Resistência Vascular/efeitos dos fármacos , Disfunção Ventricular Direita/prevenção & controle , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Hipertensão Pulmonar Primária Familiar , Feminino , Seguimentos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/mortalidade , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Estudos Prospectivos , Pressão Propulsora Pulmonar/efeitos dos fármacos , Fatores de Risco , Taxa de Sobrevida/tendências , Resultado do Tratamento , Disfunção Ventricular Direita/complicações , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Direita/efeitos dos fármacos
3.
Circ Arrhythm Electrophysiol ; 2(2): 171-8, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19808462

RESUMO

BACKGROUND: Abnormal intercellular communication caused by connexin dysfunction may contribute to atrial fibrillation (AF). The present study assessed the effect of the gap junction conduction-enhancing antiarrhythmic peptide GAP-134 on AF inducibility and maintenance in a dog model of atrial cardiomyopathy. METHODS AND RESULTS: Twenty-four dogs subject to simultaneous atrioventricular pacing (220 bpm for 14 days) were randomly assigned to placebo treatment (PACED-CTRL; 12 dogs) or oral GAP-134 (2.9 mg/kg BID; PACED-GAP-134; 12 dogs) starting on day 0. UNPACED-CTRL (4 dogs) and UNPACED-GAP-134 (4 dogs) served as additional control groups. Change in left atrial (LA) systolic area from baseline to 14 days was calculated using transoesophageal echocardiography. At 14 days, animals underwent an open-chest electrophysiological study. PACED-CTRL dogs (versus UNPACED-CTRL) had a shorter estimated LA wavelength (8.0+/-1.4 versus 24.4+/-2.5 cm, P<0.05) and a greater AF vulnerability (mean AF duration, 1588+/-329 versus 25+/-34 seconds, P<0.05). Oral GAP-134 had no effect on AF vulnerability in UNPACED dogs. Compared with PACED-CTRL dogs, PACED-GAP-134 dogs had a longer estimated LA wavelength (10.2+/-2.8 versus 8.0+/-1.4 cm, respectively, P<0.05). Oral GAP-134 did not significantly reduce AF inducibility or maintenance in the entire group of 24 PACED dogs; in a subgroup of dogs (n=11) with less than 100% increase in LA systolic area, oral GAP-134 reduced AF induction from 100% to 40% and mean AF duration from 1737+/-120 to 615+/-280 seconds (P<0.05). CONCLUSIONS: Oral GAP-134 reduces pacing-induced decrease in LA wavelength and appears to attenuate AF vulnerability in dogs with less atrial mechanical remodeling. Gap junction modulation may affect AF in some circumstances.


Assuntos
Antiarrítmicos/farmacologia , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/fisiopatologia , Benzamidas/farmacologia , Junções Comunicantes/fisiologia , Prolina/análogos & derivados , Administração Oral , Animais , Estimulação Cardíaca Artificial , Conexina 43/metabolismo , Modelos Animais de Doenças , Cães , Fibrose , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/metabolismo , Sistema de Condução Cardíaco/patologia , Imuno-Histoquímica , Prolina/farmacologia , Período Refratário Eletrofisiológico/efeitos dos fármacos
4.
J Cardiovasc Electrophysiol ; 20(2): 176-81, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18775049

RESUMO

AIMS: Patients with reentrant supraventricular tachycardia (SVT) are often highly symptomatic and the mechanism of symptoms is not well understood. We hypothesized that variation in ventriculoatrial interval (QRS to P) modulates the left atrial pressure and symptoms during tachycardia. METHODS AND RESULTS: Three hundred twenty-six patients awaiting electrophysiological study completed a questionnaire regarding "neck pounding" or "shirt flapping" during tachycardia. Mean left atrial pressure was measured during simulated atrioventricular reentry tachycardia (AVRT) and atrioventricular nodal reentry tachycardia (AVNRT) in 18 patients. Pulmonary venous flow reversal was assessed using transesophageal echocardiography in 12 dogs when pacing at 220 bpm with different VA delays (0 to 250 ms). "Shirt flapping" is present more often during AVNRT than during AVRT (58.6% vs 43.8%, respectively, P < 0.05). Simulated AVNRT is associated with higher left atrial pressure compared with AVRT (19.4 +/- 4.8 mmHg vs 13.7 +/- 3.9 mmHg, respectively, P < 0.05). In dogs, pulmonary venous flow reversal during atrial systole was observed with significantly decreasing amplitude as VA delays increased: 668 +/- 167% at 0 ms; 492 +/- 138% at 100 ms; 278 +/- 148% at 180/ms; and 134 +/- 91% at 220 ms. CONCLUSION: "Shirt flapping" and "neck pounding" frequently occur during AVNRT. LA contractions during AV valve closure increase left atrial pressure and may explain differences in certain symptoms between AVNRT and AVRT.


Assuntos
Coração/fisiopatologia , Hemodinâmica/fisiologia , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Animais , Pressão Sanguínea/fisiologia , Ablação por Cateter , Cães , Ecocardiografia Transesofagiana , Estimulação Elétrica , Átrios do Coração , Ventrículos do Coração , Humanos , Fluxometria por Laser-Doppler , Circulação Pulmonar/fisiologia , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/fisiopatologia , Inquéritos e Questionários
5.
Am J Physiol Heart Circ Physiol ; 294(3): H1206-15, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18178723

RESUMO

Rapid ventricular pacing (RVP) is a well-established animal model of atrial fibrillation (AF). However, this model is limited by a high mortality rate and severe heart failure. The purpose of our study was to assess a new canine model of inducible AF. We performed acute, short-term, simultaneous atrioventricular pacing (SAVP) and RVP (in random order) in 14 dogs for 30 s. SAVP produced more echocardiographic pulmonary venous flow reversal, a greater increase in mean pulmonary capillary wedge pressure, and a significantly greater decrease in left atrial emptying function (-84.4 +/- 38.6% vs. -23.7 +/- 27.1%, P < 0.05) than RVP. Thirty dogs were randomized to three, longer-term, study groups: eight dogs in the control group (no pacing), eight dogs in the RVP group (2 wk at 240 beats/min followed by 3 wk at 220 beats/min), and fourteen dogs in the SAVP group (2 wk at 220 beats/min). SAVP induced less left ventricular dysfunction but more left atrial dysfunction than RVP. SAVP dogs had similar atrial effective refractory periods as RVP dogs but more heterogeneity in conduction and more AF inducibility (83% vs. 40%, P < 0.05) and maintenance (median 1,660 vs. 710 s, P < 0.05) than RVP dogs. SAVP induced more collagen turnover and was associated with a significantly greater increase in type III collagen in the atria compared with RVP dogs (6.9 +/- 1.5 vs. 4.8 +/- 1.6, respectively, P < 0.05 vs. 1.1 +/- 0.7 in unpaced control dogs). In conclusion, the SAVP model induced profound mechanical and substrate atrial remodeling and reproducible sustained AF. This new model is clinically relevant and may be useful for testing AF interventions.


Assuntos
Fibrilação Atrial/fisiopatologia , Estimulação Cardíaca Artificial , Animais , Pressão Sanguínea/fisiologia , Cardiomiopatia Dilatada/fisiopatologia , Colágeno/biossíntese , Colágeno/genética , Cães , Ecocardiografia Doppler , Ecocardiografia Transesofagiana , Eletrocardiografia , Eletrofisiologia , Gelatinases/biossíntese , Gelatinases/genética , Frequência Cardíaca/fisiologia , Metaloproteinase 9 da Matriz/metabolismo , Marca-Passo Artificial , Pressão Propulsora Pulmonar/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Período Refratário Eletrofisiológico/fisiologia , Fator de Crescimento Transformador beta1/biossíntese , Fator de Crescimento Transformador beta1/genética , Remodelação Ventricular/fisiologia
6.
J Cardiovasc Electrophysiol ; 18(7): 750-6, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17578345

RESUMO

INTRODUCTION: The slow delayed rectifier K+ current (I(Ks)) contributes little to ventricular repolarization at rest. It is unclear whether I(Ks) plays a role during ventricular fibrillation (VF) or ventricular repolarization at rapid rates during beta-adrenergic stimulation. METHODS AND RESULTS: In an in vivo rabbit model, we evaluated the effects of HMR 1556 (1 mg Kg(-1) + 1 mg kg(-1) hr(-1) i.v.), a selective I(Ks) blocker, on monophasic action potential duration at 90% repolarization (MAPD90), ventricular effective refractory period (VERP), and defibrillation threshold (DFT). In perfused rabbit hearts, the effects of HMR 1556 (10 and 100 nM) in the presence of isoproterenol (5 nM) on MAPD90 and VERP were studied at cycle lengths (CLs) 200-500 msec. In vivo, HMR 1556 prolonged MAPD90 by 6 +/- 1 msec at CL 200 msec (P < 0.01, n = 6), lowered DFT from 558 +/- 46 V to 417 +/- 31 V (P < 0.01), and decreased the coefficient of variation in the VF inter-beat deflection intervals from 8.9 +/- 0.6% to 6.5 +/- 0.4% (P < 0.05) compared with control. In perfused rabbit hearts, isoproterenol shortened MAPD90 by 5 +/- 1 msec at CL 200 msec and 11 +/- 4 msec at CL 500 msec (P < 0.05, n = 7). This shortening was reversed by HMR 1556 (P < 0.05), and both effects were rate-independent. CONCLUSION: I(Ks) block increases VF temporal organization and lowers DFT, and I(Ks) that is activated following beta-adrenergic stimulation contributes to ventricular repolarization without rate dependence.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Cromanos/farmacologia , Canais de Potássio de Retificação Tardia/antagonistas & inibidores , Cardioversão Elétrica/métodos , Isoproterenol/farmacologia , Sulfonamidas/farmacologia , Potenciais de Ação/fisiologia , Animais , Cromanos/uso terapêutico , Canais de Potássio de Retificação Tardia/fisiologia , Técnicas In Vitro , Masculino , Coelhos , Sulfonamidas/uso terapêutico , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/fisiopatologia
7.
J Cardiovasc Pharmacol Ther ; 12(1): 69-77, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17495260

RESUMO

The gap junction modifier Rotigaptide (ZP123), which promotes cellular coupling, was hypothesized to decrease defibrillation thresholds during prolonged ventricular fibrillation (VF). Thirty-two New Zealand white rabbits were randomized to receive saline (control, n = 16) or Rotigaptide (n = 16). Following 4 min of untreated VF, biphasic defibrillation shocks were applied through chest wall patches, starting either at 300 volts (V) (n = 16) or 500 V (n = 16), with 200 V increasing steps to 900 V in case of shock failure. Rotigaptide significantly decreased defibrillation voltage requirements (average cumulative voltage of all shocks: 1206 +/- 709 V in control group vs. 844 +/- 546 V in treated group, P = .002). Rotigaptide had no effect on heart rate, QRS duration, QT interval, ventricular effective refractory period, monophasic action potential duration or on connexin 43 density using immunofluorescence. Rotigaptide improves the ability to defibrillate after untreated VF.


Assuntos
Junções Comunicantes/efeitos dos fármacos , Parada Cardíaca/terapia , Oligopeptídeos/uso terapêutico , Fibrilação Ventricular/terapia , Potenciais de Ação/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Conexina 43/metabolismo , Modelos Animais de Doenças , Cardioversão Elétrica/métodos , Estimulação Elétrica/métodos , Eletrocardiografia , Imunofluorescência/métodos , Junções Comunicantes/fisiologia , Parada Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Injeções Intravenosas , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/metabolismo , Oligopeptídeos/administração & dosagem , Oligopeptídeos/sangue , Coelhos , Distribuição Aleatória , Ressuscitação/métodos , Fibrilação Ventricular/fisiopatologia
8.
Br J Pharmacol ; 148(3): 255-63, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16565733

RESUMO

1. The rate-dependent contributions of the rapid and slow components of the cardiac delayed rectifier K+ current (IKr and IKs, respectively) to repolarization are not fully understood. It is unclear whether the addition of IKs block will attenuate reverse rate-dependence seen after IKr block. 2. The individual and combined electrophysiological effects of selective IKr and IKs blockers, dofetilide and HMR 1556, respectively, were evaluated using Langendorff-perfused rabbit hearts. Monophasic action potential duration at 90% repolarization (MAPD90) and ventricular effective refractory period (VERP) were determined at cycle lengths (CLs) of 200-500 ms (at 50 ms intervals). 3. Dofetilide (1-100 nM) prolonged MAPD90 in a concentration-dependent manner (P < 0.001, n = 6) with reverse rate-dependence (P < 0.0001). In contrast, HMR 1556 (10-240 nM) alone did not prolong MAPD90. However, in the presence of 7.5 nM dofetilide, HMR 1556 (100 nM) increased the extent of reverse rate-dependence by further prolonging MAPD90 at CLs of 400, 450 and 500 ms (P < 0.05, n = 9) and, to a lesser extent, at shorter CLs (e.g. by 17 +/- 4 ms at CL 500 vs 2 +/- 3 ms at CL 200 ms). 4. Effects of dofetilide and HMR 1556 on VERP were similar to those on MAPD90. The slope of the VERP vs CL relation was steeper after the combination (0.081 +/- 0.013) than after dofetilide alone (0.028 +/- 0.018, P < 0.01, n = 9). 5. Blockade of rabbit IKs increased reverse rate-dependence of IKr block.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Cromanos/farmacologia , Canais de Potássio de Retificação Tardia/antagonistas & inibidores , Canais de Potássio de Retificação Tardia/fisiologia , Fenetilaminas/farmacologia , Sulfonamidas/farmacologia , Função Ventricular , Animais , Eletrofisiologia , Técnicas In Vitro , Cinética , Bloqueadores dos Canais de Potássio/farmacologia , Coelhos
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