RESUMO
OBJECTIVE: To evaluate the hemodynamic and metabolic effects of terlipressin and naloxone in cardiac arrest. METHODS: Cardiac arrest in rats was induced by asphyxia and maintained for 3.5 minutes. Animals were then resuscitated and randomized into one of six groups: placebo (n = 7), epinephrine (0.02 mg/kg; n = 7), naloxone (1 mg/kg; n = 7) or terlipressin, of which three different doses were tested: 50 µg/kg (TP50; n = 7), 100 µg/kg (TP100; n = 7) and 150 µg/kg (TP150; n = 7). Hemodynamic variables were measured at baseline and at 10 (T10), 20 (T20), 30 (T30), 45 (T45) and 60 (T60) minutes after cardiac arrest. Arterial blood samples were collected at T10, T30 and T60. RESULTS: The mean arterial pressure values in the TP50 group were higher than those in the epinephrine group at T10 (165 vs. 112 mmHg), T20 (160 vs. 82 mmHg), T30 (143 vs. 66 mmHg), T45 (119 vs. 67 mmHg) and T60 (96 vs. 66.8 mmHg). The blood lactate level was lower in the naloxone group than in the epinephrine group at T10 (5.15 vs. 10.5 mmol/L), T30 (2.57 vs. 5.24 mmol/L) and T60 (2.1 vs. 4.1 mmol/L). CONCLUSIONS: In this rat model of asphyxia-induced cardiac arrest, terlipressin and naloxone were effective vasopressors in cardiopulmonary resuscitation and presented better metabolic profiles than epinephrine. Terlipressin provided better hemodynamic stability than epinephrine.
Assuntos
Epinefrina/farmacologia , Parada Cardíaca/tratamento farmacológico , Lipressina/análogos & derivados , Modelos Animais , Naloxona/farmacologia , Vasoconstritores/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Asfixia/complicações , Reanimação Cardiopulmonar , Epinefrina/metabolismo , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Lipressina/metabolismo , Lipressina/farmacologia , Masculino , Naloxona/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Terlipressina , Fatores de Tempo , Vasoconstritores/metabolismoRESUMO
OBJECTIVE: To evaluate the hemodynamic and metabolic effects of terlipressin and naloxone in cardiac arrest. METHODS: Cardiac arrest in rats was induced by asphyxia and maintained for 3.5 minutes. Animals were then resuscitated and randomized into one of six groups: placebo (n = 7), epinephrine (0.02 mg/kg; n = 7), naloxone (1 mg/kg; n = 7) or terlipressin, of which three different doses were tested: 50 µg/kg (TP50; n = 7), 100 µg/kg (TP100; n = 7) and 150 µg/kg (TP150; n = 7). Hemodynamic variables were measured at baseline and at 10 (T10), 20 (T20), 30 (T30), 45 (T45) and 60 (T60) minutes after cardiac arrest. Arterial blood samples were collected at T10, T30 and T60. RESULTS: The mean arterial pressure values in the TP50 group were higher than those in the epinephrine group at T10 (165 vs. 112 mmHg), T20 (160 vs. 82 mmHg), T30 (143 vs. 66 mmHg), T45 (119 vs. 67 mmHg) and T60 (96 vs. 66.8 mmHg). The blood lactate level was lower in the naloxone group than in the epinephrine group at T10 (5.15 vs. 10.5 mmol/L), T30 (2.57 vs. 5.24 mmol/L) and T60 (2.1 vs. 4.1 mmol/L). CONCLUSIONS: In this rat model of asphyxia-induced cardiac arrest, terlipressin and naloxone were effective vasopressors in cardiopulmonary resuscitation and presented better metabolic profiles than epinephrine. Terlipressin provided better hemodynamic stability than epinephrine. .
Assuntos
Animais , Masculino , Ratos , Epinefrina/farmacologia , Parada Cardíaca/tratamento farmacológico , Lipressina/análogos & derivados , Modelos Animais , Naloxona/farmacologia , Vasoconstritores/farmacologia , Pressão Arterial/efeitos dos fármacos , Asfixia/complicações , Reanimação Cardiopulmonar , Epinefrina/metabolismo , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Lipressina/metabolismo , Lipressina/farmacologia , Naloxona/metabolismo , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Vasoconstritores/metabolismoAssuntos
Doença da Artéria Coronariana/tratamento farmacológico , Células Endoteliais , Mediadores da Inflamação/sangue , Ativação Plaquetária/fisiologia , Células-Tronco , Idoso , Aspirina/uso terapêutico , Biomarcadores , Proteína C-Reativa/análise , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Testes de Função Plaquetária , Estatísticas não Paramétricas , Fatores de TempoAssuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/tratamento farmacológico , Células Endoteliais , Mediadores da Inflamação/sangue , Ativação Plaquetária/fisiologia , Células-Tronco , Aspirina/uso terapêutico , Biomarcadores , Proteína C-Reativa/análise , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Testes de Função Plaquetária , Inibidores da Agregação Plaquetária/uso terapêutico , Estatísticas não Paramétricas , Fatores de TempoRESUMO
BACKGROUND: In the setting of stable coronary artery disease (CAD), it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone. OBJECTIVE: We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10mg/simvastatin 20mg (E10/S20) with simvastatin 80 mg (S80). METHODS AND RESULTS: CAD patients (n=83, 63 ± 9 years, 57% men) receiving S20, were randomly allocated to receive E10/S20 or S80, for 6 weeks. Lipids, inflammatory markers (C-reactive protein, interleukin-6, monocyte chemoattractant protein-1, soluble CD40 ligand and oxidized LDL), and platelet aggregation (platelet function analyzer [PFA]-100) changes were determined. Baseline lipids, inflammatory markers and PFA-100 were similar between groups. After treatment, E10/S20 and S80 patients presented, respectively: (1) similar reduction in LDL-C (29 ± 13% vs. 28 ± 30%, p=0.46), apo-B (18 ± 17% vs. 22 ± 15%, p=0.22) and oxidized LDL (15 ± 33% vs. 18 ± 47%, p=0.30); (2) no changes in inflammatory markers; and, (3) a higher increase of the PFA-100 with E10/S20 than with S80 (27 ± 43% vs. 8 ± 33%, p=0.02). CONCLUSIONS: These data suggest that among stable CAD patients treated with S20, (1) both E10/S20 and S80 were equally effective in further reducing LDL-C; (2) neither treatment had any further significant anti-inflammatory effects; and (3) E10/S20 was more effective than S80 in inhibiting platelet aggregation. Thus, despite similar lipid lowering and doses 4× less of simvastatin, E10/S20 induced a greater platelet inhibitory effect than S80.