RESUMO
The antiarrhythmic effects of 100; 150; and 300microg/kg i.p. oxygen/ozone mixture were tested on arrhythmias induced by i) ischemia; ii) ischemia/reperfusion; iii) aconitine (15microg/kg/i.v.); potassium chloride (1.5% i.v.) in rats. 25min of cardiac left descending coronary artery ischemia caused severe incidence of ventricular tachycardia, ventricular fibrillation and mortality. These were significantly reduced by pre-treatment of rats with oxygen/ozone mixture at doses of 150 and 300microg/kg. In separate experiments using a protocol of 5min ischemia followed by 8min reperfusion this caused arrhythmias starting within 6+/-1s. The incidence of ventricular tachycardia was 100%, while ventricular fibrillation occurred in 75% of the animals and lasted 85+/-14s. The mortality was 62.5%. These figures were significantly (P<0.01) reduced in animals treated with 150microg/kg oxygen/ozone and a substantial increase observed with 300microg/kg, whilst not affected by the lower dose of 100microg/kg. 150 and 300microg/kg oxygen/ozone prolonged the onset time for the appearance of arrhythmias induced by aconitine (300microg/kg oxygen/ozone, approximately 81% longer). Oxygen/ozone also reduced the ventricular tachycardia duration, ventricular fibrillation incidence, arrhythmia score, and increased the rat's survival rate. As for example, this latter was increased from 25% (aconitine) to 50% (aconitine+oxygen/ozone 150microg/kg). 100microg/kg oxygen/ozone was without effect. None of the oxygen/ozone doses affected the arrhythmias caused by potassium chloride 1.5% i.v. All the oxygen/ozone antiarrhythmic effects were similar to those observed with lidocaine (1.5mg/kg i.v.). In conclusion, oxygen/ozone has antiarrhythmic effects against arrhythmias caused by aconitine, myocardial ischemia and ischemia/reperfusion.
Assuntos
Antiarrítmicos/administração & dosagem , Antiarrítmicos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Oxigênio/administração & dosagem , Oxigênio/farmacologia , Ozônio/administração & dosagem , Ozônio/farmacologia , Aconitina/toxicidade , Animais , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/etiologia , Masculino , Isquemia Miocárdica/complicações , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Oxigênio/uso terapêutico , Ozônio/uso terapêutico , Cloreto de Potássio/toxicidade , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologiaRESUMO
BACKGROUND/AIMS: Inflammatory mediators contribute to the impairment of vasculogenesis by reducing endothelial progenitor cells (EPCs) mobilization in atherosclerotic vasculopathy. We tested the hypothesis that administration of an oxygen/ozone mixture (IMT) might counteract this pathophysiological mechanism and enhance limb tissue perfusion in patients with critical limb ischemia (CLI). METHODS: Randomized patients with rest pain or ischemic ulcers and transcutaneous oxygen tension (TcPO(2)) <40 mmHg and/or toe pressure <50 mmHg received placebo (n=74) or a non-specific immunomodulation therapy (IMT) (n=77), autologous blood exposed to oxygen/ozone gas mixture by intragluteal injection, on day 1, 2, 7, and once a week thereafter for at least 22 weeks. Patients were evaluated for changes in TcPO(2), levels of circulating EPCs (CD34/KDR-positive cells) and inflammation (tumor necrosis factor-alpha-TNF-alpha). RESULTS: TcPO(2) and CD34/CD133-positive cells increased at 22 weeks in IMT group (P<0.01) whereas no changes were observed in placebo group. TNF-alpha levels decreased at 6 months in IMT group (P<0.001) whereas no changes were observed in placebo group. There was a strong positive correlation between CD34/KDR-positive cells and TcPO(2) (r=0.56, P<0.01). Moreover, there was an inverse correlation between CD34/KDR-positive cells and TNF-alpha (r=-0.51, P<0.01). CONCLUSIONS: Intramuscular injection of IMT may improve wound healing and limb salvage in patients with CLI.
Assuntos
Extremidades/patologia , Imunomodulação , Isquemia/patologia , Isquemia/terapia , Oxigênio/química , Úlcera/patologia , Adulto , Antígenos CD34/biossíntese , Células Endoteliais , Extremidades/irrigação sanguínea , Células-Tronco Hematopoéticas/citologia , Hemodinâmica , Humanos , Inflamação , Pessoa de Meia-Idade , Ozônio , Placebos , Fator de Necrose Tumoral alfa/metabolismo , Úlcera/terapia , CicatrizaçãoAssuntos
Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias/prevenção & controle , Proteína C/uso terapêutico , Anticoagulantes/metabolismo , Anticoagulantes/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ativação Enzimática/fisiologia , Humanos , Complicações Pós-Operatórias/enzimologia , Complicações Pós-Operatórias/etiologia , Proteína C/metabolismoRESUMO
The neuropathic pain model consisting of the spared nerve injury of the sciatic nerve was used in the mouse to examine whether peripheral neuropathy is capable of generating over-expression of pro-inflammatory and pro-apoptotic genes in the orbito-frontal cortex, together with allodynia and hyperalgesia. RT-PCR analysis showed increased expression of caspase-1, caspase-12 and caspase-8 genes in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve. Conversely, the expression of caspase-3 was decreased by spared nerve injury of the sciatic nerve in the same brain area. A single subcutaneous injection of ozone performed 12 h after the surgical procedure decreased mechanical allodynia and normalized the mRNA caspase-1, caspase-12 and caspase-8 gene levels, but did not the decrease caspase-3 level, 14 days post-spared nerve injury. Ozone also reduced IL-1beta staining in the orbito-frontal cortex in neuropathic mice. This study provides evidence that a single subcutaneous administration of ozone decreased neuropathic pain type behaviour, normalized the expression of pro-inflammatory caspases and reduced IL-1beta staining in the orbito-frontal cortex astrocytes in SNI mice. These preliminary data show that peripheral neuropathy induced over-expression of pro-inflammatory/pro-apoptotic caspases in the orbito-frontal cortex and that ozone, by mechanisms that are as yet unknown, can regulate the expression of the genes that play a pivotal role in the onset and maintenance of allodynia.