Factor XIII Val34Leu is a genetic factor involved in the aetiology of venous thrombosis

A mutation in the factor XIII gene (FXIII Val34Leu) gene was recently reported to confer protection against myocardial infarction, but its relationship with venous thrombosis is unknown. In addition, a mutation in the 5'-untranslated region of the FXII gene (46 C→T) was identified which is associated with low plasma levels of the protein. Its prevalence in patients with venous thrombosis is also unknown. We investigated the frequency of the FXIII Val34Leu and FXII 46 C→T mutations in 189 patients with deep venous thrombosis and in 187 age-, gender- and race-matched controls. FXIII Val34Leu was detected in 38.6% of the patients and in 41.2% of the controls. Interestingly, homozygosity for the FXIII mutation was found in 1.6% of the patients and in 9.6% of the controls. yielding an odds ratio (OR) for venous thrombosis of 0.16 (95% CI: 0.05-0.5). The OR for heterozygotes was 1.1 (95% CI: 0.7-1.7). The FXII 46 C→T mutation was detected in 46.0% of the patients and in 48.6% of the controls. The OR for heterozygotes was 0.9 (95% CI: 0.6-1.4) and for homozygotes the OR was 0.8 (95% CI: 0.3-1.9). Our data indicate that the FXII 46 C→T mutation is unlikely to be a major risk factor for venous thrombotic disease. In contrast, the homozygous state for FXIII Val34Leu is a strong protective factor against venous thrombosis, which emerges as a novel generic factor involved in the aetiology of thrombophilia.

Acao antioxidante de extratos de alecrim (Rosmarinus officinalis L.) em files de peixes da especie pacu (Piaractus mesopotamicus Holmberg)

The antioxidant effect of plant extract has been an interesting issue for many researchers in past few years. Spices have been identified as products with large amounts of antioxidants, and rosemary is one the most studied spice. Studies have shown evidences that population with high intake of these substances have less incidence of coronary heart disease. The objective of this work was verify the antioxidant action of the commercial rosemary oleoresin Herbalox® (used to feed the pacu (Piaractus mesopotamicus) fish. The juveniles pacu were fed with isocaloric and isoproteic diets, for two groups the lipid source was soybean oil and for the another it was corn oil. For each group of the different lipid sources, rosemary extract Herbalox® (were added in one lot and on the other which was used as control. The results showed that the addition of rosemary extracts to the ration protected them against peroxidation, when compared with the control, the lipid source also have influence on these protection.

β-carotene attenuates the paradoxical effect of tobacco smoke on the mortality of rats after experimental myocardial infarction

The objective of this study was to investigate the effects of exposure to tobacco smoke (ETS) in rats that were or were not supplemented with dietary β-carotene (BC), on ventricular remodeling and survival after myocardial infarction (Ml). Rats (n = 189) were allocated to 4 groups: the control group, n = 45; group BC administered 500 mg/kg diet, n = 49, BC supplemented rats; group ETS, n - 55, rats exposed to tobacco smoke; and group BC+ETS, n = 40. Wistar rats weighing 10O g were administered one of the treatments until they weighed 200 to 250 g (∼5 wk). The ETS rats were exposed to cigarette smoke for 30 min 4 times/d, in a chamber connected to a smoking device. After reaching a weight of 200-250 g, rats were subjected to experimental MI (coronary artery occlusion) and mortality rates were determined over the next 105 d. In addition, echocardiographic, isolated heart, morphometrical, and biochemical studies were performed. Mortality data were tested using Kaplan-Meyer curves and other data by 2-way ANOVA. Survival rates were greater in the ETS group (58.2%) than in the control (33.3%) (P = 0.001) and BC+ETS rats (30.0%) (P = 0.007). The groups did not differ in the other comparisons. Left ventricular end-diastolic diameter normalized to body weight was greater and maximal systolic pressures were lower in the ETS groups than in non-ETS groups. Previous exposure to tobacco smoke induced a process of cardiac remodeling after MI. There is a paradoxical protector effect with tobacco smoke exposure, characterized by lower mortality, which is offset by BC supplementation. © 2005 American Society for Nutritional Sciences.

Anthracycline-induced cardiotoxicity

The anthracyclines constitute a group of drugs widely used for the treatment of a variety of human tumors. However, the development of irreversible cardiotoxicity has limited their use. Anthracycline-induced cardiotoxicity can persist for years with no clinical symptoms. However, its prognosis becomes poor after the development of overt heart failure, possibly even worse than ischemic or idiopathic dilated cardiomyopathies. Due to the successful action of anthracyclines as chemotherapic agents, several strategies have been tried to prevent/ attenuate their side effects. Although anthracycline-induced injury appears to be multifactorial, a common denominator among most of the proposed mechanisms is cellular damage mediated by reactive oxygen species. However, it remains controversial as to whether antioxidants can prevent such side effects given that different mechanisms may be involved in acute versus chronic toxicity. The present review applies a multisided approach to the critical evaluation of various hypotheses proposed over the last decade on the role of oxidative stress in cardiotoxicity induced by doxorubicin, the most used anthracycline agent. The clinical diagnosis and treatment is also discussed. © 2008 Bentham Science Publishers Ltd.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation. © 2012 Elsevier B.V.

Sevoflurano e dexmedetomidina em isquemia e reperfusão renais no rato

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

FUNCTIONAL AND ULTRASTRUCTURAL EVALUATION OF MYOCARDIAL PROTECTION PROVIDED BY INTERMITTENT CORONARY SINUS PERFUSION IN THE ISOLATED DOG HEART

1. The protection offered by intermittent perfusion of of cardioplegic solution through the coronary sinus was investigated in isovolumic blood-perfused dog heart preparations submitted to 60 min of ischemia and 45 min of reperfusion.2. The preparations were divided into three treatment groups: a) coronary sinus, consisting of preparations (N = 10) perfused through the coronary sinus under 40 cm water pressure; b) aortic, consisting of preparations (N = 10) perfused through the aortic stump under 100 mmHg pressure; c) control, consisting of hearts (N = 9) that were not perfused with cardioplegic solution.3. Properties of contractile capacity and relaxation were markedly impaired in the control group but were preserved to a comparable extent in the groups perfused with cardioplegic solution through the aorta and coronary sinus. Developed pressure decreased in the control group (before ischemia: 70 +/- 5.5 mmHg; after reperfusion: 35 +/- 12 mmHg; P < 0.05) and didn't vary in the aortic group (from 69 +/- 4 mmHg to 65 +/- 13 mmHg; P > 0.05) and coronary sinus group (from 69 +/- 4.6 mmHg to 60 +/- 10 mmHg; P > 0.05). Myocardial relaxation was evaluated by the +/- dp/dt ratio. In the control group there was impairment of myocardial relaxation as indicated by an increase of this index after reperfusion (from 1.05 +/- 0.05 to 1.46 +/- 0.23; P < 0.05), whereas in the aortic (from 1.10 +/- 0.13 to 1.15 +/- 0.20; P > 0.05) and the coronary sinus (from 1.03 +/- 0.14 to 1.08 +/- 0.16; P > 0.05) groups there was no variation. Ultrastructural changes in the myocardium were negligible in all three groups at the end of reperfusion.4. We conclude that intermittent perfusion of a hypothermic cardioplegic solution through the coronary sinus is effective for the protection of the myocardium during total ischemia.

Formyl-peptide receptor is not involved in the protection afforded by annexin 1 in murine acute myocardial infarct

Recent interest in the annexin 1 field has come from the notion that specific G-protein-coupled receptors, members of the formyl-peptide receptor (FPR) family, appear to mediate the anti-inflammatory actions of this endogenous mediator. Administration of the annexin 1 N-terminal derived peptide Ac2-26 to mice after 25 min ischemia significantly attenuated the extent of acute myocardial injury as assessed 60 min postreperfusion. Evident at the dose of 1 mg/kg (similar to9 nmol per animal), peptide Ac2-26 cardioprotection was intact in FPR null mice. Similarly, peptide Ac2-26 inhibition of specific markers of heart injury (specifically myeloperoxidase activity, CXC chemokine KC contents, and endogenous annexin 1 protein expression) was virtually identical in heart samples collected from wild-type and FPR null mice. Mouse myocardium expressed the mRNA for FPR and the structurally related lipoxin A(4) receptor, termed ALX; thus, comparable equimolar doses of two ALX agonists (W peptide and a stable lipoxin A4 analog) exerted cardioprotection in wild-type and FPR null mice to an equal extent. Curiously, marked (>95%) blood neutropenia produced by an anti-mouse neutrophil serum did not modify the extent of acute heart injury, whereas it prevented the protection afforded by peptide Ac2-26. Thus, this study sheds light on the receptor mechanism(s) mediating annexin 1-induced cardioprotection and shows a pivotal role for ALX and circulating neutrophil, whereas it excludes any functional involvement of mouse FPR. These mechanistic data can help in developing novel therapeutics for acute cardioprotection.

Myocardial protection by continuous, blood, antegrade-retrograde cardioplegia in rabbits

OBJETIVO: Estudar a eficácia e a segurança da cardioplegia sanguínea, aterógrada-retrógrada contínua, por meio da avaliação da função ventricular. MÉTODOS: Os coelhos foram divididos em quatro grupos: Controle-C(n=10); isquêmico e cardioplegia cristaloide-IC(n=10; isquêmico e cardioplegia sanguínea-IB(n=10; isquêmico sem cardioplegia-INC(n=10. Após o período isquêmico do protocolo a função ventricular foi analisada pela técnica do balão intra-ventricular. RESULTADOS: a pressão desenvolvida intra-ventricular (IVDP) foi: C(92,90± 6,86mmHg); IC(77,78± 6,15mmHg); IB(93,64 ±5,09mmHg); INC(39,46 ±8,91mmHg) p<0,005. a primeira derivada temporal da pressão ventricular na sua deflexão positiva: C(1137,50± 92,23mmHg/sec); IC(1130,62 ±43,78mmHg/sec); IB(1187,58± 88,38mmHg/sec); INC(620,02± 43,80mmHg/se) p<0,005. A primeira derivada da pressão ventricular na sua deflexão negativa: C(770,00± 73,41mmHg/sec); IC(610,03 ±47,43mmg/sec); IB(762,53 ±46,02mmHg/sec); INC(412,35 ±84,36mmHg/sec) p<0,005. A relação do coeficiente angular logarítmico foi: C(0,108± 0,02); IC(0,159± 0,038); IB(0,114 ±0,016); INC(0,175± 0,038) p<0,05. CONCLUSÃO: No modelo experimental estudado o grupo isquêmico protegido pela cardioplegia sanguínea apresentou melhor função ventricular que os grupos protegidos por cardioplegia cristalóide e não protegido.