Novel porcine model of acute severe cardiogenic shock developed by upper-body hypoxia.

Despite the urgent need for experimental research in the field of acute heart failure and, particularly cardiogenic shock, currently there are only limited options in large animal models enabling research using devices applied to human subjects. The majority of available models are either associated with an unacceptably high rate of acute mortality or are incapable of developing sufficient severity of acute heart failure. The objective of our research was to develop a novel large animal model of acute severe cardiogenic shock. Advanced left ventricular dysfunction was induced by global myocardial hypoxia by perfusing the upper body (including coronary arteries) with deoxygenated venous blood. The model was tested in 12 pigs: cardiogenic shock with signs of tissue hypoxia developed in all animals with no acute mortality. Cardiac output decreased from a mean (+/- SD) of 6.61+/-1.14 l/min to 2.75+/-0.63 l/min, stroke volume from 79.7+/-9.8 ml to 25.3+/-7.8 ml and left ventricular ejection fraction from 61.2+/-4.3 % to 17.7+/-4.8 % (P

[Acute myocardial infarction in young patients--severe failures in the system of acute and secondary care]. / Akutní infarkt myokardu u mladých nemocných - závazné nedostatky v systému akutní a následné péce.

INTRODUCTION: The incidence of cardiovascular (CV) diseases and acute myocardial infarction (AMI) in Czech Republic is de-clining. In spite of this in a proportion of patients AMI occurs in young age. The aim of our project was to assess the character of risk factors, precipitating diseases and the quality of care in young AMI survivors. METHODS: We included 132 patients (97 men and 35 women) in whom AIM with ST elevations occurred before age of 45 years in men and age of 50 years in women. Several results were compared to a control group composed of 84 healthy volunteers of comparable age. We assessed the course of the disease, extent of coronary involvement, subsequent therapy and control of risk factors after 3 years from the index event. RESULTS: Smoking represented the main risk factor - 85% patents were active smokers at the time of AMI and 9% were former smokers, 64% patients had a positive family history of CV disease. We found a higher prevalence of dyslipidemia history in men. In spite of high rate of statin use, laboratory examination during follow-up revealed higher triglyceride values and low levels of HDL-cholesterol in both genders. All together 23% of patients had a history of provoking underlying disease or precipitating factors (inflammatory diseases, malignancies, combined thrombophilias, drug abuse). In total 95% of patients underwent coronary angiography during the acute phase of AMI, the median time from pain onset to intervention was 9 hours. Most patients had single vessel disease, 14% had even coronary angiogram without clinically significant stenosis. The subsequent care was satisfactory concerning the rate of drug prescriptions. However, target lipid values were not reached in 78% patients and blood pressure targets in 37%. CONCLUSIONS: In patients who suffered AMI in young age, risk factors are dominated by smoking and positive family history of CV diseases. One fifth of patients suffer from other underlying disease (inflammatory disease, malignancies, combined thrombophilia) or have another precipitating factor (febrile disease, drug abuse). The acute care seems unsatisfactory due to late arrival of most patients to catheterization laboratories (underestimation of the disease, incorrect initial diagnosis). Subsequent therapy is well composed but lacks in intensity.

Nitrotyrosine and nitrate/nitrite levels in cardiac arrest survivors treated with endovascular hypothermia.

The protective effect of therapeutic hypothermia in cardiac arrest survivors (CAS) has been previously well documented. Animal studies have indicated that attenuation of tissue oxidative stress (OS) may be involved in the mechanisms that lead to the beneficial effect of hypothermia. The extent of OS and nitric oxide (NO) production in adult CAS treated with endovascular hypothermia is, however, unknown. A total of 11 adult patients who experienced cardiac arrest out of hospital were included in the present study, and all were treated with mild hypothermia using the Thermogard XP (Alsius, USA) endovascular system. A target core temperature of 33 °C was maintained for 24 hours, with a subsequent rewarming rate of 0.15 °C per hour, followed by normothermia at 36.8 °C. Blood samples for the measurement of nitrotyrosine and nitrate/nitrite levels were drawn at admission and every 6 hours thereafter for two days. During the hypothermic period, the levels of nitrotyrosine and nitrates/nitrites were comparable with baseline values. During the rewarming period, serum levels of both parameters gradually increased and, during the normothermic period, the levels were significantly higher compared with hypothermic levels (nitrotyrosine, P<0.001; nitrates/nitrites, P<0.05). In our study, significantly lower levels of nitrotyrosine and nitrates/nitrites were demonstrated during hypothermia compared with levels during the normothermic period in adult CAS. These data suggest that attenuation of OS and NO production may be involved in the protective effect of hypothermia in adult CAS.

Critical evaluation of the optimal medical therapy in the cardiac resynchronization therapy candidates--single centre experience.

UNLABELLED: The aim of the present study was to evaluate the optimal medical therapy in the chronic heart failure (CHF) patients referred from the comunity centres and the outpatients cardiology clinics for the cardiac resynchronization therapy with defibrilator (CRTD) to the Department of Cardiology, Na Homolce Hospital with the device implantation between 1st January 2008 and 30st September 2009. METHODS: The optimal medical therapy was analysed retrospectively from the medical records of 179 consecutive CHF patients NYHA class III-IV. Beta-blockers (BB) were used only in 81% subjects referred for CRTD, ACE inhibitors (ACEI) were used only in 68% patients Angiotensin receptor blockers (ARB) were used in 18% subjects. ACEI or ARB were used in 81%, spironolacton was use in 59%. Recommended target DD for BB (carvedilol 25 mg bid) was used only in 13% subjects, recommended target DD for ACEI (enalapril 10 mg bid) was used only in 9.4% patients. RESULTS: In the Department of Cardiology, the optimal medical therapy was changed after CRTD, BB were used in 95% subjects at discharge (p < 0.01) and the number of patients reaching at least of 50% of recommended daily dose (DD) of BB increased (p < 0.05). ACEI were recommended after CRTD in 80% subjects after implantation (p < 0.05), the number of patients reaching at least of 50% of recommended DD for ACEIs increased too (p < 0.05). There was no significant difference in ARB use recomended in the hospital (19% after CRTD - NS). ACEI or ARB were used in 98% patients after the device implanted (p < 0.05) and spironolacton in 77% after CRTD (p < 0.05). CONCLUSIONS: Despite optimal composition of the optimal medical heart failure therapy only small number of CRTD candidates are reaching recommended drug dose. The optimization of the medical therapy in the specialized center lead to significantly higher proportion of CHF using the optimal therapy with the increased dose of BB and ACEI.

The influence of oxygen toxicity on yeast mother cell-specific aging.

The effect of deleting both catalase genes and of increased oxygen as well as paraquat (a pro-oxidant) on the replicative life span of yeast mother cells has been investigated to test the so-called oxygen theory of aging. This is well established in higher organisms, but has not been extensively tested in the unicellular yeast model system. Life span determinations were performed in ambient air or in a controlled atmosphere (55% oxygen) and an isogenic series of strains deleted for one or both yeast catalases was used and compared with wild type. In the absence of cellular catalase, increased oxygen caused a marked decrease in life span that could be completely reversed by adding 1 mM GSH, a physiological antioxidant, to the yeast growth medium. In a second unrelated strain, the effects were similar although even the wild type showed a decrease in life span when oxygen was increased. The effect could again be compensated by addition of extracellular GSH. Our results show that manipulating the detoxification of reactive oxygen species has a profound effect on yeast aging. These findings are discussed in the light of recent results relating to oxygen toxicity in the aging process of higher organisms.

Mutants in the Saccharomyces cerevisiae RAS2 gene influence life span, cytoskeleton, and regulation of mitosis.

We investigated the phenotypic consequences in Saccharomyces cerevisiae of a disruption allele (ras2::LEU2) and of a dominant mutant form (RAS2ala18,val19) of RAS2. In addition to the phenotypes described earlier for these mutants, we observed a small increase in the life span for the disruption allele and a drastic decrease of life span for the dominant mutant form, as compared with the isogenic wild type. This was found by analyzing these alleles in two different genetic backgrounds with nearly the same results. Life spans were determined by micromanipulating mother cells and counting generations until no further cell division occurred. A morphological analysis of the terminal phenotypes of very old mother cells was performed showing enlarged or rounded cells and in some cases elongated buds, some of which were difficult to separate from the mother cell. This was observed in wild-type cells, as well as mutant cells. However, the dominant RAS2 mutant (but not the wild-type or ras2::LEU2 mutant cells) after 2 days on complex media displayed phenotypes similar to the terminal phenotype of old mothers. A substantial fraction of the cells were enlarged and generated elongated buds, they lost Calcofluor staining of the bud scars, the cell surface appeared folded, the actin cytoskeleton was aberrant, and the mitotic spindle and the cytoplasmic microtubles were defective in their proper orientation, resulting in aberrant mitoses and empty buds. These phenotypic characteristics of the RAS2ala18,val19 mutation could be causative for the previously observed rapid loss of viability of these cells in stationary phase.