3-nitrotyrosine and Heart-Arrest

To investigate the protective effects and its potential mechanism of resveratrol preconditioning on rat cardiac arrest after return of spontaneous circulation (ROSC) with the study of hemodynamic parameters and nitrative stress in myocardium.. Cardiac arrest SPF SD rat model was established by transoesophageal cardiac alternating current stimulation. Intervention was implemented 15 min before cardiac arrest. Twenty four rats with ROSC after cardiac arrest were randomly assigned into five groups: vehicle, sham, resveratrol 2.3 mg/kg (A group), resveratrol 0.23 mg/kg (B group) and resveratrol 0.023 mg/kg (C group). Heart rate, mean arterial pressure, and left ventricular variables (+ dp/dtmax and - dp/dtmin) were recorded in 0.5 h, 1.0 h, 2.0 h, 3.0 h, and 4.0 h respectively. Rats were sacrificed at 4 h after ROSC, and hearts were removed for determining expression of inducible nitric oxide synthase (iNOS) protein, myocardial peroxynitrite, and nitrotyrosine.. Global ROSC rate was 72.7% after the induction of cardiac arrest. Resveratrol preconditioning did not improve ROSC rate significantly. Heart rate and blood pressure declined at early phase of ROSC, then heart rate recovered to the baseline value, but blood pressure still declined progressively. There were no significant differences between resveratrol groups and vehicle group. Myocardial function worsened progressively even after ROSC. Resveratrol improved cardiac function significantly, especially in lower concentration groups. Myocardial iNOS expression, peroxynitrite, and nitrotyrosine content increased significantly after ROSC. Resveratrol decreased these products significantly, and lower concentration groups did better.. Resveratrol preconditioning could improve cardiac dysfunction after ROSC, which may be associated with its inhibitory effect on nitrative stress.

Topics: Animals; Disease Models, Animal; Heart; Heart Arrest; Ischemic Preconditioning; Nitric Oxide Synthase Type II; Peroxynitrous Acid; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Tyrosine

The effect of hyperoxygenation at reperfusion, particularly in the setting of cardiac arrest, remains unclear. This issue was studied in a prolonged cardiac arrest model consisting of 25 min cardiac arrest in a rat resuscitated with cardiopulmonary bypass (CPB). The objective of this study was to determine the effect of hyperoxygenation following prolonged cardiac arrest resuscitation on mitochondrial and cardiac function.. Male Sprague-Dawley rats (400-450 g) were anesthetized with ketamine and xylazine and instrumented for closed chest cardiopulmonary bypass (CPB). Following a 25-min KCl-induced cardiac arrest, the animals were resuscitated by CPB with 100% oxygen. Three minutes after successful return of spontaneous circulation (ROSC), the animals received either normoxemic reperfusion (CPB with 40-50% oxygen) or hyperoxemic reperfusion (CPB with 100% oxygen) for 1 h. Post-resuscitation hemodynamics, cardiac function, mitochondrial function and immunostaining of 3-nitrotyrosine were compared between the two different treatment groups.. At 1 h after ROSC, the hyperoxemic reperfusion group had a significant higher mean arterial pressure, less metabolic acidosis and better diastolic function than the normoxemic reperfusion group. Cardiac mitochondria from the hyperoxemic reperfusion group had a higher respiratory control ratio (RCR) and cardiac tissue showed less nitroxidative stress compared to the normoxemic reperfusion group.. One hour of hyperoxemic reperfusion after 25 min of cardiac arrest in an in vivo CPB model resulted in significant short-term improvement in myocardial and mitochondrial function compared with 1h of normoxemic reperfusion. This myocardial response may differ from previously reported post-arrest hyperoxia mediated effects following shorter arrest times.

Topics: Analysis of Variance; Animals; Blood Gas Analysis; Cardiopulmonary Bypass; Heart Arrest; Hemodynamics; Hyperoxia; Immunohistochemistry; Male; Mitochondria, Heart; Oxygen Inhalation Therapy; Rats; Rats, Sprague-Dawley; Time Factors; Tyrosine

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.

Topics: Female; Heart Arrest; Humans; Hypothermia; Hypothermia, Induced; Male; Middle Aged; Nitrates; Nitrites; Oxidative Stress; Tyrosine

Emergency preservation and resuscitation (EPR) of 60 min in rats is achievable with favorable outcome, while 75 min is associated with substantial mortality and impaired neurological outcome in survivors. We hypothesized that 75 min but not 60 min of EPR would be associated with activation of two potential secondary injury cascades in brain as reflected by protein nitration and poly (ADP-ribose) polymerase (PARP) activation.. Rats were rapidly exsanguinated over 5 min. After 1 min of cardiac arrest (CA), rats were cooled to a target tympanic temperature of 15 degrees C. After either 60 min or 75 min of CA, resuscitation was achieved via cardiopulmonary bypass (CPB). Rats subjected to CPB only served as controls. Overall performance category (OPC) and neurologic deficit score (NDS) were assessed at 24 h. Protein nitration and poly-ADP-ribosylation were assessed by Western blotting and immunohistochemistry for 3-nitrotyrosine and poly-ADP ribose polymers, respectively, in multiple brain regions.. Neurologic outcome was better in the 60 min vs. the 75 min EPR group (OPC, P<0.001; NDS, P=0.001). Densitometric analysis of the major 64 kD band showed that nitration and PARP activation were significantly increased in hippocampus, cortex and striatum in the 75 min EPR group vs. other groups. However, there were no differences in cerebellum. Analysis of the full protein spectrum showed significantly increased PARP activation only in hippocampus in the 75 min EPR group vs. other groups.. Extending the duration of EPR beyond the limit that can yield favorable recovery in rats was associated with increased nitration and ribosylation of selected proteins in selectively vulnerable brain regions. The impact of these mechanisms on the outcome remains to be determined.

Topics: Animals; Brain; Cardiopulmonary Bypass; Cardiopulmonary Resuscitation; Disease Models, Animal; Heart Arrest; Hypothermia, Induced; Male; Poly(ADP-ribose) Polymerases; Rats; Rats, Sprague-Dawley; Time Factors; Tyrosine

Resuscitation and prolonged ventilation using 100% oxygen after cardiac arrest is standard clinical practice despite evidence from animal models indicating that neurologic outcome is improved using normoxic compared with hyperoxic resuscitation. This study tested the hypothesis that normoxic ventilation during the first hour after cardiac arrest in dogs protects against prelethal oxidative stress to proteins, loss of the critical metabolic enzyme pyruvate dehydrogenase complex (PDHC), and minimizes subsequent neuronal death in the hippocampus. Anesthetized beagles underwent 10 mins ventricular fibrillation cardiac arrest, followed by defibrillation and ventilation with either 21% or 100% O2. At 1 h after resuscitation, the ventilator was adjusted to maintain normal blood gas levels in both groups. Brains were perfusion-fixed at 2 h reperfusion and used for immunohistochemical measurements of hippocampal nitrotyrosine, a product of protein oxidation, and the E1alpha subunit of PDHC. In hyperoxic dogs, PDHC immunostaining diminished by approximately 90% compared with sham-operated dogs, while staining in normoxic animals was not significantly different from nonischemic dogs. Protein nitration in the hippocampal neurons of hyperoxic animals was 2-3 times greater than either sham-operated or normoxic resuscitated animals at 2 h reperfusion. Stereologic quantification of neuronal death at 24 h reperfusion showed a 40% reduction using normoxic compared with hyperoxic resuscitation. These results indicate that postischemic hyperoxic ventilation promotes oxidative stress that exacerbates prelethal loss of pyruvate dehydrogenase and delayed hippocampal neuronal cell death. Moreover, these findings indicate the need for clinical trials comparing the effects of different ventilatory oxygen levels on neurologic outcome after cardiac arrest.

Topics: Animals; Cardiopulmonary Resuscitation; Disease Models, Animal; Dogs; Female; Heart Arrest; Hippocampus; Image Processing, Computer-Assisted; Immunohistochemistry; Neurons; Oxidative Stress; Oxygen; Oxygen Inhalation Therapy; Pyruvate Dehydrogenase Complex; Tyrosine