cytochrome-c-t and Ventricular-Fibrillation

To investigate the protective effect of anisodamine on myocardial mitochondrial damage in cardiac arrest (CA) in pigs.. Twenty-three male pigs were randomly divided into three groups, epinephrine group (n=9), anisodamine group (n=9) and control group (n=5). CA following ventricular fibrillation (VF) was induced by alternating current. The blood samples were collected before CA, 8 minutes after CA and instantly after recovery of spontaneous circulation (ROSC), and 30 minutes and 24 hours later. Hearts were obtained at 24 hours after ROSC. The changes in Cytochrome C (Cyt C) and caspase-3 in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). The myocardial specimens were observed by transmission electron microscopy for ultrastructural changes, and apoptosis was assessed with Hoechst 33258 staining.. The ROSC rate of the anisodamine group was elevated by 22.22% compared with the epinephrine group (77.78% vs. 55.56%, P>0.05). All animals with resumption of ROSC survived up to 24 hours. The plasma contents of Cyt C and caspase-3 in the epinephrine group and the anisodamine group gradually increased after ROSC, and were significantly higher than those in the control group. But the plasma Cyt C level in the anisodamine group was lower than that in the epinephrine group at 30 minutes and 24 hours after ROSC (48.68±19.50 nmol/L vs. 77.51±29.87 nmol/L, 48.98±20.26 nmol/L vs. 82.11±25.09 nmol/L, both P<0.05). There was no significant difference in protein contents of both Cyt C and caspase-3 in plasma and myocardium between two resuscitate groups. Both epinephrine and anisodamine could mitigate cardiac mitochondrial damage after CA, but the anisodamine showed better effect. The myocardium apoptosis ratio in the anisodamine group was lower than that of the epinephrine group [(0.15±0.04)% vs. (0.37±0.04)%, P<0.01].. By decreasing the protein content of Cyt C, and reducing the extent of damage to myocardial mitochondria, anisodamine can protect the myocardial ultrastructure, and restrain the mitochondria-induced cell apoptosis after resuscitation.

Topics: Animals; Apoptosis; Cardiopulmonary Resuscitation; Caspase 3; Cytochromes c; Epinephrine; Heart Arrest; Male; Mitochondria, Heart; Myocardium; Random Allocation; Resuscitation; Solanaceous Alkaloids; Swine; Ventricular Fibrillation

Ca(2+) overload and reactive oxygen species can injure mitochondria during ischemia and reperfusion. We hypothesized that mitochondrial injury occurs during cardiac resuscitation, causing release of cytochrome c to the cytosol and bloodstream while activating apoptotic pathways. Plasma cytochrome c was measured using reverse-phase HPLC and Western immunoblotting in rats subjected to 4 or 8 min of untreated ventricular fibrillation and 8 min of closed-chest resuscitation followed by 240 min of postresuscitation hemodynamic observation. A sham group served as control. Plasma cytochrome c rose progressively to levels 10-fold higher than in sham rats 240 min after resuscitation (P < 0.01), despite reversal of whole body ischemia (decreases in arterial lactate). Cytochrome c levels were inversely correlated with left ventricular stroke work (r = -0.40, P = 0.02). Western immunoblotting of left ventricular tissue demonstrated increased levels of 17-kDa cleaved caspase-3 fragments in the cytosol. Plasma cytochrome c was then serially measured in 12 resuscitated rats until the rat died or cytochrome c returned to baseline. In three survivors, cytochrome c rose slightly to

Topics: Animals; Apoptosis; Biomarkers; Blotting, Western; Caspase 3; Chromatography, High Pressure Liquid; Cytochromes c; Disease Models, Animal; Electric Stimulation; Heart Arrest; Heart Ventricles; Leukocytes; Male; Mitochondria, Heart; Predictive Value of Tests; Prognosis; Rats; Rats, Sprague-Dawley; Resuscitation; Severity of Illness Index; Time Factors; Ventricular Fibrillation; Ventricular Function, Left

We investigated the contribution of dexamethasone treatment on the recovery of postischemic cardiac function and the development of reperfusion-induced arrhythmias in ischemic/reperfused isolated rat hearts. Rats were treated with 2 mg/kg of intraperitoneal injection of dexamethasone, and 24 hours later, hearts were isolated according to the 'working' mode, perfused, and subjected to 30 min global ischemia followed by 120 min reperfusion. Cardiac function including heart rate, coronary flow, aortic flow, and left ventricular developed pressure were recorded. After 60 min and 120 min reperfusion, 2 mg/kg of dexamethasone significantly improved the postischemic recovery of aortic flow and left ventricular developed pressure from their control values of 10.7 +/- 0.3 ml/min and 10.5 +/- 0.3 kPa to 22.2 +/- 0.3 ml/min (p < 0.05) and 14.3 +/- 0.5 kPa (p < 0.05), 19.3 +/- 0.3 ml/min (p < 0.05) and 12.3 +/- 0.5 kPa (p < 0.05), respectively. Heart rate and coronary flow did not show a significant change in postischemic recovery after 60 or 120 min reperfusion. In rats treated with 0.5 mg/kg of actinomycin D injected i.v., one hour before the dexamethasone injection, suppressed the dexamethasone-induced cardiac protection. Electrocardiograms were monitored to determine the incidence of reperfusion-induced ventricular fibrillation. Dexamethasone pretreatment significantly reduces the occurrence of ventricular fibrillation. Cytochrome c release was also observed in the cytoplasm. The results suggest that the inhibition of cytochrome c release is involved in the dexamethasone-induced cardiac protection.

Topics: Animals; Anti-Inflammatory Agents; Arrhythmias, Cardiac; Coronary Circulation; Cytochromes c; Dactinomycin; Dexamethasone; Dose-Response Relationship, Drug; Electrocardiography; Heart; Injections, Intraperitoneal; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Rats; Rats, Sprague-Dawley; Ventricular Fibrillation