dinoprost and Ventricular-Fibrillation

Glucagon-like peptide-1 (GLP-1) has protective effects in the heart. We hypothesized that GLP-1 would mitigate coronary microvascular and left ventricular (LV) dysfunction if administered after cardiac arrest and resuscitation (CAR). Eighteen swine were subjected to ventricular fibrillation followed by resuscitation. Swine surviving to return of spontaneous circulation (ROSC) were randomized to receive an intravenous infusion of either human rGLP-1 (10 pmol·kg(-1)·min(-1); n = 8) or 0.9% saline (n = 8) for 4 h, beginning 1 min after ROSC. CAR caused a decline in coronary flow reserve (CFR) in control animals (pre-arrest, 1.86 ± 0.20; 1 h post-ROSC, 1.3 ± 0.05; 4 h post-ROSC, 1.25 ± 0.06; P < 0.05). GLP-1 preserved CFR for up to 4 h after ROSC (pre-arrest, 1.31 ± 0.17; 1 h post-ROSC, 1.5 ± 0.01; 4 h post-ROSC, 1.55 ± 0.22). Although there was a trend toward improvement in LV relaxation in the GLP-1-treated animals, overall LV function was not consistently different between groups. 8-iso-PGF(2α), a measure of reactive oxygen species load, was decreased in post-ROSC GLP-1-treated animals [placebo, control (NS): 38.1 ± 1.54 pg/ml; GLP-1: 26.59 ± 1.56 pg/ml; P < 0.05]. Infusion of GLP-1 after CAR preserved coronary microvascular and LV diastolic function. These effects may be mediated through a reduction in oxidative stress.

Topics: Animals; Antioxidants; Cardiopulmonary Resuscitation; Coronary Circulation; Dinoprost; Endothelium, Vascular; Female; Glucagon-Like Peptide 1; Heart Arrest; Heart Ventricles; Humans; Male; Microvessels; Reactive Oxygen Species; Swine; Ventricular Dysfunction, Left; Ventricular Fibrillation

To determine whether antithrombin (AT) administration during cardiopulmonary resuscitation (CPR) increased cerebral circulation and reduced reperfusion injury.. Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. The animals were randomised into two groups. The treatment group received AT (250 U/kg) and the control group received placebo, after 7 min of CPR. Defibrillation was attempted after 9 min of CPR. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h. Cortical cerebral blood flow was measured using laser-Doppler flowmetry. Cerebral oxygen extraction was calculated to reflect the relation between global cerebral circulation and oxygen demand. Measurements of eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)), AT, thrombin-antithrombin complex (TAT) and soluble fibrin in jugular bulb plasma were performed to detect any signs of cerebral oxidative injury, inflammation and coagulation.. There was no difference between the groups in cortical cerebral blood flow, cerebral oxygen extraction, or levels of eicosanoids, TAT or soluble fibrin in jugular bulb plasma after ROSC. In the control group reduction of AT began 15 min after ROSC and continued throughout the entire observation period (P < 0.05). Eicosanoids and TAT were increased compared to baseline in all animals (P < 0.01).. In this experimental model of CPR, AT administration did not increase cerebral circulation or reduce reperfusion injury after ROSC.

Topics: Animals; Antithrombin III; Antithrombins; Brain; Cardiopulmonary Resuscitation; Cerebrovascular Circulation; Dinoprost; Fibrin; Heart Arrest; Laser-Doppler Flowmetry; Oxygen Consumption; Peptide Hydrolases; Reperfusion Injury; Swine; Time Factors; Ventricular Fibrillation

Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.

Topics: Animals; Brain; Brain Injuries; Cardiopulmonary Resuscitation; Dinoprost; Eicosanoids; F2-Isoprostanes; Female; Free Radicals; Heart Arrest; Inflammation; Male; Oxidative Stress; Radioimmunoassay; Swine; Time Factors; Ventricular Fibrillation

To determine whether activation of coagulation and inflammation during cardiac arrest results in a reduction of antithrombin (AT) and an increase in thrombin-antithrombin (TAT) complex during reperfusion.. Ventricular fibrillation (VF) was induced in ten anaesthetized pigs. After a 5-min non-intervention interval, closed-chest cardiopulmonary resuscitation (CPR) was performed for 9 min before defibrillation was attempted. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h and repeated blood samples were taken for assay of AT, TAT and eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)).. AT began to decrease 15 min after ROSC and the reduction continued throughout the observation period (P<0.05). The lowest mean value (79%) occurred 60 min after ROSC. The TAT level was increased during the first 3 h after ROSC (P<0.05), indicating thrombin generation. The eicosanoids were increased throughout the observation period (P<0.05).. AT is reduced and TAT and eicosanoids are increased after cardiac arrest, indicating activation of coagulation and inflammation.

Topics: Analysis of Variance; Animals; Antithrombins; Biomarkers; Cardiopulmonary Resuscitation; Dinoprost; Disease Models, Animal; Electric Countershock; Female; Hemodynamics; Male; Myocardial Reperfusion; Probability; Radioimmunoassay; Random Allocation; Sensitivity and Specificity; Swine; Ventricular Fibrillation

In a porcine model of cardiopulmonary resuscitation (CPR), we investigated changes in the plasma levels of 8-iso-PGF(2alpha), a marker for oxidative injury, and 15-keto-dihydro-PGF(2alpha), an inflammatory response indicator during the post-resuscitation period after cardiac arrest. Twelve piglets were subjected to either 2 or 5 min (VF2 and VF5 group) of ventricular fibrillation (VF) followed by 5 min of closed-chest CPR. Six piglets without cardiac arrest were used as controls. In VF5 group, 8-iso-PGF(2alpha) in the jugular bulb plasma (draining the brain) increased four-fold. Jugular bulb 8-iso-PGF(2alpha) in the control group remained unchanged. The 15-keto-dihydro-PGF(2alpha) also increased four-fold in the VF5 group. Thus, 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) measurements in jugular bulb plasma may be used as biomarkers for quantification of free radical catalyzed oxidative brain injury and inflammatory response in reperfusion injury.

Topics: Animals; Biomarkers; Cardiopulmonary Resuscitation; Dinoprost; Disease Models, Animal; F2-Isoprostanes; Female; Free Radicals; Heart Arrest; Jugular Veins; Male; Molecular Structure; Myocardial Reperfusion Injury; Swine; Ventricular Fibrillation