dinoprost and Aneurysm--Ruptured

Ruptured abdominal aortic aneurysm (RAAA) remains a lethal condition despite improvements in perioperative care. The consequences of RAAA are hypothesized to result from a combination of two ischemia/reperfusion events: hemorrhagic shock and lower torso ischemia. Ischemia/reperfusion results in tissue injury by diverse mechanisms, which include oxygen free radical-mediated injury produced from activated neutrophils, xanthine oxidase, and mitochondria. Oxygen-free radicals attack membrane lipids, resulting in membrane and subsequently cellular dysfunction that contributes to postoperative organ injury/failure. The purpose of this investigation was to quantify the oxidative injury that occurs as a result of the ischemia/reperfusion events in RAAAs and elective AAAs.. Blood samples were taken from 22 patients for elective AAA repair and from 14 patients for RAAA repair during the perioperative period. Plasma F(2)-isoprostanes were extracted, purified, and measured with an enzyme immunoassay. Aldehydes and acyloins were purified and quantified. Neutrophil oxidative burst was measured in response to a receptor independent stimulus (phorbol 12-myristate 13-acetate) with luminol-based chemiluminescence.. Plasma from patients with RAAAs showed significantly elevated F(2)-isoprostane levels on arrival at hospital and were significantly elevated as compared with the levels of patients for elective repair throughout the perioperative period (two-way analysis of variance, P <.0001). Multiple regression showed a significant relationship between the phagocyte oxidative activity and F(2)-isoprostane levels (P <.013). Total acyloin levels were significantly higher in patients with RAAAs as compared with the levels in elective cases.. The F(2)-isoprostane levels, specific markers of lipid peroxidation, showed that patients with RAAAs had two phases of oxidative injury: before arrival at hospital and after surgery. The significant relationship between the postoperative increases in F(2)-isoprostane levels and the neutrophil oxidant production implicates neutrophils in the oxidative injury that occurs after RAAA. New therapeutic interventions that attenuate neutrophil-mediated oxidant injury during reperfusion may decrease organ failure and ultimately mortality in patients with RAAAs.

Topics: Aldehydes; Aneurysm, Ruptured; Aortic Aneurysm, Abdominal; Biomarkers; Dinoprost; Fatty Alcohols; Humans; In Vitro Techniques; Ischemia; Luminescent Measurements; Models, Cardiovascular; Neutrophils; Oxidative Stress; Reperfusion Injury; Respiratory Burst; Shock, Hemorrhagic; Tetradecanoylphorbol Acetate

Sodium nitroprusside (SNP) is commonly used for controlled systemic hypotension during aneurysm surgery after acute subarachnoid hemorrhage (SAH). Few experimental studies have assessed cerebrovascular responsiveness to SNP acutely after a representative SAH (i.e., following arterial rupture within the subarachnoid space). Instead, most studies have focused on delayed reactivity after slow injections of unpressurized blood throughout several days. In the authors' study, SAH was created by endovascular rupture in spontaneously breathing rats under urethane anesthesia without craniotomy. After 3 hours, proximal middle cerebral arteries (MCAs) were harvested and mounted as ring preparations in vitro. After preconstriction with 30 mM prostaglandin F2a, concentration-response curves were generated to express SNP's sequential relaxation of preconstricted tone. The effective concentration of SNP for 50% relaxation was significantly lower after SAH (p < 0.001) as compared with non-operated and sham-operated controls. There was also a significantly greater maximum percentage relaxation from preconstricted tone (p < 0.001) with SNP. The results of this study suggest that SNP is a potent and efficacious dilator of MCAs in the hours immediately after acute SAH.

Topics: Acute Disease; Anesthetics, Intravenous; Aneurysm, Ruptured; Animals; Antihypertensive Agents; Cerebral Arteries; Cerebrovascular Circulation; Dinoprost; Dose-Response Relationship, Drug; In Vitro Techniques; Intracranial Aneurysm; Intracranial Pressure; Male; Nitroprusside; Rats; Rats, Wistar; Subarachnoid Hemorrhage; Urethane; Vasoconstrictor Agents; Vasodilator Agents