Effects of dopexamine on lipid peroxidation during aortic surgery in pigs: comparison with dopamine.
ABSTRACT We investigated the dose-related effect of dopexamine and dopamine on free radical production and lipid peroxidation estimated by MDA measurements in an ischaemia-reperfusion model of supraceliac aortic repair.
Prospective, randomized, blinded experimental study.
Twenty-five healthy pigs.
All experiments were performed under general endotracheal anaesthesia. Supraceliac aortic cross clamping was performed in all pigs. The pigs were randomly assigned into five groups (n=5 in each group) and received a continuous intravenous infusion of normal saline (CTL), dopamine 2 microg kg(-1)min(-1) (dopa 2), dopamine 8 microg kg(-1)min(-1) (dopa 8), dopexamine 2 microg kg(-1)min(-1) (dopex 2), dopexamine 8 microg kg(-1)min(-1) (dopex 8). Cardiac output, mean arterial pressure, arterial blood gas analysis and blood sampling for plasma MDA measurements (to reveal lipid peroxidation) were recorded after induction of anaesthesia (baseline), 60 and 120 min after cross-clamping of aorta (ischaemia phase), and 60 and 120 min after restoration of flow (reperfusion phase).
Dopexamine and dopamine at 8 microgkg(-1)min(-1) reduced MDA at 60 and 120 min after reperfusion.
Dopexamine seems superior to dopamine in reducing oxygen free radicals and subsequent lipid peroxidation during reperfusion after supraceliac aortic cross clamping in pigs.
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ABSTRACT: The studies reported in this article provide evidence that several complex mechanisms are involved in the ability of dopexamine HCl (DPX) in preventing ischemia-reperfusion induced organ damage. In a canine model of hemorrhagic shock in which shed-blood was reinfused, DPX prevented deterioration in renal blood flow via an action on beta-2 and DA-1 receptors, whereas its ability to preserve tubular function was essentially due its agonistic effects on DA-1 receptors. In a different experimental model in anesthetized rats, acute generation of oxygen free radicals (OFR) via intravenous administration of Xanthine (X) followed by Xanthine Oxidase (XO) resulted in depression of circulation and death of more than 80% of the animals within the observation period of 120 min. Pretreatment of the rats with DPX significantly enhanced survival rate in a dose dependent manner to about 70%. Neither dobutamine nor prenalterol, which are beta-1 adrenoceptor agonists and like DPX, potent chronotropic and inotropic agents were effective in preventing OFR induced lethal toxicity. In a separate series, a selective DA-1 receptor agonist felodopam had no protective effect and a DA-1 receptor antagonist SCH-23390 failed to antagonize the salutary effects of DPX. In contrast, salbutamol, a selective beta-2 adrenoceptor agonist significantly promoted the survival rate facilitated by DPX and a selective beta-2 adrenoceptor antagonist, ICI-558,551 significantly attenuated the survival rate. These later studies suggest that unlike in hemorrhagic shock, the beta-2 adrenoceptor agonistic properties are critical in the ability of DPX to attenuate lethal toxicity and these effects could be related to prevention of lipid peroxidation induced by oxygen free radicals.Clinical and Experimental Hypertension 01/1997; 19(1-2):181-90. · 1.28 Impact Factor
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ABSTRACT: Aortic surgery is associated with a high incidence of perioperative complications, affecting virtually every organ system. The development of these complications is influenced by several factors, including whether surgery was emergent or elective, the location and duration of aortic cross-clamping, and the presence of coexisting disease states. The occurrence of end-organ damage reflects two main processes which are set in motion by aortic cross-clamping. The haemodynamic response refers to the changes produced in preload, afterload, and myocardial contractility. The humoral response refers to the formation and release of a series of mediators that both reflect and cause an ischaemia–reperfusion injury process. A clear understanding of the pathophysiological mechanisms involved in these processes will aid the clinician in adopting a rational approach to the care of patients undergoing aortic surgery.Anesthesiology 05/1995; 82(4):1026-60. · 5.16 Impact Factor
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ABSTRACT: The plasma status of vitamin E has been suggested to be linked to the activity of coronary artery spasm. This study was designed to determine whether vitamin E is actually consumed in the coronary circulation in patients with active variant angina having repetitive spasm-induced transient myocardial ischemia and reperfusion. Blood samples were obtained simultaneously from the aortic root, coronary sinus and right atrium in 12 patients with variant angina due to spasm of the left coronary artery, nine patients with stable effort angina and nine control subjects. Plasma vitamin E (alpha- and gamma-tocopherol) concentrations were determined by use of high-performance liquid chromatography and plasma lipid peroxides were measured as thiobarbituric acid-reactive substances (TBARS). At baseline, both plasma alpha- (p < 0.01) and gamma- (p < 0.05) tocopherol levels were significantly lower in the coronary sinus (5.50 +/- 0.50 and 0.55 +/- 0.07 mg/l, mean +/- SEM) than in the aortic root (6.63 +/- 0.57 and 0.63 +/- 0.08 mg/l) and also in the right atrium (6.44 +/- 0.61 and 0.63 +/- 0.09 mg/l) in the variant angina group. The TBARS level was significantly (p < 0.05) higher in the coronary sinus than in the aortic in this group. In contrast, these levels were not significantly different between the samples from the coronary sinus and the aortic root or the right atrium in the control group and also in the stable effort angina group. The coronary sinus-aortic difference in plasma vitamin E levels in the variant angina group was not significantly altered after left coronary artery spasm induced by intracoronary injection of acetylcholine. Also, the plasma vitamin E levels in the aortic root, coronary sinus and right atrium all remained unchanged in the stable effort angina group after pacing-induced angina and in the control group after intracoronary administration of acetylcholine. Transcardiac reduction in plasma vitamin E concentrations concomitant with lipid peroxide formation was demonstrated in patients with active variant angina, suggesting actual consumption of this major endogenous antioxidant. Oxidative stress and vitamin E exhaustion may be involved in the pathogenesis of coronary artery spasm.Cardiovascular Research 01/1999; 41(1):291-8. · 5.94 Impact Factor