Mannitol in cardioplegia as an oxygen free radical scavenger measured by malondialdehyde

Abstract

Oxygen free radicals (OFRs) are associated with ischaemia-reperfusion injury involving many organs, including the heart, which can lead to depressed cardiac function and abnormalities in the cardiac ultrastructure. This is seen upon the release of the aortic crossclamp when the ischaemic myocardium is reperfused in patients undergoing cardiopulmonary bypass (CPB). Various studies have shown that by adding OFR scavenging agents or antioxidants to the CPB prime or cardioplegia, cardiac performance improves. Mannitol is an osmotic diuretic with free radical scavenging properties, which has been shown to reduce the extent of ischaemic injury and improve the function of the myocardium. This study evaluated how effective mannitol is as an OFR scavenger by administering different concentrations of cardioplegia antegrade into the aortic root, thus maximising its effects directly upon the myocardium rather than being diluted in the CPB prime. Thirty-three patients undergoing primary coronary artery bypass grafting (CABG) were, by double blind random selection, allocated into one of three groups: group 1, a control group (consisting of 11 patients) receiving no mannitol; group 2 (11 patients), receiving a concentration of 4 g/l; and group 3 (11 patients), receiving 8 g/l. Three blood samples were taken directly from the coronary sinus during bypass: the first sample at the start of bypass, just prior to the crossclamp being applied; the second sample just after removal of the crossclamp; and the third sample just prior to termination of bypass. All samples were then centrifuged and the plasma analysed for malondialdehyde (MDA) using high-performance liquid chromatography (HPLC). MDA, an endproduct of lipid peroxidation, causes cellular damage and disruption of cell membranes when tissue antioxidants are exhausted. The more MDA produced, the greater the depletion of tissue antioxidants secondary to OR formation during reperfusion when the aortic crossclamp is removed. HPLC is a useful biochemical study; however, it is not a direct indicator of depressed myocardial function, such as an invasive test would be, and this should be borne in mind. Statistically, the results do not show a significant difference among the three groups or among the three samples. However, a trend can be seen, which shows lower levels of MDA in the two groups receiving mannitol and there is an indication of a rise in MDA levels upon the start of reperfusion in the two groups receiving mannitol, but not the control group. It is concluded that further samples would be needed to find a significant difference in MDA concentrations.

Mitochondrial Preservation in Celsior Versus Histidine Buffer Solution During Cardiac Ischemia and Reperfusion

“…CxI produces deleterious ROS during I/R [22] and has also been identified as a target for oxidative damage probably due to ROS-mediated oxidation of cardiolipin, a phospholipid required for optimal function of CxI [23]. Cs, which afforded more protection against CxIsustained oxidative phosphorylation, has high mannitol and glutathione content, which can contribute for an enhanced ROS scavenging [24,25]. Although CxI activity was preserved, a decrease in protein oxidation was not observed in Cs preservation, which may indicate that the ROS that cause disturbance of CxI-sustained oxidative phosphorylation are not counteracted by the antioxidant species in the cardioplegic solution, either because of limited access to the site of production or because of limited enrichment in the mitochondrial membranes, which in theory is the site where oxidative damage to proteins will occur.…”

A Viable Neuroprotection Strategy Following Soman-induced Status Epilepticus

“…In studies showing reduced edema and neuroprotection by mannitol, dosages typically range between 1.0 -1.5 g/kg and produce a hypertonic bolus (e.g., Filbert et al, 1993;Ueno et al, 1994;Berger et al, 1994;Bareyre et al, 1997;Korenkov et al, 2000). However, mannitol has been reported to possess free radical scavenging properties (e.g., Willis et al, 1994;Jiang et al, 2001;Larsen et al, 2002) which may have provided an extra measure of neuroprotection. Interestingly, it was observed that body temperatures in the soman + diazepam + dantrolene group were lowered below 33 °C (i.e., 31.9 ± 0.78 °C) for more than 10 hours.…”

Protektive Wirkung eines d-Opioid-Rezeptor-Agonisten und eines Sauerstoffradikalf�ngers auf postisch�mische Herzen

“…Der δ-Opioid-Rezeptor-Agonist DAla2-D-Leu5-Enkephalin (DADLE) wirkt über eine direkte Stimulation des δ-Opioid-Rezeptors [47] und führt letztlich zur Bildung von Sauerstoffradikalen [41], welche eine pharmakologische Präkonditionierung triggern. Mannitol ist dagegen als wirkungsvoller Radikalfänger beschrieben [18,29]. Wegen seiner osmotischen Eigenschaften wird Mannitol andererseits kardioplegischen Lösungen zugesetzt und in der Herzchirurgie verwendet.…”