Thromboxane B2 in cardiac lymph. Effect of superoxide dismutase and catalase during myocardial ischemia and reperfusion.

Abstract

Neutrophils have been implicated in the genesis of myocardial ischemia-reperfusion injury, and their mechanism of action has been linked to the production of reactive oxygen species, fatty acid-derived prostanoids, and leukotrienes. In this study, we examined the potential relation between production of reactive oxygen species and cyclooxygenase-derived autacoids by studying the effects of superoxide dismutase (SOD) and catalase (CAT) on the rise in thromboxane formation observed with myocardial ischemia and reperfusion. Immunoreactive thromboxane B2 was measured in cardiac lymph from conscious dogs during reperfusion after a 60-minute occlusion in the presence of infusions of SOD alone, CAT alone, and a combination of SOD and CAT. Reperfusion after 60 minutes of ischemia causes an immediate elevation in thromboxane B2. SOD and CAT infusion prevented this rise in thromboxane B2 as did infusion of SOD alone. The ability of SOD-CAT to suppress thromboxane B2 production dissipated within 3 hours after the cessation of infusion, at which time thromboxane B2 excretion increased. The modulation of fatty acid oxygenases by reactive oxygen species may be a very important pathogenic factor in considering the origin of the protective effect of antioxidants in the setting of myocardial ischemia-reperfusion injury.

Resident Cardiac Mast Cells Degranulate and Release Preformed TNF-α, Initiating the Cytokine Cascade in Experimental Canine Myocardial Ischemia/Reperfusion

“…26 Furthermore, Ito et al 15 demonstrated in pig heart that cardiac mast cells, when exposed to C5a, rapidly degranulated and released histamine and thromboxane B 2 . In previous studies, 27 we have shown the presence of both C5a and thromboxane B 2 in postischemic cardiac lymph. This suggested to us that mast cell degranulation might be an important part of the ischemia/reperfusion process.…”

“…10,30 Although this model has been used extensively in our research, 2 important articles require review here to understand the significance of the present findings. First, in previous experiments, 27 we have demonstrated a prompt rise of thromboxane B 2 during early reperfusion, which may provide additional evidence for mast cell degranulation during the ischemia and reperfusion events. The second important point stems from one of our earliest studies, in which we measured the appearance of creatine kinase and phosphorylase b in the cardiac lymph.…”

Effect of Antioxidant Therapy on Cyclooxygenase-Derived Eicosanoid Release during Intestinal Ischemia-Reperfusion

“…If there is insufficient enzymatic protection, the presence of catalytically active metal ions will lead to the production of other, highly reactive, mem brane-destructive intermediates, such as hy droxyl radicals [23], Conflicting data have been reported on the possible connection between arachidonic-acid-derived eicosanoid production and reactive oxygen intermediates formed during ischemia-reperfusion. Since cycloox ygenase (and lipoxygenase) can be inhibited by several antioxidants and an increased production of molecular oxygen species may enhance oxygenase activity, an elevation in eicosanoid output and consequently the ef fectiveness of scavengers in limiting post ischemic eicosanoid production could be an ticipated [7,24], Such findings have actually been demonstrated in some experimental models [25,26]. Conversely, the generated oxygen radicals feed back to deactivate the cyclooxygenase, and antioxidant treatment could therefore lead to an enhanced eicosa noid synthesis [6,27], Severe free radical damage can result in major losses of mem brane phospholipids, reducing their avail ability for eicosanoid formation, and thus decreases in the production of 6-keto-PGFia and TxB2 could occur [28].…”

Complement and Polymorphonuclear Leukocyte Activation Each Play a Role in Determining Myocardial Ischemia - Reperfusion Injury

“…48 The present results are consistent with the induction of PMN chemotaxis into the ischemic myocardium by activation of the complement cascade. Activated PMNs produce chemotactic factors such as leukotriene B4, platelet-activating factor and IL-8 in ischemic myocardium 4,43,45 and our results in CVFtreated rats suggest that complement function rather than activation of PMNs is the factor involved in the accumulation of PMNs in the ischemic myocardium because the activation of PMNs, when complement was depleted, resulted in a significantly smaller accumulation of PMNs in the myocardium (group 2). With an intact complement system, in vivo myocardial ischemia -reperfusion injury may be exacerbated, accompanied by PMN infiltration, confirming that the management of complement contributes to a reduction of IS associated with myocardial PMN infiltration.…”

“…First, intravascular PMNs might cause myocardial injury, because the supernatant of activated PMNs induces injury to isolated cardiac myocytes in vitro. [37][38][39] The majority of PMNs are in the intravascular space during the first few hours after ischemia -reperfusion 40 and it is possible that the cyclooxygenase -lipoxygenase system, 41,42 reactive oxygen species, 43,44 inflammatory cytokines, 6,45 such as interleukin (IL)-8, tumor necrosis factor-and IL-6, in part derived from PMN activation, injure the myocardium at risk in an inflammatory cascade. In this context, the MPO activity in the ischemic area of groups 2 and 3 was significantly higher compared with each non-ischemic area, whereas it was less than that of group 1.…”