Inhibition of Na+/H+ exchanger attenuates neutrophil-mediated reperfusion injury

Low-volume resuscitation from traumatic hemorrhagic shock with Na+/H+ exchanger inhibitor*

“…High Ca 2ϩ i is assumed to be one of the main reasons for ischemic and reperfusion injury including arrhythmias, myocardial contractile dysfunction, stunning, and eventually necrosis (6,8,20,21). In addition, NHE activation during ischemia and reperfusion is also involved in activation of the inflammatory system, leading to tissue inflammatory injury (22,23). Thus, in addition to restoring blood pressure, the resuscitation strategies need to reduce the inflammatory response and organ injury.…”

“…The failure of tissue to maintain intracellular calcium (Ca 2ϩ i ) homeostasis during ischemia and resuscitation results in Ca 2ϩ i overload leading to cell death and tissue necrosis (20). Central to this is NHE activation during ischemia and reperfusion leading to intracellular Na ϩ (Na ϩ i ) and Ca 2ϩ i overload, through proton-dependent regulation pathway and NHE activation by endogenous mediators and oxidant stress (21,22). High Ca 2ϩ i is assumed to be one of the main reasons for ischemic and reperfusion injury including arrhythmias, myocardial contractile dysfunction, stunning, and eventually necrosis (6,8,20,21).…”

Coadministration of a Na+-H+ exchange inhibitor and sodium bicarbonate for the treatment of asphyxia-induced cardiac arrest in piglets

“…There is strong evidence suggests that NHE1, a predominant isoform in neutrophils, regulates inflammatory processes (33,34). NHE1 inhibitors have been shown to inhibit neutrophil accumulation, chemokine production, and NF-κB activation; to attenuate leukocyteendothelial cell interactions; and to improve endothelial dysfunction induced by ischemic-reperfusion (11,35,36). In the present study, prolonged asphyxial cardiac arrest and resuscitation resulting in a significant increase of accumulation of neutrophils and cytokine in lung tissues.…”

“…IL-10 induction involves ERK1/2, p38, and NFkB signaling and transcriptional activation via promoter binding of the transcription factors NFkB and AP-1 (37). NHE1 inhibitors have been shown to inhibit ERK1/2, p38, and NFkB signaling, and inhibit neutrophil activation (10,11,(33)(34)(35)(36). Therefore, it can suggest that the lower levels of IL-10, TNF-α, and IL-6 in sabiporide-treated groups reflect from the lower inflammatory response, compared to vehicle controls.…”

Contents of Lactate and Intracellular Oxygen Metabolism at Neutrophils in Patients with Acute Coronary Syndrome

“…Believe that antineutrophil interventions can effectively prevent the increase in oxygen radical concentration during reperfusion [6]. It is revealed, that the inhibition of Na + /H + exchange with using 5-methyl-N-isobutyl amiloride shows a protective effect against neutrophil-induced reperfusion injury [7].…”