Reperfusion injury in humans: A review of clinical trials on reperfusion injury inhibitory strategies

Abstract

The principal therapy in patients with myocardial infarction to limit infarct size is myocardial reperfusion by mechanical or pharmacological intervention. Reperfusion has been proposed to cause myocardial injury beyond that caused by the preceding ischaemia, termed "reperfusion injury" (RI). While the precise mechanism of RI is still incompletely understood, a large number of clinical studies have been performed over the past decade targeting some of the postulated mechanisms of RI. These clinical studies were based on experimental data demonstrating significant myocardial salvage. Nevertheless, clinical benefits were absent or very limited. The purpose of this review is to provide an overview of the various strategies that inhibit RI and to discuss potential mechanisms that may contribute to the discrepancy between the promising pre-clinical data and the rather disappointing results obtained from prospective clinical trials. There are numerous differences between the experimental models and clinical studies, including the fact that experimental studies typically use abrupt occlusion and reperfusion protocols in animals with previously healthy myocardium that apparently do not predict the therapeutic efficacy of novel cardioprotective agents in a clinical setting with pre-existing progressive coronary disease, intermittent coronary occlusion, and relatively late reperfusion. However, discrepancies also exist between experimental studies. Future experimental studies of reperfusion injury should use models that mimic the clinical situation more closely. Furthermore, future large clinical trials should only be performed in cases where the drug under investigation proved to reduce RI in a series of well-designed (possibly multicenter) experimental studies and in clinical trials with predefined subgroups.

Enzymatic Antioxidants: Next Phase of Pharmacological Effort to Fight Oxidative Stress?

“…Nevertheless, the clinical trial data had not confirmed their universal efficiency established in experimental researches [10,11]. Inconsistency of the clinical results of testing antioxidants was explained by difference of the used models of lesions on animals and cell from the human body environment [1,5], by incorrect choice of the tested antioxidant, parameters of monitoring its activity, amounts of the injected derivative doses, duration of trials, patient selection criteria [9,11]. Such situation determines the necessity to perform new clinical trials according to the strict protocol with more wide use of new antioxidant derivatives.…”

“…One of the objectives of adjacent (additional) therapy is to block it. The oxidative stress contributes to the aggravation of disorders during thrombolysis for potency of infarct-related artery ("reperfusion injury") [5,6], during vascular angioplasty procedures (development of restenosis) [7,8]. That's why the importance of search of highly efficient resources to ensure antioxidant protection of the cardiovascular system is well known and justified.…”

Effect of L-carnitinee on echocardiographic parameters in patients with acute coronary syndrome

“…Многочисленные исследования свидетельствуют об успешном примене-нии первых двух подходов и в снижении частоты леталь-ных исходов, и в уменьшении степени ремоделирования миокарда и риска развития СН. Применение же различ-ных подходов, направленных на уменьшение окисли-тельного стресса, в основном не привели к положитель-ным результатам [5]. Тем не менее такие подходы про-должают разрабатываться.…”

Treatment of hemorrhagic shock with hypertonic saline solution modulates the inflammatory response to live bacteria in lungs

“…Intravascular fluid resuscitation is the consensual treatment for patients with hypovolemic shock (1). This lifesaving procedure may, on the other hand, induce ischemia and reperfusion (I-R) injury in cells of virtually any vital organ (2).…”