Controlling Reperfusion Injury With Controlled Reperfusion: Historical Perspectives and New Paradigms

Cardiac reperfusion injury is a well-established outcome following treatment of acute myocardial infarction and other types of ischemic heart conditions. Numerous cardioprotection protocols and therapies have been pursued with success in pre-clinical models. Unfortunately, there has been lack of successful large-scale clinical translation, perhaps in part due to the multiple pathways that reperfusion can contribute to cell death. The search continues for new cardioprotection protocols based on what has been learned from past results. One class of cardioprotection protocols that remain under active investigation is that of controlled reperfusion. This class consists of those approaches that modify, in a controlled manner, the content of the reperfusate or the mechanical properties of the reperfusate (e.g., pressure and flow). This review article first provides a basic overview of the primary pathways to cell death that have the potential to be addressed by various forms of controlled reperfusion, including no-reflow phenomenon, ion imbalances (particularly calcium overload), and oxidative stress. Descriptions of various controlled reperfusion approaches are described, along with summaries of both mechanistic and outcome-oriented studies at the pre-clinical and clinical phases. This review will constrain itself to approaches that modify endogenously-occurring blood components. These approaches include ischemic postconditioning, gentle reperfusion, controlled hypoxic reperfusion, controlled hyperoxic reperfusion, controlled acidotic reperfusion, and controlled ionic reperfusion. This review concludes with a discussion of the limitations of past approaches and how they point to potential directions of investigation for the future.

The effect of controlled reperfusion on experimental ovarian torsion

The objective of our research was to study the effect of controlled reperfusion on lactate and advanced oxidation protein products (AOPP) in experimental ovarian torsion (OT), and to evaluate the possibility to reduce the reperfusion injuries applying the ON-OFF technique of reperfusion. Material and Methods — Lactate and AOPP were measured in serum and ovarian homogenates of 70 females rats, divided equally into 7 groups: no intervention (nr. 1); laparotomy (nr. 2); 3 hours OT (nr. 3); 3 hours OT + 1 hour (nr. 4) or 24 hours (nr. 6) of simple reperfusion (SR); 3 hours OT + 1 hour (nr. 5) or 24 hours (nr. 7) of controlled reperfusion (ON-OFF). The results were analyzed using Welch's ANOVA. Results — OT produced an increase of serum (66%, p<0.001) and homogenate (38%, p=0.006) lactate, that tended to return to baseline in 24 hours despite the type of reperfusion. AOPP had grown in OT animals serum (20%, p=0.007) and homogenate (26%, p>0.05) and continued to rise in the serum after SR, while in ON-OFF technique groups – decreased by about 20% (p<0.01). Homogenate AOPP levels rised after reperfusion in all groups. Conclusion — Lactate is a biomarker for ischemia in OT. Increased AOPP in experimental groups indicates that there is a degree of oxidative stress that can affect the cells after the restoration of the blood flow. Therefore, the correct management of the condition that reduces reactive oxygen species production, such as controlled method of reperfusion, could be appropriate to prevent additional injuries.

Ischemia modified albumin in experimental ovarian torsion with and without controlled reperfusion

Purpose: Ovarian torsion, being a gynecological emergency, requires to be rapidly diagnosed and treated with minimal consequences on ovarian function after the removal of torsion. As ischemia modified albumin (IMA) is considered a good biomarker in diverse ischemic diseases, the aim of our study was to determine the effect of different ovarian torsion/detorsion models on serum and ovarian homogenates levels of IMA in an experimental study. Methods: IMA was measured in the serum and ovarian homogenates of 7 groups of female rats (10 animals in each group): 1 - control (no intervention); 2 - sham (only laparotomy); 3 - ischemia group: 3 hours ovarian torsion (OT); 4 - 3 hours OT (ischemia), 1 hour simple reperfusion; 5 - 3 hours ischemia, 1 hour controlled reperfusion that was assured during the first two minutes by opening and closing the clips on the ovarian pedicles in 10 seconds intervals, followed by simple reperfusion; 6 - 3 hours ischemia, 24 hours simple reperfusion; 7 - 3 hours OT, 24 hours controlled reperfusion. The results were analyzed by Welch’s ANOVA and Spearman correlation. Results: Ischemia increases the IMA in both serum and ovarian homogenates compared to control and sham groups. The controlled reperfusion groups had a statistically significant lower IMA in serum compared to simple reperfusion groups. IMA was found to be higher in the ovarian homogenates of simple reperfusion compared to controlled reperfusion groups. Conclusion: Our results suggest that controlled reperfusion prevent the processes that increase the IMA in ovarian torsion.