FINAL REVIEW OF LITERATURE
In 1986, Murry and associates demonstrated that a brief period of repetitive myocardial ischemia/reperfusion exerted a powerful protection against a subsequent sustained period of ischemia1. Until that, IPC has been used to protect against Ischemia Reperfusion Injury (IRI) of multiple organs in the body, such as brain, kidney, skeletal muscle, liver and intestine2. Although IPC research has the potential to open a new avenue in the management of IRI, few established therapeutic strategies are based on IPC, mainly because classical IPC requires an intervention which must be implemented before the onset of the index ischemia3.
In 1993, Przyklenk and colleagues developed the idea of remote preconditioning. By an in vivo canine model, they found that brief ischemia of the circumflex artery could reduce subsequent infarct size in the territory of the left anterior descending artery; the process was termed as intra organ preconditioning4. Subsequently in a series of experiments thereafter a concept was made that transient ischemia of other organs can induce protection against subsequent myocardial ischemia.
In 2002, Kharbanda et al. produced remote ischemic preconditioning (RIPC) with tourniquet occlusion of blood flow to one hind limb of an experimental pig model; they concluded that the method might provide cardio protection, as evidenced by reducing the magnitude of ventricular dysfunction during ischemia and sparing subsequent infarct size after reperfusion5. The beneficial effects of limb ischemic preconditioning on myocardial IRI were also demonstrated by Dong et al in 20046.
In 2003, Zhao et al evolved the concept of ischemic post conditioning (IPOC), there work concluded that repetitive ischemia applied during early reperfusion, i.e., post conditioning (Post-con), is cardio-protective by attenuating reperfusion injury and post-con is as effective as pre conditioning in reducing infarct size and preserving endothelial function7. Short cycles of ischemia and reperfusion applied at the onset of reperfusion have also been shown to be successful in reducing the IRI in both animal models and clinical trials8. IPOC is certainly clinically more relevant than IPC, as it constitutes a natural protective mechanism that can be triggered during the clinically applicable period of reperfusion9.
Subsequently, the concept of a clinically applicable remote ischemic conditioning evolved from that of IPC. Brief controlled episodes of intermittent ischemia of arms or legs are used as a mechanism to confer a powerful systemic protection against prolonged ischemia in a distant organ, this conditioning referred as remote ischemia preconditioning (RIPC) or remote ischemia post conditioning (RIPOC) can be performed before or after a prolonged distant organ ischemia respectively10.
In 2005, Kerendi et al in a rat model demonstrated the beneficial effect of RIPOC. In their study, the RIPOC algorithm consisted of a 5-minute occlusion and 1 minute reperfusion of the renal artery before blood flow restoration to the left coronary artery reduced the infarct size nearly 50% compared to abrupt reperfusion11. In 2007, Andreka et al reported a similar myocardial infarct sparing effect after applying repeated limb ischemia/reperfusion as RIPOC in a porcine IRI model12.
In 2009, Gritsopoulos et al compared the differences in cardio protective effects between RIPOC and IPOC in a rabbit model, they found RIPOC, including four cycles of 1 minute of ischemia and 1 minute of reperfusion, of carotid artery could confer a stronger cardio protection than classical IPOC13.
In 2009, Gyurkovics et al in their study showed that post conditioning of a distant organ, the lower limb in this study could attenuate the reperfusion syndrome. In this study, experimental rats were subjected to 180 minutes of bilateral lower limb ischemia using an infrarenal cross-clamping of the abdominal aorta and 240 minutes of reperfusion14. The analysis reported a considerable improvement in distant organ function after post conditioning14.
In 2007, Loukogeorgakis et al conducted the first human study to compare the protective effects of RIPC and RIPOC and to show that RIPOC can be induced by transient limb ischemia. In this study of 19 health volunteers RIPOC was induced by inflating a blood pressure cuff for 5 minutes then deflated for 5 minutes. Their results showed that RIPOC was effective in preventing endothelial IRI injury, and both RIPOC and RIPC had similar effects15.
In 2009, S.P. Hoole et al performed the CRISP study which assessed the ability of remote ischemic pre conditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. Two hundred forty-two patients undergoing elective PCI were recruited in this study. Subjects were randomized to receive remote IPC (induced by three 5-minute inflations of a blood pressure cuff to 200 mm Hg around the upper arm, followed by 5-minute intervals of reperfusion) or control (an un inflated cuff around the arm) before arrival in the cath lab16. The primary outcome of the study was cTnI at 24 hours after PCI. The study concluded that remote ischemic preconditioning reduces ischemic chest discomfort during PCI and attenuates procedure-related cTnI release, and also appears to reduce subsequent cardiovascular events16.
In 2010, Botker et al performed a large clinical trial to evaluate the effect of RIPOC on clinical outcomes. In their study of 333 consecutive adult patients with first acute myocardial infarction were randomly assigned to receive primary percutaneous coronary intervention with or without RIPOC. RIPOC in this study was produced by intermittent arm ischemia through four cycles of 5-minute inflation and then 5-minute deflation with the blood-pressure cuff. Their results showed increased myocardial salvage in patients offered RIPOC therapy during transport to the hospital and before primary percutaneous coronary intervention17.
Studies have presented even long term results and benefits of post conditioning, in there study in 2010 Santiago Garcia et. al showed that a simple post conditioning protocol applied at the onset of mechanical reperfusion, resulted in reduction of infarct size, better epicardial and myocardial flow, and improvement in left ventricular function18. In this study the beneficial effects of post conditioning on cardiac function were shown to persist beyond 3 years.
The concept of conditioning the heart to prevent especially the ischemia reperfusion injury have evolved considerably through preconditioning, post conditioning and remote ischemic post conditioning. Although the concept has been tested positively in various studies with primary percutaneous intervention (PCI) and in stable angina patients undergoing PCI, there is still no clinical study, evaluating the concept in patients undergoing thrombolysis.
Our study aimed to study the concept of RIPOC in patients undergoing thrombolysis, as in our country thrombolysis is still offered to large number of patients with acute ST elevation myocardial infarction.