Can you have re-perfusion injury without ischaemia? 

Although most of the damage occurs after reperfusion, without any reperfusion the limb would turn black and "fall off", and the reperfusion injury to the limb involves intracellular mechanisms triggered by the build-up of products of anaerobic metabolism. Elsewhere in the body, the response has to be triggered by reperfusion as the triggers produced by ischaemia have to get to the cells responsible for the mediator responses.

Reperfusion injury is more damaging. As during ischemia there is energy depletion which results in secretion of various chemical messengers. During reperfusion these chemical messengers are the main reason behind the injury, as they move with reflow of blood and there is alteration in membrane polarizaion of various cell, which leads to fatal effect of reperfusion.

It is generally accepted that reperfusion is more damaging becouse of oxidative stress which occurs when oxigenized blood  comes to ischemized area. One ove the mechanisms of that - mitichondria start to produce ROS that induce mitochondria permeability transition pores opening and induction of necrosis or apoptosis. Additionally there are many other biochemical changes are present. Thus, the cell might die if only some protective mechanisms are not activated.

This is question without a clear black or white answer. Each organ has its own susceptibility for ischemia (e.g. brain vs leg). The other point is that a systemic reaction like MOF can both result from ischemic damage as from reperfusion damage (we measured Arterial Venous concentration differences over the reperfused kidney during organ transplant and found prominent cytokine release that appears to reflect a response to ischemia rather than reperfusion PMID:19459788 ; whereas reperfusion injury appears to relate to a metabolic defect PMID: 27188504 it is unclear to me how this would result in MOF).Note that we did not find indications for neutrophil, thrombocyte or complement activation in the reperfused organ.

Besides we do not find indications for gross oxidative stress during clinical reperfusion; as such a putative central role for ROS in human I/R is questionable. PMID: 23305329; 28031169; 26999803. This notion is supported by the consistent failure of clinical trials studying antioxidant-based therapy.

Thanks, Christopher C Rout, Amit Kumar, Yulia Goshovska, Jan H Lindeman for taking the trouble to answer this query. My impression was that reperfusion phase causes maximum tissue damage and ROS play the key role but experimental results are showing that metabolites rather than ROS play the crucial role. Thanks for enlightening me.