Preparatory Mindset

Paradoxically, RESTORING blood flow can cause MORE damage than the ischemia itself. This occurs because: (1) oxidative stress from sudden O₂ burst → free radicals, (2) calcium overload in cells, (3) inflammation from damaged tissue. Clinically relevant in MI (reperfusion injury after angioplasty), stroke (after thrombolysis), and transplant.

Core Concepts

• Ischemia = reduced blood flow → ↓ O₂ and nutrients.


• Reperfusion = restoration of flow, but paradoxically causes MORE damage.


• Three mechanisms: (1) Oxidative stress: sudden O₂ burst → superoxide, H₂O₂, OH• radicals → lipid peroxidation, DNA damage; (2) Calcium overload: ischemia damages Ca²⁺ pumps → ↑ intracellular Ca²⁺ → activates enzymes that damage cells; (3) Inflammation: damaged tissue releases DAMPs → neutrophil recruitment → more injury.


• Clinical scenarios: MI (reperfusion after angioplasty/thrombolysis), stroke (after tPA), organ transplant..

High-Yield Points

• Three mechanisms: oxidative stress (ROS), Ca²⁺ overload, inflammation


• Most clinically relevant in: MI (reperfusion), stroke (thrombolysis), transplant


• Prevention: gradual reperfusion, antioxidants, ischemic preconditioning

Topic Summary

IRI is paradoxically caused by restoring blood flow after ischemia. Mechanisms: oxidative stress, Ca²⁺ overload, inflammation. Clinical scenarios: MI reperfusion, stroke thrombolysis, organ transplantation.