This document discusses, among other things, systems and methods to reduce ischemic or metabolic injury to a patient's heart. A system to reduce ischemic or metabolic injury to a patient's heart may include a pulse generator for generating electrical pulses or shock, a pacing lead with at least one pacing electrode configured to deliver electrical pulses received from the pulse generator to the patient's heart, a controller configured to control timing of electrical pulses to reduce wall stress of the heart, and a reservoir, fluidically coupled to a lumen and a pump, wherein the pump is configured, under control of the controller, to move contents from the reservoir through the lumen to an area of the heart with the reduced wall stress, wherein the contents include autologous respiration-competent mitochondria or other respiratory-promoting agents.