Introduction:

We have developed an implantable device for dynamic flavin adenine dinucleotide (FAD) measurements in cardiac tissue. FAD fluorescence provides a label-free optical readout and can be used to assess metabolic changes during ischemia, reperfusion, and pharmacologically induced alterations in coronary perfusion. The device is designed for direct placement on the heart surface, enabling real-time monitoring of relative FAD levels in both ex vivo and in vivo cardiac models.

Aims:

The aim of this study was to perform dynamic FAD measurements from the heart using an implantable, suturable device format. This approach was designed to enable continuous monitoring of changes in myocardial FAD levels under controlled ischemic and perfusion-modifying conditions.

Methods:

FAD measurements were performed in one canine model, two porcine models, and one declined donor human heart maintained in an ex vivo perfusion system. In the canine model, the obtuse marginal branch was ligated to mimic localized myocardial ischemia. In the porcine models, acetylcholine injections were performed to induce coronary vascular responses and assess corresponding changes in FAD signals. In the ex vivo human heart model, perfusion was transiently interrupted for defined intervals to evaluate changes in FAD levels during ischemia and reperfusion. The implantable LED sensor array was positioned on the epicardial surface to record dynamic relative FAD signals under these experimental conditions.

Results:

Dynamic changes in relative FAD levels were successfully recorded in both in vivo large animal models and the ex vivo human heart model. In the canine ischemia model, local coronary ligation produced measurable alterations in FAD signal consistent with regional metabolic changes. In the porcine models, acetylcholine administration was associated with detectable changes in relative FAD levels during pharmacologically induced vascular responses. In the ex vivo human heart, transient interruption and restoration of perfusion resulted in dynamic FAD signal changes during ischemia-reperfusion intervals.

Conclusions:

This study demonstrates the feasibility of an implantable, suturable cardiac sensor array for dynamic measurement of relative FAD levels on the heart surface. The device enables real-time assessment of metabolic changes in both in vivo large animal models and an ex vivo human heart preparation. These findings support further development of implantable optical technologies for monitoring myocardial metabolism during ischemia, reperfusion, and altered coronary perfusion.

The animal studies were performed in compliance with animal protocols. The human donor heart was declined for transplant and hereby considered discarded tissue.

https://www.science.org/doi/full/10.1126/sciadv.ads8608 – features the previous version of the device.