Signs and signals limiting myocardial damage using PICSO: a scoping review decoding paradigm shifts toward a new encounter.

BACKGROUND: Inducing recovery in myocardial ischemia is limited to a timely reopening of infarct vessels and clearing the cardiac microcirculation, but additional molecular factors may impact recovery.

OBJECTIVE: In this scoping review, we identify the paradigm shifts decoding the branching points of experimental and clinical evidence of pressure-controlled intermittent coronary sinus occlusion (PICSO), focusing on myocardial salvage and molecular implications on infarct healing and repair.

DESIGN: The reporting of evidence was structured chronologically, describing the evolution of the concept from mainstream research to core findings dictating a paradigm change. All data reported in this scoping review are based on published data, but new evaluations are also included.

RESULTS: Previous findings relate hemodynamic PICSO effects clearing reperfused microcirculation to myocardial salvage. The activation of venous endothelium opened a new avenue for understanding PICSO. A flow-sensitive signaling molecule, miR-145-5p, showed a five-fold increase in porcine myocardium subjected to PICSO.Verifying our theory of "embryonic recall," an upregulation of miR-19b and miR-101 significantly correlates to the time of pressure increase in cardiac veins during PICSO ( r 2  = 0.90, p  < 0.05; r 2  = 0.98, p  < 0.03), suggesting a flow- and pressure-dependent secretion of signaling molecules into the coronary circulation. Furthermore, cardiomyocyte proliferation by miR-19b and the protective role of miR-101 against remodeling show another potential interaction of PICSO in myocardial healing.

CONCLUSION: Molecular signaling during PICSO may contribute to retroperfusion toward deprived myocardium and clearing the reperfused cardiac microcirculation. A burst of specific miRNA reiterating embryonic molecular pathways may play a role in targeting myocardial jeopardy and will be an essential therapeutic contribution in limiting infarcts in recovering patients.