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An innovative biologic system for photon-powered myocardium in the ischemic heart.

ABSTRACT: Coronary artery disease is one of the most common causes of death and disability, afflicting more than 15 million Americans. Although pharmacological advances and revascularization techniques have decreased mortality, many survivors will eventually succumb to heart failure secondary to the residual microvascular perfusion deficit that remains after revascularization. We present a novel system that rescues the myocardium from acute ischemia, using photosynthesis through intramyocardial delivery of the cyanobacterium Synechococcus elongatus. By using light rather than blood flow as a source of energy, photosynthetic therapy increases tissue oxygenation, maintains myocardial metabolism, and yields durable improvements in cardiac function during and after induction of ischemia. By circumventing blood flow entirely to provide tissue with oxygen and nutrients, this system has the potential to create a paradigm shift in the way ischemic heart disease is treated.

SUBMITTER: Cohen JE

PROVIDER: S-EPMC5470824 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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An innovative biologic system for photon-powered myocardium in the ischemic heart.

Cohen Jeffrey E JE Goldstone Andrew B AB Paulsen Michael J MJ Shudo Yasuhiro Y Steele Amanda N AN Edwards Bryan B BB Patel Jay B JB MacArthur John W JW Hopkins Michael S MS Burnett Casey E CE Jaatinen Kevin J KJ Thakore Akshara D AD Thakore Akshara D AD Farry Justin M JM Truong Vi N VN Bourdillon Alexandra T AT Stapleton Lyndsay M LM Eskandari Anahita A Fairman Alexander S AS Hiesinger William W Esipova Tatiana V TV Patrick William L WL Ji Keven K Shizuru Judith A JA Woo Y Joseph YJ

Science advances 20170614 6

Coronary artery disease is one of the most common causes of death and disability, afflicting more than 15 million Americans. Although pharmacological advances and revascularization techniques have decreased mortality, many survivors will eventually succumb to heart failure secondary to the residual microvascular perfusion deficit that remains after revascularization. We present a novel system that rescues the myocardium from acute ischemia, using photosynthesis through intramyocardial delivery o ...[more]

PMID: 28630913

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Project description:AimRecent studies demonstrate that sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i), two classes of antidiabetic drugs, are cardioprotective. However, the mechanisms of these benefits and their comparative efficacy remain unclear. We aimed to compare the effects of these antidiabetic agents on cardiac function, perfusion, and microvascular density using a swine model of chronic myocardial ischemia.MethodsChronic myocardial ischemia was induced in Yorkshire swine by ameroid constrictor placement to the left circumflex artery. Two weeks later, pigs were administered vehicle ("CON", 8 pigs), 300 mg SGLT2i canagliflozin, ("CANA", 8 pigs), or 100 mg DPP4i sitagliptin ("SIT", 5 pigs) daily. Five weeks later, pigs were euthanized. Cardiac function, perfusion, collateralization, and protein expression were determined by pressure-volume catheter, microsphere analysis, immunofluorescence, and immunoblotting, respectively.ResultsCompared with SIT, CANA was associated with improved stroke volume and cardiac output, with a trend towards reduced left ventricular stiffness. Both CANA and SIT trended towards improved perfusion compared to CON, but there were no differences between the two treatment groups. SIT was associated with improved capillary density with a trend towards improved arteriolar density compared to CANA. Both CANA and SIT were associated with increased expression of vascular endothelial cadherin compared to CON, without differences in treatment groups. SIT pigs had decreased 5' adenosine monophosphate-activated protein kinase activation compared to CON and CANA. There was a trend towards increased endothelial nitric oxide synthase activation in the SIT group compared to CON. There were no differences in activation of extracellular signal-regulated kinase 1/2 across groups.ConclusionsIn the setting of chronic myocardial ischemia, canagliflozin is associated with improved cardiac function compared to sitagliptin, with similar effects on perfusion despite differences in microvascular collateralization.

Dataset Information

An innovative biologic system for photon-powered myocardium in the ischemic heart.

Publications

An innovative biologic system for photon-powered myocardium in the ischemic heart.

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