Inhibition of sodium–glucose cotransporter-2 preserves cardiac function during regional myocardial ischemia independent of alterations in myocardial substrate utilization

Hana E. Baker, Alexander M. Kiel, Samuel T. Luebbe, Blake R. Simon, Conner C. Earl, Ajit Regmi, William C. Roell, Kieren Mather, Johnathan Tune, Adam G. Goodwill

Research output: Contribution to journalArticle

Abstract

The goal of the present study was to evaluate the effects of SGLT2i on cardiac contractile function, substrate utilization, and efficiency before and during regional myocardial ischemia/reperfusion injury in normal, metabolically healthy swine. Lean swine received placebo or canagliflozin (300 mg PO) 24 h prior to and the morning of an invasive physiologic study protocol. Hemodynamic and cardiac function measurements were obtained at baseline, during a 30-min complete occlusion of the circumflex coronary artery, and during a 2-h reperfusion period. Blood pressure, heart rate, coronary flow, and myocardial oxygen consumption were unaffected by canagliflozin treatment. Ventricular volumes remained unchanged in controls throughout the protocol. At the onset of ischemia, canagliflozin produced acute large increases in left ventricular end-diastolic and systolic volumes which returned to baseline with reperfusion. Canagliflozin-mediated increases in end-diastolic volume were directly associated with increases in stroke volume and stroke work relative to controls during ischemia. Canagliflozin also increased cardiac work efficiency during ischemia relative to control swine. No differences in myocardial uptake of glucose, lactate, free fatty acids or ketones, were noted between treatment groups at any time. In separate experiments using a longer 60 min coronary occlusion followed by 2 h of reperfusion, canagliflozin increased end-diastolic volume and stroke volume and significantly diminished myocardial infarct size relative to control swine. These data demonstrate that SGLT2i with canagliflozin preserves cardiac contractile function and efficiency during regional myocardial ischemia and provides ischemia protection independent of alterations in myocardial substrate utilization.

Original languageEnglish (US)
Article number25
JournalBasic Research in Cardiology
Volume114
Issue number3
DOIs
StatePublished - May 1 2019

Fingerprint

Myocardial Ischemia
Stroke Volume
Swine
Ischemia
Reperfusion
Myocardial Reperfusion Injury
Coronary Occlusion
Canagliflozin
Reperfusion Injury
Ketones
Nonesterified Fatty Acids
Oxygen Consumption
Lactic Acid
Coronary Vessels
Heart Rate
Hemodynamics
Stroke
Myocardial Infarction
Placebos
Blood Pressure

Keywords

  • Cardiac function
  • Fuel selection
  • Infarct
  • Myocardial ischemia
  • Pig
  • SGLT2 inhibition

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Inhibition of sodium–glucose cotransporter-2 preserves cardiac function during regional myocardial ischemia independent of alterations in myocardial substrate utilization. / Baker, Hana E.; Kiel, Alexander M.; Luebbe, Samuel T.; Simon, Blake R.; Earl, Conner C.; Regmi, Ajit; Roell, William C.; Mather, Kieren; Tune, Johnathan; Goodwill, Adam G.

In: Basic Research in Cardiology, Vol. 114, No. 3, 25, 01.05.2019.

Research output: Contribution to journalArticle

Baker, Hana E. ; Kiel, Alexander M. ; Luebbe, Samuel T. ; Simon, Blake R. ; Earl, Conner C. ; Regmi, Ajit ; Roell, William C. ; Mather, Kieren ; Tune, Johnathan ; Goodwill, Adam G. / Inhibition of sodium–glucose cotransporter-2 preserves cardiac function during regional myocardial ischemia independent of alterations in myocardial substrate utilization. In: Basic Research in Cardiology. 2019 ; Vol. 114, No. 3.
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AU - Kiel, Alexander M.

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AU - Simon, Blake R.

AU - Earl, Conner C.

AU - Regmi, Ajit

AU - Roell, William C.

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AU - Tune, Johnathan

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AB - The goal of the present study was to evaluate the effects of SGLT2i on cardiac contractile function, substrate utilization, and efficiency before and during regional myocardial ischemia/reperfusion injury in normal, metabolically healthy swine. Lean swine received placebo or canagliflozin (300 mg PO) 24 h prior to and the morning of an invasive physiologic study protocol. Hemodynamic and cardiac function measurements were obtained at baseline, during a 30-min complete occlusion of the circumflex coronary artery, and during a 2-h reperfusion period. Blood pressure, heart rate, coronary flow, and myocardial oxygen consumption were unaffected by canagliflozin treatment. Ventricular volumes remained unchanged in controls throughout the protocol. At the onset of ischemia, canagliflozin produced acute large increases in left ventricular end-diastolic and systolic volumes which returned to baseline with reperfusion. Canagliflozin-mediated increases in end-diastolic volume were directly associated with increases in stroke volume and stroke work relative to controls during ischemia. Canagliflozin also increased cardiac work efficiency during ischemia relative to control swine. No differences in myocardial uptake of glucose, lactate, free fatty acids or ketones, were noted between treatment groups at any time. In separate experiments using a longer 60 min coronary occlusion followed by 2 h of reperfusion, canagliflozin increased end-diastolic volume and stroke volume and significantly diminished myocardial infarct size relative to control swine. These data demonstrate that SGLT2i with canagliflozin preserves cardiac contractile function and efficiency during regional myocardial ischemia and provides ischemia protection independent of alterations in myocardial substrate utilization.

KW - Cardiac function

KW - Fuel selection

KW - Infarct

KW - Myocardial ischemia

KW - Pig

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