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Inhibition of Sodium Glucose Cotransporters Improves Cardiac Performance.

ABSTRACT: The sodium-glucose cotransporter (SGLT) inhibitors represent a new alternative for treating patients with diabetes mellitus. They act primarily by inhibiting glucose reabsorption in the renal tubule and therefore, decreasing blood glucose levels. While little is yet known about SGLT subtype 1, SGLT2 inhibitors have demonstrated to significantly reduce cardiovascular mortality and heart failure hospitalizations. This cardioprotective benefit seems to be independent of their glucose-lowering properties; however, the underlying mechanism(s) remains still unclear and numerous hypotheses have been postulated to date. Moreover, preclinical research has suggested an important role of SGLT1 receptors on myocardial ischemia. Following acute phase of cardiac injury there is an increased activity of SGLT1 cotransport that ensures adequate energy supply to the cardiac cells. Nonetheless, a long-term upregulation of this receptor may not be that beneficial and whether its inhibition is positive or not should be further addressed. This review aims to present the most cutting-edge insights into SGLT receptors.

SUBMITTER: Garcia-Ropero A

PROVIDER: S-EPMC6651487 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Inhibition of Sodium Glucose Cotransporters Improves Cardiac Performance.

García-Ropero Álvaro Á Vargas-Delgado Ariana P AP Santos-Gallego Carlos G CG Badimon Juan J JJ

International journal of molecular sciences 20190704 13

The sodium-glucose cotransporter (SGLT) inhibitors represent a new alternative for treating patients with diabetes mellitus. They act primarily by inhibiting glucose reabsorption in the renal tubule and therefore, decreasing blood glucose levels. While little is yet known about SGLT subtype 1, SGLT2 inhibitors have demonstrated to significantly reduce cardiovascular mortality and heart failure hospitalizations. This cardioprotective benefit seems to be independent of their glucose-lowering prope ...[more]

PMID: 31277431

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Project description:Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF.We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction <40%, (2) acute pulmonary oedema or respiratory failure of predominantly cardiac origin requiring mechanical ventilation and (3) currently receiving vasopressor and/or inotropic support. Patients in the intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours. The control group received only a 3 ml/kg bolus of Hartmann's solution without continuous infusion. The primary outcome was CO assessed by transthoracic echocardiography 24 hours after randomisation. Secondary outcomes included a measure of right ventricular systolic function (tricuspid annular plane systolic excursion (TAPSE)), acid-base balance, electrolyte and organ function parameters, along with length of stay and mortality.The infusion of half-molar sodium lactate increased (mean?±?SD) CO from 4.05?±?1.37 L/min to 5.49?±?1.9 L/min (P?<?0.01) and TAPSE from 14.7?±?5.5 mm to 18.3?±?7 mm (P?=?0.02). Plasma sodium and pH increased (136?±?4 to 146?±?6 and 7.40?±?0.06 to 7.53?±?0.03, respectively; both P?<?0.01), but potassium, chloride and phosphate levels decreased. There were no significant differences in the need for vasoactive therapy, respiratory support, renal or liver function tests, duration of ICU and hospital stay or 28- and 90-day mortality.Infusion of half-molar sodium lactate improved cardiac performance and led to metabolic alkalosis in AHF patients without any detrimental effects on organ function.Clinicaltrials.gov NCT01981655. Registered 13 August 2013.

Dataset Information

Inhibition of Sodium Glucose Cotransporters Improves Cardiac Performance.

Publications

Inhibition of Sodium Glucose Cotransporters Improves Cardiac Performance.

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