Chronic Intracerebroventricular Leptin Infusion Attenuates Cardiac Dysfunction After Myocardial Infarction

Abstract

Leptin is an important regulator of energy balance and substrate utilization in various tissues including the heart. In the present study we tested whether activation of leptin receptors in the central nervous system (CNS) confers protection against cardiac dysfunction after myocardial infarction (MI) induced by permanent ligation of the left anterior descending coronary artery (LAD). Male Sprague‐Dawley rats at 12 weeks of age were implanted with BP telemetry transmitters and an intracerebroventricular (ICV) cannula was inserted into the lateral ventricle. After 10 days of recovery, mean arterial pressure (MAP) and heart rate (HR) were measured 24‐hrs/day by telemetry and cardiac function was assessed by echocardiography (VisualSonics‐VEVO3100®). After stable baseline measurements for 4 days, the LAD was permanently ligated and saline vehicle (0.5 μL/hr, n=6) or leptin (15 μg/day, n=7) were infused ICV via osmotic minipump for 28 consecutive days. Compared to vehicle treatment, chronic ICV leptin infusion for 4 weeks markedly attenuated cardiac dysfunction caused by MI as evidenced by normalization of global cardiac radial strain (39±4 to 36±5 vs. 37±4 to 25±3 %), cardiac output (92±5 to 110±10 vs. 105±6 to 83±9 ml/min) and left atrium to aorta ratio, an index of cardiac congestion, (1.6±0.1 to 1.6±0.1 vs. 1.7±0.1 to 2.3±0.1). Central leptin administration also significantly improved ejection fraction (from 35±3 to 49±2 %) and fractional shortening (from 12.4±0.8 to 18.6±1.4 %, for week 1 and week 4 post‐MI, respectively), whereas no improvement was observed in vehicle‐treated rats (from 36±4 to 30±2 %, and from 12.2±1.7 to 10.1±1.3 %, respectively). In addition, ICV leptin infusion prevented the bradycardia observed in vehicle‐treated rats (354±3 to 370±6 vs. 360±7 to 323±6 bpm) but did not attenuate the reduction in MAP evoked by MI (101±4 to 94±3 vs. 102±3 to 97±2 mmHg). There was no difference in infarcted area between groups (30±3 vs. 29±5 %). These results indicate that leptin can improve cardiac function and attenuate progression of heart failure after MI via a CNS‐mediated mechanism.Support or Funding InformationNHLBI PO1HL51971, NIGMS P20GM104357 and NIGMS U54GM115428This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.