Long‐term consequences of severe food restriction on the heart of female Fischer rats

Abstract

IntroductionIndividuals under voluntary (e.g., anorexia, crash diets) or involuntary (e.g., very low food security) severe food restriction (sFR) are at increased risk for developing cardiovascular disease during the sFR period and also long term well after the sFR period has ended. During the sFR period patients present long QT interval, arrhythmia, hypotension and bradycardia and sometimes death, which is primarily due to heart failure. Unfortunately, Little is known, however, almost nothing is known about the heart function when these individuals recoveries the body weight. Cardiovascular disease due to earlier exposure to sFR is an underappreciated and understudied problem and there are no Aim: ‐consequencesof sFR on heart structure and function known therapeutic strategies designed to prevent or reverse the increased risk after recovery from the sFR period(s).MethodsFemale Fischer rats with 3‐month‐old were divided in a control (CT) (ad libitum regular chow; n=18) and sFR (60% reduction of daily food intake, n=18) group. After 2 weeks all rats received regular chow ad libitum for 3 months. The control and sFR rats were then divided into three groups each and infused with vehicle (n=8), in a bolus infusion of angiotensin II (400ng/Kg – 0.2mL; n=6), or subjected to ischemia‐reperfusion using a Langendorff preparation (n=4). At the end of the experiment, the rats were sacrificed and the hearts were removed for histology.ResultsAfter 14 of sFR body weight was reduced by 18%, Mean arterial pressure (p=0.03), heart rate (p=0.03) and wet heart weight (p=0.009) were reduced. After 3 mo of refeeding, body weight, MAP, HR, and wet heart weight were indistinguishable from the control animals. Despite normalization of some parameters,, 3 months of refeeding, analysis of H&E stained myocardium tissue in vehicle‐treated rats revealed that parallel orientation of myofiber and clear striations present in normal cardiomyocytes were lost in sFR‐refed animals indicating severe cardiac damage. Uneven blood‐filling of the vessels of the microcirculatory and prominent interstitial edema of the myocardium was observed. The cardiomyocytes were polymorphic and single cardiomyocytes also found to be atrophied. Infusion of angiotensin II to sFR‐refed animals, but not to control animals, resulted in the occurrence of focal necrotic lesions causing by multiple contractures of cardiomyocytes, indicating cardiomyocytes had disrupted of calcium homeostasis and increased calcium sensitivityof sFR‐refed animals. The magnitude of ischemia/reperfusion‐induced damage was also greater in sFR‐refed animals compared to control animals in Langendorff preparations. After ischemia/reperfusion injury, along with deeply eosinophilic myofibers, large amounts of necrotic cardiomyocytes were found in sFR‐refed rats, but not in control.ConclusionDespite normalization of body weight, blood pressure, heart rate and wet heart weight after 3 months of refeeding, the hearts from animals subjected to severe food restriction are severely damaged. These findings suggest individuals who have recovered from prior exposure to a period of sFR are at increased risk of developing cardiovascular disease.Support or Funding InformationNIH 1R01HL119380 (KS)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.