Changes in rat heart histomorphometry due to two-week dietary restriction

Area of Science:

• Toxicology
• Cardiovascular Pathology
• Preclinical Safety Assessment

Background:

• Differentiating direct drug effects from nutritional impacts on organ weights in preclinical studies is challenging.
• Reduced food consumption, body weight, and organ weight are common findings in safety studies.
• Heart weight changes due to feed restriction require careful interpretation.

Purpose of the Study:

• To investigate the impact of feed restriction on heart histology and histomorphometry in rats.
• To establish criteria for distinguishing compound-induced cardiac effects from nutritional deficits.
• To evaluate myofiber width and myofiber:interstitium ratio under varying dietary conditions.

Main Methods:

• Rats were subjected to 2-week feed restriction at 100%, 75%, 50%, and 25% of ad libitum intake.
• Histologic evaluation of heart sections stained with hematoxylin and eosin.
• Computer-assisted image analysis of picrosirius red-stained sections for myofiber width and myofiber:interstitium ratio.

Main Results:

• No histological differences were observed among dietary groups.
• The myofiber:interstitium ratio remained consistent across groups.
• Significant reduction in myofiber width was observed in groups with 50% and 25% feed intake compared to controls.
• Myofiber width decreased with increasing dietary restriction.

Conclusions:

• Feed restriction significantly impacts rat heart myofiber width.
• In preclinical studies, a feed intake reduction <50% leading to decreased myofiber width may suggest a direct test article effect.
• Reductions in myofiber width with feed intake reduction >=50% could be attributed to nutrition alone or combined effects.