The Frank-Starling mechanism is assessed in a patient with isolated left ventricular systolic dysfunction. At a given afterload and contractility, increasing preload from 8 mmHg to 14 mmHg LVEDP increases stroke volume from 60 to 80 mL. Beyond which physiological point does further preload increase stop improving or reduce stroke volume, and what is the mechanism?

• A Beyond LVEDP of 20 mmHg, calcium channels in the sarcoplasmic reticulum are inactivated by phospholamban, preventing calcium release and thus reducing contractility
• B Excessive preload activates cardiac stretch receptors that trigger parasympathetic bradycardia, reducing cardiac output despite increased filling
• C Beyond optimal preload, nitric oxide released from endocardial endothelium diffuses into cardiomyocytes and activates guanylate cyclase, directly reducing contractility
• D Beyond optimal sarcomere length (~2.2 µm), further stretch reduces overlap between thick and thin filaments, reducing cross-bridge formation and active tension (descending limb); however, in the intact heart, the descending limb is rarely reached physiologically — diastolic failure and pulmonary oedema occur first at high filling pressures ✓

Explanation

The Frank-Starling mechanism depends on sarcomere length: optimal overlap of actin-myosin at ~2.2 µm maximises cross-bridge cycling and tension. In isolated muscle, the 'descending limb' at sarcomere lengths >2.4 µm shows reduced tension as filament overlap diminishes. In the intact heart under physiological conditions, the descending limb is not reached before other limiting factors (pericardial constraint, diastolic dysfunction, pulmonary oedema) intervene. High filling pressures do not primarily inactivate SR Ca2+ channels via phospholamban — phospholamban normally inhibits SERCA2a (relieved by PKA phosphorylation). Cardiac stretch receptors (Bainbridge reflex) cause tachycardia, not bradycardia. Endocardial NO modulation of contractility is a minor effect and not the primary Starling mechanism failure point.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.