A 40-year-old man underwent cardiac transplantation two years ago and now has a completely denervated donor heart. During graded exercise testing, his cardiac output rises normally. The immediate mediator of this increase in contractility is:

• A Norepinephrine released from cardiac sympathetic nerve endings
• B Vagal withdrawal at the SA node
• C Increased venous return via the Frank-Starling mechanism alone
• D Circulating catecholamines acting on cardiac beta-1 receptors ✓

Explanation

The transplanted heart has no autonomic innervation, so neural mechanisms are absent. Its chronotropic and inotropic responses depend entirely on circulating adrenal catecholamines acting on beta-1 receptors, giving a slower onset than normal. Option C contributes through preload, but the inotropic component requires catecholamines. Vagal withdrawal and local norepinephrine release both require intact cardiac nerves, so they cannot operate.

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

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