Adaptive Reductions in Left Ventricular Diastolic Compliance Protect the Heart From Stretch-Induced Stunning

Visual Abstract

Highlights

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  A transient elevation in preload produces mechanical stretch-induced myocyte injury and measurable cardiac troponin I release that is associated with reversible contractile dysfunction and myocyte apoptosis.

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  Using a porcine model of intermittent pressure overload, this study demonstrates that repetitive exposure to cyclical elevations in preload elicits significant myocyte loss, yet left ventricular systolic function is preserved and chamber dilatation is absent.

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  Instead, myocardial remodeling characterized by myocyte hypertrophy and interstitial fibrosis produces a reduction in left ventricular diastolic compliance that protects the heart from subsequent stretch-induced myocyte injury.

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  These results support a novel paradigm that links cardiac adaptations to repetitive stretch-induced injury with the pathogenesis of myocardial stiffening and may explain how reductions in left ventricular diastolic compliance can occur in the absence of sustained hypertension or anatomic hypertrophy.

Summary

Swine subjected to 2 weeks of repetitive pressure overload (RPO) exhibited significant myocyte loss, but left ventricular (LV) systolic function was preserved, and chamber dilatation did not occur. Instead, myocardial remodeling characterized by myocyte hypertrophy and interstitial fibrosis led to a marked reduction in LV diastolic compliance, which protected the heart from stretch-induced myocyte injury and preserved LV ejection fraction without anatomic LV hypertrophy. These results support a novel paradigm that links cardiac adaptations to RPO with the pathogenesis of reduced LV diastolic compliance and may explain how LV stiffening can occur in the absence of sustained hypertension or anatomic hypertrophy.