Troponin Release and Reversible Left Ventricular Dysfunction After Transient Pressure Overload

AbstractBackground

The authors previously demonstrated that brief ischemia elicits cardiac troponin I (cTnI) release and myocyte apoptosis in the absence of necrosis. It remains uncertain whether other pathophysiological stresses can produce apoptosis and transient cTnI release without ischemia.

Objectives

This study sought to determine whether a transient increase in left ventricular (LV) preload elicits cTnI release in the absence of ischemia.

Methods

Propofol-anesthetized swine (N = 13) received intravenous phenylephrine (PE) (300 μg/min) for 1 h to increase left ventricular end-diastolic pressure (LVEDP) to ~30 mm Hg. Serial cTnI and echocardiographic function were assessed for 24 h, and myocardial tissue was analyzed for apoptosis and necrosis.

Results

PE infusion increased systolic blood pressure from 137 ± 14 mm Hg to 192 ± 11 mm Hg (mean ± SD; p < 0.001) and increased LVEDP from 17 ± 2 mm Hg to 30 ± 5 mm Hg (p < 0.001). Myocardial flow measurements demonstrated no evidence of ischemia. Hemodynamics normalized rapidly after PE, but LV ejection fraction remained depressed (32 ± 21% vs. 58 ± 7%; p < 0.01) with normalization after 24 h (51 ± 16%; p = 0.31). Baseline transcoronary cTnI release was low (16 ± 20 ng/l) but increased to 856 ± 956 ng/l (p = 0.01) 1 h after LVEDP elevation. Circulating cTnI rose above the 99th percentile within 30 min and remained elevated at 24 h (1,462 ± 1,691 ng/l). Pathological analysis demonstrated myocyte apoptosis at 3 h (31.3 ± 11.9 myocytes/cm² vs. 4.6 ± 3.7 myocytes/cm²; p < 0.01), that normalized after 24 h (6.2 ± 5.6 myocytes/cm²; p = 0.46) without histological necrosis.

Conclusions

Transient elevations of LVEDP lead to cTnI release, apoptosis, and reversible stretch-induced stunning in the absence of ischemia. Thus, preload-induced myocyte injury may explain many cTnI elevations seen in the absence of clinical signs or symptoms of myocardial ischemia.

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