Transient elevation of left ventricular preload using phenylephrine increased transcoronary cTnI release from 16 to 856 ng/l (p=0.01) and induced reversible myocyte apoptosis without ischemia.
Does transient elevation of left ventricular preload elicit cardiac troponin I release and myocyte apoptosis in the absence of ischemia in a swine model?
Transient elevations of LVEDP lead to cTnI release, apoptosis, and reversible stretch-induced stunning in the absence of ischemia, providing a mechanistic explanation for troponin elevations seen without clinical signs of myocardial ischemia.
Absolute Event Rate: 856% vs 16%
p-value: p=0.01
BACKGROUND 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.
Weil et al. (Fri,) conducted a other in Transient pressure overload (n=13). Intravenous phenylephrine vs. Baseline was evaluated on Transcoronary cardiac troponin I (cTnI) release 1 h after LVEDP elevation (p=0.01). Transient elevation of left ventricular preload using phenylephrine increased transcoronary cTnI release from 16 to 856 ng/l (p=0.01) and induced reversible myocyte apoptosis without ischemia.