Key result
Isoproterenol triggers selective cTnI release and proteolysis alongside myocardial contraction bands in TNFalpha-induced LV dysfunction.
Why the study?
The effects of early TNFalpha-induced left ventricular dysfunction and its treatment by isoproterenol on cardiac troponin I degradation and release were not well characterized.
Does isoproterenol treatment of TNFalpha-induced LV dysfunction cause myocardial injury in isolated rabbit hearts?
Does isoproterenol treatment of TNFalpha-induced LV dysfunction cause myocardial injury in isolated rabbit hearts?
Myocardial injury in severe sepsis may be driven by TNFalpha enhancing the effects of isoproterenol rather than direct early cytotoxicity of TNFalpha.
May indicate TNFα potentiates isoproterenol cardiotoxicity in sepsis models; hypothesis-generating for human septic cardiomyopathy mechanisms.
We studied the consequences of an early phase of TNFalpha-induced LV dysfunction and of its treatment by isoproterenol on an isolated rabbit heart preparation. Two dosages of TNFalpha (2 and 4 microg) were infused, followed by isoproterenol (ISO), infused by increasing concentrations from 10 to 10 M. Left ventricular developed pressure (DP) was recorded. Creatine kinase (CKtot) and cardiac Troponin I (cTnI) were measured in the effluent perfusate. An anatomic score was calculated by histologic examination of the hearts while a structural analysis of cTnI was done. TNFalpha induced a dose-dependent decrease in DP (-43 +/- 18% for 4 microg) without change in coronary vascular resistances, which was not followed by biochemical or structural abnormalities. TNFalpha reduced the maximum effect (Emax) of ISO on DP (mean DeltaDPmaxISO = -40% for 4 microg) without change in the concentration leading to half Emax (ED50ISO). ISO treatment of TNFalpha (4 microg)-induced LV dysfunction resulted in a selective release of cTnI, myocardial tissue contraction bands, and a significant proteolysis of cTnI. Within the limits of the model, the myocardial injury reported during severe sepsis would not be related to an early cytotoxic effect of TNFalpha but could be attributed to an enhancement of the effects of isoproterenol by TNFalpha.
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Felten et al. (2004) studied TNFalpha-induced LV dysfunction. Isoproterenol following TNFalpha infusion was evaluated on Left ventricular developed pressure (DP) and cardiac Troponin I (cTnI) release. Isoproterenol treatment of TNFalpha-induced LV dysfunction resulted in a selective release and significant proteolysis of cTnI, alongside myocardial tissue contraction bands.
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