Effect of isoproterenol on the cardiac troponin I degradation and release during early TNFalpha-induced ventricular dysfunction in isolated rabbit heart.
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.
Felten
Marie-Louise
ML
Laboratoire d'Anesthésie, Faculté de Médecine, Université de Paris-Sud, Le Kremlin Bicêtre, France.
Cosson
Claudine
C
Charpentier
Julien
J
Paradis
Valérie
V
Benhamou
Dan
D
Mazoit
Jean-Xavier
JX
Edouard
Alain R
AR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005602:France; D006335:Heart Injuries / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007261:Infusions, Intra-Arterial; D007545:Isoproterenol / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011817:Rabbits; D019210:Troponin I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology
D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester