title: Short term effects of milrinone on biomarkers of necrosis, apoptosis, and inflammation in patients with severe heart failure.
abstract: BACKGROUND
  Inotropes are associated with adverse outcomes in heart failure (HF), raising concern they may accelerate myocardial injury. Whether biomarkers of myocardial necrosis, inflammation and apoptosis change in response to acute milrinone administration is not well established.
  
  
  METHODS
  Ten patients with severe HF and reduced cardiac output who were to receive milrinone were studied. Blood samples were taken just before initiation of milrinone and after 24 hours of infusion. Dosing was at the discretion of the patient's attending physician (range 0.25-0.5 mcg/kg/min). Plasma measurements of troponin, myoglobin, N-terminal-pro-BNP, interleukin-6, tumor necrosis factor-alpha, soluble Fas, and soluble Fas-ligand were performed at both time points.
  
  
  RESULTS
  Troponin was elevated at baseline in all patients (mean 0.1259 +/- 0.17 ng/ml), but there was no significant change after 24 hours of milrinone (mean 0.1345 +/- 0.16 ng/ml, p = 0.44). There were significant improvements in interleukin-6, tumor necrosis factor-alpha, soluble Fas, and soluble Fas-ligand (all p < 0.05) indicative of reduced inflammatory and apoptotic signaling compared to baseline.
  
  
  CONCLUSIONS
  In conclusion, among patients with severe HF and low cardiac output, ongoing myocardial injury is common, and initiation of milrinone did not result in exacerbation of myocardial injury but instead was associated with salutary effects on other biomarkers.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Henry Ford Hospital, Detroit, Michigan, USA. dlanfea1@hfhs.org
authors.forename: David E
authors.initials: DE
authors.lastname: Lanfear
authors.forename: Reema
authors.initials: R
authors.lastname: Hasan
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: Celeste
authors.initials: C
authors.lastname: Williams
authors.forename: Barbara
authors.initials: B
authors.lastname: Czerska
authors.forename: Cristina
authors.initials: C
authors.lastname: Tita
authors.forename: Rasha
authors.initials: R
authors.lastname: Bazari
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000627:therapeutic use*; D009336:Necrosis / Q000188:drug therapy; D012720:Severity of Illness Index; D012995:Solubility; D013997:Time Factors; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019014:fas Receptor / Q000097:blood
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D053222:Fas Ligand Protein; D015850:Interleukin-6; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D020105:Milrinone