Short term effects of milrinone on biomarkers of necrosis, apoptosis, and inflammation in patients with severe heart failure.
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.
Lanfear
David E
DE
Department of Internal Medicine, Division of Cardiology, Henry Ford Hospital, Detroit, Michigan, USA. dlanfea1@hfhs.org
Hasan
Reema
R
Gupta
Ramesh C
RC
Williams
Celeste
C
Czerska
Barbara
B
Tita
Cristina
C
Bazari
Rasha
R
Sabbah
Hani N
HN
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
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