title: Human myocardial morphologic and functional changes in the first 24 hours after doxorubicin administration.
abstract: The purpose of this study was to document early structural changes in the human heart after the initial administration of doxorubicin. Endomyocardial biopsies were performed at baseline and at 4 and 24 hours after doxorubicin administration to 13 patients. Morphometric analysis of electron micrographs (x 31,200) quantitated mitochondrial and tubular sizes (sarcoplasmic reticulum and T tubules). The mitochondrial size increased from 0.25 +/- 0.01 mu 2 (mean +/- SE) at baseline to 0.27 +/- 0.03 mu 2 (not significant [NS]) at 4 hours and 0.30 +/- 0.03 mu 2 (NS) at 24 hours. The tubular size increased from 2.24 +/- 0.13 x 10(4) nm2 at baseline to 2.60 +/- 0.26 x 10(4) nm2 (P less than 0.05) at 4 hours and 2.46 +/- 0.29 x 10(4) nm2 (NS) at 24 hours. Micrographs analyzed for nuclear changes showed nucleolar contraction and segregation of granular and fibrillar components. These changes were noted in five of ten patients at 4 hours and in eight of 13 patients at 24 hours. Serial echocardiographic and systolic time interval determinations of left ventricular function demonstrated a significant improvement at both 4 and 24 hours. In conclusion, doxorubicin has its most significant effect on tubular structures. Left ventricular function improved during this time despite these findings.
mesh_terms: D000328:Adult; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000473:pathology; D002466:Cell Nucleolus / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000648:ultrastructure; D009206:Myocardium / Q000648:ultrastructure*; D012519:Sarcoplasmic Reticulum / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D004317:Doxorubicin