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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.
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