Improvement of human myocardial mitochondria after dobutamine: a quantitative ultrastructural study

Dobutamine is a new inotropic agent that may induce prolonged clinical improvement in patients with congestive cardiomyopathy. Sixteen patients with severe heart failure but without obstructive coronary disease were studied by serial functional class determinations and by noninvasive measurements of left ventricular function before and after bedrest control period and then after a 3-day infusion of dobutamine. An endomyocardial biopsy procedure was performed on 11 patients before and after the bedrest and on all 16 patients before and after dobutamine. Quantitative ultrastructural analysis of the biopsies was performed on electron micrographs (31,200 X) by a grid technique. The number of electron dense particles per 100 mitochondria did not change after bedrest but there was a significant decrease from 84 +/- 14 to 65 +/- 12 (P < .005) in the pre- to postdobutamine biopsies. The cristae to matrix ratio of the mitochondria did not change with bedrest but improved from 0.37 +/- 0.04 to 0.47 +/- 0.05 (P < .02) after dobutamine. The average mitochondrial size did not change significantly in the bedrest control nor in the dobutamine biopsy samples. However, when the 16 patients were divided into those who had a good clinical response (by functional class and noninvasive measurements of left ventricular function) and those who had no or little response, the 10 responders did decrease their average mitochondria size from 0.26 +/- 0.03 mu 2 to 0.23 +/- 0.02 mu 2 (P < .02). The mechanism by which a 3-day infusion of dobutamine induces a prolonged clinical improvement is not well understood. The use of quantitative ultrastructural technique in this study has demonstrated that there is a morphologic basis to the improvement.