Exaggerated chronotropic and energetic response to dobutamine after orthotopic cardiac transplantation

After heart transplantation, the transplanted denervated heart displays both an exaggerated chronotropic and an exaggerated inotropic response to circulating catecholamines. This study assessed whether denervated transplanted hearts also display an exaggerated energetic response when challenged with dobutamine.

A total of 18 heart transplant recipients and 14 normal volunteers underwent measurements of myocardial oxygen consumption (MVO2), external work (EW), and pressure-volume area (PVA), at rest and during infusion of dobutamine. At rest, calculated myocardial (PVA/MVO2) and mechanical (EW/MVO2) efficiencies were similar among transplant recipients and normal volunteers. During low-dose dobutamine infusion (8 microg/kg/min), transplant recipients exhibited a larger increase in heart rate (to 126 +/- 14 vs 87 +/- 26 beats/min, p < 0.001) and MVO2 (to 269 +/- 43 vs 233 +/- 19 J/min/100g, p < 0.05) and a smaller increase in EW (64 +/- 18 vs 72 +/- 13 J/min/100g, p < 0.05) and PVA (70 +/- 16 vs 81 +/- 13 J/min/100g, p < 0.05) than did normal volunteers. As a result, both myocardial (26 +/- 4 vs 35 +/- 4%, p < 0.05) and mechanical (23 +/- 4 vs 30 +/- 4%, p < 0.001) efficiencies were lower during dobutamine infusion in transplant recipients than in normal volunteers. During the infusion of a higher dose of dobutamine (19 microg/kg/min), the chronotropic and inotropic responses of heart transplant recipients were even more exaggerated. The fall in myocardial efficiency induced by dobutamine correlated with the increase in heart rate (r = -0.58) and could be reproduced in normal volunteers by coadministration of atropine.

Transplant recipients exhibit a larger fall in contractile efficiency and a larger oxygen-wasting effect during dobutamine infusion than do normal volunteers. Because normal volunteers pre-medicated with atropine presented with a similar increase in heart rate and a similar fall in efficiency, the exaggerated energetic response of transplanted hearts to dobutamine likely resulted from the same mechanisms as their chronotropic supersensitivity, i.e., the loss of inhibitory parasympathetic innervation.