Exaggerated chronotropic and energetic response to dobutamine after orthotopic cardiac transplantation

Background: After heart transplantation, the transplanted denervated heart displays both an exaggerated chronotropic and an exaggerated inotropic resp onse to circulating catecholamines. This study assessed whether denervated transplanted hearts also display an exaggerated energetic response when cha llenged with dobutamine. Methods and Results: A total of 18 heart transplant recipients and 14 norma l volunteers underwent measurements of myocardial oxygen consumption (MVO2) , external work (EW), and pressure-volume area (PVA), at rest and during in fusion of dobutamine. At rest, calculated myocardial (PVA/MVO2) and mechani cal (EW/MVO2) efficiencies were similar among transplant recipients and nor mal volunteers. During low-dose dobutamine infusion (8 mug/kg/min), transpl ant 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 norm al volunteers. During the infusion of a higher dose of dobutamine (19 mug/k g/min), the chronotropic and inotropic responses of heart transplant recipi ents were even more exaggerated. The fall in myocardial efficiency induced by dobutamine correlated with the increase in heart rate (r = -0.58) and co uld be reproduced in normal volunteers by coadministration of atropine. Conclusions: Transplant recipients exhibit a larger fall in contractile eff iciency 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 effi ciency, the exaggerated energetic response of transplanted hearts to dobuta mine likely resulted from the same mechanisms as their chronotropic superse nsitivity, i.e., the loss of inhibitory parasympathetic innervation.