HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Nathalie Roy Ingeborg Friehs Pedro J. del Nido Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Roy, N. Articles by del Nido, P. J. Search for Related Content PubMed PubMed Citation Articles by Roy, N. Articles by del Nido, P. J. Related Collections Myocardial protection

Ann Thorac Surg 2006;82:2192-2199
© 2006 The Society of Thoracic Surgeons

---

Original Articles: Cardiovascular

Dopamine Induces Postischemic Cardiomyocyte Apoptosis In Vivo: An Effect Ameliorated by Propofol

^a Department of Cardiac Surgery, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts
^b Department of Anesthesiology, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts
^c Department of Orthopedic Surgery, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts

Accepted for publication June 27, 2006.

^_* Address correspondence to Dr del Nido, Department of Cardiac Surgery, Children’s Hospital Boston, 300 Longwood Ave, Bader-2, Boston, MA 02115 (Email: pedro.delnido{at}tch.harvard.edu).

BACKGROUND: Dopamine is commonly used to improve postischemic myocardial contractile function. However, there is evidence that dopamine augments apoptosis after ischemia through increased intracellular calcium and opening of the mitochondrial permeability transition pore. Propofol (2,6-diisopropylphenol) is an anesthetic that has been shown to prevent mitochondrial permeability transition pore opening. We evaluated the effects of propofol given during reperfusion on dopamine-mediated apoptosis.

METHODS: Hearts from 8-week-old inbred New Zealand White rabbit siblings were subjected to 2 hours of cold cardioplegic ischemia and 6 hours of reperfusion in a heterotopic transplant model. Controls consisted of the recipient rabbit’s nonischemic heart. The ischemia-reperfusion (IR) group consisted of postischemic hearts reperfused with no drugs; the IR plus dopamine (IR+D) group received dopamine (20 µg · kg^–1 · min^–1) continuously; the IR+D plus propofol (IR+D+P) group received dopamine (20 µg · kg^–1 · min^–1) plus propofol (500 to 600 µg · kg^–1 · min^–1); and the IR plus propofol (IR+P) group received propofol only (500 to 600 µg · kg^–1 · min^–1) throughout reperfusion (n = 7 to 9 in each group). Myocardial function was measured using a left ventricular balloon; terminal nick-end labeling (TUNEL) staining, DNA electrophoresis, and immunoblotting for caspase-3 cleavage were performed at the end of reperfusion.

RESULTS: Dopamine increased the number of TUNEL-positive nuclei significantly (14.0 ± 2.0/1,000 for IR+D versus 6.7 ± 2.0/1,000 for IR, p = 0.01). Propofol (IR+D+P) reduced the total number of apoptotic cells in hearts receiving dopamine (7.1 ± 1.8/1,000, p = 0.01 versus IR+D) to the extent seen in IR alone. DNA laddering and caspase-3 cleavage were observed at greater frequency in the IR+D group compared with the IR and IR+D+P groups. Propofol had no effect on dopamine-mediated increased systolic function, but improved diastolic function after ischemia.

CONCLUSIONS: Dopamine infusion has a positive inotropic effect on the postischemic heart at the expense of increased cardiomyocyte apoptosis. The addition of propofol prevents dopamine-induced apoptosis after ischemia while maintaining positive inotropy.