Thorac Cardiovasc Surg 2008; 56 - V82
DOI: 10.1055/s-2008-1037800

Calcium sensitization impairs diastolic relaxation in post-ischemic myocardium: Implications for the use of Ca2+ sensitizing inotropes after cardiac surgery

YH Choi 1, I Friehs 2, DB Cowan 3, PJ del Nido 2, C Stamm 4
  • 1Universität zu Köln, Herz- und Thoraxchirurgie, Köln, Germany
  • 2Children's Hospital Boston, Cardiac Surgery, Boston, United States of America
  • 3Children's Hospital Boston, Cardiac Anaesthesia, Boston, United States of America
  • 4Deutsches Herzzentrum Berlin, Herz-, Thorax- und Gefäßchirurgie, Berlin, Germany

Objective: Calcium sensitizing inotropes such as Levosimendan are increasingly being used in cardiac surgical patients. Theoretically, increasing contractile protein sensitivity to Ca2+ prevents the Ca2+ elevation-associated arrhythmogenicity and potentiates the inotropic effect of catecholamines. On the other hand, we hypothesized that Ca2+ sensitization might exacerbate post-ischemic myocardial stunning by impairing diastolic relaxation.

Methods: In an isolated rabbit heart model, 45 minutes normothermic ischemia with potassium-induced cardioplegic arrest were followed by 120 minutes reperfusion. Isovolumetric LV contraction and relaxation as well as myocardial oxygen consumption (MVO2) were measured, and cytosolic Ca2+ was monitored by Rhod-2 spectrofluorometry. During reperfusion, ORG30029 was used as a model Ca2+ sensitizer (ORG, n=6), Ca2+ de-sensitization was induced with butanedione-monoxime (BDM, n=6=), and dopamine served as a representative catecholamine (n=6).

Results: As expected, ischemia/reperfusion induced moderate cytosolic calcium overload. Dopamine improved LV contractility and MVO2 by increasing the amplitude of the Ca2+ transient, but relaxation was unchanged due to faster diastolic Ca2+ removal. Dopamine-induced Ca2+ handling remained unchanged after uncoupling the Mg-ATPase with BDM, and MVO2 decreased in proportion with the reduced LV mechanical work load. ORG increased contractility without apparent effects on Ca2+ handling, and MVO2 remained constant despite increased contractile work. Conversely, relaxation ORG significantly impaired relaxation in post-ischemic hearts (rightward shift of the diastolic pressure-volume relationship), but not in non-ischemic control hearts

Conclusions: Calcium sensitization improves systolic function and energetic efficiency. However, Ca2+ sensitizers should be used with caution during post-ischemic reperfusion, because they may exacerbate myocardial stunning and thus impair cardiac output.