Abstract
BackgroundCardioplegia and reperfusion of the myocardium may be associated with cardiomyocyte apoptosis and subsequent myocardial injury. In order to establish a pharmacological strategy for the prevention of these events, this study aimed to verify the reliability of our human cardiac model and to evaluate the pro-apoptotic properties of the sphingolipid second messenger ceramide and the anti-apoptotic properties of the acid sphingomyelinase inhibitor amitryptiline during simulated cardioplegia and reperfusion ex vivo.MethodsCardiac biopsies were retrieved from the right auricle of patients undergoing elective CABG before induction of cardiopulmonary bypass. Biopsies were exposed to ex vivo conditions of varying periods of cp/rep (30/10, 60/20, 120/40 min). Groups: I (untreated control, n = 10), II (treated control cp/rep, n = 10), III (cp/rep + ceramide, n = 10), IV (cp/rep + amitryptiline, n = 10) and V (cp/rep + ceramide + amitryptiline, n = 10). For detection of apoptosis anti-activated-caspase-3 and PARP-1 cleavage immunostaining were employed.ResultsIn group I the percentage of apoptotic cardiomyocytes was significantly (p < 0.05) low if compared to group II revealing a time-dependent increase. In group III ceramid increased and in group IV amitryptiline inhibited apoptosis significantly (p < 0.05). In contrast in group V, under the influence of ceramide and amitryptiline the induction of apoptosis was partially suppressed.ConclusionCeramid induces and amitryptiline suppresses apoptosis significantly in our ex vivo setting. This finding warrants further studies aiming to evaluate potential beneficial effects of selective inhibition of apoptosis inducing mediators on the suppression of ischemia/reperfusion injury in clinical settings.
Highlights
Cardioplegia and reperfusion of the myocardium are essential techniques employed in many cardiac surgical procedures when a temporarily arrested myocardium is required
We conducted this study to clarify if another pathway of apoptosis induction in cardiomyocytes exists
Our aim was to evaluate during ex vivo simulated cardioplegia and reperfusion the effect of the sphingolipid second messenger ceramide and the anti-apoptotic properties of the sphingomyelinase inhibitor amitryptiline respectively the end-point apoptosis induction and reduction in cardiomyocytes which to our knowledge has not been described in such an experimental setting yet
Summary
Cardioplegia and reperfusion of the myocardium are essential techniques employed in many cardiac surgical procedures when a temporarily arrested myocardium is required. Our present pilot study was performed just as a sequel to our recent work [6,7,8] to further evaluate our presented human cardiac model during simulated cardioplegia and reperfusion ex vivo respectively the end-points feasibility and reliability. Our aim was to evaluate during ex vivo simulated cardioplegia and reperfusion the effect of the sphingolipid second messenger ceramide and the anti-apoptotic properties of the sphingomyelinase inhibitor amitryptiline respectively the end-point apoptosis induction and reduction in cardiomyocytes which to our knowledge has not been described in such an experimental setting yet. In order to establish a pharmacological strategy for the prevention of these events, this study aimed to verify the reliability of our human cardiac model and to evaluate the pro-apoptotic properties of the sphingolipid second messenger ceramide and the anti-apoptotic properties of the acid sphingomyelinase inhibitor amitryptiline during simulated cardioplegia and reperfusion ex vivo
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