Adenosine cardioplegia: reducing reperfusion injury of the ischaemic myocardium?
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D H Boehm1, P A Human, U von Oppell
1Department of Cardiothoracic Surgery, University of Cape Town Medical School, South Africa.
Insights
Adenosine preserves cardiac function during ischemia by maintaining membrane potential, outperforming standard cardioplegic solutions. This cardioprotective effect is not solely due to its role in high-energy phosphate preservation.
Area of Science:
- Cardiology
- Biochemistry
- Physiology
Background:
- Standard cardioplegic arrest can lead to hypopolarization, increasing calcium influx during reperfusion and depleting high-energy phosphates.
- Adenosine has demonstrated potential in preserving membrane hyperpolarization and inducing rapid cardiac arrest in isolated heart models.
Purpose of the Study:
- To compare the efficacy of adenosine in preserving cardiac function and high-energy phosphates during global ischemia in an in situ baboon model.
- To evaluate adenosine's effectiveness when added to Krebs-Henseleit buffer (KHB) versus standard St. Thomas' Hospital solution No. 2 (ST2).
Main Methods:
- An in situ global ischemia model was used in baboons.
- Hearts were treated with ST2 (n=8), KHB (n=7), or KHB with 10 mM adenosine (ADO; n=8).
- Hemodynamic parameters, ultrastructure, and high-energy phosphate levels were assessed.
Main Results:
- Adenosine addition to KHB (ADO) significantly improved hemodynamic recovery (cardiac index, stroke volume index) compared to KHB alone.
- ADO's hemodynamic recovery was comparable to ST2, with no statistically significant differences in cardiac index, stroke volume index, or left ventricular dP/dt.
- Adenosine triphosphate (ATP) preservation was highest with ADO, though not statistically significant.
Conclusions:
- Adenosine, when added to KHB, offers significant cardioprotection and hemodynamic recovery during ischemia, comparable to ST2.
- The cardioprotective mechanism of adenosine likely involves pathways beyond its role as a high-energy phosphate precursor.
Abstract:
Hyperkalaemia-induced hypopolarization of the sarcolemnal membrane during standard crystalloid cardioplegic arrest potentiates calcium influx during reperfusion and is associated with depletion of high-energy phosphate reserves. Adenosine has been shown to induce fast cardiac arrest whilst preserving membrane hyperpolarization in an isolated rat heart model. In this study we compared the efficacy of adenosine, both as an arresting agent and as an ultrastructural, haemodynamic and high-energy phosphate preserving agent, in an in situ global ischemia model in the baboon with St. Thomas' Hospital solution No. 2 (ST2; n = 8) and with Krebs-Henseleit buffer (KHB; n = 7). The addition of 10 mM adenosine to the non-cardioplegic KHB (ADO; n = 8) improved haemodynamic recovery significantly in terms of cardiac index (91.6% +/- 7.2 vs 59.9% +/- 9.9) and stroke volume index (101.6% +/- 8.9 vs 55.6 +/- 10.0) and was not statistically distinguishable from the ST2 with regard to cardiac index (91.6% +/- 7.2 vs 94.8% +/- 5.8), stroke volume index (101.6% +/- 8.9 vs 114.0% +/- 8.3) or left ventricular dP/dt (73.1% +/- 9.9 vs 87.0% +/- 12.4). Adenosine triphosphate was best preserved with ADO (103.5% +/- 21.1 vs 67.9% +/- 9.3 and 48.5% +/- 8.7) although this was not statistically significant. This suggests therefore that the mechanism of cardioprotection by adenosine occurs by means other than its role as high-energy phosphate precursor.