Procaine in Cardioplegia: Does It Affect the Endothelial Function?

Abstract

Objective: Cardioplegic solutions are widely used in cardiac surgery and hyperkelemia in cardioplegia has been demonstrated to impair the endothelium-derived hyperpolarizing factor (EDHF)-mediated endothelial function. The present study examined the effect of procaine in St. Thomas Hospital Cardioplegia on the EDHF-mediated response in porcine coronary arteries. Methods: Isometric force study: Porcine coronary micro-arteries were studied in a myograph. Two rings taken from the same artery (diameter 200–450 μm, n = 8) were incubated with Kreb's solution as control or Kreb's solution plus procaine (1 mM) at 37 °C for 1 h, respectively. The EDHF-mediated relaxation was induced by bradykinin (BK, −10 ∼−6.5 log M) in the presence of indomethacin (Indo, 7 μM), NG-nitro-L-arginine (L-NNA, 300 μM), and hemoglobin (HbO, 20 μM) after U46619-precontraction (−8 log M). Electrophysiological study: The membrane potential of a single smooth muscle cell in coronary arteries was measured by a microelectrode after superfusion with Kreb's solution or Kreb's containing procaine (1 mM) for 1 h. Results: Procaine had little effect on the resting force of porcine coronary micro-arteries (0.94 ± 0.74 mN vs. 0.67 ± 0.23 mN in control, P > 0.05) and did not alter the U46619-induced precontraction (10.7 ± 1.7 mN vs. 12.0 ± 1.7 mN, P > 0.05). The BK-induced, EDHF-mediated relaxation was increased by the treatment with procaine with the EC50 shifted leftward (97.3 ± 0.6% vs. 83.0 ± 5.1% at −7 log M and 99.4 ± 0.6% vs. 96.7 ± 1.6% at −6.5 log M, P 0.05) and decreased the BK-induced hyperpolarization from −70.3 ± 0.4 mV to −68.0 ± 0.8 mV (−7 log M, P < 0.05) and from −72.3 ± 0.7 mV to −68.8 ± 0.8 mV (−6.5 log M, P < 0.01). Conclusions: In the coronary arteries, procaine has depolarizing effect but it enhances the EDHF-mediated relaxation. Therefore, addition of procaine in cardioplegia may preserve the EDHF-mediated endothelial function.