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[Diltiazem abolishes the effect of ryanodine in St. Thomas' Hospital cardioplegic solution on the post-ischemic
H Yamamoto1, H Ichikawa, F Yamamoto
1Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan.
Insights
Ryanodine in cardioplegic solution enhances heart protection during ischemia. Diltiazem, an L-type calcium channel blocker, did not improve ryanodine
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Context:
- Myocardial reperfusion can lead to intracellular calcium overload.
- Calcium-induced calcium release (CICR) from the sarcoplasmic reticulum (SR) may deplete SR calcium during cardioplegia.
- This depletion might offer protection against calcium overload.
Purpose:
- To investigate if ryanodine in cardioplegic solution improves myocardial protection.
- To determine the effect of diltiazem, an L-type calcium channel blocker, on ryanodine-enhanced cardioprotection.
Summary:
- Isolated working rat hearts were perfused and infused with St. Thomas' Hospital cardioplegic solution containing ryanodine (1.75 nmol/L) with or without varying concentrations of diltiazem.
- Hearts were then subjected to global ischemia and reperfusion.
- Ryanodine alone improved aortic flow recovery and reduced creatine kinase leakage compared to control. Diltiazem at 0.13 mumol/L, 0.25 mumol/L, and 0.50 mumol/L did not further enhance the protective effects of ryanodine.
Impact:
- Ryanodine-containing cardioplegic solution demonstrates potential for enhanced myocardial protection.
- Diltiazem does not appear to augment the cardioprotective benefits of ryanodine in this model.
- Findings contribute to understanding calcium handling in myocardial preservation strategies.
Abstract:
Calcium-induced calcium release (CICR) from sarcoplasmic reticulum (SR) may contribute to calcium depletion of SR during the infusion of cardioplegic solution, which may protect the intracellular calcium overload observed during myocardial reperfusion. We have, therefore, investigated (1) the ability of ryanodine-containing cardioplegic solution to enhance myocardial protection and (2) the influence of diltiazem, L-type calcium channel blocker, on the ryanodine-enhanced cardioprotective effect in the isolated working rat heart. Hearts (n = 6-8/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer (Ca2+ = 2.4 mM). This was followed by a 3 min infusion of St. Thomas' Hospital cardioplegic solution containing (1) 0 nmol/L of ryanodine or (2) 1.75 nmol/L of ryanodine combined with various concentrations of diltiazem (0, 0.13, 0.25 and 0.50 mumol/L). Hearts were then subjected to 40 min of normothermic (37 degrees C) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). (1) The recovery of aortic flow (%AF) was 52.2 +/- 3.5% in the ryanodine-free group. (2) %AF was 72.0 +/- 1.4%, 50.0 +/- 2.6*, 61.7 +/- 3.2* and 58.3 +/- 2.8*% in the 0, 0.13, 0.25 and 0.50 mumol/L diltiazem groups, respectively (*p < 0.05 vs the 0 mumol/L diltiazem group). Creatine kinase (CK) leakage during Langendorff reperfusion was less in the 0 mumol/L diltizaem (plus 1.75 nmol/L ryanodine) group than the ryanodine-free group.(ABSTRACT TRUNCATED AT 250 WORDS)