Calcium antagonists in myocardial ischemia/reperfusion—update 2012

Abstract

The present article briefly reviews the processes underlying excitation-contraction coupling in cardiomyocytes and vascular smooth muscle cells, their perturbations during reversible and irreversible myocardial ischemia and reperfusion, notably the pathogenetic role of increased intracellular calcium concentrations, and finally the beneficial effects of calcium antagonists on the impairment of coronary vasomotor tone, on cardiac contractile dysfunction and on myocardial infarction.

Effects of intravenous diltiazem in a rat model of experimental coronary thrombotic microembolism

“…It was also demonstrated that the number of red thrombi reduced immediately after diltiazem application in H&E-stained myocardial tissue, the ischemic area in HBFP-stained myocardial samples was reduced 3 h postinjection and the CVF in Masson-stained myocardial samples was reduced 28 days postinjection. These results are thus in line with previous findings showing that treatment of the ischemic myocardium with calcium channel blockers attenuates ultrastructural myocardial injury (41,42), decreases calcium influx (42,43) and improves postischemic left ventricular segmental function (43–48). The NF area was reduced but did not disappear completely in the CME+DIL group.…”

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

“…1,4-dihydropyridines, verapamil, or diltiazem). However, protection is consistently higher when treatment is started before or during early ischemia, with little benefit seen when the agents are given at reperfusion (Kleinbongard et al, 2012). Contrary to the promising experimental data, clinical trials in acute MI have been disappointing (Opie et al, 2000), probably because the agents need to be given before the onset of ischemia or during the early ischemic phase.…”

Time to Give Up on Cardioprotection?

“…181,200 The same may be true for β-blockade, specifically for metoprolol, 201 but β-blockade may also abrogate the protection by conditioning interventions. [202][203][204] Calcium antagonist pretreatment is associated with cardioprotection, 205 but calcium antagonists seem not to interfere with conditioning. 206 In antidiabetic treatment, there are the sulfonylureas that interfere with cardioprotective signaling because they inhibit ATP-dependent potassium channel activation, 187,207 whereas some glitazones, 208,209 the glucagonlike peptide 1 analog exenatide, [210][211][212] and some dipeptidyl peptidase 4 inhibitors 213,214 protect per se.…”