Avtor/Urednik     Grašič-Kuhar, Cvetka; Budihna, Metka V; Zorc-Pleskovič, Ruda
Naslov     Mibefradil is more effective than verapamil for restoring post-ischemic function of isolated hearts of guinea pigs with acute renal failure
Tip     članek
Vir     Eur J Pharmacol
Vol. in št.     Letnik 488
Leto izdaje     2004
Obseg     str. 137-46
Jezik     eng
Abstrakt     The deleterious intracellular Ca2+ overload in the ischemic-reperfusion injury of the heart can be even more expressed in subjects with acute renal failure in whom maintenance of intracellular Ca2 + has already been disturbed in normoxia. To study the influence of acute renal failure in ischemic-reperfusion injury on the heart, we used isolated Langendorff's hearts of guinea pigs with gentamicin-induced acute renal failure. We examined arrhythmias, heart contractility and myocardial cell damage during reperfusion. Two specific Ca2+ channel antagonists, mibefradil (0.1 and 1 microM) and verapamil (0.1 microM), were used to test the possible involvement of T type and L-type Ca2+ channels in these processes. We exposed hearts to 50 min of zero-flow global ischemia and 60 min of reperfusion. During reperfusion, unrecoverable ventricular fibrillation appeared more often in hearts of animals with acute renal failure than in control hearts (80% vs. 0%, respectively). Mibefradil, but not verapamil, applied either pre- or post-ischemically, terminated ventricular fibrillation in all hearts of animals with acute renal failure. Mibefradil (0.1 microM only) improved contractility in hearts of animals with acute renal failure during reperfusion by 30%. During reperfusion, lactate dehydrogenase (LDH) release rate increased less in hearts of guinea pigs with acute renal failure than in control hearts and only verapamil decreased it additionally. Thus, our results suggest a more important role of T than of L-type Ca2+ channels in ischemic reperfusion injury in isolated guinea pig hearts with acute renal failure.
Deskriptorji     MYOCARDIAL ISCHEMIA
MYOCARDIAL REPERFUSION INJURY
VERAPAMIL
CALCIUM CHANNEL BLOCKERS
KIDNEY FAILURE, ACUTE
GUINEA PIGS
TACHYCARDIA, VENTRICULAR
VENTRICULAR FIBRILLATION
HEART RATE
BLOOD PRESSURE
LACTATE DEHYDROGENASE