Differences in protective profiles of diltiazem isomers in ischemic and reperfused guinea pig hearts.
The effects of L-cis and D-cis diltiazem on the extracellular potassium concentration ([K(+)]e), pH and cardiac function were compared in ischemic guinea pig hearts. Before inducing ischemia, L-cis diltiazem (10 and 30 microM) reduced the left ventricular developed pressure (LVDP) with a marginal inhibition of heart rate (HR), whereas lower doses of the D-cis isomer decreased both LVDP and HR. L-cis Diltiazem only slightly inhibited the increase in [K(+)]e and the decrease in pH but significantly inhibited ischemic contractures in contrast to the marked inhibition of these parameters produced by even low doses of the D-cis isomer. Notably, at equipotent doses for the ischemic parameters, L-cis diltiazem restored the left ventricular end-diastolic pressure (LVEDP) and HR after reperfusion to a greater extent than the D-cis isomer. These results suggest that the L-cis isomer may specifically improve postischemic function, in addition to the modest action on [K(+)]e and pH, in guinea pig hearts.
Sato
Ryuichi
R
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan. ryuuichi-satou@zeria.co.jp
Sakamoto
Kenji
K
Yamazaki
Jun
J
Nagao
Taku
T
D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects; D002317:Cardiovascular Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004110:Diltiazem / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007536:Isomerism; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D002317:Cardiovascular Agents; D004110:Diltiazem; D011188:Potassium