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The temperature-sensitivity of slow channel calcium blockers in relation to their effect upon the calcium paradox. Eur Heart J 1983 Dec;4 Suppl H:97-103

Date

12/01/1983

Pubmed ID

6662136

DOI

10.1093/eurheartj/4.suppl_h.97

Scopus ID

2-s2.0-0021014317   4 Citations

Abstract

The isolated perfused rat heart preparation was used to investigate the interrelationship between temperature and the ability of calcium antagonists to reduce protein leakage in the calcium paradox. Exploiting the fact that although the calcium depletion phase of calcium paradox-injury is highly temperature sensitive, the calcium repletion phase, during which time the injury is manifested, is temperature independent. Verapamil (4 mumol l-1) included in a 10 min period of calcium depletion (37 degrees C) and a 20 min period of calcium repletion (37 degrees C) was known to reduce cumulative protein leakage by 22 +/- 3%. With calcium depletion again at 37 degrees C but repletion at 21 degrees C verapamil failed to achieve any reduction in protein leakage despite the fact that leakage in the 21 degrees C control group did not differ significantly from that in the 37 degrees C control group. Temperature-response studies (repletion temperature of 4, 10, 21, 23, 25, 28, 31, 34 and 37 degrees C) revealed an abrupt loss of drug effect below 25 degrees C. Studies with D600 (10 mumol l-1), nifedipine (4 mumol l-1), terodiline (4 mumol l-1) fendiline (20 mumol l-1) and diltiazem (2 mumol l-1) revealed that while all of these drugs reduced protein leakage at 37 degrees C (24 +/- 3%, 31 +/- 2%, 31 +/- 3%, 23 +/- 3% and 29 +/- 3%, respectively), like verapamil they had no effect at 21 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List

Baker JE, Hearse DJ

Author

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Calcium Channel Blockers
Dose-Response Relationship, Drug
Hypothermia
Kinetics
Male
Myocardial Contraction
Proteins
Rats
Rats, Inbred Strains
Temperature
Verapamil
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a