PMID- 14620386
OWN - NLM
STAT- MEDLINE
DCOM- 20040316
LR  - 20190917
IS  - 0277-0008 (Print)
IS  - 0277-0008 (Linking)
VI  - 23
IP  - 11
DP  - 2003 Nov
TI  - Effects of the angiotensin II subtype 1 receptor antagonist losartan on 
      functional recovery of isolated rat hearts undergoing global myocardial 
      ischemia-reperfusion.
PG  - 1401-10
AB  - STUDY OBJECTIVE: To investigate the effects of the angiotensin II subtype 1 
      receptor (AT1R) antagonist losartan on functional recovery of isolated rat hearts 
      undergoing global myocardial ischemia-reperfusion compared with myocardial 
      protective effects of ischemic preconditioning. DESIGN: Ex vivo experiment using 
      isolated perfused rat heart. SETTING: Academic laboratory. INTERVENTION: Hearts 
      from Sprague-Dawley rats were perfused with oxygenated Krebs-Henseleit buffer and 
      randomized to one of four groups: time control, vehicle, ischemic 
      preconditioning, or losartan. MEASUREMENTS AND MAIN RESULTS: After randomization, 
      hearts underwent 30 minutes of global ischemia followed by 30 minutes of 
      reperfusion. Changes in end-diastolic pressure (EDP), left ventricular developed 
      pressure (LVDP), and infarct size were examined between treatment groups by 
      two-way analysis of variance with repeated measures. Cardiac angiotensin II 
      receptor (ATR) density and infarct size were measured in control hearts and in a 
      subgroup of hearts exposed to ischemia-reperfusion injury. Total ATR density and 
      percentage of myocardial AT1R were increased in hearts exposed to 
      ischemia-reperfusion. Myocardial ischemia-reperfusion injury resulted in a 56% 
      reduction in LVDP from baseline in hearts randomized to vehicle. However, it 
      declined by only 22% and 28% in hearts randomized to ischemic preconditioning and 
      losartan, respectively. Compared with vehicle, both ischemic preconditioning and 
      losartan decreased EDP (ischemic preconditioning 39 +/- 3 mm Hg, losartan 54 +/- 
      5 mm Hg, vs vehicle 78 +/- 8 mm Hg), and reduced infarct size (ischemic 
      preconditioning 9%, losartan 12%, vs vehicle 36%). CONCLUSION: Treatment of 
      isolated rat hearts with losartan before ischemia-reperfusion injury resulted in 
      significant cardioprotection similar to that observed with ischemic 
      preconditioning.
FAU - Flynn, Jeremy D
AU  - Flynn JD
AD  - Division of Pharmacy Practice and Science, College of Pharmacy, University of 
      Kentucky, Lexington 40536-0082, USA.
FAU - Akers, Wendell S
AU  - Akers WS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacotherapy
JT  - Pharmacotherapy
JID - 8111305
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - *Angiotensin II Type 1 Receptor Blockers
MH  - Animals
MH  - Heart/*drug effects/physiology
MH  - Ischemic Preconditioning, Myocardial/methods
MH  - Losartan/metabolism/*pharmacology/*therapeutic use
MH  - Male
MH  - Myocardial Reperfusion Injury/*drug therapy/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Angiotensin, Type 1/metabolism
EDAT- 2003/11/19 05:00
MHDA- 2004/03/17 05:00
CRDT- 2003/11/19 05:00
PHST- 2003/11/19 05:00 [pubmed]
PHST- 2004/03/17 05:00 [medline]
PHST- 2003/11/19 05:00 [entrez]
AID - 10.1592/phco.23.14.1401.31947 [doi]
PST - ppublish
SO  - Pharmacotherapy. 2003 Nov;23(11):1401-10. doi: 10.1592/phco.23.14.1401.31947.