PMID- 17874219
OWN - NLM
STAT- MEDLINE
DCOM- 20080515
LR  - 20181113
IS  - 0172-0643 (Print)
IS  - 0172-0643 (Linking)
VI  - 29
IP  - 1
DP  - 2008 Jan
TI  - Inhibition of the Na+/H+ exchanger protects the immature rabbit myocardium from 
      ischemia and reperfusion injury.
PG  - 113-20
AB  - BACKGROUND: This study investigated the cardioprotective effects of pharmacologic 
      pretreatment with HOE642, a selective Na(+)/H(+ )exchanger (NHE) isoform-1 
      inhibitor, in immature rabbit hearts, as compared with ischemic preconditioning 
      (IPC). METHODS: For this study, 36 isolated immature New Zealand white rabbit 
      hearts were equilibrated on the Langendorff apparatus. They were randomly divided 
      into three groups: control group, IPC group, and HOE642 group. The hearts in each 
      group were subjected to 60 min of ischemia plus 60 min of reperfusion (I/R). In 
      the IPC group, the hearts were preconditioned by 5 min of ischemia followed by 10 
      min of reperfusion before I/R. In the HOE642 group, the hearts were pretreated 
      with HOE642 (5 mumol/l) for 15 min before I/R. Left ventricular performance 
      (LVDP, +dp/dt(max), -dp/dt(max)), coronory artery flow (CF), myocardial water 
      content, adenosine triphosphate (ATP), cardiac-specific enzymes (creatine kinase 
      [CK], CK fraction MB [CK-MB], and lacate dehydrogenase [LDH]), and intracellular 
      calcium content were measured. Myocardial ultrastructure was observed under 
      transmission electron microscopy. RESULTS: The recovery rates for left 
      ventricular performance and CF in both the HOE642 and the IPC groups increased 
      compared with those for the control subjects (p < 0.05). Moreover, the recovery 
      rates for LVDP, +dp/dt(max), -dp/dt(max), and CF in the HOE642 group were 
      markedly higher than in the IPC group at most time points of reperfusion (p < 
      0.05). Compared with the control group, CK, CK-MB, and LDH in the HOE642 group 
      were decreased significantly (p < 0.05), whereas only LDH was reduced in the IPC 
      group (p < 0.05). Water content was significantly reduced and ATP reserve was 
      significantly increased in both the IPC and HOE642 groups (p < 0.05). However, 
      compared with the IPC group, water content in the HOE642 group was significantly 
      lower (81.26% +/- 1.26% vs 83.58% +/- 1.27%; p < 0.05) and ATP was significantly 
      higher (21.46 +/- 2.40 vs 17.66 +/- 1.50 mug/g; p < 0.05). The HOE642 
      pretreatment exerted a better effect of reducing calcium overload than IPC (265.8 
      +/- 41.1 vs 408.5 +/- 56.8 mg/kg dry weight; p < 0.05). The blinded 
      ultrastructural assessment under transmission electron microscopy showed that 
      HOE642 brought about more myocyte salvage than IPC. CONCLUSION: This study 
      demonstrated that HOE642 pretreatment is superior to IPC against ischemia and 
      reperfusion injury in isolated immature rabbit myocardium.
FAU - Zhou, R-H
AU  - Zhou RH
AD  - Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan 610041, China.
FAU - Long, C
AU  - Long C
FAU - Liu, J
AU  - Liu J
FAU - Liu, B
AU  - Liu B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070915
PL  - United States
TA  - Pediatr Cardiol
JT  - Pediatric cardiology
JID - 8003849
RN  - 0 (Anti-Arrhythmia Agents)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Guanidines)
RN  - 0 (SLC9A1 protein, human)
RN  - 0 (Sodium-Hydrogen Exchanger 1)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 0 (Sulfones)
RN  - 7E3392891K (cariporide)
SB  - IM
MH  - Animals
MH  - Anti-Arrhythmia Agents/pharmacology/*therapeutic use
MH  - Cation Transport Proteins/*antagonists & inhibitors
MH  - Guanidines/pharmacology/*therapeutic use
MH  - *Ischemic Preconditioning, Myocardial
MH  - Myocardial Reperfusion Injury/*prevention & control
MH  - Rabbits
MH  - Sodium-Hydrogen Exchanger 1
MH  - Sodium-Hydrogen Exchangers/*antagonists & inhibitors
MH  - Sulfones/pharmacology/*therapeutic use
EDAT- 2007/09/18 09:00
MHDA- 2008/05/16 09:00
CRDT- 2007/09/18 09:00
PHST- 2007/02/15 00:00 [received]
PHST- 2007/06/27 00:00 [accepted]
PHST- 2007/04/25 00:00 [revised]
PHST- 2007/09/18 09:00 [pubmed]
PHST- 2008/05/16 09:00 [medline]
PHST- 2007/09/18 09:00 [entrez]
AID - 10.1007/s00246-007-9072-4 [doi]
PST - ppublish
SO  - Pediatr Cardiol. 2008 Jan;29(1):113-20. doi: 10.1007/s00246-007-9072-4. Epub 2007 
      Sep 15.