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| Content Provider | PubMed Central |
|---|---|
| Author | Liu, H. Cala, P. M. Anderson, S. E. |
| Abstract | The results of the GUARDIAN/EXPEDITION trials demonstrate the need for more precisely controlled studies to inhibit Na/H exchange (NHE1) during ischemia/reperfusion. This is because overwhelming evidence is consistent with the hypothesis that myocardial ischemic injury results in part from increases in intracellular Na (Nai) mediated by Na/H exchange (NHE1) that in turn promote Na/Ca exchanger (NCX) mediated increases in intracellular Ca ([Ca]i) and Ca-dependent cell damage. We used a more potent and specific NHE1 inhibitor HOE 694 (HOE) to test whether inhibition of NHE1 during ischemia limits increases in Nai and [Ca]i in newborns. NMR was used to measure pHi, Nai, [Ca]i, and ATP in isolated newborn rabbit hearts. Perfusion pressure (PP) and left ventricular developed pressure (LVDP) and CK were measured. HOE was added before global ischemia. Results are reported as mean±SE. Nai (mEq/kg dry wt) rose from 11.6±0.9 prior to ischemia to 114.0±16.1 at the end of ischemia and recovered to 55.2±11.8 in the control group. During ischemia and reperfusion the corresponding values for Nai in the HOE group (63.1±8.4 and 15.9±2.5, respectively, p<0.05) were lower than control. In the control group [Ca]i (nM/L) rose from 331±41 to 1069±71 and recovered to 814±51 whereas in the HOE group [Ca]i rose less (p<0.05): 359±50, 607±85 and 413±40, respectively. Total CK release was significantly reduced in the HOE group. PP and LVDP also recovered significantly better in the HOE group than control. In conclusion, NHE1 inhibition diminishes ischemia-induced increases in Nai and therefore [Ca]i and thus diminishes myocardial injury in neonatal hearts. |
| Related Links | http://dx.doi.org/10.1097/fjc.0b013e3181cb599f |
| Ending Page | 233 |
| Page Count | 7 |
| Starting Page | 227 |
| File Format | |
| ISSN | 01602446 |
| e-ISSN | 15334023 |
| Journal | Journal of cardiovascular pharmacology |
| Issue Number | 3 |
| Volume Number | 55 |
| Language | English |
| Publisher Date | 2010-03-01 |
| Access Restriction | Open |
| Subject Keyword | Pharmacology Cardiology and Cardiovascular Medicine Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Cardiology and Cardiovascular Medicine |
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