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Ischemic preconditioning: effects on pH, Na and Ca in newborn rabbit hearts during Ischemia/Reperfusion
H Liu1, P M Cala, S E Anderson
1Department of Human Physiology, One Shields Avenue, University of California, Davis, CA 95616-8644, USA.
Insights
Ischemic preconditioning (PC) protects newborn rabbit hearts from ischemia-reperfusion injury by maintaining higher intracellular pH and reducing sodium and calcium accumulation. This protective effect improves functional recovery and reduces cardiac enzyme release.
Area of Science:
- Cardiology
- Physiology
- Biochemistry
Background:
- Ischemic preconditioning (PC) in adult hearts reduces ischemia-induced intracellular pH, calcium, and sodium changes, mitigating injury.
- Age-related differences in myocardial responses to ischemia necessitate investigation into PC effects on newborn hearts.
Purpose of the Study:
- To test the hypothesis that PC diminishes intracellular hydrogen, sodium, and calcium levels during ischemia-reperfusion in newborn rabbit hearts.
- To evaluate the impact of PC on myocardial function and injury markers in the neonatal heart.
Main Methods:
- Utilized Nuclear Magnetic Resonance (NMR) to measure intracellular pH (pHi), sodium (Nai), and calcium (Ca]i) in isolated newborn rabbit hearts.
- Employed Langendorff perfusion system with controlled ischemia-reperfusion protocols.
- Assessed left-ventricular developed pressure (LVDP) and creatine kinase (CK) release as functional and injury markers.
Main Results:
- PC hearts exhibited higher pHi at the end of ischemia compared to control hearts (6.31 vs. 5.83).
- PC significantly diminished Nai accumulation during ischemia and reperfusion and improved [Ca]i recovery during reperfusion.
- PC decreased coronary resistance, improved LVDP recovery (43.8% vs. 17.2%), and reduced CK release (607 vs. 2432 IU/g dry weight).
Conclusions:
- PC confers significant protection to newborn rabbit hearts against ischemia-reperfusion injury.
- The protective mechanisms involve maintaining higher pHi, reducing Nai and [Ca]i overload, and improving functional recovery.
- Findings support the hypothesis and highlight the potential of PC in neonatal cardiac protection.
Abstract:
In adult hearts, ischemic preconditioning (PC) has been shown to decrease ischemia-induced changes in intracellular pH (pHi) and [Ca] ([Ca]i) and decrease associated injury. These results are consistent with the interpretation that PC decreases the stimulus for Na uptake via Na/H exchange, thereby decreasing intracellular Na (Nai) accumulation, and thus decreasing the change in force driving Na/Ca exchange, which otherwise contributes to ischemia-induced increases in [Ca]i. Given documented age-related differences in myocardial responses to ischemia, we tested the hypothesis that in newborn hearts, PC will diminish intracellular [H], Nai, and [Ca]i during ischemia/reperfusion. NMR was used to measure pHi, Nai, [Ca]i, ATP, and PCr in isolated newborn (4-7 days) rabbit hearts Langendorff-perfused with Krebs-Henseleit solution equilibrated with 95% O2/5% CO2 at 36+/-1 degrees C. Control hearts were perfused 30 min before initiating 40 min global ischemia followed by 40 min reperfusion. PC hearts were treated the same except four 5-min intervals of ischemia each followed by 10 min of perfusion which preceded global ischemia. At end ischemia, pHi was higher in PC than control hearts (6.31+/-0.03 v 5.83+/-0.05; P<0.05). Similarly, PC diminished Nai-accumulation during ischemia and reperfusion (P<0.05). Control Nai rose from 16.2+/-2.6 to 108.8+/-10.3 (mEq/kg dry weight) and recovered to 55.2+/-10.1 and the corresponding values for PC hearts were 25.6+/-6.2, 70.0+/-7.9 and 21.9+/-5.2. PC also improved [Ca]i recovery during reperfusion (P<0.05). Control [Ca]i rose from 418+/-43 to 1100+/-78 (nm/l) and recovered to 773+/-63, whereas in PC hearts the values were 382+/-40, 852+/-136 and 371+/-45, respectively. In addition, PC decreased coronary resistance during reperfusion (P<0.05) as reflected by lower perfusion pressures under constant flow conditions (65.9+/-1.5 v 56. 1+/-4.1 mmHg at end of reperfusion). Finally, PC improved recovery of left-ventricular developed pressure (LVDP-43.8+/-12.0 v 17.2+/-3. 0% of control; P<0.05) and diminished CK release (607+/-245 v 2432+/-639 IU/g dry weight; P<0.05) during reperfusion. The results are consistent with the hypothesis.