Effects of sustained low-flow ischemia and reperfusion on Ca2+ transients and contractility in perfused rat hearts |
| |
Authors: | Seki Shingo Horikoshi Kazuaki Takeda Hiroshi Izumi Takehiko Nagata Akiko Okumura Hiroyuki Taniguchi Masayuki Mochizuki Seibu |
| |
Institution: | (1) Division of Cardiology, Department of Internal Medicine, Aoto Hospital, The Jikei University, School of Medicine, 6-41-2 Aoto, Katsushika-ku, Tokyo, 125-8506, Japan |
| |
Abstract: | We investigated changes in cytoplasmic Ca2+ concentration (Ca2+]i) and in left ventricular contractility during sustained ischemia and reperfusion in isolated beating rat hearts. Hearts from male Sprague-Dawley rats were perfused retrogradely and were loaded with 4 M fura-2. Low-flow global ischemia was induced by reducing perfusion flow to 10% and by electric pacing. The hearts were exposed to ischemia for 10 min or 30 min and then reperfused. Ca2+]i was measured by monitoring the ratio of 500 nm fluorescence excited at 340 and 380 nm while simultaneously measuring left ventricular pressure (LVP). To determine diastolic Ca2+]i, background autofluorescence was subtracted. LVP rapidly decreased from 82.3 ± 8.2 to 17.1 ± 2.9 mmHg , whereas the amplitude of the Ca2+ transient did not change significantly during the first 1 min of ischemia. After 10 min of ischemia, the amplitude decreased to 60.8 ± 10.6% (p < 0.05) and diastolic Ca2+]i increased by 26.3 ± 2.9% (p < 0.001) compared with the pre-ischemic value (n = 8). When the hearts were reperfused after 10 min of ischemia, the amplitude of the Ca2+ transient and LVP recovered to 79.0 ± 7.2% and 73.2 ± 7.5 mmHg, respectively. Whereas diastolic Ca2+]i decreased to the pre-ischemic value. In the hearts exposed to 30 min of ischemia (n = 10), diastolic Ca2+]i increased even further by 32.7 ± 5.3% at the end of ischemia and continued increasing during the 10 min of reperfusion by 42.6 ± 15.6%. Six of 10 hearts developed ventricular fibrillation (VF) and intracellular Ca2+ overload after reperfusion. Recovery of LVP after reperfusion was significantly smaller in the hearts exposed to 30 min of ischemia than in the hearts exposed to 10 min of ischemia (58.9 ± 11.7 vs. 97.2 ± 3.0% of pre-ischemic value, p < 0.05). Diastolic Ca2+]i also increased under hypoxic conditions (N2 bubbling) in this model. These results suggest that increases in diastolic Ca2+]i might play an important role in myocardial contractile dysfunction and viability in ischemia-reperfusion injury. |
| |
Keywords: | arrhythmia calcium fura-2 ischemia rat reperfusion |
本文献已被 PubMed SpringerLink 等数据库收录! |
|