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BACKGROUND: Ischemia is characterized by an increase in intracellular calcium and occurrence of diastolic dysfunction. We investigated whether the myocyte calcium level is an important direct determinant of ischemic diastolic dysfunction. METHODS AND RESULTS: We exposed isolated, perfused isovolumic (balloon in left ventricle) rat and rabbit hearts to low-flow ischemia and increased extracellular calcium (from 1.5 to 16 mmol/L) for brief periods. Intracellular calcium was measured by aequorin. Low-flow ischemia resulted in a 270% increase (P:<0.05) in diastolic intracellular calcium, a 50% (P:<0.05) calcium transient amplitude decrease, and a 52% (P:<0.05) slowing of calcium transient decline. Diastolic pressure increased by 6+/-2 mm Hg (P:<0.05), and rate of systolic pressure decay decreased by 65% (P:<0.05). Experimentally increasing extracellular calcium doubled both intracellular diastolic calcium and calcium transient amplitude, concomitant with a developed pressure increase; however, there was no increase in ischemic diastolic pressure, slowing of the calcium transient decay, or further slowing of systolic pressure decay. Similarly, after 45 minutes of low-flow ischemia, after diastolic pressure had increased from 8.5+/-0.6 to 19.7+/-3.5 mm Hg (P:<0.001), intracoronary high-molar calcium chloride infusion increased systolic pressure from 36+/-4 to 63+/-11 mm Hg (P:<0.001), indicating an increase in intracellular calcium, but it decreased diastolic pressure from 19. 7+/-3.5 to 17.5+/-3.7 mm Hg (P:<0.01). Conversely, EGTA infusion decreased systolic pressure, indicating a decrease in intracellular calcium, but did not decrease diastolic pressure. CONCLUSIONS: When calcium availability was experimentally altered during ischemia, there was no alteration in left ventricular diastolic pressure, suggesting that ischemic diastolic dysfunction is not directly mediated by a calcium activated tension.

Type

Journal article

Journal

Circulation

Publication Date

21/11/2000

Volume

102

Pages

2643 - 2649

Keywords

Animals, Blood Pressure, Calcium, Chelating Agents, Diastole, Dose-Response Relationship, Drug, Egtazic Acid, Extracellular Space, In Vitro Techniques, Male, Myocardial Ischemia, Myocardium, Rabbits, Rats, Rats, Wistar, Systole