Details

Autor(en) / Beteiligte

• Yarbrough, William M
• Mukherjee, Rupak
• Escobar, G.Patricia
• Hendrick, Jennifer W
• Sample, Jeffrey A
• Dowdy, Kathryn B
• McLean, Julie E
• Mingoia, Joseph T
• Crawford, Fred A
• Spinale, Francis G

Titel

Modulation of calcium transport improves myocardial contractility and enzyme profiles after prolonged ischemia-reperfusion

Ist Teil von

• The Annals of thoracic surgery, 2003-12, Vol.76 (6), p.2054-2061

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• Ischemia-reperfusion (IR) injury causes myocardial dysfunction in part through intracellular calcium overload. A recently described pharmacologic compound, MCC-135 (5-methyl-2-[1-piperazinyl] benzenesulfonic acid monohydrate, Mitsubishi Pharma Corporation), alters intracellular calcium levels. This project tested the hypothesis that MCC-135 would influence regional myocardial contractility when administered at reperfusion and after a prolonged period of ischemia. A circumflex snare and sonomicrometry crystals within remote and area-at-risk regions were placed in pigs (n = 18, 32 kg). Coronary occlusion was instituted for 120 minutes followed by 180 minutes of reperfusion. At 105 minutes of ischemia pigs were randomly assigned to IR only (n = 11) or MCC-135 (IR-MCC [300 μg · kg −1 · h −1, n = 7]) administered intravenously. Regional myocardial contractility was determined by calculation of the regional end-systolic pressure-dimension relation (RESPDR [mm Hg/cm]). Myocardial injury was determined by measurement of plasma levels of myocyte-specific enzymes. At 90 minutes ischemia, mean troponin-I was 35 ± 8 ng/mL with no significant difference between groups. At 180 minutes reperfusion, heart rate was increased by 18% ± 5% in the IR only group ( p < 0.05) and was reduced by 11% ± 4% with IR-MCC ( p < 0.05). At 90 minutes ischemia RESPDR was reduced from baseline by 51% ± 6% ( p < 0.05). By 30 minutes reperfusion, reductions in RESPDR were attenuated with IR-MCC compared with IR only values. The CK-MB levels were increased at 180 minutes reperfusion in the IR only group (52 ± 9 ng/mL) compared with baseline (6 ± 1 ng/mL, p < 0.05) but were attenuated with IR-MCC (24 ± 4 ng/mL, p < 0.05) compared with IR only values. Despite similar degrees of injury at 90 minutes ischemia MCC-135 improved regional contractility and reduced the egress of CK-MB. Moreover MCC-135 was associated with decreased heart rate, a determinant of myocardial oxygen demand. Pharmacologic modulation of calcium transport ameliorates myocardial dysfunction in the acute IR period.