MYOCARDIAL ISCHEMIC CONTRACTURE - METABOLITES AFFECT RIGOR TENSION DEVELOPMENT AND STIFFNESS

Myocardial ischemia is characterized by a decrease in phosphocreatine (PCr) and Mg2+-ATP contents as well as an accumulation of myosin ATPase reaction products (inorganic phosphate [P-i], protons, and Mg2+-ADP). The possibility that these metabolites play a role in rigor tension development was checked in rat ventricular Triton X-100-skinned fibers. Rigor tension was induced by stepwise decreasing [Mg2+-ATP] in the presence or in the absence of 12 mmol/L PCr. To mimic the diastolic ionic environment of the myofibrils, [free Ca2+] was set at 100 nmol/L (pCa 7); [free Mg2+], at 1 mmol/L; and ionic strength, at 160 mmol/L. In control conditions (pH 7.1, with no added P-i or Mg2+-ADP), the pMg(2+)-ATP for half-maximal rigor tension (pMg(2+)- ATP(50)) was 5.07 +/- 0.03 in the presence of PCr. After with drawal of PCr, the pMg(2+)-ATP(50) value was shifted toward higher Mg2+-ATP values (3.57 +/- 0.03). Addition of 20 mmol/L P-i shifted the pMg(2+)-ATP(50) to 3.71 +/- 0.04 (P < .05) in the absence of PCr and in the opposite direction to 4.98 +/- 0.02 (P < .01) in the presence of PCr. Acidic pH (6.6) strongly increased pMg(2+)-ATP(50) in both the absence (3.90 +/- 0.03, P < .001) and presence (5.44 +/- 0.02, P < .001) of PCr. Conversely, Mg2+-ADP (250 mu mol/L) decreased pMg(2+)-ATP(50) to 3.26 +/- -0.06 (P < .001) in the absence of PCr; at pMg(2+)-ATP 4, no rigor tension was observed until PCr concentration was decreased to <2 mmol/L. At acidic pH, maximal rigor tension was lower by 29% compared with control conditions, whereas in the presence of Mg2+-ADP, maximal rigor tension developed to 143% of the control value; Pi had no effect. The tension-to-stiffness (measured by the quick length-change technique) ratio was lower in rigor (no PCr and pMg(2+)-ATP 6) than during Ca2+ activation in the presence of both PCr and ATP. Compared with control rigor conditions, this parameter was unchanged by Mg2+-ADP and decreased by acidic pH, suggesting a proton-induced decrease in the amount of force per crossbridge. In addition to their known effects on active tension, Mg2+-ADP and protons affect rigor tension and influence ischemic contracture development. It is concluded that ischemic contracture and increased myocardial stiffness may be mediated by a decreased PCr and local Mg2+-ADP accumulation. This emphasizes the importance of myofibrillar creatine kinase activity in preventing ischemic contracture.