Ischemia of the heart : a study of sarcomere dynamics and cellular metabolism

textabstractSince 1628, when Harvey was the first to recognize that interruption of coronary flow results in an immediate decrease of force development, researchers were intrigued by the possible explanations of this phenomenon (Harvey, 1628). In the previous chapter I reviewed the possible hypotheses to explain the rapid decay of force development that results from hypoxia On the basis of the available xperimental and clinical evidence the most likely explanations include: a) impairment of the excitation-contraction coupling process, at least partially explained by abbreviation of the duration of the action potential by ischemia activated ATP-sensitive potassium channels (Weiss and Lamp, 1989), b) impairment of force development as a result of accumulation of metabolites from high-energy phosphates, notably protons and inorganic phosphate (Kentish, 1986), c) decreased free energy change of ATP hydrolysis at normal or slightly decreased high-energy phosphate content (Kammermeier et al., 1982; Fiolet, 1984 but see Hoerter et al, 1988), and d) interaction between myocytes and the coronary vasculature (Koretsune, 1991). The primary goal of the studies that are included in this thesis was to improve our insights in sarcomere mechanics. For this purpose not only norm.oxic but also hypoxic preparations were studied, both intact and following skinning. In addition we attempted to define the relationship between sarcomere mechanics and biochemistry, notably tb.e content of energy-rich phosphate compounds