It is well documented that pressure overload-induced cardiac hypertrophy results in altered mechanical characteristics during contraction when compared with normal heart muscle. However, few studies have investigated the mechanical alterations during relaxation in hypertrophied myocardium although the pathological alterations (increased diastolic stiffness, hindered ventricular filling) which occur in with heart disease are often first manifest during relaxation. I intend to study the alterations in relaxation mechanics in pressure overloaded, hypertrophied myocardium as compared with normal myocardium and refer the alterations to a change in crossbridge dynamics. There is a depressed maximum velocity of muscle shortening and ATPase activity in hypertrophied myocardium when compared with normal. Hypothesis: The rate of crossbridge cycling during relaxation is slower than normal in hypertrophied myocardium. A slower rate of crossbridge cycling may lead to an increased probability of crossbridge attachment at any moment during relaxation. There is an increased myofibrillar material to cell volume ratio and an increased number of sarcomeres in parallel in hypertropied myocardium when compared with normal. There is also a slower rate of calcium uptake by the sarcoplasmic reticulum in hypertrophied myocardium which results in a slower rate of tension decay. Hypothesis: Stiffness related to the number of attached crossbridges is greater than normal during relaxation in hypertrophied myocardium. The above hypotheses will be tested at the sarcomere level using laser diffraction in combination with optical-mechanical instrumentation. Isotonic (constant load), isometric (constant muscle length) and sarcomere isometric (constant sarcomere length) twitches and tetanus will be used to examine the mechanical characteristics of myocardial relaxation in hypertrophied as compared with normal right ventricular trabeculae from rabbits. Using a servo-controlled motor ergometer, rapid length changes will be imposed on a muscle and the number of attached crossbridges and the rate of crossbridge cycling will be inferred from rapid transient analysis of force and length change (Huxley and Simmonds, 1971). Caffeine, norepinephrine, temperature, and hypoxia will be used to alter crossbridge dynamics in predictable manner to further elucidate differences between the two types of preparations.
| Hamrell, B B; Hultgren, P B (1986) Sarcomere shortening in pressure overload hypertrophy. Fed Proc 45:2591-6 |
