Age-related difference in cardiac adaptation to chronic hypertension in rats, with and without nifedipine treatement

Three myosin isozymes, V1 (αα MHC = Myosin Heavy Chain gene), V2 (αβ MHC) and V3 (ββ MHC) that are identified in the cardiac ventricles of most mammals have been shown to shift to a V3 predominance pattern during cardiac growth and in response to left ventricular pressure overload, and to V1 predominance following anti hypertensive treatment. This study examined whether long-term hypertension impairs the ability of the adult heart to restructure myosin isozyme proportions. Using pyrophosphate gel electrophoresis, we studied proportions of cardiac myosin isozymes (V1 and V3) in young (16 weeks) and adult (36 weeks) spontaneously hypertensive rats (SHR), and following 12 weeks of nifedipine (N) treatment in age-matched SHR rats (SHR-N). The values of V1 and V3 myosin isozymes were derived by adding half of the value of V2 to each isozyme proportion. The V3 proportion in the young SHR control (SHR-C) group (49%) was 34% higher (p < 0.05) than in the young Wistar Kyoto control (WKY-C) group (37%). However, the proportion was similarly high, though not statistically significant, in both the adult SHRC (73%) and WKY-C (71%) groups. The proportion in the young SHR-N group (29%) was 41% lower (p < 0.05) than in the young SHR-C group (49%), and the proportion in the adult SHR-N group (47%) was 34% lower (p < 0.05) than in the adult SHR-C group (73%). The ratio of left ventricular weight to body weight (LVW/BW), which determines left ventricular hypertrophy (LVH), was higher in both young and adult SHR-C (26%, p < 0.05, and 42%, p < 0.05, respectively) than in WKY-C groups. The mean LVW/BW was 27% (p lt; 0.05) greater in adult than in young SHR-C rats. The LVW/BW in both age groups of treated SHR-N was similar to that in age matched WKY-C rats. Conclusion: Our study showed that a rise in the V3 level occurs in young hypertensive rats, but no rise occurs in the V3 level in adult hypertensive rats. High blood pressure seems to contribute to the high V3 level in young hypertensive rats, but in adult hypertensive rats, high blood pressure does not accentuate the V3 rise already acquired due to the aging process. Nifedipine treatment in both young and adult hypertensive rats prevented the V3 rise due to hypertension and to the aging process. This effect of nifedipine seems to be through its antihypertensive action.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45335/1/11010_2004_Article_199277.pd

Sarcoplasmic reticulum function: comparison of atrial and ventricular myocardium

http://www.ester.ee/record=b1053410~S1*es

Myosin and electrophysiological heterogeneity in cardiac muscle

Abstract available p. v-vi

Alpha and beta myosin isoforms and human atrial and ventricular contraction.

Human atrial and ventricular contractions have distinct mechanical characteristics including speed of contraction, volume of blood delivered and the range of pressure generated. Notably, the ventricle expresses predominantly β-cardiac myosin while the atrium expresses mostly the α-isoform. In recent years exploration of the properties of pure α- & β-myosin isoforms have been possible in solution, in isolated myocytes and myofibrils. This allows us to consider the extent to which the atrial vs ventricular mechanical characteristics are defined by the myosin isoform expressed, and how the isoform properties are matched to their physiological roles. To do this we Outline the essential feature of atrial and ventricular contraction; Explore the molecular structural and functional characteristics of the two myosin isoforms; Describe the contractile behaviour of myocytes and myofibrils expressing a single myosin isoform; Finally we outline the outstanding problems in defining the differences between the atria and ventricles. This allowed us consider what features of contraction can and cannot be ascribed to the myosin isoforms present in the atria and ventricles

Determinants of Progressive Myocardial Deterioration in Human Heart Failure

Paulus, W.J. [Promotor]Stienen, G.J.M. [Promotor]Velden, J. van der [Copromotor

Evidence of left ventricular wall movement actively decelerting aortic

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Efficient function of the left ventricle (LV) is achieved by coherent behaviour of its circumferential and longitudinal myocardial components. Little was known about the direct association between the long and minor axis velocities and the overall haemodynamics generated by ventricular systolic function such as aortic waves. The forward running expansion wave (FEW) during late systole contains important information about the condition of the LV and its interaction with the arterial system. The aim of this thesis was to underpin the mechanics and timing of the LV wall velocities, which are associated with the deceleration of flow. Both invasive and noninvasive data have been analysed in canines and humans and the following conclusions can be drawn. LV long axis peak shortening velocity lags consistently behind the minor axis, representing a degree of normal asynchrony. The FEW is seen to have a slow onset before a rapid increase in energy. The slow onset corresponds with the time that the long axis reaches its peak velocity of shortening. After both axes reach their respective maximum shortening velocity they continue to contract, although at a slow steady velocity until late ejection when there is a sudden simultaneous change of shortening velocity of both axes. This time corresponds with peak aortic pressure and the rapid increase in energy of the FEW. The time that the minor axis reaches its maximum velocity of shortening interestingly coincides with the arrival of the reflected wave at the LV during mid-systole. During canine aortic manipulation through the introduction of total occlusions along the aorta, the sequence of events observed in control conditions remains unchanged. In humans both LV wall movement and carotid wave intensity can be measured successfully using non-invasive methods. The FEW is generated when the last long axis segment begins to slow. The minor axis begins to slow before this time and corresponds to the time of peak aortic flow

Fast kinetics of human myosin heavy chain contraction in health and disease

The myosin heavy chain composition of human heart and skeletal muscles is dynamic in health and disease and is known to define the maximum velocity and force generated by contracting muscles. The study of the individual isoforms that comprise this diversity has recently been aided by the development of a recombinant expression system capable of producing functional sarcomeric human myosin motors. The eight primary human sarcomeric myosin isoforms are herein shown to differ by between 1.5- and 4.5-fold in their F-actin-activated ATPase activities. Due to the greatly differing contractile environments in which they function it has been anticipated that the kinetics of the reactions that comprise the contractile cycle vary to an even greater extent. Using pre-steady-state techniques it is possible to determine the kinetics of the steps of myosin contraction. Among the eight isoforms tested, we observe multiple biochemical patterns that differentiate the motors into fast-moving and slow, tension-maintaining categories. Additionally, we have characterized pathological point mutations associated with developmental and cardiac disease. We find that unique patterns of alteration to the reactions of the myosin ATPase cycle characterize each mutation. These alterations are predicted to cause significant disruptions to the reactions governing attachment and detachment between myosin and F-actin. These studies lay the foundation for structure vs. function analysis of pathological myosin mutations and fill an important void in understanding the contributions of the various myosin isoforms to human muscle contraction