Contractile state

MAINTAINING CARDIAC OUTPUT. The heart rate and stroke volume determine cardiac output. The stroke volume is determined in part by the contractile state of the heart and the amount of blood in the ventricle available to be pumped out. The interventions listed above help to support the cardiac output of the patient in shock. 

Smooth muscle cell activity is in general under neural control. Thus, the many transmitters of the autonomic nervous system are paired with receptors on the smooth muscle cell membrane. One of the current questions about smooth muscle function is What intracellular processes are the different transmitters modulating in the smooth muscle cells, in addition to their effects on the contractile state ... 

The smooth muscle cell does not respond in an all-or-none manner, but instead its contractile state is a variable compromise between diverse regulatory influences. While a vertebrate skeletal muscle fiber is at complete rest unless activated by a motor nerve, regulation of the contractile activity of a smooth muscle cell is more complex. First, the smooth muscle cell typically receives input from many different kinds of nerve fibers. The various cell membrane receptors in turn activate different intracellular signal-transduction pathways which may affect (a) membrane channels, and hence, electrical activity (b) calcium storage or release or (c) the proteins of the contractile machinery. While each have their own biochemically specific ways, the actual mechanisms are for the most part known only in outline. 

If MLCK activates contraction by increasing myosin phosphorylation, then an increase in the activity of myosin light chain phosphatase, MLCP, by decreasing the fraction of myosin which is phosphorylated, should lead to relaxation from the active (contractile) state. Cyclic adenosine monophosphate (AMP) is a strong inhibitor of smooth muscle contraction and it has been suggested that activation of MLCP could result from its phosphorylation via cAMP activated protein kinase (see Figure 5). 

Inotropic Relating to or influencing the force of muscular contractions, usually referring to changes in the contractile state of the heart. 

Tenderness. The contractile state of the muscle after rigor mortis is a major factor in meat tenderness, which is affected by post-mortem conditions creating differences in tenderness. Ageing of fresh pork can be used to improve tenderness. The process is based on a continuous weakening of the structural elements by different endogenous muscle peptidases along with an improved palatability (Taylor et al., 1995). 

On the other hand, if a chemical is somewhat less similar to acetylcholine, it may interact with the receptor but be unable to induce the exact molecular change necessary to allow the inward movement of sodium. In this instance the chemical does not cause contraction, but because it occupies the receptor site, it prevents the interaction of acetylcholine with its receptor. Such a drug is termed an antagonist. An example of such a compound is d-tubocurarine, an antagonist of acetylcholine at the end-plate receptors. Since it competes with acetylcholine for its receptor and prevents acetylcholine from producing its characteristic effects, administration of d-tubocurarine results in muscle relaxation by interfering with acetylcholine s ability to induce and maintain the contractile state of the muscle cells. 

Digoxin remains the mainstay of treatment for patients with chronic myocardial failure. Other drugs with inotropic and/or vasodilator properties, including the catecholamines and phosphodiesterase III (PDE) inhibitors, are used in the treatment of acute cardiac failure. The inotropic actions of most of these drugs result from a direct or indirect elevation of [Ca2-i-]i (intracellular Ca2+ concentration). This acts as a trigger for a process which leads to increased contractile state and cardiac contraction (Figures 8.3 and 8.4). Myofilament calcium sensitisers increase the sensitivity of contractile proteins to calcium. Some newer drugs, such as vesnarinone, have multiple mechanisms of action. 

Demonstrate a temporal correlation between a change in the regulatory component and a change in contractile state, consistent with a cause-and-effect relationship... 

Southgate, K., and Newby, A. C. (1990). Serum-induced proliferation of rabbit aortic smooth muscle cells from the contractile state is inhibited by 8-Br-cAMP but not 8-Br-cGMP. Atherosclerosis 82, 113-123. 

Pfitzer G, Merkel L, Riie JC, Hofmann F (1986) Cyclic GMP-dependent protein kinase relaxes skinned fibers from guinea pig taenia coli. J Pflug Arch 407 87-91 Pijuan V, Sukholutskaya I, Kerrick WG, Lam M, van Breemen C, Litosch I. (1993) Rapid stimulation of Ins (1,4,5)P3 production in rat aorta by NE correlation with contractile state. Am J Physiol 264 H126-H132... 

FIGURE 8.7 Ventricular elastance curves computed using the new analytical function of Equation 8.10. Elastance curves computed in this way are representative of the ventricle s contractile state. 

Changing only one model constant, c, in Equation 8.8 is sufficient to vary chamber contractile state. For example. Table 8.3 shows examples of congestive heart failure, resulting from decreases in c for the left ventricle and for the right ventricle. Decreasing left ventricular contractile state to one third of the control... 

The idea for this distributed muscle fiber model arose in 1990 [44]. At that time, muscle fibers were assumed to be functionally similar to muscle strips. Recently, experiments on isolated muscle libers show this to be the case. Predictions from the model have recently been borne out, for example, the magnitude of computed peak isometric force compared to that measured on isolated guinea pig myocytes [34]. Peak isometric stress measured on isolated rabbit myocytes (5.4 mN/mm ) is very close to peak stress from rabbit papillary muscle strips (6.4 mN/mm ) [45]. The distributed model generates peak isometric stress of 2.5 mN/mm. Other muscle phenomena measured on the isolated fiber include a quadratic force-length relation [45], inotropic changes in contractile state [37], quick release and stretch [37,39], and isotonic contractions [46], all in agreement with model predictions. 

Isolated Tissue Myocardial tissue harvested from an animal or even in some cases from man can be used to assess possible effects of a test article on the contractile state of the myocardium. Isolated atria, papillary muscles, trabeculae, or strips taken from papillary muscles or the ventricular wall have been used for this type of study (Toda, 1969 Brown and Erdmann, 1985 Brown et al 1987 Wilson and Broadley, 1989 Saetrum Opgaard et al 2000). 

This final section explores in a preliminary manner, an approximate method for assessing the contractile state and myocardial contractile reserve in terms of ejection fraction-afterload-preload relationships. The analysis is based on the concept of developed stress defined here to be the difference of end systolic stress and end diastolic stress. 

Figure 16 displays the stroke volume vs. relationships at constant levels of developed stress, employing the dog data from the early studies of Suga and Sagawa (1974). It is observed that at each level of developed stress, there is a critical end diastolic volume at which peak stroke volume occurs. The optimal developed stress occurs when peak stroke volume is a minimum namely zero and provides the basis for determining the optimal EF-afterload and EF-preload relationships shown in Figures 17, 18. Comparisons of the contractile state between different ventricles may thus be made with the aid of these relationships. 

Figure 17. Ejection fraction versus afterload and preload relationships. Left. Ejection fraction-end systolic stress relations at constant levels of end diastolic volume. The optimal relation corresponds to the absolute maximum value of developed stress. Right. Ejection fraction - end diastolic stress relations at constant levels of afterload. These relationships enable one to compare the contractile states between different ventricles.

The development of practical methods for the assessment of myocardial contractility continues and while the ESP-ESV concept provides one approach for quantitating changes in the contractile state, it requires further modification in order that it may be employed for patient to patient comparison. The preliminary studies described here on the basis of the developed stress concept shows some promise, however, further studies are required to examine the relationships between peak systolic pressure and end diastolic volume in order to explore an alternative definition for developed stress. 

Mirsky I, Pfeffer JM, Pfeffer MA, Braunwald E (1983) The contractile state as the major determinant in the evolution of left ventricular dysfunction in the spontaneously hypertensive rat. Circ Res 53 767-778... 

The heart is a muscular pump that provides energy to circulate blood to and from the metabolizing tissues. The pumping characteristic of each ventricle, or the relation between its pressure, volume and flow is a complex function of the contractile state of the myocardium and the mechanical interaction that takes... 

Recently, the relationship between pressure-volume or force-length at the end of systole has attracted a great deal of interest as a descriptor of the contractile state of the heart. This interest stems from a series of studies in isolated, canine left ventricular preparations (Taylor et al 1969 Suga et a/., 1973 Suga and Sagawa, 1974 Weber et /., 1976 Weber and Janicki, 1977), which demonstrated the end-systolic pressure-volume relation to be quite sensitive to variations in contractile state and relatively insensitive to variations in load. In addition, the relation is linear over a wide range of volumes so that its slope can be used to quantitate the contractile state. 

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