Nature of load dependence of relaxation in cardiac muscle

Left ventricular hypertrophy (LVH) was produced in guinea pigs after aortic stenosis (AS). The percentage of LVH in AS was determined by normalizing left ventricular (LY) weight by the mean LV weight of sham-operated controls (n = 12). After 3 weeks of cardiac overload, a mild LVH (30 ± 3%) was induced in 17 animals and a relatively severe LVH (56 ±3%) was induced in 7 animals. LV papillary muscles were rapidly excised for mechanical studies. No significant differences were observed between control and mild hypertrophy groups. In contrast, a marked decrease in myocardial performance was seen in the more severe cardiac hypertrophy group and was expressed as a percentage of sham-operated levels (Vmax, 22%; active isometric force/mm 2 ,23%; + dF/dt max/mm 2 ,26%). Relaxation in this group was still more impaired than contraction (peak lengthening velocity, 14%; -dF/dt max/mm 2 , 19%). Moreover, the load sensitivity of relaxation was present in both shamoperated controls and mild hypertrophy but almost disappeared in more severe hypertrophy. Isometric relaxation was delayed in the latter group, as shown by the 15% increase of the half-time of the decline of isometric relaxation (t w ). On the other hand, acute hypoxia (95% N 2 -5% CO 2 for 20 minutes) also induced a fall in contractility and the disappearance of the load sensitivity of relaxation but with a 67% decrease of ti.. Thus, the mechanical analysis of relaxation allows the effects of chronic overload in relatively severe cardiac hypertrophy to be separated from those of acute hypoxia. Moreover, in severe cardiac hypertrophy, the impairment of the load sensitivity of relaxation with increased ti/, strongly suggests alterations of the sarcoplasmic reticulum. especially since the moderate decrease in the myofibrillar ATPase activity, which has been observed previously in guinea pig pressure overload, cannot account completely for the marked fall in myocardial performance. (Circulation Research 1987;61:I07-116) C hronic cardiac overload appears to modify the myocyte homeostasis in a complex manner, as shown by numerous biochemical, metabolic, or mechanical alterations described in the literature, These changes observed during cardiac hypertrophy are, in part, species specific. Thus, the rat myocardium adapts to chronic overload by changing the fast V, isomyosin to the slow V,, 1 and this isomyosin shift is related linearly to alterations in contractility 21 Also, it has been shown that relaxation in the hypertrophied rat myocardium remains sensitive to the loading conditions, a mechanical property that generally seems to be present when the sarcoplasmic reticulum is normally functional and that, in the rat, is never impaired, whatever the degree or type of cardiac overload.

Section: Mechanical Analysis and Mounting Proceduresmentioning

confidence: 99%

Major alterations in relaxation during cardiac hypertrophy induced by aortic stenosis in guinea pig.

Lecarpentier¹,

Waldenström²,

Clergue³

et al. 1987

“…Diastolic relaxation in both isolated cardiac muscle and the intact heart is currently hypothesized to be controlled by the complex interaction of (1) load, (2) inactivation of forcegenerating sites, and (3) any spatial or temporal nonuniformity of the distribution of load and inactivation (LeCarpentier et al, 1979;Housmans et al, 1983;Brutsaert et al, 1984). The imposition of a greater systolic load throughout the period of tension development in the intact heart would be expected to modify the time course of relaxation (Raff and Glantz, 1981;LeCarpentier et al, 1982;Housmans et al, 1983;Brutsaert et al, 1984).…”

Section: Influences Of Load On Relaxationmentioning

confidence: 99%

“…The biochemical processes that influence the rate and extent of force inactivation and final resting cardiac tone are incompletely understood, but appear to depend in part on the ATP-dependent rate and capacity of calcium sequestration by the sarcoplasmic reticulum (Nayler et al, 1979;Lewis et al, 1979;LeCarpentier et al, 1979LeCarpentier et al, , 1982Grossman and Barry, 1980;Brutsaert et al, 1984). In our experiments, the extent of high energy phosphate depletion during hypoxia was probably comparable in the LVH and control groups as indirectly assessed by the comparable degrees of myocardial lactate production (i.e., glycolytic flux, which is the sole source of ATP synthesis during hypoxia) and the comparable degrees of contractile work done during hypoxia (i.e., developed pressure per unit left ventricular mass), which reflects the amount of ATP utilization.…”

Section: Differences In Force Inactivationmentioning

confidence: 99%

The influence of pressure overload left ventricular hypertrophy on diastolic properties during hypoxia in isovolumically contracting rat hearts.

Lorell¹,

Wexler²,

Momomura³

et al. 1986

SUMMARY. We tested the hypothesis that there is an enhanced susceptibility in hypertrophied cardiac muscle to develop decreased diastolic distensibility of the left ventricle in response to hypoxia. The effects of brief hypoxia (3 minutes) were studied in rats with and without chronic left ventricular pressure overload hypertrophy using an isolated buffer-perfused and isovolumic (balloon-in-left ventricle) heart preparation with excised pericardium and vented right ventricle. We compared hypertrophied hearts from hearts from hypertensive uninephrectomized WistarKyoto rats (» = 12) with normotensive uninephrectomized age-matched controls (n = 13). Coronary flow was held constant and adjusted so that an identical flow per gram left ventricular weight was achieved in both groups. The left ventricular balloon volume was adjusted to produce an initial left ventricular end-diastolic pressure of 10 mm Hg in both groups and was held constant thereafter so that changes in left ventricular end-diastolic pressure during hypoxia represented changes in diastolic chamber distensibility. Under aerobic conditions, left ventricular systolic pressure was 66% higher in the hypertrophied hearts than in the controls, but there was no difference in the rate or extent of left ventricular relaxation as estimated by the exponential time constant of pressure decay and the asymptote to which pressure decayed. In response to hypoxia, left ventricular end-diastolic pressure was significantly higher in the hypertrophied hearts than in the controls (37 ± 5 vs. 22 ± 5 mm Hg, P < 0.001). In response to hypoxia, the rate of left ventricular relaxation was depressed to a comparable degree in both groups, but there was a greater upward shift in the asymptote to which pressure decayed in the hypertrophied hearts. Hypoxia-induced coronary vasodilation as assessed by the change in coronary vascular resistance was similar in the hypertrophied and control hearts (2.9 ± 0.5 vs. CARDIAC hypertrophy is a compensatory response to chronic pressure or volume overload of the heart. However, adaptive cardiac hypertrophy may result in an enhanced vulnerability to ischemia or hypoxia,* as manifested by a decrease in diastolic distensibility. Bache et al. (1984a) have shown that pacing tachycardia in dogs with chronic left ventricular (LV) hypertrophy without coronary stenoses produces myocardial ischemia associated with a substantial increase in left ventricular end-diastolic pressure. A similar dramatic and reversible decrease in left ventricular diastolic distensibility has been * In this paper, hypoxia will be used to indicate an abnormally low level of tissue oxygenation due to hypoxemia, an abnormally low arterial oxygen content. Ischemia will mean an abnormally low level of myocardial perfusion.

“…In ventricular muscle, load dependence of relaxation became manifest only in the presence of a well-functioning calcium-sequestering system (Lecarpentier et al, 1979) and explains the explosive character of the early diastolic filling phase (Brutsaert et al, 1980). The variety of preparations studied demonstrated that the preponderance of load dependence or of activation dependence is not determined by the architectural nature of the preparation.…”

Section: Discussionmentioning

confidence: 97%

“…Relaxation of cardiac muscle previously has been shown to be governed by the interplay of the decay of activation and the load, the relative contribution of which differs among various species (Brutsaert et al, 1978;Chuck et al, in press;Lecarpentier et al, 1979). In ventricular muscle, load dependence of relaxation became manifest only in the presence of a well-functioning calcium-sequestering system (Lecarpentier et al, 1979) and explains the explosive character of the early diastolic filling phase (Brutsaert et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

Relaxation properties of mammalian atrial muscle.

Couttenye¹,

Clerck²,

Goethals³

et al. 1981

SUMMARYThe properties of relaxation, in particular the sensitivity of relaxation to load, were analyzed in isolated intact atrial muscle and in manually dissected, detergent-treated cellular preparations from cat, dog, and rat atria. Force and length traces under increasing afterloads and following load clamps were obtained using an electromagnetic lever-force transducer system for the intact muscles and a capacitance transducer system for the cellular preparations. In both types of preparations, the time course of relaxation was hardly affected by the load or by alterations in load (load clamps), unlike intact mammalian ventricular muscle. This load independence of relaxation, which was hardly influenced by variations of initial muscle length, resembled relaxation in intact frog ventricular muscle and in detergent-treated mammalian ventricular single cells. As relaxation of these ventricular preparations with poorly developed (frog) or absent (detergent-treated single cells) calcium-sequestering systems was shown to be governed by the dissipation of activation, these results suggest a similar control mechanism for relaxation in mammalian atrial muscle. Furthermore, load independence of relaxation of mammalian atrial muscle in late diastole may promote optimal filling of the ventricle. Circ Res 48: 352-356, 1981ALTHOUGH the contractile properties of the contraction phase of mammalian atrial muscle have been well studied and compared with the contractile performance of ventricular muscle (Fabiato and Fabiato, 1972;Tarr et al., 1979;Urthaler et al., 1975), its properties during the relaxation phase are less well understood. Because of the unquestionable contribution of atrial contraction to the pump function of the ventricle, and because of the significant differences between the contractile properties of atrial and ventricular muscles (Blinks and KochWeser, 1963;Koch-Weser and Blinks, 1963), we have analyzed, in the present study, the mechanical behavior of mammalian atrial muscle during relaxation and in particular, its sensitivity to load or load alterations and its possible role in the functioning of the heart. Two kinds of preparation were used: (1) intact atrial muscle strips from cat and dog and (2) single atrial cells of rat, obtained by manual dissection after treatment with detergent to destroy the membranous systems. MethodsAtrial muscle strips were dissected from cat (n = 9) and dog (n = 2). The basic characteristics of these preparations are summarized in Table 1.Long thin strips of longitudinally oriented bundles of muscle fibers were cut from the free left atrial wall. The muscle strips were mounted vertically, the lower end being held by a force transducer (compliance, 0.3 |iim/mN; resonant frequency in aqueous solution, 250 Hz) and the upper end being tied (7.0 braided thread, Deknatel, Surgical Tevdek, Code 103-T) to an electromagnetic lever system (compliance 0.2 jum/mN, equivalent moving mass 155 mg, step response 3 msec). The current through the coil of the electromagnet determined the load on...