State Of Heart Muscle Research Articles

AMP-activated protein kinase control of energy metabolism in the ischemic heart

Myocardial ischemia produces an energy-deficient state in heart muscle, which if not corrected can lead to cardiomyocyte death. AMP-activated protein kinase (AMPK) is a key kinase that can increase energy production in the ischemic heart. During ischemia a rapid activation of AMPK occurs, resulting in an activation of both myocardial glucose uptake and glycolysis, as well as an increase in fatty acid oxidation. This activation of AMPK has the potential to increase energy production, thereby protecting the heart during ischemic stress. However, at clinically relevant high levels of fatty acids, ischemia-induced activation of AMPK also stimulates fatty acid oxidation during and following ischemia. This can contribute to ischemic injury secondary to an inhibition of glucose oxidation, which results in a decrease in cardiac efficiency. As a result, AMPK activation has the potential to be either beneficial or harmful in the ischemic heart.

Correlation between metabolic and histopathological changes in the myocardium of the KK mouse. Effect of diltiazem on the diabetic heart.

Serial changes in myocardial parameters related to non-insulin-dependent diabetes mellitus were investigated in DDY mice (control), untreated KK mice, and KK mice treated with diltiazem (150 micrograms/kg body weight, KKd1: or 300 micrograms/kg body weight diltiazem, KKd2). The isozyme ratio of lactate dehydrogenase (LDH) [(LDH1+LDH2)/(LDH4+LDH5)] was used as an index of aerobic metabolism of myocardial tissue. Mean blood sugar levels did not vary between 5 weeks and 30 weeks of age, ranging from 108 (range 60-198) mg/dl in DDY mice to 170 (range 110-282) mg/dl in KK mice. The ratio of heart weight to body weight was larger in KK mice than in DDY mice at 20 weeks of age, but was unaffected by diltiazem treatment. The LDH isozyme ratio showed that DDY mice were in an aerobic state at 15 and 20 weeks of age, while KK mice were in an anaerobic state at 10 and 15 weeks of age. The KKd1 and KKd2 groups exhibited the same LDH isozyme ratios as untreated KK mice; diltiazem had no effect on the LDH isozyme ratio at 20 and 30 weeks of age. The mean diameter of myocytes was increased in KK mice but diltiazem had no effect on this parameter. Interstitial fibrotic changes appeared at 15 weeks in untreated KK mice and progressed with age. These changes were completely suppressed in KK mice treated with diltiazem. These results suggest that hyperglycemia induces an anaerobic state in heart muscle, leading to muscle hypertrophy, degeneration, and fibrosis and that calcium antagonists may suppress these pathological changes.

A measurement of the active state in heart muscle.

A measurement of the active state in heart muscle Get access Allan J. Brady Allan J. Brady From the Department of Physiology and the Los Angeles County Cnrdiocoscular Research Laboratory, Unicersity of Calijornia at Los Angeles, Center for Health Sciences, Los Angeles, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue supp1, July 1971, Pages 11–17, https://doi.org/10.1093/cvr/5.supp1.11 Published: 01 July 1971

Effects of abrupt load alterations on force-velocity-length and time relations during isotonic contractions of heart muscle: load clamping.

1. Abrupt alterations in load (load-clamping) have been imposed on cat papillary muscles during the course of isotonic shortening, between the onset of shortening and peak shortening.2. For any given total load, whether imposed during the course of shortening or before stimulation, the velocity of shortening is determined solely by the instantaneous length, and not by the sequence of length and tension changes through which it arrived at that length.3. This unique force-velocity-length relation is independent of time from just after the onset of shortening until just prior to peak shortening.4. These results suggest that a steady state exists for the maximum intensity of active state in heart muscle over a major portion of the time during which isometric force is rising, and that heart muscle always senses total load while shortening.

Length-tension relations in cardiac muscle.

The distinguishing mechanical characteristics of cardiac muscle are(1) the presence of a significant and sometimes labile resting tension at functional lengths. Certain invertebrate skeletal muscles also possess this property, but the structural basis seems to be different.(2)Force-velocity characteristics of heart muscle are labile and constitute a mechanism for regulating cardiac performance.(3)Data on quick-stretch and release show that the active state in heart muscle is slow in its onset, probably preceding the development of isometric tension by only a short time.The onset of the active state is labile also, and probably forms the basis of the regulatory function of the force-velocity relation. Measurements of heat show a slow rate of increase of heat during a twitch consistent with the onset of contractility.

Active state in heart muscle. Its delayed onset and modification by inotropic agents.

The course of active state in heart muscle has been analyzed using a modified quick release method. The onset of maximum active state was found to be delayed, requiring 110-500 msec from time of stimulation, while the time to peak isometric tension required 250-650 msec. Further, the time from stimulation to peak tension was linearly related to the time required to establish maximum intensity of active state as well as to the duration of maximum active state. The duration of maximum active state was prolonged (90-220 msec), occupying most of the latter half of the rising phase of the isometric contraction. Norepinephrine (10(-5) M) shortened the latency from electrical stimulus to mechanical response, accelerated the onset of maximum active state, increased its intensity, decreased its duration, and accelerated its rate of decline. These changes were accompanied by an increase in the rate of tension development and the tension developed while the time from stimulation to peak isometric tension was abbreviated. Similar findings were shown for strophanthidin (1 microgram/ml) although lesser decrements in the duration of maximum active state and time to peak tension were found than with norepinephrine for similar increments in the maximum intensity of active state.

EFFECTS OF EPINEPHRINES ON METABOLISM AND CONTRACTION OF CAT PAPILLARY MUSCLE.

The change of metabolic state and contractility of heart induced by epinephrine and norepinephrine was studied in in vitro preparations of cat papillary muscle. The oxygen consumption, glycogen content, energy-rich phosphate content, and contractility of muscles were measured simultaneously whenever possible by techniques described previously. It was found that these amines did not change significantly the tissue contents of energy-rich phosphate compounds and glycogen in these conditions. The oxygen consumption and contractility of muscles were markedly influenced by the sympathomimetic amines. The change of metabolic efficiency as measured by the ratio, contractile tension : total Qo2, following the administration of these amines were dependent on the condition of heart muscles at the time of administration of these agents. Thus, when muscles were fresh, the metabolic efficiency was not significantly changed by the amines. However, when muscles were in the hypodynamic state, the amines were found to increase the metabolic efficiency of the heart muscle significantly. This suggests that the metabolic state of heart muscle should be taken into consideration whenever the influence of these sympathomimetic amines on the mechanical efficiency of heart is investigated.