scholarly journals Oxygen wastage of stunned myocardium in vivo is due to an increased oxygen cost of contractility and a decreased myofibrillar efficiency

2001 ◽  
Vol 51 (1) ◽  
pp. 122-130 ◽  
Author(s):  
S Trines
Keyword(s):  
Stunned Myocardium ◽  
Oxygen Cost

Molecular and Cellular Mechanisms of Myocardial Stunning

1999 ◽  
Vol 79 (2) ◽  
pp. 609-634 ◽  
Author(s):  
Roberto Bolli ◽  
Eduardo Marbán
Keyword(s):  
Free Radical ◽  
Myocardial Stunning ◽  
Recovery Of Function ◽  
Myocardial Dysfunction ◽  
Calcium Overload ◽  
Global Ischemia ◽  
Stunned Myocardium ◽  
Common Mechanism ◽  
Regional Ischemia

The past two decades have witnessed an explosive growth of knowledge regarding postischemic myocardial dysfunction or myocardial “stunning.” The purpose of this review is to summarize current information regarding the pathophysiology and pathogenesis of this phenomenon. Myocardial stunning should not be regarded as a single entity but rather as a “syndrome” that has been observed in a wide variety of experimental settings, which include the following: 1) stunning after a single, completely reversible episode of regional ischemia in vivo; 2) stunning after multiple, completely reversible episodes of regional ischemia in vivo; 3) stunning after a partly reversible episode of regional ischemia in vivo (subendocardial infarction); 4) stunning after global ischemia in vitro; 5) stunning after global ischemia in vivo; and 6) stunning after exercise-induced ischemia (high-flow ischemia). Whether these settings share a common mechanism is unknown. Although the pathogenesis of myocardial stunning has not been definitively established, the two major hypotheses are that it is caused by the generation of oxygen-derived free radicals (oxyradical hypothesis) and by a transient calcium overload (calcium hypothesis) on reperfusion. The final lesion responsible for the contractile depression appears to be a decreased responsiveness of contractile filaments to calcium. Recent evidence suggests that calcium overload may activate calpains, resulting in selective proteolysis of myofibrils; the time required for resynthesis of damaged proteins would explain in part the delayed recovery of function in stunned myocardium. The oxyradical and calcium hypotheses are not mutually exclusive and are likely to represent different facets of the same pathophysiological cascade. For example, increased free radical formation could cause cellular calcium overload, which would damage the contractile apparatus of the myocytes. Free radical generation could also directly alter contractile filaments in a manner that renders them less responsive to calcium (e.g., oxidation of critical thiol groups). However, it remains unknown whether oxyradicals play a role in all forms of stunning and whether the calcium hypothesis is applicable to stunning in vivo. Nevertheless, it is clear that the lesion responsible for myocardial stunning occurs, at least in part, after reperfusion so that this contractile dysfunction can be viewed, in part, as a form of “reperfusion injury.” An important implication of the phenomenon of myocardial stunning is that so-called chronic hibernation may in fact be the result of repetitive episodes of stunning, which have a cumulative effect and cause protracted postischemic dysfunction. A better understanding of myocardial stunning will expand our knowledge of the pathophysiology of myocardial ischemia and provide a rationale for developing new therapeutic strategies designed to prevent postischemic dysfunction in patients.

Chronic and acute exposure of mouse hearts to fatty acids increases oxygen cost of excitation-contraction coupling

2011 ◽  
Vol 300 (5) ◽  
pp. H1631-H1636 ◽  
Author(s):  
Neoma T. Boardman ◽  
Terje S. Larsen ◽  
David L. Severson ◽  
M. Faadiel Essop ◽  
Ellen Aasum
Keyword(s):  
Oxidation Rate ◽  
Basal Metabolism ◽  
Oxygen Cost ◽  
Ec Coupling ◽  
Inotropic Drugs ◽  
Acute Elevation ◽  
Additive Increase ◽  
Underlying Mechanisms

The aim of the present study was to evaluate the underlying processes involved in the oxygen wasting induced by inotropic drugs and acute and chronic elevation of fatty acid (FA) supply, using unloaded perfused mouse hearts from normal and type 2 diabetic ( db/db) mice. We found that an acute elevation of the FA supply in normal hearts, as well as a chronic (in vivo) exposure to elevated FA as in db/db hearts, increased myocardial oxygen consumption (MV̇o2unloaded) due to increased oxygen cost for basal metabolism and for excitation-contraction (EC) coupling. Isoproterenol stimulation, on top of a high FA supply, led to an additive increase in MV̇o2unloaded, because of a further increase in oxygen cost for EC coupling. In db/db hearts, the acute elevation of FA did not further increase MV̇o2. Since the elevation in the FA supply is accompanied by increased rates of myocardial FA oxidation, the present study compared MV̇o2 following increased FA load versus FA oxidation rate by exposing normal hearts to normal and high FA concentration (NF and HF, respectively) and to compounds that either stimulate (GW-610742) or inhibit [dichloroacetate (DCA)] FA oxidation. While HF and NF + GW-610742 increased FA oxidation to the same extent, only HF increased MV̇o2unloaded. Although DCA counteracted the HF-induced increase in FA oxidation, DCA did not reduce MV̇o2unloaded. Thus, in normal hearts, acute FA-induced oxygen waste is 1) due to an increase in the oxygen cost for both basal metabolism and EC coupling and 2) not dependent on the myocardial FA oxidation rate per se, but on processes initiated by the presence of FAs. In diabetic hearts, chronic exposure to elevated circulating FAs leads to adaptations that afford protection against the detrimental effect of an acute FA load, suggesting different underlying mechanisms behind the increased MV̇o2 following acute and chronic FA load.

In vivo evidence that EMD 57033 restores myocardial responsiveness to intracoronary Ca2+ in stunned myocardium

2000 ◽  
Vol 403 (1-2) ◽  
pp. 99-109 ◽  
Author(s):  
Sandra de Zeeuw ◽  
Serge A.I.P Trines ◽  
Rob Krams ◽  
Dirk J Duncker ◽  
Pieter D Verdouw
Keyword(s):  
Stunned Myocardium

Parathyroid hormone-related peptide improves myocardial contractile function of stunned myocardium in vivo

2001 ◽  
Vol 33 (6) ◽  
pp. A52
Author(s):  
Johanna Janson ◽  
Petra Gires ◽  
Christian Umschlag ◽  
Heike Degenhardt ◽  
Klaus-Dieter Schluetee ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Contractile Function ◽  
Stunned Myocardium ◽  
Related Peptide ◽  
Myocardial Contractile ◽  
Parathyroid Hormone Related Peptide

scholarly journals Increased oxygen cost of contractility in stunned myocardium of dog.

1991 ◽  
Vol 69 (4) ◽  
pp. 975-988 ◽  
Author(s):  
Y Ohgoshi ◽  
Y Goto ◽  
S Futaki ◽  
H Taku ◽  
O Kawaguchi ◽  
...  
Keyword(s):  
Stunned Myocardium ◽  
Oxygen Cost

Parathyroid hormone-related peptide improves contractile function of stunned myocardium in rats and pigs

2003 ◽  
Vol 284 (1) ◽  
pp. H49-H55 ◽  
Author(s):  
Johanna Jansen ◽  
Petra Gres ◽  
Christian Umschlag ◽  
Frank R. Heinzel ◽  
Heike Degenhardt ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Myocardial Function ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Stunned Myocardium ◽  
Coronary Resistance ◽  
Regional Myocardial Function ◽  
Related Peptide

The effect of synthetic parathyroid hormone (PTH)-related peptide [PTHrP(1–34)] on regional myocardial function was studied in 11 anesthetized pigs. Intracoronary infusion of PTHrP (cumulative dose: 14 ± 1 μg) decreased coronary resistance to 33 ± 2% of baseline ( P < 0.05) and regional myocardial function to 90 ± 3% of baseline (not significant). Ischemia-reperfusion alters the activity of several kinases and therefore possibly the myocardial effects of PTHrP. In stunned myocardium, induced by 20-min ischemia and 30-min reperfusion, the dose of PTHrP reducing coronary resistance to a minimum of 29 ± 2% was decreased to 8 ± 2 μg ( P < 0.05). Regional myocardial function was no longer decreased but increased to 132 ± 9% ( P < 0.05). The increase in regional myocardial function during PTHrP was inversely related to baseline function at 30-min reperfusion in vivo ( r = 0.9) as well as in myocytes isolated from stunned pig hearts ( r = 0.7). In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, blockade of endogenous PTHrP byd-Trp12-Tyr34-PTH(7–34) attenuated the recovery of left ventricular developed pressure by 30 ± 14% ( P < 0.05). Thus endogenous and exogenous PTHrP impact on the function of stunned myocardium.

scholarly journals Dietary nitrate does not reduce oxygen cost of exercise or improve muscle mitochondrial function in patients with mitochondrial myopathy

2017 ◽  
Vol 312 (5) ◽  
pp. R689-R701 ◽  
Author(s):  
Miranda Nabben ◽  
Joep P. J. Schmitz ◽  
Jolita Ciapaite ◽  
Carlijn M. P. le Clercq ◽  
Natal A. van Riel ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Myopathy ◽  
Ex Vivo ◽  
Work Load ◽  
Oxidative Capacity ◽  
Whole Body ◽  
Oxygen Cost ◽  
Dietary Nitrate ◽  
Nitrate Supplementation

Muscle weakness and exercise intolerance negatively affect the quality of life of patients with mitochondrial myopathy. Short-term dietary nitrate supplementation has been shown to improve exercise performance and reduce oxygen cost of exercise in healthy humans and trained athletes. We investigated whether 1 wk of dietary inorganic nitrate supplementation decreases the oxygen cost of exercise and improves mitochondrial function in patients with mitochondrial myopathy. Ten patients with mitochondrial myopathy (40 ± 5 yr, maximal whole body oxygen uptake = 21.2 ± 3.2 ml·min−1·kg body wt−1, maximal work load = 122 ± 26 W) received 8.5 mg·kg body wt−1·day−1 inorganic nitrate (~7 mmol) for 8 days. Whole body oxygen consumption at 50% of the maximal work load, in vivo skeletal muscle oxidative capacity (evaluated from postexercise phosphocreatine recovery using 31P-magnetic resonance spectroscopy), and ex vivo mitochondrial oxidative capacity in permeabilized skinned muscle fibers (measured with high-resolution respirometry) were determined before and after nitrate supplementation. Despite a sixfold increase in plasma nitrate levels, nitrate supplementation did not affect whole body oxygen cost during submaximal exercise. Additionally, no beneficial effects of nitrate were found on in vivo or ex vivo muscle mitochondrial oxidative capacity. This is the first time that the therapeutic potential of dietary nitrate for patients with mitochondrial myopathy was evaluated. We conclude that 1 wk of dietary nitrate supplementation does not reduce oxygen cost of exercise or improve mitochondrial function in the group of patients tested.

Fine Structural Changes in the Microvasculature of the Mouse Pinna: Aging and Radiation Injury

1974 ◽  
Vol 32 ◽  
pp. 54-55
Author(s):  
S. Phyllis Steamer ◽  
Rosemarie L. Devine
Keyword(s):  
Structural Changes ◽  
Radiation Treatment ◽  
Arterial Stenosis ◽  
Ultrastructural Changes ◽  
Vascular Effects ◽  
Microvascular Changes ◽  
Surrounding Connective Tissue ◽  
Fission Neutrons ◽  
Total Body

The importance of radiation damage to the skin and its vasculature was recognized by the early radiologists. In more recent studies, vascular effects were shown to involve the endothelium as well as the surrounding connective tissue. Microvascular changes in the mouse pinna were studied in vivo and recorded photographically over a period of 12-18 months. Radiation treatment at 110 days of age was total body exposure to either 240 rad fission neutrons or 855 rad 60Co gamma rays. After in vivo observations in control and irradiated mice, animals were sacrificed for examination of changes in vascular fine structure. Vessels were selected from regions of specific interest that had been identified on photomicrographs. Prominent ultrastructural changes can be attributed to aging as well as to radiation treatment. Of principal concern were determinations of ultrastructural changes associated with venous dilatations, segmental arterial stenosis and tortuosities of both veins and arteries, effects that had been identified on the basis of light microscopic observations. Tortuosities and irregularly dilated vein segments were related to both aging and radiation changes but arterial stenosis was observed only in irradiated animals.

Induction and Differentiation of Dental Epithelium in Vivo and in Vitro

1982 ◽  
Vol 40 ◽  
pp. 142-145
Author(s):  
E. J. Kollar
Keyword(s):  
Connective Tissue ◽  
Oral Mucosa ◽  
Basal Lamina ◽  
Functional Derivatives ◽  
Specific Source ◽  
Dental Epithelium ◽  
Connective Tissue Stroma

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.

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