Stunning Does not Change the Relation Between Calcium and Force in Skinned Rat Trabeculae

Dietrich, D. L. L.; Leeuwen, Guido R. van; Stienen, G. J. M.; Elzinga, G.

doi:10.1006/jmcc.1993.1064

Cited by 16 publications

(3 citation statements)

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“…Such kinetic changes can effectively uncouple [Ca 2ϩ ] i from force, as shown experimentally and theoretically with the negatively inotropic drug butanedione monoxime (7). Dietrich et al (37) found no changes in steady-state myofilament calcium responsiveness following reflow after long periods of total ischemia (40 min) in isolated rat hearts; cross-bridge kinetics were not examined. Although the authors referred to this as "stunned myocardium," 40 min of total ischemia is known to produce significant irreversible injury in addition to stunning (see sect.…”

Section: Excitation-contraction Coupling In Stunned Myocardiummentioning

confidence: 98%

“…Accordingly, despite the numerous obvious differences from ischemia in vivo, myocardial stunning can be mimicked in isolated heart preparations. Obviously, the relevance to stunning becomes questionable in cases where these preparations are associated with significant cell death (3,4,32,37,51,83,108,113,138,139,167).…”

Section: Myocardial Stunning After Global Ischemiamentioning

confidence: 99%

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Molecular and Cellular Mechanisms of Myocardial Stunning

Bolli

Marbán

1999

Physiological Reviews

926

593

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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.

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Section: Excitation-contraction Coupling In Stunned Myocardiummentioning

confidence: 98%

Section: Myocardial Stunning After Global Ischemiamentioning

confidence: 99%

Molecular and Cellular Mechanisms of Myocardial Stunning

Bolli

Marbán

1999

Physiological Reviews

926

593

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“…Consistent with this hypothesis, Hofmann et al [17] reported decreased Ca 2+ sensitivity in skinned myocyte-sized preparations of stunned porcine myocardium. However, other studies using skinned preparations from ischemic/reperfused rat heart did not demonstrate a decreased Ca 2+ sensitivity of tension development [6,32]. However, other studies using skinned preparations from ischemic/reperfused rat heart did not demonstrate a decreased Ca 2+ sensitivity of tension development [6,32].…”

Section: Introductionmentioning

confidence: 90%

Ca 2+ sensitivity of stunned myocardium after skinning using retrograde infusion of detergent

Geyer¹,

Strauss²,

Rüegg³

et al. 1999

Pfl�gers Archiv European Journal of Physiology

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Myofilament Ca2+ desensitization contributes to the contractile dysfunction of ischemic/reperfused ("stunned") myocardium. We examined the presence of reduced Ca2+ sensitivity of isometric force in chemically skinned fibers obtained from stunned myocardium using different modes of applying the detergent Triton X-100. Langendorff-perfused rat hearts underwent 20 min ischemia/20 min reperfusion, which caused a 35 +/- 3% decrease in left ventricular developed pressure, compared to continuously perfused control hearts. Stunned and control hearts were randomly allocated to two different permeabilization protocols: In group A, trabeculae were dissected and immersed in skinning solution containing 1% Triton X-100 for 20 min. Group B hearts remained fixed to the aortic cannula and skinning solution was infused retrogradely for 6 min prior to dissection of trabeculae. Extraction of cytosolic marker proteins was more complete in group-B than in group-A preparations. Group-A preparations from stunned hearts exhibited significant Ca2+ desensitization (pCa50 = 5.07 and 5.15 in stunned and control myocardium, respectively). In group B no such difference was observed, all preparations showing higher Ca2+ sensitivity and maximum force than group-A preparations (pCa50 = 5.32 in stunned versus 5.33 in control hearts). Prolonging group-A skinning to 150 min also abolished the difference in Ca2+ sensitivity between stunned and control myocardium. In conclusion, compared to a conventional protocol, skinning by perfusion results in more complete permeabilization and better preservation of myocardial contractile function. Ischemia/reperfusion at this moderate degree of contractile dysfunction induces Ca2+ desensitization at least partially by factors that can be extracted by thorough skinning.

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Papillary Muscle and Left Ventricle Show Different Contractile and Metabolic Responses During Myocardial Stunning

Zuurbier

Beek

1998

Oxygen Transport to Tissue XX

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Stunning Does not Change the Relation Between Calcium and Force in Skinned Rat Trabeculae

Cited by 16 publications

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Molecular and Cellular Mechanisms of Myocardial Stunning

Molecular and Cellular Mechanisms of Myocardial Stunning

Ca 2+ sensitivity of stunned myocardium after skinning using retrograde infusion of detergent

Papillary Muscle and Left Ventricle Show Different Contractile and Metabolic Responses During Myocardial Stunning

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