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The rate of tension recovery in cardiac muscle correlates with the relative residual tension prevailing after restretch.

ABSTRACT: Isolated cardiac muscles generate tension more quickly at higher levels of Ca(2+) activation. We investigated the molecular mechanisms underlying this effect in permeabilized rat myocardial preparations by measuring the rate of tension recovery following brief shortening/restretch perturbations. Separate series of experiments used Ca(2+)-activating solutions with different pH values (pH 6.75, 7.00, and 7.25) and different phosphate (P(i)) concentrations (0, 2.5, and 5.0 mM added P(i)) to modulate the recovery kinetics. Subsequent analysis showed that the rate of tension recovery correlated (P < 0.001) with the relative residual tension, that is, the minimum tension measured immediately after restretch normalized to the steady-state isometric tension for the experimental condition. This new finding suggests that the rate at which cardiac muscles develop force increases with the proportion of cross bridges bound to the thin filament and is strong evidence of cooperative contractile activation.

SUBMITTER: Campbell KS

PROVIDER: S-EPMC2001153 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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The rate of tension recovery in cardiac muscle correlates with the relative residual tension prevailing after restretch.

Campbell Kenneth S KS Holbrook Anastasia M AM

American journal of physiology. Heart and circulatory physiology 20061222 4

Isolated cardiac muscles generate tension more quickly at higher levels of Ca(2+) activation. We investigated the molecular mechanisms underlying this effect in permeabilized rat myocardial preparations by measuring the rate of tension recovery following brief shortening/restretch perturbations. Separate series of experiments used Ca(2+)-activating solutions with different pH values (pH 6.75, 7.00, and 7.25) and different phosphate (P(i)) concentrations (0, 2.5, and 5.0 mM added P(i)) to modulat ...[more]

PMID: 17189351

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Project description:BACKGROUND:Here, we generated human cardiac muscle patches (hCMPs) of clinically relevant dimensions (4 cm × 2 cm × 1.25 mm) by suspending cardiomyocytes, smooth muscle cells, and endothelial cells that had been differentiated from human induced-pluripotent stem cells in a fibrin scaffold and then culturing the construct on a dynamic (rocking) platform. METHODS:In vitro assessments of hCMPs suggest maturation in response to dynamic culture stimulation. In vivo assessments were conducted in a porcine model of myocardial infarction (MI). Animal groups included: MI hearts treated with 2 hCMPs (MI+hCMP, n=13), MI hearts treated with 2 cell-free open fibrin patches (n=14), or MI hearts with neither experimental patch (n=15); a fourth group of animals underwent sham surgery (Sham, n=8). Cardiac function and infarct size were evaluated by MRI, arrhythmia incidence by implanted loop recorders, and the engraftment rate by calculation of quantitative polymerase chain reaction measurements of expression of the human Y chromosome. Additional studies examined the myocardial protein expression profile changes and potential mechanisms of action that related to exosomes from the cell patch. RESULTS:The hCMPs began to beat synchronously within 1 day of fabrication, and after 7 days of dynamic culture stimulation, in vitro assessments indicated the mechanisms related to the improvements in electronic mechanical coupling, calcium-handling, and force generation, suggesting a maturation process during the dynamic culture. The engraftment rate was 10.9±1.8% at 4 weeks after the transplantation. The hCMP transplantation was associated with significant improvements in left ventricular function, infarct size, myocardial wall stress, myocardial hypertrophy, and reduced apoptosis in the periscar boarder zone myocardium. hCMP transplantation also reversed some MI-associated changes in sarcomeric regulatory protein phosphorylation. The exosomes released from the hCMP appeared to have cytoprotective properties that improved cardiomyocyte survival. CONCLUSIONS:We have fabricated a clinically relevant size of hCMP with trilineage cardiac cells derived from human induced-pluripotent stem cells. The hCMP matures in vitro during 7 days of dynamic culture. Transplantation of this type of hCMP results in significantly reduced infarct size and improvements in cardiac function that are associated with reduction in left ventricular wall stress. The hCMP treatment is not associated with significant changes in arrhythmogenicity.

Dataset Information

The rate of tension recovery in cardiac muscle correlates with the relative residual tension prevailing after restretch.

Publications

The rate of tension recovery in cardiac muscle correlates with the relative residual tension prevailing after restretch.

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