Myocardial mechanical dysfunction and calcium overload following rewarming from experimental hypothermia in vivo

Kondratiev, Timofei; Wold, Ragnhild M; Aasum, Ellen; Tveita, Torkjel

doi:10.1016/j.cryobiol.2007.09.005

Cited by 45 publications

(49 citation statements)

References 34 publications

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“…Benfey, who found that the inotropic response to isoproterenol was intact during hypothermia, opposed this finding. He found sustained inotropic effects to be dependent on reduced calcium concentration in the experimental solution [1], different from the calcium overload found in hypothermic in vivo rat hearts [13,36]. In the present study, we found that Epi had negative inotropic effects at 15°C, recognized by decreased CO, despite giving a 4-fold increase of cAMP in cardiac tissue.…”

Section: Discussioncontrasting

confidence: 67%

“…The latter morphological finding is also seen after hypothermic cardioplegia in man [18], but not in spontaneously beating rat hearts exposed to prolonged hypothermia in vivo [32]. However, in rats exposed to 4 h hypothermia (15°C), cardiac calcium overload is present [13,36]. In the present study, the 4-fold increase in cardiac tissue cAMP during Epi infusion after 4 h at 15°C might therefore aggravate a hypothermia-induced calcium overload through high influx of calcium via L-type calcium channels.…”

Section: Discussionmentioning

confidence: 70%

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Negative inotropic effects of epinephrine in the presence of increased β-adrenoceptor sensitivity during hypothermia in a rat model

et al. 2015

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Section: Discussioncontrasting

confidence: 67%

Section: Discussionmentioning

confidence: 70%

Negative inotropic effects of epinephrine in the presence of increased β-adrenoceptor sensitivity during hypothermia in a rat model

et al. 2015

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“…Animal models have demonstrated that systolic function or cardiac muscle force generation is significantly reduced after hypothermia/rewarming (H/R) (14,16,38,40). The intracellular mechanisms underlying excitation-contraction coupling and muscle force generation appear to be disturbed following H/R, which could be explained either through a reduction in evoked transient cytoplasmic Ca 2ϩ ([Ca 2ϩ ] cyto ) responses or decreased Ca 2ϩ sensitivity of force generation.…”

Section: New and Noteworthymentioning

confidence: 98%

“…Although accidental hypothermia is associated with low incidence, claiming ϳ1,500 death certificates in the U.S. per year (4), it is accompanied with high mortality (estimates range from 50 -80%) (21). The underlying cause of rewarming shock is not clearly understood, which is essential to develop optimal rewarming strategies for accidental hypothermia victims.Animal models have demonstrated that systolic function or cardiac muscle force generation is significantly reduced after hypothermia/rewarming (H/R) (14,16,38,40). The intracellular mechanisms underlying excitation-contraction coupling and muscle force generation appear to be disturbed following H/R, which could be explained either through a reduction in evoked transient cytoplasmic Ca 2ϩ ([Ca 2ϩ ] cyto ) responses or decreased Ca 2ϩ sensitivity of force generation.…”

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confidence: 98%

Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes

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Han

Hoang

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Hypothermia/rewarming (H/R) is poorly tolerated by the myocardium; however, the underlying intracellular basis of H/R-induced cardiac dysfunction remains elusive. We hypothesized that in cardiomyocytes, H/R disrupts excitation-contraction coupling by reducing myofilament Ca(2+) sensitivity due to an increase in cardiac troponin I (cTnI) phosphorylation. To test this hypothesis, isolated rat cardiomyocytes (13-15 cells from 6 rats per group) were electrically stimulated to evoke both cytosolic Ca(2+) ([Ca(2+)]cyto) and contractile (sarcomere shortening) responses that were simultaneously measured using an IonOptix system. Cardiomyocytes were divided into two groups: 1) those exposed to hypothermia (15°C for 2 h) followed by rewarming (35°C; H/R); or 2) time-matched normothermic (35°C) controls (CTL). Contractile dysfunction after H/R was indicated by reduced velocity and extent of sarcomere length (SL) shortening compared with time-matched controls. Throughout hypothermia, basal [Ca(2+)]cyto increased and the duration of evoked [Ca(2+)]cyto transients was prolonged. Phase-loop plots of [Ca(2+)]cyto vs. contraction were shifted rightward in cardiomyocytes during hypothermia compared with CTL, indicating a decrease in Ca(2+) sensitivity. Using Western blot, we found that H/R increases cTnI phosphorylation. These results support our overall hypothesis and suggest that H/R disrupts excitation-contraction coupling of cardiomyocytes due to increased cTnI phosphorylation and reduced Ca(2+) sensitivity.

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“…18,19 Furthermore, myocardial calcium overload may cause myocardial Oxidative stress, calcium channels and selenium deficiency failure. 20,21 Oxidative stress leads to lipid peroxidation, and sulphydryl group oxidation seems to be among the mechanisms that may produce membrane defects, causing intracellular calcium overload and cardiac contractile dysfunction in the myocardium. 22 A change in the properties of the L-type calcium channel may be related directly to the structure of the channel or to the number of channels, both of which are regulated by Cacna1c, although this remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Oxidative Stress and L-type Calcium Channel Expression in the Ventricular Myocardia of Selenium-deficient Mice

et al. 2012

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OBJECTIVE: Expression of the Cacna1c(calcium channel, voltage-dependent, Ltype, a1C subunit) gene was studied to investigate the relationship between oxidative stress and L-type calcium channels in the myocardium of seleniumdeficient mice. METHODS: Selenium levels in liver and heart tissue samples from mice fed normal or selenium-deficient diets were evaluated by fluorometry. In the same mice, glutathione peroxidase (GPx) and Cacna1c gene expression were analysed, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured, oxidoreductase gene expression profiles were analysed (by DNA microarray), and myocardial structural changes were studied. RESULTS: In selenium-deficient versus control mice, Research has shown that deregulation of calcium through L-type calcium channels plays a crucial role in the pathogenesis of cell death, which results in calcium overload and eventually leads to cardiomyocyte injury. 5 Nevertheless, considerable uncertainty remains about whether L-type calcium channels are involved in cardiomyocyte damage induced by oxidative stress, and the degree to which the abundance and function of the L-type calcium channels are affected by oxidative stress. The present study assessed the relationship between oxidative stress and Ltype calcium channel levels in the myocardium, using a selenium-deficient mouse model. Materials and methods EXPERIMENTAL ANIMAL MODEL OF SELENIUM DEFICIENCYThe animal model of selenium deficiency was established according to the method of Vanderlelie et al. 6 , with slight modifications. The basal diet of the mice was low in selenium, containing 47% low-selenium yeast, 42% sucrose, 5% coconut oil, 5% premixed minerals and 1% premixed vitamins. Adult male and female C57BL/6 mice weighing 20 -25 g (10 weeks old) were housed in a pathogen-free environment at room temperature (22 -25°C) and maintained on the basal diet and tap water ad libitum before the selenium-deficient state was achieved. Animals were divided into six groups (n = 6 per group). Mice in seleniumdeficient groups were then fed a special mouse food that contained 4.5 µg/kg total selenium for 4, 12 or 24 weeks (groups SD-4w, SD-12w and SD-24w, respectively); control mice were fed standard mouse food containing 219 µg/kg total selenium for 4, 12 or 24 weeks (groups Ctr-4w, Ctr-12w and Ctr24w, respectively). At 4, 12 or 24 weeks, mice were sacrificed by severing the spinal cord. The heart, liver, brain and kidneys were perfused with ice-cold physiological saline (0.9% NaCl) until the blood was sufficiently removed; These organs were retained (and stored in ice-cold conditions) for use in the following experiments.Animal protocols were reviewed and approved by the Animal Care and Ethics

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Myocardial mechanical dysfunction and calcium overload following rewarming from experimental hypothermia in vivo

Cited by 45 publications

References 34 publications

Negative inotropic effects of epinephrine in the presence of increased β-adrenoceptor sensitivity during hypothermia in a rat model

Negative inotropic effects of epinephrine in the presence of increased β-adrenoceptor sensitivity during hypothermia in a rat model

Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes

Correlation between Oxidative Stress and L-type Calcium Channel Expression in the Ventricular Myocardia of Selenium-deficient Mice

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