Different Responses of Non-ischemic and Post-ischemic Myocardium Towards Ca2+Sensitization

Korbmacher, B.; Sunderdiek, Ulrich; Arnold, G; Schipke, Jochen D.

doi:10.1006/jmcc.1997.0440

Cited by 8 publications

(8 citation statements)

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“…This is supported by the observation that the β‐adrenoceptor agonist dobutamine also produces a preferential increase in systolic shortening of stunned myocardium, whereas E es responses were similar in normal and stunned region (McFalls et al ., 1992; Fan et al ., 1995). Similar to the present study, Korbmacher et al . (1997) observed that EMD 60263 at an optimal dose of 3 μ M produced similar increments in LVdP/dt max in normal (from 1415 to 1885 mmHg s −1 ) and globally stunned (from 845 to 1300 mmHg s −1 ) isolated rabbit hearts in which afterload was held constant.…”

Section: Discussionmentioning

confidence: 99%

“…In view of the progressive increase in plasma levels over time, this observation suggests that the maximum effect in normal myocardium was reached at a lower dose than that in stunned myocardium. Indeed, Korbmacher et al . (1997) observed in their in vitro study that a further increase in dose of EMD 57033 to 10 μ M did not further increase LVdP/dt max in stunned hearts, while it slightly decreased LVdP/dt max in normal myocardium.…”

Section: Discussionmentioning

confidence: 99%

“…In rat skinned right ventricular trabeculae these authors have shown that EMD 57033 can even cause contraction in the absence of Ca 2+ . Consequently, contraction could be prolonged thereby delaying the onset of relaxation (Solaro et al ., 1993; Ravens et al ., 1996), the rate of relaxation could be attenuated (Hajjar et al ., 1997; Korbmacher et al ., 1997) and end‐diastolic stiffness could be increased (Hgashiyama et al ., 1995; Hajjar et al ., 1997) even when Ca 2+ concentrations are normal.…”

Section: Discussionmentioning

confidence: 99%

“…Stunned myocardium is characterized by both a depressed systolic and diastolic function (Charlat et al ., 1989; Ehring et al ., 1993; Bolli & Marban, 1999). Since a decreased responsiveness of the myofilaments to calcium (Ca 2+ ) has been implicated in the mechanism underlying stunning, several groups of investigators have successfully employed ‘Ca 2+ ‐sensitizing agents’ to restore systolic function of stunned myocardium in a variety of in vivo (Soei et al ., 1994; Abe et al ., 1995) and in vitro (Korbmacher et al ., 1994; 1995; 1997) models. It has been suggested that the inotropic response to Ca 2+ ‐sensitizers may differ between stunned and normal myocardium.…”

Section: Introductionmentioning

confidence: 99%

“…However, systolic shortening is strongly load-dependent, even more so in stunned myocardium, and does not necessarily re¯ect myocardial contractility (Fan et al, 1995). That also the lusitropic response to Ca 2+ -sensitizers in stunned and normal myocardium may dier was suggested by Korbmacher et al (1997), who showed that in response to high doses of EMD 60263 global diastolic function deteriorated more in normal than in globally stunned isolated rabbit hearts. However, data on diastolic functional responses of stunned myocardium to Ca 2+ -sensitizing agents in vivo are currently lacking.…”

Section: Introductionmentioning

confidence: 99%

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Cardiovascular profile of the calcium sensitizer EMD 57033 in open‐chest anaesthetized pigs with regionally stunned myocardium

Zeeuw

Trines

Krams

et al. 2000

British J Pharmacology

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1 Ca 2+ sensitizers enhance systolic function, but may impair relaxation in vitro; these e ects may di er in stunned and normal myocardium. We therefore studied the e ect of EMD 57033 on systolic and diastolic function of normal and stunned porcine myocardium in vivo. 2 Myocardial stunning by 15 min coronary occlusion and 30 min reperfusion abolished systolic shortening (SS) (baseline 13+1%) and decreased end-systolic elastance (E es ) from 67+7 to 47+5 mmHg mm 71 (both P50.05). Maximum rate of fall of myocardial elastance (dE/dt min ) decreased from 7850+100 to 7320+30 mmHg mm 71 s 71 , while the time constant t e of the decay of elastance increased from 58+3 to 68+6 ms (both P50.05). End-diastolic elastance (E ed ) was unchanged although the zero pressure intercept (L 0,ed ) had increased. 3 In the stunned region, EMD 57033 (0.2 mg kg 71 min 71 for 60 min, i.v., n=7) increased SS to 19+2%, E es to 287+40 mmHg mm 71 , dE/dt min to 73630+640 mmHg mm 71 s 71 and decreased t e to 50+3 ms, while E ed remained unchanged. In the normal region, EMD 57033 increased SS from 14+2 to 18+3%, E es from 59+4 to 263+23 mmHg mm 71 , dE/dt min from 7480+70 to 72280+700 mmHg mm 71 s 71 and decreased t e from 91+12 to 61+3 ms (all P50.05), while E ed remained unchanged. These responses were minimally a ected by adrenoceptor blockade (n=7). Vehicle (n=7) had no e ect on either region. 4 EMD 57033 increased cardiac output (up to 27+8%) and LVdP/dt max (86+19%). Mean aortic pressure decreased (19+7%) due to systemic vasodilation that was not amenable to blockade of adrenoceptors or NO synthesis. 5 In conclusion, EMD 57033 restored systolic and diastolic function of stunned myocardium, and produced similar improvements in systolic and diastolic function in normal myocardium. British Journal of Pharmacology (2000)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cardiovascular profile of the calcium sensitizer EMD 57033 in open‐chest anaesthetized pigs with regionally stunned myocardium

Zeeuw

Trines

Krams

et al. 2000

British J Pharmacology

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Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy

et al. 2018

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PurposeTo describe the earliest features of ABCA4-associated retinopathy.DesignCase series.ParticipantsChildren with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy.MethodsThe retinal phenotype was characterized by color fundus photography, OCT, fundus autofluorescence (FAF) imaging, electroretinography, and in 2 patients, adaptive optics scanning laser ophthalmoscopy (AOSLO). Sequencing of the ABCA4 gene was performed in all patients.Main Outcome MeasuresVisual acuity, OCT, FAF, electroretinography, and AOSLO results.ResultsEight children with ABCA4-associated retinopathy without macular atrophy were identified. Biallelic variants in ABCA4 were identified in all patients. Four children were asymptomatic, and 4 reported loss of VA. Patients were young (median age, 8.5 years; interquartile range, 6.8 years) with good visual acuity (median, 0.155 logarithm of the minimum angle of resolution [logMAR]; interquartile range, 0.29 logMAR). At presentation, the macula appeared normal (n = 3), had a subtly altered foveal reflex (n = 4), or demonstrated manifest fine yellow dots (n = 1). Fundus autofluorescence identified hyperautofluorescent dots in the central macula in 3 patients, 2 of whom showed a normal fundus appearance. Only 1 child had widespread hyperautofluorescent retinal flecks at presentation. OCT imaging identified hyperreflectivity at the base of the outer nuclear layer in all 8 patients. Where loss of outer nuclear volume was evident, this appeared to occur preferentially at a perifoveal locus. Longitudinal split-detector AOSLO imaging in 2 individuals confirmed that the greatest change in cone spacing occurred in the perifoveal, and not foveolar, photoreceptors. Electroretinography showed a reduced B-wave–to–A-wave ratio in 3 of 5 patients tested; in 2 children, recordings clearly showed electronegative results.ConclusionsIn childhood-onset ABCA4-associated retinopathy, the earliest stages of macular atrophy involve the parafovea and spare the foveola. In some cases, these changes are predated by tiny, foveal, yellow, hyperautofluorescent dots. Hyperreflectivity at the base of the outer nuclear layer, previously described as thickening of the external limiting membrane, is likely to represent a structural change at the level of the foveal cone nuclei. Electroretinography suggests that the initial site of retinal dysfunction may occur after phototransduction.

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Cardiotonic drugs differentially alter cytosolic [Ca2+] to left ventricular relationships before and after ischemia in isolated guinea pig hearts

Chen

Camara

Rhodes

et al. 2003

Cardiovascular Research

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Different Responses of Non-ischemic and Post-ischemic Myocardium Towards Ca2+Sensitization

Cited by 8 publications

References 0 publications

Cardiovascular profile of the calcium sensitizer EMD 57033 in open‐chest anaesthetized pigs with regionally stunned myocardium

Cardiovascular profile of the calcium sensitizer EMD 57033 in open‐chest anaesthetized pigs with regionally stunned myocardium

Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy

Cardiotonic drugs differentially alter cytosolic [Ca2+] to left ventricular relationships before and after ischemia in isolated guinea pig hearts

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