Effects of 2,3-butanedione monoxime in isolated hearts: Protection during reperfusion after global ischemia

Boban, Mladen; Stowe, David F.; Kampine, John P.; Goldberg, Alan H.; Bošnjak, Željko J.

doi:10.1016/s0022-5223(19)34237-0

Cited by 21 publications

(6 citation statements)

References 15 publications

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“…Second, we used the excitation-contraction uncoupler BDM in this study. On one hand, BDM is known to have an antifibrillatory effect (27,35), and the protective effect of BDM from ischemia-reperfusion injury is also well known (2,4,45). These effects of BDM could bias our estimates of vulnerable window toward smaller degree.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of shock-induced arrhythmogenesis during acute global ischemia

Cheng

Mowrey

Nikolski

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Little is known about the mechanisms of vulnerability and defibrillation under ischemic conditions. We investigated these mechanisms in 18 Langendorff-perfused rabbit hearts during 75% reduced-flow ischemia. Electrical activity was optically mapped from the anterior epicardium during right ventricular shocks applied at various phases of the cardiac cycle while the excitation-contraction decoupler 2,3-butanedione monoxime (BDM; 15 mM) was used to suppress motion artifacts caused by contraction of the heart. During ischemia, vulnerable window width increased [from 30-90% of the action potential duration (APD) in the control to -10 to 100% of the APD in ischemia]. Moreover, arrhythmia severity increased along with the reduction of APD (176 +/- 9 ms in control and 129 +/- 26 ms in ischemia, P < 0.01) and increased dispersion of repolarization (45 +/- 17 ms in control and 73 +/- 28 ms in ischemia, P < 0.01). Shock-induced virtual electrode polarization was preserved. Depolarizing (contrary to hyperpolarizing) response time constants increased. Virtual electrode-induced wavefronts of excitation had much more tortuous pathways leading to wavefront fractionation. Defibrillation failure at all shock strengths was observed in four hearts. Optical mapping revealed that the shock extinguished the arrhythmia; however, the arrhythmia self-originated after an isoelectric window of 339 +/- 189 ms. In conclusion, in most cases, virtual electrode-induced phase singularity (VEIPS) was responsible for shock-induced arrhythmogenesis during acute global ischemia. Enhancement of arrhythmogenesis was associated with an increased dispersion of repolarization and altered deexcitation. In four hearts, arrhythmogenesis could not be explained by VEIPS.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of shock-induced arrhythmogenesis during acute global ischemia

Cheng

Mowrey

Nikolski

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…The heart was reperfused in the MR scanner using an oxygenated Krebs‐Henseleit bicarbonate buffer (pH 7.4, temperature 38°C), mixed with heparinized blood (4:1 proportion). 2,3 Butanedione monoxime (BDM 97%; Aldrich, Paris, France), a potent reversible inhibitor of the actin‐myosin interaction, was added at a concentration of 30 mmol/l to the perfusate to inhibit motion artifacts related to contraction and to favor the homogeneity of myocardial perfusion through its vasodilation and protective effects on microvascularization (25).…”

Section: Methodsmentioning

confidence: 99%

Mapping myocardial perfusion with an intravascular MR contrast agent: Robustness of deconvolution methods at various blood flows

Neyran

Janier

Casali

et al. 2002

Magnetic Resonance in Med

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Evaluation of quantitative parameters such as regional myocardial blood flow (rMBF), blood volume (rMBV), and mean transit time (rMTT) by MRI is gaining acceptance for clinical applications, but still lacks robust postprocessing methods for map generation. Moreover, robustness should be preserved over the full range of myocardial flows and volumes. Using experimental data from an isolated pig heart preparation, synthetic MR kinetics were generated and four deconvolution approaches were evaluated. These methods were then applied to the firstpass T 1 images of the isolated pig heart using an intravascular contrast agent and rMBF, rMBV and rMTT maps were generated. In both synthetic and experimental data, the fit between calculated and original data reached equally good results with the four techniques. rMBV was the only parameter estimated correctly in numerical experiments. Moreover, using the algebraic method ARMA, abnormal regions were well delineated on rMBV maps. At high flows, rMBF was underestimated at the experimental noise level. Finally, rMTT maps appeared noisy and highly unreliable, especially at high flows. In conclusion, over the myocardial flow range, i.e., 0 -400 ml/min/100g, rMBF identification was biased in presence of noise, whereas rMBV was correctly identified. Thus, rMBV mapping could be a fast and robust way to detect abnormal myocardial regions. Magn Reson Med 48:166 -179, 2002.

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“…For example, BDM shortens the APD in sheep and guinea pig, 9 but prolongs the APD in the mouse 10 . BDM has also been shown to enhance shock‐induced arrhythmias, 11 and to provide a protective effect during reperfusion after ischemia 12 . As a result of these side effects, and in particular the effects directly related to ischemia, BDM may not be suitable as a motion blocker for ischemia studies.…”

Section: Introductionmentioning

confidence: 99%