Evaluation of Cardiac Ischemia by NADH Fluorescence Photography

Barlow, Clyde H.; Harken, Alden H.; Chance, B.

doi:10.1097/00000658-197712000-00013

Cited by 51 publications

(17 citation statements)

References 6 publications

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“…This technique has been shown to be a very sensitive indicator of myocardial oxygenation (Barlow et al, 1977). Moreover, tissue injury by toxic agents such as oxygen free radicals also induces an increase in NADH-fluorescence intensity (Rump et al, 1993b,c (Rump et al, 1993a).…”

Section: Discussionmentioning

confidence: 99%

A quantitative comparison of functional and anti‐ischaemic effects of the phosphodiesterase‐inhibitors, amrinone, milrinone and levosimendan in rabbit isolated hearts

Rump

Açar

Klaus

1994

British J Pharmacology

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1 The functional and anti-ischaemic effects of the phosphodiesterase (PDE)-inhibitors, amrinone, milrinone and levosimendan, a new agent combining PDE-inhibitory with calcium-sensitizing properties, were investigated in rabbit isolated hearts (Langendorff, constant pressure: 70 cmH2O, Tyrode solution, Ca2+ 1.8 mmol 1', 37°C). Anti-ischaemic effects were studied in electrically-driven hearts (200 beats min '). Acute regional ischaemia was induced by ligature of a branch of the circumflex coronary artery and quantified from epicardial NADH-fluorescence photography. 2 Cumulative concentration-response curves in spontaneously beating hearts in the presence of isoprenaline (10-1 M), showed a higher inotropic and coronary vasodilator potency for levosimendan (ECm: 7 X 1O-7M) compared to milrinone (ECm: 7.7 x 10-6 M) or amrinone (EC5: 2 x 10-M).Although the maximal coronary dilator activity was similar for the three agents, the maximal inotropic and chronotropic effects were lower for levosimendan than for amrinone or milrinone (P <0.05).3 In regionally ischaemic hearts, milrinone (10-5 M) or levosimendan (5 x 10-6 M) similarly enhanced the left ventricular pressure (+ 15-20%) (P<0.05) and the global coronary flow (+ 40-50%) (P <0.05). The epicardial NADH-fluorescence area was significantly diminished by milrinone or levosimendan (-20-30%) (P<0.05) and there was no significant difference between the anti-ischaemic effects of either agent (P>0.05). 4 It is concluded that amrinone and milrinone possess similar functional profiles in rabbit isolated hearts and a higher inotropic and chronotropic efficacy than levosimendan. At functionally equieffective concentrations, milrinone and levosimendan show similar anti-ischaemic effects, related to an improvement of myocardial perfusion. The calcium-sensitizing properties seem not to be relevant for cardioprotection by levosimendan at the concentration used.

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Section: Discussionmentioning

confidence: 99%

A quantitative comparison of functional and anti‐ischaemic effects of the phosphodiesterase‐inhibitors, amrinone, milrinone and levosimendan in rabbit isolated hearts

Rump

Açar

Klaus

1994

British J Pharmacology

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“…The reduced state is required for reaction with HNE, a condition satisfied when the reduction potential (NADH͞NAD ϩ ) is high (11). During ischemia, the ratio of NADH͞NAD ϩ increases because of the absence of O 2 as a terminal electron acceptor (39,40). KGDH is therefore a prime candidate for inactivation on reoxygenation and subsequent lipid peroxidation.…”

Section: Biochemistry: Lucas and Szwedamentioning

confidence: 99%

Declines in mitochondrial respiration during cardiac reperfusion: Age-dependent inactivation of α-ketoglutarate dehydrogenase

Lucas

Szweda

1999

Proc. Natl. Acad. Sci. U.S.A.

135

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We previously reported that cardiac reperfusion results in declines in mitochondrial NADH-linked respiration. The degree of inactivation increased with age and was paralleled by modification of protein by the lipid peroxidation product 4-hydroxy-2-nonenal. To gain insight into potential sites of oxidative damage, the present study was undertaken to identify specific mitochondrial protein(s) inactivated during ischemia and reperfusion and to determine which of these losses in activity are responsible for observed declines in mitochondrial respiration. Using a Langendorff rat heart perfusion protocol, we observed age-dependent inactivation of complex I during ischemia and complex IV and ␣-ketoglutarate dehydrogenase during reperfusion. Although losses in complex I and IV activities were found not to be of sufficient magnitude to cause declines in mitochondrial respiration, an age-related decrease in complex I activity during ischemia may predispose old animals to more severe oxidative damage during reperfusion. It was determined that inactivation of ␣-ketoglutarate dehydrogenase is responsible, in large part, for observed reperfusion-induced declines in NADHlinked respiration. ␣-Ketoglutarate dehydrogenase is highly susceptible to 4-hydroxy-2-nonenal inactivation in vitro. Thus, our results suggest a plausible mechanism for age-dependent, reperfusion-induced declines in mitochondrial function and identify ␣-ketoglutarate dehydrogenase as a likely site of free radical-mediated damage.Cardiac mitochondria exhibit declines in the rate of NADHlinked respiration and ATP synthesis as a result of myocardial ischemia and reperfusion (1-5). Loss in mitochondrial respiratory function because of reperfusion is more pronounced in senescent relative to adult heart (1). Because mitochondria are a site of free radical production and oxidative damage during reperfusion (6-9), it is likely that free radical events contribute to reperfusion-induced declines in mitochondrial function. The goals of this study were to (i) identify and distinguish between specific mitochondrial protein(s) inactivated as a result of ischemia and͞or reperfusion; (ii) determine which of these losses in activity are responsible for observed declines in NADH-linked respiration; and (iii) evaluate the effects of age on these processes. Identification of enzymes inactivated during ischemia and reperfusion is necessary for rigorous assessment, at the molecular level, of events responsible for enzyme inactivation. Evaluation of which losses in activity are responsible for declines in the rate of overall mitochondrial respiration indicates the physiological consequences of enzyme inactivation. Distinguishing between ischemia-and reperfusioninduced declines in function will provide insight into factors contributing to free radical production and mitochondrial dysfunction. Thus, these studies are critical to elucidating mechanism(s) by which free radicals mediate declines in mitochondrial function during cardiac reperfusion.We have previously demonstrated ...

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“…This change can be detected optically because NADH is a fluorescent molecule (excitation wavelength 340 nm, emission wavelength 480 nm), but NAD is not. NADH fluorescence has proven to be a particularly sensitive and specific method of monitoring metabolism [1][2][3][4][5][6][7][8][9][10][11][12]. Using NADH fluorescence, we investigated the effects of an enriched oxygen reperfusion solution on an isolated perfused rat heart model after a period of global ischemia.…”

Section: Introductionmentioning

confidence: 99%

Monitoring myocardial reperfusion injury with NADH fluorometry

et al. 1992

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Using NADH fluorometry to monitor myocardial metabolism, the mechanism of reperfusion injury was investigated after the delivery of an experimental reperfusate. Using an isolated working heart preparation, rat hearts underwent 15 min of global ischemia at 37 degrees C. Following the ischemic insult, an oxygenated enriched reperfusion solution was given for 5 min. The hearts were then returned to a working state and aortic flow recorded to evaluate recovery. NADH levels were monitored throughout the experiment with a fluorometer and glycogen, AMP, ADP, and ATP were measured biochemically pre- and postischemia, after reperfusion and after recovery. In this study, reperfusion injury was best abated by an enriched reperfusate. Our results indicate the mechanism for this amelioration is not high-energy phosphate replenishment. Rather, as indicated by NADH fluorescence, the hearts attain an intermediate level of metabolism that permits glycogen to be restored and functional recovery to be improved.

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Evaluation of Cardiac Ischemia by NADH Fluorescence Photography

Cited by 51 publications

References 6 publications

A quantitative comparison of functional and anti‐ischaemic effects of the phosphodiesterase‐inhibitors, amrinone, milrinone and levosimendan in rabbit isolated hearts

A quantitative comparison of functional and anti‐ischaemic effects of the phosphodiesterase‐inhibitors, amrinone, milrinone and levosimendan in rabbit isolated hearts

Declines in mitochondrial respiration during cardiac reperfusion: Age-dependent inactivation of α-ketoglutarate dehydrogenase

Monitoring myocardial reperfusion injury with NADH fluorometry

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