NADH Changes During Hypoxia, Ischemia, and Increased Work Differ Between Isolated Heart Preparations

Overview

Journal Am J Physiol Heart Circ Physiol

Publisher American Physiological Society

Specialties Cardiology & Vascular Diseases
Physiology

Date 2013 Dec 17

PMID 24337462

Citations 34

Authors

Anastasia M Wengrowski

Sarah Kuzmiak-Glancy

Rafael Jaimes 3rd

Matthew W Kay

Affiliations

Soon will be listed here.

Abstract

Langendorff-perfused hearts and working hearts are established isolated heart preparation techniques that are advantageous for studying cardiac physiology and function, especially when fluorescence imaging is a key component. However, oxygen and energy requirements vary widely between isolated heart preparations. When energy supply and demand are not in harmony, such as when oxygen is not adequately available, the imbalance is reflected in NADH fluctuations. As such, NADH imaging can provide insight into the metabolic state of tissue. Hearts from New Zealand white rabbits were prepared as mechanically silenced Langendorff-perfused hearts, Langendorff-perfused hearts, or biventricular working hearts and subjected to sudden changes in workload, instantaneous global ischemia, and gradual hypoxia while heart rate, aortic pressure, and epicardial NADH fluorescence were monitored. Fast pacing resulted in a dip in NADH upon initiation and a spike in NADH when pacing was terminated in biventricular working hearts only, with the magnitude of the changes greatest at the fastest pacing rate. Working hearts were also most susceptible to changes in oxygen supply; NADH was at half-maximum value when perfusate oxygen was at 67.8 ± 13.7%. Langendorff-perfused and mechanically arrested hearts were the least affected by low oxygen supply, with half-maximum NADH occurring at 42.5 ± 5.0% and 23.7 ± 4.6% perfusate oxygen, respectively. Although the biventricular working heart preparation can provide a useful representation of mechanical in vivo heart function, it is not without limitations. Understanding the limitations of isolated heart preparations is crucial when studying cardiac function in the context of energy supply and demand.

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References

Gillis A, Kulisz E, Mathison H . Cardiac electrophysiological variables in blood-perfused and buffer-perfused, isolated, working rabbit heart. Am J Physiol. 1996; 271(2 Pt 2):H784-9. DOI: 10.1152/ajpheart.1996.271.2.H784. View

Katz L, Koretsky A, Balaban R . Respiratory control in the glucose perfused heart. A 31P NMR and NADH fluorescence study. FEBS Lett. 1987; 221(2):270-6. DOI: 10.1016/0014-5793(87)80939-0. View

Fedorov V, Lozinsky I, Sosunov E, Anyukhovsky E, Rosen M, Balke C . Application of blebbistatin as an excitation-contraction uncoupler for electrophysiologic study of rat and rabbit hearts. Heart Rhythm. 2007; 4(5):619-26. DOI: 10.1016/j.hrthm.2006.12.047. View

Brandes R, Bers D . Simultaneous measurements of mitochondrial NADH and Ca(2+) during increased work in intact rat heart trabeculae. Biophys J. 2002; 83(2):587-604. PMC: 1302172. DOI: 10.1016/S0006-3495(02)75194-1. View

Ingwall J . Energy metabolism in heart failure and remodelling. Cardiovasc Res. 2008; 81(3):412-9. PMC: 2639129. DOI: 10.1093/cvr/cvn301. View

Ince C, Ashruf J, Avontuur J, Wieringa P, Spaan J, Bruining H . Heterogeneity of the hypoxic state in rat heart is determined at capillary level. Am J Physiol. 1993; 264(2 Pt 2):H294-301. DOI: 10.1152/ajpheart.1993.264.2.H294. View

Bose S, French S, Evans F, Joubert F, Balaban R . Metabolic network control of oxidative phosphorylation: multiple roles of inorganic phosphate. J Biol Chem. 2003; 278(40):39155-65. DOI: 10.1074/jbc.M306409200. View

McCormack J, Halestrap A, Denton R . Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev. 1990; 70(2):391-425. DOI: 10.1152/physrev.1990.70.2.391. View

Demmy T, Magovern G, Kao R . Isolated biventricular working rat heart preparation. Ann Thorac Surg. 1992; 54(5):915-20. DOI: 10.1016/0003-4975(92)90649-o. View

10.

Asfour H, Wengrowski A, Jaimes 3rd R, Swift L, Kay M . NADH fluorescence imaging of isolated biventricular working rabbit hearts. J Vis Exp. 2012; (65). PMC: 3476403. DOI: 10.3791/4115. View

11.

WEGRIA R, Frank C, Wang H, LAMMERANT J . The effect of atrial and ventricular tachycardia on cardiac output, coronary blood flow and mean arterial blood pressure. Circ Res. 1958; 6(5):624-32. DOI: 10.1161/01.res.6.5.624. View

12.

Koretsky A, Katz L, Balaban R . Determination of pyridine nucleotide fluorescence from the perfused heart using an internal standard. Am J Physiol. 1987; 253(4 Pt 2):H856-62. DOI: 10.1152/ajpheart.1987.253.4.H856. View

13.

Ashruf J, Coremans J, Bruining H, Ince C . Increase of cardiac work is associated with decrease of mitochondrial NADH. Am J Physiol. 1995; 269(3 Pt 2):H856-62. DOI: 10.1152/ajpheart.1995.269.3.H856. View

14.

Brandes R, Bers D . Intracellular Ca2+ increases the mitochondrial NADH concentration during elevated work in intact cardiac muscle. Circ Res. 1997; 80(1):82-7. DOI: 10.1161/01.res.80.1.82. View

15.

Kay M, Swift L, Sangave A, Zderic V . High resolution contrast ultrasound and NADH fluorescence imaging of myocardial perfusion in excised rat hearts. Annu Int Conf IEEE Eng Med Biol Soc. 2009; 2008:969-72. DOI: 10.1109/IEMBS.2008.4649316. View

16.

Blinova K, Levine R, Boja E, Griffiths G, Shi Z, Ruddy B . Mitochondrial NADH fluorescence is enhanced by complex I binding. Biochemistry. 2008; 47(36):9636-45. PMC: 3515876. DOI: 10.1021/bi800307y. View

17.

Tune J, Gorman M, Feigl E . Matching coronary blood flow to myocardial oxygen consumption. J Appl Physiol (1985). 2004; 97(1):404-15. DOI: 10.1152/japplphysiol.01345.2003. View

18.

Swift L, Asfour H, Posnack N, Arutunyan A, Kay M, Sarvazyan N . Properties of blebbistatin for cardiac optical mapping and other imaging applications. Pflugers Arch. 2012; 464(5):503-12. PMC: 3586237. DOI: 10.1007/s00424-012-1147-2. View

19.

Kedem J, Breuer J, Acad B, Sonn J . Coronary vasodilation produced by tachycardia under various basal flow conditions. Arch Int Physiol Biochim. 1981; 89(4):287-94. DOI: 10.3109/13813458109069478. View

20.

Opie L . Metabolism of the heart in health and disease. I. Am Heart J. 1968; 76(5):685-98. DOI: 10.1016/0002-8703(68)90168-3. View