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Regulation of myocardial oxygen delivery in response to graded reductions in hematocrit: role of K+ channels

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Abstract

This study was designed to identify mechanisms responsible for coronary vasodilation in response to progressive decreases in hematocrit. Isovolemic hemodilution was produced in open-chest, anesthetized swine via concurrent removal of 500 ml of arterial blood and the addition of 500 ml of 37 °C saline or synthetic plasma expander (Hespan, 6% hetastarch in 0.9% sodium chloride). Progressive hemodilution with Hespan resulted in an increase in coronary flow from 0.39 ± 0.05 to 1.63 ± 0.16 ml/min/g (P < 0.001) as hematocrit was reduced from 32 ± 1 to 10 ± 1% (P < 0.001). Overall, coronary flow corresponded with the level of myocardial oxygen consumption, was dependent on arterial pressures ≥ ~ 60 mmHg, and occurred with little/no change in coronary venous PO2. Anemic coronary vasodilation was unaffected by the inhibition of nitric oxide synthase (l-NAME: 25 mg/kg iv; P = 0.92) or voltage-dependent K+ (K V) channels (4-aminopyridine: 0.3 mg/kg iv; P = 0.52). However, administration of the K ATP channel antagonist (glibenclamide: 3.6 mg/kg iv) resulted in an ~ 40% decrease in coronary blood flow (P < 0.001) as hematocrit was reduced to ~ 10%. These reductions in coronary blood flow corresponded with significant reductions in myocardial oxygen delivery at baseline and throughout isovolemic anemia (P < 0.001). These data indicate that vasodilator factors produced in response to isovolemic hemodilution converge on vascular smooth muscle glibenclamide-sensitive (K ATP) channels to maintain myocardial oxygen delivery and that this response is not dependent on endothelial-derived nitric oxide production or pathways that mediate dilation via K V channels.

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References

  1. Bagger H (1978) Distribution of maximum coronary blood flow in the left ventricular wall of anesthetized dogs. Acta Physiol Scand 104:48–60. doi:10.1111/j.1748-1716.1978.tb06250.x

    Article  CAS  PubMed  Google Scholar 

  2. Berwick ZC, Dick GM, Moberly SP, Kohr MC, Sturek M, Tune JD (2012) Contribution of voltage-dependent K(+) channels to metabolic control of coronary blood flow. J Mol Cell Cardiol 52:912–919. doi:10.1016/j.yjmcc.2011.07.004

    Article  CAS  PubMed  Google Scholar 

  3. Brazier J, Cooper N, Buckberg G (1974) The adequacy of subendocardial oxygen delivery: the interaction of determinants of flow, arterial oxygen content and myocardial oxygen need. Circulation 49:968–977. doi:10.1161/01.CIR.49.5.968

    Article  CAS  PubMed  Google Scholar 

  4. Canty JM Jr, Schwartz JS (1994) Nitric oxide mediates flow-dependent epicardial coronary vasodilation to changes in pulse frequency but not mean flow in conscious dogs. Circulation 89:375–384. doi:10.1161/01.CIR.89.1.375

    Article  CAS  PubMed  Google Scholar 

  5. Case RB, Berglund E, Sarnoff SJ (1955) Ventricular function. VII. Changes in coronary resistance and ventricular function resulting from acutely induced anemia and the effect thereon of coronary stenosis. Am J Med 18:397–405. doi:10.1016/0002-9343(55)90219-9

    Article  CAS  PubMed  Google Scholar 

  6. Chen Y, Traverse JH, Zhang J, Bache RJ (2001) Selective blockade of mitochondrial K(ATP) channels does not impair myocardial oxygen consumption. Am J Physiol Heart Circ Physiol 281:H738–H744

    CAS  PubMed  Google Scholar 

  7. Crystal GJ (1988) Coronary hemodynamic responses during local hemodilution in canine hearts. Am J Physiol 254:H525–H531

    CAS  PubMed  Google Scholar 

  8. Crystal GJ, El-Orbany M, Zhou X, Salem MR, Kim SJ (2008) Hemodilution does not alter the coronary vasodilating effects of endogenous or exogenous nitric oxide. Can J Anaesth 55:507–514. doi:10.1007/BF03016670

    Article  PubMed  Google Scholar 

  9. Crystal GJ, Kim SJ, Salem MR (1993) Right and left ventricular O2 uptake during hemodilution and beta-adrenergic stimulation. Am J Physiol 265:H1769–H1777

    CAS  PubMed  Google Scholar 

  10. Crystal GJ, Rooney MW, Salem MR (1988) Regional hemodynamics and oxygen supply during isovolemic hemodilution alone and in combination with adenosine-induced controlled hypotension. Anesth Analg 67:211–218. doi:10.1213/00000539-198803000-00002

    Article  CAS  PubMed  Google Scholar 

  11. Crystal GJ, Ruiz JR, Rooney MW, Salem MR (1988) Regional hemodynamics and oxygen supply during isovolemic hemodilution in the absence and presence of high-grade beta-adrenergic blockade. J Cardiothorac Anesth 2:772–779. doi:10.1016/0888-6296(88)90101-9

    Article  CAS  PubMed  Google Scholar 

  12. Crystal GJ, Salem MR (1991) Myocardial and systemic hemodynamics during isovolemic hemodilution alone and combined with nitroprusside-induced controlled hypotension. Anesth Analg 72:227–237. doi:10.1213/00000539-199102000-00016

    Article  CAS  PubMed  Google Scholar 

  13. Dart C, Standen NB (1995) Activation of ATP-dependent K+ channels by hypoxia in smooth muscle cells isolated from the pig coronary artery. J Physiol 483(Pt 1):29–39. doi:10.1113/jphysiol.1995.sp020565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dart C, Standen NB (1993) Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery. J Physiol 471:767–786. doi:10.1113/jphysiol.1993.sp019927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Deussen A, Borst M, Kroll K, Schrader J (1988) Formation of S-adenosylhomocysteine in the heart. II: a sensitive index for regional myocardial underperfusion. Circ Res 63:250–261. doi:10.1161/01.RES.63.1.250

    Article  CAS  PubMed  Google Scholar 

  16. Dick GM, Bratz IN, Borbouse L, Payne GA, Dincer UD, Knudson JD, Rogers PA, Tune JD (2008) Voltage-dependent K+ channels regulate the duration of reactive hyperemia in the canine coronary circulation. Am J Physiol Heart Circ Physiol 294:H2371–H2381. doi:10.1152/ajpheart.01279.2007

    Article  CAS  PubMed  Google Scholar 

  17. Dick GM, Tune JD (2010) Role of potassium channels in coronary vasodilation. Exp Biol Med (Maywood) 235:10–22. doi:10.1258/ebm.2009.009201

    Article  CAS  Google Scholar 

  18. Duncker DJ, Bache RJ (2008) Regulation of coronary blood flow during exercise. Physiol Rev 88:1009–1086. doi:10.1152/physrev.00045.2006

    Article  CAS  PubMed  Google Scholar 

  19. Feigl EO (1983) Coronary physiology. Physiol Rev 63:1–205

    CAS  PubMed  Google Scholar 

  20. Feigl EO, Neat GW, Huang AH (1990) Interrelations between coronary artery pressure, myocardial metabolism and coronary blood flow. J Mol Cell Cardiol 22:375–390. doi:10.1016/0022-2828(90)91474-L

    Article  CAS  PubMed  Google Scholar 

  21. Gauthier-Rein KM, Bizub DM, Lombard JH, Rusch NJ (1997) Hypoxia-induced hyperpolarization is not associated with vasodilation of bovine coronary resistance arteries. Am J Physiol 272:H1462–H1469

    CAS  PubMed  Google Scholar 

  22. Geha AS (1976) Coronary and cardiovascular dynamics and oxygen availability during acute normovolemic anemia. Surgery 80:47–53

    CAS  PubMed  Google Scholar 

  23. Gewirtz H, Olsson RA, Most AS (1987) Role of adenosine in mediating the coronary vasodilative response to acute hypoxia. Cardiovasc Res 21:81–89. doi:10.1093/cvr/21.2.81

    Article  CAS  PubMed  Google Scholar 

  24. Gisselsson L, Rosberg B, Ericsson M (1982) Myocardial blood flow, oxygen uptake and carbon dioxide release of the human heart during hemodilution. Acta Anaesthesiol Scand 26:589–591. doi:10.1111/j.1399-6576.1982.tb01820.x

    Article  CAS  PubMed  Google Scholar 

  25. Goodwill AG, Dick GM, Kiel AM, Tune JD (2017) Regulation of coronary blood flow. Compr Physiol 7:321–382. doi:10.1002/cphy.c160016

    Article  PubMed  Google Scholar 

  26. Goodwill AG, Fu L, Noblet JN, Casalini ED, Sassoon D, Berwick ZC, Kassab GS, Tune JD, Dick GM (2016) KV7 channels contribute to paracrine, but not metabolic or ischemic, regulation of coronary vascular reactivity in swine. Am J Physiol Heart Circ Physiol 310:H693–H704. doi:10.1152/ajpheart.00688.2015

    Article  PubMed  PubMed Central  Google Scholar 

  27. Goodwill AG, Noblet JN, Sassoon D, Fu L, Kassab GS, Schepers L, Herring BP, Rottgen TS, Tune JD, Dick GM (2016) Critical contribution of KV1 channels to the regulation of coronary blood flow. Basic Res Cardiol 111:56. doi:10.1007/s00395-016-0575-0

    Article  PubMed  PubMed Central  Google Scholar 

  28. Guarini G, Kiyooka T, Ohanyan V, Pung YF, Marzilli M, Chen YR, Chen CL, Kang PT, Hardwick JP, Kolz CL, Yin L, Wilson GL, Shokolenko I, Dobson JG Jr, Fenton R, Chilian WM (2016) Impaired coronary metabolic dilation in the metabolic syndrome is linked to mitochondrial dysfunction and mitochondrial DNA damage. Basic Res Cardiol 111:29. doi:10.1007/s00395-016-0547-4

    Article  PubMed  PubMed Central  Google Scholar 

  29. Herrmann SC, Feigl EO (1992) Adrenergic blockade blunts adenosine concentration and coronary vasodilation during hypoxia. Circ Res 70:1203–1216. doi:10.1161/01.RES.70.6.1203

    Article  CAS  PubMed  Google Scholar 

  30. Hirose Y, Kimura H, Kitahata H, Kawahito S, Oshita S (2000) Nitric oxide does not play a major role in the regulation of systemic hemodynamic responses to acute normovolemic hemodilution. Acta Anaesthesiol Scand 44:96–100. doi:10.1034/j.1399-6576.2000.440117.x

    Article  CAS  PubMed  Google Scholar 

  31. Holtz J, Bassenge E, von Restoriff W, Mayer E (1976) Transmural differences in myocardial blood flow and in coronary dilatory capacity in hemodiluted conscious dogs. Basic Res Cardiol 71:36–46. doi:10.1007/BF01907781

    Article  CAS  PubMed  Google Scholar 

  32. Ishibashi Y, Duncker DJ, Zhang J, Bache RJ (1998) ATP-sensitive K+ channels, adenosine, and nitric oxide-mediated mechanisms account for coronary vasodilation during exercise. Circ Res 82:346–359. doi:10.1161/01.RES.82.3.346

    Article  CAS  PubMed  Google Scholar 

  33. Jan KM, Chien S (1977) Effect of hematocrit variations on coronary hemodynamics and oxygen utilization. Am J Physiol 233:H106–H113

    CAS  PubMed  Google Scholar 

  34. Khouri EM, Gregg DE, Rayford CR (1965) Effect of exercise on cardiac output, left coronary flow and myocardial metabolism in the unanesthetized dog. Circ Res 17:427–437. doi:10.1161/01.RES.17.5.427

    Article  CAS  PubMed  Google Scholar 

  35. Kuramoto K, Matsushita S, Matsuda T, Mifune J, Sakai M, Iwasaki T, Shinagawa T, Moroki N, Murakami M (1980) Effect of hematocrit and viscosity on coronary circulation and myocardial oxygen utilization. Jpn Circ J 44:443–448. doi:10.1253/jcj.44.443

    Article  CAS  PubMed  Google Scholar 

  36. Lee SC, Mallet RT, Shizukuda Y, Williams AG Jr, Downey HF (1992) Canine coronary vasodepressor responses to hypoxia are attenuated but not abolished by 8-phenyltheophylline. Am J Physiol 262:H955–H960

    CAS  PubMed  Google Scholar 

  37. Levy PS, Kim SJ, Eckel PK, Chavez R, Ismail EF, Gould SA, Ramez Salem M, Crystal GJ (1993) Limit to cardiac compensation during acute isovolemic hemodilution: influence of coronary stenosis. Am J Physiol 265:H340–H349

    CAS  PubMed  Google Scholar 

  38. Liu Y, Gutterman DD (2009) Vascular control in humans: focus on the coronary microcirculation. Basic Res Cardiol 104:211–227. doi:10.1007/s00395-009-0775-y

    Article  PubMed  PubMed Central  Google Scholar 

  39. Martinez RR, Setty S, Zong P, Tune JD, Downey HF (2005) Nitric oxide contributes to right coronary vasodilation during systemic hypoxia. Am J Physiol Heart Circ Physiol 288:H1139–H1146. doi:10.1152/ajpheart.01139.2003

    Article  CAS  PubMed  Google Scholar 

  40. Laughlin MH, Korthuis RJ, Duncker DJ, Bache RJ (1996) Control of blood flow to cardiac and skeletal muscle during exercise. Compr Physiol Handb Physiol Exerc Regul Integr Mult Syst. doi:10.1002/cphy.cp120116

    Google Scholar 

  41. McMahon TJ, Stamler JS (1999) Concerted nitric oxide/oxygen delivery by hemoglobin. Methods Enzymol 301:99–114. doi:10.1016/S0076-6879(99)01073-3

    Article  CAS  PubMed  Google Scholar 

  42. Merrill GF, Downey HF, Jones CE (1986) Adenosine deaminase attenuates canine coronary vasodilation during systemic hypoxia. Am J Physiol 250:H579–H583

    CAS  PubMed  Google Scholar 

  43. Merrill GF, Downey HF, Yonekura S, Watanabe N, Jones CE (1988) Adenosine deaminase attenuates canine coronary vasodilatation during regional non-ischaemic myocardial hypoxia. Cardiovasc Res 22:345–350. doi:10.1093/cvr/22.5.345

    Article  CAS  PubMed  Google Scholar 

  44. Miura H, Wachtel RE, Loberiza FR Jr, Saito T, Miura M, Nicolosi AC, Gutterman DD (2003) Diabetes mellitus impairs vasodilation to hypoxia in human coronary arterioles: reduced activity of ATP-sensitive potassium channels. Circ Res 92:151–158. doi:10.1161/01.RES.0000052671.53256.49

    Article  CAS  PubMed  Google Scholar 

  45. Murakami H, Kim SJ, Lee SC, Strete D, Downey HF (1990) Adenosine exacerbates ischemic myocardial injury during regional coronary hypoxemia in the dog. Jpn Heart J 31:365–383. doi:10.1536/ihj.31.365

    Article  CAS  PubMed  Google Scholar 

  46. Murray JF, Escobar E, Rapaport E (1969) Effects of blood viscosity on hemodynamic responses in acute normovolemic anemia. Am J Physiol 216:638–642

    CAS  PubMed  Google Scholar 

  47. Nelson RR, Gobel FL, Jorgensen CR, Wang K, Wang Y, Taylor HL (1974) Hemodynamic predictors of myocardial oxygen consumption during static and dynamic exercise. Circulation 50:1179–1189. doi:10.1161/01.CIR.50.6.1179

    Article  CAS  PubMed  Google Scholar 

  48. Nichols CG, Lederer WJ (1991) Adenosine triphosphate-sensitive potassium channels in the cardiovascular system. Am J Physiol 261:H1675–H1686

    CAS  PubMed  Google Scholar 

  49. Ohanyan V, Yin L, Bardakjian R, Kolz C, Enrick M, Hakobyan T, Kmetz J, Bratz I, Luli J, Nagane M, Khan N, Hou H, Kuppusamy P, Graham J, Fu FK, Janota D, Oyewumi MO, Logan S, Lindner JR, Chilian WM (2015) Requisite role of Kv1.5 channels in coronary metabolic dilation. Circ Res 117:612–621. doi:10.1161/CIRCRESAHA.115.306642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Richardson RS, Poole DC, Knight DR, Kurdak SS, Hogan MC, Grassi B, Johnson EC, Kendrick KF, Erickson BK, Wagner PD (1993) High muscle blood flow in man: is maximal O2 extraction compromised? J Appl Physiol (1985) 75:1911–1916

    CAS  Google Scholar 

  51. Rogers PA, Chilian WM, Bratz IN, Bryan RM Jr, Dick GM (2007) H2O2 activates redox- and 4-aminopyridine-sensitive K v channels in coronary vascular smooth muscle. Am J Physiol Heart Circ Physiol 292:H1404–H1411. doi:10.1152/ajpheart.00696.2006

    Article  CAS  PubMed  Google Scholar 

  52. Rogers PA, Dick GM, Knudson JD, Focardi M, Bratz IN, Swafford AN Jr, Saitoh S, Tune JD, Chilian WM (2006) H2O2-induced redox-sensitive coronary vasodilation is mediated by 4-aminopyridine-sensitive K+ channels. Am J Physiol Heart Circ Physiol 291:H2473–H2482. doi:10.1152/ajpheart.00172.2006

    Article  CAS  PubMed  Google Scholar 

  53. Saitoh S, Zhang C, Tune JD, Potter B, Kiyooka T, Rogers PA, Knudson JD, Dick GM, Swafford A, Chilian WM (2006) Hydrogen peroxide: a feed-forward dilator that couples myocardial metabolism to coronary blood flow. Arterioscler Thromb Vasc Biol 26:2614–2621. doi:10.1161/01.ATV.0000249408.55796.da

    Article  CAS  PubMed  Google Scholar 

  54. Setty S, Zong P, Sun W, Tune JD, Downey HF (2008) Hypoxia-induced vasodilation in the right coronary circulation of conscious dogs: role of adrenergic activation. Auton Neurosci 138:76–82. doi:10.1016/j.autneu.2007.10.004

    Article  CAS  PubMed  Google Scholar 

  55. Shizukuda Y, Mallet RT, Lee SC, Downey HF (1992) Hypoxic preconditioning of ischaemic canine myocardium. Cardiovasc Res 26:534–542. doi:10.1093/cvr/26.5.534

    Article  CAS  PubMed  Google Scholar 

  56. Song Y, Srinivas M, Belardinelli L (1996) Nonspecific inhibition of adenosine-activated K+ current by glibenclamide in guinea pig atrial myocytes. Am J Physiol 271:H2430–H2437

    CAS  PubMed  Google Scholar 

  57. Stamler JS, Jia L, Eu JP, McMahon TJ, Demchenko IT, Bonaventura J, Gernert K, Piantadosi CA (1997) Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276:2034–2037. doi:10.1126/science.276.5321.2034

    Article  CAS  PubMed  Google Scholar 

  58. Stepp DW, Merkus D, Nishikawa Y, Chilian WM (2001) Nitric oxide limits coronary vasoconstriction by a shear stress-dependent mechanism. Am J Physiol Heart Circ Physiol 281:H796–H803

    CAS  PubMed  Google Scholar 

  59. Stepp DW, Nishikawa Y, Chilian WM (1999) Regulation of shear stress in the canine coronary microcirculation. Circulation 100:1555–1561. doi:10.1161/01.CIR.100.14.1555

    Article  CAS  PubMed  Google Scholar 

  60. Stumpe T, Schrader J (1997) Phosphorylation potential, adenosine formation, and critical PO2 in stimulated rat cardiomyocytes. Am J Physiol 273:H756–H766

    CAS  PubMed  Google Scholar 

  61. Tarnow J, Eberlein HJ, Hess W, Schneider E, Schweichel E, Zimmermann G (1979) Hemodynamic interactions of hemodilution, anaesthesia, propranolol pretreatment and hypovolaemia. II: Coronary circulation. Basic Res Cardiol 74:123–130. doi:10.1007/BF01907815

    Article  CAS  PubMed  Google Scholar 

  62. Thorling EB, Erslev AJ (1968) The “tissue” tension of oxygen and its relation to hematocrit and erythropoiesis. Blood 31:332–343

    CAS  PubMed  Google Scholar 

  63. Tune JD (2014) Coronary circulation. Morgan & Claypool Life Sciences, Williston

    Google Scholar 

  64. Van Woerkens EC, Trouwborst A, Duncker DJ, Koning MM, Boomsma F, Verdouw PD (1992) Catecholamines and regional hemodynamics during isovolemic hemodilution in anesthetized pigs. J Appl Physiol (1985) 72:760–769

    Google Scholar 

  65. Van Wylen DG, Williams AG Jr, Downey HF (1993) Interstitial purine metabolites and lactate during regional myocardial hypoxia. Cardiovasc Res 27:1498–1503. doi:10.1093/cvr/27.8.1498

    Article  PubMed  Google Scholar 

  66. Vatner SF, Higgins CB, Franklin D (1972) Regional circulatory adjustments to moderate and severe chronic anemia in conscious dogs at rest and during exercise. Circ Res 30:731–740. doi:10.1161/01.RES.30.6.731

    Article  CAS  PubMed  Google Scholar 

  67. von Restorff W, Hofling B, Holtz J, Bassenge E (1975) Effect of increased blood fluidity through hemodilution on coronary circulation at rest and during exercise in dogs. Pflugers Arch 357:15–24. doi:10.1007/BF00584541

    Article  Google Scholar 

  68. Wilkerson DK, Rosen AL, Sehgal LR, Gould SA, Sehgal HL, Moss GS (1988) Limits of cardiac compensation in anemic baboons. Surgery 103:665–670

    CAS  PubMed  Google Scholar 

  69. Woodson RD, Auerbach S (1982) Effect of increased oxygen affinity and anemia on cardiac output and its distribution. J Appl Physiol Respir Environ Exerc Physiol 53:1299–1306

    CAS  PubMed  Google Scholar 

  70. Yao X, Chang AY, Boulpaep EL, Segal AS, Desir GV (1996) Molecular cloning of a glibenclamide-sensitive, voltage-gated potassium channel expressed in rabbit kidney. J Clin Invest 97:2525–2533. doi:10.1172/JCI118700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Young SH, Stone HL (1976) Effect of a reduction in arterial oxygen content (carbon monoxide) on coronary flow. Aviat Sp Environ Med 47:142–146

    CAS  Google Scholar 

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Acknowledgements

The authors wish to thank Joshua Sturek for expert technical assistance. This study was supported by U01HL118738.

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  1. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA

    Alexander M. Kiel, Adam G. Goodwill, Jillian N. Noblet, April L. Barnard, Daniel J. Sassoon & Johnathan D. Tune

  2. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA

    Alexander M. Kiel

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Kiel, A.M., Goodwill, A.G., Noblet, J.N. et al. Regulation of myocardial oxygen delivery in response to graded reductions in hematocrit: role of K+ channels. Basic Res Cardiol 112, 65 (2017). https://doi.org/10.1007/s00395-017-0654-x

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