| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 1996 American Heart Association, Inc.
Articles |
Nitric Oxide Attenuates Neutrophil-Mediated Myocardial Contractile Dysfunction After Ischemia and Reperfusion
From the Department of Medicine (A.J.B., D.M.F., S.A.B., A.M.S., D.J.L.), Cardiology Section, Tulane University School of Medicine, New Orleans, La, and the Cardiovascular Research Laboratories (R.P., M.J.C.), Department of Pharmacology, Division of Biomedical Sciences, King's College, University of London (UK).
Correspondence to David J. Lefer, PhD, Department of Medicine/Cardiology Section, SL48, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112.
Abstract With the knowledge of NO as an antiadhesion molecule, we performed studies to investigate the effects of NO on postischemic polymorphonuclear leukocyte (PMN)–mediated myocardial contractile dysfunction. Studies were performed with isolated perfused rat hearts subjected to 20 minutes of global ischemia and 45 minutes of reperfusion. Human PMNs (50 million) were infused over the first 5 minutes of reperfusion, and the recovery of left ventricular function was compared with baseline values. Infusion of PMNs alone (n=10) led to a 61% reduction in left ventricular developed pressure (LVDP) and a 57% reduction in the pressure-rate product (PRP) at 45 minutes of reperfusion. Infusion of an NO donor, CAS-754 (n=9), resulted in 80.2±6.7% recovery of LVDP and 77.0±8.6% recovery of PRP. Treatment with L-arginine (2.5 mmol/L, n=10) resulted in a similar improvement in the postischemic contractile state of the heart. In contrast, NG-nitro-L-arginine methyl ester (L-NAME) treatment (250 µmol/L, n=10) resulted in an exacerbation of contractile dysfunction, as evidenced by a 93% reduction in LVDP at 45 minutes of reperfusion and a 91% reduction in PRP. The deleterious effects of L-NAME were prevented by L-arginine coperfusion. We failed to observe any cardioprotective effects when NO or L-arginine was administered to hearts subjected to 25 minutes of ischemia and 45 minutes of reperfusion in the absence of PMNs. In conclusion, PMN-mediated myocardial contractile dysfunction is attenuated by NO and exacerbated by blockade of NO synthesis.
Key Words: nitric oxide • ischemia • reperfusion • NG-nitro-L-arginine methyl ester • L-arginine
This article has been cited by other articles:
 |
|
 |
|
  J. W. Calvert and D. J. Lefer Myocardial protection by nitrite Cardiovasc Res, July 15, 2009; 83(2): 195 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. S. Bryan, J. W. Calvert, J. W. Elrod, S. Gundewar, S. Y. Ji, and D. J. Lefer Dietary nitrite supplementation protects against myocardial ischemia-reperfusion injury PNAS, November 27, 2007; 104(48): 19144 - 19149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dezfulian, N. Raat, S. Shiva, and M. T. Gladwin Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics Cardiovasc Res, July 15, 2007; 75(2): 327 - 338. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-J. Kim, X. Zhang, X. Xu, A. Chen, J. B. Gonzalez, S. Koul, K. Vijayan, G. J. Crystal, S. F. Vatner, and T. H. Hintze Evidence for enhanced eNOS function in coronary microvessels during the second window of protection Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2152 - H2158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Fiedler, R. Feil, F. Hofmann, C. Willenbockel, H. Drexler, A. Smolenski, S. M. Lohmann, and K. C. Wollert cGMP-dependent Protein Kinase Type I Inhibits TAB1-p38 Mitogen-activated Protein Kinase Apoptosis Signaling in Cardiac Myocytes J. Biol. Chem., October 27, 2006; 281(43): 32831 - 32840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Cohen, X.-M. Yang, and J. M. Downey Nitric oxide is a preconditioning mimetic and cardioprotectant and is the basis of many available infarct-sparing strategies Cardiovasc Res, May 1, 2006; 70(2): 231 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Manukhina, H. F. Downey, and R. T. Mallet Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia. Experimental Biology and Medicine, April 1, 2006; 231(4): 343 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Omiyi, R. J. Brue, P. Taormina II, M. Harvey, N. Atkinson, and L. H. Young Protein Kinase C {beta}II Peptide Inhibitor Exerts Cardioprotective Effects in Rat Cardiac Ischemia/Reperfusion Injury J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 542 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Phillipson, E. E. Peterman, P. Taormina Jr., M. Harvey, R. J. Brue, N. Atkinson, D. Omiyi, U. Chukwu, and L. H. Young Protein kinase C-{zeta} inhibition exerts cardioprotective effects in ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H898 - H907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Liang, E. Gao, L. Tao, H. Liu, Y. Qu, T. A Christopher, B. L Lopez, and X. L Ma Critical timing of L-arginine treatment in post-ischemic myocardial apoptosis--role of NOS isoforms Cardiovasc Res, June 1, 2004; 62(3): 568 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schulz, M. Kelm, and G. Heusch Nitric oxide in myocardial ischemia/reperfusion injury Cardiovasc Res, February 15, 2004; 61(3): 402 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Jones, J. J. M. Greer, A. K. Kakkar, P. D. Ware, R. H. Turnage, M. Hicks, R. van Haperen, R. de Crom, S. Kawashima, M. Yokoyama, et al. Endothelial nitric oxide synthase overexpression attenuates myocardial reperfusion injury Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H276 - H282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Kown, M. A. Lijkwan, C. L. Jahncke, S. Murata, J. B. Rothbard, and R. C. Robbins L-arginine polymers enhance coronary flow and reduce oxidative stress following cardiac transplantation in rats J. Thorac. Cardiovasc. Surg., October 1, 2003; 126(4): 1065 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hayashi, Y. Sawa, N. Fukuyama, H. Nakazawa, and H. Matsuda Preoperative Glutamine Administration Induces Heat-Shock Protein 70 Expression and Attenuates Cardiopulmonary Bypass-Induced Inflammatory Response by Regulating Nitric Oxide Synthase Activity Circulation, November 12, 2002; 106(20): 2601 - 2607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Jones, M. F. Gibson, D. M. Rimmer III, T. M. Gibson, B. R. Sharp, and D. J. Lefer Direct vascular and cardioprotective effects of rosuvastatin, a new HMG-CoA reductase inhibitor J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1172 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Sharp, S. P. Jones, D. M. Rimmer, and D. J. Lefer Differential response to myocardial reperfusion injury in eNOS-deficient mice Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2422 - H2426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Gao, C.-L. Yao, E. Gao, Q.-Z. Mo, W.-L. Yan, R. McLaughlin, B. L. Lopez, T. A. Christopher, and X. L. Ma Enhancement of Glutathione Cardioprotection by Ascorbic Acid in Myocardial Reperfusion Injury J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 543 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. ZINGARELLI, P. W. HAKE, Z. YANG, M. O'CONNOR, A. DENENBERG, and H. R. WONG Absence of inducible nitric oxide synthase modulates early reperfusion-induced NF-{kappa}B and AP-1 activation and enhances myocardial damage FASEB J, March 1, 2002; 16(3): 327 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, J. W. Bissing, L. Xu, A. J. Ryan, S. M. Martin, F. J. Miller Jr, K. C. Kregel, G. R. Buettner, and R. E. Kerber Nitric oxide synthase inhibitors decrease coronary sinus-free radical concentration and ameliorate myocardial stunning in an ischemia-reperfusion model J. Am. Coll. Cardiol., August 1, 2001; 38(2): 546 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Iwata, S. Sai, Y. Nitta, M. Chen, R. de Fries-Hallstrand, J. Dalesandro, R. Thomas, and M. D. Allen Liposome-Mediated Gene Transfection of Endothelial Nitric Oxide Synthase Reduces Endothelial Activation and Leukocyte Infiltration in Transplanted Hearts Circulation, June 5, 2001; 103(22): 2753 - 2759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Young, Y. Ikeda, and A. M. Lefer Caveolin-1 peptide exerts cardioprotective effects in myocardial ischemia-reperfusion via nitric oxide mechanism Am J Physiol Heart Circ Physiol, June 1, 2001; 280(6): H2489 - H2495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Costa, N. J. Christensen, G. Farley, and I. Biaggioni NO modulates norepinephrine release in human skeletal muscle: implications for neural preconditioning Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2001; 280(5): R1494 - R1498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ikeda, L. H Young, R. Scalia, C. R Ross, and A. M Lefer PR-39, a proline/arginine-rich antimicrobial peptide, exerts cardioprotective effects in myocardial ischemia-reperfusion Cardiovasc Res, January 1, 2001; 49(1): 69 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Young, Y. Ikeda, R. Scalia, and A. M. Lefer C-peptide exerts cardioprotective effects in myocardial ischemia-reperfusion Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1453 - H1459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Okazaki, Z.-L. Cao, S. Ohtsubo, M. Hamada, K. Naito, K. Rikitake, M. Natsuaki, and T. Itoh Leukocyte-depleted reperfusion after long cardioplegic arrest attenuates ischemia-reperfusion injury of the coronary endothelium and myocardium in rabbit hearts Eur. J. Cardiothorac. Surg., July 1, 2000; 18(1): 90 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Kudej, S.-J. Kim, Y.-T. Shen, J. B. Jackson, A. B. Kudej, G.-P. Yang, S. P. Bishop, and S. F. Vatner Nitric oxide, an important regulator of perfusion-contraction matching in conscious pigs Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H451 - H456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Padilla, D. Garcia-Dorado, L. Agullo, J. Inserte, A. Paniagua, S. Mirabet, J. A. Barrabes, M. Ruiz-Meana, and J. Soler-Soler L-Arginine administration prevents reperfusion-induced cardiomyocyte hypercontracture and reduces infarct size in the pig Cardiovasc Res, June 1, 2000; 46(3): 412 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-L. Cao, Y. Okazaki, K. Naito, T. Ueno, M. Natsuaki, and T. Itoh Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart Ann. Thorac. Surg., April 1, 2000; 69(4): 1121 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Ronson, V. H. Thourani, X.-L. Ma, S. L. Katzmark, D. Han, Z.-Q. Zhao, M. Nakamura, R. A. Guyton, and J. Vinten-Johansen Peroxynitrite, the Breakdown Product of Nitric Oxide, Is Beneficial in Blood Cardioplegia but Injurious in Crystalloid Cardioplegia Circulation, November 9, 1999; 100 (2009): II-384 - II-391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Jordan, Z.-Q. Zhao, and J. Vinten-Johansen The role of neutrophils in myocardial ischemia-reperfusion injury Cardiovasc Res, September 1, 1999; 43(4): 860 - 878. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Lefer, B. Campbell, Y.-K. Shin, R. Scalia, R. Hayward, and D. J. Lefer Simvastatin Preserves the Ischemic-Reperfused Myocardium in Normocholesterolemic Rat Hearts Circulation, July 13, 1999; 100(2): 178 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Lefer, S. P. Jones, W. G. Girod, A. Baines, M. B. Grisham, A. S. Cockrell, P. L. Huang, and R. Scalia Leukocyte-endothelial cell interactions in nitric oxide synthase-deficient mice Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H1943 - H1950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Kersten and D. C. Warltier Modulation of the adaptive response to myocardial ischemia by coexisting disease Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H2268 - H2270. [Full Text] [PDF]
|
|
|
|
|
|
S. P. Jones, W. G. Girod, A. J. Palazzo, D. N. Granger, M. B. Grisham, D. Jourd'Heuil, P. L. Huang, and D. J. Lefer Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1567 - H1573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Lefer, B. Campbell, R. Scalia, and D. J. Lefer Synergism Between Platelets and Neutrophils in Provoking Cardiac Dysfunction After Ischemia and Reperfusion : Role of Selectins Circulation, September 29, 1998; 98(13): 1322 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T Gonon, Q.-D. Wang, and J. Pernow The endothelin A receptor antagonist LU 135252 protects the myocardium from neutrophil injury during ischaemia/reperfusion Cardiovasc Res, September 1, 1998; 39(3): 674 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Campbell, Y. K. Shin, R. Scalia, and A. M. Lefer Beneficial effects of N,N,N-trimethylsphingosine following ischemia and reperfusion in the isolated perfused rat heart Cardiovasc Res, August 1, 1998; 39(2): 393 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. U Sys, G. W De Keulenaer, and D. L Brutsaert Physiopharmacological evaluation of myocardial performance: how to study modulation by cardiac endothelium and related humoral factors? Cardiovasc Res, July 1, 1998; 39(1): 136 - 147. [Full Text] [PDF]
|
|
|
|
|
|
D. S. Morse, D. Adams, and B. Magnani Platelet and Neutrophil Activation During Cardiac Surgical Procedures: Impact of Cardiopulmonary Bypass Ann. Thorac. Surg., March 1, 1998; 65(3): 691 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Kouretas, A. K. Myers, Y. D. Kim, P. A. Cahill, J. L. Myers, Y.-N. Wang, J. V. Sitzmann, R. B. Wallace, and R. L. Hannan Heparin And Nonanticoagulant Heparin Preserve Regional Myocardial Contractility After Ischemia-Reperfusion Injury: Role Of Nitric Oxide J. Thorac. Cardiovasc. Surg., February 1, 1998; 115(2): 440 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. O. Nossuli, R. Hayward, R. Scalia, and A. M. Lefer Peroxynitrite Reduces Myocardial Infarct Size and Preserves Coronary Endothelium After Ischemia and Reperfusion in Cats Circulation, October 7, 1997; 96(7): 2317 - 2324. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. A. Kelly, J.-L. Balligand, and T. W. Smith Nitric Oxide and Cardiac Function Circ. Res., September 1, 1996; 79(3): 363 - 380. [Full Text]
|
|
|
|
|
|
B. R. Sharp, S. P. Jones, D. M. Rimmer, and D. J. Lefer Differential response to myocardial reperfusion injury in eNOS-deficient mice Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2422 - H2426. [Abstract] [Full Text] [PDF]
|
|