New approaches to prevention and treatment of radial artery graft vasospasm

David G. Cable, James A. Caccitolo, Paul J. Pearson, Timothy O'Brien, Charles J. Mullany, Richard C. Daly, Thomas A. Orszulak, Hartzell V Schaff

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Background - There has been renewed interest in radial artery (RA) conduits for coronary artery bypass because of the relative resistance of arterial grafts to atherosclerosis compared with autogenous vein grafts. Although improved drug therapy for arterial spasm is now available, vasospasm still occurs in at least 5% to 10% of RA grafts. We systematically evaluated the effectiveness of calcium channel blockers and organic nitrates for inhibition or reversal of RA contraction in vitro. Additionally, we investigated the efficacy of novel gene therapy with endothelial nitric oxide synthase (eNOS) to inhibit RA contractions. Methods and Results - Segments of RA from 28 patients undergoing coronary artery bypass grafting were mounted in organ chambers. In control experiments, KCl (5 to 50 mmol/L) produced dose-dependent increases in tension (maximum tension, 14.3±3.0 g, n=7). Addition of diltiazem or verapamil had no significant effect on KCl contraction (128±36% and 88±24% control, respectively); however, nifedipine markedly inhibited KCl contraction (27±4% control, P=0.005). Norepinephrine (NE, 10-9 to 10-4 M) produced dose-dependent increases in tension (maximum tension, 15.7±2.7 g in control rings, n=8). Diltiazem and verapamil pretreatment had no significant effect on NE contraction (103±14% and 90±14% control, respectively); nifedipine significantly inhibited NE contraction (70±11% control, P=0.02). Isosorbide dinitrate and nitroglycerin markedly inhibited KCl contractions (47±9% and 30±8% of controls, n=6) and NE contractions (42±10% and 31±9% of controls, n=6). Nifedipine, isosorbide, and nitroglycerin were further evaluated for the ability to reverse an established contraction (KCl 40 mmol/L); nitroglycerin was most effective in reversing RA contraction. In separate experiments, RA underwent adenoviral-mediated gene transfer with vehicle, Escherichia coli β- galactosidase, or eNOS (eNOS, 1010 PFU/mLx1 hour). Transgene expression was confirmed by β-galactosidase activity and eNOS immunohistochemistry after 40 hours of ex vivo incubation. Immunohistochemistry demonstrated recombinant NOS in adenovirus encoding bovine eNOS (Ad.CMVeNOS) RA only. Ad.CMVeNOS arteries contracted only 46.6±13.7% of controls to KCl (n=5) and 48.2±11.4% of controls to prostaglandin F2(αa) (10-9 to 10-6 M, n=5). Conclusions - Diltiazem, which is used empirically to prevent RA vasospasm, had little effect on human RA contractions (receptor-independent and receptor- dependent). Organic nitrates inhibited and reversed RA contractions. Adenoviral transfer of NOS suggests that future clinical application of gene therapy may play an important role in prevention of RA vasospasm.

Original languageEnglish (US)
JournalCirculation
Volume98
Issue number19 SUPPL.
StatePublished - Nov 10 1998

Fingerprint

Radial Artery
Transplants
Nitric Oxide Synthase Type III
Diltiazem
Nitroglycerin
Therapeutics
Nifedipine
Galactosidases
Verapamil
Coronary Artery Bypass
Genetic Therapy
Nitrates
Immunohistochemistry
Isosorbide
Isosorbide Dinitrate
Dinoprost
Calcium Channel Blockers
Spasm
Transgenes
Adenoviridae

Keywords

  • Arteries
  • Genes
  • Grafting
  • Nitroglycerin
  • Vasospasm

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Cable, D. G., Caccitolo, J. A., Pearson, P. J., O'Brien, T., Mullany, C. J., Daly, R. C., ... Schaff, H. V. (1998). New approaches to prevention and treatment of radial artery graft vasospasm. Circulation, 98(19 SUPPL.).

New approaches to prevention and treatment of radial artery graft vasospasm. / Cable, David G.; Caccitolo, James A.; Pearson, Paul J.; O'Brien, Timothy; Mullany, Charles J.; Daly, Richard C.; Orszulak, Thomas A.; Schaff, Hartzell V.

In: Circulation, Vol. 98, No. 19 SUPPL., 10.11.1998.

Research output: Contribution to journalArticle

Cable, DG, Caccitolo, JA, Pearson, PJ, O'Brien, T, Mullany, CJ, Daly, RC, Orszulak, TA & Schaff, HV 1998, 'New approaches to prevention and treatment of radial artery graft vasospasm', Circulation, vol. 98, no. 19 SUPPL..
Cable DG, Caccitolo JA, Pearson PJ, O'Brien T, Mullany CJ, Daly RC et al. New approaches to prevention and treatment of radial artery graft vasospasm. Circulation. 1998 Nov 10;98(19 SUPPL.).
Cable, David G. ; Caccitolo, James A. ; Pearson, Paul J. ; O'Brien, Timothy ; Mullany, Charles J. ; Daly, Richard C. ; Orszulak, Thomas A. ; Schaff, Hartzell V. / New approaches to prevention and treatment of radial artery graft vasospasm. In: Circulation. 1998 ; Vol. 98, No. 19 SUPPL.
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abstract = "Background - There has been renewed interest in radial artery (RA) conduits for coronary artery bypass because of the relative resistance of arterial grafts to atherosclerosis compared with autogenous vein grafts. Although improved drug therapy for arterial spasm is now available, vasospasm still occurs in at least 5{\%} to 10{\%} of RA grafts. We systematically evaluated the effectiveness of calcium channel blockers and organic nitrates for inhibition or reversal of RA contraction in vitro. Additionally, we investigated the efficacy of novel gene therapy with endothelial nitric oxide synthase (eNOS) to inhibit RA contractions. Methods and Results - Segments of RA from 28 patients undergoing coronary artery bypass grafting were mounted in organ chambers. In control experiments, KCl (5 to 50 mmol/L) produced dose-dependent increases in tension (maximum tension, 14.3±3.0 g, n=7). Addition of diltiazem or verapamil had no significant effect on KCl contraction (128±36{\%} and 88±24{\%} control, respectively); however, nifedipine markedly inhibited KCl contraction (27±4{\%} control, P=0.005). Norepinephrine (NE, 10-9 to 10-4 M) produced dose-dependent increases in tension (maximum tension, 15.7±2.7 g in control rings, n=8). Diltiazem and verapamil pretreatment had no significant effect on NE contraction (103±14{\%} and 90±14{\%} control, respectively); nifedipine significantly inhibited NE contraction (70±11{\%} control, P=0.02). Isosorbide dinitrate and nitroglycerin markedly inhibited KCl contractions (47±9{\%} and 30±8{\%} of controls, n=6) and NE contractions (42±10{\%} and 31±9{\%} of controls, n=6). Nifedipine, isosorbide, and nitroglycerin were further evaluated for the ability to reverse an established contraction (KCl 40 mmol/L); nitroglycerin was most effective in reversing RA contraction. In separate experiments, RA underwent adenoviral-mediated gene transfer with vehicle, Escherichia coli β- galactosidase, or eNOS (eNOS, 1010 PFU/mLx1 hour). Transgene expression was confirmed by β-galactosidase activity and eNOS immunohistochemistry after 40 hours of ex vivo incubation. Immunohistochemistry demonstrated recombinant NOS in adenovirus encoding bovine eNOS (Ad.CMVeNOS) RA only. Ad.CMVeNOS arteries contracted only 46.6±13.7{\%} of controls to KCl (n=5) and 48.2±11.4{\%} of controls to prostaglandin F2(αa) (10-9 to 10-6 M, n=5). Conclusions - Diltiazem, which is used empirically to prevent RA vasospasm, had little effect on human RA contractions (receptor-independent and receptor- dependent). Organic nitrates inhibited and reversed RA contractions. Adenoviral transfer of NOS suggests that future clinical application of gene therapy may play an important role in prevention of RA vasospasm.",
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T1 - New approaches to prevention and treatment of radial artery graft vasospasm

AU - Cable, David G.

AU - Caccitolo, James A.

AU - Pearson, Paul J.

AU - O'Brien, Timothy

AU - Mullany, Charles J.

AU - Daly, Richard C.

AU - Orszulak, Thomas A.

AU - Schaff, Hartzell V

PY - 1998/11/10

Y1 - 1998/11/10

N2 - Background - There has been renewed interest in radial artery (RA) conduits for coronary artery bypass because of the relative resistance of arterial grafts to atherosclerosis compared with autogenous vein grafts. Although improved drug therapy for arterial spasm is now available, vasospasm still occurs in at least 5% to 10% of RA grafts. We systematically evaluated the effectiveness of calcium channel blockers and organic nitrates for inhibition or reversal of RA contraction in vitro. Additionally, we investigated the efficacy of novel gene therapy with endothelial nitric oxide synthase (eNOS) to inhibit RA contractions. Methods and Results - Segments of RA from 28 patients undergoing coronary artery bypass grafting were mounted in organ chambers. In control experiments, KCl (5 to 50 mmol/L) produced dose-dependent increases in tension (maximum tension, 14.3±3.0 g, n=7). Addition of diltiazem or verapamil had no significant effect on KCl contraction (128±36% and 88±24% control, respectively); however, nifedipine markedly inhibited KCl contraction (27±4% control, P=0.005). Norepinephrine (NE, 10-9 to 10-4 M) produced dose-dependent increases in tension (maximum tension, 15.7±2.7 g in control rings, n=8). Diltiazem and verapamil pretreatment had no significant effect on NE contraction (103±14% and 90±14% control, respectively); nifedipine significantly inhibited NE contraction (70±11% control, P=0.02). Isosorbide dinitrate and nitroglycerin markedly inhibited KCl contractions (47±9% and 30±8% of controls, n=6) and NE contractions (42±10% and 31±9% of controls, n=6). Nifedipine, isosorbide, and nitroglycerin were further evaluated for the ability to reverse an established contraction (KCl 40 mmol/L); nitroglycerin was most effective in reversing RA contraction. In separate experiments, RA underwent adenoviral-mediated gene transfer with vehicle, Escherichia coli β- galactosidase, or eNOS (eNOS, 1010 PFU/mLx1 hour). Transgene expression was confirmed by β-galactosidase activity and eNOS immunohistochemistry after 40 hours of ex vivo incubation. Immunohistochemistry demonstrated recombinant NOS in adenovirus encoding bovine eNOS (Ad.CMVeNOS) RA only. Ad.CMVeNOS arteries contracted only 46.6±13.7% of controls to KCl (n=5) and 48.2±11.4% of controls to prostaglandin F2(αa) (10-9 to 10-6 M, n=5). Conclusions - Diltiazem, which is used empirically to prevent RA vasospasm, had little effect on human RA contractions (receptor-independent and receptor- dependent). Organic nitrates inhibited and reversed RA contractions. Adenoviral transfer of NOS suggests that future clinical application of gene therapy may play an important role in prevention of RA vasospasm.

AB - Background - There has been renewed interest in radial artery (RA) conduits for coronary artery bypass because of the relative resistance of arterial grafts to atherosclerosis compared with autogenous vein grafts. Although improved drug therapy for arterial spasm is now available, vasospasm still occurs in at least 5% to 10% of RA grafts. We systematically evaluated the effectiveness of calcium channel blockers and organic nitrates for inhibition or reversal of RA contraction in vitro. Additionally, we investigated the efficacy of novel gene therapy with endothelial nitric oxide synthase (eNOS) to inhibit RA contractions. Methods and Results - Segments of RA from 28 patients undergoing coronary artery bypass grafting were mounted in organ chambers. In control experiments, KCl (5 to 50 mmol/L) produced dose-dependent increases in tension (maximum tension, 14.3±3.0 g, n=7). Addition of diltiazem or verapamil had no significant effect on KCl contraction (128±36% and 88±24% control, respectively); however, nifedipine markedly inhibited KCl contraction (27±4% control, P=0.005). Norepinephrine (NE, 10-9 to 10-4 M) produced dose-dependent increases in tension (maximum tension, 15.7±2.7 g in control rings, n=8). Diltiazem and verapamil pretreatment had no significant effect on NE contraction (103±14% and 90±14% control, respectively); nifedipine significantly inhibited NE contraction (70±11% control, P=0.02). Isosorbide dinitrate and nitroglycerin markedly inhibited KCl contractions (47±9% and 30±8% of controls, n=6) and NE contractions (42±10% and 31±9% of controls, n=6). Nifedipine, isosorbide, and nitroglycerin were further evaluated for the ability to reverse an established contraction (KCl 40 mmol/L); nitroglycerin was most effective in reversing RA contraction. In separate experiments, RA underwent adenoviral-mediated gene transfer with vehicle, Escherichia coli β- galactosidase, or eNOS (eNOS, 1010 PFU/mLx1 hour). Transgene expression was confirmed by β-galactosidase activity and eNOS immunohistochemistry after 40 hours of ex vivo incubation. Immunohistochemistry demonstrated recombinant NOS in adenovirus encoding bovine eNOS (Ad.CMVeNOS) RA only. Ad.CMVeNOS arteries contracted only 46.6±13.7% of controls to KCl (n=5) and 48.2±11.4% of controls to prostaglandin F2(αa) (10-9 to 10-6 M, n=5). Conclusions - Diltiazem, which is used empirically to prevent RA vasospasm, had little effect on human RA contractions (receptor-independent and receptor- dependent). Organic nitrates inhibited and reversed RA contractions. Adenoviral transfer of NOS suggests that future clinical application of gene therapy may play an important role in prevention of RA vasospasm.

KW - Arteries

KW - Genes

KW - Grafting

KW - Nitroglycerin

KW - Vasospasm

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VL - 98

JO - Circulation

JF - Circulation

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