Controlled periadventitial administration of verapamil inhibits neointimal smooth muscle cell proliferation and ameliorates vasomotor abnormalities in.

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Controlled periadventitial administration of verapamil inhibits neointimal smooth muscle cell proliferation and ameliorates vasomotor abnormalities in experimental vein bypass grafts Ron Brauner, MDa, Hillel Laks, MDa, Davis C. Drinkwater, MDa, Gautam Chaudhuri, MDa, Oleg Shvarts, MSa, Thomas Drake, MDa, Sunita Bhuta, MDa, David Mishaly, MDb, Ilia Fishbein, MDb, Gershon Golomb, PhDb The Journal of Thoracic and Cardiovascular Surgery Volume 114, Issue 1, Pages 53-63 (July 1997) DOI: 10.1016/S0022-5223(97)70117-X Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 1 A, Placement of a verapamil-EVA polymeric matrix around the proximal third of a jugular vein graft bypassing the carotid artery. The matrix is flexible and provides good suture handling. B, Final appearance of the graft with the matrix in place. Anchoring the polymer to the proximal carotid stump (not seen) prevents distal migration. At reoperation, dissection was facilitated by the presence of the device. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 1 A, Placement of a verapamil-EVA polymeric matrix around the proximal third of a jugular vein graft bypassing the carotid artery. The matrix is flexible and provides good suture handling. B, Final appearance of the graft with the matrix in place. Anchoring the polymer to the proximal carotid stump (not seen) prevents distal migration. At reoperation, dissection was facilitated by the presence of the device. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 2 Release kinetics of EVA polymeric systems (0.2 mm thick) containing 0.5% or 2% wt/wt of verapamil. Two percent verapamil matrices were used in the present study. Drug release rate decreases over time, with an initially high delivery rate that may be beneficial at the early stages of vascular injury. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 3 Representative photomicrographs of vein graft segments directly under plain control EVA polymers (A), under verapamil-EVA matrices (B), and distal segments of verapamil-treated grafts (C). The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 3 Representative photomicrographs of vein graft segments directly under plain control EVA polymers (A), under verapamil-EVA matrices (B), and distal segments of verapamil-treated grafts (C). The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 3 Representative photomicrographs of vein graft segments directly under plain control EVA polymers (A), under verapamil-EVA matrices (B), and distal segments of verapamil-treated grafts (C). The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 4 Cross sections of the vein graft wall under control EVA (A), under verapamil-EVA (B), and downstream of verapamil-EVA polymeric matrices (C). NI, Neointima; M, media. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 4 Cross sections of the vein graft wall under control EVA (A), under verapamil-EVA (B), and downstream of verapamil-EVA polymeric matrices (C). NI, Neointima; M, media. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 4 Cross sections of the vein graft wall under control EVA (A), under verapamil-EVA (B), and downstream of verapamil-EVA polymeric matrices (C). NI, Neointima; M, media. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 5 Representative transmission electron micrographs of vein graft intima. All visualized cells are proliferated smooth muscle cells. A, Directly under empty control EVA matrices. B, Under verapamil-EVA matrices. C, Distal segments of verapamil-treated grafts. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 5 Representative transmission electron micrographs of vein graft intima. All visualized cells are proliferated smooth muscle cells. A, Directly under empty control EVA matrices. B, Under verapamil-EVA matrices. C, Distal segments of verapamil-treated grafts. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 5 Representative transmission electron micrographs of vein graft intima. All visualized cells are proliferated smooth muscle cells. A, Directly under empty control EVA matrices. B, Under verapamil-EVA matrices. C, Distal segments of verapamil-treated grafts. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions

Fig. 6 Dose-response contraction curves to serotonin in distal vein graft segments. Values are percent of KCl-induced maximal contraction and are expressed as mean ± standard error of the mean. HC control , Hypercholesterolemic vein graft segments, distal to empty polymers; HVC distal , hypercholesterolemic vein graft segments distal to verapamil-EVA polymers; NC, normocholesterolemic graft midsegments. The Journal of Thoracic and Cardiovascular Surgery 1997 114, 53-63DOI: (10.1016/S0022-5223(97)70117-X) Copyright © 1997 Mosby, Inc. Terms and Conditions