Guo-Wei He

Arterial grafts for coronary artery bypass grafting: biological characteristics, functional classification, and clinical choice

Various arterial grafts have been used for coronary artery bypass grafting, but a unanimous opinion on how to best use these grafts has not been formed. Arterial grafts are not uniform in their biological characteristics. Differences between the perioperative behavior of the grafts and their long-term patency may be related to different characteristics. These characteristics should be taken into account in the use of arterial grafts, some of which are subject to more active pharmacologic intervention during and after operation to obtain satisfactory results. Clinical choice of grafts must be based on the general condition of the patient, the biological characteristics of the graft, the anatomy of the coronary artery, the match between the coronary artery and the graft, and technical considerations, including antispastic management.

Radial artery has higher receptor-mediated contractility but similar endothelial function compared with mammary artery

BACKGROUND The radial artery (RA) has been used as an alternative arterial graft for coronary artery bypass grafting, but this artery has been suggested to be spastic. Endothelin-1 (ET) and angiotensin II (AII) have been measured with increased plasma concentrations during cardiopulmonary bypass. However, whether RA is reactive to these two important receptor-mediated vasoconstrictors is unknown. Also unknown is the endothelial function of this arterial conduit. This study was designed to compare RA and the internal mammary artery regarding the contractile characteristics to ET-1 and AII and endothelial function. METHODS Ring segments of the RA and internal mammary artery taken from patients undergoing coronary artery bypass grafting were studied in organ chambers at a physiologic pressure. The contractility was determined from the contraction induced by ET-1 and AII as contraction force and the force normalized by circumference (g/mm). The endothelium-dependent relaxation was induced by the calcium ionophore A23187, a nonreceptor agonist, and substance P, a receptor agonist for endothelium-derived relaxing factors. Nitroglycerin was used to study the endothelium-independent relaxation. RESULTS Both ET-1 and AII induced a higher contraction force (9.0 +/- 0.9 g, n = 12, versus 4.5 +/- 0.4 g, n = 38, p < 0.0001 for ET and 6.5 +/- 1.9 g, n = 7, versus 1.7 +/- 0.3 g, n = 8, p = 0.015 for AII) and normalized force (0.95 +/- 0.1 g/mm versus 0.66 +/- 0.05 g/mm, p = 0.007 for ET-1 and 0.8 +/- 0.2 g/mm versus 0.2 +/- 0.05 g/mm, p < 0.01 for AII) in RA than in the internal mammary artery. There were no significant differences detected between these arteries with regard to either endothelium-dependent (to substance P and A23187) or endothelium-independent (to nitroglycerin) relaxation (p > 0.05). CONCLUSIONS We conclude that the human RA has a higher receptor-mediated contractility (to ET-1 and AII) but similar endothelial function compared to the internal mammary artery. The study reveals the nature of the more spastic characteristics of the RA, supports the necessity of a more active pharmacologic intervention to relieve spasm in the RA, and suggests that the similar endothelium-derived relaxing factor-mediated endothelial function of the RA compared with the internal mammary artery may be the basis for a satisfactory long-term patency.

Pharmacology of Coronary Artery Bypass Grafts

Spasm of arterial and venous graft conduits can occur both during harvesting and after the graft is connected. Attempts to overcome spasm during harvesting by probing or hydraulic distension can cause structural damage to the graft, which may impair short- and long-term patency. After a coronary artery bypass graft is connected, spasm can cause major problems with myocardial perfusion. To select the best pharmacologic agent to prevent or reverse vasoconstriction in a graft requires an understanding of the reactivity of that particular type of graft to vasoconstrictor and vasodilator agents. The pharmacologic reactivity of venous and arterial graft conduits has been documented through extensive studies of isolated vessels in the organ bath and of in situ grafts in the body. In this review we summarize the current state of knowledge of the reactivity of arterial and venous grafts to vasoconstrictor and vasodilator agents and describe the practical application of this knowledge in the operating room and in the postoperative period.

Reactivity of the canine isolated internal mammary artery, saphenous vein, and coronary artery to constrictor and dilator substances : relevance to coronary bypass graft surgery

The internal mammary artery (IMA) and saphenous vein (SV) are used routinely in coronary artery (CA) bypass graft surgery. The IMA may develop spasm during surgery, and the SV often develops spasm during removal from the leg. We sought to determine the relative reactivity of the canine CA, IMA, and SV to potential vasoconstrictor substances and especially to determine which vasodilator agents were effective in these different blood vessels. All vessels were arranged as ring segments suspended at optimal stretch in organ baths. Glyceryl trinitrate (GTN) caused relaxation of the three vessels but was less sensitive, less potent (as determined by EC50 values), and had a reduced range of relaxation in the IMA. Papaverine was less sensitive in the IMA as compared with the CA and SV. Nifedipine, verapamil, and diltiazem were potent relaxing agents in all three vessels when precontracted by K+, but were less potent in vessels contracted by the thromboxane mimetic U46619 or phenylephrine, especially in the SV. These studies highlight the marked differences in the response of IMA and CA to constrictor and dilator agents and reinforce the notion that calcium antagonists of different chemical classes have widely differing activities in vascular tissue.

Use of verapamil and nitroglycerin solution in preparation of radial artery for coronary grafting

BACKGROUND The radial artery (RA) has been used as an alternative arterial graft for coronary artery bypass grafting. This artery has been reported to be spastic; therefore, use of spasmolytic drugs (vasodilators) during the preparation of the RA is recommended. The combination of calcium antagonists and nitroglycerin (verapamil plus nitroglycerin, VG solution) has been suggested to be effective in other bypass grafts. This study was designed to investigate (1) the effect of the VG solution during preparation of the RA for coronary artery bypass grafting and (2) whether the effect would last for a prolonged period after topical use. METHODS Ring segments of the RA taken from coronary artery bypass grafting patients were studied in organ chambers at a physiologic pressure. The relaxation effect of VG (30 mumol/L verapamil and 30 mumol/L nitroglycerin, n = 5) or papaverine (30 mumol/L, n = 5) was recorded in K+ (25 mmol/L potassium chloride)-precontracted RA segments. Other segments taken from the RA were treated (n = 5) or not treated (n = 20, as the control) with the VG solution for 45 minutes before used for coronary artery bypass grafting. Both the VG-treated and nontreated segments were immersed in oxygenated Krebs solution and stored in a refrigerator at 4 degrees C for 24 hours. The contraction force to 100 mmol/L K+ was compared between the two groups. RESULTS The VG solution induced more rapid relaxation than papaverine (p < 0.05 from the first to the ninth minute). After 10 minutes, both solutions induced full relaxation. The contraction to K+ (100 mmol/L) in rings treated with VG solution for 45 minutes during operation was almost abolished 24 hours later (0.86 +/- 0.1 g). In contrast, the control segments (n = 20) taken from nontreated RA contracted with K+ to high force (5.0 +/- 0.6 g; p < 0.001). CONCLUSIONS The present study suggests that the combination of verapamil and nitroglycerin may provide a rapid onset, a complete relaxation, and a long-lasting vasorelaxant effect when used to prepare the RA for grafting. This study adds a new method to prevent RA spasm during coronary artery bypass grafting.

KDR (VEGF Receptor 2) Is the Major Mediator for the Hypotensive Effect of VEGF

Vascular endothelial growth factor (VEGF) exerts vasodilation-induced hypotension as a major side effect for treatment of ischemic diseases. VEGF has 2 receptor tyrosine kinases, KDR and Flt-1. Little is known about which receptor mediates VEGF-induced hypotension. To elucidate the role of each receptor in mediating hypotension, KDR-selective and Flt-1–selective mutants were used for in vitro and in vivo studies. The KDR-selective mutant induced vascular endothelial cell proliferation comparable to VEGF, whereas the Flt-1– selective mutant had no effect on proliferation. Intravenous injection of KDR-selective mutant, Flt-selective mutant, or VEGF caused a dose-related decrease in mean arterial pressure in conscious rats. The hypotensive response to KDR-selective mutant was significantly less than that to VEGF (P <0.01) but was greater than that to Flt-selective mutant (P <0.01). Similarly, VEGF and KDR-selective mutant induced more potent vasorelaxation than Flt-selective mutant or placenta growth factor that binds Flt-1 only (P <0.01), and the vasorelaxation to KDR-selective mutant was not significantly different at low concentrations but less than that to VEGF at high concentrations. The results indicate that the vasodilation and hypotensive effect of VEGF may involve both receptors, but KDR is the predominant receptor mediating this effect. Because KDR-selective mutant induced proliferation and angiogenesis similar to VEGF but was associated with 36% attenuation in hypotension, the data suggest that the KDR-selective mutant may represent an alternative treatment for ischemic diseases.

Overview of the nature of vasoconstriction in arterial grafts for coronary operations

Many vasoconstrictors (spasmogens) may cause arterial graft spasm; however, there is lack of an overview of the nature of vasoconstriction in grafts. This study was designed to investigate the response of three major arterial grafts currently used for coronary artery bypass grafting to various vasoconstrictor substances. Segments of three arterial grafts (gastroepiploic [GEA], n = 28; internal mammary [IMA], n = 213; inferior epigastric [IEA], n = 24) taken from patients undergoing coronary artery bypass grafting were studied in organ baths under a physiologic pressure. Cumulative concentration-contraction curves were established for the following vasoconstrictor substances: endothelin-1, U46619, prostaglandin F2 alpha, norepinephrine, methoxamine, phenylephrine, 5-hydroxytryptamine, and potassium chloride (K+). In IMA, the highest contraction force was induced by U46619 (5.69 +/- 0.48 g), endothelin-1 (4.43 +/- 0.4 g), PGF2 alpha (6.29 +/- 1.42 g), and K+ (4.58 +/- 0.5 g). Internal mammary artery is highly sensitive to endothelin-1 (EC50, -8.13 +/- 0.08 log M) and U46619 (EC50, -8.21 +/- 0.21 log M) (lower than any other vasoconstrictors, p < 0.001). Next sensitive vasoconstrictors were PGF2 alpha and norepinephrine. 5-Hydroxytryptamine induced significantly higher contraction force in the IMA without endothelium (2.8 +/- 0.64 g versus 1.4 +/- 0.23 g, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological Relaxation of the Saphenous Vein During Harvesting for Coronary Artery Bypass Grafting

Spasm of the saphenous vein frequently occurs during harvesting from the leg and high-pressure distension is required to restore an adequate diameter for grafting. Forceful distention has been shown to damage the intima and media and may predispose to subsequent occlusion of the vein graft. Various pharmacologic vasodilators are capable of relaxing veins; in this study, we carried out a systematic investigation to determine the appropriate agents and concentrations for use during vein graft operations. In organ baths, human saphenous vein segments were contracted with potassium or a thromboxane mimetic, and vasodilator agents were then applied. Glyceryl trinitrate, 7.2 micrograms/mL, or papaverine hydrochloride, 11.9 micrograms/mL, caused 80% to 100% relaxation of contraction induced by potassium or thromboxane. Verapamil, 15.5 micrograms/mL, relaxed the potassium contraction by 100% and the thromboxane contraction by 75%. Comparison of the time course of action showed that glyceryl trinitrate had a rapid onset and a short duration of maximal action, whereas verapamil (like papaverine) had delayed onset and a long duration. A mixture of glyceryl trinitrate and verapamil combined rapid onset with long duration of action. We now use a mixture of glyceryl trinitrate and verapamil (pH 7.4) topically and intraluminally during harvesting of the saphenous vein to provide a relaxed conduit for coronary artery bypass grafting.

Repair of ruptured sinus of valsalva aneurysm: Determinants of long-term survival

BACKGROUND Ruptured sinus of Valsalva aneurysm is a rare cardiac anomaly and long-term survival after surgical treatment is not well established. This study was designed to investigate the determinants of long-term survival after repair of ruptured sinus of Valsalva aneurysm. METHODS From April 1978 to April 1996, 53 patients underwent operation for ruptured sinus of Valsalva aneurysm. The incidence among our cardiac surgical population was 0.56%. Long-term survival was investigated in 46 patients (13 to 65 years) who survived the operation, with 96.2% follow-up completeness (mean+/-standard deviation, 6.5+/-4.9 years; maximum, 17.2 years), by univariate and multivariate analyses. RESULTS There was no early operative death and no recurrence after the initial repair. Actuarial survival was 83.8%+/-8.4% at 15 years. Reoperation, aneurysm draining into the left ventricle, aortic prosthetic dehiscence, bacterial endocarditis, and aortic cross-clamp time (<70 minutes) were significant factors in long-term survival (p < 0.05). Multivariate analysis revealed that only aortic prosthesis dehiscence was the significant factor influencing late survival (p = 0.0001). CONCLUSIONS Surgical treatment for ruptured sinus of Valsalva aneurysm is safe and has satisfactory results. Aortic prosthesis dehiscence is the independent determinant for long-term survival. Other factors including bacterial endocarditis, concomitant ventricular septal defect repair, and aortic valve replacement did not independently influence long-term survival.

Vascular endothelial growth factor-induced nitric oxide- and PGI2-dependent relaxation in human internal mammary arteries: a comparative study with KDR and Flt-1 selective mutants.

The role of the vascular endothelial growth factors (VEGF) receptors (KDR and Flt-1) and their characteristics in VEGF-induced vasodilation in human vessels is unclear. This study investigated the in vitro vasorelaxant effects of KDR-selective (KDR-SM) and Flt-1-selective mutants (Flt-1-SM) in the human internal mammary artery (IMA). IMA segments (n = 183) taken from 48 patients were studied in organ baths. The cumulative concentration (−12 to −8 log10M)-relaxation curves were established for VEGF, KDR-SM, Flt-1-SM, and placenta growth factor (PlGF) in the absence or presence of indomethacin (INDO, 7 μM), Nω-nitro-L-arginine (L-NNA, 300 μM), L-NNA + oxyhemoglobin (HbO, 20 μM), or INDO + L-NNA + HbO. The VEGF-induced relaxation was abolished in endothelium-denuded IMA. In the endothelium-intact vessel rings, VEGF (63.2 ± 3.9%) induced significantly more (P < 0.001) relaxation than Flt-1-SM (28.5 ± 4.3%, 95% CI 18.1-51.3%), and PlGF (26.0 ± 4.7%, 95% CI 17.6-56.8%). The maximal relaxation induced by KDR-SM (53.0 ± 4.0%) was only slightly less than that by VEGF (P = 0.075) but significantly more than that by Flt-1-SM (P = 0.001, 95% CI 7.8-41.1%). Pretreatment of INDO or L-NNA + HbO significantly (P < 0.001) inhibited the relaxation by VEGF (21.2 ± 3.9% or 23.3 ± 4.3%) and KDR-SM (9.8 ± 8.2% or 10.1 ± 17.8%). INDO + L-NNA + HbO completely inhibited the relaxation by VEGF, KDR-SM, or Flt-1-SM. KDR may be the dominant receptor in mediating the VEGF-mediated relaxation, which is regulated by both PGI2 and nitric oxide but probably not by endothelium-derived hyperpolarizing factor, in the human IMA. This study gives insight into the characteristics of the VEGF-mediated vasodilation and provides a scientific basis for potential clinical application of VEGF/KDR-SM in ischemic heart disease.