Reduction of arterial graft smooth muscle mass by moderate heat therapy.

Radial artery (RA) graft spasm is a major cause of early graft failure in coronary artery bypass grafting surgeries. We explored the feasibility of thermal reduction of smooth muscle mass to attenuate vasoconstriction. Rat and rabbit femoral arteries were treated thermally in situ (45°C to 65°C; 0 s to 120 s) and then excised at various time points for histological and physiological study (pressure-diameter relationships). Human radial arteries were treated in vitro and studied in similar fashion. Weeks after thermal treatment, no overt indication was noted of vasospasm, thrombosis, or scarring in the arterial wall; however, this intervention led to a thermal dose-dependent reduction of vasoconstriction (to phenylephrine or potassium chloride) and to a conspicuous loss of smooth muscle. Pressure-diameter relationships showed no aneurismal dilation of these demuscularized arteries up to 200 mmHg. Qualitatively identical results were obtained in human radial arteries. Thermal ablation of RAs may provide a simple, safe, and effective solution to postsurgical vasospasm.

Structural and electrophysiological changes in atherosclerotic radial artery grafts account for impairment of vessel reactivity.

To evaluate the potential impact of using atherosclerotic radial artery (RA) conduits as grafts in coronary artery bypass surgery, we examined the vasoconstrictor and electrophysiological properties of mildly and severely atherosclerotic RAs. Vasoconstrictor responses were measured in cannulated and pressurized (85mmHg) RA segments and K(+) currents were measured in single smooth muscle cells. In the cannulated and pressurized vessel preparation, the pressure-induced dilation was attenuated in both the mildly and severely atherosclerotic RAs when compared to normal samples. Contractile responses to potassium chloride, thromboxane A(2) (TXA(2)) analog U-46619 and to E-ring and F-ring isoprostanes were also attenuated. Smooth muscle cells (SMCs) from atherosclerotic arteries manifested significantly greater K(+) current density (76.6+/-22.4pA/pF) when compared to normal SMCs (18.6+/-3.3pA/pF). Our results show that vasocontractile properties of both mildly and severely atherosclerotic arteries are reduced when compared to normal RAs. A possible explanation for this could be decreased vascular compliance due to arterial stiffening and a substantial augmentation of K(+) currents in sclerotic smooth muscle cells. We conclude that caution should be exercised when using RA grafts with atherosclerotic lesions since they could significantly impact the clinical outcome of CABG surgery.

Isoprostanes constrict human radial artery by stimulation of thromboxane receptors, Ca2+ release, and RhoA activation.

OBJECTIVES: Radial artery vasospasm remains a potential cause of early graft failure after coronary bypass graft surgery, despite pretreatment with alpha-adrenergic or calcium channel blockers. We examined the roles of isoprostanes and prostanoid receptors selective for thromboxane A2 in the vasoconstriction of human radial arteries. METHODS: Human radial arterial segments were pretreated intraoperatively with verapamil/papaverine or nitroglycerine/phenoxybenzamine, or not treated. In the laboratory, we measured isometric contractions in ring segments, vasoconstriction in pressurized segments, and changes in [Ca2+] and K+ currents in single cells. RESULTS: Although phenoxybenzamine eliminated adrenergic responses, the isoprostane 15-F(2t)-IsoP and 2 closely related E-ring molecules (15-E(1t)-IsoP and 15-E(2t)-IsoP) still evoked powerful contractions; 15-E(2t)-IsoP was approximately 10-fold more potent than the other 2 agents. Responses were mediated through thromboxane receptors because they were sensitive to ICI-192605. Furthermore, they were sensitive to the Rho-kinase inhibitors Y-27632 or H-1152 (both 10(-5) mol/L) or to cyclopiazonic acid (which depletes the internal Ca2+ pool), but not to nifedipine. In single cells, 15-E(2t)-IsoP elevated [Ca2+]i and suppressed K+ current. CONCLUSIONS: Isoprostanes accumulate after coronary artery bypass graft surgery, yet none of the currently available antispasm treatments for radial artery grafts is effective against isoprostane-induced vasoconstriction. It is imperative that more specific treatment strategies be developed. We found that isoprostane responses in radial arteries are mediated by prostanoid receptors selective for thromboxane A2 with activation of Rho-kinase and release of Ca2+. Pretreatment of radial artery grafts with Rho-associated kinase inhibitors may potentially reduce postoperative graft spasm. Clinical studies to test this are indicated.