15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and Graft-Occlusion--Vascular

Potential disadvantages, such as lower graft patency rates, that could lead to the need for more subsequent revascularization after off-pump coronary artery bypass grafting are discussed. One mechanism may involve endothelial damage originating from tools to facilitate a bloodless surgical field during anastomosis. We investigated the effect of the use of a blower-mister device on in vitro endothelial and contractile functions of human internal thoracic arteries and greater saphenous veins.. The distal ends of both bypass graft types were exposed to the air and water stream of the device for 10 minutes, representing the usual time needed for completion of an anastomosis using the off-pump technique. Vessel segments of both groups were cut into 4-mm rings and stored in a modified Krebs-Henseleit solution. Contraction responses to U44619 and relaxation responses to acetylcholine, substance P, papaverine, and nitroprusside were evaluated.. Forty-eight artery ring segments from 8 patients were studied. Absolute maximum contraction to U44619 was significantly less in rings subjected to the blower-mister device than in controls (internal thoracic artery: 17.17 ± 2.57 mN vs 8.67 ± 4.54 mN, P < .048; greater saphenous vein: 28.33 ± 9.71 mN vs 11.42 ± 7.97 mN, P < .026). Control rings had significantly greater endothelium-dependent relaxation response to acetylcholine (mean difference 29.2% ± 3.4%, P < .001), whereas those subjected to the blower-mister device had reduced responses. Endothelium-independent relaxation to nitroprusside was not significantly different among the groups.. Vessels exposed to the air and water stream of a blower-mister device showed a reduced vasoreactivity. This effect should be studied further, especially if it contributes to lower graft patency rates in off-pump surgery.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetylcholine; Aged; Coronary Artery Bypass, Off-Pump; Dose-Response Relationship, Drug; Equipment Design; Graft Occlusion, Vascular; Humans; Mammary Arteries; Nitroprusside; Saphenous Vein; Vascular Patency; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

This study was carried out to determine whether early failure of infrainguinal bypass grafts is associated with increased expression of platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors. A prospective correlation of preoperative platelet TXA2/PGH2 receptor-mediated activity with lower extremity graft patency was sought.. Twenty-five patients who underwent infrainguinal bypass surgery for limb salvage were studied at an inpatient academic tertiary referral center and Department of Veterans Affairs Medical Center. Outcome measures were primary graft patency rate at 3 months, platelet TXA2/PGH2 receptor activity by equilibrium binding with 125I-BOP, and aggregation to the TXA2-mimetic U46619.. Preoperative platelet TXA2/PGH2 receptor density was higher (Bmax, 3100 +/- 1300 vs 1500 +/- 1100 sites/platelet [mean +/- SD]; p = 0.004) in the five patients who had graft thrombosis within 3 months. The EC50 for U46619 was lower (26 +/- 6 nmol/L vs 57 +/- 30 nmol/L; p < 0.05) in these patients as well, confirming the functional effect of the increased receptor density. Early graft thrombosis was more likely in patients with a platelet TXA2/PGH2 receptor density greater than 3000 sites/platelet (odds ratio, 76; 95% confidence interval, 3.9 to 1500) or an EC50 for U46619 less than 30 nmol/L (odds ratio, 16; 95% confidence interval, 1.4 to 180).. Elevated platelet TXA2/PGH2 receptor levels and enhanced sensitivity of platelet aggregation to TXA2 predict early arterial graft thrombosis. Specific TXA2/PGH2 receptor antagonism may prevent one of the mechanisms that contributes to early graft occlusion.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Aged; Blood Platelets; Female; Graft Occlusion, Vascular; Humans; Male; Peripheral Vascular Diseases; Platelet Aggregation; Prospective Studies; Prostaglandins H; Receptors, Prostaglandin; Receptors, Thromboxane; Receptors, Thromboxane A2, Prostaglandin H2; Thrombosis; Vascular Patency

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)

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Abdominal Muscles; Adrenergic alpha-Agonists; Arteries; Coronary Artery Bypass; Dinoprost; Endothelins; Endothelium, Vascular; Graft Occlusion, Vascular; Humans; Mammary Arteries; Potassium Chloride; Prostaglandin Endoperoxides, Synthetic; Serotonin; Thromboxane A2; Vasoconstriction; Vasoconstrictor Agents

Coronary artery bypass grafting using bifurcation of the internal mammary artery (IMA) has been reported to have a poor patency rate. To test the hypothesis that the contractility (tendency for spasm) is greater at the bifurcation than at the main IMA, segments of the bifurcation and the distal section of IMA taken from patients with coronary artery bypass grafts were studied in organ baths. The IMA rings were set up at a physiologic pressure. Concentration-response curves were established for norepinephrine, endothelin-1, U46619, potassium, and glyceryl trinitrate (precontracted with 10 nmol/L U46619). Contraction forces were standardized (gram per mm circumference) at a pressure of 100 mm Hg. The diameter was 1.50 +/- 0.08 mm (n = 38) for the bifurcation and 2.03 +/- 0.07 (n = 42) for the main IMA (p < 0.0001). The standardized contraction force was greater in the bifurcation than in the main IMA for norepinephrine (0.82 +/- 0.06 versus 0.54 +/- 0.1; p = 0.02) and endothelin-1 (1.07 +/- 0.11 versus 0.69 +/- 0.07; p = 0.02). No differences were seen for potassium, U46619, or glyceryl trinitrate, whereas the effective concentration that induced 50% of maximal effect for U46619 was 6.17-fold lower in the bifurcation than in the main IMA (9.14 +/- 0.28 versus 8.35 +/- 0.09 -log M; p = 0.003), indicating higher sensitivity in the bifurcation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Endothelins; Graft Occlusion, Vascular; Humans; In Vitro Techniques; Internal Mammary-Coronary Artery Anastomosis; Mammary Arteries; Nitroglycerin; Norepinephrine; Potassium; Prostaglandin Endoperoxides, Synthetic; Thromboxane A2; Vasoconstriction; Vasoconstrictor Agents

The rat femoral artery was used as a free graft and was studied after 2, 7, 14, 30, and 60 days. The patency of the grafts was 100% (2 days, n = 6), 78% (7 days, n = 9), 63% (14 days, n = 8), 33% (30 days, n = 12), and 18% (60 days, n = 11). Histology showed an intimal thickening after 14 days and the media, which in the controls consisted of eight to ten layers of myocytes, was reduced to six to eight cell layers. During the first 2 weeks the graft segments had an impaired contraction when exposed to Krebs solution with 124 mmol/L K+, whereas after 1 month and later the graft segments approached the controls or had even higher contractile force. The thromboxane mimic U-46619 elicited full contractile force at all times whereas the potency was significantly lower during the first 14 days. Noradrenaline was unable to induce contraction in the graft segments during the first 14 days, but at 30 and 60 days it had regained full contractile force and was significantly more potent (approximately 60 times) in the graft segments compared with the controls. This study suggests that intimal thickening and hypercontractility might be a problem in free muscular arterial grafts.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Endothelium, Vascular; Femoral Artery; Graft Occlusion, Vascular; Male; Norepinephrine; Potassium; Prostaglandin Endoperoxides, Synthetic; Rats; Rats, Inbred Strains; Time Factors; Vascular Patency; Vasoconstriction