L-arginine reverses low coronary reflow and enhances postischaemic recovery of cardiac mechanical function.

OBJECTIVE: To evaluate the effect of L-arginine, the physiological substrate of nitric oxide (NO), upon coronary flow (CF) and mechanical function during reperfusion following cardioplegic arrest. METHODS: Two groups of isolated rat hearts were subjected to cardioplegic arrest for 4 h at 4 degrees C. In group 1 (n = 10) cardioplegic arrest was followed by 4 consecutive periods of reperfusion with Krebs buffer (control), Krebs plus L-lysine (1 mmol/1), Krebs plus L-arginine (1 mmol/1) and Krebs plus L-NGmonomethylarginine (L-NMMA), a specific inhibitor of NO synthesis, (0.5 mmol/1). In group 2, hearts (n = 8) were perfused by Krebs, then L-NMMA, during both pre- and postischaemic periods. In group 3, hearts (n = 8) were perfused by Krebs, then L-arginine (1, 2 and 4 mmol/1). In group 4 (n = 5), NO released into the perfusate was measured before ischaemia and during reperfusion. RESULTS: In group 1, L-arginine enhanced the postischaemic CF (ml/min +/- s.e.m.) from 15.0 +/- 0.4 to 17.2 +/-0.4. This was reduced by L-NMMA to 11.3 +/- 0.3. Postischaemic cardiac output (% of preischaemic value +/- s.e.m.) was increased from 55.8 +/- 2.4 to 80.1 +/- 2.5 by L-arginine and dropped to 54.3 +/- 2.3 with L-NMMA. In group 2, the pre- and postischaemic loss of coronary flow (CF) by L-NMMA was 51% and 31% respectively. In group 3, L-arginine did not modify CF. In group 4 the preischaemic level of NO (in nmol/ml/min) in the coronary effluent, measured by chemiluminescence, was 14.84 +/- 0.83 and dropped significantly (P < 0.05) to levels ranging from 3.80 +/- 0.56 to 4.75 +/- 0.51 during the postischaemic period. CONCLUSION: Exogenous administration of L-arginine improves low coronary reflow and postischaemic mechanical function.

Endothelial function and vasodilator profile of the inferior epigastric artery.

In the inferior epigastric artery, endothelium-dependent relaxations in response to substance P, histamine, and acetylcholine were present. These were greater than reported values in saphenous veins but less than the documented responses in internal mammary and gastroepiploic arteries. Endothelium-independent stimulation with nifedipine, papaverine, sodium nitroprusside, and glyceryl trinitrate induced relaxations that also were reduced compared with established arterial conduits. These findings appear to justify the clinical use of the inferior epigastric artery as a coronary bypass graft with monitoring of its long-term results and possibly perioperative pharmacologic manipulations.

Effect of mode of application of papaverine on the contractile response of the internal mammary artery.

A study was performed to investigate the duration of action of papaverine applied either intraluminally or in a combined intraluminal and extraluminal fashion in vitro, and how the reactivity of the internal mammary artery (IMA) to a range of vasoconstrictors is affected. Segments of IMA exposed to only intraluminal papaverine (10(-4) mol/l) for 15 min recovered their contractile response to 90 mmol/l potassium chloride to pretreatment levels within 2 h. In contrast, combined intraluminal and extraluminal administration of papaverine resulted in a significant depression of the contractile response to 90 mmol/l potassium chloride (P < 0.001), which persisted for at least 5 h. Responses to 5-hydroxytryptamine, noradrenaline, the thromboxane mimetic U46619, histamine and dopamine were not significantly different between control tissues and those that had received intraluminal papaverine. The duration of action of papaverine is affected by its route of delivery and there are no significant short-term effects on the contractile mechanisms in the arterial wall after intraluminal administration.

Effect of surgical preparation and arterialization on vasomotion of human saphenous vein.

To gain an insight into venous physiologic adaptation to arterialization, this study examined the effects of thromboxane, 5-hydroxytryptamine, endothelin, leukotriene C4, and norepinephrine on isolated segments of native and distended human saphenous vein, short-term (up to 1 year) grafts, and long-term (1 to 10 year) grafts. The mean maximum constrictor responses, expressed as percentage of maximum potassium depolarization, were as follows: thromboxane analog U46619: native vein 147.0% +/- 10.5%, distended vein 251.2% +/- 29.1%, short-term graft 174.6% +/- 33.8%, long-term graft 220.9% +/- 21.7%; 5-hydroxytryptamine: native vein 115.6% +/- 6.1%, distended vein 129.9% +/- 13.3%, short-term graft 80.0% +/- 15.0%, long-term graft 95.1% +/- 12.1%; endothelin-1: native vein 126.5% +/- 22.1%, distended vein 138.1% +/- 24.7%, short-term graft 120.7% +/- 43.3%, long-term graft 171.4% +/- 26.0%; leukotriene C4: native vein 49.9% +/- 8.7%, distended vein 78.9% +/- 11.8%, short-term graft 90.8% +/- 39.1%, long-term graft 7.4% +/- 5.0%; and norepinephrine: native vein 127.0% +/- 9.3%, distended vein 155.0% +/- 17.8%, short-term graft 61.6% +/- 11.3%, long-term graft 80.1% +/- 7.7%. The vasoconstriction elicited by each agonist, in absolute terms (in millinewtons), diminished with age of graft. We conclude that surgical treatment of saphenous vein immediately renders it more responsive to U46619, norepinephrine, and leukotriene C4. An agonist-specific profile of response was evident up to 10 years after operation, which may affect myocardial blood supply when luminal bore is diminished by vein graft disease.

Vasoconstrictor profile of the inferior epigastric artery.

The inferior epigastric artery is a putative arterial bypass graft. The receptor mechanisms that control vascular tone are thought to play a role in the performance of bypass conduits. We have compared the vascular reactivity of the inferior epigastric artery with that of the internal mammary artery. Segments from a total of 15 inferior epigastric and 12 internal mammary arteries were examined for their response to increasing concentrations of noradrenaline, 5-hydroxytryptamine, dopamine, histamine, endothelin-1, or the thromboxane analogue U46619. The responsiveness of the smooth muscle was significantly greater in the inferior epigastric artery (p < 0.05) as judged by contractions elicited by 90 mmol/L potassium chloride. However, although the response of the inferior epigastric artery tended to be greater, this significant enhancement of smooth muscle function was not paralleled by the maximal responses of noradrenaline, 5-hydroxytryptamine, dopamine, histamine, or endothelin-1. However, the tension generated in response to U46619 did differ significantly, with maximal responses in the inferior epigastric and internal mammary arteries of 59.2 +/- 8.3 mN and 35.0 +/- 3.6 mN, respectively. When receptor function was compared by expressing the response as a percentage of that of 90 mmol/L potassium chloride, it was revealed that noradrenaline was capable of inducing significantly greater relative contractions in the internal mammary artery (114.8% +/- 20.5%) as compared with the inferior epigastric artery (49.9% +/- 19.1%); the potency of this constrictor was sixfold greater in the internal mammary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of cyclic GMP in human internal mammary artery and saphenous vein: implications for coronary artery bypass graft patency.

OBJECTIVE: The aim was to examine the capacity of the human saphenous vein (native and surgically prepared) and the internal mammary artery to generate cyclic GMP, the second messenger that mediates smooth muscle relaxation following production of nitric oxide. METHODS: 209 vessel segments were used from 22 patients undergoing coronary revascularisation. Isolated vessel segments were stimulated with a range of endothelium dependent and endothelium independent agonists and flash frozen for radioimmunoassay for cyclic GMP. RESULTS: Control/basal levels of cyclic GMP were significantly higher in the internal mammary artery than either native or distended saphenous vein. Endothelium dependent agonist stimulation with acetylcholine, bradykinin, or substance P induced significant increases in cyclic GMP in internal mammary artery and native saphenous vein, whereas distended veins showed non-significant changes in response to agonist stimulation. Endothelium removal abolished agonist stimulated increases in cyclic GMP. Glyceryl trinitrate and sodium nitroprusside elicited significant further increases in cyclic GMP in native vein and internal mammary artery. All values obtained were significantly greater in arterial than in venous tissue. CONCLUSION: Differences in basal and stimulated cyclic GMP activity in arteries and veins have been shown. This could represent an additional protective mechanism against constrictor influences in arterial bypass grafts, which may explain their documented better long term performance.

Vascular reactivity of human internal mammary and gastroepiploic arteries.

Patency rates of bypass graft conduits are thought to be influenced by the determinants of vascular tone. This study has comparatively examined the response of the human internal mammary and gastroepiploic arteries to potassium, noradrenaline, dopamine, 5-hydroxytryptamine, thromboxane, and histamine. The response to potassium was significantly greater in the gastroepiploic artery (Emax = 79.5 +/- 9.6 mN) than in the internal mammary artery (Emax = 27.0 +/- 6.4 mN). Dose-related constrictions were observed in both vessels to all agonists except histamine, which was ineffective in the gastroepiploic artery. Noradrenaline and dopamine produced comparable dose-related constrictions in each vessel, with similar EC50 and Emax (expressed as a percentage of potassium response) values, but 5-hydroxytryptamine (Emax, gastroepiploic = 10.8% +/- 1.9%; internal mammary = 71.8% +/- 21.2%) and thromboxane (Emax, gastroepiploic = 116.7% +/- 4.0%; internal mammary = 169.6% +/- 19.4%) were more efficacious in their constriction of the mammary artery; the potencies were similar. We conclude that there is a heterogeneity of response to some vasoconstrictors between the human internal mammary and gastroepiploic arteries. The internal mammary artery may be more predisposed to events that initiate vasospastic disorders.