Histamine H1 and H2 receptor-mediated vasoreactivity of human internal thoracic and radial arteries

BACKGROUND: Although internal thoracic arteries (ITAs) and radial arteries (RAs) have been shown to have similar patency, RAs tend to be more vasospastic postoperatively compared with ITAs. Therefore, the purpose of this study was to examine the effect of histamine subclass 1 (H1) receptors and histamine subclass 2 (H2) receptors on vasoreactivity in human ITAs and RAs. METHODS: Vessels were obtained from coronary artery bypass grafting patients. Human arterial rings (2 mm) were mounted in tissue baths, and baseline contractility was determined. Histamine concentration response curves (10(-9)-10(-3) mol/L) were performed in the absence or presence of diphenhydramine (H1 antagonist, 10(-4) mol/L) or famotidine (H2 antagonist, 10(-4) mol/L). Comparison of curves was performed by 2-way analysis of variance with repeated measures and a Bonferroni post-t test. RESULTS: Maximal contraction to histamine was significantly greater in RA (8.3 +/- 0.8 g, n = 6) than in ITA (2.9 +/- 0.3, n = 6), (P < .05). However, there was no difference in sensitivity. Histamine-mediated responses of both RA and ITA were blocked by pre-exposure to H1 antagonist, whereas an H2 antagonist only partially inhibited RA responses while blocking most of the ITA response to histamine. CONCLUSION: These studies suggest that H1 receptors alone cause contraction in RA but not in ITA, which may have potential linkage to patency and vasospasm. Further studies are necessary to identify the exact role of H2 receptors in ITA.     

Influence of low molecular weight heparin preparations on human internal thoracic artery contraction.

OBJECTIVE: Low molecular weight heparins (LMWHs) offer practical and potential pharmacological advantages over unfractionated heparin in multiple applications but have not been studied as vasoactive agents. The purpose of this study was to investigate the effects of two commercial preparations of LMWHs, enoxaparin sodium and nadroparin calcium, on vasoconstriction in the human internal thoracic artery (ITA) in vitro. METHODS: Samples of redundant ITA segments obtained from 36 patients who underwent coronary artery bypass surgery were cut into 3mm wide rings and suspended in 20 ml organ bath. Activity of ITA rings precontracted with 80 mM KCl, 0.1 microM endothelin-1 (ET-1) and 1 microM norepinephrine (NE) after administration of enoxaparin and nadroparin in accumulative concentration ranging from 0.1 to 13.2 UI AXa/ml were recorded under isometric conditions by means of force transducers with digital output. The contraction after 80 mmol KCl, 0.1 microM ET-1 and 1 microM NE administration was treated as a control. RESULTS: Both studied LMWHs in concentration ranging from 0.12 to 13.2 UI AXa/ml did not change basal tonus and KCl precontracted ITA rings. When used in concentrations higher than 13.2 UI AXa/ml nadroparin but not enoxaparin significantly increased the tension in KCl precontracted arterial rings. In NE and ET-1 precontracted rings enoxaparin and nadroparin caused dose dependent relaxation without significant differences between both preparations. Incubation with nitric oxide blocker-Nomega-NITRO-L-ARGININE (L-NNA) in concentration 0.2 mM caused a significant attenuation of relaxant responses to both studied LMWHs in NE and ET-1 precontracted rings. CONCLUSION: LMWHs can have vasorelaxant effects on the receptor-mediated ITA vasoconstriction. The results suggest that LMWHs-induced relaxation in the human ITA is at least partially caused by nitric oxide release. Although the vasoactive effects are not the primary advantage of these drugs used as antithrombotics, such effects might have some clinical importance in the treatment and prophylaxis of graft spasm.     

Does skeletonization compromise the integrity of internal thoracic artery grafts?

BACKGROUND: There are few reports that demonstrate the chronologic changes in the functional integrity of the internal thoracic artery (ITA) wall after skeletonization. We investigated the impact of skeletonization on ITA wall integrity by immunohistochemical analyses in acute and chronic phases. METHODS: Nine mongrel dogs underwent bilateral ITA dissection with one skeletonized vessel and the other pedicled. The following studies were performed 1 week (acute phase, n = 3) and 12 weeks (chronic phase, n = 6) after ITA harvesting. All specimens of the ITAs were stained by antibodies against von Willebrand Factor (VWF), endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and proliferating cell nuclear antigen (PCNA). After observation with confocal laser scanning microscopy, quantitative analyses of the staining signal for VWF and eNOS expressed on endothelial cells were performed. RESULTS: There were significantly more microvessels positive for VWF in the adventitia of skeletonized ITAs than in the adventitia of pedicled ITAs but the expression of PCNA in both groups was minimal, as in normal vessels. iNOS was not detected in any specimen. The intensity of VWF and eNOS expressed by endothelial cells had no significant differences between groups at either phase. CONCLUSIONS: The functional integrity of skeletonized ITA was similar to that of pedicled ITA in both acute and chronic phases. Although skeletonization induced neovascularization in the adventitia it did not induce proliferation of smooth muscle cells in the media, which is supposed to be a feature of vascular remodeling.     

The inhibitory action of protamine on human internal thoracic artery contractions: the effect of free hemoglobin

Objective: We investigated the mechanism of the protamine action and the effects of free hemoglobin on protamine-induced responses in endothelium-denuded and-intact human internal thoracic artery (ITA) rings precontracted with phenylephrine (PE) or high KCl. Methods: Samples of redundant ITA obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system. Results: Acetylcholine (Ach, 10⁻⁸–10⁻⁵ M) caused a concentration-dependent relaxation of PE-precontracted ITA rings. Free hemoglobin (0.1 and 0.5 μM) produced a concentration-dependent and significant decrease in sensitivity (pD₂) and maximal contractility (E_max) in response to Ach in PE-precontracted ITA rings (P<0.0001). Protamine (50–800 μg/ml), free hemoglobin (0.1 and 0.5 μM), nitric oxide (NO) blocker N^ω-nitro- -arginine methyl ester (L-NAME, 100 μM) or soluble guanylate cyclase inhibitor methylene blue (10 μM) administration did not cause a significant alteration on basal tonus of endothelium-intact or -denuded ITA rings. Protamine (50–800 μg/ml) induced concentration-dependent relaxation responses in ITA rings precontracted by either PE or high KCl. There was no difference in sensitivity or maximal response to protamine between the endothelium-intact and -denuded rings. Incubation of endothelium-intact or -denuded ITA rings with L-NAME or free hemoglobin or methylene blue did not cause a significant inhibition on relaxation responses to protamine. ITA ring contractions induced by stepwise addition of calcium to high KCl solution with no calcium were almost completely inhibited by protamine (P<0.0001). Conclusions: It was suggested that protamine induced relaxation responses in human ITA rings is not NO- or endothelium-dependent but seems to depend on the interactions of protamine with calcium influxes and/or calcium release from intracellular stores in this tissue.     

Improved endothelial function after a modified harvesting technique of the internal thoracic artery

Objective: One of the most important factors in bypass surgery is the preservation of endothelial function in the arterial graft. It was of interest, therefore, whether a slightly modified preparation procedure during surgery could contribute to improved endothelial function of the graft. We compared the functional activity of internal thoracic arteries (ITA) prepared according to the traditional harvesting method with occlusion by a clip, dissection at the distal end and storage of the artery in papaverine until its implantation (CA) with the functional activity of arteries which were also prepared and wrapped in papaverine, but were left perfused and dissected immediately before their anastomoses (PA). Methods: Samples of ITA were obtained from a total number of 28 patients, undergoing bypass surgery, and randomly distributed into two groups. The arteries were cut into rings and suspended in organ baths, containing Krebs-Henseleit solution, for isometric tension recording. Cumulative concentration response curves were determined for the contractile agents endothelin-1 (ET-1), 5-hydroxytryptamine (5-HT), noradrenaline (NA) and potassium chloride (KCl) and the relaxant compounds acetylcholine (ACH) and sodium nitroprusside (SNP) during active tone induced by 30 mM KCl. Results: ET-1 and 5-HT stimulated rings from both groups within the same concentration ranges but elicited significantly (P<0.05) higher contractile responses in CA compared to PA. By contrast, concentration response curves for KCl and NA where nearly superimposable. On the other hand, maximal endothelium-dependent relaxant responses to ACH proved to be significantly stronger in PA (0.84±0.20 g) as compared to CA (0.31±0.05 g, P<0.05) while endothelium independent relaxant responses to SNP where similar in both groups. Conclusion: These data suggest that leaving the ITA perfused during harvesting might improve considerably the endothelial function of the graft.     

Effects of ultrasonic skeletonization on internal thoracic and gastroepiploic arteries for coronary artery bypass grafting.

OBJECTIVE: There are few data available on the effect of ultrasonic skeletonization with the harmonic scalpel on internal thoracic artery (ITA) and gastroepiploic artery (GEA) vessel function. METHODS: Rings of segments of the skeletonized ITA, pedicled ITA, skeletonized GEA, and pedicled GEA were studied. Arterial segments were treated with high KCl and norepinephrine (NE) to obtain smooth muscle contractions. Endothelium-dependent and independent vasorelaxant potencies in 10(-6)mol/l NE-pre-constricted arteries were assessed by acetylcholine (ACh), and isosorbide dinitrate (ISDN) and diltiazem, respectively. RESULTS: There were no differences in contractile potencies induced by high KCl and NE between the rings cut from skeletonized and pedicled grafts. The rings from skeletonized and pedicled vessels also showed equal sensitivity to ISDN and diltiazem. However, the rings from pedicled grafts showed greater relaxation responses to ACh than rings from skeletonized grafts. CONCLUSION: Ultrasonic complete skeletonization with the harmonic scalpel may retain smooth muscle function of skeletonized grafts, whereas endothelial function of ultrasonic skeletonized grafts may be significantly compromised.     

Isoflurane produces endothelium-independent relaxation in canine middle cerebral arteries.

Although it is generally accepted that isoflurane can cause cerebral vasodilation, the sensitivity of the cerebral vessels to this anesthetic agent remains controversial. Furthermore, the mechanism by which isoflurane produces its direct effects on the cerebral vasculature remains unknown. The purpose of this study was to determine if isoflurane-induced relaxation of canine middle cerebral arteries is dose-dependent and/or endothelium-dependent. In an additional series of experiments, isoflurane-induced relaxation was studied in the presence of indomethacin to inhibit prostacyclin release, and endothelium-independent relaxation was examined with sodium nitroprusside. The response to isoflurane was examined in middle cerebral arteries prior to and following pretreatment with 300 microM NG-monomethyl-L-arginine (LnMMA), an inhibitor of endothelium-dependent vasodilation. Vascular rings (2.5 mm in length and 600-800 microns in diameter) were suspended in tissue baths and isometric tension recorded. The rings were constricted with either 0.2 microM 5-hydroxytryptamine or 5 microM prostaglandin F2 alpha and subsequently exposed to increasing concentrations of isoflurane (0.65-4.9%). In separate experiments the procedure was repeated in vessels with and without endothelium. Isoflurane produced a dose-dependent relaxation in all vessels. This relaxation was not inhibited by LnMMA and was unaffected by the absence of endothelium. The isoflurane response was independent of cyclooxygenase inhibition. These results demonstrate that isoflurane-induced relaxation of canine middle cerebral arteries: 1) is dose-dependent; 2) is not mediated by modulation of endothelium-derived relaxing factor or a release of prostacyclin; and 3) is endothelium-independent.     

Vasoreactivity of arterial grafts in the patient with diabetes mellitus: investigations on internal thoracic artery and radial artery conduits.

OBJECTIVE: Arterial revascularization with either internal thoracic artery (ITA) or radial artery (RA) appears to be particularly attractive in diabetic patients. Previous investigations have shown that endothelial dysfunction and artherosclerosis are seen more often in these patients. The aim of this study was to compare the vasoreactive properties of ITA and RA grafts in diabetic and non-diabetic patients. METHODS: Arterial rings were harvested from 57 patients who underwent complete arterial revascularization. The patients were divided into a non-diabetic group (I: n = 30) and patients with diabetes mellitus (II: n = 27). Arterial rings of the ITA (I: n = 30; II: n = 27) and RA (I: n = 28; II: n = 19) were mounted on a strain gauge in oxygenated, normothermic Krebs's--Henseleit solution at optimal resting tension. With KCL (80 mM) serving as the control, assessment of force of contraction (norepinephrine), endothelium-dependent relaxation (acetylcholine) and smooth muscle-dependent relaxation (glyceroltrinitrate) were obtained. RESULTS: After KCL, the RA showed a trend to lower maximum contraction forces in diabetics (I: 76 +/- 25 mN; II: 69 +/- 29 mN), which was pronounced in patients with diabetes of more than 10 years duration (55 +/- 23 mN; P = 0.1). Maximum contraction force of the ITA was similar in both groups (I: 41 +/- 20 mN; II: 34 +/- 19 mN) and not influenced by the duration of diabetes. The two groups showed no significant differences of the relative vasoconstriction after norepinephrine in RA (I: 53 +/- 18%; II: 61 +/- 19%) and ITA rings (I: 70 +/- 23%; II: 69 +/- 25%). Also, endothelium-dependent relaxation with acetylcholine in RA (I: 53 +/- 14%; II: 57 +/- 16%) and ITA rings (I: 42 +/- 17%; II: 44 +/- 20%), and smooth muscle relaxation with glyceroltrinitrate of RA (I: 72 +/- 8%; II: 73 +/- 12%) and ITA rings (I: 64 +/- 12%; II: 58 +/- 20%) was comparable in both groups. No influence of duration of the diabetic disease was noted. CONCLUSIONS: Although RA rings of patients with a long duration of diabetes have decreased maximum contraction forces, their relative vasoconstriction after norepinephrine, endothelium-dependent relaxation and smooth muscle relaxation was similar to non-diabetic patients. We thus conclude that the RA is an adequate arterial conduit in the patient with diabetes mellitus.     

Coronary-coronary bypass using the internal thoracic artery: a sparing procedure of the arterial conduit

BACKGROUND: The internal thoracic artery (ITA) is well known to be the best conduit for coronary artery bypass grafting. However, the bilateral use of ITAs remains limited because in situ right ITAs (RITAs) do not possess an adequate length to be directed to the posterolateral myocardium. We thus considered using free ITAs for conduits between the two segments of the same coronary artery. METHODS: From March 1997 to May 1999, 17 patients underwent coronary-coronary bypass grafting (C-CBG) using free ITAs. Early operative results were analyzed. C-CBG was indicated when the right ITA had an inadequate length or when a distal part of the ITA was left unused. RESULTS: No patient died after C-CBG and none have experienced angina since C-CBG (mean follow-up period 27.3 +/- 19.8 months). Postoperative angiography was performed in all subjects at discharge. Only one coronary-coronary bypass graft was occluded, the other grafts were patent, and there were no stenotic changes. Bilateral ITAs were used in 75% of the patients undergoing CABG during the period of this study. CONCLUSIONS: C-CBG can expand the use of bilateral ITAs and can provide an alternative method for revascularization of the posterolateral myocardium.     

Even short-time storage in physiological saline solution impairs endothelial vascular function of saphenous vein grafts

Objectives: A faultless endothelial layer is decisive for vascular function and therewith graft's patency. Functional impairment of the endothelium increases risk of graft thrombosis, intimal hyperplasia, and consecutive accelerated graft atherosclerosis. Storage solutions for intra-operatively harvested saphenous vein segments (SVS) might have significant impact on endothelial function. We investigated the impact of short-time storage in physiological saline solution (PSS) and a potassium-chloride- and N-acetylhistidine-enriched storage solution on venous endothelial function. Methods: Intra-operatively isolated SVSs (n = 19) were stored in different storage solutions for 90 min. They were then immediately studied in tissue bath at 36 °C with continuous oxygen insufflation. Following preconstriction with norepinephrine, dose–response relaxation curves of bradykinine (Brad) and sodium nitroprusside (SNP) were determined. We compared developed maximum wall tension, vessel constriction kinetics, endothelial cell- and smooth muscle cell (SMC)-dependent vasodilatory function. Results: Maximum vessel wall tension was reduced significantly in PSS-stored vessels (10.1 ± 9.8 mN mm⁻¹ vs 3.5 ± 3.4 mN mm⁻¹; p = 0.0372). Endothelium-derived vasodilatory function was likewise significantly reduced after short-time storage (20.6 ± 34.4% vs 35.0 ± 27.0%; p = 0.0437). SNP-mediated SMC-vasodilatory function was maintained equally well in both groups (88.2 ± 21.8% vs 83.0 ± 30.6% in PSS; p = n.s.). Conclusion: Even short-time storage in PSS significantly impairs endothelial vascular function. Concerning the essential role of a faultless endothelial layer, the quite common use of PSS as a storage solution for SVSs in CABG surgery has to be discussed critically.     

Vascular smooth muscle contraction is an independent regulator of endothelial nitric oxide production

This investigation was conducted to determine whether endothelial nitric oxide (NO) production is regulated by vascular smooth muscle contraction. Unperfused ring segments of rat aorta and mesenteric artery were studied using isometric tension recording (n = 6-8 in all experiments). Following a reference contraction to K+ 80 mM (100%), arteries were left either unstimulated or stimulated by different concentrations of K+ or prostaglandin F2alpha (PGF2alpha) to induce different levels of vascular precontraction. N(G)-nitro-L-arginine methyl ester (L-NAME 0.1-300 microM) or NS 2028 (0.03-3 microM), which is a new specific inhibitor of the NO-sensitive guanylate cyclase, was then added at increasing concentrations to evaluate endothelial NO production. L-NAME and NS 2028 produced a concentration-dependent vasoconstrictor response which was progressively enhanced with increasing levels of precontraction. For L-NAME, this amounted in aorta to (% of reference contraction): 35+/-1% and 105 +/- 4% (precontraction by K(+) 20 and 30 mM) and 22+/-1%, 89+/-1%, 138+/-1% and 146+/-2% (precontraction by PGF2alpha 0.5, 1, 2 and 3 microM). A similar coupling was found in the mesenteric artery. A precontraction as little as 2% was enough to trigger a vasoconstrictor response to L-NAME. In contrast, L-NAME and NS 2028 had no effect in non-contracted arteries, not even when passive mechanical stretch was increased by 100%. The results suggest (i) that endothelial NO formation is progressively increased with increasing vascular tone, and (ii) that vascular isometric contraction per se stimulates endothelial NO formation. It is concluded, that active vascular smooth muscle contraction is an independent regulator of endothelial NO production.     

Skeletonization of internal thoracic artery affects its innervation and reactivity.

OBJECTIVE: The studies showing the superior characteristics of ITA graft and its impact on the clinical results of coronary artery surgery were performed with ITA harvested almost exclusively as a pedicle. This study assesses the impact of ITA skeletonization on its innervation and reactivity. METHODS: Segments of skeletonized and non-skeletonized ITA were stained with antibodies against protein S-100 to look for the presence of sympathetic nerve fibers. The functional studies were performed on segments of discarded human pedicled ITA that were divided into two 3mm rings, one skeletonized and another non-skeletonized. We compared concentration-effect relationships for the contraction to norepinephrine and endothelium-dependent relaxation to acetylcholine and bradykinin, as well as endothelium-independent relaxation to sodium nitroprusside in skeletonized and non-skeletonized segments of the same ITA. RESULTS: Skeletonized ITA was devoid of protein S-100 positive nerve fibers. It contracted stronger (maximal response 37.0+/-2.04 vs. 25.4+/-1.83mN (P<0.001)) and was twice as sensitive to norepinephrine: pD(2) 6.03+/-0.10 vs. 5.70+/-0.12 (P=0.035). The endothelium-dependent relaxation responses did not differ between skeletonized and non-skeletonized ITA rings. The skeletonized ITA rings appeared over 10 times more sensitive to sodium nitroprusside: pD(2) 6.66+/-0.20 vs. 5.59+/-0.37 (P=0.012)-potency ratio 11.61. The maximal responses did not differ significantly: 112.0+/-6.71 vs. 129.4+/-16.4% (P=0.33). CONCLUSIONS: Skeletonization results in sympathectomy of ITA. It has no effect on endothelium-dependent relaxation but increases reactivity of ITA to norepinephrine. This augmented response to alpha-agonist is small, in comparison with over a ten-fold increase in sensitivity to sodium nitroprusside. Pedicled and skeletonized ITA are functionally significantly different vessels when studied in vitro.     

Effect of K+ channel blockade with tetraethylammonium on anesthetic-induced relaxation in canine cerebral and coronary arteries.

The mechanism by which volatile anesthetics produce their direct effects on vascular smooth muscle remains unknown. The authors previously reported that volatile anesthetics decrease both Ca2+ and K+ currents, however the role of Ca(2+)-activated K+ channels during the vasorelaxation by anesthetics has not been investigated. The purpose of this study was to determine whether blockade of the K+ channel alters the response to volatile anesthetics. Responses were studied in canine middle cerebral arteries and proximal and distal canine coronary arteries. Vascular rings (2-mm length) were suspended in tissue baths, and isometric tension was recorded. Rings were constricted with 40 mM KCl and prostaglandin F2 alpha (middle cerebral arteries only) and subsequently exposed to enflurane (3.25%), halothane (1.35%), and isoflurane (2.1%). Volatile anesthetics produced vasorelaxation with relative potency in order: enflurane > halothane > isoflurane. The procedure was repeated in the presence of the K+ channel blocker tetraethylammonium chloride (TEA, 20 mM). In all groups of vessels TEA alone elicited either no increase or only a transient increase in tension, however constrictions to both agonists were augmented in the presence of TEA. The presence of TEA significantly augmented anesthetic-induced vasorelaxation in small and large coronary vessels and in middle cerebral arteries. However, this effect was more pronounced in the cerebral as compared to coronary arteries. Constrictions produced in cerebral vessels by 15 microM prostaglandin F2 alpha were comparable with constrictions produced by 5 microM prostaglandin F2 alpha in the presence of TEA. The subsequent relaxant response of these vessels to enflurane was also comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

A dose-response study of anticholinesterase drugs on contractile and phosphatidylinositol responses of rat trachea

We investigated whether anticholinesterase drugs in large doses inhibit muscarinic receptors of airway smooth muscle. In vitro measurements of isometric tension and [(3)H]inositol monophosphate (IP(1)) that formed were conducted by using rat tracheal rings or slices. Neostigmine and pyridostigmine caused muscular contraction and IP(1) accumulation in small doses (10 microM and < or = 100 microM, respectively), but they attenuated muscular contraction and IP(1) accumulation in larger doses (1000 microM). Edrophonium did not affect the smooth muscle tone and IP(1) levels. Neostigmine, pyridostigmine, and edrophonium attenuated the carbachol (5.5 microM)-induced smooth muscle contraction and IP(1) accumulation, when administered in large doses (1000 microM). The attenuation of contraction by neostigmine at large doses was not affected by methoctramine, an M(2) muscarinic receptor antagonist, but was reversed by washing with fresh Krebs-Henseleit solution. The results suggest that anticholinesterase drugs have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy. Implications: Neostigmine and pyridostigmine, but not edrophonium, have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy.     

Does competitive flow reduce internal thoracic artery graft patency?

BACKGROUND: In coronary arteries with moderate stenosis, competitive flow may lead to internal thoracic artery (ITA) graft occlusion. The goals of this study were to determine if competitive flow reduces ITA patency, and if there is a degree of coronary stenosis below which ITAs should not be used. METHODS: From 1972 to 1999, 50,278 patients underwent primary coronary artery bypass grafting (CABG). Of these, 2,002 had at least one ITA graft and postoperative angiography before coronary reintervention; 2,999 angiograms of 2,121 ITAs were made. Time-related ITA occlusion was modeled using longitudinal analysis to identify its risk factors while accounting for lack of independence introduced by repeated angiography and multiple ITA anastomoses per patient. Proximal coronary stenosis (maximum preoperative stenosis between ITA anastomosis and aorta) was the surrogate for competitive flow. RESULTS: Unadjusted ITA patency was 93%, 89%, 90%, and 92% at 1, 5, 10, and 15 years after CABG. Risk factors associated with ITA occlusion were lesser degree of proximal coronary stenosis (p < 0.0001); longer time from CABG in grafts to non-left anterior descending coronary arteries (p < 0.0001); female sex (p = 0.0003); later date of CABG (p = 0.01); right ITA (p < 0.0001); and smoking (p < 0.0001). In all arteries, as preoperative proximal coronary stenosis decreased, ITA patency declined; however, at no degree of stenosis was there a sharp decline. CONCLUSIONS: Internal thoracic artery patency decreases as coronary competitive flow increases. However, the nature of this relationship indicates ITAs should not be abandoned at moderate grades of stenosis.     

Isoflurane causes endothelium-dependent inhibition of contractile responses of canine coronary arteries

The authors sought to determine if isoflurane would attenuate effects of three different types of vasoconstrictors on isolated segments of canine epicardial coronary arteries removed from healthy dogs. As the endothelium has a major role in regulating epicardial coronary artery tone, and as it modulates the effect of many vasoactive substances, experiments were conducted both on normal rings and on rings whose endothelium had been mechanically removed. In addition, the endothelium is thought to be damaged in human atherosclerosis. Rings were suspected in organ chambers filled with modified Krebs-Ringer bicarbonate solution, aerated with 95% oxygen and 5% carbon dioxide, and connected to strain gauges for the measurement of isometric tension. Isoflurane 2.3% (1.5 MAC in the dog) was added to the aerating gas mixture in half the preparations, while the other rings served as control. The vasoconstrictors serotonin, phenylephrine, or prostaglandin F2 alpha were added in increasing concentrations to the bath solution. In the presence of endothelium, vasoconstrictor evoked contractions were attenuated by isoflurane. Maximal tension generated by prostaglandin F2 alpha in untreated rings was 114 +/- 18% (mean +/- SEM) of a reference contraction, while, following isoflurane, it was 46 +/- 8% (P less than 0.005). In the absence of endothelium, isoflurane attenuated neither prostaglandin F2 alpha nor serotonin evoked contraction, and had decreased effectiveness against phenylephrine mediated contraction (P less than 0.001). It is concluded that isoflurane attenuates vasoconstrictor-evoked contraction of isolated canine epicardial coronary arteries, and that this effect is mediated by the endothelium.     

Endothelin blockade potentiates endothelial protective effects of ACE inhibitors in saphenous veins

BACKGROUND: Angiotensin II and endothelin-1 are potent endothelium-derived contracting factors. The effects of acute endothelin antagonism on endothelial function in saphenous vein from patients treated with and without angiotensin-converting enzyme inhibitors were compared. METHODS: Vascular segments of saphenous vein were obtained perioperatively from 14 patients on angiotensin-converting enzyme inhibitors and 29 controls. In vitro endothelium-dependent and -independent responses to acetylcholine and sodium nitroprusside were assessed by constructing isometric dose-response curves in precontracted rings in the presence and absence of bosentan (endothelinA/B receptor antagonist) and BQ-123 (endothelinA antagonist) using isolated organ baths. Percent maximum relaxation and sensitivity were compared between interventions. RESULTS: Endothelium-dependent relaxation to acetylcholine was augmented in the angiotensin-converting enzyme inhibitor-treated group (p < 0.005). Both specific and mixed endothelin receptor blockade improved acetylcholine-mediated relaxation in the angiotensin-converting enzyme inhibitor-treated and untreated groups (p < 0.02). The effects of these antagonists were endothelium specific as endothelium-independent responses to sodium nitroprusside remain unaltered. CONCLUSIONS: These data demonstrate that (1) chronic angiotensin-converting enzyme inhibition improves endothelial function in saphenous veins, and (2) this effect can be further augmented by acute endothelin blockade. These data suggest that antagonism of both angiotensin II and endothelin may be important in attenuating saphenous vein arteriosclerosis.     

Feasibility and suitability of the routine use of bilateral internal thoracic arteries

BACKGROUND: It has been demonstrated that bilateral use of internal thoracic arteries (ITAs) confers better long-term results in patients than does unilateral use. However, routine use of bilateral ITAs has usually been avoided. METHODS: Since 1997, we have used bilateral ITAs extensively for patients who required multivessel bypasses. Recently, 243 consecutive patients, including 127 diabetic patients, were reviewed. RESULTS: Every patient received at least one ITA graft, and 200 patients (82%) received bilateral ITAs. The majority (93%) of ITA grafts were used as in situ grafts. The hospital mortality rate was 0.41%, and deep sternal infections were observed in 5 patients (2.0%). There was no difference in the incidence of chest wound infection between the group treated with bilateral ITA grafting and that treated by unilateral ITA grafting. CONCLUSIONS: These observations suggest that ITAs can be used bilaterally for treatment in the majority of patients who require multivessel bypass, with low mortality and morbidity.     

Early results of coronary grafting using ultrasonically skeletonized internal thoracic arteries

BACKGROUND: We have developed an ultrasonic complete skeletonization technique for obtaining internal thoracic artery (ITA) grafts and have used this method clinically since January 1998. In this report, we discuss the early results of bilateral ITA grafts obtained with our method. METHODS: We studied 200 consecutive patients who underwent coronary artery bypass grafting using ITAs obtained by this technique. Angiography of the grafts was performed in 188 patients (94%) within 1 month after coronary artery bypass grafting. RESULTS: The ITA grafts were about 4 cm longer than pedicled ITA grafts. The free flow through the grafts was at least 30% higher than through pedicled ITAs. The early patency rate determined by postoperative angiography of the grafts was 99.7% for left ITAs and 100% for right ITAs. No patient required postoperative intervention or repeated surgery. CONCLUSIONS: Ultrasonic complete skeletonization increases the effective length of ITA bypasses, improves free flow through the bypasses, and it is less invasive than conventional pedicled harvesting. These excellent early results indicate that this technique is a straightforward, safe, less invasive, and optimal method for obtaining ITA bypass grafts.     

Arterial myocardial revascularization with in situ crossover right internal thoracic artery to left anterior descending artery

BACKGROUND: The extra length obtained by skeletonizing the internal thoracic arteries (ITAs) enables versatile use of in situ bilateral ITAs for coronary artery bypass grafting, as the longer skeletonized right ITA more easily reaches the anastomotic site on the left anterior descending coronary artery. METHODS: Between April 1996 and November 1999, 365 consecutive patients underwent revascularization with bilateral in situ ITAs (29% of 1,250 grafting procedures performed with both ITAs in our department during this period). The right ITA was routed anterior to the aorta to graft the left anterior descending coronary artery, and the in situ left ITA was used to graft circumflex branches. Right coronary artery branches were grafted with right gastroepiploic artery or saphenous vein graft. The right ITA crossed the midline above the aorta at the most cranial point to avoid damage in case of a repeat sternotomy in the future. RESULTS: The operative mortality rate was 2.2% (8 patients). Postoperative morbidity included seven strokes (1.9%), eight sternal wound infections (2.2%), and four perioperative myocardial infarctions (1.1%). Follow-up (6 to 49 months) of 97% of hospital survivors showed a return of angina in 3%. Postoperative coronary angiography (22 patients) revealed a 95% patency rate of both ITAs. One-year and 4-year survival rates (Kaplan-Meier) were 95% and 92.4%, respectively. Important predictors of an early unfavorable event were chronic obstructive pulmonary disease, old age (> or = 70 years), emergency operation, and diabetes. Chronic obstructive pulmonary disease was the only independent predictor of sternal wound infection (odds ratio, 15; 95% confidence interval, 2.8 to 80). It also predicted decreased late survival (hazard ratio, 8.3; 95% confidence interval, 3 to 21.5). CONCLUSIONS: With skeletonized dissection of ITAs, the right ITA easily reaches the left anterior descending coronary artery for left-sided arterial revascularization with in situ bilateral ITAs. This procedure is safe, but we recommend avoiding its use in patients with chronic obstructive pulmonary disease.