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The role of potassium channels in the vasodilatory effect of levosimendan in human internal thoracic arteries.

OBJECTIVE: We investigated the role of potassium channels in vasodilatory effect of levosimendan in human internal thoracic arteries. METHODS: Samples of redundant internal thoracic arteries 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: Levosimendan (10(-8)-10(-5) M) or cromakalim (10(-8)-10(-5) M) produced concentration-dependent relaxation responses in human internal thoracic arteries precontracted by 10(-6) M phenylephrine. The relaxant responses to levosimendan did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human internal thoracic artery rings with adenosine 3',5'-triphosphate (ATP)-dependent potassium channel blocker glibenclamide (10(-6) M) for 30 min significantly inhibited the relaxant responses to both levosimendan and cromakalim. The Ca2+-activated potassium channel blocker iberiotoxin (10(-7) M) also caused a significant but smaller inhibition on relaxant responses to levosimendan. Incubation of the rings with the voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) for 10 min did not cause significant alterations in relaxant responses to levosimendan. CONCLUSIONS: The findings of this study suggested that levosimendan-induced relaxation responses in human internal thoracic arteries were depended on the activation of ATP-dependent and Ca2+-activated potassium channels.

Aged↗

Bilateral skeletonized internal thoracic artery grafts in patients with diabetes mellitus.

OBJECTIVE: Increased risk of deep sternal infections has prohibited routine bilateral internal thoracic artery grafting in diabetic patients. The technique for harvesting the skeletonized internal thoracic artery provides the potential to minimize this risk. The purpose of this study was to compare the outcome of bypass grafting with bilateral skeletonized internal thoracic arteries in diabetic and nondiabetic patients. METHODS: From May 1996 to April 1998, 231 consecutive diabetic and 534 nondiabetic patients underwent bilateral skeletonized internal thoracic artery grafting. Mean age was 66 years. Compared with the nondiabetic group, the diabetic group comprised more women (29% vs 18%, P =.001), had a greater prevalence of hypertension (53% vs 44%, P =.019) and congestive heart failure (20% vs 14%, P =.016), but a lower prevalence of preoperative acute myocardial infarction (26% vs 34%, P =.027). RESULTS: Operative mortality of diabetic patients was comparable with that of nondiabetic patients (3% vs 2.6%). The two groups also had similar occurrences of deep sternal infection (2.6% vs 1.7%, respectively, P =.40). Deep sternal infection was significantly more prevalent in obese, diabetic women (3/20 = 15%) than in diabetic patients without this combination of risk factors (3/211 = 1.4%, P <.0001) (odds ratio 11.1, confidence interval 2.1-59.4). Diabetic patients also had a higher incidence of stroke (3.5% vs 0.9%, P =.014). Three-year actuarial survival of diabetic patients was lower (91.3% vs 94.7%, P =.083). CONCLUSIONS: Bilateral skeletonized internal thoracic artery grafting is a good surgical revascularization option in diabetic patients. Operative mortality and prevalence of sternal infection are comparable with those of nondiabetic patients. However, the risk of sternal infection in obese diabetic women is high, and for them we advocate the use of a single artery instead of bilateral internal thoracic arteries.

Aged↗

Preparation of the internal thoracic artery by vasodilator drugs: is it really necessary? A randomized double-blind placebo-controlled clinical study.

OBJECTIVE: The internal thoracic artery has become the conduit of choice for coronary artery bypass grafting. To avoid spasm of the artery, and increases in its diameter and flow, various vasodilators have been used either intraluminally or by topical application by different surgeons. In order to define the best vasodilating agent for preparation of the internal thoracic artery, a randomized double-blind placebo-controlled clinical study was performed in a group of patients submitted for elective coronary artery bypass grafting. METHODS AND RESULTS: Eighty (80) consecutive patients submitted for elective first time coronary artery bypass grafting were randomly subdivided into five treatment groups. Free flow of the left internal thoracic artery was measured using an electromagnetic flow meter. The first measurement was performed shortly after the internal thoracic artery was dissected from the chest wall and the second just prior to performing distal anastomosis to the left anterior descending coronary artery. During the time interval between the two measurements the internal thoracic artery was immersed in a special applicator tube containing 20 ml solution of one of the following drugs: papaverin 2 mg/ml, nitroglycerin 1 mg/ml, verapamil 0.5 mg/ml, nitroprusside 0.5 mg/ml, normal saline 0.9%. RESULTS: No statistically significant differences were found between the groups in respect to age, body surface area, bypass time, cross clamping time, and time interval between the two flow measurements. Mean arterial pressure at the time of the first and second internal thoracic artery flow measurements did not show statistically significant differences either within or between the groups. In all five groups, the free flow of the internal thoracic artery increased significantly with time. However, no statistically significant differences were shown between the five groups with respect to second flow (P = 0.2). CONCLUSIONS: Within the limits of our study design, we suggest that preparation of the LITA by topical vasodilator drugs using a special applicator tube does not result in a significantly superior free flow than placebo.

Aged↗

Late regression of left internal thoracic artery graft stenosis at the anastomotic site without intervention therapy.

OBJECTIVE: Intervention therapy has been recently performed on the left internal thoracic artery graft stenosis. The purpose of this study was to evaluate the natural course of the left internal thoracic artery graft stenosis at the anastomotic site and clarify whether intervention therapy should be performed early after surgery. METHODS: We investigated early angiographic results of the left internal thoracic artery graft in 343 consecutive patients who underwent coronary bypass surgery. In 100 of 343 patients who underwent follow-up angiography, the graft diameter and percentage diameter stenosis at the anastomotic site were compared between early postoperative and follow-up angiography. None of these patients underwent intervention therapy on the left internal thoracic artery graft. RESULTS: Of 343 patients, 46 showed 50% or greater diameter stenosis, and 20 showed 70% or greater diameter stenosis at the anastomotic site. In the 100 patients with follow-up angiography, the graft diameter significantly increased (1.8 +/- 0.4 vs 2.1 +/- 0.5 mm, P < .0001) at follow-up angiography. The percentage diameter stenosis significantly decreased (69% +/- 13% vs 35% +/- 20%, P < .0001) at follow-up angiography in the patients with 50% or greater diameter stenosis at early postoperative angiography. Regression of left internal thoracic artery graft stenosis was detected in most patients with 70% or greater diameter stenosis. CONCLUSIONS: Our study demonstrated that left internal thoracic artery graft stenosis at the anastomotic site at early postoperative angiography might improve without intervention therapy. We should consider the natural course of the left internal thoracic artery graft stenosis in determining the indication of intervention therapy early after surgery.

Adult↗

Origin of the internal thoracic artery and its relationship to the phrenic nerves.

The internal thoracic artery was studied because of its recent use in the revascularization of the myocardium in patients with coronary artery disease. The artery of 50 cadavers of adult individuals of either sex, whose age ranged from 20 to 84 years, was studied after neoprene latex injection. Its origin, relation to the phrenic nerve and origin of the pericardiacophrenic artery were investigated. The left and right phrenic nerves cross the artery anteriorly in 54% of the cases and posteriorly in 14%. The right nerve crosses the artery anteriorly and the left posteriorly in 22%, and the reverse occurs in 10%. The origin of the internal thoracic artery is much more frequent from the subclavian artery (80%) than from a common trunk with other arteries (20%). The pericardiacophrenic artery is a branch of the internal thoracic artery in 99% of the cases and the average distance between the origins of these two arteries is 3.9 +/- 1.3 cm.

Adult↗

Five-year follow-up of microsurgical multiple internal thoracic artery grafts.

In a consecutive series of 143 patients requiring multiple coronary artery bypass grafts, 317 of 441 anastomoses (72%) were constructed from internal thoracic arteries. Of these 143 patients, 103 had bilateral, 51 sequential, and 49 free internal thoracic artery grafts. When compared with an earlier series of 494 patients who underwent only one internal thoracic artery anastomosis, the surgical morbidity and mortality were not increased, but, during 5 years of follow-up, the incidences of postoperative angina and myocardial infarction were found to decrease significantly--32.5% versus 10.5% (p < 0.001) and 5.7% versus 1.4% (p < 0.03), respectively. We conclude that, for patients with multivessel disease, multiple internal thoracic artery grafts confer better protection from the clinical manifestations of ischemic heart disease than does one internal thoracic artery graft. The use of high magnification (8 to 12x, surgical microscope) was essential to the success of this method.

Coronary Disease↗

A macroscopic study of the internal thoracic artery of the rat.

The internal thoracic artery (ATI) of rats was macroscopically studied. In this study, the overall features of the artery were virtually elucidated in entirety. The artery was found to arise from the subclavian artery in the thoracic cavity and to immediately break up into the following branches: (1) the pericardiacophrenic artery, (2) the superior epigastric artery, (3) the thymic branch, (4) the comitans branch to the brachiocephalic veins, and finally (5) the bronchoesophageal trunk. As is well known, rats are devoid of the superior caval veins, retaining instead a pair of brachiocephalic veins into adulthood; this is a greatly beneficial condition as it enables us to consider the essential relationships of the ATI to relevant structures which are thought to be directly involved in the development of the ATI. In fact, the rat ATI revealed topographically a remarkable intimacy with the phrenic nerve, the brachiocephalic and inferior caval veins, the heart and lungs and also with the diaphragm; in their development all are in close relationship with the pleuropericardial fold. This fact leads us to the opinion that, for a better understanding of the morphological meanings of the ATI, an understanding of the relationship of this artery to the pleuropericardial fold seems to be a prerequisite.

Animals↗

[Experience of double internal thoracic artery grafts in coronary artery revascularization].

We have started employing two internal thoracic artery grafts in coronary artery revascularization since February 1988. We have carried out seven such operative procedures in a 15 month period since then. Ages ranged from 55 to 67 years with a mean of 60.6. Six patients were male and one patient was female. One patient was in Canadian Cardiovascular Society angina Class I, one in Class II, four in Class III, and one in Class IV, preoperatively. There were no operative deaths. Postoperatively, six patients were in CCS Class I and one was in Class II. All of the internal thoracic artery grafts were patent at hospital discharge in six angiographically examined patients. We feel that use of double internal thoracic artery grafts in coronary revascularization carries minimal additional risk, when performed in selected case.

Aged↗

[Left internal thoracic artery as a collateral vessel in chronic occlusion of the pelvic artery].

Four years after implantation of an aorto-bi-iliac artery graft, a 53-year-old man suffered from intermittent claudication with a walking distance of 50 meters. By transaxillary aortography the left femoral artery could not be visualized. Selective angiography of the internal thoracic artery revealed a collateral circulation from the subclavian artery via the left internal thoracic artery, the superior epigastric artery and the inferior epigastric artery into the left external iliac artery (Winslow's pathway). Prior to using the internal thoracic artery for coronary bypass surgery, a function of this vessel as a collateral to the lower extremities should be excluded.

Aorta, Abdominal↗

Benefits accruing to grafting of the right internal thoracic artery to the left anterior descending artery in coronary artery bypass grafting.

OBJECTIVES: We have investigated the effects and outcome from grafting the right internal thoracic artery to the left anterior descending artery in coronary artery bypass grafting. METHODS: We analyzed the findings in 185 patients who underwent coronary artery bypass grafting involving right internal thoracic artery-left anterior descending artery bypass. The survival rate, cardiac events related to the right internal thoracic artery-left anterior descending artery graft, and graft patency were investigated. In cardiac catheterization, the production of nitric oxide from the endothelium of the internal thoracic artery was measured as the plasma nitrite and nitrate levels by the Griess reaction. The reactions to acetylcholine infusion (5 micrograms) in the right internal thoracic artery (n = 4) were compared to those in the left internal thoracic artery (n = 9) grafts. RESULTS: The hospital mortality rate was 0.5%. The actuarial survival rate at 11 years after operation was 98.81%. The rate of freedom from cardiac events at 11 years after operation was 92.08%. The rate of patency of the right internal thoracic artery-left anterior descending artery was 97.0% in 133 patients. Nitric oxide production was calculated as (total nitrite plus nitrate production in response to stimulation by acetylcholine-total nitrite plus nitrate level before acetylcholine load)/(total nitrite plus nitrate level before acetylcholine load). There was no significant difference in changes in plasma concentration in response to acetylcholine stimulation between the right internal thoracic artery-left anterior descending artery and left internal thoracic artery-left anterior descending artery groups (20 +/- 29% versus 5 +/- 10%). CONCLUSIONS: The right internal thoracic artery-left anterior descending artery grafts exhibited good patency and release of nitric oxide in response to acetylcholine loading, similar to left internal thoracic artery-left anterior descending artery grafts.

Coronary Artery Bypass↗

Surgical anatomy of the internal thoracic artery.

BACKGROUND: The internal thoracic artery (ITA) has become increasingly important in coronary artery bypass grafting due to the excellent long-term results. This study reviews its anatomic characteristics. METHODS: The ITAs of 100 cadavers were examined and their origin, relation to the phrenic nerve, presence of lateral costal branch; origin of pericardiacophrenic arteries, length, level and type of ITA termination, relation with the transverse muscle of thorax, collateral parietal branches, and distance between the ITA and sternal margins were studied. RESULTS: The ITA was present in all cases, originating directly from the subclavian artery or from a common trunk with other arteries. Its length was 20.4 cm on average, and the most frequent level of termination was at the sixth intercostal space, existing as a bifurcation in 93% and as a trifurcation in 7%. The pericardiacophrenic artery originated from the ITA in 89%. The lateral costal branch was present in 15% of the cases. The ITA was covered by the transverse muscle of the thorax for 7.5 cm (average) and was crossed anteriorly by the phrenic nerve in 70.0%. CONCLUSIONS: Information provided by this study may contribute to knowledge of its anatomic characteristics and in turn help prevent complications in ITA dissections.

Adult↗

Fractional flow reserve of pedicled internal thoracic artery and saphenous vein grafts 6 months after bypass surgery.

BACKGROUND: Although the internal thoracic artery was proven superior to saphenous vein graft in long-term patency, it is thought to be a more resistive conduit than the vein graft. Moreover, patency studies comparing both left and right internal thoracic arteries have provided results favoring the former. Fractional flow reserve is an established functional index of coronary blood flow. METHODS: To compare the fractional flow reserve between both internal thoracic arteries and saphenous vein grafts, 43 bypass grafts were studied 6 months after revascularization. Intra-graft pressures were measured during cardiac catheterization using a pressure-wire advanced to the first distal anastomosis of 12 left internal thoracic arteries (ITAs), 10 right ITAs and of 21 vein grafts. Pressure gradients between the aorta and the graft were measured at baseline and during a maximal hyperemia. RESULTS: At baseline, pressure gradient was recorded in the left ITA (2.9+/-2.2 mmHg), in the right ITA (1.2+/-1.2 mmHg) and in the vein graft (0.4+/-0.7 mmHg). During maximal hyperemia, pressure gradient increased to 9.6+/-3.2 mmHg in left ITA, to 4.5+/-2.0 mmHg in the right ITA (p<0.001 vs left ITA) and to 3.3+/-2.7 mmHg in vein (p<0.001 vs left ITA; NS vs right ITA). Fractional flow reserve was 0.90+/-0.04 in left ITA, 0.95+/-0.03 in right ITA (p<0.01 vs left ITA) and 0.96+/-0.03 in vein (p<0.001 vs left ITA). CONCLUSION: Internal thoracic arteries and saphenous vein grafts allow myocardial revascularization with minimal resistance to maximal blood flow. The resistance appears significantly higher in left ITA compared to both the right ITA and venous grafts.

Blood Pressure↗

Inverted T graft: novel technique using composite radial and internal thoracic arteries.

BACKGROUND: Multiple arterial revascularization is feasible because of the excellent long-term patency of the arterial grafts compared with venous grafts. We present a new operative technique for multiple arterial revascularization using composite radial and internal thoracic arterial grafts. METHODS: Between January and September 1997, 12 patients had coronary artery bypass grafting with inverted T graft. The indications for inverted T graft were aortic calcification in 4 patients, repeat coronary artery bypass grafting in 1 patient, and total arterial revascularization in 7 young patients. The inverted T graft was constructed by interconnecting the coronary arteries and radial artery with end-to-side and side-to-side anastomoses, and by anastomosing the internal thoracic artery to the side of radial artery. RESULTS: Overall, 38 distal anastomoses (average number per patient, 3.2) were made with an inverted T graft. There were no deaths or perioperative myocardial infarctions. Postoperative angiography disclosed that all of the anastomoses were patent. CONCLUSION: This technique allows multiple arterial revascularizations without technical difficulty. It is useful in patients with aortic calcification, repeat coronary artery bypass grafting patients, and young patients who are candidates for total arterial revascularization.

Adult↗

Off-pump awake coronary revascularization using bilateral internal thoracic arteries.

BACKGROUND: A new technique has been developed that permits complete arterial revascularization of the lateral and/or inferior wall of the heart using in situ bilateral internal thoracic artery grafts in awake patients. This technique, without cardiopulmonary bypass and mechanical ventilation, creates the least invasive revascularization method for the lateral and/or posterior wall of the heart yet described. METHODS: In 7 patients double or triple vessel coronary artery bypass grafting was performed without general anesthesia. A high thoracic epidural anesthesia was started one hour before surgery. Bilateral internal thoracic arteries were harvested and all anastomoses were performed with the off-pump technique by standard median sternotomy. Circumflex, or the right coronary artery, were anastomosed with bilateral internal thoracic arteries using a heart positioner. Six patients received double bypass grafting and one patient received triple bypass grafts (bilateral internal thoracic arteries and one radial artery). RESULTS: All patients remained awake throughout the whole procedure. There was no perioperative myocardial infarction or mortality. Pneumothorax was observed in three patients, but it was repaired in two. Only one patient completed the procedure with unilateral pneumothorax. There were no hemodynamic and pulmonary problems during lateral or posterior wall revascularization. Two patients required unexpected coronary endarterectomy during circumflex and right coronary artery anastomoses. CONCLUSIONS: Complete arterial revascularization by median sternotomy using in situ bilateral internal thoracic artery grafts without general anesthesia is a feasible and safe procedure for multivessel disease. This approach gives a chance for awake revascularization of the right and/or circumflex coronary artery.

Adult↗

Transcutaneous ultrasound assessment of internal thoracic artery to coronary artery grafts in patients with and without ischaemic symptoms.

OBJECTIVE: To evaluate transcutaneous duplex ultrasound in the assessment of internal thoracic artery to coronary artery grafts. SETTING: Regional cardiothoracic centre. METHODS: Prospective duplex ultrasound evaluation of 83 consecutive patients undergoing left internal thoracic artery to coronary artery grafts, together with combined angiographic and duplex ultrasound evaluation of 17 patients with suspected recurrent myocardial ischaemia after internal thoracic artery grafting. RESULTS: The grafted internal thoracic artery was imaged in 65 (78%) of 83 consecutive postoperative patients, and in 13 (75%) of 17 patients with suspected graft dysfunction. Grafts were recognised by their characteristic position and biphasic blood flow pattern. Resting graft flow was estimated from the time averaged velocity and graft cross sectional area. Median resting flow in patients without ischaemic symptoms was 36 ml/min (interquartile range 24 to 49 ml/min). Of 13 patients with recurrent ischaemia in whom the graft could be imaged, nine patients with estimated flow in the lowest quartile or abnormal flow profiles, or both, had graft disease or anastomotic problems on angiography, while four with satisfactory graft flow on ultrasound examination had normal graft flow on angiography, but had evidence of native disease progression in other vessels. Two of four patients in whom it was not possible to image the graft on ultrasound had satisfactory graft function on angiography. CONCLUSIONS: For those patients whose internal thoracic artery graft can be imaged, transcutaneous duplex ultrasound is a helpful non-invasive guide to graft function. The main limitations to the technique are an inability to image the graft in about 20% of patients, and possible inaccuracy in estimating graft diameter.

Coronary Artery Bypass↗

Healing of the intimal dissection of the internal thoracic artery graft.

We report healing of the intimal dissection of an internal thoracic artery graft. Triple coronary artery bypass grafting was performed using left internal thoracic artery and saphenous vein grafts. One month after operation, the intimal dissection of the internal thoracic artery graft was clearly visible by coronary angiography; however, after 1 year of only medical treatment consisting of warfarin, ticlopidine, and nitrate, the intimal dissection was undetectable by coronary angiography.

Aged↗

The human internal thoracic artery releases more nitric oxide in response to vascular endothelial growth factor than the human saphenous vein.

OBJECTIVE: Endothelial nitric oxide inhibits smooth muscle cell proliferation, reducing the chance of vascular intimal thickening. In this study we investigated whether the superior long-term patency of the internal thoracic artery in human coronary bypass grafting compared with that of the saphenous vein could be explained by different levels of nitric oxide production. METHODS: The baseline endogenous nitric oxide production appeared to be 50% higher in the internal thoracic artery than in the saphenous vein. Previously, it was shown that vascular endothelial growth factor and the vascular endothelial growth factor receptors KDR (Flk-1) and Flt-1 are expressed in both internal thoracic arteries and saphenous veins and that vascular endothelial growth factor receptor density was higher in internal thoracic arteries than in saphenous veins. Therefore, we also investigated the influence of vascular endothelial growth factor on nitric oxide release in both the internal thoracic artery and the saphenous vein. RESULTS: Vascular endothelial growth factor augmented nitric oxide production by approximately 50% in the saphenous vein and 100% in the internal thoracic artery. As shown by means of immunohistochemistry, expression of endothelial constitutive nitric oxide synthase was similar in the internal thoracic artery and the saphenous vein, and no inducible nitric oxide synthase was expressed in any of the vascular segments. CONCLUSION: Vascular endothelial growth factor augments endothelial constitutive nitric oxide synthase-dependent nitric oxide release to a greater extent in the internal thoracic artery than in the saphenous vein. These findings may help to explain the long-term superiority of the internal thoracic artery versus the saphenous vein as a conduit for coronary artery bypass.

Analysis of Variance↗

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.

Adult↗