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Ann Thorac Surg 2005;80:1728-1731
© 2005 The Society of Thoracic Surgeons
a Department of Cardiovascular Surgery, National Medical Centre, Budapest, Hungary
b Research Laboratory, National Medical Centre, Budapest, Hungary
Accepted for publication May 9, 2005.
* Address correspondence to Dr Tarr, 1135 Budapest, Szabolcs u.35, Hungary (Email: tarr{at}ogyik.hu).
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Abstract |
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 Top Abstract IntroductionPatients and MethodsResultsCommentReferences |
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METHODS: Nitrite levels in the anterior interventricular vein, before and after anastomosis completion, in the left internal mammary artery free flow, and in the subclavian vein were measured. Fluroscopy after 4-hydroxycoumarin nitrozation was utilized to measure nitrite content of blood samples in 50 consecutive, partly heparinized patients undergoing off-pump coronary bypass surgery. Nitrate content of all samples was removed by Cadmium pearls.
RESULTS: One hundred and sixty-four samples taken from 41 patients were feasable to analyze. A significant increase of nitric oxide (nitrite) level was found in the anterior interventricular vein, when comparing concentrations measured before and after the anastomosis between the left internal mammary artery and the left anterior descending artery. Mean values in the anterior inteventricular vein before and after anastomosis completion were as follows: 44.8 µMol (SD 4.9) and 70.7 µMol (SD 8.1), respectively.
CONCLUSIONS: The increased production of nitric oxide by the internal mammary arterial graft may provide a perpetual vasodilatory response and partially protect the distal coronary vessel from atherosclerosis.
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsCommentReferences |
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In vitro studies described endothelial function of the internal mammary artery in detail. Experimental and clinical data revealed, that the production of endothelium-derived nitric oxide in the internal mammary artery is significantly greater than that observed in saphenous vein [9–11]. Besides the mentioned vessel wall structure, the high concentration (55 to 81 µMol; data of this study) of continuously produced nitric oxide may play a role in resistence to atheroclerosis since, in case of intimal injury, this substance maintains an inhibition of local platelet aggregation and adhesion, while in the tunica media it blocks smooth muscle cell mitogenesis. Meanwhile, intravasally, endothelium-derived nitric oxide induces local and downstream vasodilatation. It is also known that, in the balance of endothelium-dependent vasoregulation of the internal mammary artery, there is a tendency toward vasodilatation (nitric oxide plus prostacyclin against endothelin plus thromboxane) [12–14].
In this study—utilizing a modified method for screening stable metabolite of endothelium-derived nitric oxide (described in detail in other work of ours)—we investigated whether the internal mammary artery bypass graft would increase nitric oxide concentration in the recipient coronary vessel [15]. We hypothesized, that an enhancement of stable metabolite concentration of nitric oxide could be measured in the venous drainage of the recipient coronary artery.
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentReferences |
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Patient inclusion criteria included a usable internal mammary artery (free flow greater than 80 mL/min). Intact anatomy of the left subclavian and internal mammary artery was proved by angiography. Feasable sampling site for insertion a polyethylene canula into the anterior interventricular vein (AIV) was also a prerequisite. No drug containing nitrates was given to patients in the perioperative period. (Patients requiring nitrates for clinical reasons were excluded from the study.)
Preoperative demographics and relevant clinical data are summarized in Table 1.
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After heparinization a polyethylene canula with a diameter of 1 mm was inserted into the anterior interventricular vein for passive sampling. The quantity taken was 4 mL (AIV1).
This was followed by taking a left internal mammary artery (LIMA) free flow sample at 75 mm Hg mean systemic pressure. As a third step, a sample was taken from the anterior interventricular vein, 5 minutes after the anastomosis completion (AIV2). Finally, a sample from the subclavian vein was collected before protamine administration, as a reference point. (In the first 9 patients, a steel needle was used for sampling from the anterior interventricular vein with active suction, which resulted in severe hemolysis, making these samples unsuitable for evaluation.)
All test tubes containing 4 mL sampled blood were stored in a tank with ice cubes (2°C to 4°C) and transported to the laboratory without delay, where all were deep frozen for later analysis. (Nitrite is stable in frozen blood samples for at least 1 year). Nitrite level determination was carried out utilizing the modified Takafumi Ohta method, details of which are given elsewhere [14]. Nitrate content of all samples was removed on Cadmium pearls. Sample analysis was carried out without the knowledge of its origin.
Statistical Analysis
Values are expressed as the mean ± SEM. Comparisons of the four kinds of samples were carried out by analysis of variance (ANOVA) and the Tukey method. A p value of less than 0.05 was considered as statistically significant.
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Results |
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Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentReferences |
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Another important factor, however, seems to be its endothelial function: the production of endothelium-derived nitric oxide, which apparently keeps on functioning when the vessel has been diverted from its original anatomic site and is used as a coronary bypass graft. There are data from Cosgrove and colleagues [8] that an IMA bypass graft macroscopically may modify (slow down or prevent) atherosclerotic process in the recipient artery. Pearson and coworkers [16] found that the IMA appears to release a greater amount of nitric oxide than the saphenous vein.
Based on the results of this study, there is a definite alteration in the micromilieu of the recipient vessel. The internal mammary artery–produced nitric oxide can be detected in the recipient artery. There is a significant increase of its stable metabolite concentration, measured in the venous drainage. The beneficial effects of endothelium-derived nitric oxide–related vasodilatation and inhibition of platelet adhesion may form the basis of structural preservation of the recipient coronary artery. The described model of investigation—off-pump coronary revascularization—is regarded as more physiologic than coronary bypass surgery with a heart lung machine, as the patient's blood has no direct contact with nonendothelial surfaces. One factor is "aphysiologic," namely, heparin administration, which has an inductive effect on nitric oxide production, but it increases the baseline levels as well [17, 18]. The significant increase of nitric oxide concentration in the venous drainage of the left anterior descending artery—which is also significantly greater than that of the coronary sinus [14]—gives the idea that the internal mammary artery bypass graft creates a different micromilieu in the left anterior descending system, which per se will differ from other coronary systems of the same individual. We presume that all classical factors related to atherogeneses are persistently present in the given patient, and create primordial atheromas in all coronary arteries except the left anterior descending branch, which is protected by the internal mammary artery [19]. It is evident that the only change affecting the recipient artery is related to the endothelial function of the bypass graft. However, the observation of higher nitrite level in certain AIV1 samples, and lesser increase in the respective AIV2 ones, probably relates to the extent of the stenosis in the LAD. We think that significant but not critical stenosis generates lesser flow and velocity reduction, accordingly the inductive effect of shear stress on endothelium-derived nitric oxide production in the LAD is less diminished, and the additive endothelium-derived nitric oxide of the IMA bypass graft is also less pronounced. We believe that the described model elucidate the additive effect of higher flow induced shear stress, on one hand, and of the originally increased endothelium-derived nitric oxide production of the IMA graft, on the other.
This is the first report in the literature to describe measuring stable metabolite measurement of endothelium-derived nitric oxide in the clinical environment, namely, in the operating theater with a simple but reliable method originally designed to identify the nitrite content of the saliva. As the origin of the samples sent to the research laboratory has not been disclosed, it is very much reassuring to realize that there is a firm correlation regarding numeric data of the four analyzed samples.
It has been revealed that different nitric oxide concentrations can be detected in the coronary system accordingly, which received the internal mammary artery (anatomically, the easiest to measure the venous drainage of the left anterior descending artery), and as a consequence, coronary circulation tends to show differences in the three major coronary systems regarding vasoactive substances.
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