HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Thomas Schachner Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hangler, H. B. Articles by Antretter, H. Search for Related Content PubMed PubMed Citation Articles by Hangler, H. B. Articles by Antretter, H. Related Collections Coronary disease

Ann Thorac Surg 2004;77:776-780
© 2004 The Society of Thoracic Surgeons

---

Original article: cardiovascular

Effects of intracoronary shunts on coronary endothelial coating in the human beating heart

^a Department of Cardiac Surgery, Institute of Anatomy Histology and Embryology, Leopold-Franzens-University, Innsbruck, Austria
^b Department of Institute of Anatomy Histology and Embryology; and Department of Histology and Molecular Cell Biology, Leopold-Franzens-University, Innsbruck, Austria

Accepted for publication August 19, 2003.

^* Address reprint requests to Dr Hangler, Leopold-Franzens-University, Department of Cardiac Surgery, Anichstrasse 35, 6020 Innsbruck, Austria
e-mail: herbert.hangler{at}uibk.ac.at

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
BACKGROUND: Local occlusion of coronary arteries during beating heart revascularization leads to injury of the arterial wall especially disturbing the integrity of the endothelium. The aim of this study was to elucidate the effects of intracoronary shunts versus local occlusion with elastic silicone loops on the beating heart in human coronary arteries by scanning electron microscopy.

METHODS: Coronary arteries of patients with dilated cardiomyopathy (n = 4) or ischemic heart disease (n = 8) undergoing heart transplantation were locally occluded either with a silicone loop or with a shunt inserted after arteriotomy. Unmanipulated segments of the coronary arteries served as controls. Integrity of the endothelial lining was observed with scanning electron microscopy.

RESULTS: Scanning electron microscopy revealed a statistically significant higher injury after shunting compared with controls (p < 0.001) and vessel loop occlusion (p < 0.001). There was no difference between both patient groups according to control specimens or after manipulation.

CONCLUSIONS: From this investigation we conclude that insertion of intracoronary shunts during beating heart surgery leads to severe endothelial denudation in human coronary arteries. Therefore, at present we recommend using intracoronary shunts selectively in cases in which critical ischemia or technical difficulties as a result of anatomic conditions are expected during anastomosis and avoiding routine shunt insertion into coronary arteries during beating heart revascularization.

	Introduction

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Coronary revascularization without cardiopulmonary bypass has emerged in recent years, although there is no convincing evidence by randomized controlled trials that postoperative morbidity and mortality is lower in patients operated without cardiopulmonary bypass [1–4].

Hemodynamic disturbances seen during cardiac displacement in off-pump coronary artery bypass graft surgery has led to surgical techniques that minimize mechanical compression of the heart during the anastomosis period. Despite enormous technical development of exposure and stabilization techniques [5–8], it is necessary to have a dry field for an exact coronary anastomosis, the main objective in coronary surgery. This is usually achieved by encircling sutures around the coronary arteries for external compression of the target vessel or by inserting properly sized intracoronary shunts after arteriotomy. Our group as well as others has shown that hemostatic devices may be harmful to the endothelium of the target coronary vessel, potentially leading to intimal hyperplastic responses with consequent stenosis in the region of local occlusion. In this study we compare two popular hemostatic techniques, intracoronary shunting and silicone loop occlusion, in the human beating heart by scanning electron microscopy.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Experimental groups and operative design
The left anterior descending coronary artery or the right coronary artery of patients undergoing orthotopic heart transplantation for dilative cardiomyopathy (group 1, n = 4) or ischemic coronary heart disease (group 2, n = 8) were incised, and intracoronary shunts (Anastaflow RMI intravascular shunts; Research Medical Inc, Midvale, UT) were placed into the coronary artery using the shunt shuffle technique [9]. The shunt size was chosen according to the diameter of the coronary artery. The number of insertion attempts as well as the leaking severity beside the shunt were documented. Furthermore the coronary artery was double-looped with an elastic silicone loop (Retract-o-tape Air cushion vascular loop; Quest Medical Inc, Allen, TX), and gentle traction was applied on both ends for coronary artery compression. These maneuvers were performed after cannulation before cardiopulmonary bypass was started and left in place for a period of 10 minutes to simulate the average duration of a coronary anastomosis. When necessary, cardiopulmonary bypass was started without unloading the heart to keep a pulsatile flow. Uninstrumented segments adjacent to the occlusion site of the same coronary artery served as controls. After a shunting or occlusion period of 10 minutes, the aorta was cross-clamped and the heart immediately excised.

Procurement of tissue
Instantly after excision of the diseased recipient heart, the coronary arteries were perfused with a physiologic pressure of 120 mm Hg for 10 minutes with 2.5% glutaraldehyde in 0.1 mol/L cacodylate buffer (pH 7.4) through a perfusion cannula inserted into the left or right coronary ostium and postfixed for 1 hour. In this way, the endothelium was fixed in situ before being further processed for scanning electron microscopy. Subsequently the vessels were dissected free from the adherent epicardial tissue in a careful way under high magnification and cut in transverse sections 5 mm apart from the occlusion area on each side. Control samples were taken from the adjacent uninstrumented areas of the same coronary artery.

Preparation of the coronary arteries for scanning electron microscopy
The coronary artery cylinders were cut longitudinally, pinned on cork plates, and postfixed in 1% osmium tetroxide (OsO₄), then dehydrated in a graded ethanol series and subjected to critical-point drying (Bal-Tec CPD 030; Bal-Tec AG, Balzers, Liechtenstein). After drying, samples were mounted on specimen stubs using colloidal silver and coated with 15 nm of gold (Bal-Tec CPD 020; Bal-Tec AG). The entire endothelial surface of each specimen was examined with a scanning electron microscope (Zeiss DSM 982 Gemini; Zeiss, Oberkochen, Germany) operated at 5 kV.

Histomorphology of the endothelial layer was classified into four grades: grade 0: the entire surface was covered by intact endothelial cells with tight intercellular attachment (intact endothelial layer) as depicted in Figure 1; grade 1: dehiscent intercellular junctions of endothelial cells; grade 2: isolated detachment of endothelial cells as shown in Figure 2 (minor endothelial injury); grade 3: focal areas devoid of endothelial cells as displayed in Figure 3; and grade 4: expansive local endothelial denudation with the subendothelial tissue exposed (Fig 4; severe endothelial injury).

View larger version (118K): [in this window] [in a new window]   Fig 1. (A) Control specimen from patient 2; scanning electron micrograph depicts an overview of a coronary artery cut into half longitudinally after pressure fixation with an intact endothelial surface. (B) Inset, higher magnification with tight endothelial cell attachment completely covering the vascular surface, corresponding to a grade 0 classification.

View larger version (110K): [in this window] [in a new window]   Fig 2. (A) Dehiscent intercellular junctions and detachment of endothelial cells (grade 2: minor endothelial injury). (B) Inset, higher magnification. (# = endothelial cell.)

View larger version (137K): [in this window] [in a new window]   Fig 3. (A) Focal endothelial denudation after vessel loop occlusion. Note denuded area (*), with subendothelial tissue exposed (grade 3). (# = remnant endothelial cells.) (B) Inset, higher magnification.

View larger version (140K): [in this window] [in a new window]   Fig 4. (A) Severe endothelial injury (grade 4) after shunt (outer diameter, 2.5 mm) insertion in vessel from patient 2. Note denuded area (*), with subendothelial tissue exposed. (# = remnant endothelial cells.) (B) Inset, higher magnification.

Statistical analysis
All data were stored in a computerized database (Microsoft Excel for Windows; Microsoft Corp, Redmond, WA), and statistical assessments were performed using the SPSS for Windows statistical software package (SPSS 11.0; SPSS, Inc, Chicago, IL). Analysis of the severity of endothelial lesions within the control as well as the manipulated vessel specimens were compared using nonparametric Mann-Whitney U test after testing for normal distribution using Kolmogorow-Smirnow test. A p value of less than 0.05 was considered to be statistically significant. Data are shown as median and range.

The study was approved by the local human research committee, January 21, 1998. Informed consent was obtained by all patients participating in the study.

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
In this study we examined 12 coronary artery segments manipulated with silicone loops passed twice around the coronary artery (double-looped) and 15 segments after inserting an intravascular shunt. The shunts had an outer diameter of 6 at 2.0 mm, 6 at 2.5 mm, or 3 at 3.0 mm. Two of the shunts (both 2.5 mm) appeared negligibly leaking, whereas all other shunts inserted were leakproof. No dissection was macroscopically evident after shunt insertion or vessel loop occlusion.

All coronary artery segments manipulated with a shunt exhibited a severe injury with nearly complete denudation of the endothelial layer without difference between the proximal and distal sites of the arteriotomy where the occluding bulb of the shunt was situated. Endothelial injury was statistically significantly higher after manipulation with intracoronary shunts when compared with control specimens (p < 0.001) as well as after vessel loop occlusion (p = 0.006) of the human coronary artery. Table 1 depicts the severity of endothelial injury according to the occlusion method. The number of shunt insertion attempts (10 one time, 5 two times) had no statistically significant influence on the degree of endothelial injury.

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Knowledge of the effects of coronary occlusion devices gains importance with the expanding numbers of off-pump coronary artery bypass grafting procedures that require control of the target coronary arteries during performance of the delicate coronary anastomosis. Previous studies investigating the effects of hemostatic devices on endothelial function and morphology have been performed in animal coronary arteries not burdened with preexisting arteriosclerosis. These investigations, performed in organ chamber experiments, revealed that extravascular devices such as bulldog clamps, extravascular balloon occlusion [10], and double-looped Gore-Tex suture snaring [11] created a lesser degree of endothelial dysfunction when compared with intracoronary shunts [12]. This is in accordance with the results of our study demonstrating a nearly total endothelial cell loss after shunt insertion into human coronary arteries. In contrast, when the effects on endothelial function of intracoronary shunts, silicone–air cushion snaring, and clamping of coronary arteries were compared in coronary arteries with preexisting arteriosclerosis, none of the techniques did cause a significantly greater dysfunction of G_I protein endothelium-dependent relaxation. Moreover, in another experimental setup of particular importance, Perrault and colleagues [13] did not find a difference in the device application groups compared with the arteriosclerotic controls in the relaxation to serotonin. However, when endothelial-mediated relaxation in coronary arteries with preexisting arteriosclerosis is not different after manipulation with hemostatic devices, intraluminal shunting could be of theoretical advantage. The medial and adventitial layer, two other important vascular tissue components that influence unfavorable restrictive arterial remodeling [14], may be less impaired with intraluminal than extraluminal occlusion devices as there is no uncontrolled and immoderate tension or compression of the vascular wall. This may occur with manually operated force leading to disruption of the media, resulting in the exposure of the adventitia to the coronary lumen with consequent activation of adventitial fibroblasts and subsequently amplified neointimal formation [15]. Additionally Gerola and associates [16] have shown compression and buckling of the elastic lamellae with medial fractures when snares were applied to a region with marked arteriosclerotic disease. Moreover, our group reported rupture of arteriosclerotic plaques after encircling human coronary arteries in a beating heart experiment with snaring sutures [17].

In this study we demonstrate a loss of endothelial cell coverage after insertion of intracoronary shunts in human arteriosclerotic-burdened coronary arteries. Endothelial cell loss alone can trigger intimal hyperplasia [18]. However, regrowth of endothelium occurs, which may subsequently downregulate intimal smooth muscle cell proliferation with less unfavorable arterial remodeling.

When the endothelial layer of vessels is seriously injured after shunt placement in human coronary arteries, as approved in our study, the nonthrombogenic properties of the endothelium may be disturbed, and in particular, anastomosis after off-pump coronary artery bypass graft surgery could be at higher risk for thrombosis as there is less impairment of platelet count and function and an increased procoagulant activity in the first 24 hours after surgery than in on-pump operations [19].

Experimental animal and clinical studies have shown a benefit when shunts are inserted into the left anterior descending coronary artery during minimally invasive direct coronary artery bypass (MIDCAB) or off-pump coronary artery bypass grafting. In a porcine MIDCAB model Dapunt and coworkers [20] assessed a reduced ischemia-reperfusion injury and a preserved left ventricular function after introducing intracoronary shunts in contrast to local occlusion of the left anterior descending coronary artery. Menon and colleagues [21] investigated 35 patients undergoing a MIDCAB procedure either with snaring or inserting a shunt into the left anterior descending coronary artery beyond a high-grade coronary artery stenosis during MIDCAB procedures. In their study, the authors conclude that shunt insertion had two positive effects. First, acute intraoperative benefits resulted in preserved left ventricular function during the time of anastomosis as well as after reperfusion. However, there is conflicting data about the clinical impact of ischemia-reperfusion injury in MIDCAB operations [22–24]. And second, more interestingly, a superior early patency rate of the performed anastomosis with less need for reinterventions up to 6 months postoperatively was reported when compared with local external occlusion of the left anterior descending coronary artery. This may be in part contrary to our results because after denudation of the endothelium in the region where the occluding bulbs of the shunts are situated, an unfavorable arterial remodeling process with consequent target coronary artery stenosis could be presumed. The better patency rate in the shunted group after MIDCAB from Menon and colleagues [21] has been attributed to a minor technical anastomosis failure rate, but may at least in part be attributed to the regenerative capacity of the endothelium. A longer follow-up of these patients by means of angiographic or intravascular ultrasound studies would be of importance in this setting. A theoretical concern is dissection of the coronary artery caused by manipulation during insertion of the shunt, but this has not been reported so far in the literature and could not be observed in our investigation.

Drawback of the study
In this protocol stabilization of the target coronary artery that potentially influences the effects on the coronary artery wall has not been performed.

Conclusions
From this investigation we conclude that insertion of intracoronary shunts during beating heart surgery leads to severe endothelial denudation in human coronary arteries. Therefore, at present we recommend using intracoronary shunts selectively in cases in which critical ischemia or technical difficulties as a result of anatomic conditions are expected during anastomosis and avoiding routine shunt insertion into coronary arteries during beating heart revascularization.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
We thank Karin Gutleben and Angelika Flörl for aid in preparation of the coronary artery samples for scanning electron microscopy.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

1. Bull D.A., Neumayer L.A., Stringham J.C., Meldrum P., Affleck D.G., Karwande S.V. Coronary artery bypass grafting with cardiopulmonary bypass versus off-pump cardiopulmonary bypass grafting: does eliminating the pump reduce morbidity and cost?. Ann Thorac Surg 2001;71:170-173.[Abstract/Free Full Text]
2. Kim K.B., Lim C., Lee C., et al. Off-pump coronary artery bypass may decrease the patency of saphenous vein grafts. Ann Thorac Surg 2001;72(Suppl):S1033-1037.[Abstract/Free Full Text]
3. Ascione R., Lloyd C.T., Underwood M.J., Lotto A.A., Pitsis A.A., Angelini G.D. Economic outcome of off-pump coronary artery bypass surgery: a prospective randomized study. Ann Thorac Surg 1999;68:2237-2242.[Abstract/Free Full Text]
4. Puskas J.D., Williams W.H., Duke P.G., et al. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay. A prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003;125:797-808.[Abstract/Free Full Text]
5. Akpinar B., Guden M., Sagbas E., Sanisoglu I., Aytekin V., Bayindir O. Off-pump coronary artery bypass grafting with use of the octopus 2 stabilization system. Heart Surg Forum 2000;3:282-286.[Medline]
6. Jansen E.W., Borst C., Lahpor J.R., et al. Coronary artery bypass grafting without cardiopulmonary bypass using the octopus method: results in the first one hundred patients. J Thorac Cardiovasc Surg 1998;116:60-67.[Abstract/Free Full Text]
7. Dullum M.K., Resano F.G. Xpose: a new device that provides reproducible and easy access for multivessel beating heart bypass grafting. Heart Surg Forum 2000;3:113-117.[Medline]
8. Ricci M., Karamanoukian H.L., D'Ancona G., Bergsland J., Salerno T.A. Exposure and mechanical stabilization in off-pump coronary artery bypass grafting via sternotomy. Ann Thorac Surg 2000;70:1736-1740.[Abstract/Free Full Text]
9. Patel N.C., Pullan D.M., Fabri B.M. 'Shunt shuffle'—a simple technique of introducing intracoronary shunts for off-pump coronary artery bypass. Eur J Cardiothorac Surg 2002;21:1121-1122.[Abstract/Free Full Text]
10. Perrault L.P., Menasche P., Wassef M., et al. Endothelial effects of hemostatic devices for continuous cardioplegia or minimally invasive operations. Ann Thorac Surg 1996;62:1158-1163.[Abstract/Free Full Text]
11. Perrault L.P., Menasche P., Bidouard J.P., et al. Snaring of the target vessel in less invasive bypass operations does not cause endothelial dysfunction. Ann Thorac Surg 1997;63:751-755.[Abstract/Free Full Text]
12. Chavanon O., Perrault L.P., Menasche P., Carrier M., Vanhoutte P.M. As originally published in 1996: endothelial effects of hemostatic devices for continuous cardioplegia or minimally invasive operations. Updated in 1999. Ann Thorac Surg 1999;68:1118-1120.[Free Full Text]
13. Perrault L.P., Desjardins N., Nickner C., Geoffroy P., Tanguay J., Carrier M. Effects of occlusion devices for minimally invasive coronary artery bypass surgery on coronary endothelial function of atherosclerotic arteries. Heart Surg Forum 2000;3:287-292.[Medline]
14. Christen T., Verin V., Bochaton-Piallat M., et al. Mechanisms of neointima formation and remodeling in the porcine coronary artery. Circulation 2001;103:882-888.[Abstract/Free Full Text]
15. Shi Y., O'Brien J.E., Fard A., Mannion J.D., Wang D., Zalewski A. Adventitial myofibroblasts contribute to neointimal formation in injured porcine coronary arteries. Circulation 1996;94:1655-1664.[Abstract/Free Full Text]
16. Gerola L.R., Moura L.A., Leao L.E., Soares H.C., Branco J.N., Buffolo E. Arterial wall damage caused by snaring of the coronary arteries during off-pump revascularization. Heart Surg Forum 2000;3:103-106.[Medline]
17. Hangler H.B., Pfaller K., Antretter H., Dapunt O.E., Bonatti J.O. Coronary endothelial injury after local occlusion on the human beating heart. Ann Thorac Surg 2001;71:122-127.[Abstract/Free Full Text]
18. Fingerle J., Au Y.P., Clowes A.W., Reidy M.A. Intimal lesion formation in rat carotid arteries after endothelial denudation in absence of medial injury. Arteriosclerosis 1990;10:1082-1087.[Abstract/Free Full Text]
19. Mariani M.A., Gu Y.J., Boonstra P.W., Grandjean J.G., van Oeveren W., Ebels T. Procoagulant activity after off-pump coronary operation: is the current anticoagulation adequate?. Ann Thorac Surg 1999;67:1370-1375.[Abstract/Free Full Text]
20. Dapunt O.E., Raji M.R., Jeschkeit S., et al. Intracoronary shunt insertion prevents myocardial stunning in a juvenile porcine MIDCAB model absent of coronary artery disease. Eur J Cardiothorac Surg 1999;15:173-178.[Abstract/Free Full Text]
21. Menon A.K., Albes J.M., Oberhoff M., Karsch K.R., Ziemer G. Occlusion versus shunting during MIDCAB: effects on left ventricular function and quality of anastomosis. Ann Thorac Surg 2002;73:1418-1423.[Abstract/Free Full Text]
22. Yeatman M., Caputo M., Narayan P., et al. Intracoronary shunts reduce transient intraoperative myocardial dysfunction during off-pump coronary operations. Ann Thorac Surg 2002;73:1411-1417.[Abstract/Free Full Text]
23. Van Aarnhem E.E., Nierich A.P., Jansena E.W.L. When and how to shunt the coronary circulation in off-pump coronary artery bypass grafting. Eur J Cardiothorac Surg 1999;16(Suppl 2):S2-6.[Abstract/Free Full Text]
24. Malkowski M.J., Kramer C.M., Parvizi S.T., et al. Transient ischemia does not limit subsequent ischemic regional dysfunction in humans: a transesophageal echocardiographic study during minimally invasive coronary artery bypass surgery. J Am Coll Cardiology 1998;31:1035-1039.[Abstract/Free Full Text]

This article has been cited by other articles:

				J. Bergsland, P. S. Lingaas, H. Skulstad, P. K. Hol, P. S. Halvorsen, R. Andersen, M. Smastuen, R. Lundblad, J. Svennevig, K. Andersen, et al. Intracoronary Shunt Prevents Ischemia in Off-Pump Coronary Artery Bypass Surgery Ann. Thorac. Surg., January 1, 2009; 87(1): 54 - 60. [Abstract] [Full Text] [PDF]

				M. Emmiler, C. U. Kocogullari, Y. Ela, and A. Cekirdekci Influence of intracoronary shunt on myocardial damage: a prospective randomized study Eur. J. Cardiothorac. Surg., November 1, 2008; 34(5): 1000 - 1004. [Abstract] [Full Text] [PDF]

				S. P. Collison, A. Agarwal, and N. Trehan Controversies in the use of intraluminal shunts during off-pump coronary artery bypass grafting surgery. Ann. Thorac. Surg., October 1, 2006; 82(4): 1559 - 1566. [Abstract] [Full Text] [PDF]

				W. J.L. Suyker, J. P. Matonick, P. T.W. Suyker, A. Brutel de la Riviere, M. P. Buijsrogge, R. P.J. Budde, C. W.J. Verlaan, G. Pasterkamp, P. F. Grundeman, and C. Borst S2 Connector Versus Suture: Distal Coronary Anastomosis Remodeling, Patency, and Function in the Pig Circulation, July 4, 2006; 114(1_suppl): I-390 - I-395. [Abstract] [Full Text] [PDF]

				A. Gurbuz, B. Emrecan, L. Yilik, I. Ozsoyler, M. Kestelli, C. Ozbek, and N. Karahan Intracoronary shunt reduces postoperative troponin leaks: a prospective randomized study Eur. J. Cardiothorac. Surg., February 1, 2006; 29(2): 186 - 189. [Abstract] [Full Text] [PDF]

				G. Watanabe, H. Kamiya, H. Nagamine, S. Tomita, Y. Koshida, S. Nishida, H. Ohtake, S. Arai, and T. Yasuda Off-Pump CABG with Synchronized Arterial Flow Ensuring System Ann. Thorac. Surg., November 1, 2005; 80(5): 1893 - 1897. [Abstract] [Full Text] [PDF]

				R. G. Demaria and L. P. Perrault On Decreasing Distal Endothelial Damage After Intracoronary Shunt Insertion Ann. Thorac. Surg., May 1, 2005; 79(5): 1826 - 1826. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Thomas Schachner Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hangler, H. B. Articles by Antretter, H. Search for Related Content PubMed PubMed Citation Articles by Hangler, H. B. Articles by Antretter, H. Related Collections Coronary disease