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Ann Thorac Surg 2000;70:1111-1114
© 2000 The Society of Thoracic Surgeons

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Supplement: cardiothoracic techniques & technologies

Effects on coronary endothelial function of the Cohn stabilizer for beating heart bypass operations

^a Research Center and Department of Surgery, Montreal Heart Institute, Montreal, Quebec, Canada

Address reprint requests to Dr Perrault, Research Center, Montreal Heart Institute, 5000 Belanger St E, Montreal PQ, H1T 1C8, Canada
e-mail: lpperrau{at}icm.umontreal.ca

Presented at the Sixth Annual Cardiothoracic Techniques and Technologies Meeting 2000, Ft Lauderdale, FL, Jan 27–29, 2000.

	Abstract

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Background. The effects of different stabilizing methods for minimally invasive beating heart coronary artery bypass grafts (CABG) on coronary endothelial function are unknown.

Methods. We compared the effects on endothelial function of the Cohn stabilizer (used with proximal snaring by Retract-o-tape silicone air cushion) and a coronary shunt (CTS flow coil shunt) on an in vivo model of beating heart CABG. The two techniques were applied for 15 minutes on porcine epicardial coronary arteries. Control rings were taken from the same coronary artery. Endothelial function of control and instrumented arterial rings was studied in organ chamber experiments. Evaluation of endothelial coverage was performed with silver nitrate staining.

Results. Endothelium-dependent relaxation to serotonin and bradykinin was significantly decreased in the shunt group compared to control, Cohn stabilizer, and snare groups. There were no significant differences in the endothelium-independent relaxation to sodium nitroprusside between groups.

Conclusions. Greater endothelium-dependent relaxation with the Cohn stabilizer suggests better preservation of endothelial coverage at the site of application and reduced propensity for coronary spasm and later development of intimal hyperplasia.

	Introduction

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Coronary artery bypass grafting (CABG) has been performed on the beating heart without cardiopulmonary bypass (CPB) for a number of years. The use of "minimally invasive" CABG (MIDCABG) has become popular [1]. Because most of these techniques avoid cross-clamping of the aorta, they are performed on the beating heart. Technical aids are required for optimal visualization of the operative field during the performance of coronary anastomoses and for stabilization during MIDCABG. In the beginning of the CABG procedure visualization and stabilization was obtained by different devices: suspension with epicardial sutures placed around the coronary artery, pressure with different instruments. Progressively, more sophisticated techniques were developed such as snaring of the coronary artery, introduction of a shunt, or application of a forklike retractor. Since the initial reports of MIDCABG, there have been advances in the surgical technique, including the use of coronary stabilizers (Cohn coronary artery stabilizer; Genzyme, Cambridge, MA). The Cohn stabilizer is a new atraumatic technique developed to provide superior stabilization by avoiding pushing or pulling forces. The Cohn cardiac stabilizer with Retract-o-tape vessel loops captures the arteriotomy site with gentle epicardial herniation through the anastomotic window.

Operative manipulations [2] and ischemia-reperfusion can lead to local coronary endothelial dysfunction. Such dysfunction may favor the occurrence of acute vasospasm, leading to hypoperfusion and the development of chronic intimal hyperplasia and atherosclerosis. The effects of the different stabilizing devices on coronary endothelial function are unknown. The present experiments were designed to assess the effects of two commonly used stabilizing techniques: one using the Cohn stabilizer (used with proximal snaring by Retract-o-tape silicone air cushion) and the other by coronary shunting (CTS flow coil shunt; CardioThoracic Systems, Inc, Cupertino, CA) on the endothelial function of target coronary arteries.

	Material and methods

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Surgical technique
All experiments were performed using Landrace swines of either sex, aged 8 ± 1 weeks and weighing 23.69 ± 0.95 kg. Animals were treated in compliance with the recommendations of the Guidelines on the Care and Use of Laboratory Animals issued by the Canadian Council on Animal and the Guidelines of the Animal Care and were approved by a local committee.

Devices were applied for 15 minutes on the right and left anterior descending coronary arteries at random. The CTS flow coil shunt was applied with proximal snaring by the Retract-o-tape silicone air cushion, which was removed after application to allow the coronary circulation. The Cohn stabilizer was applied with a proximal and distal snaring of the coronary artery recommended by the manufacturer (Genzyme). Control rings were taken from the same coronary artery at random (Fig 1).

View larger version (24K): [in this window] [in a new window]   Fig 1. Schematic depicting the sites of instrumented and control coronary rings for vascular reactivity studies. (LAD = left anterior descending coronary artery; RC = right coronary artery.)

The endothelial function of control and artery rings submitted to devices application in the same population were studied as previously reported [2]. The maximal contraction was determined with potassium chloride (60 mmol/L). Endothelium-dependent relaxations were determined by serotonin (10^-10 to 10^-5 mol/L), a Gi-protein-dependent agonist and with bradykinin (10^-12 to 10^-6 mol/L), a Gi-protein-independent agonist after contraction to prostaglandin F₂ (2 x 10^-6 mol/L). Endothelium-independent relaxations were determined with sodium nitroprusside (10^-10 to 10^-5 mol/L), a nitric oxide donor.

Examination of the endothelium coverage
The endothelial coverage was studied by silver nitrate staining of segments of epicardial coronary arteries following the device applications. The rings were fixed first for 10 minutes with buffered paraformaldehyde (4%). They were then washed for 1 minute with a HEPES sucrose buffer solution. Silver nitrate 0.25% was applied for 1 minute. Washing was performed for 1 minute before a second fixation for 2 minutes. The rings were exposed to light for 2 to 4 hours in a cacodylate buffer solution. Preparations were read by a blinded investigator and representative photomicrographs were taken.

Statistical analysis
Contractions to PGF₂ are expressed as a percentage of the maximal contraction to potassium chloride (60 mmol/L) for each group and expressed as means ± standard error of the mean (SEM); n refers to the number of animals studied. Relaxations are expressed as percentage of the maximal contraction to PGF₂ for each ring. Analysis of variance studies were performed to compare dose–response curves. Differences were considered to be statistically significant when p was less than 0.05.

	Results

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Vascular reactivity
There were no significant differences in the amplitude of the contraction to potassium chloride (60 mmol/L) and prostaglandin F₂ (range 2 x 10^-6 to 10^-5 mol/L) among all segments of the left anterior descending coronary artery and the right coronary artery, namely at the sites of snare, Cohn stabilizer, CTS flow coil shunt, and the control segments (Table 1).

View this table: [in this window] [in a new window]   Table 1. Porcine Coronary Artery Contractions with Potassium Chloride (KCl 60 mmol/L) and Prostaglandin F2 Following Device Applications

View larger version (19K): [in this window] [in a new window]   Fig 2. Cumulative concentration-relaxation curves to bradykinin (BK) in rings of porcine left anterior descending and right coronary arteries with endothelium submitted to CTS flow coil shunt (n = 7, ), to Cohn stabilizer (n = 7, ), and snare (n = 7, ) applications (15 minutes) compared with the control (n = 7, •). Responses are given as a percentage of relaxation to the contraction induced by prostaglandin F2 (PGF2). Results are presented as mean ± standard error of the mean. *p < 0.05 versus control, snare, and Cohn stabilizer groups.

View larger version (17K): [in this window] [in a new window]   Fig 3. Cumulative concentration-relaxation curves to serotonin (5-HT) in rings of porcine left anterior descending and right coronary arteries with endothelium submitted to CTS flow coil shunt (n = 7, ), to Cohn stabilizer (n = 7, ), and snare (n = 7, ) applications (15 minutes) compared with the control (n = 7, •). Responses are given as a percentage of relaxation to the contraction induced by prostaglandin F2 (PGF2). Results are presented as mean ± standard error of the mean. *p < 0.05 versus control group.

View larger version (16K): [in this window] [in a new window]   Fig 4. Cumulative concentration-relaxation curves to sodium nitroprusside (SNP) in rings of porcine left anterior descending and right coronary arteries with endothelium submitted to CTS flow coil shunt (n = 5, ), to Cohn stabilizer (n = 5, ), and snare (n = 5, ) applications (15 minutes) compared with the control (n = 5, •). Responses are given as a percentage of relaxation to the contraction induced by prostaglandin F2 (PGF2). Results are presented as mean ± standard error of the mean.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
Performance of CABG without aortic cross-clamping is becoming more popular because this technique limits the inflammatory response to CPB as well as ischemia and reperfusion and preserves renal, pulmonary, and cognitive function. Since the onset of MIDCABG, the complexity of the anesthetic technique has decreased, related to changes in surgical design and technology. One way of avoiding ischemia is clearly to keep the heart beating, which necessitates manipulation of the target coronary vessel by the use of hemostatic techniques to achieve a dry operative field and stabilize the heart.

Endothelial cells play a key role in the regulation of vascular homeostasis. Clamping of coronary arteries with commercially available clamps may injure the vascular endothelium, resulting in a denudation of the endothelial cell coverage and consequently a decrease of endothelium-dependent relaxations [3].

Application of bulldog clamps [2], perfusion catheters, and Anastaflo catheters [4] are followed by endothelial denudation associated with insertion and removal of the catheters and a selective dysfunction of Gi-protein-mediated relaxations. However, the hemostatic technique involving snaring of the coronary artery with double looping of a Gore-Tex (W. L. Gore and Assoc, Flagstaff, AZ) suture over a silicone tubing does not cause endothelial dysfunction [5]. In the present study, application of the Cohn stabilizer had no significant effects on endothelium-dependent relaxations when applied for 15 minutes, whereas introduction of a shunt in epicardial coronary artery altered these responses. The contractile function and endothelium-independent relaxation were unaffected by the use of all techniques, demonstrating the integrity of the underlying smooth muscle cells.

Loss of endothelial cell coverage may be important clinically because regenerated endothelium presents a selective dysfunction manifested by decreased endothelium-dependent relaxations mediated by pertussis toxin-sensitive G-proteins. These alterations may accelerate the occurrence of vasospasm and atherosclerosis [6]. Endothelial denudation was observed on segments submitted to 15 minutes of shunt application. These results suggest that use of the shunt removes the endothelial cells and consequently induces an endothelial dysfunction. However, coronary arteries exposed to the Cohn stabilizer had an intact endothelial cell coverage.

Utilization of the Cohn stabilizer in beating heart CABG could be better to prevent the coronary spasm and later a development of intimal hyperplasia because this technique compared with others used in clinical surgery demonstrated greater endothelium-dependent relaxations and better preservation of the endothelial coverage at the site of application.

	References

Top Abstract Introduction Material and methods Results Comment References

 

1. Acuff T.E., Landreneau R.J., Griffith B.P., Mack M.J. Minimally invasive coronary artery bypass grafting. Ann Thorac Surg 1996;61:135-137.[Abstract/Free Full Text]
2. Perrault L., Menasché 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]
3. Fonger J., Yang X., Cohen R., Haudenschild C., Shemin R. Human mammary artery endothelial sparing with fibrous jaw clamping. Ann Thorac Surg 1995;60:551-555.[Abstract/Free Full Text]
4. Chavanon O., Perrault L., Menasché P., Carrier M., Vanhoutte P. Endothelial effects of hemostatic devices for continuous cardioplegia or minimally invasive operations. Ann Thorac Surg 1999;68:1118-1120.[Free Full Text]
5. Perrault L., Menasché P., Bidouard J., 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]
6. Shimokawa H., Flavahan N.A., Vanhoutte P.M. Loss of endothelial pertussis toxin-sensitive G protein function in atherosclerotic porcine coronary arteries. Circulation 1991;83:652-660.[Abstract/Free Full Text]

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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): Louis P. Perrault Michel Carrier Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perrault, L. P. Articles by Carrier, M. Search for Related Content PubMed PubMed Citation Articles by Perrault, L. P. Articles by Carrier, M.