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Ann Thorac Surg 1997;63:1063-1069
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Cryopreserved Veins in Myocardial Revascularization: Possible Mechanism for Their Increased Failure

Division of Cardiothoracic Surgery, Cardiac Research Program, State University of New York at Stony Brook, Stony Brook, New York

Accepted for publication October 31, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
Background. Cryopreserved veins are used as conduits for myocardial revascularization. However, a high failure rate associated with their use has been reported anecdotally.

Methods. To find an explanation for the poor performance of cryopreserved vein grafts, we conducted a retrospective 5-year study on all patients at a single institution in whom cryopreserved vein grafts were used. We further performed in vitro studies measuring cell adhesion, nitric oxide production, and contractile capacity of saphenous vein, internal thoracic artery, and cryopreserved veins.

Results. Forty-one patients were identified in whom one or more cryopreserved veins were used as a last resort. Sixteen had events (death or recatheterization). Seven deaths occurred (17%). Event-free survival was 50% at 12 months. Activated granulocyte/monocyte endothelial adherence could be lowered in internal thoracic arteries and saphenous veins with morphine incubation (50% and 57%, respectively), but not in cryopreserved veins. Simultaneous increases in nitric oxide release were also found in internal thoracic arteries and saphenous veins, but not cryopreserved veins. In addition, cryopreserved veins showed a diminished contractile capacity under experimental conditions.

Conclusions. In this highly select group of patients, cryopreserved veins had a high early failure rate, which may be partially due to the inability of the endothelium to participate in immunovascular processes.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
The most frequent vessel employed as an aortocoronary bypass conduit remains the saphenous vein, which shows atherosclerotic plaque formation in a year. Approximately 45% of removed veins 5 to 10 years after implantation contain ruptured plaques with superimposed thrombus in the graft lumen. Arterial conduits that are more resistant to atherosclerosis, such as the internal thoracic or gastroepiploic artery, have enjoyed increased use. However, a sharp increase in the median age of patients presenting with advanced atherosclerosis and an increase in the number of patients who require multiple operations for coronary revascularization have resulted in a critical need for alternative conduits. Intense interest has been generated in the use of nonautogenous materials for revascularization, not only synthetic materials, but also homologous materials such as cryopreserved homograft veins. Anecdotal reports of these materials, however, paint a bleak picture of their patency rates.

To find a possible explanation for the failure of cryopreserved vein grafts, we conducted a retrospective 5-year study of patients with such grafts. In addition, vascular function of cryopreserved veins was compared with that of autologous fresh saphenous veins to identify possible mechanisms that contribute to the loss of vessel patency.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
Patient Population
Between January 1, 1991, and December 31, 1995, at University Hospital of the State University of New York at Stony Brook, 41 patients had a minimum of one cryopreserved venous homograft conduit inserted. All veins were procured from Cryolife, Inc, Marietta, GA, and stored in liquid nitrogen. All veins were matched to the patient by ABO blood groups. Before implantation, the cryopreserved veins underwent a complete thawing according to Cryolife instructions. The patients were a mixed group, all of whom required revascularization as part of the procedures they had undergone. In 6 patients, homografts were the sole means of revascularization. In all other patients, homografts were used as only part of the revascularization. Autologous veins and bilateral internal mammary arteries as well as gastroepiploic arteries were the first choice in all cases (radial artery grafts were not used during the study period). Follow-up was complete in all patients.

This group of patients received surgical revascularization as part of a salvage operation, either for intractable symptoms or because of a poor hemodynamic situation judged to be refractory to other forms of therapy.

	Operative Technique

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
Radial and pulmonary artery catheters were introduced under local anesthesia. Anesthesia was induced and maintained with fentanyl. As muscle relaxants either pancorium bromide or vecuronium bromide was used. Cardiopulmonary bypass was initiated with an ascending aortic cannula and a two-stage right-atrial cannula for coronary artery bypass grafting cases, and biatrial cannulation was used for all other cases. The circuit was primed with crystalloid solution and mannitol. All patients receiving homograft veins were started on a warfarin regimen on the second postoperative day and maintained with an international normalized ratio of 2.0 based on our clinical observation of early graft closure. No reoperations for bleeding were necessary. Blood cardioplegia was used in all cases with antegrade administration. Only in the last 2 years was retrograde administration used.

	Venous and Arterial Measurements

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
Parts of saphenous veins and internal thoracic arteries from volunteers undergoing routine elective coronary artery bypass grafting were stored in an electrolyte solution of 4°C (500 mL Plasmalyte with 5,000 U heparin and 60 mg papaverine). The specimens were immediately transported to the laboratory for processing. All experiments involving the use of human tissue were approved by the institutional review board for human experimentation and were performed with informed consent of the patients.

	Experimental Study

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
Human granulocytes and monocytes were obtained for evaluation of cellular conformation and endothelial cell adhesion. Blood was obtained and processed as previously described [1, 2]. A total of 5 patients qualified for the study (not included in the 41 patients).

	Analysis of Cellular Activity

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
FLUORESCENCE STAINING.
After Ficoll-Hypaque isolation [1, 2], 10^-6 mol/L granulocytes and monocytes were centrifuged at 8,000 rpm for 5 minutes. The supernatant was discarded, and the cells were then treated with the fluorescent vital dye PKH26-GL (Sigma, St. Louis, MO) in accordance with the detailed instructions of the commercially available kit. The cells were divided into 100-µL volumes, which contained approximately 412 ± 15 cells.

CELLULAR CONFORMATION.
The cells were analyzed by phase-contrast microscopy using a Zeiss Axiophot epifluorescent microscope (see [3]). Human granulocytes or monocytes were evaluated for conformational changes indicative of either activation (ameboid and mobile) or inhibition (round and stationary) 30 minutes after dye treatment as described elsewhere in detail [3]. The lower the number, the higher the perimeter and the more amoeboid the cellular shape. The proportion of activated cells was determined as described elsewhere [3].

IN VITRO EVALUATION OF INTERNAL THORACIC ARTERY AND SAPHENOUS VEIN FUNCTION.
The blood vessels were washed extensively with phosphate-buffered saline solution and cut into 2-mm rings and prepared as described elsewhere [1]. Additional experiments were performed using cells exposed to leukotriene B₄ (LTB₄; 100 nmol/L; 5 minutes) as an endothelial activating stimulus before their addition to untreated or LTB₄-stimulated vascular preparations.

To evaluate the effect of morphine on cellular adhesion, we added fluorescently labeled cells to endothelial rings pretreated with morphine, 10^-6 mol/L, in the absence or presence of 10^-6 mol/L naloxone, an opiate/opioid receptor antagonist. Cells were allowed to interact for 30 minutes, whereupon the numbers of cells adherent to the vascular preparation or remaining in the medium were determined. Nonadherent cells were removed by tilting and gentle washing of the vascular preparation with three drops of phosphate-buffered saline solution. The endothelium was examined for adherent cells by placing a glass slide over the vascular preparation followed by rapid counting using color detection software from American Innovision (San Diego, CA).

Cryopreserved saphenous veins (obtained from Cryolife) after thawing were mounted onto metal supports for measurement of developed isometric tension exactly as described [4]. For evaluation of the viability of the cryopreserved saphenous veins, the preparations were digested with a tissue dissociation cocktail containing collagenase (169 units/mL), elastase (1.5 units/mL), soybean trypsin inhibitor (0.5 mg/mL), and deoxyribonuclease I (459 units/mL) exactly in accordance with described methods [5], and cell viability was determined by the ability of the cell to exclude trypan blue dye. No attempt was made to identify individual cell types (eg, smooth muscle, endothelial cells) within the preparations.

DIRECT MEASUREMENT OF NITRIC OXIDE RELEASE.
In addition to measuring the numbers of cells sticking to the endothelium of the saphenous vein, we measured constitutive and morphine-induced nitric oxide (NO) production as noted in detail elsewhere [1]. The system was calibrated daily using different concentrations of a nitrosothiol donor S-nitroso-N-acetyl-DL-penicillamine (Sigma, St. Louis, MO) to generate a standard curve. Nitric oxide gas in solution was measured in real-time with the DUO 18 computer data acquisition system (World Precision Instruments, Inc, Sarasota, FL). Each experiment was repeated five times, and the mean NO values obtained were graphed. Each experiment was simultaneously performed with a control (vehicle minus drug) from the same tissue to avoid an interpretation that could be viewed as "drift."

	Statistics

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
One-tailed and two-tailed Student's t tests were used because each experiment and data point had its own control value. A p value of less than 0.05 was considered significant. For descriptive statistics, the standard error of the mean was used. The event-free survival was determined by the Kaplan-Meier method. The experimental values were then transferred to Sigma-Plot and Sigma-Stat (Jandel, San Rafael, CA) for graphic representation and evaluation. All experimental data were collected with the investigators unaware of the experimental treatments.

	Results

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
Patients
Between January 1, 1991, and December 31, 1995, 2,415 adult patients underwent open heart operations. Of these, 41 patients were identified in whom homograft veins were used. The mean age was 68.5 ± 1.34 years, and the number of grafts implanted was 3.66 ± 0.19. Of these grafts, 1.60 ± 0.93 were homografts and 1.92 ± 0.12 autologous conduits. The mean ejection fraction was 0.38 ± 0.02, with a median of 0.35. Nineteen of these patients were male and 22 were female. In 19 of these patients one internal thoracic artery, and in another 7 patients bilateral internal thoracic arteries were used. Eleven patients underwent redo operations and 13 patients underwent, in addition to coronary artery revascularization, other procedures such as valve replacements or aortic root replacements. Five patients underwent a concomitant carotid endarterectomy. Mean cross-clamp time was 90.4 ± 4.5 minutes. Mean length of stay in the hospital was 25 ± 4.8 days (median, 17 days). Mean postoperative stay was 20 ± 4.35 days (median, 13 days).

Follow-up was complete. Mean follow-up was 21.5 ± 2.87 months with a median follow-up of 16.0 months. Sixteen patients during this time period had events defined either as death (n = 7) or recatheterization (n = 9). In every patient in whom coronary angiography was performed, the homograft veins were completely occluded. In 2 of the 7 deaths at autopsy, the homograft veins were harvested for histologic examination and showed partially denuded epithelium. Based on the data, a Kaplan-Meier curve for event-free survival was constructed, which showed a 50% event-free survival at 12 months (Fig 1).

View larger version (13K): [in this window] [in a new window]   Fig 1. . Kaplan-Meier curve of event free survival with 95% confidence limits. Events are defined as death or recatheterization.

	Experimental Results

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
Figure 2A shows that monocytes adhere in sufficient numbers to the endothelial surface of the saphenous vein. Preincubation of the vein with morphine (10^-6 mol/L) reduced the number of adhering cells (Fig 2B). Coincubation of the vein with morphine (10^-6 mol/L) and the opiate antagonist naloxone (10^-6 mol/L) increased the number of adhering cells to control values, strongly demonstrating that this opiate action is mediated by way of a peripherally located opiate receptor [1] (Fig 2C). The NO synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME; 10^-4 mol/L) diminished the action of morphine, again returning the number of adhering cells to that of controls (Fig 2D).

View larger version (109K): [in this window] [in a new window]   Fig 2. . Digital images of the saphenous vein coincubated with monocytes. (A) A control incubation with the monocytes adhering to the endothelial surface. The cells were stained with PKH26-GL. Bar = 50 µm for all images. (B) The endothelium exposed to 10-6 mol/L morphine is found to have fewer monocytes attached. (C) This preparation was coincubated with 10-6 mol/L morphine and 10-6 mol/L naloxone, resulting in greater adherence. (D) Coincubation with 10-6 mol/L morphine and 10-4 mol/L NG-nitro-L-arginine methyl ester, the nitric oxide synthase inhibitor resulted in greater adherence. The images were obtained by the Compix Image Analysis system (Mars, PA) and brought into Photostyler for positioning and final printing on a Tektronix Phaser 440 color printer.

Furthermore, the immunocytes that adhered exhibited ameboid conformations (form factor = 0.47 ± 0.6) indicative of activation [3]. The addition of morphine to the in vitro bioassay significantly reduced cell adherence to 67 ± 25 (standard error of the mean) for both cell types and vessels. The few granulocytes and monocytes found on the endothelial surface exhibited form factors of 0.71 ± 1.1 and 0.82 ± 0.9, respectively, indicative of rounding and inactivation. The opiate alkaloid exposure also significantly reduced the enhancement of cell adherence in the presence of LTB₄ (77 ± 32 [standard error of the mean]) toward values obtained in tissue exposed to morphine but not LTB₄. Concomitant exposure of the morphine-exposed vessels to naloxone blocked the opiate-induced loss of cells from the endothelial surface (form factor = 0.51 ± 0.3 for granulocytes and 0.47 ± 0.7 for monocytes). A similar result was obtained when morphine was administered 5 minutes after the NO synthase inhibitor L-NAME (combined value for both vessels and cells, 208 ± 21 [standard error of the mean]). The number of cells adhering was similar to control values, and the cells exhibited more ameboid conformations (granulocytes, 0.49 ± 0.6; monocytes, 0.49 ± 0.5).

Because of the observed damage to endothelial cells during harvesting seen in autologous and cryopreserved conduits, we also assumed that superoxide may be produced, which in turn would react rapidly with NO [6], thus reducing the levels of NO. To test this hypothesis, we added a superoxide scavenger, superoxide dismutase, to determine if we would get an enhanced effect of morphine on cell adherence. In the presence of superoxide dismutase (10^-4 mol/L) and morphine 10^-6 mol/L) there was a further significant drop in the cells adhering to the vessels (granulocytes = 14 ± 10.2; monocytes = 12.3 ± 5.7 for both vessels; p < 0.01).

Given the recent demonstration that human and rat endothelial cells produce NO in a naloxone- and L-NAME-sensitive manner when exposed to morphine [1], it was of interest to examine further this phenomenon. Both noncryopreserved vessels exhibited an enhanced release of NO upon exposure to morphine (10^-6 mol/L) (Fig 3). In this context, cryopreserved veins were examined for their ability to inhibit immunocyte adherence after their exposure to morphine as well as their ability to release NO upon opiate alkaloid exposure. In cryopreserved saphenous vein, constitutive NO (speed of release), as well as that stimulated by morphine, could not be detected (Fig 3, inset). This result was supported by hematoxylin and eosin histologic examination of the vessels taken at autopsy, indicating a "patchy" and severely depleted endothelium (data not shown). Examination of cell adhesion (Fig 4) showed large clumping on "patches" of the vessel.

View larger version (31K): [in this window] [in a new window]   Fig 3. . Morphine (Mor.) stimulation of nitric oxide (NO) release from human internal thoracic artery (Thor.) and saphenous vein (Saph.). After the addition of morphine (10-6 mol/L), nitric oxide is released from the saphenous vein and internal thoracic artery. (Inset) In cryopreserved vessels there is a lack of constitutive nitric oxide release upon morphine exposure. The 10-, 15-, and 20-minute values were compared with control levels: p < 0.001, p < 0.004, and p < 0.05, respectively.

View larger version (60K): [in this window] [in a new window]   Fig 4. . Digital images of the saphenous vein coincubated with monocytes. (A) A control vein not frozen or thawed. (B) A cryopreserved saphenous vein. In B we find large cellular clumping and areas completely devoid of cell adhering after morphine (10-6 mol/L) exposure.

View larger version (21K): [in this window] [in a new window]   Fig 5. . Representative contractile capacity of fresh and Cryolife-preserved saphenous veins: Human saphenous veins, fresh explants (solid line) or Cryolife-preserved veins (dashed line), were exposed to 100 mmol/L KCl and developed isometric tension was evaluated for approximately 10 minutes. Marked increases in contractile force were observed in fresh but not Cryolife-preserved veins, suggesting that the contractile capacity of Cryolife-preserved veins is markedly impaired.

	Comment

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

The clinical data should be interpreted with caution. The events (death, recatheterization) may severely underestimate patency because it is not known how many patients were treated medically for recurrent angina or were pain free with occluded grafts. The events described may be due to the severity of the underlying disease rather than to the choice of grafts. Because cryopreserved veins were used as a last resort, this group of patients is not comparable with an age- and ejection fraction-matched population.

In regard to the role of NO in cellular adherence, a recent report further substantiates the observations in the present study. DeCaterina and colleagues [7] demonstrated that NO, in a cytokine-stimulated process, inhibits VCAM-1 expression, which results in diminished monocyte adherence to human saphenous vein endothelium. Nitric oxide also decreased endothelial expression of E-selectin as well as secretable cytokines. DeCaterina and colleagues concluded that NO does limit endothelial activation including immunocyte adherence. Thus, the observations of the present study are directly in line with their observations.

In other studies concerned with the influence of morphine's action as an immunocyte downregulatory substance, the same logic has been applied. Morphine downregulates many types of immunocytes, especially monocytes and granulocytes, as well as the actions of many excitatory signal molecules, eg, interleukin-8 [8]. It also inhibits the secretion of various cytokines that have the potential for tissue damage [8]. Furthermore, human granulocytes, monocytes, and endothelial cells have the unique µ₃ opiate receptor, which is opiate alkaloid selective and opioid peptide insensitive [8]. In regard to endothelium, this receptor mediates the morphine-stimulated production of NO [1]. Thus, the results of the present study support the previous experimental data in that L-NAME can diminish morphine's ability to produce NO.

Thus, although leukocyte adherence and transport across the endothelium to extravascular tissue is essential for defense against foreign bodies, there may be occasions when this activity is not beneficial [10]. In this regard, the adhesion by activated immunocytes [10] may cause detrimental effects on the host tissues, eg, during reperfusion. Thus, under proinflammatory conditions, the inhibition of immunocyte adherence may allow for less tissue injury and most likely faster recovery.

In regard to the use of cryopreserved material, valve conduits have provided excellent long-term results [11]. However, following initial favorable patency rates, clinical failures in regard to cryopreserved veins were reported anecdotally [12]. The clinical failures of these homografts were associated with the decreased function of endothelial cells [13–15] as also suggested in this study. Other data suggest a patency rate at 12 months of 76% for a group of 16 patients who received homograft veins only (Cryolife data). In a mixed group of patients in whom a mixture of autologous and cryopreserved conduits were used, a 4-year survival of 85% in 290 patients was reported [16]. If and to what degree the often-cited slow rejection reaction plays a role remains unclear.

Conflicting results have been reported for the preservation of endothelial cells in this cryopreserved tissue, which ranges from 50% to 80% [16]. A decreased thrombomodulin activity with resultant impaired anticoagulant function of the remaining cells also has been described [16]. The remaining endothelial cells showed poor adherence and retarded proliferation in primary cultures [16]. The results of our functional analysis place the cryopreserved vein at the opposite end of the spectrum of an autologous arterial conduit, with an autologous venous conduit being in an intermediate position. Our clinical results are in agreement with results for arterial revascularization of lower limbs using cryopreserved veins in showing a poor patency [17].

The relatively poor long-term performance of autologous saphenous veins and increasing plaque formation over time suggest a functional incompetence of these veins [18–22]. The question if this functional disability is due to a constant local proinflammatory state remains unclear. There is increasing evidence, including the present data, that the initial graft failures are in part due to the local proinflammatory environment created by the endothelial cell and activated leukocytes [23]. In this regard, a role for NO is emerging [8, 24, 25].

In summary, endothelial NO production appears to be quite important in maintaining a healthy patent conduit. It also may provide an important index of tissue viability. Furthermore, a reevaluation of morphine's action in regard to its role in surgery is warranted based on the newly discovered µ₃ opiate receptor and its role in immunoregulation and vascular regulation [8].

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
These studies were supported in part by National Institutes of Health grants MH/DA 17138 and DA 09010, the State University of New York Central Administration and Research Foundation, and the Cardiac Research Program of the University Hospital and Medical Center, State University of New York at Stony Brook (G.B.S., T.V.B.). We are indebted to Mr Frederico Casares (National Institute of Mental Health/National Institute on Drug Abuse Career Opportunity Research Program Fellow) for excellent technical assistance.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 
Address reprint requests to Dr Bilfinger, Cardiac Research Program, Health Sciences Center T-19, State University of New York at Stony Brook, Stony Brook, NY 11794-8191.

* Detailed instructions are available from Cryolife, Inc, Marietta, GA, or the authors.

	References

Top Footnotes Abstract Introduction Material and Methods Operative Technique Venous and Arterial Measurements Experimental Study Analysis of Cellular Activity Statistics Results Experimental Results Comment Acknowledgments References

 

1. Stefano GB, Hartman A, Bilfinger TV, et al. Presence of the m3 opiate receptor in endothelial cells: coupling to nitric oxide production and vasodilation. J Biol Chem 1995;270:30290–3.[Abstract/Free Full Text]
2. Stefano GB, Digenis A, Spector S, et al. Opiatelike substances in an invertebrate, a novel opiate receptor on invertebrate and human immunocytes, and a role in immunosuppression. Proc Natl Acad Sci USA 1993;90:11099–103.[Abstract/Free Full Text]
3. Stefano GB, Melchiorri P, Negri L, Hughes TKJ, Scharrer B. (D-Ala2)-Deltorphin I binding and pharmacological evidence for a special subtype of delta opioid receptor on human and invertebrate immune cells. Proc Natl Acad Sci USA 1992;89:9316–20.[Abstract/Free Full Text]
4. Magazine HI, Bruner CA, Andersen TT, Malik AB. Vascular contractile potency of endothelin-1 is increased in the presence of macrophages or monocytes. Am J Physiol 1994;266:H1620–5.[Abstract/Free Full Text]
5. Wagner-Mann C, Hu Q, Sturek M. Multiple effects of ryanodine on intracellular free Ca²⁺ in smooth muscle cells from bovine and porcine coronary artery: modulation of sarcoplasmic reticulum function. Br J Pharmacol 1992;105:903–11.[Medline]
6. Colton CA, Snell J, Chernyshev O, Gilbert DL. Induction of superoxide anion and nitric oxide production in cultured microglia. Ann N Y Acad Sci 1994;738:54–63.[Medline]
7. DeCaterina R, Libby P, Peng HB, et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 1995;96:60–81.
8. Stefano GB, Scharrer B, Smith EM, et al. Opioid and opiate immunoregulatory processes. Crit Rev Immunol (in press).
9. Cardinale GJ, Donnerer J, Finck AD, Kantrowitz JD, Oka K, Spector S. Morphine and codeine are endogenous components of human cerebrospinal fluid. Life Sci 1987;40:301–6.[Medline]
10. Stefano GB, Bilfinger TV, Fricchione GL. The immune-neuro link and the macrophage: postcardiotomy delirium, HIV-associated dementia and psychiatry. Prog Neurobiol 1994;42:475–88.[Medline]
11. Matsuki O, Robles A, Gibbs S, Bodnar E, Ross DN. Long term performance of 555 aortic homografts in the aortic position. Ann Thorac Surg 1988;46:187–91.[Abstract]
12. Brockbank KGH, McNally RT, Walsh KT. Cryopreserved vein transplantation. J Cardiovasc Surg 1992;7:170–6.
13. Laub GW, Muralidharan S, Clancy R. Cryopreserved allograft veins as alternative coronary artery bypass conduits: early phase results. Ann Thorac Surg 1992;54:826–31.[Abstract]
14. Louagie YA, Legrand-Monsieur A, Lavenne-Pardonge E. Viability of long term cyropreserved human saphenous veins. J Cardiovasc Surg 1990;31:92–100.[Medline]
15. Ku D, Winn MJ, Grigsby T, Caulied JB. Human coronary vascular smooth muscle and endothelium-dependent responses after storage at -75°C. Cryobiology 1992;29:199–209.[Medline]
16. Bambang LS, Mazzucotelli JP, Maczar M, Baeujean F, Loisance D. Effects of cryopreservation on the proliferation and anticoagulant activity of human saphenous vein endothelial cells. J Thorac Cardiovasc Surg 1995;110:998–1004.[Abstract/Free Full Text]
17. Marshin RS, Edwards WH, Mulherin JL, Edwards WH Jr, Jenkins JM, Hoff SJ. Cryopreserved saphenous vein allografts for below knee lower extremity revascularization. Ann Surg 1994;219:664–72.[Medline]
18. Campeau L, Enjalbert M, Lesperance J, Vaislic C, Grondin CM, Bourassa MG. Artherosclerosis and late closure of aortocoronary saphenous vein grafts: sequential angiographic studies at 2 weeks, 1 year, 5 to 7 years, and 10 to 12 years after surgery. Circulation 1983;68(Suppl 2):1–7.
19. Angelini GD, Passani SE, Breckenridge IM, Newly AC. Native and pressure dependence of damage induced by distention of human saphenous vein coronary artery bypass grafts. Cardiovasc Res 1987;21:902–7.[Medline]
20. Ramos JR, Berger K, Mansfield PB, Sauvage LR. Histology and endothelial changes of distended and nondistended veins. Ann Surg 1976;183:205–8.[Medline]
21. Spray TL, Roberts WC. Changes in saphenous veins used for coronary artery bypass grafts. Am Heart J 1977;94:500–16.[Medline]
22. Rusch NJ, Woodridge TA, Kulig CC. Reactivity of human saphenous veins at atrial perfusion pressures. J Thorac Cardiovasc Surg 1995;110:1005–12.[Abstract/Free Full Text]
23. Rinder C, Titch J. Amplification of the inflammatory response: adhesion molecules associated with platelet/white cell response. J Cardiovasc Pharmacol 1996;27:506–12.
24. Engelman DT, Wakanabe M, Engelman RM. Constitutive nitric oxide release is impaired after ischemia and reperfusion. J Thorac Cardiovasc Surg 1995;110:1047–53.[Abstract/Free Full Text]
25. Wanna FS, Obayashi DY, Young JN, DeCampty WM. Simultaneous manipulation of the nitric oxide and prostanoid pathways reduces myocardial reperfusion injury. J Thorac Cardiovasc Surg 1995;110:1054–62.[Abstract/Free Full Text]

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				J. Chanda, R. Kuribayashi, T. Abe, T. V. Bilfinger, A. R. Hartman, Y. Liu, H. I. Magazine, and G. B. Stefano Nitric Oxide in Homograft Vein Function Ann. Thorac. Surg., November 1, 1997; 64(5): 1524 - 1525. [Full Text]

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