Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1121 Harvesting of Saphenous Vein for Coronary Artery Bypass Grafting An Improved Technique that Maintains Vein Wall Integrity and Provides a High Early Patency Rate Domingos Sávio Ramos de Souza ACTA UNIVERSITATIS UPSALIENSIS UPPSALA 2002
55
Embed
Harvesting of Saphenous Vein for Coronary Artery …161270/FULLTEXT01.pdf · Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1121 Harvesting of Saphenous
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Medicine 1121
Harvesting of Saphenous Vein forCoronary Artery Bypass Grafting
An Improved Technique that Maintains Vein WallIntegrity and Provides a High Early Patency Rate
Domingos Sávio Ramos de Souza
ACTA UNIVERSITATIS UPSALIENSISUPPSALA 2002
Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Medicine 1121
Harvesting of Saphenous Vein forCoronary Artery Bypass Grafting
An Improved Technique that Maintains Vein WallIntegrity and Provides a High Early Patency Rate
BY
DOMINGOS SÁVIO RAMOS DE SOUZA
ACTA UNIVERSITATIS UPSALIENSISUPPSALA 2002
Dissertation for the Degree of Doctor of Philosophy (Faculty of Medicine) in Thoracic Surgerypresented at Uppsala University in 2002
AbstractSouza, DR. 2002. Harvesting of Saphenous Vein for Coronary Artery Bypass Grafting. AnImproved Technique that Maintains Vein Wall Integrity and Provides a High Early PatencyRate. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations fromthe Faculty of Medicine 1121. 49pp. Uppsala. ISBN 91-554-5232-9.
The primary aim of this thesis was to modify saphenous vein (SV) harvesting technique andevaluate its clinical importance. A new “no touch” (NT) technique of SV preparation wasdeveloped where the vein is harvested with a pedicle of surrounding tissue, which protects thevein from spasm therefore obviating the need for distension.
Firstly, a prospective randomised study in 156 patients who underwent coronaryartery bypass grafting was done to compare this new “no touch” technique to two others, theconventional (C) and the intermediate (I) techniques. A morphological study of the endotheliumshowed an endothelial integrity of 97% in NT vessels while about half of endothelial surface ofveins harvested by the other two techniques was devoid of endothelium. At angiographic followup, the patency for NT was 95.4%, 88.9% for grafts in group C and 86.2% for grafts in group I.A statistically significant difference in patency rate was found between the NT group and groupC (p=0.025) and the poorest result was observed in group I.
Secondly, the immunohistochemistry assessment using CD31-antibody confirmed a better-preserved endothelium for NT vessels. Putative NOS was identified by NADPH-diaphorasehistochemistry and autoradiographic localization of [3H] L-nitroarginine (NOARG) binding.NADPH staining was almost continuous on the luminal aspect and was also present in the intactadventitia of NT vessels, which was markedly reduced in conventionally harvested veins.Autoradiographic analysis of specific NOARG binding showed greater binding in the no-touchvessels, confirming the histochemistry results. All three NOS isoforms were identified in themedia of SV grafts. In NT, NOS I was abundant in adventitial nerves; NOS II was found inadventitial vasa vasorum and NOS III was associated with endothelial cells lining both the vessellumen and microvessels within the adventitia.
In conclusion, this study demonstrated that the endothelial integrity and NOS activity arebetter maintained when using the no-touch technique for vein graft harvesting. The vasorelaxantand thromboresistent activities of NO may be responsible for the reduced venospasm andimproved early patency rates observed. Furthermore, the mechanical properties provided by thecushion of surrounding tissue in grafts harvested by NT technique may contribute to theobserved high patency rate.
Hyperlipidemia, n (%) Preoperative 18 months after surgery
29 (63%)22 (48%)
19 (46%)20 (49%)
29 (64%)27 (60%)
Smoker, n (%) Preoperative 18 months after surgery
9 (20%)9 (20%)
4 (10%)1 (2%)
9 (20%)6 (13%)
The anti-platelet drug, Aspirin, was started on the day after the operation with a dose of 160
mg/day. At the time of the angiographic examination, 42 patients in group C were receiving 160
mg/day, three had 75 mg/day and one was not on antiplatelet drug therapy. In group I, 35
patients were taking 160 mg/day, four had 75 mg/day and two were not on drug therapy. In
group NT, 35 patients were receiving 160 mg/day; seven patients 75 mg/day and three were not
taking any anti-platelet drug.
21
In papers IV and V the mean age of the ten patients was 66 (range 57-81) years. Two were
females. Three were smokers. There was one insulin-dependent diabetic and one non-insulin
dependent diabetic. All ten patients were on Aspirin, nine were on β-blockers and anti-
hypertensives and eight were on lipid-lowering medication.
Morphological findings
Paper I was designed to describe in detail the new ”no-touch” SV harvesting technique. It also
gave the preliminary results of the morphologic investigation of the endothelial integrity by
using SEM, which indicated that preservation of endothelial integrity was better with the new
”no-touch” technique, fig 2 and 3.
Fig. 2. SEM from “no-touch” graft. Theendothelium is intact, and the endothelial cells(E) exhibit prominent cell borders (arrows)and microvilli, indicating a preservedmetabolic activity at the moment of fixation.
Fig. 3. SEM from conventional harvestingtechnique. The summoned effect of mechanical,chemical and thermal trauma duringpreparation is observed as the loss ofendothelial cell (E) integrity.
Endothelial cell integrity
The morphological data of quantitative SEM are shown in paper II, fig 2. Secondary specimens
in group NT had an endothelial cell integrity similar to that of their primary specimens. In
contrast, roughly half of the luminal surface of secondary specimens from group C was devoid of
endothelium. The secondary specimens in group I exhibited endothelial cell integrity between
the secondary specimens of group C and NT. A significant difference between groups was
found. The posterior tests between the control specimens and each of the three treatment groups
resulted in the following p-values, control versus conventional p<0.01, control versus
intermediate p<0.05 and control versus “no-touch“ p>0.50.
22
Qualitative SEM
In primary specimens from all three groups, the endothelium was essentially intact with
prominent nuclear bulges and microvilli. The picture was similar in secondary specimens from
group NT. In preparations from the conventional procedure, patchy areas of endothelial
denudation were frequently found, usually with adherent and activated platelets, which
confirmed the preliminary findings of paper I. The secondary specimens from group I, exhibited
less extensive endothelial cell damage than the secondary specimens from group C. In five
specimens, the section surface had hit venous vasa vasorum in the graft wall that was continuous
with the graft lumen (paper II, fig 4).
Qualitative TEM
In all three procedures, areas in which the endothelium was well fixed could be found, with
intact mitochondria and parallel membranes in the granular endoplasmic reticulum (paper II, fig
6a). In the primary specimens from all three groups and the secondary specimen from group NT,
the endothelium was continuous and attached to the basal membrane. In the secondary specimen
from group C, discontinuous endothelium was frequently observed with detached endothelial
cells separated from the basal membrane (paper II, fig 6b). Again, secondary specimens from
group I represented a morphological intermediate between the other two groups.
Immunohistochemical findings
Endothelium
The CD31 immunostaining, identifying endothelial cells, shown in paper IV and V, confirmed
that the endothelial cell integrity of “no-touch” grafts was well preserved, whereas in
conventionally harvested veins it was reduced. Apart from a reduction in the luminal
endothelium of veins prepared using the conventional technique, immunostaining of the
endothelial cells of the vasa vasorum within the adventitia was also decreased compared to
abundant staining in segments of ”no-touch” saphenous vein (paper IV, fig 3).
Collagen
Collagen immunostaining showed the intact adventitia surrounding vessels harvested using the
”no-touch” technique and revealed microvessels within this area. This was absent in segments of
SV prepared with the conventional technique (paper IV, fig. 2).
23
Autoradiographic localisation of NOS
NOS was identified on sections by incubating tissue in buffer containing NOARG. There was
endothelium-dependent radioligand binding on the luminal aspect of vessels, which was almost
continuous on the ”no-touch” segments, but reduced on the conventionally prepared segments
(fig. 4).
Fig. 4. [3H]-L-NG nitroarginine binding to a conventionally harvested and b no-touch vein grafts. NOSwas identified by in vitro autoradiography. Binding is shown on the left-hand panels under dark-fieldillumination, as white grains on a black background. The panels on the right are haematoxylin and eosin-stained tissue underlying the autoradiographs. The endothelium is continuous on “no-touch” sections (b),whereas only a few endothelial cells remain in the conventional segment.
NADPH-diaphorase histochemistry
NADPH-diaphorase staining of ”no-touch” samples was almost continuous and folded on the
luminal aspect of the veins, as compared to poor staining of conventionally harvested veins. The
pattern of NADPH-diaphorase staining revealed in this study corresponded to endothelial cells
lining the vessel lumen and vasa vasorum in the adventitia. In the media, NADPH-diaphorase
staining was also greatest in sections of ”no-touch” samples. This was reduced to some degree in
control (non-distended) sections with a further reduction seen in conventionally harvested
(distended) sections.
Image analysis showed that tissue NADPH-diaphorase staining was reduced by 19.5% in control
(non-distended) sections compared to ”no-touch” sections with the reduction in conventionally
harvested (distended) sections being even greater, up to 35.5% compared to “no-touch” sections,
p<0.05 (paper V, fig 5).
24
NOS immunohistochemistry
Positive NOS III immunostaining was identified on the luminal aspect of vessels, that was
almost continuous on ”no-touch” and control sections, but reduced and patchy on conventional
sections (paper V). All three isoforms were identified in the media, contributing to the positive
NADPH-diaphorase staining. In the intact adventitia of ”no-touch” vessels, abundant NOS III
positive staining was associated with microvessels, and this coincided with positive CD31
staining. These microvessels also stained positive for NOS II. NOS I immunostaining was
associated with adventitial perivascular nerves.
Surgical data
Paper III and VI. The mean duration of cardiopulmonary bypass and aortic cross clamp time was
121 minutes (range 59-187) and 64 (range 34-95) minutes respectively for group C; 126 (range
90-180) and 69 (range 41-117) respectively in group I; 139 (range 88-195) and 72 (range 41-
113) respectively in group NT. The majority of patients in all groups received three vein grafts
and a mammary artery. A total of 127 vein grafts and 41 LIMA grafts were inserted in group C.
In group I, a total of 116 vein grafts and 35 LIMA grafts were used and in group NT, a total of
124 vein grafts and 42 LIMA grafts were implanted. There were 107 single grafts, 16 double
sequential grafts and four triple sequential grafts in group C. In group I, 100 single grafts 14
double sequential grafts and two triple sequential grafts were used and in group NT we had 109
single grafts and 15 double sequential grafts. LIMA grafts were considered not suitable in five
patients in group C, five in group I and three in group NT. It was necessary to perform
thrombendarterectomy (TEA) in two posterior descending coronary artery (PDA) in group C,
one PDA in group I, but no TEA was necessary in any coronary artery in group NT.
No operative mortality occurred in the three groups. Peroperative myocardial infarction occurred
in two patients in group C. There was one reoperation to control postoperative bleeding
performed in one patient in group NT, where the source of the bleeding was from the LIMA bed.
Only minor wound complications were seen in a few cases in all the three groups. Two of 46
patients (4.3%) in group C, Three of 41 patients (7.3%) in group I and five of 45 (11.1%) in
group NT developed superficial infection or cellulitis. We had no major complication that
required subsequent surgical intervention
25
Graft patency
One hundred and thirty-two patients, 46 patients from group C, 41 from group I and 45 from
group NT underwent an angiographic follow-up. The time to angiography was 17.2 (SD ±4.4)
range 9-31 months for group C, 16.0 (SD ±2.6) range 11-25 months for group I and 16.3 (SD
±2.7) range 11 – 28 months for group NT. The remaining 24 patients declined further
angiographic assessment.
The results of the NT group were first reported in paper III. The patency rate was 118/124
(95.4%) for vein grafts and 39/42 (93.3%) for LIMA. In this study there were two surgical
factors that affected the outcome of the vein graft. The occlusion was statistically significant
when related to the size of the coronary artery (p=0.03) and to the quality of SV before
harvesting (p=0.02). However, other surgical factors such as the quality of the recipient target
arteries, the graft length and the graft flow rate did not play an important role in the graft
occlusion. When we compared the flow rate to the size of the coronary arteries we found a trend
toward graft occlusion (24%) for those grafts anastomosed to small coronary arteries (1 mm)
with a flow rate of ≤20 mL/min. However, all grafts that were anastomosed to 1 mm arteries and
had a flow rate of more than 20 mL/min or those that had a flow rate of ≤20 mL/min but were
anastomosed to arteries of ≥1.5 mm were patent (paper III, table 1). No association between vein
occlusion and the use of antiplatelet therapy was observed. Fig. 5 illustrates a ”no-touch” graft
anastomosed to a 1 mm coronary artery. When the vein is supported by the surrounding tissue no
kinking will occur (fig 6).
Fig 5. A “no-touch graft anastomosed to a small size coronary artery.
Fig. 6. Excessively long “no-touch” graft withoutkinking.
26
Paper VI shows the final angiographic results performed in 132 patients from all three groups.
The patency for NT was 118/124 (95.4%), for grafts in group C was 113/127 (88.9%) and for
grafts in group I was 100/116 (86.2%). The patency for LIMA was 108/118 (91.5%).
Low flow associated with small size coronary artery increased the occlusion rate in all groups
and by itself had a greater effect on the occlusion rate for grafts in group I. The quality of target
coronary artery did not influence the patency in any group, and both grafts which were
anastomosed to PDA after TEA in group C were open but the graft in group I was not. The
occlusion rate for veins of poor quality prior to implantation was 4/10 (44.4%) in group C, 6/19
(31.6%) in group I and 3/29 (10.3%) in group NT.
All sequential grafts in the NT and I groups were open whilst in group C two sequential grafts
were totally occluded and two others were partially occluded. Thus, 47/51 (92.2%) of all
sequential grafts were completely open.
A logistic regression analysis of the most important factors that affected the graft outcome, i.e.
the patency rate are shown in paper VI, table 3. A statistically significant difference in patency
rate was found between the NT group and group C (p=0.025) and the poorest result was
observed in group I. The odds ratio (OR) for ”no-touch” in comparison with group C was 3.9
with a 95% confidence interval (CI) of 1.2 to 12.6. The analysis showed high OR for increasing
coronary artery diameter (OR 4.7 for diameter ≥2.0 mm compared with 1.0 mm) and increased
flow (OR 4.9 for flow ≥41 ml/min compared with ≤20 ml/min). Poor vein quality gave a low
odds ratio (OR 0.2). Odds ratios of 0.2 were observed for central and proximal parts compared
with distal parts of the vein. All these parameters were based on multivariate adjustment and
were statistically significant.
No association between vein occlusion and classical clinical factors which are reported to
influence the graft patency such as age, preoperative infarctions, cholesterol level, smoking
habits or hypertension was observed in any group.
27
Discussion
For many reasons both the SV and the LIMA will continue to be the most important conduits in
CABG. The high incidence of vein graft occlusion is a major and unsolved problem in
myocardial revascularization. Improvement of SV graft patency rate is therefore a big challenge
in the field of cardiovascular surgery. The widespread use of complete arterial grafting with
LIMA and other arterial conduits cannot yet be justified on scientific grounds, as there are few
late survival data and no controlled studies (122, 123).
This is the first study to show that the surrounding tissue of the SV contributes to a high early
patency rate of SV grafts compared to SV graft prepared with conventional technique.
Different structural and functional properties between arteries and veins are probably the
explaination for the better results of the arterial grafts (124). Nevertheless, the trauma to the SV
wall that occurs during its harvesting for CABG may also contribute to the poor results of
venous grafts. At the time of implantation, endothelial damage is almost absent in internal
mammary artery (IMA) grafts. In contrast, the endothelium of harvested human saphenous vein
shows greater thrombogenic defects with exposed collagenous fibrils (125). It was shown (126)
that although the smooth muscle proliferation was similar in undamaged saphenous vein and
IMA, muscle proliferation was significantly greater in damaged veins. This implies that the
greater intimal proliferation seen in saphenous vein grafts may arise not from intrinsic
differences in arterial and venous smooth muscle cells but from a greater susceptibility to injury.
In an animal model, free internal mammary artery that was stripped from its surrounding tissue,
showed a higher incidence of thrombosis, intimal thickening, and medial injury than the pedicled
grafts did (127).
Many strategies have been used both to prevent vein occlusion and to improve the short- and
long-term patency rate. Apart from established adjuvant medical therapy, new pharmacological
agents, gene therapy, and also mechanical devices are presently undergoing evaluation. Many of
these strategies have shown to be promising in experimental vein bypass models, but a few have
successfully been transferred into clinical practice. In addition, an important point is the
continuing improvement of surgical techniques to prevent vein wall damage during harvesting
and implantation.
28
Harvesting the saphenous vein together with a pedicle of surrounding tissue protects the vein
from spasm, thereby obviating the need for vein distension. The cushion of surrounding tissue
allows for careful handling of the vein, from harvesting to implantation. Our results suggest that
this technique could be an additional strategy to improve vein graft patency. Papers I and II show
that this new ”no-touch” technique results in excellent maintenance of endothelial cell integrity,
as measured by SEM. However, with the other two techniques there was extensive damage to the
endothelial layer. TEM permitted analysis of both endothelial integrity and the morphology at
the subcellular level. The ”no-touch” technique provided a more gentle approach to the handling
of SV, which was confirmed by a continuous layer of endothelial cells showing better attachment
to the basal membrane in comparison with the other two techniques.
We could demonstrate that the adventitia and the cushion of surrounding tissue, that remains
intact after harvesting by the ”no-touch” technique, has high collagen content. This may act as a
buffer against the pulsatile stress that the graft is exposed to, and it works in a similar manner as
an external stent (paper IV). There is evidence, that even in the absence of intraluminal blood
flow, the vasa vasorum maintained endothelial integrity, and that the endothelium is very
sensitive to the loss of the vasa vasorum (56). Thus, the endothelial surface of an arterialized
vein bypass is probably nourished by both the luminal blood and through the vasa vasorum blood
supply. In paper II, we found that the vasa vasorum drains into the lumen, so it is possible that
arterial blood from the lumen to some extent perfuses retrogradely through the vasa vasorum,
thereby decreasing ischemic damage.
NADPH-diaphorase staining and NOARG binding, as indicators of putative activity, suggest that
NOS availability is also preserved on the luminal endothelium of grafts harvested by the ”no-
touch” technique. Veins harvested by this technique may maintain their nitric oxide-producing
capacity in vivo, which could reduce the incidence of vein occlusion by promoting
vasodilatation, reducing platelet aggregation and preventing thrombus formation. Apart from
being located on the luminal endothelium, NOS was also found in microvascular endothelium
within the adventitia.
The alterations in NOS distribution of SV harvested by the ”no-touch” technique was
demonstrated and compared to that of veins harvested with the conventional technique. In
addition to the preservation of NOS associated with luminal endothelial cells, NOS in the media
and adventitia of ”no-touch” vessels was also preserved. In the adventitia, NOS sources were
29
identified, and they were associated with microvessels and perivascular nerves. NOS levels were
not only reduced by removal of the surrounding tissue from the SV but also by distension, which
suggests that both of these measures contribute to the reduction in NOS levels seen in
conventionally harvested vessels. Distension appears to have a greater effect on luminal
endothelial and medial NOS, whilst removal of perivascular tissue eliminates important
adventitial NOS sources. This preservation of NOS sources suggests that NO availability, which
is usually reduced by conventional surgical preparation (43), may be improved by using the ”no-
touch” technique, and that the NO pathway contributes to the improved results of SV harvested
by this new technique.
During surgery and in the immediate postoperative period, venospasm is often encountered and
NO donors have been shown to reduce venospasm via their vasodilator action (128).
Preservation of adequate endogenous NO may provide protection against venospasm; no
significant venospasm occurs intraoperatively when using the ”no-touch” technique. This
precludes the need for distension and resultant vascular damage. The protective mechanism
against venospasm may be maintained during the early postoperative period, and counteract any
effects of endogenous vasoconstrictors to which the vein graft is highly sensitive (129-131).
All three NOS isoforms were identified in the media of SV grafts, where NO production would
modulate vessel tone. NOS I, II and III expression in vascular smooth muscle has been
previously reported (132-135), and has been thought to be particularly important following
vascular injury where NOS III-derived NO may be reduced due to endothelial cell injury. In ”no-
touch” vessels, NOS I was abundant in adventitial nerves; NOS II was found in adventitial vasa
vasorum; NOS III was associated with endothelial cells lining both in the vessel lumen and in the
microvessels within the adventitia. The potentially beneficial involvement of all three isoforms
of NOS supports data from studies showing that all isoforms are vasculoprotective. NOS I,
produced by perivascular nerves has been shown to modulate vascular tone of cerebral arteries
(136), and may play a similar role in the saphenous vein, causing vasodilation. NOS III reduces
intimal hyperplasia in NOS III-knockout mice (137) and NOS III-transgenic mice studies (138).
Similar studies, using the carotid artery ligation model in NOS II-knockout mice, have described
suppressed constrictive remodelling by this isoform (137). The presence of these isoforms in
”no-touch” vessels may reduce both intermediate and late occlusions via attenuation of intimal
hyperplasia and constrictive vascular remodelling.
30
Patency rate
The early patency rate of saphenous veins harvested with its surrounding tissue is very high
(95.4%), even in saphenous vein grafts that demonstrated low blood flow. Such a high patency
rate has not been demonstrated when using other harvesting techniques. We investigated whether
a cushion of surrounding tissue might improve venous graft patency rate by comparing early
angiographic results between the ”no-touch” and two other techniques. There was a significant
improvement of vein graft patency using this new ”no-touch” technique over the other
techniques (p=0.02).
When the vein is stripped from its surrounding tissue, the accurate adjustment of the length of
the graft is an important technical aspect, as kinking will certainly occur if the graft is too long.
Many techniques have been applied for dealing with aortocoronary graft length to prevent kinks
and twists in the graft (139). The preservation of the surrounding tissue when using the NT
technique protects the vein graft, and prevents such complications to occur.
Because endothelial injury is inevitable when the SV is handled by the conventional harvesting
technique, the use of antithrombotic therapy should also be started preoperatively with a dose of
325 mg /day of Aspirin (140). In the present study we started to use Aspirin the day after the
operation at a low dose of 160 mg/day. At the time of the angiographic assessment, some
patients were on a dose of only 75 mg/day, and a few patients were not using Aspirin at all. On
the basis of our results, pharmacological inhibition of platelet function has not been found to be
of major importance in preventing vein graft occlusion, if the SV endothelium remains intact
during harvesting and implantation.
The intermediate group was devised to demonstrate the importance of the surrounding tissue to
vein grafts, since after dissection, the handling of the SV vein was identical to that of the ”no-
touch” group, except that the vein in the intermediate group was stripped. Removal of
surrounding tissue generally resulted in pronounced spasm, and mechanical distension was
required despite local application of papaverine. In contrast, grafts retaining a pedicle of
surrounding tissue required neither pharmacological relaxation nor mechanical distension.
The ”no-touch” group provides both the best endothelial protection and the highest patency rate.
However, an unexpected finding was that veins harvested conventionally showed a higher
patency rate than the intermediate technique, despite our previous observation that the
31
endothelial lining is better protected in the intermediate group than it is in the conventional group
(141). This suggests that it is not only the endothelial layer that plays an important role in
protecting the grafts from occlusion, but also that the adventitial layer makes a significant
contribution to improved graft patency.
In paper III, the quality of the vein before its harvesting was an important factor in determining
the fate of the graft (p<0.002). This is in agreement with another study (142), which shows that
many of the changes are present prior to grafting and may be important in graft failure. The
incidence of occlusion rate was also statistically significant (p<0.03) when taking into account
the size of the coronary artery. Other registered surgical and clinical factors did not contributed
to vessel occlusion.
In paper VI, in agreement with another study (143), the graft flow rate and diameter of the lumen
of the target coronary arteries are important factors in predicting the outcome of the grafts,
irrespective of the method of vein harvesting used. We corroborate a previous study, which
reported an improved patency rate for sequential grafts (144). Poor vein quality had an important
effect on the occlusion rate for all groups. Thus, when analysing all groups together, not only the
size of coronary arteries and the quality of the vein before implantation, but also the graft flow
rate, the segment of the vein and the technique of harvesting the SV were important factors in
determining the outcome of the grafts. In agreement with a recently published article (145),
traditional cardiovascular risk factors for arteriosclerosis did not seem to predict the early fate of
SV grafts. However, it is likely that atherosclerotic changes will become more evident at long-
term follow-up.
Surgical comments
The “no-touch” technique can be used in most patients, but in our experience it is more difficult
to accomplish in obese patients, or if the vein is situated superficially. So far, we have not
experienced problems regarding reoperation for bleeding from unligated side branches. The
likelihood to miss an unligated side branch is greater in the vein segment from the thigh than
from the calf region. Therefore we use, in most cases, the proximal vein to the right coronary
artery branches, as it is easier to deal with bleeding side branches if the graft is placed in front of,
or on the right side of the heart. With regards to damage to the saphenous nerve a double blind
study was performed in 22 patients of which 8 had veins harvested by the conventional
32
technique. The sensory impairment around the wound was found in both groups but it was more
pronounced in patients from the ”no-touch” harvesting technique. However, none of the patients
complained about neurological disturbances that affected their quality of life.
No major wound complication occurred and we attribute this to our exclusion criteria and the
meticulous surgical technique used. However, it is expected that wound complications are more
likely to occur in patients who have their veins harvested by the ”no-touch” technique; therefore
we recommend some approaches to avoid serious complications. Firstly, it is imperative to apply
a surgical technique as presented in paper I, and not perform it on patients at risk, in particular
those with peripheral vascular disease. Secondly, we suggest whenever possible, to perform a
preoperative SV mapping using ultrasonographic imaging the day before surgery, whereby the
course of the vein in the leg can be marked on the overlying skin. This will allow us to make the
incision exactly above the vein, avoiding a long flap of subcutaneous tissue, which might be a
major cause of wound complication. Also excessive use of electrocautery is an important cause
of postoperative complications. The operation time is somewhat longer using the ”no-touch”
technique than the other two techniques. Inasmuch as the success of bypass grafting procedures
is critically related to the quality of the conduit, the extra time and effort required are warranted.
In conclusion, the technique of harvesting the SV has a great influence on the fate of the venous
graft. This thesis is based on a novel harvesting technique of SV preparation for CABG, whereby
the vein is protected by its cushion of surrounding tissue. The adventitial layer and the structures
contained within the cushion of surrounding tissue possess both mechanical and functional
properties that protect the vein from spasm and ischemia. The endothelial integrity was better
maintained using the ”no-touch” technique. NOS activity was preserved on the endothelium, and
from both neuronal and adventitial microvessel sources, suggesting that NO availability is
retained by these grafts. The vasorelaxant and thromboresistent activities of NO may be
responsible for the reduced venospasm, and the observed improved early patency rates. In
contrast, removal of surrounding tissue results in spasm and mechanical distension is often
required, even when vasodilators are used during harvesting. This compromises endothelial,
medial and adventitial integrity, and influences the short-term and also probably the long-term
success of venous graft in CABG. In addition, the surrounding tissue supports excessively long
vein grafts and prevents kinking. Whilst short-term results are encouraging when using the ”no-
touch” technique, long-term results remain to be established.
33
General summary
The findings in the present series of studies can be summarized as follows:
– Retaining a cushion of surrounding tissue has provided a better conduit for SV graft by
protecting the vein from spasm and obviating the need for distension.
– The endothelial integrity was much better preserved in veins harvested by the ”no-touch”
technique than in veins harvested by the other two techniques.
– Both the endothelial integrity and the availability of NOS in SV graft were higher in
veins harvested by the ”no-touch” technique than in veins harvested by the conventional
technique.
– All NOS isoforms, as well as their distribution throughout the vein wall, were present and
better preserved in SV graft harvested by the ”no-touch” technique.
– The early patency rate assessed by angiography was found to be higher in veins harvested
by the "no-touch" technique than the other two techniques, and the difference was
statistically significant.
34
Acknowledgements
I wish to express my sincere gratitude to a large number of people, who with their help, support
and encouragement during my introduction into the field of research, have made this thesis
possible. I would particularly like to thank:
Derek Filbey, co-supervisor, and incredible friend. For the privilege and the pleasure of working
with you during my research experience. You were in the front position, you were always
available, you let me share your great experience in research, and you gave me strong support.
Your generosity is larger than yourself, and I cannot be grateful enough. I am also grateful to
your wife, who let me spend so much time with you, working with my thesis. Gun-Britt, thank
you, and thank you for your delicious cakes!
Vollmer Bomfim, co-supervisor, co-author and friend. For introducing me into the field of
cardiothoracic surgery, and for inviting me to work with you in Sweden. You gave me
inspiration and excellent conditions to perform my research. You also provided me your great
experience as a surgeon and researcher.
Jan Borowiec, head-supervisor from Uppsala University. Ever since you became involved with
my thesis, you have been a great support. Your help, experience in research and your knowledge
in this field of work made it possible for me to continue and finish what I had started.
Michael Dashwood, co-author, and “amigo”. Luckily I met you at a scientific meeting just at the
right time. Your scientific contributions to my work gave substance and depth and have been of
crucial importance. You introduced me into the field of nitric oxide and intoxicated me with your
knowledge. Janice Tsui, co-author and friend. You inspired me in my work and without your
expertise the results would be far poorer.
My co-authors, Rolf Christofferson, Lennart Bodin, Helge Skoglund, Mats G. Karlsson and
Benny Johansson for all the fruitful discussions and practical help.
Asgrimur Ragnarsson for the angiographic analyses and the nurses at the Radiology Department,
who spent hours with my patients during the angiographies.
35
Birger Wandt, my colleague, for your knowledge, your encouragement, good advice and
“forcing” me to go on when times seemed difficult.
Jane Strand, Laila Örtensjö, Eva Norgren-Holst and Ulla-Britt Lindqvist for helping me to take
care of the patients, for helping me to administrate all data, and to Margaretha Sandin, for your
secretarial skills.
The Staff of the operating theatres, particularly the assisting nurses, for your incredible patience
and hard work, for your accuracy with the surgical protocols and for your cheerful
temperaments. Also, my gratitude to the doctors and nurses at the Department of
Anaesthesiology for your contributions.
My colleagues at the Department of Cardiothoracic Surgery for your patience while assisting me
at surgery, all the way from harvesting to implantation of the “fat vein”.
My family, my deceased father José Martins and especially my mother Julia for their support
throughout my life. Also, my daugther Letícia.
Most of all I want to thank my family: my beloved, Anette, for your support and love, for all
your efforts at work and at home that has made this possible. To our children, Johanna, Josef
and Filip, who patiently have seen all this work taking place. Thank you, I love you all.
The expert help from the staff at the Medical Library, a special thanks to Margareta Gawell for
her database searches and compilations.
Lars-Göran Jansson at the Department of Medical Photography, for providing me with your
excellent work every time I needed.
Last but not least, I want to thank both Örebro University Hospital’s Medical Research
Committee and Mälarsjukhus in Eskilstuna for their support by supplying grants to cover some
of this work.
36
References
1. Eisenberg MS. The problem of sudden cardiac death. In: Eisenberg MS, Hallstrom AP,
editors. Sudden Cardiac Death in the Community. New York: Praeger, 1984:2.
2. Rahimtoola SH. Coronary bypass surgery - a perspective. In: Rahimtoola SH, Brest AN,
editors. Coronary Bypas Surgery. Philadelphia: F A Davis, 1977:11.
3. Carrel A. On the experimental surgery of the thoracic aorta and the heart. Ann Surg
1910;52:83-95.
4. Beck CS. The development of a new blood supply to the heart by operation. Ann Surg
1935;102:801-13.
5. Beck CS, Leighninger DS. Operations for coronary artery disease. JAMA 1954;156:1226-
33.
6. Vineberg A, Buller W. Technical factors which favor mammary-coronary anastomosis
with report of forty-five cases of human coronary artery disease thus treated. J Thorac
Surg 1955;30:411-35.
7. Sones Jr FM, Shirey EK. Cine coronary arteriography. Mod Concepts Cardiovasc Dis
1962;31:735-8.
8. Effler DB, Groves LK, Sones Jr FM, Shirey EK. Endarterectomy in the treatment of