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Ann Thorac Surg 1997;63:382-387
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

High-Dose Isosorbide Dinitrate for Myocardial Revascularization With Composite Arterial Grafts

Departments of Thoracic and Cardiovascular Surgery and Cardiology, Ichilov Hospital, Elias Sourasky Tel-Aviv Medical Center, Tel-Aviv University, Tel-Aviv, Israel

Accepted for publication July 29, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. Composite arterial grafting for myocardial revascularization is a surgical technique in which free arterial conduits are proximally attached to an in situ internal mammary artery.

Methods. Composite arterial grafting was performed in 78 patients with internal mammary artery (n = 24), inferior epigastric artery (n = 21), or radial artery (n = 33) connected to the internal mammary artery. Overall, 254 distal anastomoses were performed (average number, 3.3 per patient), 225 of which were arterial. All patients were treated postoperatively with high-dose isosorbide dinitrate (4 to 20 mg/h for 24 hours).

Results. The in-hospital mortality rate was 2.6% (2 patients). Early recatheterization studies performed 3 weeks (range, 1 to 20 weeks) after operation in 30 patients demonstrated patency rates of 100%, 93%, and 100% for the composite internal mammary artery, inferior epigastric artery, and radial artery groups, respectively. In addition, two inferior epigastric artery conduits had major intraluminal constriction. At a mean follow-up of 20 months (range, 1 to 42 months) all patients are alive, and all but 2 in the inferior epigastric group (97%) are angina free.

Conclusions. This surgical technique can be safely used. On the basis of our experience, the right internal mammary artery and the radial artery are the most suitable conduits for this procedure. High-dose nitrates given perioperatively prevent spasm and ensure early patency rates.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The search for suitable and multiple arterial grafts for myocardial revascularization continues as a consequence of disappointing long-term results with vein grafts. The patency rate of saphenous vein grafts after 10 years is only 40% to 60%, and there is evidence of graft atherosclerosis in most remaining patent veins [1]. The internal mammary artery (IMA) is the preferred bypass graft to the left anterior descending coronary artery, with 10-year patency rates of 90% to 95% [2, 3]. In addition to the left IMA, which is routinely used for myocardial revascularization, the right IMA (RIMA), the inferior epigastric artery (IEA), and the radial artery (RA) might serve as supplementary arterial grafts.

The right IMA and the left IMA have comparable patency rates [4–8]. There are, however, some technical limitations to the routine use of the in situ RIMA. It might be too short to reach all coronary segments to be grafted. Transferring the RIMA pedicle through the transverse sinus is not ideal because of flow limitations and occlusions in the early postoperative period [9]. Other risks are overstretching and rotation of the RIMA and difficulties in the management of pedicle bleeding.

Grafting the pediculate RIMA across the midline to revascularize the left anterior descending coronary artery while the left IMA vascularizes the left circumflex marginal branches [7] increases the potential for injury during subsequent sternotomy. Using the RIMA as a free graft with the proximal anastomosis constructed on the ascending aorta is not recommended, as its patency rate is not much better than that of vein grafts [6, 10].

Connecting the proximal free RIMA end-to-side to an in situ left IMA, the composite technique, might be the preferred solution in many instances. These include the presence of a diseased aortic wall, the unavailability of vein grafts, and a relatively short IMA graft [11–14]. This technique was recently expanded to include the IEA and the RA as alternative free arterial conduits, with some promising short-term results [5, 14–16]. Intravenous diltiazem hydrochloride has been used to prevent spasm of the RA grafts [5, 14]. As intravenous diltiazem was not commercially available in Israel, high-dose isosorbide dinitrate was used as our main antispastic agent. This study describes our experience using the composite technique with the IMA, the IEA, or the RA as free grafts.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Patient Data
Composite arterial grafting was performed on a total of 78 patients from July 1, 1992, to December 12, 1995. Patients had end-to-side IMA to IMA grafting (n = 24), the composite IEA procedure (n = 21), or the composite RA operation (n = 33). In 61 patients (78%), both mammary arteries were used. Average age was 58.7 years (range, 39 to 78 years). There were 68 men and 10 women.

There were more women in the RA group than in the IMA and IEA groups (8, 1, and 1, respectively; p < 0.05). More patients in the composite IMA and RA groups than the IEA group had unstable angina (67%, 79%, and 33%, respectively; p < 0.05), peripheral vascular disease (29%, 24%, and 10%), and left main coronary artery disease (38%, 45%, and 29%). Also, patients in the composite IMA and RA groups underwent more reoperations than those in the IEA group (8%, 15%, and 0%, respectively). Mean left ventricular ejection fraction was 0.59 (range, 0.23 to 0.78).

Indications
The indications for the composite operation were as follows: unavailability of veins for grafting because of varicose veins or previous stripping of varicose veins (n = 18); severe peripheral vascular disease (n = 12); previous deep vein thrombophlebitis (n = 7); limitations of RIMA length (n = 5), injury to IMA segment during harvesting (n = 2); subclavian artery stenosis (n = 1); severely calcified aorta (n = 9); and reoperations that precluded proximal aortic connections (n = 5) or involved hyperlipidemic patients less than 60 years old (n = 20) in whom only arterial grafts were to be used. One woman from the RA group asked us to avoid using vein grafts for cosmetic reasons.

Surgical Technique
HARVESTING AND PREPARATION OF CONDUITS.
Both IMAs were harvested from the chest wall as a pedicle. After systemic heparinization, they were transected distally to determine flow rates and soaked in warm gauze with papaverine hydrochloride (30 mg/100 mL of saline solution pH 5.2). To avoid intimal injury or dissection, no intraluminal injection of papaverine or mechanical dilatation of the IMA was done. Pediculate IMA flow was pulsatile and ample in all patients. The IEA was harvested as described previously [15, 16]. Most IEA grafts were shorter than 10 cm to avoid small diameters at the site of distal anastomoses. The RA was harvested using a recently described technique [17]. Unlike the IMA graft preparations, a gentle intraluminal injection of papaverine was routinely administered to all IEA and RA grafts [5, 14].

MYOCARDIAL PRESERVATION TECHNIQUE.
Cardiopulmonary bypass was instituted using a hollow-fiber membrane oxygenator, (SAFE II; Polystan A/S, Vaerlose, Denmark), and the ascending aorta was cross-clamped. Myocardial preservation included intermittent anterograde and retrograde cold blood cardioplegia and "last shot" warm blood cardioplegia. In 6 patients with a severely calcified aorta, clamping of the aorta was avoided by using a cold fibrillation technique and lowering body temperature to 20°C.

CONSTRUCTION OF ANASTOMOSES.
All arterial distal anastomoses were performed using a continuous suture technique with 8-0 polypropylene (Prolene; Ethicon, Somerville, NJ). When IMAs were sequentially used, a diamond-shaped technique was employed [9]. The most distal end-to-side anastomosis was performed first and the most proximal side-to-side anastomosis, last. In 25 patients, the composite anastomosis was performed during ischemia while the myocardium was perfused retrogradely with continuous warm blood cardioplegia. However, recently in the RA group, the composite anastomoses were constructed before the start of cardiopulmonary bypass. In all patients, the diameter of the IMA exceeded 3 mm at this anastomotic site.

To prevent arterial spasm, all patients were treated during and after operation with maximally tolerated doses of intravenous isosorbide dinitrate (4 to 20 mg/h for 24 hours). Systolic blood pressure was always maintained greater than 110 mm Hg. Patients in the RA group were treated orally with diltiazem (60 mg three times a day) for at least 3 months postoperatively.

Statistical Analysis
Data are expressed as the mean ± the standard deviation or as percentages. Data were analyzed using Student's unpaired t test and Fisher's exact test. A p value of less than 0.05 was considered significant.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
A total of 254 distal anastomoses were performed (average number, 3.3 distal anastomoses per patient), 225 (89%) of which were arterial and 29 (11%), vein grafts (Table 1). Forty-five additional coronary arteries were sequentially grafted in 10 patients (42%) in the IMA group, 16 patients (49%) in the RA group, and no patient in the IEA group (p < 0.01). Saphenous vein bypass was performed in addition to arterial bypass in 20 patients in the IMA and IEA groups and in 1 patient in the RA group (p < 0.01). Patients in the RA group had a shorter ischemic time than patients in the IEA group and shorter cardiopulmonary bypass times than patients in the other two groups (p < 0.05 see Table 1).

Three patients experienced complications. One patient in the RA group had hypoperfusion syndrome, which eventually responded to high doses of nitrates. One patient in the IEA group had development of complete heart block and required pacemaker implantation. One patient in the IMA group experienced transient renal failure, and 1 patient in the RA group (the patient with hypoperfusion) sustained a minor enzymatic perioperative myocardial infarction. All other patients had an uneventful postoperative course. There were no sternal wound infections. Daily neurologic examinations of the arms from which the RA was harvested in patients in the RA group revealed no sign of ischemia or neurologic deficits.

Clinical and Angiographic Follow-up
Early recatheterization studies were performed an average of 3 weeks (range, 1 to 20 weeks) postoperatively in 39% of the patients (Table 2; Figs 1–3). In all patients but 1 in the IEA group, the composite and distal anastomoses were patent (patency rates, 97% and 99%, respectively). The obstructed IEA composite anastomosis was most probably due to technical error. In two additional IEA conduits, intraluminal constriction sites were noted on the postoperative recatheterization studies. These patients remain asymptomatic. All operative survivors are alive at a mean follow-up of 24 months (range, 8 to 34 months). All patients in the IMA and RA groups and all but 2 in the IEA group are angina free (97%). Similar findings were observed in postoperative ergometric and thallium single-photon emission computed tomographic studies (see Table 2).

View larger version (69K): [in this window] [in a new window]   Fig 1. . (A) Composite double internal mammary artery (IMA) grafting and (B) angiographic study at 4 weeks. Pediculate left IMA (LIMA) is anastomosed to midportion of left anterior descending coronary artery (LAD). Free right IMA (RIMA) graft (proximally attached to LIMA) goes sequentially to two marginal branches (M2, arrows) and continues to right posterior descending coronary artery (RPD). (D1 = first diagonal branch.)

View larger version (72K): [in this window] [in a new window]   Fig 3. . (A) Composite radial artery (RA) grafting to left internal mammary artery (LIMA) and (B) angiographic study at 23 days. The LIMA is distally attached to left anterior descending coronary artery (LAD, thin arrow), and the RA is sequentially grafted to marginal circumflex (M2, upper arrowhead) and right posterior descending coronary (lower arrowhead) arteries. (Ao = aorta, PA = pulmonary artery.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

Dion and associates [6] found a significant decrease in patency rates when free IMAs were implanted on the aorta compared with patency rates of in situ IMAs (79.6% versus 96.1%; p < 0.001). The early IEA graft failure reported when the graft is proximally attached to the aorta [18] might be attributed to differences in wall thickness [14]. Calafiore and coauthors [20] suggested that improved patency rates might theoretically be achieved using a composite anastomosis because of different shear forces and more natural rates of rise in pressure than those obtained in proximal connections to the ascending aorta.

Connecting one IMA end to side to the other was described by Sauvage and colleagues [12] in 1986. Early encouraging results with composite arterial grafting [11] have expanded the indications for this technique. Included now are other groups of patients requiring arterial revascularization, apart from those in whom there is no choice, such as patients with a diseased aortic wall, unavailability of vein grafts, or a relatively short IMA graft, and other arterial conduits such as the IEA and the RA.

The recent revival of use of the RA for coronary artery bypass grafting and its promising early and late patency rates reported by Acar and colleagues [5] have encouraged us to use this conduit in conjunction with one IMA (or both IMAs) as a composite arterial graft. Improved results have been attributed to the use of a new antispastic pharmacologic agent (diltiazem) and to improved surgical technique, ie, intraluminal hydrostatic rather than mechanical dilatation [5], thus lowering the incidence of early reported failure caused by spasm and intimal hyperplasia [19]. Avoiding proximal aortic connections by anastomosing the RA proximally to the IMA might further increase patency rates to 93% to 100% [14].

The concern about "putting all the eggs in one basket" [21] and relying on sufficient flow from a single IMA pedicle has gradually subsided after follow-up recatheterization studies as well as normal findings on postoperative ergometric and scintigraphic studies. The left IMA had no flow limitations, even during maximal myocardial demand. Experimental studies [22] have shown that a main determinant of IMA flow is the distal runoff. Recent extensive clinical work by Tector and associates [13] and Calafiore and colleagues [14] provides further encouraging data showing early and midterm [20] patency rates of 94% to 100% with this technique.

Tector [13], Calafiore [14], and their co-workers performed the composite anastomoses prior to initiating bypass. We recently adopted this approach, which allows assessment of flow adequacy through the anastomoses before going on bypass and shortens the cardiopulmonary bypass and ischemic times.

Two patients (2.6%) in our series manifested hypoperfusion syndrome [23] immediately after the operation, and 1 of them died. As a result of that death, we now routinely use high-dose nitrates in the first postoperative 24 hours to prevent hypoperfusion. If there is arterial spasm, doses should be increased, even, paradoxically, in the presence of relatively low blood pressure. Our experience using this maneuver in patients with arterial grafting has been surprisingly good. A safer approach, however, may be to place a vein graft to the distal left anterior descending coronary artery or to a suspected hypoperfused area. Although hypoperfusion is not very frequent (2.4% to 5%) [13, 14, 20, 23], surgeons should be aware of its existence, particularly when using multiple arterial conduits, and treat it according to the protocols mentioned. After the immediate postoperative period, the IMA adapts itself to flow requirements [24], even in cases of multiple distal anastomoses, as has been well established in previous clinical and angiographic reports of multiple sequential and complex IMA grafting [9].

The comparison between the three groups in this study showed that even though the patients in the composite IMA and RA groups were more symptomatic and had more peripheral vascular disease than patients in the IEA group, the outcomes were comparable or even slightly better in the first two groups. More patients in the IMA and RA groups underwent sequential grafting, whereas in the IEA group, three arterial grafts were used-bilateral IMAs and the IEA.

Use of the RA was more convenient for the surgeon than either the IMA or IEA. Harvesting the RA is very simple, with practically no morbidity to the harvesting site. The length of this artery allows unlimited access to all desired myocardial segments requiring revascularization. We noted easy handling during the construction of anastomoses with the RA, making it favorable for technical use.

These features were especially apparent compared with the IEA and IMA conduits. The former is a relatively short, thin graft, attributes making its technical use tedious. Had the results with the RA and the IEA been comparable, we nevertheless would have preferred the RA. This preference is strengthened by the unfavorable results with the IEA: in 1 patient, the composite and distal anastomoses were obstructed; in two additional conduits, intraluminal constriction sites were observed in postoperative recatheterization studies; and 2 other patients had recurrence of angina after the operation. For these reasons, use of the IEA graft on our service has fallen considerably.

In conclusion, the composite operation, although technically demanding, provides extensive options to the surgeon attempting to accomplish arterial revascularization. The early and midterm results are encouraging and emphasize its feasibility. The use of high-dose isosorbide dinitrate rendered the RA as reliable as the RIMA. However, longer follow-up is required to evaluate its patency rate.

View larger version (83K): [in this window] [in a new window]   Fig 2. . (A) Complete arterial revascularization using both internal mammary arteries (IMA) and composite inferior epigastric artery (IEA) and (B) angiographic study at 14 days. Composite IEA [distally grafted to marginal branch (M2)] is attached to in situ left IMA (LIMA) [distally grafted to left anterior descending coronary artery (LAD)]. (Ao = aorta; PA = pulmonary artery; RIMA = right internal mammary artery.)

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Address reprint requests to Dr Gurevitch, Department of Thoracic and Cardiovascular Surgery, Ichilov Hospital, Elias Sourasky, Tel-Aviv Medical Center, 6 Weizman St, Tel-Aviv 64239, Israel.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

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