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J Thorac Cardiovasc Surg 1994;108:82-85
© 1994 Mosby, Inc.
SURGERY FOR ACQUIRED HEART DISEASE |
Bristol and Cardiff, United Kingdom
Received for publication Sept. 8, 1993. Accepted for publication Jan. 18, 1994. Address for reprints: G.D. Angelini, MD, Professor of Cardiac Surgery, Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom.
Abstract
Postoperative spasm of the internal mammary artery graft can cause morbidity and mortality after myocardial revascularization. To our knowledge, the ability of systemic vasodilators to overcome internal mammary artery spasm has not been studied clinically. In 50 patients in whom the left internal mammary artery was used for myocardial revascularization, we have investigated the effect of five agents on internal mammary artery free flow: normal saline, dobutamine, glyceryl trinitrate, sodium nitroprusside, and enoximone, a phosphodiesterase III inhibitor. After the internal mammary artery was harvested, free flow was measured under controlled hemodynamic conditions before any pharmacologic intervention (flow 1) and a mean of 18.5 ± 3 (standard deviation) minutes after a systemic infusion of one of the five agents was begun (flow 2). The increase in free flow expressed as a percentage of initial flow was greater for enoximone (94% ± 24%) than for normal saline (18% ± 11%), dobutamine (40% ± 27%), and glyceryl trinitrate (52% ± 36%) (all three p < 0.01). The increase in flow for sodium nitroprusside (78% ± 37%) was greater than for normal saline and dobutamine (both p < 0.05). We therefore recommend the systemic use of enoximone and sodium nitroprusside, in rank order, to prevent and treat postoperative spasm of the internal mammary artery. (J THORAC CARDIOVASC SURG 1994;108:82-5)
The internal mammary artery (IMA) is the conduit of choice for myocardial revascularization owing to its long-term patency rate and the lower incidence of myocardial infarctions and reoperations associated with its use. 
1-3 Perioperative and postoperative spasm of the IMA with reduction in graft flow is known to happen and could cause hemodynamic instability, perioperative morbidity, and even mortality in high-risk patients. 4-7 We 8 have previously reported the topical use of sodium nitroprusside to overcome perioperative IMA spasm. However, the beneficial effect of this topical application is brief and may not prevent postoperative spasm of the IMA. To our knowledge no formal clinical study has been conducted testing the ability of systemic vasodilators to overcome IMA spasm. We therefore compared the effect on IMA free flow of normal saline, dobutamine, glyceryl trinitrate, sodium nitroprusside, and enoximone so that we could identify the best drug for treatment of postoperative IMA spasm.
Patients and methods
Fifty consecutive patients undergoing elective coronary artery bypass operations with the IMA were randomly allocated to one of five equal-sized groups. Permission was obtained from the United Bristol Healthcare Trust Research Ethical Committee. The IMA was dissected on a pedicle, from the subclavian vein to just beyond the bifurcation into the superior epigastric and musculophrenic arteries, with the aid of diathermy and metal clips. Five minutes after systemic heparinization, the artery was divided distally and occluded at its tip with a metal bulldog clamp. The sternum-lifting retractor, used to expose the IMA, was replaced with a sternum-spreading retractor and the pedicle was trimmed, excising the occluded portion, to expose the end of the artery proximal to its bifurcation. Flow was determined by measuring the volume of blood expelled from the end of the freely bleeding artery in a 30-second period. Time of measurement, heart rate, and mean arterial and central venous pressures were recorded. The tip of the artery was again occluded with a metal bulldog clamp, and the artery was laid on a moist swab beneath the left sternal edge. Infusion of the vasodilator was then started, beginning with the minimum dose (see Systemic infusions section) and increasing gradually to the maximum dose providing this maintained the mean blood pressure within ±20 mm Hg. Enoximone was administered as a single bolus. After cannulation in preparation for cardiopulmonary bypass, blood was transfused from or returned to the pump to restore the mean arterial and central venous pressures as nearly as possible to the previous values. The IMA then was unwrapped and its end trimmed to remove the part that had been occluded by the metal bulldog clamp. Time, heart rate, and mean arterial and central venous pressures were recorded, and the "second" flow was measured. The surgeon making the measurements was blinded to the pharmacologic agent used.
Systemic infusions.
The following were infused systemically: (1) normal saline (0.9% sodium chloride solution, 1.5 ml/min), (2) glyceryl trinitrate 0.5 to 3 µg/kg per minute (Schwarz Pharma Ltd., Bucks, United Kingdom), (3) sodium nitroprusside 0.5 to 2 µg/kg per minute (David Bull Lab., Warwick, United Kingdom), (4) dobutamine 1 to 3 µg/kg per minute (Eli Lilly & Co. Ltd., Basingstoke, United Kingdom), and (5) enoximone 50 µg/kg (Marion Merrell Dow Ltd., Uxbridge, United Kingdom).
Statistical analysis.
Two-tailed Wilcoxon rank sum tests for paired and independent data as appropriate were used to test statistical significance. Data are expressed as mean ± standard deviation and standard error.
RESULTS
Sex ratios and ages of the five groups are shown in Table I. The differences between groups in body surface area and time between flow measurements were not significant. Heart rates, mean arterial pressures, and central venous pressures at the time of different measurements were not significantly different, either within or between groups (Table I).
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Table II. Sodium nitroprusside appeared to have a lower initial flow, but the difference was not statistically significant. Increase in flow (second flow compared with first flow) was found to be significantly associated with initial flow (p = 0.01 for enoximone, p = 0.03 for normal saline, and p = 0.07 for sodium nitroprusside), but not with blood pressure or change in blood pressure. The increase in flow (expressed as a percentage of initial flow) was significantly greater for enoximone than for normal saline, dobutamine, and glyceryl trinitrate (all three p < 0.01). The increase in flow for sodium nitroprusside was significantly greater than for normal saline and dobutamine (p < 0.05) (Fig. 1). This observation suggests a rank order for flow increase of enoximone, sodium nitroprusside, glyceryl trinitrate, and dobutamine. During the study, no patient had clinically apparent spasm of the IMA after the operation, and no untoward reactions to the vasodilators were noted.
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In the past decade, the IMA has replaced the saphenous vein as the conduit of choice for myocardial revascularization because of its relative freedom from atherosclerosis. 3,9 However, the IMA has a smaller lumen than the saphenous vein and a greater tendency to spasm. These characteristics can cause significant flow deprivation in the early postoperative period with increased morbidity and mortality. 4,7 The mechanisms of IMA spasm are not clear. Previous discussions have implicated 
-adrenergic activity, increased blood pH, decreased body temperature, and manipulation or probing of the artery causing endothelial cell damage and impaired production of prostacyclin and endothelium-derived relaxing factor. 4,10-12
Different approaches have been advocated for the management of severe postoperative IMA spasm, such as coronary angiography with intracoronary infusions of nitroglycerin or sublingual administration of nifedipine. For acute refractory hemodynamic collapse, immediate reoperation with probing, topical application, or intramammary injection of a vasodilator have been suggested. 4,7 Nevertheless, less aggressive measures may hold the solution to this complication, and the systemic infusion of vasodilators appears to be a reasonable choice.
To our knowledge a comparison of the effects of systemic administration of vasodilators on IMA free flow in the clinical setting has not been done before. Sodium nitroprusside, as in our previous study 8 where it was used topically, relieved IMA spasm when given systemically, although it was not as effective as enoximone. It is possible that the doses used for this work were not equivalent, because these were the maximum infusion rates that could be used without incurring an undesirable change in systemic blood pressure. In this setting, comparison of equivalent doses did not have important clinical relevance.
The drugs investigated in our study are commonly used clinically after coronary revascularization to restore or improve the hemodynamics of the patient. When a choice is being made among these agents, consideration should be given not only to the effects of the drug on the coronary and systemic vasculature, but also on its effect on graft flow. Enoximone, a synthesized imidazolone derivative, has been shown to be a nonglycosidic, nonsympathomimetic cardiotonic agent, acting mainly by inhibition of phosphodiesterase- III. This effect inhibits the breakdown of cyclic adenosine monophosphate in cardiac and peripheral vascular smooth muscle, therefore exerting a potent inotropic effect as well as a direct vasodilatory action. 13-15 Enoximone, with its half-life of 3 hours, being administered in a bolus dose at the end of the operation, may therefore be effective in the early postoperative period when the risk of IMA spasm is greater and when maximum flow through the graft is desirable to restore myocardial perfusion.
Footnotes
From the Department of Cardiac Surgerya, University of Bristol, Bristol, and Centre for Public Health Studiesb, University of Wales College of Medicine, Cardiff, United Kingdom. 
References
This article has been cited by other articles:
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  G.-W. He, L. Fan, A. Furnary, and Q. Yang A new antispastic solution for arterial grafting: Nicardipine and nitroglycerin cocktail in preparation of internal thoracic and radial arteries for coronary surgery J. Thorac. Cardiovasc. Surg., September 1, 2008; 136(3): 673 - 680. [Abstract] [Full Text] [PDF]
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C. Izumi, H. Hayashi, Y. Ueda, M. Matsumoto, Y. Himura, H. Gen, and T. Konishi Late regression of left internal thoracic artery graft stenosis at the anastomotic site without intervention therapy J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1661 - 1667. [Abstract] [Full Text] [PDF]
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 Y. Tabel, H. Hepaguslar, C. Erdal, H. Catalyurek, U. Acikel, Z. Elar, and O. Aslan Diltiazem provides higher internal mammary artery flow than nitroglycerin during coronary artery bypass grafting surgery Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 553 - 559. [Abstract] [Full Text] [PDF]
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M. J. Flynn, D. Winters, P. Breen, G. O'Sullivan, G. Shorten, D. O'Connell, A. O'Donnell, and T. Aherne Dopexamine increases internal mammary artery blood flow following coronary artery bypass grafting Eur. J. Cardiothorac. Surg., October 1, 2003; 24(4): 547 - 551. [Abstract] [Full Text] [PDF]
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 M.-H. Liu, H. S. Floten, A. P. Furnary, A. P.C. Yim, and G.-W. He Effects of potassium channel opener aprikalim on the receptor-mediated vasoconstriction in the human internal mammary artery Ann. Thorac. Surg., February 1, 2001; 71(2): 636 - 641. [Abstract] [Full Text] [PDF]
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D. Zabeeda, B. Medalion, S. Jackobshvilli, S. Ezra, A. Schachner, and A. J. Cohen Comparison of systemic vasodilators: effects on flow in internal mammary and radial arteries Ann. Thorac. Surg., January 1, 2001; 71(1): 138 - 141. [Abstract] [Full Text] [PDF]
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 M. B. Vroom Pharmacologic Management of Acute Heart Failure: A Review Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 1998; 2(3): 191 - 203. [Abstract] [PDF]
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J.-L. Cracowski, O. Chavanon, M. Durand, E. Borrel, P. Devillier, J.-M. Mallion, and D. Blin Effect of Low-Dose Positive Inotropic Drugs on Human Internal Mammary Artery Flow Ann. Thorac. Surg., December 1, 1997; 64(6): 1742 - 1746. [Abstract] [Full Text]
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M. B. Izzat, S. Bolsin, A. J. Bryan, and G. D. Angelini Enoximone in internal mammary artery hypoperfusion J. Thorac. Cardiovasc. Surg., September 1, 1995; 110(3): 868 - 870. [Full Text]
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