Use of Nitrates as Vasodilators for Internal Mammary Artery During Bypass Graft Surgery
Intravenous nitroglycerin is the recommended systemic vasodilator for managing the internal mammary artery during CABG surgery, as it significantly increases IMA flow in vivo and is superior to other systemic agents for this specific purpose. 1
Physiologic Rationale for Vasodilator Use
The internal mammary artery is inherently resistant to atherosclerosis due to its continuous internal elastic lamina and endothelial release of prostacyclin and nitric oxide. 2 However, all mammary arteries are in spasm immediately after harvest, with inadequate flow before pharmacologic intervention. 3 This perioperative spasm represents a critical management issue that must be addressed to ensure adequate graft function.
Systemic Vasodilator Selection
Nitroglycerin as First-Line Agent
Intravenous nitroglycerin is the only systemic vasodilator proven to significantly increase both IMA and radial artery flow in vivo during CABG. 1 In a randomized controlled trial comparing five different agents (nitroglycerin, nitroprusside, dobutamine, milrinone, and saline), multivariate analysis identified nitroglycerin as the sole predictor of increased IMA flow (p < 0.001) and radial artery flow (p = 0.009). 1
The mechanism involves nitrate-induced relaxation of vascular smooth muscle through conversion to nitric oxide, which acts as an endothelium-derived relaxing factor. 2 This is particularly relevant for the IMA, whose natural resistance to atherosclerosis depends on endogenous nitric oxide production. 2
Nitroprusside Paradox
Despite being more potent than nitroglycerin at inhibiting IMA contraction in vitro, nitroprusside actually decreases IMA graft flow by 12 ± 2% in vivo. 4 This paradoxical effect makes nitroprusside unsuitable as a systemic vasodilator for IMA management during CABG, despite its effectiveness as a topical agent (discussed below). 4
Other Systemic Agents
Dobutamine and milrinone showed no significant benefit for increasing IMA flow compared to control. 1 These agents should not be relied upon for managing IMA vasospasm during harvest and preparation.
Topical Vasodilator Application
Sodium Nitroprusside (Topical)
For topical application directly to the IMA pedicle, sodium nitroprusside is the most effective agent, increasing free flow by 250% over control (from median 26 to 108 ml/min, p < 0.001). 5 This represents superior efficacy compared to all other topical agents tested. 5
Glyceryl Trinitrate and Nifedipine (Topical)
Both agents produce approximately threefold increases in IMA free flow when applied topically. 5 Glyceryl trinitrate increased flow from median 23 to 62 ml/min (p < 0.001), while nifedipine increased flow from 23 to 71 ml/min (p < 0.001). 5 These represent viable alternatives to topical nitroprusside.
Papaverine (Topical)
Traditional papaverine wrapping produces modest increases in IMA flow, from median 25 to 43 ml/min (p < 0.01). 5 However, intraluminal papaverine injection with hydrostatic dilatation dramatically increases free flow to 150-333 ml/min (mean 229 ml/min), raising flow to maximal capacity. 3 This technique is superior to simple topical application.
Recommended Algorithm for IMA Vasodilator Management
During Harvest and Preparation
- Administer intravenous nitroglycerin systemically as the primary vasodilator to increase IMA flow during harvest 1
- Apply topical sodium nitroprusside to the IMA pedicle by spraying and wrapping in soaked sponges for approximately 18-21 minutes 3, 5
- Perform intraluminal papaverine injection (60 mg diluted in 40 ml normal saline) with hydrostatic dilatation immediately before anastomosis to achieve maximal flow capacity 3
Hemodynamic Monitoring
Monitor mean arterial pressure closely, as nitroglycerin decreases MAP (p = 0.007) through peripheral vasodilation. 1 The primary mechanism involves reduction in preload through venous pooling and modest afterload reduction. 2, 6
Critical Pitfalls and Caveats
Hypotension Risk
Severe hypotension and shock may occur with even small doses of nitroglycerin, particularly in volume-depleted patients. 6 Nitroglycerin-induced hypotension may be accompanied by paradoxical bradycardia and increased angina. 6 Careful titration is essential, especially in patients with right ventricular infarction who depend on adequate preload. 2
Tolerance Development
Continuous nitroglycerin infusions lose almost all hemodynamic effect after 48 hours due to tolerance. 6 This is less relevant for the acute intraoperative period but important if prolonged postoperative infusions are considered.
Drug Interactions
Nitroglycerin interferes with heparin's anticoagulant effect in some patients. 6 Activated partial thromboplastin time should be monitored frequently during concomitant therapy. 6 Additionally, nitroglycerin should not be mixed with any other medication and cannot be administered through the same line as blood products. 6
Timing Considerations
IMA flow reserve is significantly lower in the early postoperative period (2.70 ± 0.62) compared to late postoperative assessment (3.66 ± 0.81, p < 0.01). 7 This appears related to microvascular injury during operation rather than conduit issues, and normalizes over time. 7 Vasodilator responsiveness to papaverine and nitrates remains intact both early and late postoperatively. 7
Measurement Validation
Free IMA flow before any pharmacologic intervention ranges from 5-44 ml/min (mean 18 ml/min), confirming universal spasm after harvest. 3 Adequate IMA diameter at the anastomosis site should be 1.75-2.5 mm. 3 These benchmarks help verify successful vasodilator therapy.