J Thorac Cardiovasc Surg 1994;107:1156-1157
© 1994 Mosby, Inc.
The in vitro response of human internal mammary artery to vasodilators
G. Kimble Jett, MD
Director
Mechanical Circulatory Assistance
Baylor University Medical Center
3409 Worth St., Suite 720
Dallas, TX 75256
Reply to the Editor:
I have reviewed the letter by Drs. Cooper and Locke with interest. I believe the essence of their letter is to detail their results, which they state contrast with my recent publication. 
1 I believe that Cooper and Locke are trying to compare results using two different protocols. My study evaluated the ability of vasodilators to prevent contraction of the internal mammary artery (IMA), whereas their study appears to investigate the ability of vasodilators to relax a precontracted IMA. The differences in our results are easily explained by the different drug treatment protocols, as detailed recently by He and associates. 2
He and colleagues looked at both protocols (preventing IMA contraction and relaxing a contracted IMA), and their data support both those presented by Cooper and Locke and those detailed in my recent publication. He's group also found that glyceryl trinitrate did not prevent potassium-induced contraction of the IMA, whereas nifedipine was effective at preventing contraction. In addition, the data referred to He in Cooper and Locke's letter are from drug treatment of a precontracted IMA, and this certainly appears to support their table. The lack of effectiveness of glyceryl trinitrate to prevent contraction or spasm of the IMA is due to its mechanism of action, as detailed in He's study. Glyceryl trinitrate will not prevent intercellular calcium rise in response to membrane depolarization (potassium solution) and calcium influx through voltage-operated channels; it will, however, lower the intracellular calcium via nitric oxide stimulation of guanylate cyclase, which subsequently leads to removal of calcium from the cell and its relocation. The net result is the relaxation of a contracted artery, but not the prevention of arterial contraction. Calcium channel blockers (nifedipine) will prevent calcium influx (arterial contraction) and enhance intracellular calcium removal (arterial relaxation). Since the mechanisms of action for glyceryl trinitrate and nifedipine are different, the different effects of the two drugs in preventing arterial contraction and in relaxing a precontracted artery can be easily explained (Fig. 1). The data from He and associates therefore support both my data and Cooper and Locke's letter.
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Fig. 1. Schematic diagram of calcium entry into a smooth muscle cell through receptor-operated (ROC)and voltage-operated (VOC)channels (upper panel). Calcium entry blocking drugs selectively reduce the open state of VOC. Glyceryl trinitrate (GTN)releases nitric oxide (NO) into thecell, which stimulates guanylate cyclase to raise cyclic guanosine 5' -monophosphate (cGMP)that subsequently leads to Ca++ being removed from the cell and its relocation (lower panel). EM, Membrane potential; [Ca++]o, extracellular calcium concentration; TXA2, thromboxane A2.(From He GW, Rosenfeldt FL, Buxton BF, Angus JA. Reactivity of Isolated Human Internal Mammary Artery to Constrictor and Dilator Agents. Circulation 1989;80 (Suppl):I140-50; published with permission of the American Heart Association.)
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I agree with Drs. Cooper and Locke that it is difficult to extrapolate in vitro data to clinical situations. This can also be stated concerning the recent in vivo study of Cooper, Wilkinson, and Angelini 3 measuring free flow through the IMA. Once the IMA anastomosis is completed, many factors are involved in determining IMA flow (heart rate, blood pressure, cardiac output, IMA/coronary vascular resistance). Caution should be exercised, however, when using sodium nitroprusside after completion of the IMA anastomosis because recent animal experimental data 4 have demonstrated a reduction in IMA blood flow with sodium nitroprusside administration but an increase in IMA flow with glyceryl trinitrate administration. Again, it is difficult to extrapolate from the canine model to the human being, but the information may be clinically very pertinent.
Combining all of the cited studies, perhaps a few guidelines for treating/preventing IMA spasm and altering IMA flow may be suggested: (1) Nifedipine may be the best drug to prevent IMA spasm. It may also treat spasm but requires time to achieve relaxation. (2) Sodium nitroprusside may be the most effective drug to topically apply to the IMA during the operation. (3) Postoperative vasospasm of the IMA or mere augmentation of IMA flow may be best provided by glyceryl trinitrate or nifedipine. (4) Caution should be taken in the postoperative administration of sodium nitroprusside to patients with IMA grafts because nitroprusside has the potential to reduce IMA blood flow.
References
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Jett GK, Guyton RA, Hatcher CR, Abel PW. Inhibition of human internal mammary artery contractions: an in vitro study of vasodilators. J THORAC CARDIOVASC SURG 1992;104:977-82.[Abstract]
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He GW, Rosenfeldt FL, Buxton BF, Angus JA. Reactivity of isolated human internal mammary artery to constrictor and dilator agents. Circulation 1989;80(Suppl):I140-50.
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Cooper GJ, Wilkinson GAL, Angelini GD. Overcoming perioperative spasm of the internal mammary artery: Which is the best vasodilator? J THORAC CARDIOVASC SURG 1992;104:465-8.[Abstract]
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Jett GK, Arcidi JM, Dorsey LMA, Hatcher CR, Guyton RA. Vasoactive drug effects on blood flow in internal mammary artery and saphenous vein grafts. J THORAC CARDIOVASC SURG 1987;94:2-11.[Abstract]
