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J Thorac Cardiovasc Surg 1994;107:1155-1156
© 1994 Mosby, Inc.

LETTERS TO THE EDITOR

The in vitro response of human internal mammary artery to vasodilators

G. J. Cooper, FRCS(Ed), T. J. Locke, FRCS(Ed)

Department of Cardiothoracic Surgery
Northern General Hospital
Sheffield, England

To the Editor:

Jett and colleagues Go 1 compared the ability of different vasodilators to prevent contraction of segments of human internal mammary artery in vitro. We similarly compared the ability of vasodilators to relax potassium-constricted artery, but we caution against extrapolating the results to the clinical situation.

Thirty-two rings of left internal mammary artery from above the bifurcation were provided by 17 patients. There were no significant differences in preoperative drug treatment between patients. Rings were mounted in an organ bath containing oxygenated, modified Krebs buffer at 37° C. Each ring was set at a resting tension equivalent to that required to stretch the ring to 90% of its internal circumference when distended by a transmural pressure of 100 mm Hg2 and then contracted with potassium 25 mmol/L. Concentration response curves were constructed for nifedipine, sodium nitroprusside, glyceryl trinitrate, and papaverine.

At a concentration of -4 logM units each agent produced almost full relaxation (Fig. 1). However, there were significant differences in the potencies of the four agents (Table I).



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  		Fig. 1. Concentration-response curves of human internal mammary artery to four vasodilators. Each point represents the means of eight observations. PAP, Papaverine; GTN, glyceryl trinitrate; NIF, nifedipine; NIP, sodium nitroprusside.

 

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  		Table I. In vitro sensitivity of human internal mammary artery to fourvasodilators
 
These results contrast with those of Jett and colleagues, Go 1 who found the maximum inhibition of potassium-induced contraction to be 96% with papaverine, 92% with nifedipine, and 55% with sodium nitroprusside. Glyceryl trinitrate was not effective in inhibiting contraction to potassium. Ranked by 50% effective concentration, nifedipine was more potent than sodium nitroprusside, which in turn was more potent than papaverine. In similar experiments, He and coworkers Go 2 found that nifedipine but not glyceryl trinitrate inhibited potassium-induced contraction. In potassium-contracted artery, however, the 50% effective concentration of glyceryl trinitrate was -7.27 logM, papaverine -5.94 logM, and nifedipine about -8 logM. Go 2 Other workers have found that internal mammary artery from patients taking glyceryl trinitrate before operation shows reduced in vitro relaxation to this drug and reduced contraction to phenylephrine and U46619. Go 3

These differences in the in vitro ability of vasodilators to prevent contraction of internal mammary artery or to relax precontracted internal mammary artery are of interest. More relevant, however, if this work is aimed at identifying a clinically useful dilator, is the difference between the in vitro and in vivo responses. In a clinical study, free flow through the internal mammary artery was measured before and after topical application of papaverine (-2.40 logM), glyceryl trinitrate (-2.66 logM), nifedipine (-3.54 logM), and sodium nitroprusside (-2.77 logM). Go 4 Sodium nitroprusside produced a significantly greater increase in flow than did the other agents. Our studies suggest that sodium nitroprusside is a potent agent in vivo, but more important it is of superior potency in the clinical situation.

References

  1. Jett GK, Guyton RA, Hatcher CR Jr, Abel PW. Inhibition of human internal mammary artery contractions: an in vitro study of vasodilators. J THORAC CARDIOVASC SURG 1992;104:977-82.[Abstract]
  2. He GW, Rosenfeldt FL, Buxton BF, Angus JA. Reactivity of isolated human internal mammary artery to constrictor and dilator agents: implications for treatment of internal mammary artery spasm. Circulation 1989;80(3 Pt 1):I141-50.
  3. Du ZY, Buxton BF, Woodman OL. Tolerance to glyceryl trinitrate in isolated human internal mammary arteries. J THORAC CARDIOVASC SURG 1992;104:1280-4.[Abstract]
  4. 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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