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Ann Thorac Surg 2001;71:636-641
© 2001 The Society of Thoracic Surgeons

Original article: cardiovascular

Effects of potassium channel opener aprikalim on the receptor-mediated vasoconstriction in the human internal mammary artery

Ming-Hui Liu, MDa,b, H. Storm Floten, MDa,b, Anthony P. Furnary, MDa,b, Anthony P.C. Yim, MDa,b, Guo-Wei He, MD, PhDa,b

a Cardiovascular Research, Starr Academic Center for Cardiac Surgery, Providence Heart Institute, St. Vincent Hospital, Portland, Oregon, USA
b Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China

Accepted for publication June 3, 2000.

Address reprint requests to Prof. He, Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Block B, 5A, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR, China
e-mail: gwhe{at}cuhk.edu.hk


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Background. Arterial grafts for coronary artery bypass grafting such as the internal mammary artery (IMA) may develop spasm perioperatively. The purpose of this study was to investigate the effects of the potassium channel opener, aprikalim, on the receptor-mediated vasoconstriction in the human IMA in vitro.

Methods. We studied 160 IMA rings taken from coronary artery surgery in organ baths. The interaction between aprikalim and four vasoconstrictors 5-hydroxytryptamine (5-HT), norepinephrine (NE), endothelin-1 (ET-1), and angiotensin II (AII) was investigated in two ways.

Results. Aprikalim relaxed IMA rings precontracted by the vasoconstrictors to 66.40 ± 5.9% for 5-HT (EC50: -6.78 ± 0.26 LogM), 57.40 ± 5.5% for NE (-6.54 ± 0.39 LogM), 81.00 ± 6.7% for ET-1 (-6.58 ± 0.26 LogM), and 93.90 ± 2.5% for AII (-7.80 ± 0.23 LogM). The relaxation in endothelium-denuded rings contracted by AII was similar to that in the endothelium-intact rings. The relaxation was attenuated by glibenclamide (3 µM) in 5-HT or NE-precontracted IMA. Pretreatment with aprikalim at 1 µM depressed AII-induced contraction (33.20 ± 7.5% versus 59.70 ± 7.3%, p < 0.01) but only shifted the curves rightward for 5-HT or NE (EC50 3.1 or 4.3-folds higher, p < 0.05), whereas at 30 µM it also significantly depressed the maximal contraction for 5-HT (35.70 ± 4.9% versus 103.30 ± 9.8%, p < 0.001) and NE (90.60 ± 15.6% versus 125.60 ± 7.9%, p < 0.05). In contrast, aprikalim did not significantly depress the contraction induced by ET-1 (p > 0.05).

Conclusions. We conclude that aprikalim has vasorelaxant effects on IMA and the effect is vasoconstrictor-selective and endothelium-independent. Aprikalim may provide clinically useful vasorelaxant effects in coronary bypass surgery.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
ATP-sensitive potassium channels (KATP) exist in a wide range of cells, particularly in vascular smooth muscle cells, endocrine cells, skeletal muscle cells, myocardial cells, and neurons [1]. It is believed that there are at least two kinds of KATP channels in these cells: the sarcolemmal KATP channels [2] and the mitochondrial KATP channels [3]. Aprikalim, as a potent KATP channel opener, induces smooth muscle dilatation by repolarizing or hyperpolarizing the cell membrane, whereas stimulation of the mitochondrial KATP channels has a potentiation of mimicking ischemic preconditioning and pharmacological cardioprotection [4]. These understandings provide information on the possible application of potassium channel openers (KCOs) in various clinical settings, particularly in the area of cardiovascular disorders.

Although many kinds of vasodilators such as calcium antagonists, ACE-inhibitors, long-lasting nitrates, and phosphodiesterase inhibitors have been extensively used for patients with coronary artery disease, little is known about the vasorelaxation action of KCOs on the human conduit arteries used as coronary bypass grafts. Our previous study [5] has demonstrated that aprikalim has vasorelaxant effects in the human internal mammary artery (IMA) contracted by various vasoconstrictors such as {alpha}1-adrenoceptor agonist phenylephrine, depolarizing agent K+, and thromboxane A2 mimetic U46619. We have found that the relaxant effect of aprikalim in human IMA is greater for {alpha}1-adrenoceptor agonists than for depolarizing agent K+. The effect of aprikalim on the vasoconstriction mediated by other receptors, however, is still unknown. The present study was therefore designed to investigate the effects of aprikalim on the vasoconstriction mediated by a number of receptors in the human IMA in vitro.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
General
One hundred and sixty human IMA segments were collected from 42 patients undergoing coronary artery bypass surgery. There were 34 men and 8 women with a mean age of 63.1 ± 1.9 years. Approval to use discarded IMA tissue was given by the Institutional Review Board of St. Vincent Hospital. The discarded IMA segments were collected and placed in a container with oxygenated physiological solution (Krebs) maintained at 4°C and delivered to the laboratory. The Krebs solution has the following composition (in mM): Na+ 144, K+ 5.9, Ca2+ 2.5, Mg2+ 1.2, Cl- 128.7, HCO3- 25, SO42- 1.2, H2PO4- 1.2, and glucose 11. The solution was aerated with a gas mixture of 95% O2/5% CO2 at 37°C ± 0.1°C.

Organ bath technique
The IMA was placed in a glass dish with oxygenated Krebs solution and the surrounding connective tissue was dissected out. The vessel was cut into 3-mm-long rings and the number of rings taken from each patient varied from two to eight. Artery rings were mounted on two parallel stainless steel wire hooks in a 25-ml glass organ bath containing Krebs solution, maintained at 37 ± 0.1°C and continuously bubbled with 95% O2–5% CO2. The lower wire hook was attached to a micrometer-adjustable support leg and the upper to an isometric force transducer (model FT03, Grass Instruments, Astro-Med, Inc, West Warwick, RI) to record changes in isometric force, which were amplified and recorded on a polygraph chart recorder (model 79, Grass Instruments). After a 60-minute equilibration period, a normalization technique was applied to set the vascular rings at a pressure comparable with that at the in vivo situation. The details of this technique were published previously [6]. Briefly, the rings were stretched up in progressive steps to determine the length-tension curve. A computer iterative fitting program (VESTAND 2.1, Yang-Hui He, Princeton University, NJ) was used to determine the exponential curve, the pressure, and the internal diameter. When the transmural pressure on the rings reached 100 mm Hg, determined from their own length-tension curves, the stretch-up procedure was stopped and the rings were released to 90% of their internal circumference at 100 mm Hg. This degree of the passive tension was then maintained throughout the experiment. After the normalization procedure, the IMA rings were equilibrated for at least 45 minutes.

The endothelium was intentionally preserved by cautiously dissecting and mounting the rings in our study since endothelium plays a modulation role in the contractility of the human IMA. We previously found that this technique allowed the experiment to be carried out with functionally intact endothelium, as determined by the relaxation response to bradykinin in the coronary artery [7] and acetylcholine in the isolated human IMA rings [8].

Protocol
Relaxation
Aprikalim-induced relaxation was studied in IMA rings precontracted with 5-hydroxytryptamine (5-HT, 1 µM, n = 8), norepinephrine (NE, 3 µM, n = 8), angiotensin II (AII, 3 nM, n = 8), and endothelin-1 (ET-1, 10 nM, n = 8). Another group of eight rings contracted by ET-1 (10 nM) was studied as the time control, because in a previous study [9], we found that the contraction induced by ET-1 in the human IMA was not sustained. Relaxant responses of aprikalim were also observed in a group of eight endothelium-denuded rings contracted by AII. The concentrations of these vasoconstrictors were determined from the logistic curve fitting equation. These concentrations are equal to EC50-EC80 for the 5-HT, NE, AII, and ET-1-induced contraction in the human IMA from previous studies [5, 6, 9]. Cumulative concentration-relaxation curves to aprikalim were then established. Only one concentration-relaxation curve was obtained from each IMA ring. From eight rings (taken from 8 patients), a mean concentration-relaxation curve was constructed. The concentration-relaxation curve to aprikalim was also established in rings treated with glibenclamide, a KATP blocker, for 30 minutes before the concentration-relaxation curve was induced in either 5-HT or NE-contracted human IMA rings (n = 8 in each group). The relaxation was expressed as a percentage of the agonist-induced precontraction.

Role of endothelium on the aprikalim-induced relaxation
To study the possible role of endothelium on the aprikalim-induced relaxation, in eight IMA rings, the endothelium was carefully removed by mechanically rubbing the intima of the ring as described before [6, 7]. The rings were then contracted with AII (3 nM). Cumulative concentration-relaxation curves for aprikalim were then established in these rings and compared with the relaxation in endothelium-intact IMA rings.

Depression of contraction by pretreatment with aprikalim
After equilibration of IMA rings for at least 45 minutes, 100 mM potassium chloride (K+) was added into the organ bath and the contraction force was recorded. The ring was repeatedly washed with Krebs solution to restore the baseline. To determine whether pretreatment with aprikalim would alter the contraction response to the vasoconstrictors (5-HT, NE, AII, and ET-1), cumulative concentration-contraction curves were constructed in IMA rings. These rings were equilibrated for 10 minutes with -6 or -4.5 LogM (1 or 3 µM) aprikalim. The time for the pretreatment was decided by the average time to reach a plateau for each dose of aprikalim in the relaxation experiment from the present study. Cumulative concentration-contraction curve was established in an IMA ring taken from the same patient without pretreatment of aprikalim as control. The contraction was expressed as percentage of the contraction force induced by 100 mM K+.

Data analysis
The sensitivity of both vasoconstrictors and vasodilators was expressed as EC50, the effective concentration causing 50% of maximal contraction or relaxation. The EC50 was determined from each concentration-contraction (or relaxation) curve by a logistic curve-fitting equation: E = MAp/(Ap + Kp), where E is response, M is maximal contraction (or relaxation), A is concentration, K is EC50 concentration, and p is the slope parameter. A computerized program (Baker Medical Research Institute, Melbourne, Australia) was used for the curve fitting.

All values were expressed as mean ± SEM with 95% confidence intervals where appropriate. Statistical comparisons of the percentage relaxation or contraction under different treatments were performed by 2-way ANOVA with repeated measures, followed by the Bonferroni test to detect individual differences. Percent maximal relaxation, percent maximal contraction, and EC50 values were compared by one-way ANOVA followed by Bonferroni test; p < 0.05 was considered statistically significant.

Materials
Drugs used in this study and their sources were: (-)norepinephrine bitartrate, 5-hydroxytryptamine, and angiotensin II (Sigma Chemical company, St. Louis, MO); and endothelin-1 (Peptides International, Louisville, KY). Stock solutions of AII and ET-1 were held frozen until required. Aprikalim is a generous gift provided by Rhone-Poulenc Rorer Recherche-Developpement, Vitry Sur Seine Cedex, France.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
Resting parameters of IMA rings
The internal diameter of the 160 IMA rings at an equivalent transmural pressure of 100 mm Hg (D100) was 2.7 ± 0.1 mm as determined from the normalization procedure. When the IMA rings were set at a resting diameter of 0.9 x D100, the equivalent transmural pressure was 75.8 ± 0.6 mm Hg, and the resting force was 4.2 ± 0.2 g.

Relaxant effect of aprikalim on IMA rings contracted by 5-HT, NE, ET-1, or AII
Aprikalim caused nearly full relaxation in AII-precontracted IMA rings and it also relaxed IMA rings precontracted by other vasoconstrictors. The maximal relaxation and EC50 values of aprikalim in IMA rings precontracted by various vasoconstrictors are shown in Table 1. The EC50 values indicated that aprikalim was more sensitive to relax the vasoconstriction induced by AII than that by 5-HT, NE, or ET-1 (p <= 0.02, 1-way ANOVA). Aprikalim-induced relaxation on AII was significantly greater than that on 5-HT, NE, and ET-1 (p < 0.01). In addition, aprikalim elicited more relaxation in IMA rings precontracted by ET-1 than by NE (p < 0.05, 2-way ANOVA, Fig 1A). In endothelium-denuded rings contracted by AII, aprikalim-induced relaxation was not significantly different when comparing with that in the endothelium-intact IMA rings (Fig 1B).


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  		Table 1. Maximal Relaxation and EC50 Values for Aprikalim in Human Internal Mammary Artery Rings Precontracted by the Four Vasoconstrictors

 


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  		Fig 1. (A) Mean concentration (LogM)-relaxation (percent reversal of the agonist-induced contraction) curves for aprikalim in human internal mammary artery precontracted by norepinephrine (NE), 5-hydroxytryptamine (5-HT), endothelin-1 (ET), or angiotensin II (AII). (B) Aprikalim induced relaxation in endothelium-intact (E+) or endothelium-denuded (E-) IMA rings contracted by AII. N = 8 in each group. Values are expressed as mean ± standard error of the mean. *p < 0.01, compared with angiotensin II, {dagger}p = 0.04 versus endothelin-1 (2-way ANOVA).

 
In IMA rings precontracted by ET-1, although the contraction was not sustained, it was stable enough for testing the effect of aprikalim. The difference between the aprikalim-induced relaxation and the time control was significant (p = 0.00001, 2-way ANOVA, Fig 2).



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  		Fig 2. Mean concentration (LogM)-relaxation (percent reversal of endothelin-1-induced contraction) curves for aprikalim (APK) in human internal mammary artery. N = 8 in each group. Values are expressed as mean ± standard error of the mean. *p = 0.0001, compared with the control group (2-way ANOVA).

 
In glibenclamide-pretreated IMA rings, aprikalim evoked significantly less relaxation than that in IMAs pretreated with vehicle. In the 5-HT-induced contraction (Fig 3A), the maximal relaxation was 33.9% ± 4.8% (95% CI, 24.2% to 43.5%) (p = 0.0005) and the EC50 was shifted 36.3-fold higher (p = 0.0003). In IMA rings contracted by NE (Fig 3B), glibenclamide also significantly reduced the relaxation induced by aprikalim. The maximal relaxation was 31.5% ± 6.2% (95% CI, 16.7% to 46.3%) (p = 0.008) and the EC50 was 12.9-fold higher (p = 0.03).



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  		Fig 3. Mean concentration (LogM)-relaxation (percent reversal of the agonist-induced contraction) curves for aprikalim in human internal mammary artery precontracted by 5-hydroxytryptamine (A) or norepinephrine (B). Glibenclamide (GBC, 3 µM) or vehicle (0.3% ethanol, Control) were added 30 minutes before the contraction started. N = 8 in each group. Values are expressed as mean ± standard error of the mean. *p < 0.05 versus control (2-way ANOVA).

 
Depression of contraction by pretreatment with aprikalim on IMA rings
The percentage maximal contraction and EC50 values for various vasoconstrictors in IMA rings pretreated with or without aprikalim incubation were listed in Table 2. The mean concentration-contraction curves to these vasoconstrictors were depicted in Figure 4. In comparison with the control rings, pretreatment of IMA with aprikalim at the concentration of 1 µm for 10 minutes did not significantly depress the magnitude of 5-HT or NE-induced maximal contraction, but shifted the EC50 3.1 or 4.3-fold higher (p < 0.05). Pretreatment of IMA with aprikalim for 10 minutes at the concentration of 30 µm significantly depressed the magnitude of the 5-HT or NE-induced contraction (p < 0.05) and shifted the EC50 5.0 or 13.8-fold higher (p < 0.05).


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  		Table 2. Maximal Contraction and EC50 Values for the Vasoconstrictors and Contraction Forces to 100 mM Potassium Chloride in Human Internal Mammary Artery Rings With or Without Incubation of Aprikalim

 


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  		Fig 4. Mean concentration (LogM)-contraction (percentage of the contraction induced by 100 mM K+) curves to 5-hydroxytryptamine (A), norepinephrine (B), angiotensin II (C), and endothelin-1 (D) in control or aprikalim-treated IMA rings. Aprikalim -6 log M (APK [-6]) or -4.5 log M (APK [-4.5]) was added 10 minutes before the contraction started. N = 8 in each group. Values are expressed as mean ± standard error of the mean. *p < 0.05, versus control (2-way ANOVA).

 
In comparison with control rings, pretreatment of IMA with aprikalim for 10 minutes at the concentrations of 1 or 30 µM significantly depressed the magnitude of AII-evoked contraction. However, the EC50 values in AII-induced contraction did not significantly shift in IMA rings pretreated with aprikalim.

In contrast, aprikalim at 1 or 30 µm concentration did not demonstrate significant depression effects on ET-1-induced contraction in IMA, and did not significantly shift the EC50 values either, in comparing with the control rings.


   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
In this study, we have found in the human IMA, the most commonly used arterial graft for coronary artery bypass surgery, that: 1) aprikalim has vasorelaxant effect on various receptor-mediated vasoconstriction, and the effect is vasoconstrictor-selective and endothelium-independent; and 2) the potency of aprikalim on spasm prevention may also be spasmogen-selective, and the effect may be more significant against 5-HT, NE, or AII than against ET-1.

The IMA is widely used as a conduit for coronary artery surgery. Numerous clinical studies have demonstrated the superiority of the IMA regarding the long-term patency compared with the saphenous vein. However, vasospasm sometimes occurs during IMA grafting and this may limit graft function by reducing luminal blood flow.

The mechanism of graft spasm is still unclear and may include mechanical, physical, and pharmacological stimulations. Vasospasm may result from endothelial injury during surgical preparation, which initiates the abnormal platelet-endothelium interaction. In addition, elevated plasma levels of NE, 5-HT, AII, and ET-1 have been measured during or after coronary artery bypass grafting [10, 11]. These factors, either alone or in combination, may have implications in the genesis of graft spasm mediated by different sarcolemmal receptor agonists.

Further, reversal of vasospasm is often challenging and the most effective therapy for IMA spasm is still in controversy. Nitrovasodilators, calcium antagonists, papaverine, or other vasodilators are currently used either systemically or topically [12–15]. However, in some cases, the above vasodilators may not provide the expected benefit in prevention and treatment of graft spasm due to the complexity of the mechanism of spasm. Moreover, some unwanted side effects have been associated with these drugs. For instance, the occurrence of rapid tolerance to nitroglycerin can abolish its therapeutic effect [15]. The negative inotropic effect of nifedipine is not desirable after coronary artery bypass grafting. The lack of tissue specificities of the available vasodilators can cause coronary steal [16]. In this respect, KCOs such as aprikalim may offer some advantages over classical vasodilators because of their relative selectivity for coronary blood flow and their potential cardioprotective effect via opening of mitochondrial KATP channels.

In the present study, we aimed to test the effectiveness of aprikalim in the reversal and prevention of arterial graft spasm in vitro. For this purpose, we selected four receptor-mediated vasoconstrictors, namely, 5-HT, NE, ET-1, and AII to mimic the graft spasm. These agents produce vasoconstrictions at least partially depending on Ca++ influx or Ca++ mobilization from intracellular stores by interfering with the synthesis of inositol triphosphate (IP3) and consequently lead to an increase in intracellular free Ca++ level. Conversely, aprikalim, by causing hyperpolarization, prevents Ca++ entry through Ca++ channels or inhibits agonist-stimulated IP3 synthesis and, thus, reverses the contraction due to a decrease in intracellalar free Ca++ concentration [17].

In the present study, aprikalim relaxed the contraction induced by all of the four spasmogens to a certain extent. The maximal relaxation was greater for AII than for 5-HT and NE (p < 0.05). In addition, there was a significant difference (p = 0.01) with regard to the EC50. Compared with that for AII, the EC50 was 10.4-fold higher for 5-HT, 18.1-fold higher for NE, and 16.9-fold higher for ET-1 (p < 0.05).

The selectivity of aprikalim is also shown in depression experiments. The most significant depression effect was seen in AII-induced contraction. Incubation with aprikalim at either 1 or 30 µM significantly inhibited the contraction induced by AII (Fig 4C). In contrast, aprikalim did not affect the contraction induced by ET-1 (Fig 4D).

In IMA rings, the relaxation to each dose of aprikalim was completed in approximately 10 minutes. Our previous study in the IMA demonstrated that the time to reach a plateau for glyceryl trinitrate was 3 minutes, whereas for nifedipine, it was 25 minutes [6]. Our results suggested that aprikalim is a more rapid relaxant agent than calcium antagonists are. This may have a clinical value to release graft spasm.

Recent studies reported that KCOs can fully reverse ET-1-induced contractions in the isolated vessels [18] and the vasoconstriction in human subjects in vivo [19]. In the present study, aprikalim evoked significant relaxation in ET-1-precontracted IMA but had little effect on the prevention of ET-1-induced contraction. This result is consistent with that from others [20], as well as our previous studies [9], showing that it is more effective for KCOs and other vasodilators to reverse than to prevent the contraction induced by ET-1 [10, 20]. As described by Maurice and colleagues [21], there may be critical differences in the state of the vascular smooth muscle, before and after induction of contraction, that affect the responses to vasodilator substances. Increases in intracellular Ca2+ concentration and the phosphorylation of myosin light chain are important in the contraction of vascular smooth muscle, and therefore, compounds that block these processes will inhibit contraction. However, relaxation of smooth muscle that involves reversal of a latch state is less dependent on the inhibition of Ca2+ mobilization or on dephosphorylation of myosin [22]. This may explain the discrepancy between the aprikalim-induced relaxation in the ET-1-precontracted vessels and its limited inhibitory effect before applied to the contraction.

KCOs have been proven to have an effect of myocardial protection with similarity to "ischemic preconditioning." Recent studies show that mitochondrial KATP channels may serve as effectors of cardioprotection by KATP channel openers [23]. It is suggested that aprikalim may have a potential advantage for myocardial protection against ischemia and as cardioplegia during open-heart surgery [24, 25]. Combining with the vasorelaxant effect on the graft, KCOs such as aprikalim may have clinical implications for patients undergoing coronary artery bypass surgery.

In conclusion, the present study suggests that aprikalim has a vasorelaxant effect in human IMA contracted by a variety of receptor agonists, and its vasorelaxant effect is vasoconstrictor-selective and endothelium-independent. Pretreatment with aprikalim may prevent graft spasm to a certain degree. KCOs such as aprikalim may provide clinically useful vasorelaxant effects in coronary artery bypass surgery.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
This study was supported by St. Vincent Medical Foundation, Portland, OR and Hong Kong Research Grants Council grants (CUHK7280/97M and CUHK7246/99M). The technical assistance of the surgical team and Kay Metsger and other nurses in the Cardiac Operating Room, St. Vincent Hospital, are also gratefully acknowledged. Dr Liu is a Starr-He International Postdoctoral Fellow.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Lazdunski M. ATP-sensitive potassium channels: an overview. J Cardiovasc Pharmacol 1994;24:S1-S5.
  2. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature 1983;305:147-148.[Medline]
  3. Inoue I., Nagase H., Kishi K., Higuti T. ATP-sensitive K+ channel in the mitochondrial inner membrane. Nature 1991;352:244-247.[Medline]
  4. Sato T., O’Rourke B., Marbàn E. Modulation of mitochondrial ATP-dependent K+ channels by protein kinase C. Circ Res 1998;83:110-114.[Abstract/Free Full Text]
  5. He G.W., Yang C.Q. Inhibition of vasoconstriction by potassium channel opener aprikalim in human conduit arteries used as bypass grafts. Br J Clin Pharmacol 1997;44:353-359.[Medline]
  6. He G.W., Rosenfeldt F.L., Buxton B.F., Angus J.A. Reactivity of human isolated internal mammary artery to constrictor and dilator agents: implications for treatment of internal mammary artery spasm. Circulation 1989;80:I141-I150.
  7. He G.W., Yang C.Q. Hyperkalemia alters EDHF-mediated hyperpolarization and relaxation in coronary arteries. Am J Physiol 1996;271:H760-H767.[Abstract/Free Full Text]
  8. He G.W., Yang C.Q. Effects of thromboxane A2 antagonist GR32191B on prostanoid and nonprostanoid receptors in the human internal mammary artery. J Cardiovasc Pharmacol 1995;26:13-19.[Medline]
  9. He G.W., Yang C.Q., Mack M.J., Acuff T.E., Ryan W.H., Starr A. Interaction between endothelin and vasodilators in the human internal mammary artery. Br J Clin Pharmacol 1994;38:505-512.[Medline]
  10. He G.W., Yang C.Q., Starr A. Overview of the nature of vasoconstriction in arterial grafts for coronary operations. Ann Thorac Surg 1995;59:676-683.[Abstract/Free Full Text]
  11. Downing S.W., Edmunds L.H. Release of vasoactive substances during cardiopulmonary bypass. Ann Thorac Surg 1992;54:1236-1243.[Abstract]
  12. Izzat M.B., West R.R., Ragoonanan C., Angelini G.D. Effect of systemic vasodilators on internal mammary artery flow. J Thorac Cardiovasc Surg 1994;108:82-85.[Abstract/Free Full Text]
  13. Sasson L., Cohen A.J., Hauptman E., Schachner A. Effects of topical vasodilators on internal mammary arteries. Ann Thorac Surg 1995;59:494-496.[Abstract/Free Full Text]
  14. He G.W., Acuff T.A., Ryan W., et al. Inhibitory effects of calcium antagonists on {alpha}-adrenoceptor-mediated contraction in the human internal mammary artery. Br J Clin Pharmacol 1994;37:173-179.[Medline]
  15. He G.W., Yang C.Q. Comparison of nitroprusside and nitroglycerin in inhibition of angiotensin II and other vasoconstrictor-mediated contraction in human coronary bypass conduits. Br J Clin Pharmacol 1997;44:361-367.[Medline]
  16. Anderson K.E. Clinical pharmacology of potassium channel openers. Pharmacol Toxicol 1992;264:285-293.
  17. Quast U. Do the K+ channel openers relax smooth muscle by opening K+ channels?. Trends Pharmacol Sci 1993;14:332-337.[Medline]
  18. Haynes W.G., Webb D.J. Venoconstriction to ET-1 in humans: role of calcium and potassium channels. Am J Physiol 1993;265:H1676-H1681.[Abstract/Free Full Text]
  19. Borg C., Mondot S., Cavero I. Nicorandil: differential contribution of K+ channel opening and guanylate cyclase stimulation to its vasorelaxant effects on various endothelin-1-contracted arterial preparations. Comparison to aprikalim (RP 52891) and nitroglycerin. J Pharmacol Exp Ther 1991;259:526-534.[Abstract/Free Full Text]
  20. Akar F., Uydes-Dogan B.S., Tufan H., Aslamaci S., Köksoy C., Kanzik I. The comparison of the responsiveness of human isolated internal mammary and gastroepiploic arteries to levcromakalim: an alternative approach to the management of graft spasm. Br J Clin Pharmacol 1997;44:49-56.[Medline]
  21. Maurice D.H., Crankshaw D., Haslam R.J. Synergistic actions of nitrovasodilators and isoprenaline on rat aortic smooth muscle. Eur J Pharmacol 1991;192:235-242.[Medline]
  22. Dillon P.F., Aksoy M.O., Driska S.P., Murphy R.A. Myosin phosphorylation and the cross-bridge cycle in arterial smooth muscle. Science 1981;221:495-497.
  23. Liu Y.G., Sato T., O’Rourke B., Marban E. Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?. Circulation 1998;97:2463-2469.[Abstract/Free Full Text]
  24. He G.-W., Yang C.-Q. Superiority of hyperpolarizing to depolarizing cardioplegia in protection of coronary endothelial function. J Thorac Cardiovasc Surg 1997;114:643-650.[Abstract/Free Full Text]
  25. He G.-W. Potassium channel opener in cardioplegia may restore coronary endothelial function. Ann Thorac Surg 1998;66:1318-1322.[Abstract/Free Full Text]



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H. Storm Floten
Anthony P. Furnary
Anthony P.C. Yim
Guo-Wei He
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