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Ann Thorac Surg 2005;80:1803-1811
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Hypoxia-Reoxygenation, St. Thomas Cardioplegic Solution, and Nicorandil on Endothelium-derived Hyperpolarizing Factor in Coronary Microarteries

^a Department of Surgery, The Chinese University of Hong Kong, Hong Kong
^b Department of Surgery, Providence Heart Institute, Albert Starr Academic Center, Oregon Health and Science University, Portland, Oregon; and Wuhan Heart Institute, The Central Hospital of Wuhan, Wuhan, China

Accepted for publication April 25, 2005.

^_* Address correspondence to Prof He, Department of Surgery, The Chinese University of Hong Kong, Block B, 5A, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR, China (Email: gwhe{at}cuhk.edu.hk).

	Abstract

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BACKGROUND: We investigated effects of hypoxia-reoxygenation (H-R) with and without St. Thomas solution under clinically relevant temperatures and effects of nicorandil on endothelium-derived hyperpolarizing factor (EDHF)–mediated relaxation in porcine coronary microarteries.

METHODS: In a myograph, rings of porcine microarteries (diameter 200 to 450 µm) were subjected to hypoxia (PO₂ <5 mm Hg) for 30 minutes in Krebs at 37°C, or for 60 minutes in Krebs and St. Thomas solution with or without nicorandil (0.1 µM) at 37°C or 4°C, followed by 30-minute reoxygenation. The EDHF-mediated relaxation by bradykinin (–10 to approximately –6 logM) with inhibitors of nitric oxide and prostacyclin was studied.

RESULTS: The maximal EDHF-mediated relaxation was reduced after hypoxia for 30 minutes (59.9%% ± 1.6% versus 81.2%% ± 3.5%, p < 0.05) or 60 minutes (44.4% ± 6.0% versus 82.7% ± 7.4%, p < 0.001) in Krebs or St. Thomas (28.9% ± 1.8% versus 78.1% ± 3.0%, p < 0.001) at 37°C and at 4°C (Krebs: 49.3% ± 3.0%, p < 0.001; ST: 43.1% ± 2.6%, p < 0.001) and it was less in St. Thomas solution at 37°C than at 4°C (p < 0.001). The reduced relaxation was recovered by nicorandil (Krebs at 37°C: 81.7% ± 3.4%, p < 0.001; St. Thomas at 37°C: 71.0% ± 7.9%, p <0.001; St. Thomas at 4°C: 85.3% ± 3.3%, p < 0.001).

CONCLUSIONS: We conclude that (1) H-R impairs EDHF-mediated relaxation in the coronary microarteries with more injury during prolonged H-R, and this can be partially eliminated by St. Thomas at 4°C but not at 37°C; and (2) as an additive, nicorandil may fully restore EDHF-mediated endothelial function after prolonged H-R.

	Introduction

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Ischemia-reperfusion (or hypoxia-reoxygenation [H-R]) injury remains the major cause of cardiac dysfunction in open heart surgery including heart transplantation. Cardioplegia was designed to protect the heart from ischemia-reperfusion injury. Although blood cardioplegia is popular in current cardiac surgery, St. Thomas cardioplegic solution is still used either as crystalloid cardioplegia or the basis of blood cardioplegia in combination with hypothermia or normothermia. This solution has also been used in donor heart preservation under hypothermia for transplantation and has been demonstrated to be effective in protecting the myocardium against ischemia [1]. Hyperkalemia (potassium at high concentration), as the key component, contributes to cardiac protection by depolarizing the myocyte membrane and causing asystole, which avoids the depletion of the high-energy phosphate pool by ischemia and conserves the myocardial energy reserves [2]. However, studies also showed that cardioplegia damages coronary endothelial function [3, 4]. Our previous studies further demonstrated that in both large and microcoronary arteries, endothelium-derived hyperpolarizing factor (EDHF)–mediated function is impaired by hyperkalemic solutions such as St. Thomas [5–8].

In recent years, studies have been focused on H-R injury to the coronary circulation [9, 10]. It has been demonstrated that both nitric oxide (NO) [11, 12] and EDHF [13, 14]–mediated relaxations may be affected by H-R injury in coronary arteries.

Endothelium plays an important role in regulating the activity of the underlying vascular smooth muscle. Endothelium-dependent relaxation is known to be due to a variety of different endothelium-derived relaxing factors, including NO [15, 16], prostacyclin [17], and EDHF [18–20]. It has been demonstrated that EDHF plays a role in blood flow homeostasis in both conduit and resistance arteries under the physiologic states, and may be a crucial compensatory or reserve mechanism for the maintenance of nutritive organ blood flow after inhibition or impairment of the NO/prostacyclin pathway, particularly in the coronary microarteries [19, 20]. Endothelium-derived hyperpolarizing factor induces vascular smooth muscle relaxation by hyperpolarization of the smooth muscle cell [18, 19], which may involve potassium (K⁺) channels, particularly Ca²⁺-activated K⁺ channels [21, 22]. Adenosine triphosphate (ATP)-sensitive potassium channel is expressed in vascular smooth muscle and endothelial cells. Nicorandil, a hybrid compound of an ATP-sensitive potassium channel opener and a NO donor, has been reported to preserve microvascular integrity in patients with reperfused myocardial infarction [23], and it has been shown to be beneficial to the coronary function from our laboratory [24]. However, it remains unknown whether it has the protective effect on the EDHF-mediated function in coronary microarteries under H-R. Further, the effect of nicorandil as an additive to St. Thomas on EDHF-mediated function under H-R has not been studied yet.

The present study was therefore designed to examine the effects of H-R with or without St. Thomas solution under normothermia or hypothermia and the possible protective effect of nicorandil on EDHF-mediated relaxation in porcine coronary microarteries.

	Material and Methods

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All experiments were in accordance with institutional guidelines. This investigation conformed to the Guide for the Care and Use of Laboratory Animals, published by the National Institutes of Health (NIH Publication No. 85-23, revised 1996).

Preparation and Mounting of Microvessels
Fresh porcine hearts from hogs (either sex) weighing about 30 kg, collected from a local slaughterhouse, were placed in a container filled with cold (4°C) Krebs solution and immediately transferred to the laboratory. Upon receipt of the heart, intramyocardial coronary microarteries (usually the tertiary branches of the left anterior descending artery) in diameter of 200 to 450 µm were carefully dissected and removed under a microscope, with care taken to protect the endothelium. The vessels were cleaned of fat and connective tissue and cut into cylindrical rings of 2-mm length under a microscope. The rings were mounted on two parallel stainless steel wires (40 µm in diameter) in a four-channel myograph (Model 610M; J.P.Trading, Aarhus, Denmark) [25, 26]. The myograph was modified by our workshop to have a well-sealed plastic cover that is specially designed for hypoxia experiments. A calibrated force transducer was used to measure the force, with the output shown on a computer screen and printed in a printer.

Normalization
All rings were equilibrated for 45 minutes to reach stability of the vessel before and after normalization in the myograph. For normalization, the artery rings were progressively stretched until the passive transmural pressure reached 100 mm Hg, and then the pressure was immediately released. The details of the normalization are reported in previous studies [25–28].

Hypoxia
During normalization or relaxation studies, the solution was aerated with a gas mixture of 95% O₂ and 5% CO₂ (normoxia, the partial pressure of oxygen [PO₂] was more than 200 mm Hg). Hypoxic condition was induced by switching bubbling gas from 95% O₂ and 5% CO₂ to 95% N₂ and 5% CO₂ (hypoxia, PO₂ < 5 mm Hg) in the plastic cover-sealed chamber. The PO₂ was measured by an Oxygen Meter (Model 781; Strathkelvin Instrument, Glasgow, Scotland).

Experimental Protocol
Bradykinin-induced, EDHF-mediated relaxation
The nitric oxide synthase inhibitor N^G-nitro-L-arginine (_L-NNA [300 µM]), oxyhemoglobin (HbO [20 µM]), a NO scavenger, and indomethacin (7 µM), a cycloxygenase inhibitor, were added into the chamber for 30 minutes; U₄₆₆₁₉ (a thromboxane A₂ mimetic; 10 nM) was then added to contract the rings. When the contraction reached a stable plateau (usually 15 minutes), cumulative concentration-relaxation curves to BK (-10 to -6 log M) were established. From each group of rings, a mean concentration-relaxation curve was constructed. In pilot experiments under normalization, after a wash procedure with Krebs solution and equilibrium for a certain period, the BK-induced EDHF-mediated relaxation in U₄₆₆₁₉-precontraction remained unchanged.

Effect of H-R on EDHF-mediated relaxation
Group IA: 30-minute hypoxia, followed by 30-minute reoxygenation in Krebs solution at 37°C. The rings were incubated in Krebs solution at 37°C and subjected to hypoxia (PO₂ < 5 mm Hg) for 30 minutes followed by 30-minute reoxygenation (n = 6). Before (as the control) and after H-R, the EDHF-mediated relaxation was induced by BK. In group IB, 60-minute hypoxia was followed by 30-minute reoxygenation in Krebs solution at 37°C. The protocol was similar as in group IA, except that the hypoxia was prolonged to 60 minutes.

Combined effect of H-R and St. Thomas cardioplegic solution on EDHF-mediated relaxation
For group IIA, 60-minute hypoxia in St. Thomas solution was followed by 30-minute reoxygenation at 37°C. The rings were incubated in Krebs solution (as the control) at 37°C for 30 minutes and the EDHF-mediated relaxation was induced by BK. The rings were washed with Krebs solution and then incubated in St. Thomas at 37°C, subjected to hypoxia for 60 minutes followed by 30-minute reoxygenation (n = 6). The EDHF-mediated relaxation was then induced by BK again. For group IIB, 60-minute hypoxia in St. Thomas solution was followed by 30-minute reoxygenation at 4°C. Two rings from the same microartery were allocated into two groups. One was incubated in St. Thomas and the other in Krebs (as the control) at 4°C for 60-minute hypoxia, followed by 30-minute reoxygenation at 37°C. The EDHF-mediated relaxation to BK was established.

Effect of nicorandil on EDHF-mediated relaxation
For group IIIA, 60-minute hypoxia with nicorandil added into Krebs was followed by 30-minute reoxygenation at 37°C. The rings were incubated in Krebs solution with addition of nicorandil (0.1 µM) at 37°C and subjected to hypoxia for 60 minutes. The solution was then repeatedly washed with Krebs solution and reoxygenated at 37°C for 30 minutes (n = 6). Before (as the control) and after H-R, the EDHF-mediated relaxation to BK was induced. For group IIIB, 60-minute hypoxia with nicorandil added into St. Thomas at 37°C was followed by 30-minute reoxygenation at 37°C. The rings were incubated in Krebs solution (control) at 37°C for 30 minutes and the EDHF-mediated relaxation to BK was induced. The rings were then washed with Krebs solution and subjected to 60-minute hypoxia with nicorandil (0.1 µM) added to St. Thomas solution. The solution was then repeatedly washed with Krebs solution and reoxygenated at 37°C for 30 minutes (n = 6). The EDHF-mediated relaxation was induced by BK again. For group IIIC, 60-minute hypoxia with nicorandil added into St. Thomas at 4°C was followed by 30-minute reoxygenation at 37°C. The protocol was similar as in group IIIB, except that the microarteries were incubated in nicorandil added St. Thomas at 4°C.

The Krebs solution had the following composition (in mM): Na⁺ 144, K⁺ 5.9, Ca²⁺ 2.5, Mg²⁺ 1.2, Cl^- 128.7, HCO₃ ^- 25, SO₄ ^2- 1.2, H₂PO₄ ^- 1.2, and glucose 11. The St. Thomas solution (David Bull Laboratory, Mulgrave, Victoria, Australia) has the following composition (in mM): Na⁺ 138, K⁺ 20, Ca²⁺ 2.7, Mg²⁺ 16, Cl^- 157, HCO₃ ^- 8, lactate 28, and procaine 1. The osmolarity is 370. The pH was 7.54 ± 0.07 in St. Thomas solution and 7.56 ± 0.08 in Krebs at 4°C. After 60 minutes of H-R, it reduced to 7.22 ± 0.08 (p = 0.02) and 7.40 ± 0.05 (p = 0.03; p = 0.18 between the two groups).

Data Analysis
Relaxation is expressed as the percentage decrease of the U₄₆₆₁₉-induced contraction. Mean maximal relaxation for each group was calculated from the maximal relaxation of different rings induced by bradykinin. The effective concentration of bradykinin that caused 50% of maximal relaxation was defined as EC₅₀. The EC₅₀ was determined from each concentration-relaxation curve by a logistic, curve-fitting equation: E = MA^P/ (A^P + K^P), where E is response, M is maximal relaxation, A is concentration, K is EC₅₀ concentration, and p is the slope parameter. From this fitted equation, the mean EC₅₀ ± SEM was calculated for each group.

Statistical Analysis
All statistical analysis was performed with SPSS9.0 software (SPSS, Chicago, Illinois). Data are expressed as mean ± SEM and were analyzed with paired t test, unpaired t test, or analysis of variance (ANOVA) followed by Scheffé F test when appropriate. Values of p less than 0.05 were considered significant.

Drugs
Drugs used and their sources are as follows: bradykinin, _L-NNA, indomethacin, HbO (Sigma, St. Louis, Missouri); nicorandil (Fujigotemba Research Laboratories, Chugai Pharmaceutical Co., Komakado, Gotemba, Japan), and U₄₆₆₁₉ (Cayman Chemical, Ann Arbor, Michigan). The _L-NNA (dissolved in distilled water) and indomethacin (dissolved in ethanol) were stored at 4°C. The solutions of U₄₆₆₁₉, HbO, nicorandil, and bradykinin were held frozen until needed. The St. Thomas solution was purchased from David Bull Laboratories (Mulgrave, Victoria, Australia).

	Results

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Resting Force
There were no significant differences among the arteries incubated with Krebs and St. Thomas solution with or without nicorandil either at 37°C or at 4°C for H-R (p > 0.05).

Precontraction Induced by U₄₆₆₁₉
The concentration of U₄₆₆₁₉ varied from -8 log M to -7 log M to maintain a similar stable contraction force between the control and H-R condition in each group (p > 0.05).

Partial Pressure of Oxygen in Hypoxia
The normal PO₂ (greater than 200 mm Hg) was quickly lowered to 30 mm Hg in 5 minutes and further lowered to less than 5 mm Hg in another 10 minutes and maintained a low level throughout the experiment. In 30-minute hypoxia group, the PO2 was 4.6 ± 0.3 mm Hg and in 60-minute hypoxia group, it was 2.7 ± 0.2 mm Hg (Fig 1).

View larger version (15K): [in this window] [in a new window]   Fig 1. Concentration-relaxation curves for bradykinin in the U46619 (10 nM) precontracted microarteries (see Methods) with (open circles) and without (control, solid circles) indomethacin (7 µM), NG-nitro-L-arginine (300 µM), and oxyhemoglobin (20 µM) in Krebs solution. Data are shown as mean ± SEM. **p less than 0.01 compared with the control (n = 6; two-way ANOVA).

EDHF-Mediated Relaxation After H-R in Krebs Solution at 37°C
Group IA
After exposure to hypoxia for 30 minutes in Krebs solution at 37°C followed by 30-minute reoxygenation, the BK-induced maximal relaxation was significantly reduced (81.2% ± 3.5% versus 59.9% ± 1.6%, p < 0.001; Table 1, Figs 2A and 3A), although there was no change on the EC₅₀ (Table 2).

View larger version (14K): [in this window] [in a new window]   Fig 2. Concentration-relaxation curves for bradykinin in the U46619 (10 nM) precontracted microarteries (see Methods) with indomethacin (7 µM), NG-nitro-L-arginine (300 µM), and oxyhemoglobin (20 µM). (A) Group IA, before (control, solid circles) and after (open circles) 30-minute hypoxia followed by 30-minute reoxygenation in Krebs solution at 37°C. (B) Group IB, before (control, solid circles) and after (open circles) 60-minute hypoxia followed by 30-minute reoxygenation in Krebs solution at 37°C. Data are shown as mean ± SEM. **p less than 0.01 compared with the control (n = 6, two-way ANOVA).

View larger version (17K): [in this window] [in a new window]   Fig 3. Original tracings of bradykinin (-10 to -6 log M) induced relaxation in coronary microarteries precontracted by U46619 (U [10 nM]) with indomethacin (I [7 µM]), NG-nitro-L-arginine (L [300 µM]), and oxyhemoglobin (Hb [20 µM]). (A) Group IA, before (control) and after 30-minute hypoxia (H) followed by 30-minute reoxygenation (R) in Krebs solution at 37°C. (B) Group IB, before (control) and after 60-minute hypoxia (H) followed by 30-minute reoxygenation (R) in Krebs solution at 37°C. (min = minutes.)

EDHF-Mediated Relaxation After H-R in ST at Different Temperatures
Group IIA
Exposure to St. Thomas solution at 37°C for 60-minute hypoxia significantly decreased EDHF-mediated relaxation from 78.1% ± 3.0% to 28.9% ± 1.8% (Table 1, Fig 4A) with unchanged EC₅₀ (Table 2). Comparing St. Thomas with Krebs solution, the relaxation was significantly less after exposure to St. Thomas (28.9% ± 1.8% versus 44.4% ± 6.0%, p = 0.03; Table 1).

View larger version (14K): [in this window] [in a new window]   Fig 4. Concentration-relaxation curves for bradykinin in the U46619 (10 nM) precontracted microarteries (see Methods) with indomethacin (7 µM), NG-nitro-L-arginine (300 µM), and oxyhemoglobin (20 µM). (A) Group IIA, before (control, solid circles) and after (open circles) 60-minute hypoxia followed by 30-minute reoxygenation in St. Thomas solution at 37°C. (B) Group IIB, 60-minute hypoxia followed by 30-minute reoxygenation in Krebs solution (solid circles) or in St. Thomas solution (open circles) at 4°C. Data are shown as mean ± SEM. **p less than 0.01 compared with the control group (n = 6, two-way ANOVA).

EDHF-Mediated Relaxation After Nicorandil Treatment
Group IIIA
Addition of nicorandil to Krebs solution for 60-minute hypoxia at 37°C significantly increased the EDHF-mediated relaxation (81.7% ± 3.4%, compared with 44.4% ± 6.0% without nicorandil, p < 0.001; Fig 5A) without change of EC₅₀ (Table 2).

View larger version (12K): [in this window] [in a new window]   Fig 5. Concentration-relaxation curves for bradykinin in the U46619 (10 nM) precontracted microarteries (see Methods) with indomethacin (7 µM), NG-nitro-L-arginine (300 µM), and oxyhemoglobin (20 µM) after exposure to (A) Krebs solution without (solid circles) or with (open circles) nicorandil at 37°C for 60-minute hypoxia (group IIIA); (B) St. Thomas solution without (open circles) or with (solid circles) nicorandil at 37°C for 60-minute hypoxia (group IIIB); or (C) St. Thomas solution without (open circles) or with (solid circles) nicorandil at 4°C for 60-minute hypoxia (group IIIC). Data are shown as mean ± SEM. **p less than 0.01 compared with nicorandil treatment group (n = 6, two-way ANOVA).

	Comment

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The present study for the first time demonstrates in porcine coronary microarteries that (1) H-R impairs EDHF-mediated relaxation in the coronary microarteries, and the injury is more severe during prolonged H-R; (2) under the condition of either profound hypothermia (4°C) or normothermia (37°C), St. Thomas does not provide protection to the EDHF-mediated relaxation impaired by H-R, although its detrimental effect at 37°C is eliminated at 4°C; and (3) as an additive to Krebs or St. Thomas during hypoxia under normothermia or profound hypothermia, the potassium channel opener nicorandil may restore EDHF-mediated endothelial function, and therefore this study supports the use of nicorandil as an additive in cardioplegia to protect the coronary endothelial function.

The present study used coronary microarteries (resistance arteries with diameter ranging from 200 to 450 µm) at a normalized physiologic pressure to examine the effect of H-R with or without preservation solutions and the effect of supplementation of nicorandil in the solutions on the EDHF-mediated endothelial function.

As a cardioplegic solution, St. Thomas is used under either hypothermia or normothermia and as a preservation solution; it is used at 4°C. During such period, the myocardial temperature is moderately or profoundly hypothermic. The present study mimics the clinical settings for cardiac surgery or for the donor heart preservation.

Bradykinin-Induced, EDHF-Mediated Relaxation
In this study, bradykinin was used to evoke the endothelium-dependent relaxation. Bradykinin, through a receptor mechanism, increases the intracellar Ca²⁺ concentration and stimulates the release of endothelium-derived relaxing factors (NO, prostacyclin, and EDHF) in the endothelial cell [29]. Because the other two main components (NO and cyclooxygenase pathways) were abolished by _L-NNA, HbO, and indomethacin [27], the residual relaxation is through the non-NO and noncyclooxygenase mechanism (ie, related to EDHF; Fig 1) [5, 27, 30].

Effect of H-R on EDHF-Mediated Relaxation
It is widely recognized that the microvasculature is very vulnerable to the deleterious consequences of ischemia and reperfusion. Evidence that 90-minute period of ischemia followed by 1-hour reperfusion leads to coronary endothelial dysfunction was first obtained by Ku [32]. Later studies found that NO-mediated relaxation was impaired by H-R [31]. Although the effect of H-R on membrane hyperpolarization has been studied [33], there were few reports on the effect of H-R on EDHF-mediated relaxation [10, 14].

In the present study, EDHF-mediated (_L-NNA, HbO, and indomethacin-resistant) relaxation was significantly reduced after H-R for 30 minutes, and it was more severe after 60-minute hypoxia followed by 30-minute reoxygenation. Interestingly, the U₄₆₆₁₉-induced contraction was slightly affected by H-R. To fairly compare the relaxation, a similar precontraction force was essential, and this was achieved in the present study by adding a higher concentration of U₄₆₆₁₉ (between 10 and 100 nM) after H-R to reach a similar precontraction.

EDHF-Mediated Relaxation After H-R in St. Thomas at Different Temperatures
As an extracellular type of preservation solution, St. Thomas was initially designed to eliminate the H-R injury of myocardium and has been demonstrated to be effective in cardiac protection. However, recent studies have provided evidence of the impairment of this solution on the endothelial function [5, 34, 35]. The combined effect of H-R and St. Thomas solution on the EDHF-related endothelial function under clinically relevant temperatures remains unknown. The present study indicates that exposure to St. Thomas solution under 60-minute hypoxia at 4°C or at 37°C reduced EDHF-mediated relaxation, and therefore St. Thomas does not provide protection to the EDHF-mediated relaxation impaired by H-R, although its detrimental effect at 37°C is eliminated at 4°C.

Effect of Nicorandil Added to Krebs or St. Thomas Solution During H-R on EDHF-Mediated Relaxation
Over the years, there are numerous modifications to the composition of cardioplegic solution. As an ATP-sensitive potassium channel opener, nicorandil has been demonstrated effective in myocardial protection against ischemia-reperfusion [23]. When nicorandil is used as a component of St. Thomas [36] or blood cardioplegia [37], it improves preservation of energy and function in pig hearts; and when added in hyperkalemic solution, it is beneficial to the indomethacin and _L-NNA–resistant endothelial function in the pig [38]. Nicorandil is the only K⁺ channel opener used clinically as cardioplegia to protect the myocardial function, and a recent clinical study in coronary surgery by Hayashi and colleagues [39] suggests that nicorandil administration during cardiopulmonary bypass provides enhanced myocardial protective effects against ischemia-reperfusion in patients undergoing coronary artery bypass grafting.

Our data demonstrated that the addition of nicorandil to Krebs or St. Thomas solution at different temperatures under H-R may restore the EDHF-mediated relaxation in coronary microarteries. This effect may be related to the mechanism that nicorandil relaxes blood vessels. As a K⁺ channel opener, nicorandil opens K⁺ channels, and this effect is similar to the effect of EDHF. Therefore, nicorandil-related effect may be synergetic to EDHF. Further, as reported, nicorandil is a NO donor [24] that may also be related to relaxation, although this does not seem to be important in our experiments because in the presence of NO synthase inhibitors and NO scavenger HbO, the effect of NO was abolished to ensure the effect was mediated by EDHF.

Clinical Implications
During cardiac surgery, the heart is inevitably subjected to ischemia and subsequent reperfusion injury. Hyperkalemic solutions are commonly used in cardiac surgery to protect the heart to produce better postoperative recovery of myocardial function. The perfect heart protection should include the preservation of cardiac myocytes as well as endothelium. Furthermore, perfect preservation of the endothelial function should involve all three endothelium-derived relaxing factors. The present study indicates that under the normothermic and hypothermic condition, addition of nicorandil to St. Thomas solution under H-R may restore the EDHF-mediated relaxation. The recovery of EDHF function in nicorandil-containing St. Thomas solution supports the use of nicorandil as an additive to St. Thomas cardioplegia to preserve the endothelial cell function in order to improve the performance of hearts subjected to global myocardial ischemia during cardiac surgery. The protective effect of nicorandil from this study provides new insights into the further development of cardioplegia and organ preservation solutions.

	The Society of Thoracic Surgeons: Forty-Second Annual Meeting—New Location

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The city of New Orleans and part of the Gulf region have been devastated by the effects of Hurricane Katrina. Relief efforts have begun, but the clean-up and recovery processes will be slow. For this reason, The Society of Thoracic Surgeons will host its 42nd Annual Meeting in Chicago, Illinois. Please note: the meeting dates have not changed. The Annual Meeting will be held at McCormick Place, January 30–February 1, 2006, and STS/AATS Tech-Con 2006 will be held in the same location, January 28–29.

The Workforce on Annual Meeting's Program Task Force is meeting to discuss program details, and to organize an outstanding educational event. Chicago also offers a wide array of exciting social activities.

Please continue to visit www.sts.org for important program information as it develops!

	Acknowledgments

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This study was supported in full by grants from the Research Grant Council of the Hong Kong Special Administrative Region (Projects CUHK4127/01M and CUHK4383/03M), China, and the Providence St. Vincent Medical Foundation, Portland, Oregon.

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