Diabetes Care
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Diabetes Care 29:202-206, 2006
DOI: 10.2337/diacare.29.02.06.dc05-1588
© 2006 by the American Diabetes Association
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ishii, H.
Right arrow Articles by Murohara, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishii, H.
Right arrow Articles by Murohara, T.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Clinical Care/Education/Nutrition
Original Article

Effects of Intravenous Nicorandil Before Reperfusion for Acute Myocardial Infarction in Patients With Stress Hyperglycemia

Hideki Ishii, MD1,2, Satoshi Ichimiya, MD, PHD2, Masaaki Kanashiro, MD, PHD2, Tetsuya Amano, MD, PHD1, Tatsuaki Matsubara, MD, PHD3 and Toyoaki Murohara, MD, PHD1

1 Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
2 Department of Cardiology, Yokkaichi Municipal Hospital, Yokkaichi, Mie, Japan
3 Department of Internal Medicine, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan

Address correspondence and reprint requests to Hideki Ishii, The Department of Cardiology, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. E-mail: hkishii{at}med.nagoya-u.ac.jp


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
OBJECTIVE—Stress hyperglycemia increases the risk of mortality and poor outcomes in patients with acute myocardial infarction (AMI). We aimed to assess effects of intravenous nicorandil administered before reperfusion on AMI patients with stress hyperglycemia.

RESEARCH DESIGN AND METHODS—This study consisted of 158 consecutive first AMI patients with stress hyperglycemia who underwent percutaneous coronary intervention (PCI) within 24 h from the onset. They were randomly assigned to receive 12 mg of nicorandil (n = 81) or a placebo (n = 77) intravenously just before reperfusion. Stress hyperglycemia was defined as a blood glucose level ≥10 mmol/l (180 mg/dl). We examined various aspects of epicardial flow and microvascular function as immediate data and major adverse cardiac events (MACEs) (coronary heart disease death or unplanned readmission due to congestive heart failure) as late-phase data.

RESULTS—The incidence of slow flow after PCI was lower in the nicorandil group (13.6 vs. 27.3%, P < 0.04). ST segment resolution >50% was observed in 70.4 and 53.2% on nicorandil and placebo, respectively (P < 0.03). Patients treated with nicorandil had a lower peak creatine kinase level (3,137 ± 2,577 vs. 4,333 ± 3,608, P < 0.02). Upon Kaplan-Meier analysis, 5 years’ freedom from MACEs was 86.4% in the nicorandil group and 74.0% in the placebo (P < 0.05).

CONCLUSIONS—Adjunctive therapy with administration of intravenous nicorandil before reperfusion on AMI patients with stress hyperglycemia significantly improves epicardial flow and prevents the occurrence of severe microvascular reperfusion injury, resulting in better outcomes in these patients.

Abbreviations: AMI, acute myocardial infarction • ECG, electrocardiogram • KATP channel, ATP-sensitive K+ channel • MACE, major adverse cardiac event • PCI, percutaneous coronary intervention • TIMI, thrombolysis in myocardial infarction • TNF, tumor necrosis factor


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
An association between admission plasma glucose levels and an increased risk of mortality and poor prognosis after acute myocardial infarction (AMI) was well noted (1–4). In patients with AMI, glucose metabolism is modified and stress hyperglycemia can be observed. These phenomena are observed not only in patients with diabetes but also in patients without diabetes. Some mechanism for the association between stress hyperglycemia and adverse outcomes after AMI are possible (5–8) but are not well understood. Furthermore, there are limited data about pharmacological intervention, which has beneficial effects for AMI patients with stress hyperglycemia.

On the other hand, nicorandil, a hybrid compound of ATP-sensitive K+ channel (KATP channel) opener and nitric oxide donor, has a pharmacological preconditioning effect in the human heart (9). In some reports, intravenous nicorandil has been reported to ameliorate early functional and clinical problems in patients with AMI (10–12). In the present study, we assessed the cardioprotective effects of single intravenous nicorandil before reperfusion with percutaneous coronary intervention (PCI) for AMI with stress hyperglycemia.


   RESEARCH DESIGN AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
RESULTS
 CONCLUSIONS
 References
 
Between November 1998 and October 2003, we did a randomized study of single intravenous administration of nicorandil before reperfusion in 368 patients with ST-segment elevation AMI (12). Of those patients, 158 (81 in the nicorandil group and 77 in the placebo group) had stress hyperglycemia at admission and they were enrolled in the study.

AMI was diagnosed by chest pain, persisting between 30 min and 24 h and proving unresponsive to nitrates, electrocardiogram (ECG) ST-segment elevation with at least two contiguous ECG leads, and more than double creatine kinase elevation above the normal upper limit. Stress hyperglycemia was defined as a blood glucose level ≥10 mmol/l (180 mg/dl) at admission to the hospital as stated by previous studies (13,14). Patients were diagnosed with diabetes if they had a previous or current diagnosis of diabetes at hospital admission or if an abnormal oral glucose tolerance test or HbA1c ≥6.5% was found after admission.

The physicians obtained written informed consent from each patient, and the study was approved by the hospital ethics committee.

The details of the study design, methods, patient characteristics, and inclusion and exclusion criteria have been previously described (12). In brief, the patients were randomized by the concealed-envelope method. They were divided into two groups: those who received intravenous nicorandil before reperfusion with PCI and those who received placebo. In the nicorandil group, 12 mg dissolved in 100 ml of 0.9% saline was administered by intravenous injection over a 20- to 30-min period before the procedure. In the placebo group, 100 ml of 0.9% saline was administered intravenously. Other protocols were the same for the two groups.

Oral medications were also similar in both groups. For all patients, aspirin (162 mg/day) was administered orally, and ticlopidine or cilostazol was applied when the stent was implanted. In the absence of contraindications such as hyperkalemia, ACE inhibitors, or angiotensin II receptor blockers were administered.

The following immediate data were assessed after reperfusion: 1) thrombolysis in myocardial infarction (TIMI) trial grade after PCI, 2) resolution of ST-segment elevation on ECG after PCI, 3) corrected TIMI frame count after PCI, and 4) maximum serum creatine kinase.

The first ECG was done just before coronary angiography and the second was done 15 min after PCI. The amount of ST-segment elevation was measured 20 ms after the end of QRS complex in leads I, aVL and V1 through V6 for anterior, and leads II, III, aVf, and V5 through V6 for nonanterior myocardial infarction. The corrected TIMI frame count was measured as the number of cine frames required for contrast to first reach standardized distal coronary landmarks in the culprit coronary artery (15). The filming speed was 30 frames/s in the present study. In the case of occluded vessels, a frame count of 100 was used. Samples for serum creatine kinase were obtained at admission and every 3–48 h, and from these data, maximum creatine kinase level was checked. All measurements were performed by an experienced observer who was blinded to randomization.

We also analyzed follow-up data for major adverse cardiac events (MACEs) (coronary heart disease death or unplanned readmission due to congestive heart failure) and the composite end point of all-cause mortality or all-cause admission. Data were obtained from hospital charts and telephone interviews with the patients.

All measurements were performed by an experienced observer who was blinded to randomization.

Statistical analysis
All values are expressed as means ± SD or incidences (%). Univariate analysis of differences between the two groups was performed by the two-tailed unpaired t test for continuous outcome variables and by {chi}2 or Fisher’s exact tests for discrete outcome variables. Differences in long-term cardiac event-free survival between the two groups was examined with the Kaplan-Meier method and compared using the log-rank test. We also used Cox proportional hazards models for long-term follow-up. Differences were considered significant at P < 0.05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
CONCLUSIONS
 References
 
Intravenous nicorandil was assigned to 81 patients and placebo was given to 77 patients. In Table 1 and Table 2, the baseline characteristics of the nicorandil and placebo groups are presented. There were no significant differences in age, sex, time to reperfusion, incidence of coronary risk factors, blood pressure, heart rate, pulmonary capillary wedge pressure, or culprit lesions between the two groups.


View this table:
[in this window]
[in a new window]
  		Table 1— Baseline patient characteristics

 

View this table:
[in this window]
[in a new window]
  		Table 2— Angiographic and ECG findings

 
Table 3 provides a summary of detailed information for the angiographic results and ECG observations. Good myocardial reperfusion on ECG after PCI (ST-segment elevations <50% of initial value) was seen in 70.4% of the nicorandil group and 53.2% of the placebo (P = 0.027). Slow flow phenomena after PCI (TIMI flow grade ≤2 after PCI) occurred statistically less frequently in the nicorandil group (13.6 vs. 27.3%, P = 0.032). Corrected TIMI frame count was furthermore lower in the nicorandil group (22.2 ± 8.9 vs. 28.0 ± 17.8, P = 0.01). From samples for serum creatine kinase, the maximum serum level of creatine kinase was much lower in the nicorandil group than in the placebo group (3,137 ± 2,577 vs. 4,333 ± 3,608 IU, P = 0.018) (Fig. 1). These data show that intravenous nicorandil improved epicardial flow and accelerated ST-segment resolution in patients with AMI and furthermore infarct size measured by enzyme release was lower in the group on treatment with nicorandil.


View this table:
[in this window]
[in a new window]
  		Table 3— Angiographic results and ECG observations

 

Figure 1
View larger version (13K):
[in this window]
[in a new window]
  		Figure 1— The maximum serum creatine kinase: The maximum serum level of creatine kinase was much lower in the nicorandil group than in the placebo group (3,137 ± 2,577 vs. 4,333 ± 3,608 IU, P = 0.018)

 
Figure 2 shows Kaplan-Meier curves of follow-up data for freedom from MACEs. Over a 5-year period, the rate at which subjects avoided MACEs was 86.4% in the nicorandil group and 74.0% in the placebo group (hazard ratio 0.48 [95% CI 0.23–0.99], P = 0.048). A total of 5 (6.2%) patients in the nicorandil group and 11 (14.3%) in the placebo group experienced unplanned hospital admission for congestive heart failure. The rate of cardiovascular death was 7.4% (six patients) in the nicorandil group and 11.7% (nine patients) in the placebo group, respectively.


Figure 2
View larger version (20K):
[in this window]
[in a new window]
  		Figure 2— Kaplan-Meier estimates: freedom from MACE defined as coronary heart disease death or unplanned hospital admission for congestive heart failure.

 
Intravenous nicorandil was also of significance for the composite end point of all-cause mortality or all-cause admission (hazard ratio 0.60 [95% CI 0.36–1.01], P = 0.052).


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
References
 
Several studies have reported that stress hyperglycemia with AMI is an important risk factor for the development of cardiovascular events. For both patients with and without diabetes, acute stress hyperglycemia at the time of AMI is a common phenomenon. To our knowledge, this is the first reported study that demonstrates that intravenous nicorandil just before reperfusion has beneficial effects in AMI patients with stress hyperglycemia. Our study shows not only early but also long-term effects after administration of nicorandil, with improvements in prognosis after AMI with stress hyperglycemia.

Several mechanisms can be postulated to explain the effectiveness of nicorandil. First, nicorandil may prevent diminution of cardioprotective effects such as preconditioning phenomenon, which contributes to cardioprotection (16–18). Recent experimental studies have reported that the mitochondrial KATP channel is recognized as an end factor of ischemic preconditioning and KATP channel openers act like ischemic preconditioning effect (19), but some studies demonstrated that stress hyperglycemia abolishes the protective effects of ischemic preconditioning and attenuates reductions of myocardial infarct size because stress hyperglycemia impairs activation of mitochondrial KATP channels and exacerbates myocardial ischemic injury (8,19–21). By contrast, nicorandil directly opens the KATP channels on the mitcondrial membrane at a much lower concentration than is required to open the same channels on the cell membrane (22). In addition, KATP channels opening activation results in a reduction in calcium overload during ischemia secondary to action potential shortening and prevention or attenuation of membrane depolarization. These actions would be also expected to protect cardiac function because calcium overload in cardiac muscle causes cellular damage. Through their activation, nicorandil might exert salutary effects and decrease in infarct size (23).

The second possible examination is that nicorandil acts on antioxidant stress. Hyperglycemia is related to oxidant stress. In the heart, elevated oxidative stress is associated with severely compromised mitochondrial functions and poor prognosis (24). Patients with hyperglycemia are prone to have elevated tumor necrosis factor (TNF)-{alpha} (25). TNF-{alpha} levels and its negative effects are increased in patients with AMI (26). It is reported that potassium channel openers protect cardiac mitochondria by attenuating oxidant stress at reoxygenation, mimicking the protective efficacy of conventional free radical scavengers (27). Furthermore, nicorandil inhibits the release of TNF-{alpha} from lymphocytes (28).

The third possible examination is that nicorandil has vasodilatory effect on coronary blood flow (29). Acute hyperglycemia impairs endothelium-dependent vasodilation (7), and collateral circulation to the risk area might be less frequently observed in patients with stress hyperglycemia (30). Therefore, this action might be associated with lower incidence of slow flow and might increase collateral blood flow in the nicorandil group.

Some studies show that intravenous glucose-insulin-potassium may have a positive metabolic influence in patients with AMI (31,32). However, another study (33) shows that glucose-insulin-potassium infusion as adjunctive therapy to PCI or thrombolysis in AMI may not result in enhanced myocardial salvage or a significant mortality reduction. Until now, there are limited reports as to whether other pharmacological intervention in the treatment for AMI with stress hyperglycemia has beneficial effects on microcirculatory impairment and clinical prognosis. Our findings are of great significance in this context.

Several issues need to be considered with respect to our study. The first study limitation is that we did not analyze serum insulin, catecholamine levels, or free fatty acids, which may have provided important additional information. Second, the present trial was of single-center design.

Our findings suggest that AMI patients with stress hyperglycemia receiving nicorandil continue to have markedly lower major complications in both early and late phase with much better outcomes. We conclude that adjunctive therapy with administration of intravenous nicorandil before reperfusion on AMI patients with stress hyperglycemia significantly improves epicardial flow and prevents the occurrence of severe microvascular reperfusion injury, resulting in better outcome in these patients.


   Footnotes
 
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

Received for publication August 24, 2005. Accepted for publication November 11, 2005.


   References
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 

  1. Fava S, Aquilina O, Azzopardi J, Muscat HA, Fenech FF: The prognostic value of blood glucose in diabetic patients with acute myocardial infarction. Diabet Med 13:80–83, 1996[Medline]
  2. Norhammar AM, Rydén L, Malmberg K: Independent risk factor for long-term prognosis after myocardial infarction even in nondiabetic patients. Diabetes Care 22:1827–1831, 1999[Abstract/Free Full Text]
  3. Bolk J, van der Ploeg T, Cornel JH, Arnold AER, Sepers J, Umans VAWM: Impaired glucose metabolism predicts mortality after a myocardial infarction. Int J Cardiol 79:207–214, 2001[Medline]
  4. Capes SE, Hunt D, Malmberg K, Gerstein HC: Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 355:773–778, 2000[Medline]
  5. Davi G, Catalano I, Averna M, Notarbartolo A, Strano A, Ciabattoni G, Patrono C: Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med 322:1769–1774, 1990[Abstract]
  6. Juhan-Vague I, Alessi MC, Vague P: Increased plasma plasminogen activator inhibitor 1 levels: a possible link between insulin resistance and atherothrombosis. Diabetologia 34:457–462, 1991[Medline]
  7. Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy MA, Simonson DC, Creager MA: Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation 97:1695–1701, 1998[Abstract/Free Full Text]
  8. Ishihara M, Inoue I, Kawagoe T, Shimatani Y, Kurisu S, Nishioka K, Umemura T, Nakamura S, Yoshida M: Effect of acute hyperglycemia on the ischemic preconditioning effect of prodromal angina pectoris in patients with a first anterior wall acute myocardial infarction. Am J Cardiol 92:288–291, 2003[Medline]
  9. Matsubara T, Minatoguchi S, Matsuo H, Hayakawa K, Segawa T, Matsuno Y, Watanabe S, Arai M, Uno Y, Kawasaki M, Noda T, Takemura G, Nishigaki K, Fujiwara H: Three minute, but not one minute, ischemia and nicorandil have a preconditioning effect in patients with coronary artery disease. J Am Coll Cardiol 35:345–351, 2000[Abstract/Free Full Text]
  10. Ito H, Taniyama Y, Iwakura K, Nishikawa N, Masuyama T, Kuzuya T, Hori M, Higashino Y, Fujii K, Minamino T: Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction. J Am Coll Cardiol 33:654–660, 1999[Abstract/Free Full Text]
  11. Okamura A, Rakugi H, Ohishi M, Yanagitani Y, Shimizu M, Nishii T, Taniyama Y, Asai T, Takiuchi S, Moriguchi K, Ohkuro M, Komai N, Yamada K, Inamoto N, Otsuka A, Higaki J, Ogihara T: Additive effects of nicorandil on coronary blood flow during continuous administration of nitroglycerin. J Am Coll Cardiol 37:719–725, 2001[Abstract/Free Full Text]
  12. Ishii H, Ichimiya S, Kanashiro M, Amano T, Imai K, Murohara T, Matsubara T: Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment elevation myocardial infarction. Circulation 112:1284–1288, 2005[Abstract/Free Full Text]
  13. Gwilt DJ, Petri M, Lamb P, Nattrass M, Pentecost BL: Effects of intravenous insulin infusion on mortality among diabetic patients after myocardial infarction. Br Heart J 51:626–630, 1984[Abstract/Free Full Text]
  14. Lynch M, Gammage MD, Lamb P, Nattrass M, Pentecost BL: Acute myocardial infarction in diabetic patients in the thrombolytic era. Diabet Med 11:162–165, 1994[Medline]
  15. Gibson CM, Cannon CP, Daley WL, Dodge JT, Alexander B, Marble SJ, McCabe CH, Raymond L, Fortin T, Poole WK, Braunwald E, the TIMI 4 Study Group: TIMI framecount: a quantitative method of assessing coronary artery flow. Circulation 93:879–888, 1996[Abstract/Free Full Text]
  16. Li GC, Vasquez JA, Gallagher KP, Lucchesi BR: Myocardial protection with preconditioning. Circulation 82:609–619, 1990[Abstract/Free Full Text]
  17. Schott RJ, Rohmann S, Braun ER, Schaper W: Ischemic preconditioning reduces infarct size in swine myocardium. Circ Res 66:1133–1142, 1990[Abstract/Free Full Text]
  18. Ottani F, Galvani M, Ferrini D, Sorbello F, Limonetti P, Pantoli D, Rusticali F: Prodromal angina limits infarct size: a role for ischemic preconditioning. Circulation 91:291–297, 1995[Abstract/Free Full Text]
  19. Liu Y, Sato T, O’Rourke B, Marban E: Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection? Circulation 97:2463–2469, 1998[Abstract/Free Full Text]
  20. Kersten JR, Schmeling TJ, Orth KG, Pagel PS, Warltier DC: Acute hyperglycemia abolishes ischemic preconditioning in vivo. Am J Physiol 275:H721–H725, 1998
  21. Kersten JR, Montgomery MW, Ghassemi T, Gross ER, Toller WG, Pagel PS, Warltier DC: Diabetes and hyperglycemia impair activation of mitochondrial KATP channels. Am J Physiol Heart Circ Physiol 280:H1744–H1750, 2001[Abstract/Free Full Text]
  22. Sato T, Sasaki N, O’Rourke B, Marbán E: Nicorandil, a potent cardioprotective agent, acts by opening mitochondrial ATP-dependent potassium channels. J Am Coll Cardiol 35:514–518, 2000[Abstract/Free Full Text]
  23. Auchampach JA, Maruyama M, Cavero I, Gross GJ: Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning. Circulation 86:311–319, 1992[Abstract/Free Full Text]
  24. Dzeja PP, Holmuhamedov EL, Ozcan C, Pucar D, Jahangir A, Terzic A: Mitochondria: gateway for cytoprotection. Circ Res 89:744–746, 2001[Free Full Text]
  25. Pickup JC, Chusney GD, Thomas SM, Burt D: Plasma interleukin-6, tumour necrosis factor {alpha} and blood cytokine production in type 2 diabetes. Life Sci 67:291–300, 2000[Medline]
  26. Cain BS, Harken AH, Meldrum DR: Therapeutic strategies to reduce TNF-{alpha} mediated cardiac contractile depression following ischemia and reperfusion. J Mol Cell Cardiol 31:931–947, 1999[Medline]
  27. Ozcan C, Bienengraeber M, Dzeja PP, Terzic A: Potassium channel openers protect cardiac mitochondria by attenuating oxidant stress at reoxygenation. Am J Physiol Heart Circ Physiol 282:H531–H539, 2002[Abstract/Free Full Text]
  28. Wei XM, Heywood GJ, Di Girolamo N, Thomas PS: Nicorandil inhibits the release of TNF{alpha} from a lymphocyte cell line and peripheral blood lymphocytes. Int Immunopharmacol 3:1581–1588, 2003[Medline]
  29. Akai K, Wang Y, Sato K, Sekiguchi N, Sugimura A, Kumagai T, Komaru T, Kanatsuka H, Shirato K: Vasodilatory effect of nicorandil on coronary arterial microvessels: its dependency on vessel size and the involvement of the ATP-sensitive potassium channels. J Cardiovasc Pharmacol 26:541–547, 1995[Medline]
  30. Kersten JR, Toller WG, Tessmer JP, Pagel PS, Waltier DC: Hyperglycemia reduces coronary collateral blood flow through a nitric oxide-mediated mechanism. Am J Physiol Heart Circ Physiol 281:H2097–H2104, 2001[Abstract/Free Full Text]
  31. Malmberg K, Norhammar A, Wedel H, Rydén L: Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the diabetes and insulin-glucose infusion in acute myocardial infarction (DIGAMI) study. Circulation 99:2626–2632, 1999[Abstract/Free Full Text]
  32. Malmberg K, Rydén L, Efendic S, Herlitz J, Nicol P, Wardenström A, Wedel H: Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol 26:57–65, 1995[Abstract]
  33. van der Horst ICC, Zijlstra F, van’t Hof AWJ, Doggen CJM, de Boer MJ, Suryapranata H, Hoorntje JCA, Dambrink JHE, Grans ROB, Bilo HJG, the Zwolle Infarct Study Group: Glucose-insulin-potassium infusion in patients treated with primary angioplasty for acute myocardial infarction: the Glucose-insulin-potassium study: a randomized trial. J Am Coll Cardiol 42:784–791, 2003[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Eur Heart JHome page
K. P. Goran
The consensus is clearly needed for the definition of stress hyperglycaemia in acute myocardial infarction
Eur. Heart J., August 2, 2007; 28(16): 2042 - 2042.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ishii, H.
Right arrow Articles by Murohara, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishii, H.
Right arrow Articles by Murohara, T.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum