Release of serum S-100ß protein and neuron-specific enolase after off-pump coronary artery bypass grafting with and without intracranial and cervical artery stenosis.

PURPOSE: The aim of this study was to quantify the amount of brain damage suffered by patients who underwent off-pump coronary artery bypass grafting (OPCAB) in which S-100ß protein and neuron-specific enolase were used. METHODS: Thirty-four patients undergoing scheduled OPCAB were enrolled in the study. The patients were divided into two groups according to the results of their magnetic resonance angiography (MRA) and cervical ultrasonography: 13 patients had cervical or intracranial arterial stenosis (Group A), and 21 patients did not (Group B). Blood samples were collected from the arterial catheters immediately before surgery, upon arrival to the intensive care unit, and 6 and 24 hours after surgery. RESULTS: In blood samples collected from patients upon arrival to the intensive care unit, the maximum concentration of serum s-100ß protein in Group A was significantly higher than that of Group B (p = 0.029). Though patients in Group A tended to have higher maximum neuron-specific enolase (NSE) concentrations, there were no significant differences in NSE concentrations at any point between the two groups. CONCLUSIONS: Our findings show a correlation between the stenosis detected by MRA or cervical ultrasonography and brain damage after OPCAB.

Sonic hedgehog is a critical mediator of erythropoietin-induced cardiac protection in mice.

Erythropoietin reportedly has beneficial effects on the heart after myocardial infarction, but the underlying mechanisms of these effects are unknown. We here demonstrate that sonic hedgehog is a critical mediator of erythropoietin-induced cardioprotection in mice. Treatment of mice with erythropoietin inhibited left ventricular remodeling and improved cardiac function after myocardial infarction, independent of erythropoiesis and the mobilization of bone marrow-derived cells. Erythropoietin prevented cardiomyocyte apoptosis and increased the number of capillaries and mature vessels in infarcted hearts by upregulating the expression of angiogenic cytokines such as VEGF and angiopoietin-1 in cardiomyocytes. Erythropoietin also increased the expression of sonic hedgehog in cardiomyocytes, and inhibition of sonic hedgehog signaling suppressed the erythropoietin-induced increase in angiogenic cytokine expression. Furthermore, the beneficial effects of erythropoietin on infarcted hearts were abolished by cardiomyocyte-specific deletion of sonic hedgehog. These results suggest that erythropoietin protects the heart after myocardial infarction by inducing angiogenesis through sonic hedgehog signaling.

Global ST-segment elevation associated with impending cardiac rupture during diagnostic cardiac catheterization.

Cardiac rupture is a life-threatening complication during diagnostic cardiac catheterization, however, it rarely occurs nowadays. The present case report describes cardiac rupture during diagnostic cardiac catheterization using a 4F pigtail catheter and a 0.035" flexible guidewire, and global ST-segment elevation associated with impending cardiac rupture.

Off-pump coronary artery bypass grafting for poorly controlled diabetic patients.

OBJECTIVE: To estimate the postoperative outcome of off-pump coronary artery bypass grafting (OPCAB) for patients with poorly controlled diabetes mellitus as evaluated by preoperative hemoglobin A1c (HbA1c). PATIENTS AND METHODS: The preoperative value of HbA1c in 101 diabetic patients who had undergone OPCAB from January 2000 to January 2007 was reviewed. A value of 6.5% was used as an indicator of poorly controlled hyperglycemia, and patients were distributed into a well-controlled group (group A: HbA1c <6.5, n = 47) or a poorly controlled group (group B: HbA1c >6.5, n = 54). The average follow-up period was 2.2 +/- 1.3 years. RESULTS: There was no difference in the number of anastomoses (group A: 2.76 +/- 1.00 vs. group B: 2.63 +/- 0.80; p = 0.45) or the use of bilateral internal thoracic arteries (78.7% vs. 81.4%; p = 0.80). Postoperative angiography was carried out in 97 patients. The graft patency rate was 96.9% (126/130) in group A and 99.2% (131/132) in group B (p = 0.37). The stenosis free rate was 92.3% (120/130) in group A and 93.1% (123/132) in group B (p = 0.82). There were no operative deaths, no hospital deaths, and no late cardiac deaths. Postoperative atrial fibrillation occurred in 14 patients (29.7%) of group A and 12 (22.2%) of group B (p = 0.49). Wound dehiscence occurred in 2 patients (4.3%) of group A and 5 (9.3%) of group B (p = 0.44). Postoperative hospital stay lasted 22.1 +/- 9.5 days in group A and 21.7 +/- 9.1 days in group B (p = 0.86). CONCLUSIONS: OPCAB is feasible in patients having poorly controlled diabetes mellitus, and their condition does not compromise the surgical outcome.

Efficacy of Elective Intra-aortic Balloon Pump Therapy for High-Risk Off-Pump Coronary Artery Bypass: A Prospective Comparative Study.

OBJECTIVE: This study evaluated the usefulness of elective intra-aortic balloon pumping (IABP) in high-risk off-pump coronary artery bypass grafting (OPCAB). MATERIALS AND METHODS: From October 2002 through September 2006, total of 143 patients were operated with OPCAB. These patients were divided into two groups and clinical outcomes were compared: Group E (N = 30): Elective IABP group and Group C (N = 113): Control group, OPCAB without IABP. The criteria of elective application of IABP were severe stenosis of left main coronary artery (LMCA) or left ventricular dysfunction with an ejection fraction of less than 35%. RESULTS: No significant difference was noted in the duration of ICU stay (Group E: 1.13 ± 0.43 days; Group C: 1.18 ± 0.60 days, p = 0.710), the number of patients on a respirator for 24 hours or longer after surgery (Group E: 10.0%; Group C: 5.3%, p = 0.397), hospital mortality (Group E: 0%; Group C: 0%), or the frequency of postoperative major complications between two groups. CONCLUSIONS: The outcomes of OPCAB using elective IABP in high-risk patients, such as those with severe LMCA stenosis or left ventricular dysfunction, were similar to those of OPCAB in low-risk patients, suggesting the usefulness of elective IABP in OPCAB.

Limitations of right internal thoracic artery to left anterior descending artery bypass: a comparative quantitative study of postoperative angiography of the bilateral internal thoracic artery bypass grafts.

BACKGROUND: It remains controversial whether right internal thoracic artery (RITA) to left anterior descending artery (LAD) bypass has qualitative limitations which cannot be evaluated based on the patency rate alone. METHODS: The 111 subjects underwent graft angiography after bypass grafting of the left or right internal thoracic artery (ITA) to the LAD. The vascular caliber was measured at the origin of the ITA, at an ITA site adjacent to the anastomotic site, and at an LAD site immediately below the anastomotic site, regarding the outer diameter of the catheter as a reference. RESULTS: The caliber of the ITA immediately above the anastomotic site of the LAD was significantly lower in the RITA group. In the left internal thoracic artery (LITA) group, no patient showed a caliber of less than 1.25 mm, but five patients (7.8%) did in the RITA group. The preoperative cardio-thoracic ratio was significantly higher than that in patients in whom the caliber of the ITA immediately above the anastomotic site was 1.25 mm or more, and the height was significantly lower. CONCLUSIONS: In many patients, the RITA is appropriate as a graft material to the LAD. However, in patients with a high cardio-thoracic ratio and those with a low height, the RITA may not reach the LAD in a favorable state, and the LITA should be anastomosed to the LAD in some patients.

Low systemic vascular resistance state following off-pump coronary artery bypass grafting.

OBJECTIVE: To determine the prevalence, hemodynamic characteristics, and risk factors for low systemic vascular resistance (SVR) state following after off-pump coronary artery bypass (OPCAB). PATIENTS AND METHODS: SVR data could be obtained for 116 OPCAB patients. Low SVR was defined as an indexed systemic vascular resistance (SVRi) of <1,800 dyne x s/cm(5) x m(2) at the end of operation. Hemodynamic data were recorded preoperatively, at the end of operation, just after entering ICU, and the following morning. RESULTS: Low SVR state was noted in 54 of 116 patients (53%). The SVRi values in low-SVR and non-low-SVR patients were 1,406+/-253 and 2,326+/-509 dyne x s/cm(5) x m(2) at the end of operation (p<0.0001). Increased CI level, decreased MAP level, but unchanged CVP level was observed postoperatively in the low-SVR patients. The increase in CI and decrease in MAP were maximal at the end of operation. Patients with low SVR were more likely to have a higher body mass index (24.5+/-3.6 vs. 22.9+/-2.9; p=0.013) and to be male (82% vs. 62%; p=0.036) than no-low-SVR patients. In low-SVR patients, fluid balance was more positive intraoperatively (3,537+/-1,411 vs. 3,068+/-1,597; p=0.09), but more negative at 6 hours postoperatively (-136+/-978 vs. 234+/-844; p=0.034) and 12 h postoperatively (-282+/-1,321 vs. 268+/-1,238; p=0.024). CONCLUSIONS: Low SVR state, a probable manifestation of systemic inflammatory response (SIRS), is common in patients who have undergone OPCAB. For these patients it is more reasonable to maintain MAP with vasopressors by restoring vascular tone, than by volume loading.

Intracoronary injection of granulocyte colony-stimulating factor ameliorates the progression of left ventricular remodeling after myocardial ischemia/reperfusion in rabbits.

BACKGROUND: Although granulocyte colony-stimulating factor (G-CSF) is known to prevent left ventricular (LV) remodeling after acute myocardial infarction (AMI), the best method of administration is unknown. METHODS AND RESULTS: A rabbit ischemia/reperfusion model was created and G-CSF was administered into the coronary artery immediately after reperfusion. The LV size and contraction were determined by echocardiography, and the extent of infarcted myocardium was measured by Masson-Trichrome staining. The benefits of intracoronary injection of G-CSF on LV remodeling were similar to subcutaneous injection. CONCLUSIONS: Direct intracoronary G-CSF injection may become a new therapy for AMI with lower adverse effects.

Granulocyte colony stimulating factor directly inhibits myocardial ischemia-reperfusion injury through Akt-endothelial NO synthase pathway.

OBJECTIVE: Granulocyte colony stimulating factor (G-CSF) has been reported recently to prevent cardiac remodeling and dysfunction after acute myocardial infarction through signal transducer and activator of transcription 3 (STAT3). In this study, we examined acute effects of G-CSF on the heart against ischemia-reperfusion injury. METHODS AND RESULTS: Rat hearts were subjected to global 35-minute ischemia and 120-minute reperfusion in Langendorff system with or without G-CSF (300 ng/mL). G-CSF administration was started at the onset of reperfusion. Triphenyltetrazolium chloride staining revealed that G-CSF markedly reduced the infarct size. G-CSF strongly activated Janus kinase 2 (Jak2), STAT3, extracellular signal-regulated kinase (ERK), Akt, and endothelial NO synthase (NOS) in the hearts subjected to ischemia followed by 15-minute reperfusion. The G-CSF-induced reduction in infarct size was abolished by inhibitors of phosphatidylinositol 3-kinase, Jak2, and NOS but not of mitogen-activated protein kinase kinase (MEK). CONCLUSIONS: These results suggest that G-CSF acts directly on the myocardium during ischemia-reperfusion injury and has acute nongenomic cardioprotective effects through the Akt-endothelial NOS pathway.

G-CSF prevents the progression of atherosclerosis and neointimal formation in rabbits.

Granulocyte colony-stimulating factor (G-CSF) prevents left ventricular remodeling after myocardial infarction, but its effect on atherosclerosis is unknown. We examined two kinds of rabbit atherosclerosis models. Myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHL-MI) rabbits were treated with G-CSF or saline for 7 days from 14 months old. The vascular injury models were created by inflating angioplasty balloon in the iliac artery of rabbits and were divided into G-CSF and saline group. G-CSF significantly reduced the stenosis score of coronary artery and lipid plaque area of thoracic aorta in WHHL-MI rabbits at 4 weeks after the treatment. In the vascular injury model, G-CSF significantly prevented an increase in neointima/media ratio at 4 weeks after the treatment. G-CSF accelerated the reendothelialization of denuded arteries, and the pretreatment with nitric oxide synthase inhibitor significantly inhibited it. These results suggest that G-CSF has a therapeutic potential for the progression of atherosclerosis.

Cardioprotective effects of granulocyte colony-stimulating factor in swine with chronic myocardial ischemia.

OBJECTIVES: The aim of this study was to investigate the effect of granulocyte colony-stimulating factor (G-CSF) on chronic myocardial ischemia in swine. BACKGROUND: We recently have reported that G-CSF prevents cardiac remodeling and dysfunction after acute myocardial infarction in mice and swine. It remains unclear whether G-CSF has beneficial effects on chronic myocardial ischemia. METHODS: An ameroid constrictor was placed on left circumflex coronary artery of swine. The presence of myocardial ischemia was verified at four weeks after the operation, and the animals were randomly assigned into the following two groups: 1) administration of vehicle (control group, n = 10), and 2) administration of G-CSF (10 microg/kg/day) for seven days (G-CSF group, n = 10). RESULTS: Echocardiographic examination revealed that the G-CSF treatment prevented left ventricular dilation and dysfunction at eight weeks after the operation. Stress echocardiography revealed that G-CSF ameliorated the regional contractility of chronic myocardial ischemia. Morphological analysis revealed that the extent of myocardial fibrosis of the ischemic region was less in the G-CSF group than in control group. There were more vessels and less apoptotic cells at the ischemic region of the heart of the G-CSF group than control group. Moreover, Akt1 was more strongly activated in the heart of the G-CSF group than control group. CONCLUSIONS: These findings suggest that G-CSF improves cardiac function of chronic myocardial ischemia through decreases in fibrosis and apoptotic death and an increase in vascular density in the ischemic region.

Effects of G-CSF on left ventricular remodeling and heart failure after acute myocardial infarction.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that promotes proliferation and differentiation of neutrophil progenitors. G-CSF also possesses immunomodulatory properties. G-CSF-induced hematopoietic stem cell mobilization is widely used clinically for transplantation. After it was recently reported that G-CSF mobilizes bone marrow stem cells (BMSCs) into the infarcted hearts and accelerates the differentiation into vascular cells and cardiac myocytes, myocardial regeneration utilizing mobilization of BMSCs by G-CSF is attracting the attention of investigators. In animal models, G-CSF prevents left ventricular remodeling and dysfunction after acute myocardial infarction, at least in part, through a decrease in apoptotic cells and an increase in vascular cells. Although it is controversial whether BMSCs mobilized by G-CSF can differentiate into cardiac myocytes, G-CSF-induced angiogenesis is indeed recognized in infarcted heart. The cardioprotective effects of G-CSF are recognized even in isolated perfused heart. In addition, G-CSF activates various signaling pathways such as Akt, extracellular signal-regulated kinase, and Janus kinase 2/signal transducer and activator of transcription 3 through G-CSF receptors in cardiac myocytes. These observations suggest that G-CSF not only induces mobilization of stem cells and progenitor cells but also acts directly on cardiomyocytes. Therefore, G-CSF may be utilized as a novel agent to have protective and regenerative effects on injured myocardium. Although the effects of G-CSF on the progression of atherosclerosis are still unclear, there is a possibility that G-CSF will become a promising therapy for ischemic heart diseases.

Amelioration of hypertensive heart failure by amlodipine may occur via antioxidative effects.

Although recent clinical studies have suggested that long-acting calcium channel blockers (CCBs) have beneficial effects on heart failure, the precise mechanism is unknown. In this study, Dahl salt-sensitive rats fed a high salt diet were treated with the long-acting CCB amlodipine, the low-molecular-weight membrane permeable superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol), or saline from 11 weeks after birth. The cardiac geometry and function, and gene expression profiles were determined at 17 weeks. Dahl salt-sensitive rats fed a high salt diet followed by saline as a non-treatment control (HS group) showed a marked increase in blood pressure and developed concentric hypertrophy at 11 weeks, followed by left ventricular (LV) dilation and congestive heart failure by 17 weeks. The treatment with amlodipine (AMLO group) or Tempol (TEMP group) significantly inhibited the development of LV hypertrophy and cardiac dysfunction. Analysis using an Affymetrix GeneChip U34 revealed that the expression levels of 195 genes were changed by the treatment with amlodipine. Among these 195 genes, 110 genes were increased in HS rats and decreased in AMLO rats. And of these 110 genes, 54 genes were also decreased in TEMP rats. In contrast, 85 genes were decreased in HS rats and increased in AMLO rats. Of these 85 genes, 38 genes were also increased in TEMP rats. Approximately 48% of the genes were changed in similar fashion in AMLO and TEMP rats, suggesting that amlodipine shows beneficial effects on heart failure mainly via antioxidative mechanisms.

Early results of off-pump coronary artery bypass: retrospective consecutive comparative study.

OBJECTIVE: The purpose of this study is to compare the operative results of off-pump coronary artery bypass (OPCAB) and on-pump (conventional) coronary artery bypass (CCAB), to clarify qualitative problems and whether OPCAB is less invasive or not. METHODS: OPCAB was consecutively performed in 63 patients and CCAB in 63 patients between July 1998 and December 2003. RESULTS: The mean number of bypass grafts was 2.43 +/- 0.82 in the OPCAB group and 2.70 +/- 0.71 in the CCAB group (p = 0.096). In-hospital mortality was 0% in the OPCAB group and 3.2% in the CCAB group. The incidence of perioperative myocardial infarction was 0% in the OPCAB group and 3.2% in the CCAB group. The incidence of postoperative major complications was significantly lower in the OPCAB group than in the CCAB group (OPCAB group=4 complications, CCAB group=13 complications). Cerebrovascular accidents occurred in 1.6% of patients in both groups. The incidence of sternal infection or mediastinitis was 0% in the OPCAB group and 3.2% in the CCAB group. The early patency rate of graft was 94.0% in the OPCAB group and 92.8% in the CCAB group, and was not significantly different (p = 0.822). CONCLUSION: Operative mortality and major complications after surgery in OPCAB were lower than that in CCAB. The early patency rate in OPCAB was as good as that in CCAB. It is considered that OPCAB is less invasive and the quality of bypass in OPCAB is as good as that in CCAB.