Prognostic significance of baseline low-density lipoprotein cholesterol in patients undergoing coronary revascularization; a report from the CREDO-Kyoto registry.

BACKGROUND: The impact of very low baseline levels of low-density lipoprotein cholesterol (LDL-C) on patients with coronary artery disease remains unclear. METHOD: We enrolled 39,439 patients of the pooled population from the CREDO-Kyoto registries Cohorts 1, 2, and 3. The study population consisted of 33,133 patients who had undergone their first coronary revascularization. We assessed the risk for mortality and cardiovascular events according to quintiles of the baseline LDL-C levels. RESULTS: Patients in the very low LDL-C quintile (<85 mg/dL) had more comorbidities than those in the other quintiles. Lower LDL-C levels were strongly associated with anemia, thrombocytopenia, and end-stage renal disease. The cumulative 4-year incidence of all-cause death increased as LDL-C levels decreased (very low: 19.4 %, low: 14.5 %, intermediate: 11.1 %, high: 10.0 %, and very high: 9.2 %; p < 0.001), which was driven by both the early and late events. After adjusting for baseline characteristics, the adjusted risks of the very low and low LDL-C quintiles relative to the intermediate LDL-C quintile remained significant for all-cause death (very low: HR 1.29, 95 % CI 1.16-1.44, p < 0.001; low: HR 1.15, 95 % CI 1.03-1.29, p = 0.01). The excess adjusted risks of the lowest LDL-C quintile relative to the intermediate LDL-C quintile were significant for clinical outcomes such as cardiovascular death (HR 1.17, 95 % CI 1.01-1.35), non-cardiovascular death (HR 1.35, 95 % CI 1.15-1.60), sudden death (HR 1.44, 95 % CI 1.01-2.06), and heart failure admission (HR 1.11 95 % CI 1.01-1.22), while there was no excess risk for the lowest LDL-C quintile relative to the intermediate LDL-C quintile for myocardial infarction and stroke. CONCLUSIONS: Lower baseline LDL-C levels were associated with more comorbidities and a significantly higher risk of death, regardless of cardiovascular or non-cardiovascular causes, in patients who underwent coronary revascularization.

Safety advantage of modified minimally invasive cardiac surgery for pediatric patients.

Minimally invasive cardiac surgery (MICS) using a small surgical incision in children provides less physical stress. However, concern about safety due to the small surgical field has been noted. Recently, the authors developed a modified MICS procedure to extend the surgical field. This report assesses the safety and benefit of this modified procedure by comparing three procedures: the modified MICS (group A), conventional MICS (group B), and traditional open heart surgery (group C). A retrospective analysis was performed with 111 pediatric patients (age, 0-9 years; weight, 5-30 kg) who underwent cardiac surgery for simple cardiac anomaly during the period 1996-2010 at Juntendo University Hospital. The modified MICS method to extend the surgical view has been performed since 2004. A skin incision within 5 cm was made below the nipple line, and the surgical field was easily moved by pulling up or down using a suture or a hemostat. The results showed no differences in terms of gender, age, weight, or aortic cross-clamp time among the groups. Analysis of variance (ANOVA) indicated significant differences in mean time before cardiopulmonary bypass (CPB), CPB time, operation time, and bleeding. According to the indices, modified MICS was similar to traditional open surgery and shorter time or lower bleeding volume than conventional MICS. No major mortality or morbidity occurred. In conclusion, the modified MICS procedure, which requires no special techniques, was as safe as conventional open heart surgery and even reduced perioperative morbidity.

Modifiers of the Risk of Diabetes for Long-Term Outcomes After Coronary Revascularization: CREDO-Kyoto PCI/CABG Registry.

Background: Diabetes is a well-known risk factor for adverse outcomes after coronary revascularization. Objectives: This study sought to determine high-risk subgroups in whom the excess risks of diabetes relative to nondiabetes are particularly prominent and thus may benefit from more aggressive interventions. Methods: The study population consisted of 39,427 patients (diabetes: n = 15,561; nondiabetes: n = 23,866) who underwent first percutaneous coronary intervention (n = 33,144) or coronary artery bypass graft (n = 6,283) in the pooled CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Graft) registry. The primary outcome measure was major adverse cardiovascular and cerebral endpoints (MACCE), which was defined as a composite of all-cause death, myocardial infarction, and stroke. Results: With median follow-up of 5.6 years, diabetes was associated with significantly higher adjusted risks for MACCE. The excess adjusted risks of diabetes relative to nondiabetes for MACCE increased with younger age (≤64 years: adjusted HR: 1.30; 95% CI: 1.19-1.41; P < 0.001; 64-73 years: adjusted HR: 1.24; 95% CI: 1.16-1.33; P < 0.001; >73 years: adjusted HR: 1.17; 95% CI: 1.10-1.23; P < 0.001; P interaction < 0.001), mainly driven by greater excess adjusted mortality risk of diabetes relative to nondiabetes in younger tertile. No significant interaction was observed between adjusted risk of diabetes relative to nondiabetes for MACCE and other subgroups such as sex, mode of revascularization, and clinical presentation of acute myocardial infarction. Conclusions: The excess risk of diabetes relative to nondiabetes for MACCE was profound in the younger population. This observation suggests more aggressive interventions for secondary prevention in patients with diabetes might be particularly relevant in younger patients.

Percutaneous coronary intervention using new-generation drug-eluting stents versus coronary arterial bypass grafting in stable patients with multi-vessel coronary artery disease: From the CREDO-Kyoto PCI/CABG registry Cohort-3.

AIMS: There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease. METHODS AND RESULTS: The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04-1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96-1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79-1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05-2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06-3.43, P<0.0001). CONCLUSIONS: In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD.

Successful surgical transmitral removal of left ventricular thrombus after acute anterior myocardial infarction without left ventriculotomy.

Left ventricular thrombus (LVT) is known as a life-threatening complication of acute myocardial infarction, in terms of sequential systemic embolization. When an LVT is found to be sufficiently large or mobile, not only anticoagulation therapy but also surgical thrombectomy should be administered immediately to prevent embolic events. Generally, since infarcted myocardium is comparatively fragile, ventriculotomy may result in anastomotic failure or further deterioration of LV function. We report herein a case of transmitral removal of LVT by which we successfully avoided ventriculotomy. A 50-year-old Japanese man was hospitalized due to ST-segment elevation myocardial infarction and emergency coronary angiography revealed total occlusion at the proximal left anterior descending artery. On hospital day 9, transthoracic echocardiography detected a massive LVT at the apex, protruding into the left ventricle. Considering the risk of embolization, urgent thrombectomy via a transmitral approach was performed. The LVT was easily removed through the mitral valve under endoscopic support, without any embolic events or postoperative complications. .

Coronary Revascularization in the Past Two Decades in Japan (From the CREDO-Kyoto PCI/CABG Registries Cohort-1, -2, and -3).

The treatment of coronary artery disease has substantially changed over the past two decades. However, it is unknown whether and how much these changes have contributed to the improvement of long-term outcomes after coronary revascularization. We assessed trends in the demographics, practice patterns and long-term outcomes in 24,951 patients who underwent their first percutaneous coronary intervention (PCI) (n = 20,106), or isolated coronary artery bypass grafting (CABG) (n = 4,845) using the data in a series of the CREDO-Kyoto PCI/CABG Registries (Cohort-1 [2000 to 2002]: n = 7,435, Cohort-2 [2005 to 2007]: n = 8,435, and Cohort-3 [2011 to 2013]: n = 9,081). From Cohort-1 to Cohort-3, the patients got progressively older across subsequent cohorts (67.0 ± 10.0, 68.4 ± 9.9, and 69.8 ± 10.2 years, ptrend < 0.001). There was increased use of PCI over CABG (73.5%, 81.9%, and 85.2%, ptrend < 0.001) and increased prevalence of evidence-based medications use over time. The cumulative 3-year incidence of all-cause death was similar across the 3 cohorts (9.0%, 9.0%, and 9.3%, p = 0.74), while cardiovascular death decreased over time (5.7%, 5.1%, and 4.8%, p = 0.03). The adjusted risk for all-cause death and for cardiovascular death progressively decreased from Cohort-1 to Cohort-2 (HR:0.89, 95%CI:0.80 to 0.99, p = 0.03, and HR:0.80, 95%CI:0.70 to 0.92, p = 0.002, respectively), and from Cohort-2 to Cohort-3 (HR:0.86, 95%CI:0.78 to 0.95, p = 0.004, and HR:0.77, 95%CI:0.67-0.89, p < 0.001, respectively). The risks for stroke and repeated coronary revascularization also improved over time. In conclusions, we found a progressive and substantial reduction of adjusted risk for all-cause death, cardiovascular death, stroke, and repeated coronary revascularization over the past two decades in Japan.

Comparison of Outcomes of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting Among Patients With Three-Vessel Coronary Artery Disease in the New-Generation Drug-Eluting Stents Era (From CREDO-Kyoto PCI/CABG Registry Cohort-3).

There is a scarcity of data comparing long-term clinical outcomes between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel coronary artery disease (3VD) in the new-generation drug-eluting stents era. CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who had undergone first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. We identified 2525 patients with 3VD (PCI: n = 1747 [69%], and CABG: n = 778 [31%]). The primary outcome measure was all-cause death. Median follow-up duration was 5.7 (interquartile range: 4.4 to 6.6) years. The cumulative 5-year incidence of all-cause death was significantly higher in the PCI group than in the CABG group (19.8% vs 13.2%, log-rank p = 0.001). After adjusting confounders, the excess risk of PCI relative to CABG for all-cause death remained significant (HR, 1.45; 95% CI, 1.14 to 1.86; p = 0.003), which was mainly driven by the excess risk for non-cardiovascular death (HR, 1.88; 95% CI, 1.30 to 2.79; p = 0.001), while there was no excess risk for cardiovascular death between PCI and CABG (HR, 1.19; 95% CI, 0.87 to 1.64; p = 0.29). There was significant excess risk of PCI relative to CABG for myocardial infarction (HR, 1.77; 95% CI, 1.19 to 2.69; p = 0.006), whereas there was no excess risk of PCI relative to CABG for stroke (HR, 1.24; 95% CI, 0.83 to 1.88; p = 0.30). In conclusion, in the present study population reflecting real-world clinical practice in Japan, PCI compared with CABG was associated with significantly higher risk for all-cause death, while there was no excess risk for cardiovascular death between PCI and CABG.

Echocardiographic assessment of the effects of mitral valve repair on mitral valve geometry in rheumatic mitral stenosis.

BACKGROUND AND AIM OF THE STUDY: While mitral valve replacement is generally considered as the standard surgical treatment for rheumatic mitral stenosis (MS), mitral valve repair may be an alternative therapeutic option. Several techniques have been used to overcome the anatomic difficulties involved in the repair of a rheumatic mitral valve. In the present study, quantitative echocardiography was used to investigate the effects of mitral valve repair and the influence of surgical procedures on mitral valve geometry in patients with rheumatic MS. METHODS: Mitral valve repair was successfully performed in seven patients with MS, by the same surgeon. Ring annuloplasty and slicing of the anterior mitral leaflet (AML) were performed in all patients. Concomitant surgical techniques included commissurotomy, decalcification, chordal resection, and division of the papillary muscles. The preoperative and postoperative echocardiographic findings in these patients were compared. RESULTS: The thickness of both the AML and posterior mitral leaflet (PML) (p = 0.01 for both), the opening angles of the AML (p = 0.02) and PML (p = 0.01), and the closing angle of the PML, the extent of calcification in the AML, and the pressure half-time (PHT) (p = 0.03 for all three parameters) were all significantly improved after mitral valve repair. CONCLUSION: In the present study, the transmitral peak velocity and mean pressure gradient were not significantly changed after mitral valve repair, whereas the PHT showed a marked improvement. Hence, the PHT may represent a suitable marker for evaluating the efficacy of mitral valve repair for MS.

Successful Treatment of Cardiac Tamponade due to Rupture of the Heart Performing an Open-chest Pericardiotomy.

A 78-year-old woman with mild dementia was found unconscious by her family. She was transported by an ambulance to our emergency room (ER). Initially, she was comatose and in a state of shock. The echocardiographic findings suggested cardiac tamponade by hematoma. Computed tomography also showed tamponade without aortic dissection. After imaging, she went into cardiac arrest, was returned to the ER, and tracheal intubation and left thoracotomy for pericardiotomy were performed. A return of spontaneous circulation was obtained by following this procedure. Bleeding from a rupture of the left cardiac free wall was confirmed, and the rupture was closed with TachoSil®. After closing the thoracotomy, electrocardiography revealed ST elevation in the precordial leads. Subsequently, placement of an indwelling intra-aortic balloon pump and coronary angiography (CAG) were performed. CAG showed an occlusion of the anterior interventricular branch and circumflex branch of the left coronary artery. She underwent conservative therapy in a coronary care unit. Finally, after obtaining hemodynamic stability and baseline mental status, she was transferred to another medical facility. We herein report a rare case involving the successful treatment of cardiac tamponade due to rupture of the heart performing an open-chest pericardiotomy and additionally discuss the key points for obtaining a favorable outcome.

Controlled release of matrix metalloproteinase-1 plasmid DNA prevents left ventricular remodeling in chronic myocardial infarction of rats.

BACKGROUND: The present study investigated whether administration of controlled release matrix metalloproteinase-1 (MMP-1) plasmid DNA prevents left ventricular (LV) remodeling in a rat chronic myocardial infarction (MI) model. METHODS AND RESULTS: Rats with a moderate-sized MI were randomized to 2 groups: injection of phosphate buffered saline (PBS) containing microspheres into the peri-infarct area (MI group, n=14) and injection of cationized gelatin microspheres incorporating MMP-1 plasmid DNA (MI+MMP-1 group, 50 microg MMP-1/20 microl; n=14). As a control group (n=14), rats received neither the coronary artery ligation nor the injection of PBS. Echocardiography, cardiac catheterization and histological studies were performed. At 2 and 4 weeks after the treatment, the MI+MMP-1 group had smaller LV end-diastolic and end-systolic dimensions, better fractional area change and smaller akinetic areas than the MI group. The LV end-systolic elastance and time constant of isovolumic relaxation were also better in the MI+MMP-1 group compared with the MI group 4 weeks after the treatment. Fibrosis evaluated with Masson's trichrome staining was less in the MI+MMP-1 group than the MI group. CONCLUSIONS: Gelatin microspheres for the controlled release of MMP-1 plasmid DNA are promising for improving cardiac remodeling and function when they are administered during the chronic phase of MI.

Successful repair of thoracoabdominal aortic aneurysm secondary to chronic dissection by hybrid therapy comprising surgical visceral reconstruction and dual Inoue stent graft implantation.

Crawford type II thoracoabdominal aortic aneurysm (TAAA) secondary to chronic dissection was successfully treated with hybrid therapy comprising surgical visceral reconstruction and dual Inoue stent graft implantation. The proximal single-branched Inoue stent graft effectively sealed the entry located near the left subclavian artery and simultaneously excluded the TAAA, while the distal tubular Inoue stent graft sealed the reentry; thus, the artery of Adamkiewicz was left unexcluded and intact between the two Inoue stent grafts. The visceral arteries were reconstructed using a quadrifurcated retrograde bypass with posterior aortic tunneling and end-to-end distal anastomosis to all four vessels to achieve a curved and smooth configuration.

[Aortic root replacement as redo operation].

Aortic root replacement (ARR) after aortic valve replacement (AVR) or ARR is often a major challenge. We performed 12 cases (7 men and 5 women) of ARR as redo operation from July 2002 to June 2009 in our institution. There was no mortality. Among them. ARR was performed in 5 cases, and AVR in 6 cases, at the previous operation. The age at the redo operation was 59.6 +/- 12.7 years. The mean interval between the previous and the redo operations was 6.8 years. In the cases of previous AVR, enlargement of the aortic root or the Valsalva sinus was recognized in 3, artificial valve failure with pannus formation below the valve was in 2, and perivalvular and regurgitation with infection was in 1. In the cases of previous ARR, surgical site infection was seen in 4, among which pseudoaneurysm formation or bleeding from the suture line at the aortic root was the reason for the redo operation in 3 cases. Pseudoaneurysm formation and artificial valve failure may be involved in some type of infection. ARR may be necessary in patients with aortitis.

A novel approach to restore atrial function after the maze procedure in patients with an enlarged left atrium.

OBJECTIVE: Left atrial (LA) volume reduction surgery concomitant with the maze procedure has been reported to facilitate sinus rhythm recovery even in patients with refractory atrial fibrillation (AF) with an enlarged LA. However, it is unknown whether the procedures can also restore effective atrial function of the enlarged LA with over-stretched myocardium. METHODS: The maze procedures in association with mitral valve surgery were performed to 57 AF patients with an enlarged LA (LA diameter >or=60mm). Among them, 32 patients had concomitant LA volume reduction surgery (VR group). Another 25 patients did not have the volume reduction (control group). RESULTS: Three months postoperatively LA end-diastolic volume (LAEDV, ml) assessed by magnetic resonance (MR) imaging was larger in the VR group than that in the control group (291+/-117 vs 223+/-81 ml, p<0.05). Postoperatively, sinus rhythm recovery rate was better (84 vs 68%, p<0.05) and LAEDV was drastically smaller (118+/-48 vs 203+/-76 ml, p<0.001) in the VR group than those in the control group. Among the patients with sinus rhythm recovery in both groups, LA contraction ejection fraction (%) improved in the VR group but not in the control group (22.3+/-7.8 vs 10.3+/-4.7%, p<0.001). CONCLUSIONS: The LA volume reduction surgery concomitant with the maze procedure restored contraction of the enlarged LA; however, the maze procedure alone did not restore LA contraction in spite of successful sinus rhythm recovery. LA volume reduction surgery may be desirable to the patients with refractory AF with over-stretched LA.

AORTIC INJURY DUE TO PARAGLIDING: A CASE REPORT.

A 64-year-old male fell from an altitude of 10 m while paragliding after stalling due to the wind. The purpose of this case report is to describe the outcomes after multiple injuries sustained during a paragliding accident, including a potentially life-threating injury to the thoracic aorta. The subject sustained a bite wound on his tongue, injuries to his chest (left side) and back, and a right forearm deformity. Enhanced whole body computed tomography (CT) revealed fractures of the bilateral laminae of the second and third cervical bones, right first rib, the tenth thoracic vertebral body (compression type), second lumbar vertebral body (burst type) and the right radius, Other injuries included an injury to the thoracic aortic arch and the presence of intraabdominal fluid collection without perforation of the digestive tract. Endovascular treatment was selected for the aortic injury because of multiple injuries. Immediate management included hypotensive rate control therapy using calcium and a beta blocker. On the fourth hospital day, the subject underwent deployment of a stent-graft to the aorta and subsequent surgical immobilization for the lumbar burst fracture. He also underwent surgical immobilization of the radial fracture and was discharged on the 28th hospital day. First responders or physicians should consider the possibility of aortic injury when treating patients who suffer falls while paragliding and provide appropriate management. Failure to provide appropriate management of an aortic injury could result in death. LEVEL OF EVIDENCE: 4.

Administration of control-released hepatocyte growth factor enhances the efficacy of skeletal myoblast transplantation in rat infarcted hearts by greatly increasing both quantity and quality of the graft.

BACKGROUND: We investigated whether simultaneous administration of control-released hepatocyte growth factor (HGF) enhances the efficacy of skeletal myoblast (SM) transplantation (Tx) through its antiapoptotic, angiogenic, and antifibrotic effects in myocardial infarction (MI). METHODS AND RESULTS: Forty-eight Lewis rats with chronic MI were divided into 4 groups. In Group I (n=14), neonatal SMs (5 x 10(6)) were transplanted in the MI area with a gelatin sheet incorporating 40 microg (1 g/L) of HGF applied. Group II (n=14) had SM Tx and placement of a saline sheet. Groups III (n=10) and IV (n=10) had culture medium injection plus HGF and saline sheet application, respectively. Four rats each from Groups I and II were sacrificed at day 1 for TUNEL assay on donor SMs. The percentage of TUNEL-positive donor cells was much lower in Group I than in Group II (P<0.05). At 4 weeks, in Group I, left ventricular diastolic dimension was smallest in echocardiography, end-systolic elastance was highest, and tau was the lowest (both P<0.0005 in ANOVA) in cardiac catheterization. Vascular density inside the graft was higher in Group I than in Group II (P<0.0001). The percentage of fibrotic area inside the graft was smaller in Group I than in Group II (P<0.001). The graft volume as estimated by fast skeletal myosin heavy chain-positive areas was approximately 7-fold larger in Group I than in Group II (P<0.0001). CONCLUSIONS: In SM Tx, HGF can greatly increase the graft volume and vascularity and reduce fibrosis inside the graft, which enhances the efficacy of SM Tx to infarcted hearts.

Transplanted skeletal myoblasts can fully replace the infarcted myocardium when they survive in the host in large numbers.

BACKGROUND: It is not clear how many skeletal myoblasts (SM) can survive and exert beneficial effects in the host myocardial infarction (MI) area. We assessed the hypothesis that a large number of SM can replace the MI area with reverse left ventricular (LV) remodeling. METHODS AND RESULTS: MI was created by left coronary artery ligation in male Lewis rats. Four weeks after ligation, 45 rats had skeletal myoblast transplantation in the MI area. They were randomized into 3 groups according to the number of SM: group I (n=15), 5 x 10(7); group II (n=15), 5 x 10(6); and group III (n=15), 5 x 10(5) cells. Donor SM were obtained from neonatal Lewis rats and directly used without expansion. Another four weeks later, all rats were sacrificed following hemodynamic assessment. All heart sections were stained with anti-fast skeletal myosin heavy chain (FSMHC) antibody to determine the spacial extent of donor myocytes. RESULTS: Four weeks after transplantation, LV diastolic dimension was decreased, fractional area change was increased, and MI size was decreased maximally in group I. Histological study showed that donor cells positive for FSMHC occupied the MI area with nearly normal wall thickness in group I, in which estimated volume of donor-derived muscle tissue was 40 mm3. In the other groups, FSMHC-positive cells were found only partly in the MI area. CONCLUSIONS: A large number of freshly isolated neonatal SM can survive in the host and fully replace the infarcted myocardium with reverse LV remodeling in rats with MI.

Combined procedure of surgical repair and cell transplantation for left ventricular aneurysm: an experimental study.

BACKGROUND: This study was designed to investigate the efficacy of the combined procedure of left ventricular (LV) repair and fetal cardiomyocyte transplantation (CM-TX) in a rat myocardial infarction model. METHODS AND RESULTS: A moderate-sized LV aneurysm was created by proximal ligation of the left coronary artery in 47 Lewis rats. Four weeks later, they were underwent another operation and received culture medium injection (n=10; group I), fetal CM-TX (n=10; group II), purse-string LV repair with culture medium injection (n=14; group III), or LV repair with fetal CM-TX (n=13; group IV). They were echocardiographically followed-up during the subsequent 4 weeks, and cardiac catheterization was performed in the final week. In the late period, LV dimension in group IV was smaller than that in group III (end-diastolic dimension, 0.92+/-0.02 versus 1.01+/-0.03 cm, P=0.0090; end-systolic dimension, 0.62+/-0.02 versus 0.74+/-0.04 cm, P=0.0093; at the fourth week), although they initially showed similar decreases in both groups. At the final week, end-systolic elastance was higher in group IV than in groups I, II, or III (0.61+/-0.10 versus 0.19+/-0.03, 0.30+/-0.09, 0.33+/-0.07 mm Hg/ micro L, P=0.0002, 0.0037, and 0.0042, respectively). CONCLUSIONS: Fetal CM-TX exerted preventive effects against late LV dilation and dysfunction after LV repair in the rat model. The results suggest that repair surgery combined with fetal CM-TX may enhance the surgical benefits for patients with LV aneurysm in the long term.

Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway.

BACKGROUND: Infusion of adrenomedullin (AM) has beneficial hemodynamic effects in patients with heart failure. However, the effect of AM on myocardial ischemia/reperfusion remains unknown. METHODS AND RESULTS: Male Sprague-Dawley rats were exposed to a 30-minute period of ischemia induced by ligation of the left coronary artery. They were randomized to receive AM, AM plus wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), or saline for 60 minutes after coronary ligation. Hemodynamics and infarct size were examined 24 hours after reperfusion. Myocardial apoptosis was also examined 6 hours after reperfusion. The effect of AM on Akt phosphorylation in cardiac tissues was examined by Western blotting. Intravenous administration of AM significantly reduced myocardial infarct size (28+/-4% to 16+/-1%, P<0.01), left ventricular end-diastolic pressure (19+/-2 to 8+/-2 mm Hg, P<0.05), and myocardial apoptotic death (19+/-2% to 9+/-4%, P<0.05). Western blot analysis showed that AM infusion accelerated Akt phosphorylation in cardiac tissues and that pretreatment with wortmannin significantly attenuated AM-induced Akt phosphorylation. Moreover, pretreatment with wortmannin abolished the beneficial effects of AM: a reduction of infarct size, a decrease in left ventricular end-diastolic pressure, and inhibition of myocardial apoptosis after ischemia/reperfusion. CONCLUSIONS: Short-term infusion of AM significantly attenuated myocardial ischemia/reperfusion injury. These cardioprotective effects are attributed mainly to antiapoptotic effects of AM via a PI3K/Akt-dependent pathway.

Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation.

OBJECTIVE: The effects of cell transplantation on the ischemic failing heart have already been documented. However, the area in and around infarct regions is not a good environment for cells to survive in because they are exposed to poor conditions in which certain requirements cannot be adequately supplied. We therefore designed a study to investigate the efficacy of prevascularization in ischemic regions before cell transplantation. METHODS: Rats with myocardial infarction were randomized into 4 groups: 11 rats received a culture medium injection to the left ventricular wall (control group), 11 received fetal cardiomyocyte transplantation (TX group), 11 received gelatin hydrogel microspheres incorporating basic fibroblast growth factor (FGF group), and 11 received basic fibroblast growth factor pretreatment sequentially, followed by cardiomyocyte transplantation (FGF-TX group). Four weeks later, left ventricular function was assessed by means of echocardiography and cardiac catheterization. RESULTS: In the FGF and FGF-TX groups neovascularization was found in the scar tissue 1 week later. The TX, FGF, and FGF-TX groups showed better fractional shortening than the control group (TX, FGF, FGF-TX, and control: 28% +/- 4.4%, 24% +/- 8.6%, 27% +/- 7.3%, and 17% +/- 4.6%, respectively; P <.01). Left ventricular maximum time-varying elastance was higher in the FGF-TX group than in the TX and FGF groups (FGF-TX, TX, and FGF: 0.52 +/- 0.23, 0.30 +/- 0.08, and 0.27 +/- 0.20 mm Hg/microL, respectively; P <.01). Histologically, more transplanted cells survived in the FGF-TX group than in the TX group. CONCLUSIONS: Prevascularization with basic fibroblast growth factor-incorporated microspheres enhances the benefits of cardiomyocyte transplantation. We expect that this system will contribute to regeneration medicine through its extensive application to other growth factors.