PubMed Health⌕ Search

Biomedical subjects

Keiichi Tambara

Publications and source records attributed to Keiichi Tambara.

At least 19 recordsLinked to original sources
PubMed2007

Successful aortic valve replacement for Heyde syndrome with confirmed hematologic recovery.

Aortic valve stenosis can be complicated by recurrent gastrointestinal bleeding, particularly that due to angiodysplasia, also called Heyde syndrome. Recently, acquired type 2A von Willebrand disease, which is characterized by the loss of the large multimer of von Willebrand factor by the shear stress of aortic valve stenosis, was reported to be associated with this hemorrhagic syndrome. A 78-year-old woman, with severe aortic stenosis, presented with advanced anemia due to recurrent gastrointestinal bleeding and was diagnosed Heyde syndrome. By perioperative supplementation of von Willebrand factor and factor VIII, aortic valve replacement was safely performed without gastrointestinal bleeding. After the operation, the multimer of von Willebrand factor was normalized and thereafter no gastrointestinal bleeding occurred. This case reports the successful aortic valve replacement for Heyde syndrome, with confirmed hematologic recovery.

Aged↗
PubMed2007

Sustained-release erythropoietin ameliorates cardiac function in infarcted rat-heart without inducing polycythemia.

BACKGROUND: The usefulness of sustained-release erythropoietin for improving left ventricular (LV) function without polycythemia was evaluated in a rat chronic myocardial infarction model. METHODS AND RESULTS: Four weeks after left coronary artery ligation, 50 Sprague-Dawley rats were assigned to 5 groups (n=10, each). Control group had a gelatin sheet (20x20 mm) containing saline applied to the infarct area, whereas the 4 treatment groups had gelatin sheets incorporating erythropoietin 0.1 U, 1 U, 10 U and 100 U, respectively. Endpoint measurements performed at 8 weeks after the coronary ligation revealed that the fractional area change was larger for erythropoietin 1 U and 10 U than in the other 3 groups. The LV end-systolic elastance and the time constant of isovolumic relaxation were better for erythropoietin 1 U and 10 U than in the other 3 groups. The density of vessels larger than 50 microm in diameter was the highest in the erythropoietin 1 U group. The number of red blood cells was significantly increased in groups receiving erythropoietin 10 U and 100 U. CONCLUSIONS: Gelatin hydrogel sheets incorporating 1 U erythropoietin improved LV function without inducing polycythemia in a rat chronic myocardial infarction model.

Animals↗
PubMed2006

Insulin-like growth factor-1 enhances the efficacy of myoblast transplantation with its multiple functions in the chronic myocardial infarction rat model.

BACKGROUND: Myoblast transplantation (Tx) is promising for the improvement of cardiac function in ischemic cardiomyopathy. Insulin-like growth factor-1 (IGF-1) has anti-apoptotic and angiogenic effects, and induces myocyte hypertrophy. Our hypothesis is that topical and slow-release IGF-1 enhances the efficacy of Tx through its multiple functions. METHODS: Four weeks after coronary artery ligation, Lewis rats were divided into four groups: (1) IGF-1+Tx, injection of 6 x 10(6) myoblasts into the infarcted area with placement of an IGF-1-impregnated sheet on the left ventricular (LV) free wall; (2) Tx, Tx alone; (3) IGF-1, IGF-1 sheet alone; and (4) control. We measured cardiac function and performed immunohistochemical examinations. RESULTS: At 4 weeks after treatment, LV diastolic dimension was the smallest, end-systolic elastance was the highest, and tau was the smallest in the IGF-1+Tx group. The graft volume in the IGF-1+Tx group was 3-fold larger than in the Tx group. One day after transplantation, TUNEL-positive donor cells were fewer in the IGF-1+Tx than in the Tx group. Western blot analysis demonstrated that the phosphorylation of Akt increased and the expression of Bax decreased in the transplanted area of IGF-1+Tx rats compared with Tx rats. The vascular density in the peri-infarcted area was larger in IGF-1+Tx than in Tx rats. The mean diameter of graft-derived myotubes was larger in IGF-1+Tx than in Tx animals. CONCLUSIONS: IGF-1 increases the graft volume and enhances the efficacy of Tx in the chronic myocardial infarction model due to its multiple effects of preventing apoptosis, inducing angiogenesis, and promoting myoblast growth.

Administration, Topical↗
PubMed2006

A novel atrial volume reduction technique to enhance the Cox maze procedure: initial results.

OBJECTIVE: Large left atrial diameter is reported to be a predictor for recurrent atrial fibrillation after the Cox maze procedure, and left atrial diameter by itself influences the chance of sinus rhythm recovery, as well as maintenance of sinus rhythm. However, additional cut-and-sew procedures to decrease left atrial diameter extend operative time and can cause bleeding. Thus we developed a no-bleeding, faster, and therefore less invasive left atrial volume reduction technique to enhance the Cox maze procedure. METHODS: The modified Cox maze III procedure with cryoablation or the left atrial maze procedure in association with mitral valve surgery was performed in 80 patients with atrial fibrillation and enlarged left atria (> or =60 mm). Among them, 44 patients had the concomitant volume reduction technique (VR group); continuous horizontal mattress sutures for left atrial plication were placed on the left atrial wall along the pulmonary vein isolation line. Cryoablation was applied to the suture line so that the plicated left atrium is anatomically and electrically isolated. Another 36 patients did not have the volume reduction technique (control group). RESULTS: The VR group had preoperative left atrial diameters similar to those of the control group (67.1 +/- 7.8 vs 64.5 +/- 6.7 mm) and a longer preoperative duration of atrial fibrillation (14.1 +/- 5.4 vs 9.5 +/- 5.1 years, P < .05) but had smaller postoperative left atrial diameters (47.6 +/- 6.3 vs 62.1 +/- 7.9 mm, P < .01). There were no differences in mean crossclamp/bypass time and chest tube drainage for 12 hours between the groups. Twelve months after surgical intervention, the sinus rhythm recovery rate of the VR group was better than that of the control group (90% vs 69%, P < .05). CONCLUSIONS: Even in patients with long-standing atrial fibrillation and an enlarged left atrium, maze procedures concomitant with the novel left atrial volume reduction technique improved the sinus rhythm recovery rate without increasing complications. Although further study with a larger number of patients and a longer follow-up period is needed, this safe and thus far potent technique that catheter-based ablation cannot copy might extend indication of the Cox maze procedure for patients with tough atrial fibrillation.

Aged↗
PubMed2006

Repeated implantation is a more effective cell delivery method in skeletal myoblast transplantation for rat myocardial infarction.

BACKGROUND: Several clinical trials are underway to determine whether autologous skeletal myoblast transplantation is an effective and safe therapeutic strategy for severe heart failure due to myocardial infarction (MI). It remains unclear whether repeated skeletal myoblast implantation is a feasible and effective cell delivery method for the infarcted myocardium. METHODS AND RESULTS: Four weeks after a coronary ligation, male syngeneic Lewis rats were assigned to 3 treatment groups: 3 episodes of skeletal myoblasts (6x10(6)) transplantation (group I), a bolus transplantation of myoblasts (18x10(6)) (group II), or culture medium injection (group III). Eight weeks after the first treatment, echocardiography, cardiac catheterization and histological examination were performed to compare the therapeutic effects on left ventricular (LV) systolic and diastolic functions, and the engrafted myoblast volume. Repeated myoblast implantation significantly improved LV function and resulted in significantly larger engrafted volume and LV contractility compared with a bolus transplantation with the same number of myoblasts. CONCLUSIONS: Repeated skeletal myoblast transplantation is a safe and effective therapeutic strategy for the infarcted myocardium.

Animals↗
PubMed2005

Beta-adrenergic stimulation does not activate Na+/Ca2+ exchange current in guinea pig, mouse, and rat ventricular myocytes.

The effect of beta-adrenergic stimulation on cardiac Na(+)/Ca(2+) exchange has been controversial. To clarify the effect, we measured Na(+)/Ca(2+) exchange current (I(NCX)) in voltage-clamped guinea pig, mouse, and rat ventricular cells. When I(NCX) was defined as a 5 mM Ni(2+)-sensitive current in guinea pig ventricular myocytes, 1 microM isoproterenol apparently augmented I(NCX) by approximately 32%. However, this increase was probably due to contamination of the cAMP-dependent Cl(-) current (CFTR-Cl(-) current, I(CFTR-Cl)), because Ni(2+) inhibited the activation of I(CFTR-Cl) by 1 microM isoproterenol with a half-maximum concentration of 0.5 mM under conditions where I(NCX) was suppressed. Five or ten millimolar Ni(2+) did not inhibit I(CFTR-Cl) activated by 10 microM forskolin, an activator of adenylate cyclase, suggesting that Ni(2+) acted upstream of adenylate cyclase in the beta-adrenergic signaling pathway. Furthermore, in a low-extracellular Cl(-) bath solution, 1 microM isoproterenol did not significantly alter the amplitude of Ni(2+)-sensitive I(NCX) at +50 mV, which is close to the reversal potential of I(CFTR-Cl). No change in I(NCX) amplitude was induced by 10 microM forskolin. When I(NCX) was activated by extracellular Ca(2+), it was not significantly affected by 1 microM isoproterenol in guinea pig, mouse, or rat ventricular cells. We concluded that beta-adrenergic stimulation does not have significant effects on I(NCX) in guinea pig, mouse, or rat ventricular myocytes.

Adrenergic beta-Agonists↗
PubMed2005

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.

Animals↗
PubMed2005

Control-released hepatocyte growth factor prevents the progression of heart failure in stroke-prone spontaneously hypertensive rats.

BACKGROUND: We have developed a hepatocyte growth factor (HGF)-incorporating gelatin hydrogel sheet (HGF sheet), which was designed to release HGF more than 2 weeks in vivo. The present study investigated whether the HGF sheet could prevent the progression of heart failure in stroke-prone spontaneously hypertensive rats. METHODS: Stroke-prone spontaneously hypertensive rats at the age of 25 weeks received placement of an HGF sheet on the left ventricular free wall (HGF, n = 10) or sham-operation (control, n = 10). All animals were followed up with Doppler echocardiography during the next 4 weeks and then underwent histologic analysis. The influence of the hydrogel sheet alone was assessed by echocardiography and left ventricular pressure measurements. Survival study was performed (each group, n = 11) at the age of 30 weeks. RESULTS: There were two deaths in the control group and no deaths in the HGF group during the 4 weeks. Fractional shortening was significantly higher, and left ventricular diastolic dimension was significantly smaller in the HGF than in the control group. The slope of the peak early diastolic filling velocity and the ratio of that slope to the slope of the peak filling velocity at atrial contraction were significantly lower in the HGF than the control group. Myocardial fibrosis was lower and capillary density was significantly higher in the HGF than the control group. Placement of the hydrogel sheet alone did not affect any cardiac function compared with sham operation. The survival rate at 10 weeks after the surgery was much higher in the HGF than the control group. CONCLUSIONS: The HGF sheet improves cardiac function, reverses left ventricular remodeling, and markedly improves survival in spontaneously hypertensive rats. These beneficial effects are associated with angiogenesis and reduced fibrosis in the left ventricular myocardium.

Animals↗
PubMed2005

Cough reflex by ventricular premature contractions.

A 72-year-old man was referred for further assessment of a chronic cough. He noticed an association between the episodes of coughing and palpitations. Electrocardiography (ECG) revealed normal sinus rhythm and sporadic unifocal ventricular premature contractions (VPCs). Each cough was preceded by a premature beat. Continuous wave Doppler echocardiography revealed a VPC-induced transient increase in the pulmonary artery blood flow. He was successfully treated for VPCs with oral disopyramide, resulting in subsidence of both the coughing and palpitations. We suspect that the VPC-induced hemodynamic changes in the pulmonary circulation might be responsible for coughing in our patient. Premature contractions should be considered as a possible cause of chronic dry cough in the clinical setting.

Anti-Arrhythmia Agents↗
PubMed2004

Beneficial effect of candesartan treatment on cardiac autonomic nervous activity in patients with chronic heart failure: simultaneous recording of ambulatory electrocardiogram and posture.

BACKGROUND: Reclining in the right lateral decubitus position in chronic heart failure (CHF) is a self-protective mechanism for normalizing impaired cardiac autonomic nervous activity (CANA). HYPOTHESIS: Candesartan, an angiotensin II receptor blocker, exerts beneficial effects on CANA and postural preferences in patients with CHF. METHODS: We studied 15 patients with CHF due to coronary artery disease. Cardiac autonomic nervous activity was assessed using spectral heart rate variability (HRV) analysis based on 24-h ambulatory electrocardiogram monitoring before and after an 8-week treatment with candesartan. The patients' posture was simultaneously recorded using a specially devised detector, as the right (R) or left (L) lateral decubitus or supine (S) positions, to evaluate postural modulations of CANA. Normalized high-frequency (0.15 to 0.40 Hz) power (nHF) and the low-frequency (0.04 to 0.15 Hz)/high-frequency power ratio (LF/HF) were used as indices of vagal activity and sympathovagal balance, respectively. RESULTS: When HRV was analyzed in each position, CANA was changed in L and S, but not in R, from sympathetic to parasympathetic prevalence by the treatment (R, nHF, 50 +/- 20 vs. 52 +/- 19 nu, p = 0.87; LF/HF, 1.39 +/- 1.11 vs. 1.32 +/- 1.32, p =0.93; L, nHF, 28 +/- 13 vs. 47 +/- 19 nu, p = 0.019; LF/HF, 3.34 +/- 2.48 vs. 1.56 +/- 1.39, p = 0.029; S, nHF, 38 +/- 17 vs. 53 +/- 16 nu, p = 0.0023; LF/HF, 2.43 +/- 2.21 vs. 1.03 +/- 0.59, p = 0.025). The fractions of the time in R and L were decreased and increased, respectively, by the treatment (R, 40 +/- 30 vs. 18 +/- 24%, p = 0.0018; L, 11 +/- 20 vs. 27 +/- 26%, p = 0.025). CONCLUSIONS: In patients with CHF, candesartan treatment improves cardiac autonomic balance, and the preference for the right lateral decubitus position disappears after the treatment.

Aged↗
PubMed2004

Therapeutic angiogenesis by the controlled release of basic fibroblast growth factor for ischemic limb and heart injury: toward safety and minimal invasiveness.

We review our studies on therapeutic angiogenesis using basic fibroblast growth factor (bFGF) released in a controlled manner from biodegradable gelatin hydrogel (GH). The bFGF-GH was intramuscularly injected in rabbits with limb ischemia. The group treated with bFGF showed an increase in tissue blood flow under laser Doppler imaging and histology showed a greater vascular density compared with controls. Also, bFGF-GH was subepicardially injected into old heart infarcts in rats. In the group treated with bFGF, improved left ventricular function was shown by echocardiography and cardiac catheterization, increased regional blood flow in the peri-infarct area was detected by pinhole single-photon emission computed tomography using (201)Tl, and increased vascular density was demonstrated by histology. In rabbits with acute myocardial infarction, the heart was wrapped with the omentum (including the gastroepiploic artery) and a bFGF-GH sheet was applied. Postoperative assessment revealed rich communication from the gastroepiploic artery to the coronary artery and improved cardiac function. The controlled release of bFGF was effective for both limb and heart ischemia and is considered to be suitable for clinical use because its application in animals was feasible and safe with minimal invasiveness.

Angiography↗
PubMed2004

Residual fibrosis affects a long-term result of left ventricular volume reduction surgery for dilated cardiomyopathy in a rat experimental study.

OBJECTIVES: The aim of this study is to evaluate the relationship between left ventricular (LV) wall property and the results of LV volume reduction surgery (LVR) to treat dilated cardiomyopathy (DCM) in an experimental model. METHODS: DCM was introduced in 18 Lewis rats by autoimmunization with cardiac myosin. Among them, 12 rats underwent LVR and the rest were served as controls. They were subjected to echocardiography and cardiac catheterization for dimensional and functional measurements. The animals were sacrificed 4 weeks after surgery, and the fraction of myocardial fibrosis was calculated in 4 divided parts of the LV wall. RESULTS: Percent fibrosis varied widely from 4.7 to 45.2%. LV volume reduction surgery improved cardiac function immediately after surgery in all rats (Emax, 0.28+/-0.14 to 0.48+/-0.18 mmHg/microl; LV end-diastolic pressure, 21.0+/-6.1 to 13.3+/-5.1 mmHg, P<0.05, respectively). Four weeks later, 6 hearts remained in good shape with smaller LV end-diastolic dimension (Dd) than baseline values (LV Dd, 9.7+/-0.6mm; fractional area change (FAC), 40.3+/-8.4%) and the other 6 had more redilation in diameter and more deterioration in function than baseline values (LV Dd, 10.9+/-0.6mm; FAC, 25.8+/-6.9%; P<0.05, respectively). Percent fibrosis in the septum differed 11.1+/-3.4 vs. 27.8+/-2.8% between the two groups (P<0.01). There was a significant correlation between the ratio of LV redilatation after surgery and percent fibrosis in the septum (r=0.951, P<0.01). CONCLUSIONS: Although the initial benefit of LVR was confirmed, the long-term result was affected by the amount of residual fibrosis. This information suggests that surgical site selection is important to achieve a good result of LV restoration surgery for DCM.

Animals↗
PubMed2004

Right lateral decubitus position reduces QT dispersion in patients with chronic heart failure.

A greater QT dispersion in patients with chronic heart failure (CHF) appears to be a non-invasive marker of susceptibility to malignant ventricular arrhythmias. We evaluated whether QT dispersion in CHF patients is modified by the patients' recumbent position. In 12 CHF patients, and age and sex-matched 12 normal subjects, a single 12-lead surface ECG was recorded in each postural position [left lateral decubitus position (L), supine position (S), and right lateral decubitus position (R)]. In normal subjects, the QT dispersion was comparable in the three recumbent positions [L: 47+/-15 (SD) ms, S: 40+/-9 ms, R: 38+/-14 ms, P=NS]. In contrast, in CHF patients, QT dispersion was significantly shorter in R than those in L and S (L: 93+/-42 ms*, S: 81+/-29 ms*, R: 63+/-24 ms, *P <.05 vs. R). In conclusion, reclining in R reduces the prolonged QT dispersion in CHF patients.

Aged↗
PubMed2004

Circadian variation of cardiac autonomic nervous activity is well preserved in patients with mild to moderate chronic heart failure: effect of patient position.

BACKGROUND: It remains unclear whether circadian variation (CV) of cardiac autonomic nervous activity (CANA) is preserved in patients with chronic heart failure (CHF) as in healthy subjects. We have demonstrated that CANA in CHF patients is largely affected by patient recumbent position. METHODS: We studied eight mild to moderate CHF patients and eight age, sex-matched healthy subjects. Each subject underwent 24-h ambulatory ECG monitoring. One channel was used to record the CM5 lead, and another to record the signal of patient position from a newly developed, small-sized detector. By using spectral analysis of heart rate variability, frequency-domain measures were calculated. Normalized high-frequency (HF: 0.15-0.40 Hz) power was used as an index of vagal activity and the low frequency (LF: 0.04-0.15 Hz)/HF power ratio was used as an index of sympathovagal balance. These indexes in the same recumbent position were compared between night (2:00-4:00 a.m.) and morning (6:00-8:00 a.m.). RESULTS: In healthy subjects, a definite CV of CANA was observed in each recumbent position. In patients with CHF, in each position, normalized HF power was lower in the morning than at night, whereas LF/HF was higher in the morning than at night. Thus, CANA in CHF patients is influenced not only by patient position but also by the time of day. CONCLUSION: CV of CANA in mild to moderate CHF patients is well preserved when taking patient position into consideration.

Aged↗
PubMed2004

Pericardial fluid level of heart-type cytoplasmic fatty acid-binding protein (H-FABP) is an indicator of severe myocardial ischemia.

BACKGROUND: Heart-type cytoplasmic fatty acid-binding protein (H-FABP) has been reported as a sensitive and specific marker for the early diagnosis of acute myocardial infarction. Our hypothesis was that serum or pericardial fluid levels of H-FABP can reflect not only myocardial infarction but also myocardial ischemia. METHODS: A total of 34 patients with unstable angina, who had anginal symptoms and/or ST-changes in ECG monitoring within 24 h before operation, were classified into group A (n=17), and those without these symptoms and changes into group B (n=17). Blood and pericardial fluid samples were obtained immediately after median sternotomy, and serum and pericardial fluid levels of creatine kinase-MB, cardiac troponin-T, and H-FABP were measured. RESULTS: Serum H-FABP levels were slightly elevated compared with their normal values in both groups. While they showed no difference between groups A and B (group A vs. B: 8.5+/-1.0 vs. 7.1+/-0.7 ng/ml, P=0.25), pericardial fluid levels of H-FABP were significantly higher in group A than in group B (16.3+/-2.0 vs. 9.6+/-1.0 ng/ml, P=0.0046). H-FABP showed a weak correlation between its serum levels and pericardial fluid levels (r=0.40). CONCLUSIONS: Pericardial fluid levels of H-FABP reflect myocardial ischemia occurring within 24 h of their measurements. H-FABP may be secreted into the interstitial space by increased permeability of the myocardial cell membrane associated with severe myocardial ischemia. Thus, pericardial fluid reflects pathophysiological conditions of cardiomyocytes more sensitively than circulating blood.

Aged↗
PubMed2003

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.

Adrenomedullin↗
PubMed2003

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.

Animals↗