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Biomedical subjects

Takeshi Nishina

Publications and source records attributed to Takeshi Nishina.

At least 19 recordsLinked to original sources

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↗

Saphenous vein graft rupture eighteen years after coronary artery bypass grafting.

Delayed saphenous vein graft (SVG) rupture following coronary artery bypass graft (CABG) is an unusual but potentially fatal complication. Herein we report a case of SVG rupture 18 years after CABG. A 75-year-old man had undergone a CABG with SVG in 1987 at another institution. In 2004 the patient developed angina and underwent re-CABG with arterial conduits in our hospital. On the preoperative cineangiogram, the SVG to the right coronary artery (RCA) was irregularly dilated, yet still providing flow to the distal RCA. In 2005 he was readmitted to our hospital for abdominal pain. Chest computed tomography revealed a huge round mass adjacent to the heart. Cineangiogram showed leakage of the contrast in the midportion of the SVG. At operation, graft rupture was evident and repaired under cardiopulmonary bypass. Although cardiac function was well maintained, after the surgery he developed ischemic colitis and died of multiple organ failure on the 17th postoperative day.

Aged↗

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↗

Chymase inhibition prevents cardiac fibrosis and dysfunction after myocardial infarction in rats.

Human chymase activates not only angiotensin II but also transforming growth factor-beta, a major stimulator of myocardial fibrosis, while rat chymase activates transforming growth factor-beta, but not angiotensin II. To clarify the role of chymase-dependent transforming growth factor-beta activation, we evaluated whether chymase inhibition prevents cardiac fibrosis and cardiac dysfunction after myocardial infarction in rats. Myocardial infarction was induced by ligation of the left anterior descending coronary artery. One day after the ligation, rats were randomized into 2 groups: 1) a chymase-treated group that received 10 mg/kg per day of the chymase inhibitor NK3201 orally for 4 weeks; and 2) a vehicle group of non-treated rats with myocardial infarction. We also included a control group who underwent sham-operation and no treatment. Four weeks after ligation, echocardiography revealed that chymase inhibitor treatment reduced the akinetic area and increased fractional area change but did not significantly change left ventricular end-diastolic area. Chymase inhibition significantly reduced left ventricular end-diastolic pressure, increased the maximal end-systolic pressure-volume relationship and decreased the time constant of left ventricular relaxation. Chymase activity in the non-infarcted myocardium was significantly increased in the vehicle group, but it was significantly reduced by chymase inhibitor treatment. The fibrotic area in the cardiac tissues and the mRNA levels of collagen I and collagen III were also significantly lower in the chymase inhibitor-treated group than in the vehicle group. Therefore, the pathway forming chymase-dependent transforming growth factor-beta may play an important role in myocardial fibrosis and cardiac dysfunction rather than left ventricular dilatation after myocardial infarction.

Acetamides↗

Pesticide multiresidue analysis of 303 compounds using supercritical fluid extraction.

Compared to generally used solvent extraction methods, supercritical fluid extraction (SFE) with carbon dioxide has the advantages of automation and simple operation in preparing samples for pesticide residue analysis. This report is the outcome of our evaluation of the practicality of SFE for the preparation of samples for pesticide residue analysis. We studied the recovery of 303 compounds with several crops by a simultaneous analytical method of SFE, cartridge column purification, followed by GC/MS determination. We achieved 70 to 120% recovery for more than 80% of the examined compounds.

Journal Article↗

Does the beta2-agonist clenbuterol help to maintain myocardial potential to recover during mechanical unloading?

OBJECTIVE: Chronic mechanical unloading induces left ventricular (LV) atrophy, which may impair functional recovery during support with an LV-assist device. Clenbuterol, a beta2-adrenergic receptor (AR) agonist, is known to induce myocardial hypertrophy and might prevent LV atrophy during LV unloading. Furthermore, beta2-AR stimulation is reported to improve Ca2+ handling and contribute to antiapoptosis. However, there is little information on the effects of clenbuterol during LV unloading. METHODS AND RESULTS: We investigated LV atrophy and function after LV unloading produced by heterotopic heart transplantation in isogenic rats. After transplantation, rats were randomized to 1 of 2 groups (n=10 each). The clenbuterol group received 2 mg.kg(-1).d(-1) of the drug for 2 weeks; the control group received normal saline. The weight of unloaded control hearts was 48% less than that of host hearts after 2 weeks of unloading. Clenbuterol significantly increased the weight of the host hearts but did not prevent unloading-induced LV atrophy. Papillary muscles were isolated and stimulated, and there was no difference in developed tension between the 2 groups. However, the inotropic response to the beta-AR agonist isoproterenol significantly improved in the clenbuterol group. The mRNA expression of myocardial sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a) and fetal gene shift (myosin heavy chain [MHC] mRNA isozyme) was also significantly improved by clenbuterol treatment. There was no difference in beta1-AR mRNA expression between the 2 groups. In contrast, beta2-AR mRNA was significantly decreased in the clenbuterol-treated, unloaded heart. This indicates that clenbuterol may downregulate beta2-ARs. In the evaluation of apoptosis, mRNA expression of caspase-3, which is the central pathway for apoptosis, tended to be better in the clenbuterol group. CONCLUSIONS: During complete LV unloading, clenbuterol did not prevent myocardial atrophy but improved gene expression (SERCA2a, beta-MHC) and beta-adrenergic responsiveness and potentially prevented myocardial apoptosis. However, chronic administration of clenbuterol may be associated with downregulation of beta2-ARs.

Adrenergic beta-Agonists↗

Cardiac functional analysis with multi-detector row CT and segmental reconstruction algorithm: comparison with echocardiography, SPECT, and MR imaging.

PURPOSE: To evaluate accuracy of cardiac functional analysis with multi-detector row computed tomography (CT) and segmental reconstruction algorithm over a range of heart rates. MATERIALS AND METHODS: Institutional review board approval was obtained. Informed consent was not required. Multi-detector row CT (500-msec rotation time, 8 x 1-mm detector collimation) and magnetic resonance (MR) imaging were performed in 50 patients (28 men, 22 women; age range, 46-84 years; mean age, 67 years). Two-dimensional echocardiography was performed in 41 patients, and electrocardiographically (ECG)-gated single photon emission computed tomography (SPECT) was performed in 27. End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), and left ventricular (LV) mass were estimated with multi-detector row CT and compared with values estimated with MR imaging, which served as the reference standard. Additionally, EF values estimated with multi-detector row CT, echocardiography, and SPECT were compared with those estimated with MR imaging. Systemic error and degree of agreement of global functional parameters measured with MR imaging and other modalities were assessed. In a second analysis, linear regression analysis was added. RESULTS: EF estimated with multi-detector row CT agreed and correlated well with EF estimated with MR imaging (bias +/- standard deviation, -1.2% +/- 4.6; r = 0.96). Agreement and correlation were similar for EDV (-0.35 mL +/- 15.2; r = 0.97), ESV (1.1 mL +/- 8.6; r = 0.99), and LV mass (2.5 mL +/- 15.0; r = 0.96). Standard deviation of EF difference between multi-detector row CT and MR imaging was significantly less than that between echocardiography and MR imaging (P < .001) or that between SPECT and MR imaging (P < .001). CONCLUSION: Various LV functional parameters were measured with multi-detector row CT with a segmental approach, and measurements correlated and agreed with those obtained with MR imaging. Moreover, functional analysis with multi-detector row CT was more accurate than that with two-dimensional echocardiography or ECG-gated SPECT.

Aged↗

Atrial natriuretic peptide helps prevent late remodeling after left ventricular aneurysm repair.

BACKGROUND: Left ventricular aneurysm repair (LVR) reduces LV wall stress and improves LV function. However, as we reported previously, the initial improvement of LVR was short-term because of LV remodeling but could be maintained longer with postoperative use of an angiotensin-converting enzyme (ACE) inhibitor. Atrial natriuretic peptide (ANP) has been used to treat patients with heart failure by natriuretic and vasodilatory actions. Recent reports have suggested that ANP inhibits the rennin-angiotensin system. In this study, the effects of ANP after LVR were evaluated. METHODS AND RESULTS: Rats that had an LV aneurysm 4 weeks after left anterior descending artery ligation underwent LVR by plicating the LV aneurysm and were randomized into 2 groups: LVR+A group was intravenously administrated with 10 microg/h of carperitide, recombinant alpha-hANP, by osmotic-pump for 4 weeks, and the LVR group was given normal saline. Echocardiography revealed better LV remodeling and function in LVR+A group than in LVR group. Four weeks after LVR, left ventricular end diastolic pressure (LVEDP) and Tau were significantly lower in LVR+A group (LVEDP: 10+/-4 in LVR+A group versus 18+/-6 mm Hg in LVR group, Tau: 13+/-2 versus 17+/-2ms). End-systolic elastance (Ees) was higher in LVR+A group (Ees: 0.34+/-0.2 versus 0.19+/-0.11 mm Hg/microL). The levels of myocardial ACE activity in LVR+A group was significantly lower than in LVR group. The mRNA expressions of brain natriuretic peptide and transforming growth factor beta1 inducing fibrosis significantly decreased in LV myocardium in LVR+A group. Histologically, myocardial fibrosis was significantly reduced in LVR+A group. CONCLUSIONS: Intravenous administration of ANP had beneficial effects on LV remodeling, function, and fibrosis after LVR. ANP could be a useful intravenous infusion drug for postoperative management after LV repair surgery.

Animals↗

Pharmacological assessment of composite arterial conduits using angiography early in the postoperative period.

OBJECTIVES: Muscular arteries are vulnerable to vasospasm unlike elastic arteries. Having developed experimental models of composite arterial grafts, we assessed and compared the responses of the grafts with different pharmacological agents using angiography early in the postoperative period. SUBJECTS AND METHODS: We harvested the internal thoracic artery (ITA) and brachial-median artery (BMA) from 10 sheep. BMA was used as an alternative to the radial artery. Each vessel was assessed histologically and morphologically. Then, a serial composite graft was constructed so that BMA was interposed. On postoperative day one or two, angiography was performed on the composite graft to measure the diameter of each vessel in response to phenylephrine (alpha-adrenergic receptor agonist), nitroglycerin+phenylephrine, and milrinone+phenylephrine. RESULTS: The BMA had a wide media layer which consisted of abundant smooth muscle cells. The combined intima and media were thicker in BMA than in ITA (p<0.01). After injection of phenylephrine, the BMA diameter decreased (2.5+/-0.4 mm to 1.9+/-0.3 mm, p<0.01), while the ITA diameter remained unchanged (3.7+/-0.2 mm to 3.6+/-0.2 mm). Continuous infusion of nitroglycerin or milrinone prevented phenylephrine-induced vasoconstriction of the BMA (p<0.05). CONCLUSIONS: These results suggest that muscular arteries have a more pronounced vasoconstrictive response to alpha-adrenergic receptor agonists than the elastic arteries. To avoid potential decrease in graft flow of muscular artery, it is advisable to use a vasodilator nitroglycerin or milrinone early in the postoperative period.

Animals↗

Visualization of intramuscular left anterior descending coronary arteries during off-pump bypass surgery.

In off-pump coronary artery bypass surgery, an appropriate method for intraoperative evaluation of grafts and vessels has been awaited. We report the usefulness of a 15-MHz linear transducer for this purpose. A 15-MHz linear transducer with a SONOS 5500 (Philips Medical Systems, Best, Netherlands) was applied epicardially in off-pump coronary artery bypass surgery patients. Vascular anatomy was easily discerned when the transducer was applied in an appropriate way. In 6 patients, intramuscular coronary arteries were easily detected, and in all of these patients, anastomoses were successful. The shapes of the anastomoses were very clearly shown, and the flow and its phase in the bypass graft or coronary artery were measured with synchronization of electrocardiograms in all patients. The total left internal thoracic artery (LITA) flow (28.4 +/- 6.8 mL/s) and the pattern of the flow was dominantly diastolic in all patients. The 15-MHz linear transducer system (Philips) is very useful for detecting intramuscular left anterior descending coronary arteries and may become one of the standard tools for intraoperative evaluation in off-pump coronary artery bypass surgery.

Coronary Artery Bypass↗

Down-regulation of endothelin-1 and alteration of apoptosis signaling following left ventricular volume reduction surgery in heart failure of adult rats.

While left ventricular (LV) reduction surgery (LVR) is a novel treatment for severe heart failure, alteration of signal transduction pathways by this surgery is unknown. LV endothelin-1 plays a critical role in LV remodeling following myocardial infarction (MI). Another possible mechanism of remodeling is myocardial cell loss due to apoptosis. The purpose of the present study was to determine whether the LV endothelin-1 level and apoptosis signaling change after LVR. Adult rats were divided into two groups: non-MI group and MI group, and the MI group was subjected to permanent ligation of the left anterior descending artery. Four weeks later, rats in the MI group were subjected to LVR (LVR group) or a sham operation (OMI group). Two weeks after the second operation, echocardiography revealed that LVR improved LV systolic function and remodeling. Upregulation of LV endothein-1 was detected only in the OMI group but not in the non-MI group nor in the LVR group. The percentage of terminal deoxynucleotidyl transfer-mediated end-labeling of fragmented nuclei (TUNEL)-positive cardiac myocytes was significantly higher in the OMI group than in the LVR group or the non-MI group. Western blotting of extracts from the left ventricle showed that bcl-2 and bcl-xL levels were restored and caspase-3 activation was repressed after LVR. Thus, LVR modulates the expression of endothelin-1 and apoptosis signaling in failing hearts. These alterations of signal transduction pathways might contribute to the beneficial effects of LVR on systolic function in heart failure.

Animals↗

Upregulation of SR-PSOX/CXCL16 and recruitment of CD8+ T cells in cardiac valves during inflammatory valvular heart disease.

OBJECTIVE: SR-PSOX/CXCL16 is a transmembrane chemokine and is implicated in activated CD8+ T cell trafficking. In the present study, we examined the expression pattern of SR-PSOX/CXCL16 in the heart and investigated a potential role of SR-PSOX/CXCL16 in inflammatory valvular heart disease. METHODS AND RESULTS: Initial expression of SR-PSOX/CXCL16 in murine embryos was detected in endothelial cells lining endocardial cushions in the forming heart at E11.5. From mid-gestation to adult, expression of this gene in the heart was exclusively observed in valvular endothelial cells. Examination of SR-PSOX/CXCL16 expression in human cardiac valves demonstrated that SR-PSOX/CXCL16 was strongly expressed in valvular and neocapillary endothelial cells in patients with infective endocarditis. SR-PSOX/CXCL16 expression in neocapillary endothelial cells was also observed in patients with rheumatic and atherosclerotic valvular disease. Moreover, CD8+ T cells were distributed closely to endothelial cells expressing SR-PSOX/CXCL16. In vitro adhesion assays showed that SR-PSOX/CXCL16 induced adhesion of activated CD8+ T cells to vascular cell adhesion molecule-1 (VCAM-1) through very late antigen-4 (VLA-4) activation. Furthermore, SR-PSOX/CXCL16 stimulated interferon-gamma (IFN-gamma) production by CD8+ T cells. CONCLUSIONS: SR-PSOX/CXCL16 may be involved in CD8+ T cell recruitment through VLA-4 activation and stimulation of IFN-gamma production by CD8+ T cells during inflammatory valvular heart disease.

Animals↗

Autosynchronized systolic unloading during left ventricular assist with a centrifugal pump.

OBJECTIVES: The purpose of this study was to investigate how the inflow cannulation site of the left ventricular assist system with a centrifugal pump would influence cardiac function on failing heart models. METHODS: In 10 sheep, a left ventricular assist system was instituted by an outflow cannula in the descending aorta, two inflow cannulas in the left atrium and the left ventricle, and connecting those cannulas to a magnetically suspended centrifugal pump. A conductance catheter and a tipped micromanometer for monitoring the pressure-volume loop were also inserted into the left ventricle. Myocardial oxygen consumption was directly measured. Heart failure was induced by injection of microspheres into the left main coronary artery. The assist rate was varied from 0% to 100% at each inflow cannulation site. RESULTS: The pump flow with left ventricular cannulation increased during the systolic phase and decreased during the diastolic phase, whereas it was constant with left atrial cannulation. Ejection fraction with left atrial cannulation decreased as the assist rate increased, whereas that with left ventricular cannulation was maintained up to 75% assist. The external work with left atrial cannulation decreased gradually as the assist rate increased, whereas the external work with left ventricular cannulation did not decrease until the assist rate reached 75%. The myocardial oxygen consumption in both cannulations decreased proportionally as the assist rate increased; they were significantly less with left ventricular cannulation at the 100% assist rate than with left atrial cannulation. CONCLUSION: Left ventricular cannulation during left ventricular assistance maintains ejection fraction and effectively reduces oxygen consumption.

Analysis of Variance↗

Angiotensin-converting enzyme inhibitor helps prevent late remodeling after left ventricular aneurysm repair in rats.

BACKGROUND: We reported in a previous study that the initial effects of left ventricular (LV) repair (LVR) for LV aneurysm were not long lasting. Angiotensin-converting enzyme inhibitor (ACE-I) is known to attenuate remodeling after myocardial infarction, and could be effective after LVR. METHODS AND RESULTS: Left ventricular aneurysms were developed in rats after left anterior descending artery ligation. Rats were divided into 3 groups: sham operation with ACE-I (lisinopril 10 mg/kg/d) (n=10; group A), LVR (by plicating the LV aneurysm) with placebo (n=8; group R), and LVR with ACE-I (n=10; group RA). LV function was evaluated by echocardiography and catheterization. Oxidative stress in the myocardium was estimated by immunohistochemistry for 8-hydroxy-2'-deoxyguanosine. One week after LVR, LV end-diastolic area was smaller and fractional area change was better in the 2 LVR groups. Four weeks after LVR, LV end-diastolic area, and fractional area change deteriorated in group R but not so much in group RA; E-max was higher in group RA (0.79+/-0.20 mm Hg/mL) than in groups A (0.25+/-0.03 mm Hg/mL; P<0.01) and group R (0.27+/-0.03 mm Hg/mL; P<0.01). Oxidative stress was much lower in the 2 ACE-I groups. CONCLUSIONS: LVR improved LV size and systolic function only in the early phase. Adjuvant use of ACE-I was useful for preventing redilation and maintaining LV systolic function, was associated with suppressed oxidative stress, and may make LVR a more effective surgical procedure for LV aneurysm.

8-Hydroxy-2'-Deoxyguanosine↗

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.

Animals↗

Up to 8-year follow-up of valve replacement with carbomedics valve.

BACKGROUND: The aim of this study was to report midterm valve replacement (VR) results with the Carbo-Medics valve (Sulzer Carbomedics, Austin, TX). METHODS: From 1991 to 1999, 468 patients aged 13 to 76 years (mean 56 years) underwent VR with CarboMedics valve: 239 aortic (A), 167 mitral (M), and 62 A+M or double valve replacement (DVR). Mean follow-up time was 4.4 years; follow-up was 99.1% complete for 2,016 patient-years (PY). The anticoagulation level was targeted to an international normalized ratio of 1.47 to 2.8. RESULTS: The hospital mortality rate was 1.2%. Actuarial analysis for the entire group at 7 years for survival was 87%+/-2.3%. Freedom from valve-related death was 94%+/-1.9%. Freedom from thromboembolic and bleeding events, respectively, were as follows: for AVR, 82%+/-4.9% (2.4%/PY) and 88%+/-2.9% (1.6%/PY); for MVR, 95%+/-2.1% (0.8%/PY) and 91%+/-3.1% (1.3%/PY); and for DVR, 96%+/-3.2% (0.7%/PY) and 85%+/-9.7% (1.0%/PY). Actuarial freedom from reoperation was 98%+/-1.4%. CONCLUSIONS: The CarboMedics valve can be implanted with satisfactory early mortality and a low incidence of valve-related events even under low-intensity anticoagulation, as shown in a Japanese population.

Adolescent↗

Cardiomyocyte transplantation does not reverse cardiac remodeling in rats with chronic myocardial infarction.

BACKGROUND: Several reports have documented the potential benefits of cell transplantation as an alternative to cardiac transplantation. This study was designed to investigate whether cardiomyocyte transplantation is effective in rats with chronic myocardial infarction. METHODS: Syngeneic Lewis rats were used in this study. Chronic myocardial infarction was induced in rats by ligating the left anterior descending artery. Four weeks later, after left ventricular (LV) dysfunction with akinetic regions was confirmed by echocardiography, the rats were randomized into two groups: a group that received fetal cardiomyocyte transplantation (TX group; n = 11); and a group that received an intramyocardial injection of culture medium only (control group; n = 12). RESULTS: Four weeks after treatment, the TX group had smaller end-systolic dimension (LVDs) (7.5 +/- 0.9 vs 8.9 +/- 0.8 mm, p < 0.01) and better fractional shortening (FS) (26.2 +/- 5.9 vs 17.7% +/- 5.1%, p < 0.01) than the control group. However, there were no differences in LV end-diastolic dimension, LVDs, and FS between baseline and post-treatment values in the TX group. In addition, plasma levels of atrial natriuretic peptide were not significantly different between the two groups 4 weeks after treatment. In microscopic examination, small amounts of transplanted cardiomyocytes were found only in the periinfarct area, not in the center of scar area, and a thicker ventricular wall in the infarct area was detected in the TX group. CONCLUSIONS: Fetal cardiomyocyte transplantation prevented, but did not reverse, cardiac remodeling that was accompanied with heart failure in myocardial infarction rats. Further investigation is warranted for optimal clinical application to the failing heart.

Animals↗

A rat model of ischaemic or dilated cardiomyopathy for investigating left ventricular repair surgery.

1. The effects of left ventricular repair (LVR) surgery for ischaemic or dilated cardiomyopathy are not fully understood. The development of a proper animal model will help to resolve this issue. 2. The ischaemic cardiomyopathy (ICM) model used was as follows. Twenty-six rats developed ICM with a large akinetic left ventricular (LV) area after ligation of the left anterior descending artery (LAD). Four weeks after surgery, 13 rats underwent LVR by placating the akinetic area (LVR group), while 13 underwent rethoracotomy alone (sham group). 3. The dilated cardiomyopathy (DCM) model is as follows. Six Dahl salt-sensitive (DS) rats were fed an 8% NaCl diet from the age of 9 weeks and developed DCM. These rats had LVR by plicating the LV area between the papillary muscle bases (LVR group), while other rats underwent rethoracotomy alone (sham group). 4. Before LAD ligation in the ICM model or starting the high-salt diet in the DCM model and just before and after LVR or sham surgery, LV dimensions were measured by echocardiography and the heart rate and systolic blood pressure were recorded by the tail-cuff method. 5. In the ICM model, all rats survived the second surgery, after which LV end-diastolic diameter (EDD) decreased, LV fractional shortening (FS) increased (both P < 0.001 vs sham) and heart rate increased (P < 0.05) in the LVR group. 6. In the DCM model, LV EDD decreased and LV FS increased (both P < 0.001) in the LVR group. 7. Both models developed LV dilatation, tolerated LVR and enable reproducible physiological evaluation of the LV. Because the rats survived thereafter, both models may provide a useful tool for various investigations.

Animals↗