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Kazunobu Nishimura

Publications and source records attributed to Kazunobu Nishimura.

35 records · Page 2Linked to original sources

Improved therapeutic efficacy in cardiomyocyte transplantation for myocardial infarction with release system of basic fibroblast growth factor.

Several studies have demonstrated that cell transplantation was effective for the therapy of myocardial infarction. However, little care has been taken for the blood supply indispensable to cell transplantation. This study is an investigation to evaluate the feasibility of in advance angiogenesis by gelatin microspheres incorporating basic fibroblast growth factor (bFGF) for the transplantation therapy of cardiomyocytes with an ischemic cardiomyopathy model. Rats with myocardial infarction received the intramuscular injection of culture medium (Control), or that containing fetal cardiomyocytes (TX) or gelatin microspheres incorporating bFGF (FGF), and gelatin microspheres incorporating bFGF plus fetal cardiomyocytes 1 week later (FGF-TX). The left ventricle (LV) function of rat hearts was assessed by echocardiography and cardiac catheterization 4 weeks later. The LV maximum time-varying elastance was significantly higher in the FGF-TX group than in other groups. The combination of bFGF-induced angiogenesis and cardiomyocyte transplantation is a promising procedure to improve the LV function in rats with myocardial infarction.

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↗

Importance of preserving the apex and plication of the base in left ventricular volume reduction surgery.

OBJECTIVE: Volume reduction surgery for dilated cardiomyopathy has not yielded predictable outcomes. The purpose of this study was to clarify the efficacy of modified volume reduction surgery in preserving the left ventricular apex and reducing the left ventricular diameter at the base to maintain fiber continuity. METHODS: Heart failure was induced with propranolol in 12 dogs, and the animals were randomized into 2 groups. In one group the left ventricular wall was plicated between the 2 papillary muscles from the middle to the apex (apex-sacrificing volume reduction surgery, group A, n = 6), and in the other group plication was done from the base to the middle (apex-sparing volume reduction surgery, group B, n = 6). Left ventricular function was then compared between the groups by using echocardiography and sonomicrometry crystals. RESULTS: After volume reduction surgery, the fractional area change at the base in group B was greater than that in group A (40% +/- 3% vs 27% +/- 4%, P =.003). Cardiac output in group B was better than that in group A (2.5 +/- 0.2 vs 1.8 +/- 0.2 L/min, P =.023). Left ventricular end-diastolic pressure in group A was higher than that in group B (16 +/- 2 vs 8 +/- 1 mm Hg, P =.001). Fractional shortening in the long axis, as assessed by means of sonomicrometry, was better in group B than in group A. CONCLUSIONS: Apex-sparing volume reduction surgery capable of maintaining left ventricular fiber continuity provided better left ventricular function in both the systolic and diastolic phases than apex-sacrificing volume reduction surgery in the acute heart failure model. This modification might improve the results of left ventricular volume reduction surgery.

Acute Disease↗

The effect of nitroglycerin on myocardial blood flow in various segments characterized by rest-redistribution thallium SPECT.

UNLABELLED: The use of nitrates is reported to be effective in viability detection in scintigraphic perfusion imaging. The purpose of the study was to evaluate the effect of nitroglycerin (NTG) on myocardial blood flow (MBF) and coronary vascular resistance (CVR) in various segments characterized by rest-redistribution (201)Tl SPECT. METHODS: Twenty-three patients with coronary artery disease underwent rest-redistribution (201)Tl SPECT and (15)O-labeled water PET at rest and after NTG spray (0.3 mg). In addition, 11 healthy volunteers were also studied using PET. RESULTS: NTG did not change global MBF in the volunteers or in the patients. In segments with normal (201)Tl uptake and in those with a severe irreversible (201)Tl defect, NTG significantly reduced MBF without changing CVR. NTG reduced CVR in segments with a reversible (201)Tl defect (141 +/- 50 to 114 +/- 29 mm Hg/[mL/min/g], P = 0.004) and in those with a mild-to-moderate irreversible (201)Tl defect (165 +/- 64 to 149 +/- 60 mm Hg/[mL/min/g], P = 0.003), while maintaining MBF. CONCLUSION: NTG preferentially reduces CVR in the viable myocardium with ischemia. After NTG, tracer uptake in the ischemic myocardium will be relatively increased compared with that in the nonviable and nonischemic myocardium, leading to improvements in viability detection.

Aged↗

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↗

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↗

Composite arterial Y graft has less coronary flow reserve than independent grafts.

BACKGROUND: It is not known whether a composite Y graft of the left internal thoracic artery can provide sufficient blood flow to the whole left coronary system. The aim of this study was to compare regional myocardial blood flow (MBF) and coronary flow reserve after coronary artery bypass grafting using arterial composite Y graft or independent arterial grafts. METHODS: Positron emission tomography was performed at rest and after dipyridamole infusion using oxygen-15-labeled water 2 weeks after coronary artery bypass grafting. Regional MBF was calculated in seven segments of the left ventricle. Coronary flow reserve was defined as the ratio of MBF after dipyridamole infusion to MBF at rest. In the Y graft group (n = 22), a free arterial graft to obtuse marginal arteries was anastomosed to the proximal side of in situ left internal thoracic artery, which was anastomosed to the left anterior descending artery. In the independent graft group (n = 13), left anterior descending and obtuse marginal arteries were independently revascularized using in situ left internal thoracic artery and a free arterial graft. RESULTS: There was no difference between the groups in MBF at rest. Coronary flow reserve in the Y graft group was lower than that in the independent group in the anterobasal (1.43 +/- 0.07 versus 1.90 +/- 0.13, p = 0.038), apical (1.24 +/- 0.06 versus 1.64 +/- 0.12, p = 0.003), septal (1.34 +/- 0.05 versus 1.75 +/- 0.13, p = 0.023), and lateral regions (1.19 +/- 0.04 versus 1.66 +/- 0.09, p = 0.001). CONCLUSIONS: Although arterial composite Y graft improved MBF at rest, it was not as effective as independent grafts for improving coronary flow reserve soon after coronary artery bypass grafting.

Aged↗

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↗

Chordal-sparing mitral valve replacement using artificial chordae tendineae for rheumatic mitral stenosis: experience of the "oblique" method.

Chordal-sparing mitral valve replacement (CSMVR) has been proven to be beneficial for postoperative left ventricular (LV) function. In patients with mitral stenosis, however, diseased chordae tendineae (CT) often have to be replaced using artificial CT to achieve CSMVR. Previously, we reported that resusupension of artificial CT in an oblique direction enhances systolic LV function. Among 40 consecutive patients with mitral valve replacement (MVR), 17 (4 men and 13 women; mean age 66.5 years) with rheumatic mitral stenosis underwent CSMVR with oblique resuspension. Echocardiography was done before the operation, early (mean 25 days) after the operation, and at a late stage (mean 14 months). There was no mortality or major morbidity. LV ejection fraction late after the operation (68 +/- 8%) was better than that in the early period (61 +/- 8%, p < 0.01), and comparable to the preoperative level (65 +/- 9%). The oblique method may help to improve the results of MVR.

Aged↗

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.

Animals↗

Spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine levels in cardiomyocytes after myocardial infarction in rats.

Temporary or persistent heart failure is one of the major complications after myocardial infarction (MI). In order to elucidate the pathogenesis of MI, we studied the spaciotemporal alteration of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in cardiomyocytes in a rat model of ligation of the left anterior descending branch of the coronary artery. The lethality in this model was 18%. Hearts were dissected at 0, 3, 6, 12, 24, 48 h, and 1, 2, 4, 6 weeks after the operation. The cardiac level of 8-OHdG was evaluated biochemically as well as by immunohistochemistry with monoclonal antibody N45.1. Three to 6h after ligation, the 8-OHdG levels were increased in the cardiomyocytes of MI (six-fold) and peri-MI (four-fold) areas. After 24 h, the myocardium in the MI area was necrotized, and thereafter the 8-OHdG level decreased. 8-OHdG levels in the myocardium of peri-MI areas returned once to a normal level, but were significantly increased at 2-4 weeks along with the appearance of apoptotic cardiomyocytes in this area. The heart after MI has been generally considered as clinically stable after four weeks. However, cardiomyocytes near the infarcted area were oxidatively stressed even after four weeks when the affected lesion was extensive. The present data support the use of supplementary antioxidant therapies to save functional myocardium after MI. (213 words)

8-Hydroxy-2'-Deoxyguanosine↗

Effects of two inhibitors of renin-angiotensin system on attenuation of postoperative remodeling after left ventricular aneurysm repair in rats.

We reported that the initial beneficial effects of left ventricular repair (LVR) surgery for LV aneurysm after myocardial infarction (MI) did not persist because of postoperative LV remodeling in a rat model. The renin-angiotensin system (RAS) plays an important role in postinfarction LV remodeling. Inhibition of RAS may be useful to preserve LV function by preventing remodeling. We studied the effects of two inhibitors of RAS in an attempt to improve the operative results of LVR. LV aneurysms were created in rats after ligating the left anterior descending artery. These rats underwent LVR by plicating the LV aneurysm and were treated by three methods: no treatment, treatment with angiotensin-converting enzyme inhibitor (ACE-I) (lisinopril 10 mg/kg per day), and treatment with angiotensin II receptor blocker (ARB) (candesartan 5 mg/kg per day). One week after LVR, echocardiography revealed smaller LV size and better LV motion than before surgery. Four weeks after LVR, LV size returned to the preoperative value in the untreated group, but not as much in the treated groups. Cardiac catheterization revealed lower LV end-diastolic pressure and higher E-max in the treated groups. There was no difference between ACE-I and ARB groups except for systolic blood pressure. LVR decreased LV size and improved systolic function only in the early phase. Adjuvant therapy of ACE-I or ARB-attenuated LV remodeling and maintained LV function at the same level after LVR. This probably indicates that tissue RAS is associated with postoperative remodeling. Concomitant use of RAS inhibitors may make LVR a longer-lasting procedure for LV aneurysm.

Angiotensin Receptor Antagonists↗

Two cases using "epi-endocardial patch repair" for postinfarction left ventricular rupture.

The treatment points of left ventricular (LV) free wall rupture after acute myocardial infarction (MI), so far, are to prevent a deterioration of LV function after MI and to prevent a recurrence or extension of the dissection of the infarcted/necrotic myocardium to stop bleeding. We report two cases of LV rupture after myocardial infarction that underwent epicardial patch repair using deep epicardial sutures reaching LV subendocardial area ("epi-endocardial patch" repair). The procedure was done under beating condition with cardiopulmonary bypass in the first case and with preoperatively percutaneous cardiopulmonary support system (PCPS) in the second case to prevent a deterioration of LV function. Hemostasis was effective and complete, and extension of the intramuscular dissection was well blocked. The patients recovered LV function soon. The epi-endocardial sutures can be placed safely without inducing new ischemia, and the method might be possible with beating condition.

Aged↗

Quantitative fluorine 18 deoxyglucose uptake by myocardial positron emission tomography in rats.

BACKGROUND: In vivo quantitative assessment of positron emission tomography (PET) with 2-deoxy-2-[fluorine 18]fluorodeoxyglucose (FDG) for rat heart has not been explored because of the theoretical limitation of spatial resolution. Our objective was to assess whether FDG uptake measured by PET is correlated with tissue radioactivity of FDG in rat heart directly measured by an automated gamma counter. METHODS AND RESULTS: Ten Sprague-Dawley rats were used for echocardiographic assessment and FDG-PET. Rats were sacrificed immediately after PET scanning, and the radioactivity of FDG in 4 segmental tissue samples of the middle transverse section was measured. Quantitative PET values in a total of 40 regions of interest, in which partial volume effect was corrected based on the phantom study and wall thickness obtained by echocardiogram, were compared with radioactivity of the corresponding 40 tissue samples. Linear regression analysis revealed that tissue radioactivity of FDG was well correlated with the quantitative PET value (Y = 1.17X; r = 0.985, P <.0001). CONCLUSIONS: Quantitative FDG-PET for rat heart is a reliable approach for assessing glucose metabolism in vivo after correction is made for partial volume effect. These results can be used for various models of heart disease with repeated studies over the disease process in the same animal.

Animals↗

Heterotopic transplantation of the failing rat heart as a model of left ventricular mechanical unloading toward recovery.

The left ventricular assist device (LVAD) is usually used in patients with end-stage heart failure as a bridge to transplantation. Recently, some studies have reported functional recovery with the use of an LVAD, although the mechanisms responsible for recovery are not fully understood. We investigated the functional recovery of the infarcted, failing rat heart in response to mechanical unloading after heterotopic transplantation. Heart failure was induced in Lewis rats by ligating the left anterior descending artery. After 4 weeks, the infarcted hearts were harvested and heterotopically transplanted. The transplanted infarcted heart was removed after 2 weeks of unloading and examined for hypertrophy and fibrosis, as well as for mRNA levels encoding for brain natriuretic peptide, sarco(endo)plasmic reticulum Ca(2+)-ATPase2a (SERCA2a), and beta1- and beta2-adrenergic receptors. Normal and infarcted rats without transplantation served as control animals. The infarcted heart was hypertrophied as evidenced by an increase in heart weight and myocyte diameter. After unloading the infarcted heart for 2 weeks, there was a decrease in heart weight and myocyte diameter. However, the percentage of myocardial fibrosis increased after unloading. The mRNA expression of brain natriuretic peptide and the beta2-adrenergic receptor significantly improved after mechanical unloading. The levels of SERCA2a mRNA tended to increase after unloading. In conclusion, unloading the failing, infarcted heart can help normalize left ventricular hypertrophy and cardiac gene expression. This unloading model appears to partially mimic the conditions of hemodynamic support with an LVAD in heart failure patients and potentially offers insights into the mechanisms of functional recovery.

Animals↗

A rat model of ischemic cardiomyopathy for investigating left ventricular volume reduction surgery.

OBJECTIVE: The effects of volume reduction surgery (VRS) for ischemic cardiomyopathy are not fully understood. The development of a proper animal model will help to resolve this issue. METHODS: Study 1 (Noninvasive study): Twenty-six rats developed large akinetic left ventricular (LV) aneurysms or ischemic cardiomyopathy after anterior descending artery ligation (first surgery). Four weeks after the surgery, 13 rats underwent volume reduction surgery (second surgery) (VRS group), while 13 underwent rethoracotomy alone (sham group). Before the first surgery, and before and after the second surgery, the LV dimensions were measured by echocardiography, and the heart rate and systolic blood pressure were recorded by the tail cuff method. Study 2 (Invasive study): In 7 rats undergoing the VRS and 9 undergoing the sham operation, LV pressure was measured with a manometer-tipped catheter, immediately before and after the second surgery. RESULTS: Study 1: All rats survived the second surgery, after which LV end-diastolic diameter decreased and LV fractional shortening increased (both p < 0.001) in the VRS group. This group also increased heart rate after the second surgery (p < 0.05). Study 2: There were no differences in LV end-systolic or end-diastolic pressure between the two groups before and after the second surgery. CONCLUSIONS: This model enables reproducible physiological evaluation of the LV after VRS, and since the rats show postoperative survival, it provides a useful tool for various investigations.

Animals↗