Biomedical subjects

Kazunobu Nishimura

Publications and source records attributed to Kazunobu Nishimura.

At least 19 recordsLinked to original sources

PubMed2006

Human gastroepiploic artery has greater chymase activity than the internal thoracic artery.

OBJECTIVE: Recent reports have demonstrated that long-term patency of the gastroepiploic artery (GEA) in coronary artery bypass grafting (CABG) is less satisfactory compared with the internal thoracic artery (ITA). However, the reason has not been fully elucidated. Angiotensin II is known to play an important role in the development of intimal hyperplasia, we hypothesized that the GEA is different from the ITA with respect to angiotensin II-forming ability. Accordingly, we measured activities of angiotensin II-forming enzymes, angiotensin-converting enzyme (ACE) and chymase, in human GEA and ITA. METHODS: Remnant of the GEAs and ITAs were obtained from 24 patients who underwent CABG in which both conduits were used simultaneously. Activities of ACE and chymase were measured by using the extract form the GEA or ITA. Sections of the GEA or ITA were immunohistochemically stained with anti-human chymase antibody. RESULTS: The ACE activity of the GEA (0.28+/-0.16 mU/mg protein) was greater than that of the ITA (0.18+/-0.11, p < 0.001). The chymase activity of the GEA (11.11+/-7.15 mU/mg protein) was also greater than that in the ITA (7.13+/-4.89, p < 0.001). The density of chymase-positive cells in the GEA (3.8+/-4.2 cells/mm2) was greater than that in the ITA (1.1+/-1.2, p < 0.01). CONCLUSION: Activities of both ACE and chymase were significantly greater in the GEA compared with the ITA. The GEA may be different from the ITA with respect to potential ability of angiotensin II-formation.

Aged↗

PubMed2006

Comparison of efficacy of medium-sized cutting balloons versus standard balloons for dilation of peripheral pulmonary stenosis.

The efficacy of medium-sized cutting balloons (CBs) 5 to 8 mm in diameter was compared with that of standard balloons (SBs) in the dilation of peripheral pulmonary stenosis (PPS). Nine vascular lesions in 7 patients were primarily dilated by CBs, and 13 vascular lesions in 11 patients were dilated by SBs alone. The efficacy of balloon dilation was evaluated by angiography and intravascular ultrasound (IVUS). There was no significant difference between the 2 groups in the success rate (66% vs 62%), the percentage increase in minimal lesion diameter (MLD; median 71% vs 52%) on angiography, and the number of new tears (2 vs 1) on IVUS. However, in the subgroup of vascular lesions with MLDs of <4.0 mm, for which CBs with diameters >200% of the MLD could have been applied, the percentage increase in MLD (95% vs 53%, p <0.05) and the number of tears (2 vs 1, p <0.05) with CBs were significantly greater than with SBs, requiring significantly smaller maximum balloon pressure (10 vs 13 atm, p <0.05). CBs are as effective as conventional balloons in the dilation of PPS and may be more effective when larger balloons are available.

Catheterization↗

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

Maintenance of pulmonary vasculature tone by blood derived from the inferior vena cava in a rabbit model of cavopulmonary shunt.

INTRODUCTION: After cavopulmonary shunt in which the superior vena cava is anastomosed to the right pulmonary artery, the right lung is in a unique condition without flow pulsatility and hepatic venous effluent. In a previous study, we reported that hypoxic pulmonary vasoconstriction disappeared in the pulmonary circulation after cavopulmonary shunt. In this study, however, to investigate the influence of pulsatility and hepatic venous effluent on hypoxic pulmonary vasoconstriction in the pulmonary circulation, we developed an alternative cavopulmonary shunt rabbit model that included hepatic venous effluent in the pulmonary circulation and reduced the pulsatility of the pulmonary arterial blood flow. We then observed the physiologic characteristics of the peripheral pulmonary artery after cavopulmonary shunt, specifically the disappearance of hypoxic pulmonary vasoconstriction. METHODS: Sixteen Japanese white rabbits (12-16 weeks old) were used in this study. With general anesthesia, a cavopulmonary shunt was established by anastomosing the right superior vena cava to the right pulmonary artery in an end-to-side fashion. Of the 16 rabbits for the study, the proximal right pulmonary artery was completely ligated in 5 (atresia group) and partially ligated in 6 (stenosis group). Sham operation was performed in the remaining 5 rabbits. Two weeks later, we analyzed the response of the pulmonary artery (which was divided into three categories: segmental, lobular, and acinar level artery) to hypoxia (8% oxygen inhalation) with a specially designed video radiographic system. Morphometric analysis of the resistance pulmonary artery was done in each group after angiography. RESULTS: Mean pressure and pulse pressure in the right pulmonary artery were not significantly different between the atresia and stenosis groups. The mean pulmonary artery pressures in the atresia and stenosis groups were 8 and 11 mm Hg, respectively. However, the pulse pressure was less than 2 mm Hg in both groups. The baseline internal diameter of the resistance pulmonary artery of the atresia group was significantly different from those of the stenosis and sham groups. In the atresia group, the resistance pulmonary arteries did not respond to hypoxia. In contrast, significant constriction (as assessed by percentage change of internal diameter of the resistance pulmonary arteries in the acinar and lobular level arteries) was observed in the pulmonary arteries of the sham and stenosis groups (atresia vs stenosis vs sham 0.4% vs - 19.0% vs - 18.8%, P = .01). In our morphometric study, we observed vasodilation of the resistance pulmonary artery with a thinner medial layer in the atresia group, consistent with the result of microangiography. CONCLUSION: We developed a cavopulmonary shunt rabbit model in which the inferior vena caval blood was derived from the right ventricle. Hypoxic pulmonary vasoconstriction was maintained in the model with the blood flow from the right ventricle. When the blood flow was not maintained, however, hypoxic pulmonary vasoconstriction disappeared. This phenomenon strongly suggests that a substance in hepatic venous effluent partially regulates the physiological pulmonary vascular function in the rabbit lung.

Angiography↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

Prevention of myocardial reperfusion injury by poly(ADP-ribose) synthetase inhibitor, 3-aminobenzamide, in cardioplegic solution: in vitro study of isolated rat heart model.

OBJECTIVE: Cardioplegic arrest remains the method of choice for myocardial protection in cardiac surgery. Poly(adenosine 5'-diphosphate-ribose) synthetase (PARS) inhibitor has been suggested to attenuate the ischemia-reperfusion injury in myocardial infarction by preventing energy depletion associated with oxidative stress. We investigated the efficacy of a cardioplegic solution containing a PARS inhibitor, 3-aminobenzamide (3-AB), for myocardial protection against ischemia-reperfusion injury caused by cardioplegic arrest. METHODS: Isolated hearts were set on a Langendorff apparatus and perfused. The hearts were arrested for 90 min with a cardioplegic solution given at 30-min intervals and then reperfused for 20 min. The hearts of rat in the 3-AB(-) group (n = 8) were perfused with a standard cardioplegic solution and terminal warm cardoplegia, whereas the 3-AB(+) group (n = 8) received these solutions supplemented with 3-AB (100 microM). Left ventricular function and release of cardiac enzymes were monitored before and after cardioplegic arrest. After reperfusion, NAD+ (nicotinamide-adenine dinucleotide) levels were assessed, and the tissues were examined immunohistochemically for oxidative stress and apoptosis. RESULTS: During reperfusion, the 3-AB(+) group showed significantly higher (P = 0.005)dp/dt and lower creatine phosphokinase (CPK) level and glucotamic-oxaloacetic transaminase (GOT) in the effluent (CPK; P = 0.003 GOT; P < 0.001) The cardiomyocytes of the 3-AB(+) group also preserved a higher NAD+ level (P < 0.001). Immunohistochemical study of oxidative stress revealed a lesser extent (P = 0.007) of nuclear staining and a lower fraction of apoptosis in the 3-AB(+) group. CONCLUSION: Cardioplegic solution supplemented with 3-AB provides efficient myocardial protection in cardioplegic ischemic reperfusion by suppressing oxidative stress and overactivation of PARS.

Animals↗

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

Development of biologic coronary artery bypass grafting in a rabbit model: revival of a classic concept with modern biotechnology.

OBJECTIVE: We have developed a technique for biologic coronary artery bypass grafting, which is a revival of a classic concept with modern biotechnology. METHODS: Acute myocardial infarction was created by ligating the major branch of the circumflex artery in rabbits. Animals were divided into four groups: a nontreated group (group N), a group in which omentum was used to wrap the infarcted area (group G), a group in which a gelatin hydrogel sheet incorporating 100 microg basic fibroblast growth factor was placed over the infarcted area (group F), and a group in which the infarcted area was similarly treated with basic fibroblast growth factor followed by omental wrapping (group FG). Cardiac function was subsequently assessed by echocardiography. Postmortem angiography through the gastroepiploic artery was done in groups G and FG. Infarct size and arteriolar density were evaluated. RESULTS: Group FG showed a better fractional area change than did the other groups (group N P <.001, group G P =.002, group F P <.001). Angiography revealed that communication from the gastroepiploic artery to the coronary artery was created through a rich bed of neovascularization in all 7 animals of group FG, whereas poor collaterals were recognized in only 2 of 7 animals in group G. Infarct size was reduced to a greater extent in group FG than in groups F, G, and N (10% +/- 3%, 16% +/- 5%, 19% +/- 7%, 23% +/- 2%, respectively, group F P =.04, groups G and N P <.01). The number of arterioles 20 to 100 microm in diameter was increased to a greater extent in group FG than in groups F, G, and N (23 +/- 5 arterioles/mm(2), 14 +/- 3 arterioles/mm(2), 10 +/- 1 arterioles/mm(2), 4 +/- 2 arterioles/mm(2), respectively), with the differences being significant. CONCLUSIONS: These results show that bypass from the gastroepiploic artery to coronary arteries can be achieved without surgical anastomosis through slow release of basic fibroblast growth factor in this rabbit acute myocardial infarction model. This new revascularization concept, biologic coronary artery bypass grafting, could be applicable for revascularizing many tiny coronary vessels in patients who are difficult to treat with conventional surgery or catheter intervention.

Analysis of Variance↗

PubMed2004

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↗

PubMed2004

Attenuation of adhesion formation after cardiac surgery with a chymase inhibitor in a hamster model.

OBJECTIVE: Chymase is one of the inflammatory mediators and is released from mast cells, which are closely associated with adhesion formation. Chymase also activates transforming growth factor beta1, which promotes tissue fibrosis. However, the role of chymase in cardiac adhesion formation has not yet been elucidated. We have assessed whether a specific chymase inhibitor, Suc-Val-Pro-Phe(p) (OPh)(2), prevents postoperative cardiac adhesions in hamsters. METHODS: In 66 hamsters the epicardium was abraded, and then either chymase inhibitor or placebo was injected into the left thoracic cavity, leaving the pericardium open. Cardiac chymase activity, the level of transforming growth factor beta1 in the pleural fluid, and the density of epicardial mast cells were measured 3 days postoperatively. The degree of adhesion formation was evaluated macroscopically and histologically 2 weeks postoperatively by using a grading score ranging from 0 (no adhesions) to 4 (severe adhesions). RESULTS: The cardiac chymase activity and level of transforming growth factor beta1 were lower in the chymase inhibitor-treated group compared with in the placebo-treated group (45.8 +/- 18.7 vs 79.7 +/- 13.7 microU/mg protein [P <.025] and 15.6 +/- 6.5 vs 33.2 +/- 9.8 microg/mL [P <.01], respectively). The density of mast cells was higher in the placebo-treated group, and there was suppression to 60% of this value in the chymase inhibitor-treated group. The adhesion scores were lower in the chymase inhibitor-treated group compared with in the placebo-treated group (1.3 +/- 1.3 vs 3.0 +/- 1.1, P <.01). CONCLUSION: Use of a chymase inhibitor suppresses not only cardiac chymase activity but also the level of transforming growth factor beta1, and this results in a reduction in postoperative cardiac adhesion.

Animals↗

PubMed2004

Hypoxic pulmonary vasoconstriction disappears in a rabbit model of cavopulmonary shunt.

BACKGROUND: Cavopulmonary shunt is widely known as an interim staging procedure in patients with single-ventricle physiology. However, the physiologic characteristics of the pulmonary arterial system after cavopulmonary shunt are not clearly understood. In this article, we developed a rabbit cavopulmonary shunt model and studied the morphologic changes and physiologic characteristics (namely, hypoxic pulmonary vasoconstriction) of pulmonary arteries after cavopulmonary shunt. METHODS: Male Japanese white rabbits aged 12 to 16 weeks were used for the study. In 5 rabbits, the superior vena cava was anastomosed to the right pulmonary artery in an end-to-side fashion, followed by a proximal side ligation of the right pulmonary artery (cavopulmonary shunt group). In 4 rabbits, the superior vena cava and the right pulmonary artery were dissected and clamped for 10 minutes without making a cavopulmonary shunt (sham group). Two weeks after the operation, we then measured the internal diameter of the acinar (internal diameter, 164 +/- 7 microm), the lobular (305 +/- 13 microm), and the segmental (669 +/- 16 microm) pulmonary arteries in both controlled and hypoxic conditions by using a specially designed x-ray television system. Also, morphometric measurements were made in the pulmonary arteries around the terminal bronchioles. RESULTS: Two weeks after the operation, the arterial oxygen tension under room air conditions was significantly lower in the cavopulmonary shunt group than in the sham group (68.2 +/- 2.2 mm Hg vs 91.1 +/- 1.9 mm Hg; P =.01). The baseline internal diameters in the acinar and the lobular (resistance), but not the segmental (conduit), pulmonary arteries on the anastomosed side of the cavopulmonary shunt group were significantly larger than those of pulmonary arteries on the nonanastomosed side of the cavopulmonary shunt group and the sham group. Moreover, the pulmonary arteries on the anastomosed side of the cavopulmonary shunt group did not respond to hypoxia, whereas those on the nonanastomosed side of the cavopulmonary shunt and sham groups did have local internal diameter reductions in the acinar and lobular arteries (-1.1% +/- 1.0% in the anastomosed side vs -17.7% +/- 3.5% in the nonanastomosed side vs -20.9% +/- 6.1% in the sham group; P =.03). In the morphometric studies, the internal diameter of the pulmonary artery accompanying the terminal bronchiole in the anastomosed side of the cavopulmonary shunt group was significantly larger, and the ratio of medial thickness relative to the outer diameter was smaller compared with ratios in the nonanastomosed side of the cavopulmonary shunt group and the sham group. CONCLUSIONS: We developed a rabbit cavopulmonary shunt model. In the anastomosed side of the cavopulmonary shunt group, the peripheral pulmonary arteries, which contributed greatly in regulating the pulmonary vascular resistance, had a local reduction in the basal vascular tone and no hypoxic vasoconstriction 2 weeks after the operation.

Animals↗

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

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↗

PubMed2003

A pig model of chronic heart failure by intracoronary embolization with gelatin sponge.

BACKGROUND: We produced a large-animal model of left ventricular (LV) failure induced by transcatheter embolization of the left coronary artery using a gelatin sponge. METHODS: Fourteen male pigs underwent transcatheter embolization of the left anterior descending artery (LAD) using gelatin sponge to produce anteroapical myocardial infarction. Coronary angiography was performed 1 week after the coronary embolization. The animals were followed up with echocardiography and LV pressure-volume study for the subsequent 8 weeks, and the data were compared with those of the control group (n = 13). RESULTS: The procedure mortality was 2 of 14 (14%). Coronary angiography revealed the occluded LAD was recanalized with poor run-off. The LV end-diastolic dimension progressively increased (control versus myocardial infarction: 39 +/- 2 mm versus 49 +/- 4 mm, p < 0.001 at week 4; and 40 +/- 2 mm versus 57 +/- 6 mm, p < 0.001 at week 8). Fractional area change decreased over 8 weeks (77% +/- 10% versus 43% +/- 6%, p < 0.001 at week 4; and 77% +/- 10% versus 40% +/- 8%, p < 0.001 at week 8). End-systolic elastance progressively decreased over 8 weeks (3.04 +/- 0.73 mm Hg/mL versus 1.54 +/- 0.51 mm Hg/mL, p < 0.0001 at week 4; and 2.88 +/- 0.44 mm Hg/mL versus 1.05 +/- 0.21 mm Hg/mL, p < 0.001 at week 8). The plasma levels of brain natriuretic peptide were significantly higher in the study group (543 +/- 131 pg/mL versus 1,321 +/- 364 pg/mL, p < 0.001 at week 4; and 610 +/- 152 pg/mL versus 1,523 +/- 232 pg/mL, p < 0.001 at week 8). CONCLUSIONS: This pig model of chronic heart failure is reliable, reproducible, and amenable to investigate other surgical procedures.

Animals↗

PubMed2003

Gelatin sheet incorporating basic fibroblast growth factor enhances sternal healing after harvesting bilateral internal thoracic arteries.

OBJECTIVE: We previously reported that a gelatin sheet incorporating basic fibroblast growth factor accelerated sternal healing after bilateral internal thoracic artery removal in normal and diabetic rats. The aim of this study was to evaluate the effects of this therapeutic modality on sternal healing in a large-animal model before performing a clinical trial. METHODS: After median sternotomy and bilateral internal thoracic artery removal in a pedicled fashion, 14 beagle dogs received either a gelatin sheet incorporating basic fibroblast growth factor (100 mug per sheet) on the posterior table of the sternum (FGF group, n = 7) or did not receive a gelatin sheet (control, n = 7). We compared sternal healing 4 weeks after surgical intervention between the groups. RESULTS: Scintigraphic images obtained by using technetium 99 methylene diphosphonate bone scanning were assessed visually, and the impulse rate was quantified 30 and 60 minutes after injection of technetium 99 methylene diphosphonate to evaluate the sternal perfusion. Sternal uptake was significantly increased in the FGF group (30 minutes: 221% +/- 30% vs 180% +/- 36%; 60 minutes: 267% +/- 26% vs 197% +/- 42%; P <.01). Apparent sternal dehiscence, as assessed radiographically, was observed only in the control animals. Histologically, complete healing of the sternum with marked angiogenesis was observed in the FGF group, whereas poor healing with limited angiogenesis was seen in the control animals. Both bone mineral content (134 +/- 49 vs 52 +/- 32 mg, P <.01) and bone mineral density (133 +/- 53 vs 66 +/- 32 mg/mm(2), P <.05) along the incision line of the sternum, as assessed by means of dual-energy x-ray absorptometry, were higher in the FGF group. CONCLUSIONS: A gelatin sheet incorporating basic fibroblast growth factor enhances sternal perfusion and accelerates sternal bone healing in large animals.23

Animals↗

PubMed2003

Toward surgical angiogenesis using slow-released basic fibroblast growth factor.

OBJECTIVE: Therapeutic angiogenesis using basic fibroblast growth factor (bFGF) in coronary artery disease has been documented in a number of papers. However, the effectiveness is discrepant among documents. In this study, we evaluated the distribution of bFGF in the rat heart by different administration methods, and investigated the efficacy of slow-released administration of bFGF using biodegradable hydrogel microspheres (bFGF microspheres) in a pig infarction model toward an enhanced coronary bypass surgery. METHODS: Heart failure due to myocardial infarction was induced in rats and pigs. In the rat study, free form of bFGF (central venous injection, intracoronary injection, and intramyocardial administration) and bFGF microspheres (intramyocardial administration) were given 4 weeks later. The remaining radioactivity of bFGF in the hearts was estimated 1, 24, and 72 h later. On the other hand, the pigs were randomized into two groups 4 weeks after myocardial infarction. While the control group (n=8) had gelatin hydrogel microspheres with saline, the FGF group (n=8) received bFGF microspheres in the left ventricular (LV) wall. RESULTS: In the rat study, after intramyocardial administration of bFGF microspheres, more bFGF remained in the rat heart 72 h later compared with the other methods (P<0.0001). In the pig study, 4 weeks after the treatment, the FGF group had smaller LV diastolic diameter (48.7+/-5.3 vs. 56.7+/-5.2 mm, P<0.01) than the control group. LV end-systolic elastance was higher in the FGF group (2.96+/-1.2 vs. 1.06+/-0.3 mmHg/ml, P<0.01). In microscopic examinations, many neovessels were found in and around the scar tissue, and the vascular density in the FGF group was significantly higher (61.5+/-18.3 vs. 153.0+/-29.0/mm2, P<0.01). In addition, the infarcted LV walls were less expanded and more thickened in the FGF group. CONCLUSIONS: Biodegradable hydrogel microspheres with bFGF improved LV function and inhibited LV remodeling by angiogenesis in pigs with chronic myocardial infarction. bFGF microspheres into ischemic myocardium may revascularize small ungraftable vessels and may potentially increase distal run-off when applied in coronary bypass surgery.

Animals↗

PubMed2003

Simplified chordal reconstruction: 'oblique' placement of artificial chordae tendineae in mitral valve replacement.

We describe a novel chordal-sparing technique of mitral valve replacement using minimum number of artificial chordae tendineae in patients with rheumatic mitral stenosis. Continuity between the papillary muscles and mitral annulus is restored by placing two 3-0 expanded polytetrafluoroethylene mattress sutures: one for the anterior papillary muscle at the 9-10 o'clock position (as defined by mid-anterior annulus to be 0 o'clock) on the mitral annulus, and the other for the posterior papillary muscle at the 5-6 o'clock position.

Artificial Organs↗