[Cardiac Tumor on All Cusps of the Aortic Valve;Report of a Case].

An 80-year-old woman was incidentally found to have a cardiac tumor on the aortic valve by echocardiography. Papillary fibroelastoma(PFE) was strongly suspected, and urgent operation was performed to prevent embolism. Two tumors were identified arising from the left and right cusps with wide stalks, and aortic valve replacement was performed. By pathological examination, the tumors were diagnosed as PFEs. A small tumor was also found on the non-coronary cusp, which was considered as possible PFE or Lambl's excrescence. In the case of multiple PFEs on one valve, valve replacement, instead of simple excision of tumors, should be considered.

Diagnostic Performance of the Simultaneous Acquisition Rest 99 mTc-Tetrofosmin/Stress 201Tl Dual-Isotope Protocol With a Semiconductor Camera　- Comparison With the Rest-Stress 99 mTc-Tetrofosmin Protocol.

BACKGROUND: This study compared the diagnostic value of myocardial perfusion imaging (MPI) between the rest-stress 99 mTc-tetrofosmin protocol (Tc/Tc protocol) and simultaneous acquisition rest 99 mTc-tetrofosmin/stress 201Tl dual-isotope protocol (SDI protocol) with a semiconductor camera.Methods and Results: We retrospectively studied 147 patients who underwent stress MPI using a cadmium-zinc-telluride camera and invasive coronary angiography within a 3-month interval. The Tc/Tc and SDI protocols were used in 59 and 88 patients, respectively. The sensitivity, specificity, and accuracy of the summed difference score in per-patient analysis were 56%, 85%, and 69%, respectively, for the Tc/Tc protocol and 89%, 82%, and 85%, respectively, for the SDI protocol. The area under the receiver operating characteristic curve was significantly better for the SDI than Tc/Tc protocol for the left anterior descending artery (0.836 vs. 0.674; P=0.0380), the left circumflex artery (0.754 vs. 0.599; P=0.0441), and in per-patient analysis (0.875 vs. 0.707; P=0.0135). There was no significant difference in the diagnostic accuracy of the summed stress score for any vessel or in per-patient analysis between the 2 protocols. CONCLUSIONS: The SDI protocol had a higher diagnostic accuracy for the detection of coronary ischemia than the Tc/Tc protocol.

The side-to-side fashion for individual distal coronary anastomosis using venous conduit.

Regarding to coronary artery bypass grafting (CABG), the end-to-side anastomosis (ESA) has been performed as a gold standard. Recently, the effectiveness of the distal side-to-side anastomosis (SSA) in CABG using internal mammary artery has been reported. The benefit of SSA comparing to ESA also has been disclosed by computing simulation. However, use of SSA by venous conduit for individual CABG has not been reported. In this study, we investigated feasibility of SSA. From January 2013 to October 2014, we conducted 114 CABGs. There were 92 venous distal anastomoses without sequential anastomotic site (61 SSA and 31 ESA). The anastomosis was evaluated before discharge and at 1 year after the procedure by angiography or multi-detector row computed tomographic coronary angiography. The median values for time to anastomosis were 13 min in the two group (p = 0.89). There was no revision of anastomosis in both groups. Additional stitches for hemostasis were required significantly less in SSA than ESA (18.0 vs 45.2 %, respectively, p < 0.05). Early angiographic patency; 96.6 % for SSA vs 93.5 % for ESA (p = 0.50), and percentage of good anastomotic figure; 91.2 % for SSA vs 87.1 % for ESA (p = 0.54) were similar in both groups. The angiographic patency at 1 year were 92.9 % for SSA and 81.0 % for ESA (p = 0.16). There was no predictive factor for early and late graft failure. Our study showed feasibility of SSA using venous conduit in individual CABG based on early and mid-term angiographic results. This anastomotic fashion is easy to perform and maybe beneficial in blood flow pattern.

Health-related quality of life prospectively evaluated by the 8-item short form after endovascular repair versus open surgery for abdominal aortic aneurysms.

Open repair for infra-renal abdominal aortic and iliac artery aneurysms (AAAs) is a robust treatment. On the other hand, endovascular aneurysm repair (EVAR) has been widespread because of its less invasiveness. However, patients after EVAR frequently require postoperative radiographic examinations and may feel anxiety for their endoleaks. We prospectively evaluated Health-related Quality of Life of the patients with these two fashions using the 8-item Short Form (SF-8). From 2011 to 2013, 89 consecutive elective cases of AAAs were treated. They were prospectively divided into EVAR and open repair groups but not randomly. The exclusion criteria were as follows: perioperative status for other surgeries, infectious aneurysm, severely deteriorated conditions, and patients who cannot answer for these questionnaire or show their consent. The SF-8 questionnaire was completed through interviews preoperatively, and at 1, 3, 6, and 12 months after treatment. The SF-8 questionnaire was completed for 55 cases [EVAR group (ER): 25, open repair group (OR): 30]. There was no significant difference between these groups regarding patients' characteristics except congestive heart disease. The preoperative scores of the SF-8 were similar in both groups except physical function and social function, which were lower in ER (p < 0.05). There was no operative death in both groups. Operative duration and hospital stay in EVAR were significantly shorter than those in OR (p < 0.05). Follow-up rate at 1, 3, 6, and 12 months was 100, 100, 68.0, and 64.0% in ER, and 100, 90.0, 80.0, and 66.6% in OR, respectively. During follow-up, both groups had no AAAs associated death. Regarding changes of the SF-8 scales, there were some trends at physical component summary score (PCS) and mental component summary score (MCS) in ER. The PCS decreased at 1 month, gradually increased at 3 months, and levelled off until 12 months. The MCS increased at 1 and 3 months, but gradually went down and almost stayed at the same level as preoperative one at 12 months. In OR, PCS and MCS decreased at 1 month and after that increased gradually at 3 and 6 months, and stayed the same at 12 months. The MCS recovered to preoperative score earlier than the PCS. In this study, EVAR did not show any significant mental disturbance based on the SF-8 for 1-year comparing to open repair.

Estimated pulmonary capillary wedge pressure assessed by speckle tracking echocardiography predicts successful ablation in paroxysmal atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with left atrial (LA) remodeling caused by pressure and/or volume (LAV) overload. Increased pulmonary capillary wedge pressure (PCWP) represents LA pressure overload. We recently reported that pulmonary capillary wedge pressure (ePCWP) can be estimated by the kinetics-tracking (KT) index that combines LA function and volume using speckle tracking echocardiography (STE), and has a strong correlation with PCWP measured by right heart catheterization (r = 0.92). Therefore, we hypothesized that ePCWP is the best echocardiographic predictor of successful AF ablation. METHODS: We enrolled 137 patients with paroxysmal AF (age: 61 ± 10 years) who underwent pulmonary vein isolation. We measured LAV index, LA emptying function (EF) and LA stiffness during sinus rhythm before ablation using STE. PCWP was noninvasively estimated by STE as we previously reported. Parameters were compared between a group with AF recurrence (n = 30, age: 59 ± 11 years) and a group with successful ablation (sinus rhythm maintained for >1 year) (n = 107, age 61 ± 11 years). RESULTS: The ePCWP was correlated with PCWP measured by right heart catheterization (r = 0.76, p < 0.01). Compared with the non-recurrence group (n = 107, age: 61 ± 11), the AF recurrence group had significantly increased ePCWP (10.6 ± 3.5 vs 14.6 ± 2.9 mmHg, p < 0.01), minimum LAV index (29 ± 12 ml/m(2) vs 37 ± 14 ml/m(2), p < 0.01) and LA stiffness (0.47 ± 0.33 vs 0.83 ± 0.59, p < 0.01), but lower total LA EF (44 ± 11% vs 39 ± 13%, p < 0.01) before ablation. In multivariate logistic regression analysis, ePCWP was the most significant independent predictor of successful ablation. Using 13 mmHg of PCWP as the optimal cutoff value, the sensitivity and specificity for successful ablation were 73 and 77% (area under the curve = 0.81), respectively. CONCLUSION: The ePCWP that is measured by the combination of LA function and volume before ablation was a better predictor of the successful ablation compared with LA function and volume separately. The ePCWP estimated by STE is useful to predict the successful ablation in paroxysmal AF, and could be useful to improve candidate selection for AF ablation.

Inflammatory myofibroblastic tumor of the heart.

An inflammatory myofibroblastic tumor (IMFT) is recognized as benign tissue proliferative response comprising a variety of inflammatory and mesenchymal cells, and presents commonly at a young age. Although it occurs most frequently in the lung, it has also been observed in other organs and tissues such as the liver, spleen, bladder, and lymph nodes. However, IMFT of the heart is rare, and previously only 38 cases have been reported in the English literature. We herein report the case of a 65-year-old woman with asymptomatic IMFT in the right ventricular outflow tract. Previously reported cases are reviewed.

Varicose vein treatment reduces edema not only in the treated legs but also in the entire body.

OBJECTIVES: We explored the connection between varicose vein and edema, by investigating extracellular water ratio (E/T) using bioelectrical impedance analysis. METHODS: In a prospective cohort study 120 patients underwent varicose vein surgery with extracellular fluid to total body water ratio (E/T) and E/T postop divided by E/Tpreop (E/T ratio) measured using a body composition analyzer. Edema was defined as E/T ≥0.390. Seventy-nine patients received unilateral treatment, while 41 underwent bilateral. p < .05 is statistically significant. RESULTS: Preoperatively, patients exhibited edema (E/T) in the treated leg (0.394 ± 0.009), untreated leg (0.392 ± 0.009), trunk (0.390 ± 0.007), and whole body (0.391 ± 0.007). Postoperatively, E/T decreased across body (p < .05). The lowest E/T ratio was observed in the treated leg (0.991 ± 0.012), followed by the untreated leg (0.994 ± 0.012), the trunk (0.995 ± 0.009), and the whole body (0.994 ± 0.009). E/T ratio of bilateral group were lower than unilateral group (p < .05). CONCLUSION: Varicose vein contributes to generalized edema, and treatment alleviates edema in the treated leg and the entire body.

Neuromuscular electrical stimulation after cardiovascular surgery mitigates muscle weakness in older individuals with diabetes.

BACKGROUND: Cardiovascular surgery leads to postsurgical muscle weakness, probably because of muscle proteolysis and peripheral nerve dysfunction, which are augmented by aging and diabetes mellitus. OBJECTIVE: We examined the effect of neuromuscular electrical stimulation (NMES) on postsurgical muscle weakness in older individuals with diabetes mellitus. METHODS: We conducted a multicentre, randomized, controlled trial, and screened consecutive patients with diabetes who underwent cardiovascular surgery for eligibility (age ≥ 65 years). Those included were randomly assigned to the NMES or the sham group. The primary outcome was the percent change in isometric knee extension strength (%ΔIKES) from preoperative to postoperative day 7. Secondary outcomes were the percent change in usual (%ΔUWS), maximum walking speed (%ΔMWS), and grip strength (%ΔGS). A statistician who was blinded to group allocation used intention-to-treat analysis (student t test). RESULTS: Of 1151 participants screened for eligibility, 180 (NMES, n = 90; sham, n = 90) were included in the primary analysis. %ΔIKES was significantly lower in the NMES than sham group (NMES: mean -2%, 95% confidence interval [CI] -6 to 1; sham: -13%, 95% CI -17 to -9, p < 0.001). Among the secondary outcomes, %ΔMWS was significantly lower and %ΔUWS and %ΔGS were lower, although not significantly, in the NMES than sham group. CONCLUSIONS: A short course of NMES (< 1 week) mitigated postsurgical muscle weakness and functional decline in older persons with diabetes mellitus. NMES could be recommended as a part of postsurgical rehabilitation in older people with diabetes mellitus, especially those with a low functional reserve.

A Case of Collapsed Stent Graft, Severe Lower Limb Ischemia, and Ruptured Abdominal Aortic Aneurysm Due to Type B Acute Aortic Dissection 3 Years after Endovascular Aneurysm Repair.

We report a case of stent graft occlusion, severe lower extremity ischemia, and ruptured abdominal aortic aneurysm due to type B acute aortic dissection 3 years after endovascular aneurysm repair. He admitted our hospital because of abrupt back pain and dysesthesia of bilateral lower limb. Contrast-enhanced computed tomography (CT) scan showed type B acute aortic dissection and occlusion of the stent graft due to dynamic compression by the false lumen. Emergent right axillo-bifemoral bypass operation was done for his critical limb ischemia. Immediately after the successful operation, he fell into shock vital and dissecting abdominal aortic aneurysm rupture was revealed by CT scan. We performed the stump occlusion of the infrarenal abdominal aorta and the bilateral common iliac arteries by abdominal midline incision. Postoperative myonephropathicmetabolic syndrome due to the left ischemia resulted in amputation of his left lower leg for lifesaving. While EVAR cases are increasing, various its complications come to be reported. We consider that this case report might be cautious about the indication of EVAR for the younger generation. (This is a translation of Jpn J Vasc Surg 2019; 28: 367-371.).

Clinical benefits of fast-track rehabilitation program for patients with uncomplicated type B acute aortic dissection.

OBJECTIVES: Uncomplicated type B acute aortic dissection (UTBAAD) has traditionally been treated medically. Although patients are treated based on the rehabilitation program established by the Japanese Circulation Society, we sometimes encounter patients with complications related to the long duration of bed rest. We performed novel fast-track rehabilitation for UTBAAD, which consisted of short-duration bed rest and the early initiation of walking under secure blood pressure control. METHODS AND RESULTS: From April 2009 to February 2017, there were 73 consecutive cases of UTBAAD. Conventional medical treatment was administered to 39 patients (group G) during the early period. From August 2013, 34 patients (group F) received our 'fast-track' rehabilitation program, which consisted of the following: oral intake and assuming a sitting position from day 1 after the onset, standing by the bed from day 2, walking in their room from day 4, and discharge from day 16 if all goes smoothly. Group F had a significantly earlier initiation of standing and walking, first defecation, and weaning from oxygen and intravenous antihypertensive agents than group G. The pneumonia complication rate was significantly lower in group F than in group G. The hospitalization duration was markedly shorter and the in-hospital expense lower in group F than in group G. There were no significant differences in the rate of late adverse aortic events within 12 months after onset. CONCLUSIONS: Our fast-track rehabilitation program for patients with UTBAAD resulted in a better in-hospital clinical course and lower expense than conventional medical treatment without any adverse aortic events.

Bilateral internal thoracic artery grafting: propensity analysis of the left internal thoracic artery versus the right internal thoracic artery as a bypass graft to the left anterior descending artery.

OBJECTIVES: To compare different configurations of the bilateral internal thoracic arteries for the left coronary system and examine early and late outcomes, including mid-term graft patency. METHODS: We reviewed 877 patients who underwent primary isolated coronary artery bypass grafting using in situ bilateral internal thoracic arteries [in situ right internal thoracic artery (RITA)-to-left anterior descending artery (LAD) grafting, n = 683; in situ left internal thoracic artery (LITA)-to-LAD grafting, n = 194]. We compared mid-term patency between the grafts. Propensity score matching was performed to investigate early and long-term outcomes. RESULTS: The 2-year patency rate for RITA-to-LAD and LITA-to-LAD grafts were similar. Multivariate analysis revealed that RITA-to-non-LAD anastomosis (P = 0.029), postoperative length of stay (P = 0.003) and chronic obstructive pulmonary disease (P = 0.005) were associated with graft failure. After statistical adjustment, 176 propensity-matched pairs were available for comparison. RITA-to-LAD grafting enabled a more distal anastomosis. Kaplan-Meier analysis revealed that the incidences of death, repeat revascularization and myocardial infarction were significantly higher in the LITA-to-LAD group among both the unmatched and matched samples (P = 0.045 and 0.029, respectively). CONCLUSIONS: The mid-term patency and outcomes of RITA-to-LAD grafting are good and reduces future cardiac event, in contrast to LITA-to-LAD grafting.

The Prevalence and Distribution of Occlusive Lesions of the Cerebral Arteries in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Intracranial cerebral atherosclerosis is a significant predictor of stroke after coronary artery bypass grafting (CABG). However, there is limited information on intracranial occlusive lesions in patients undergoing CABG. The purpose of the study was to elucidate the precise prevalence and distribution of occlusive lesions of the extracranial and intracranial arteries in patients undergoing CABG. Between 2009 and 2016, 205 patients underwent preoperative magnetic resonance angiography and elective CABG. The prevalence and the distribution of occlusive lesions were retrospectively examined by preoperative magnetic resonance angiography. Association between postoperative central nervous system (CNS) complications and the occlusive lesions was analyzed. Fifty-six patients (27.3%) and 60 patients (29.3%) had occlusive lesions of the extracranial and intracranial arteries, respectively. Twenty-eight patients (13.7%) had both extracranial and intracranial occlusive lesions. Thirty-one (15.1%) and 45 (22.0%) patients had severe stenosis or occlusion of the extracranial and intracranial arteries, respectively. The intracranial internal carotid artery was the most commonly affected intracranial artery (60 vessels; 62.5%), followed by the middle cerebral arteries (20 vessels; 20.8%). Sixteen patients (7.8%) suffered from postoperative CNS complications, including 2 permanent strokes. The etiology of the stroke was attributable to a predefined intracranial lesion in 1 patient. In multivariate analysis, the presence of intracranial occlusive lesions was found to have an independent association with the development of CNS complications (odds ratio 4.05; 95% confidence interval 1.13-14.6). The prevalence of intracranial occlusive lesions was higher than that of extracranial lesions in patients undergoing CABG. There was a solid trend toward the anterior distribution of the intracranial occlusive lesions.

Validation by Cardiac Catheterization of Noninvasive Estimation of Time Constant of Left Ventricular Pressure Decline as an Index of Relaxation by Speckle Tracking Echocardiography.

There has been no established echocardiographic parameter to accurately assess left ventricular (LV) relaxation. Impaired LV relaxation assessed by the time constant of LV pressure decline (Tau) is one of the major components of diastolic dysfunction. We sought to noninvasively estimate Tau (eTau) by speckle tracking echocardiography (STE) and to validate the eTau against Tau by catheterization. Tau was reported to be calculated using the isovolumic relaxation time (IVRT), LV end-systolic pressure, and left atrial (LA) pressure. We reported that pulmonary capillary wedge pressure (ePCWP) can be noninvasively and accurately estimated as 10.8 - 12.4 × Log (LA active emptying function/minimum LA volume index). Therefore, the eTau by STE is noninvasively calculated using the formula: eTau = IVRT / (ln 0.9 × systolic blood pressure-ln ePCWP). Echocardiographic parameters were measured just before catheterization in 110 patients with cardiac disease (age 72 ± 8). There was a good correlation between the eTau and Tau by catheterization (r = 0.69, p <0.001), whereas IVRT and the e' had a poor correlation with Tau (r = 0.33 and -0.33, respectively). The sensitivity and specificity of the eTau to predict prolonged Tau (>48 ms) was 77% and 91%, respectively, with area under curve of 0.87 using an optimal cutoff of 48 ms. Bland-Altman analysis revealed a good agreement between the eTau and Tau. In conclusion, this study demonstrated that the eTau by our noninvasive method has a good correlation with Tau obtained by cardiac catheterization. LV relaxation may be noninvasively and accurately estimated by STE.

Impact of glucose control on early vein graft failure after coronary artery bypass grafting: one-month angiographic results.

Objectives: To identify factors that determine early saphenous vein graft failure (VGF) within 1 month after coronary artery bypass grafting (CABG). Methods: Seven hundred forty-nine consecutive patients underwent primary isolated CABG with saphenous vein grafts at three Japanese centres from 1 January 2005 to 31 December 2014. According to angiographic findings within 1 month of CABG surgery, 63 patients (8.4%) developed early VGF. We examined the relationships between variables and early VGF by using multivariable logistic regression analysis. Results: The preoperative clinical characteristics were similar between patients with and without early VGF, except for median preoperative haemoglobin A1c levels, which were significantly higher among patients with early VGF (6.7 vs 6.4%, P = 0.046). Additionally, anastomosis to the vessel with chronic total obstruction was performed more frequently among patients with early VGF (22/63 [34.9%] vs 140/686 [20.4%], P = 0.007), and myocardial infarction during the hospital admission occurred more frequently among patients with early VGF (4/63 [6.3%] vs 2/686 [0.3%], P < 0.0001). Results of multivariable analysis showed that the preoperative haemoglobin A1c level was associated with early VGF (odds ratio per unit increase, 1.30; 95% confidence interval, 1.06-1.60; P = 0.013). Conclusions: An increased preoperative haemoglobin A1c level was strongly associated with early VGF after CABG. Thus, VGF happened more frequently in patients with poorly controlled diabetes mellitus.

Aneurysm of the sinus of Valsalva dissecting into the intraventricular septum.

Aneurysm of the sinus of Valsalva is an uncommon entity and especially rare when it dissects into the intraventricular septum. This uncommon clinical manifestation often takes a drastic clinical course with life-threatening arrhythmia, coronary ischemia, rupture, and heart failure. We present the case of a 36-year-old man with an aneurysm of the sinus of Valsalva dissecting into the intraventricular septum, which induced severe aortic insufficiency and heart block.

Noninvasive estimation of pulmonary capillary wedge pressure in patients with mitral regurgitation: A speckle tracking echocardiography study.

BACKGROUND: Echocardiographic parameters to predict pulmonary capillary wedge pressure (PCWP) in mitral regurgitation (MR) are not yet elucidated. We reported that PCWP could be accurately estimated by novel KT index which is defined as log10[left atrial (LA) emptying function (EF)/LA volume]. We examined the usefulness of the KT index as a predictor of PCWP in primary and secondary MR with sinus rhythm and also MR with atrial fibrillation. METHODS: LA dimension, strain, volume, EF, and E/e' were measured in moderate to severe MR with sinus rhythm (n=58, age: 67±8 years) and MR with atrial fibrillation (n=24, age: 69±11 years) just before catheterization and in normal subjects (n=26, age: 67±11 years) using speckle tracking echocardiography. MR with sinus rhythm was divided into primary MR (n=27) and secondary MR (n=31). The estimated PCWP (ePCWP) was calculated as 10.8-12.4×KT index. RESULTS: There was a correlation between PCWP and LA dimension, E/e', minimum LA volume index, active LAEF, total LAEF, or LA strain (r=0.32, r=0.31, r=0.55, r=-0.61, r=-0.51, and r=-0.50, respectively, p<0.05). The better correlation was found between PCWP and ePCWP in MR including both primary and secondary MR and also MR with atrial fibrillation (r=0.70, r=0.67, and r=0.58, respectively, p<0.01). Multiple regression analysis revealed that ePCWP was an independent predictor of PCWP in MR. The ePCWP demonstrated good diagnostic accuracy (area under the curve of 0.86) and sensitivity (81%) and specificity (71%) to predict elevated PCWP >15mmHg using a cut-off of 16mmHg. CONCLUSION: The ePCWP was the reliable echocardiographic parameter to predict PCWP in primary and secondary MR and might also be useful in MR with atrial fibrillation. The ePCWP may have an incremental value in a clinical setting.

A novel application of myocardial contrast echocardiography to evaluate angiogenesis by autologous bone marrow cell transplantation in chronic ischemic pig model.

OBJECTIVES: We investigated the feasibility of myocardial contrast echocardiography (MCE) to evaluate regional perfusion after bone marrow cell transplantation. BACKGROUND: The myocardial microvessels improved by cell transplantation are too small to visualize with conventional angiography. METHODS: Fourteen mini-pigs from the Nippon Institute for Biological Science were used. The proximal left anterior descending coronary artery was ligated. One month later, nine pigs survived. Six pigs received autologous cell transplantation into the left ventricular anterior wall: bone marrow mononuclear cells (BMMNCs) (n = 3) and bone marrow stromal cells (BMSCs) (n = 3). The other three pigs received saline (control group, n = 3). The pigs were sacrificed one month later. Myocardial contrast intensity (MCI) with a contrast agent was measured using the SONOS 5500 system (Philips). Capillary density (CD) and MCI were measured at four areas: anteroseptum (nontransplanted infarct area), anterior wall (transplanted infarct area), septum (border zone), and lateral wall (normal). We compared the anteroseptum with the anterior wall by MCI and CD. RESULTS: In the BMMNC and BMSC subsets, the CD of the anterior wall was higher than that of the anteroseptum (p < 0.001). There was a linear relation between MCI and CD (acoustic unit [AU2] = 0.234 CD + 0.010, r = 0.92, p < 0.001). At one month after cell transplantation, MCI of the anterior wall increased in the BMMNC and BMSC subsets (p < 0.05), although it did not change in the control group. The ratio of wall thickness (systole/diastole) in the transplanted infarct area was larger than that in the nontransplanted infarct area (p < 0.01). CONCLUSIONS: Myocardial contrast echocardiography is useful to evaluate regional perfusion, which was enhanced by bone marrow cell transplantation.

Endogenous bone-marrow-derived stem cells contribute only a small proportion of regenerated myocardium in the acute infarction model.

BACKGROUND: Our recent study showed that granulocyte-colony stimulating factor (G-CSF) promoted bone-marrow cells (BMC) to migrate into the infarcted heart and that they differentiated into cardiomyocytes. However, we still do not know to what degree bone-marrow-derived cardiomyocytes contribute to myocardial regeneration after injury. In this study, we verified the proportional contribution of cells from bone marrow (BM) and from non-bone marrow (n-BM) in regenerating neomyocardium after myocardial infarction. METHODS: Eight C57BL/6 mice were irradiated (900 cGy), and green fluorescent protein (GFP) mouse-derived BMCs (GFP-BMC, 1 x 10(6) cells) were injected. Four weeks later, the left descending coronary artery was ligated. Recombinant human G-CSF (200 microg/kg/day, 8 days) was injected. At 4 weeks after ligation, hearts were fixed for histology. We calculated the proportions of cardiomyocytes derived from BM and n-BM after taking the chimeric rate into consideration. RESULTS: The chimeric rate was 54.6% +/- 5.9%. At the infarcted border area, the total cell number was 1000.3 +/- 56.5/mm(2), and mobilized BM-derived GFP-BMC was 103.3 +/- 13.1/mm(2). After compensation with the chimeric rate, we found BM-derived troponin I-positive cells at 23.9 +/- 4.1/mm(2), nestin-positive cells at 12.9 +/- 2.6/mm(2), and Ki67-positive cells at 18.3 +/- 2.6/mm(2), respectively. We found significant differences in the contribution of troponin I-(6.7% +/- 1.7% vs 93.3% +/- 1.7%), nestin- (2.4 +/- 0.5 vs 97.6 +/- 0.5), and Ki67-positive (3.9 +/- 1.0 vs 96.1 +/- 1.0) cells derived from BM and n-BM. CONCLUSIONS: Bone marrow was one of the origins of regenerated cardiomyocytes; however, the contribution of cells from BM was very small compared with those of n-BM origin in the infarction model.

Direct cell-cell interaction of cardiomyocytes is key for bone marrow stromal cells to go into cardiac lineage in vitro.

OBJECTIVES: Cardiac environmental factors are thought to be powerful inducers in cardiomyogenic differentiation. In this study we simulated the cardiac environment using coculture and evaluated the cardiomyogenic differentiation in bone marrow stromal cells. METHODS: In group 1 only bone marrow stromal cells derived from transgenic mice expressing green fluorescent protein (GFP-BMCs) were cultured (n = 5). In group 2 cardiomyocytes from neonatal rats were grown on inserts, which we applied to culture dishes seeded with GFP-BMCs (n = 5). In group 3 GFP-BMCs were cocultured with cardiomyocytes on the same dishes (n = 5). We cultured these cells for 7 days and evaluated the synchronous contraction and the cardiomyogenic differentiation of GFP-BMCs by means of immunostaining. RESULTS: In groups 1 and 2 GFP-BMCs protein did not show any myogenic phenotypes for 7 days. In contrast, in group 3 some GFP-BMCs were incorporated in parallel with cardiomyocytes and revealed myotube-like formation on day 1. On day 2, some GFP-BMCs started to contract synchronously with cardiomyocytes. Myosin heavy chain-positive GFP-BMCs were recognized in 2.49% +/- 0.87% of the total GFP-BMCs on day 5 (P <.0001). Cardiac-specific troponin I-positive GFP-BMCs were in 1.86% +/- 0.53% of the total cells on day 5 (P <.0001). Atrial natriuretic peptide was also seen in GFP-BMCs, and connexin 43 was detected between GFP-BMCs and cardiomyocytes. CONCLUSIONS: Direct cell-cell interaction with cardiomyocytes was important for bone marrow stromal cells to differentiate into cardiomyocytes. This coculture was useful for simulating the cardiac environment in vitro for the research of cell transplantation in the heart.