Ruptured Vertebral Artery Dissection Treated with Endovascular Intervention.

OBJECTIVE: A retrospective study of cases of endovascular treatment of dissection of the vertebral artery with subarachnoid hemorrhage was conducted. MATERIAL AND METHODS: Data were 11 cases of vertebral artery dissecting aneurysm (VADA) among 291 consecutive subarachnoid hemorrhage patients who underwent clipping or endovascular treatment at Ota Memorial Hospital. Classified into 4 patterns based on the location of the dissection and posterior inferior cerebellar artery (PICA): pre-PICA, post-PICA, involved PICA, and non-PICA. And one of the cases had bilateral vertebral artery dissection, and computational fluid dynamics analysis was included in the study. RESULTS: Ruptured VADA occurred in 11 of the 291 patients (3.8%). Endovascular treatment was performed in 8 of these 11 patients. Postoperative diffusion-weighted imaging detected no high-intensity lesions and no postoperative ischemic complications or rebleeding occurred in any patient. In a case of bilateral VADA, computational fluid dynamics analysis of very low or high wall shear stress at the dissection, low aneurysm formation indicator, and high oscillatory shear index may be considered rupture factors. CONCLUSIONS: Treatment strategies for each branching pattern of PICA can prevent rupture and avoid ischemic complications. And prediction of the rupture side is important in patients with bilateral dissection to consider the appropriate treatment and timing.

Histone H3 K27M mutations in adult cerebellar high-grade gliomas.

Adult cerebellar high-grade gliomas (HGG) are rare and their molecular basis has not been fully elucidated. Although a diffuse midline glioma H3 K27M-mutant, a recently characterized variant of HGG, was reported to occasionally occur in the cerebellum, adult cases were rarely tested for this mutation; only five mutant cases have been reported to date. It currently remains unknown whether H3 K27M-mutant cerebellar gliomas share common histological features or have a uniformly dismal prognosis. In the present study, we assessed the prevalence of histone H3 K27M mutations in ten adult cerebellar HGG, identifying two H3F3A-mutant cases. One case was a 70-year-old female with a cystic lesion. Histologically, the tumor was considered to be glioblastoma; however, a part of the tumor exhibiting low proliferative activity appeared to be consistent with long-standing H3 K27M-mutant tumors in the literature. Another case was a 69-year-old male. The tumor showed a distinct circumscribed histology with minimal astrocytic differentiation, suggesting a nosological issue in the diagnosis of diffuse midline glioma. More cerebellar tumors need to be tested for H3 K27M mutations to clarify the clinical and histopathological spectra of this tumor.

Oculomotor nerve schwannoma associated with acute hydrocephalus: case report.

A 37-year-old woman presented with an extremely rare large oculomotor schwannoma associated with acute hydrocephalus manifesting as semicoma and anisocoria. Brain computed tomography and magnetic resonance imaging revealed a tumor in the oculomotor cistern. Cerebral angiography revealed separation of the posterior cerebral artery (PCA) and superior cerebellar artery (SCA). The tumor was removed subtotally by two stage surgery. Histological examination revealed ordinary schwannoma. The diagnosis of oculomotor nerve schwannoma was based on the intraoperative finding of the tumor origin in the oculomotor nerve. Oculomotor nerve schwannoma can cause acute hydrocephalus and manifest as impaired consciousness. The angiographical separation of the PCA and SCA was very useful for the preoperative diagnosis of oculomotor nerve schwannoma.

Attenuation of ischemic myocardial injury and dysfunction by cardiac fibroblast-derived factor(s).

Fibroblasts, the majority of non-cardiomyocytes in the heart, are known to release several kinds of substances such as cytokines and hormones that affect cell and tissue functions. We hypothesized that undefined substance (s) derived from cardiac fibroblasts may have the potential to protect against ischemic myocardium. To assess our hypothesis, using rats, we investigated: (1) the effect of cardiac fibroblast-conditioned medium (CM) on the viability of hypoxic cardiomyocytes in vitro, (2) the effect of CM on left ventricular (LV) function in global ischemia-reperfusion in an ex vive model, (3) the mechanism underlying cardioprotection by CM. Seventy-two hours after starting a hypoxic culture, the viability of cardiomyocytes was higher (P < 0.05) in the CM treated group (41.4%) compared to the control (20.5%). In Langendorff's preparation, 30 min after ischemia-reperfusion, LV end-diastolic pressure was lower, and LV developed pressure and -LVdP/dt were higher (P < 0.01 or P < 0.05) in the CM group than in the control, although coronary flow did not differ between the two groups. Pretreatment with a protein kinase C inhibitor or a mitochondrial ATP-sensitive K+ channel blocker attenuated these changes of LV function in the CM group. Such cardioprotection was achieved by a fraction of the CM having a molecular weight (MW) > 50,000, but not by that of the CM with a lower MW. In addition, a specific antibody against hepatocyte growth factor (HGF, MW is 84,000) did not reduce the cardioprotection afforded by CM. There may be an unknown cardioprotective substance other than HGF in rats, which mimics ischemic preconditioning and has MW > 50,000.

An outbreak of aseptic meningitis due to echovirus 30 in a high school baseball club--possible role of severe exercise for a high attack rate.

In September 2008, an outbreak of aseptic meningitis caused by echovirus 30 occurred in Ota City, Gunma. Among the 26 people hospitalized, 17 were members of a high school baseball club. The attack rate within the club was as high as 40%. The other 9 patients were either their families or close relatives of the baseball club members, indicating the outbreak was confined to a limited community. Although numerous outbreaks of echoviral meningitis have been reported worldwide, those with such a high attack rate within a limited community are rare. Severe physical exercise in a hot temperature could be associated with this high attack rate.

Mast cells contribute to flow restoration by bone marrow cell transplantation in rats with ischemic limbs.

The aim of this study was to assess whether mast cells are involved in the recovery of diminished cutaneous blood flow (CBF) by bone marrow cell transplantation (BMCT) in limb arterial occlusion. In a hindlimb ischemia model, CBF was measured by laser Doppler perfusion imaging in White spot (Ws) rats which genetically lack mast cells, and their wild-type with or without BMCT. After 14 days, tissue mast cell density was assessed by toluidine blue staining. To evaluate angiogenesis, we also determined CD 31-positive capillary density in the ischemic limbs.CBF in ischemic limbs decreased to 36 +/- 2% of nonischemic limbs, but 7 to 14 days later it naturally recovered to 65 +/- 2% and reached a plateau in both types of rats. BMCT further (P < 0.05) increased CBF with increases in tissue mast cell and capillary densities in wild-type rats, but not in Ws rats. Treatment with sodium cromoglycate, an inhibitor of mast cell degranulation, diminished the increases in mast cell and capillary densities, and CBF by BMCT in ischemic limbs of wild-type rats. Mast cells may not be involved in ischemia-induced natural angiogenesis and a partial recovery of CBF, however, they appear to be involved in the therapeutic angiogenesis by BMCT.

Participation of mast cells in angiogenesis in the border zone of myocardial infarction in rats.

BACKGROUND: We hypothesized that mast cells may participate in coronary angiogenesis in acute myocardial infarction, contributing to myocardial salvage. METHODS: The left coronary artery was occluded in control (n = 30) and Ws rats (n = 30), which genetically lacked c-kit, resulting in a mast cell deficiency. Four weeks later, the infarct area, i.e., infarct core and surrounding infarct areas, and the non-infarct area were assessed histopathologically. The mast cell and small vessel densities were assessed using toluidine blue and alkaline phosphatase staining. Myocardial perfusion was assessed by myocardial contrast echocardiography (MCE). RESULTS: In Ws rats, the percentage infarct core area increased (p < 0.05) compared with the controls, whereas the percentage surrounding infarct area decreased (p < 0.01). Mast cell density increased most in the surrounding infarct area (p < 0.01) in control rats, whereas mast cells were absent in Ws rats. Compared with the controls, coronary microvessel density decreased in the surrounding infarct area in Ws rats (p < 0.01). MCE showed that the percentage infarct core area, i.e., perfusion defect, increased (p < 0.05) and the percentage surrounding infarct area, i.e., reduced perfusion area, decreased (p < 0.01) in Ws rats. CONCLUSION: Mast cells may participate in promoting coronary angiogenesis in the infarct area surrounding the infarct core, contributing to attenuation of left ventricular dysfunction.

Attenuation of cardioprotective effect by postconditioning in coronary stenosed rat heart and its restoration by carvedilol.

BACKGROUND: The aim of this study was to assess whether and how infarct size (IS) reduction by postconditioning is modified in the heart with coronary stenosis (CS), and how beta-blocker treatment affects it. METHODS AND RESULTS: The IS was assessed by 30-min acute coronary occlusion and 24-h reperfusion in rat hearts in which CS had been induced. Modification of IS by postconditioning and the effects of daily carvedilol treatment were measured, together with reperfusion injury - salvage kinase activities. Four weeks after CS induction, any reduction of IS by postconditioning was lost, whereas it reduced IS in rats without CS. In the hearts without CS, postconditioning activated both the ERK and Akt pathway. However, in the hearts with CS, postconditioning failed to do so. In hearts with CS plus daily carvedilol treatment, postconditioning reduced IS compared with the hearts without carvedilol, although postconditioning did not activate the Akt and ERK pathways. CONCLUSION: CS impaired Akt and ERK activation, resulting in a failure to reduce IS by postconditioning. Carvedilol treatment restored the IS reduction by postconditioning, possibly via other mechanism(s) of the ERK and Akt pathways.

Prediction of remote left ventricular volumes and functions after acute myocardial infarction with successful coronary intervention.

BACKGROUND: The scintigraphic perfusion defect size (DS) at 1 week after acute myocardial infarction (AMI) predicts remote left ventricular (LV) volumes and LV ejection fraction (LVEF). The present study examined whether LV volumes and LVEF 6 months after AMI may be better predicted by the combination of LV volumes and LVEF just after reperfusion, and DS at 1 week, after AMI in patients with Thrombolysis In Myocardial Infarction (TIMI) grade III reperfusion by percutaneous coronary intervention. METHODS AND RESULTS: In 48 patients with AMI and TIMI grade III reperfusion, quantitative gated SPECT (QGS) was performed just after reperfusion, and at 1 week and 6 months after AMI. LV end-diastolic volume index decreased (108+/-8 to 93+/-6 ml/m(2), p<0.05) and LVEF increased (44+/-3 to 50+/-2%, p<0.05) 6 months after AMI. In addition, they were better predicted by a combination of LV volumes and LVEF just after reperfusion and DS at 1 week after AMI. CONCLUSIONS: In AMI with TIMI grade III reperfusion, LV volumes and LVEF at 6 months after MI correlate with the values obtained just after reperfusion. Myocardial perfusion imaging combined with QGS at reperfusion may predict these late-phase parameters.

Attenuation of diastolic heart failure and life-threatening ventricular tachyarrhythmia after peripheral blood stem cell transplantation combined with cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis.

A patient had multiple myeloma and associated cardiac amyloidosis, which caused diastolic dysfunction and recurrent ventricular fibrillation. After implantation of a cardioverter-defibrillator (ICD), the patient underwent autologous peripheral blood stem cell transplantation (PBSCT). The life-threatening arrhythmias, such as ventricular fibrillation, disappeared, and diastolic dysfunction assessed by quantitative gated single photon emission computed tomography and Doppler echocardiography improved 7 months later. This may be the first report to document improvement of both a lethal rhythm disorder and diastolic dysfunction by PBSCT following ICD implantation in a case of cardiac amyloidosis associated with multiple myeloma.

Intervention for apoptosis in cardiomyopathy.

Apoptosis plays an important role in pathogenesis of primary and secondary cardiomyopathies. It is proposed that antiapoptotic interventions may constitute an effective strategy for these diseases. Some of the antiapoptotic interventions are "old wine in a new bottle" measures already included in the conventional pharmacotherapy. As specific antiapoptotic treatment, caspase inhibitors and anti-TNF-alpha antibody are in early phases of clinical trials in non-cardiac diseases or being contemplated for clinical studies. Non-pharmacotherapies such as cardiac resynchronization and left ventricular assist device also exert cardioprotection partly by antiapoptotic mechanisms. In the field of regenerative medicine, myocardial transplantation of bone marrow-derived stem cells has been performed. Although it is controversial whether it is a true regenerative medicine or the cytokine therapy, antiapoptotic effect of transplanted cells may also have a role in cardioprotection. Moreover, apoptosis may develop despite efforts for cardioprotection in some severe situations of heart failure. Cardiac repair and regeneration by cardiac stem cells may compensate a loss of cardiomyocytes avoiding a deleterious situation. Therefore, protection and/or potentiation of such effects by cardiac stem cells appear to be promising therapeutic strategy in the future. In this review, we discuss about the antiapoptotic interventions for cardiomyopathies in the "real world" and the future of clinical cardiology.

Optimal noninvasive assessment of diastolic heart failure in patients with atrial fibrillation: comparison of tissue doppler echocardiography, left atrium size, and brain natriuretic peptide.

OBJECTIVE: The aim of this study was to evaluate whether the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity (E/E') can be applied to identify diastolic heart failure (HF) noninvasively rather than using brain natriuretic peptide (BNP) or enlargement of left atrium (LA) in patients with atrial fibrillation (AF) by comparing the severity of HF symptoms. Moreover, we investigated the relationship between the changes in E/E' and the severity of HF or LA remodeling in the follow-up period. METHODS: We examined 73 patients with nonvalvular AF disease and preserved left ventricular ejection fraction (>50%), ie, patients with diastolic HF accompanied with New York Heart Association (NYHA) functional class I to IV (n = 32, HF group) and those without HF (n = 41, non-HF group). No patients showed dyspnea caused by anemia, renal failure, lung disease, or other disease states except HF. We evaluated E, E', and E/E' by Doppler echocardiography, and the LA area (LAA) by 2-dimensional echocardiography. BNP levels were also examined. A follow-up study was performed in 18 of the 32 patients with HF. RESULTS: E/E', LAA, and BNP were higher in the HF group than in the non-HF group (E/E', 15 +/- 5 vs 9 +/- 2; LAA, 24 +/- 6 vs 20 +/- 6 cm(2); and BNP, 321 +/- 200 vs 140 +/- 76 pg/mL, each P < .01). Using the receiver operating characteristic curve for identification of symptomatic diastolic HF with NYHA functional class II to IV, the areas under the curves were: E/E', 0.96 (95% confidence interval 0.91-1.0); LAA, 0.77 (95% confidence interval 0.64-0.89); and BNP, 0.85 (95% confidence interval 0.75-0.95). In the HF group, 18 patients who were re-examined 17 +/- 9 weeks after were divided into two groups, depending on the improvement in NYHA functional class, ie, improved group (n = 10) and unchanged group (n = 8). In the follow-up period, E (112 +/- 20-94 +/- 21 cm/s), E/E' (17.1 +/- 5-13.1 +/- 3), and LAA (28 +/- 5-24 +/- 4) decreased in the improved group (each P < .05), but E' and BNP did not. CONCLUSIONS: E/E' could be useful in identifying symptomatic diastolic HF and evaluating the functional state in the process of HF in patients with AF. Moreover, E/E' is able to assess the improvement of diastolic HF in AF.

A case of recurrent myocardial infarction caused by a giant right coronary artery aneurysm.

We report a rare case of a giant coronary artery aneurysm with recurrent myocardial infarction (MI) in a 52-year-old man. He was admitted with severe chest pain and was diagnosed with acute MI. Ten days after thrombolysis, a transthoracic echocardiogram demonstrated a spherical mass apposed to the outer wall of the right atrium. Computed tomography with angiography showed this mass to be a huge aneurysm of the right coronary artery with a maximal diameter of 4 cm and filled with mural thrombus. Surgical resection of the aneurysm and coronary arterial bypass grafting were recommended. On day 60, while the patient awaited surgical treatment, recurrent MI caused by thrombotic occlusion occurred in the aneurysm site despite anticoagulant therapy. Two days after thrombolytic therapy, he underwent coronary artery bypass grafting and aneurysmal resection.

Vasoconstrictive response in the vascular beds of the non-exercising forearm during leg exercise in patients with mild chronic heart failure.

BACKGROUND: Reduced exercise capacity may be related to decreased redistribution of blood flow from the non-exercising tissues to the exercising skeletal muscle in patients with mild chronic heart failure (CHF). METHODS AND RESULTS: In the present study 14 patients with mild CHF and 10 healthy subjects (N) underwent symptom-limited multistage-ergometer exercise, during which forearm vascular resistance (FVR), cardiac index (CI), systemic vascular resistance index (SVRI), and oxygen uptake (VO(2)) were measured non-invasively using the plethysmograph, impedance, and respiratory gas analysis methods, respectively. The VO(2) and CI at peak exercise were lower (p<0.01 each), and SVRI and FVR at both rest and peak exercise were higher in the CHF group than in N. However, both the percent increase in FVR and percent decrease in SVRI from the resting state to peak exercise were lower in CHF than N, and both of them correlated with not only peak VO(2), but also the corresponding resting value of FVR and SVRI (p<0.01 each). CONCLUSIONS: Redistribution of blood flow from the non-exercising tissues to the working skeletal muscles, which may participate in exercise capacity, can be blunted in CHF. The decreased vasoconstrictive response in the non-exercising tissues is intimately related to the increased resting vascular tone in CHF.

Difference in early effects of statin therapy on coronary and forearm flow reserve in postmenopausal hypercholesterolemic women.

BACKGROUND: The relationships between flow reserves in coronary and peripheral circulation and their modification by statin therapy have not been assessed in the same patients, especially females. METHODS AND RESULTS: To assess the effect of pravastatin on both circulation, in 20 postmenopausal female patients with hypercholesterolemia but a low probability of coronary artery disease, the forearm blood flow reserve (FBFR) using the plethysmographic method and coronary flow velocity reserve (CFVR) by Doppler echocardiography were measured before, 4 and 8 weeks after starting the pravastatin and/or diet therapy. At baseline, CFVR and FBFR had a positive linear correlation (r=0.63, p<0.01) while each of them had a negative linear correlation (r=-0.53 to -0.63, p<0.05 each) with total or LDL-cholesterol levels. Four weeks after starting the pravastatin therapy when the decrease in total cholesterol reached a plateau, FBFR increased (p<0.05) by 38+/-14%, whereas CFVR did not. Such an increase in FBFR by pravastatin was related to the degree of total or LDL-cholesterol lowering. CONCLUSIONS: In postmenopausal hypercholesterolemic women with a low probability of coronary artery disease, the cholesterol-lowering with pravastatin improved FBFR as early as 4 to 8 weeks after starting the therapy, whereas its effect on CFVR was unclear at that time.

Attenuated cardioprotection by ischemic preconditioning in coronary stenosed heart and its restoration by carvedilol.

OBJECTIVE: Infarct size (IS) reduction by ischemic preconditioning (IPC) has been assessed in the heart in which coronary stenosis (CS)-induced chronic ischemia was not present. The aim of this study is to assess whether and how IS reduction by IPC is modified in the heart in which CS has occurred, and how further therapeutics, if any, modify it. METHODS: We assessed the IS produced by a 30-minute acute coronary occlusion and a 24-hour reperfusion (COR) in rat hearts in which CS had developed for 1-12 weeks. Modifications of IS by IPC and the mitochondrial KATP channel (mitoKATP) opener and blocker, and the effects of daily beta-blocker treatment with carvedilol on them, were also assessed. Myocardial protein kinase C (PKC)-epsilon activities in the risk areas were measured by Western blotting. RESULTS: One to 4 weeks after CS induction, myocardial PKC-epsilon was activated in the risk area of CS even without IPC, but such CS-induced PKC activation as well as that by IPC was attenuated 8-12 weeks after CS. The IS reductions by the mitoKATP opener as well as by IPC were attenuated 8-12 and 4-12 weeks after CS, respectively. Daily carvedilol treatment after inducing CS restored the malfunctioning PKC-mitoKATP signal cascade and the attenuated IPC and mitoKATP effect on IS. CONCLUSION: CS activates the PKC-mitoKATP signal cascade, mimicking the IPC effect, whereas this cardioprotective effect is attenuated late after CS via their downregulation. Restoration of these changes may be a novel mechanism for cardioprotection by carvedilol in the CS-induced ischemic heart.

Effects of angiotensin-converting enzyme inhibitors or an angiotensin receptor blocker in combination with aspirin and cilostazol on in-stent restenosis.

It remains to be determined whether adding an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to antiplatelet therapy has a therapeutic benefit on in-stent restenosis. After successful coronary stenting, 165 patients (167 lesions) were randomly assigned to a basal (aspirin 162 mg + cilostazol 200 mg/day), ACEI (basal treatment + quinapril 10 mg or perindopril 4 mg/day), or ARB (basal treatment + losartan 50 mg/day) treatment group. Quantitative coronary angiography was performed before, immediately following, and 6 months after stenting. Follow-up coronary angiography was completed in 126 patients (128 lesions). Restenosis rates tended to be higher (12, 26, and 12% for the basal, ACEI, and ARB groups, respectively), and target lesion revascularization rates were higher in the ACEI group than in the other groups (9, 23,* and 5%, respectively, *P < 0.05 versus basal group). Moreover, late lumen loss was higher in the ACEI group than in the basal group (0.60 +/- 0.55, 0.98 +/- 0.61* and 0.73 +/- 0.64 mm in the basal, ACEI, and ARB groups, respectively). The combinations of an ACEI or ARB with aspirin and cilostazol are ineffective for the prevention of in-stent restenosis, and an ACEI may even promote intimal proliferation after stent implantation.

Left ventricular dysfunction and remodeling in streptozotocin-induced diabetic rats.

BACKGROUND: It is not fully clarified how diabetes mellitus (DM)-induced cardiac dysfunction is associated with histopathological changes of the heart in a long lasting period of DM. METHODS AND RESULTS: Eighteen weeks after a streptozotocin injection was given to Wistar - Kyoto rats (D rats), echocardiography and hemodynamic studies including the dobutamine infusion test were performed. After perfusion fixation, immunofluorescent staining and histopathology of the heart were analyzed, and analysis with electron microscopy was also conducted. Systolic blood pressure in the conscious state and left ventricular (LV) ejection fraction by 2-dimensional echocardiography were reduced in D rats. LV mechanical responses to dobutamine assessed by maximal LV pressure derivative (+LVdP/dt) also decreased with higher dobutamine doses in D rats. Although LV and right ventricular (RV) wall thickness were smaller in D rats, there were increased RV volumes, indicating LV and RV dilatational remodeling in D rats. The cardiomyocyte transverse diameter and actin staining in cardiomyocytes in both the LV and RV were significantly reduced, and capillary tortuosity and type IV collagen were increased, indicating microangiopathy in D rats. CONCLUSIONS: Advanced insulin-dependent DM incurred not only RV remodeling but also overt resting LV systolic dysfunction and decreased LV responsiveness to beta adrenergic stimulation with dilatational remodeling, accompanied by pathological changes of capillaries and cardiomyocytes including actin filaments.

[Heart failure in the elderly].

Heart failure (HF) is a major disease of the elderly. Since their symptoms of HF are generally light, on admission of the hospitals HF is sometimes in an advanced stage. Therefore, preventive medicine for those with the risk factors of HF is needed as a future strategy of cardiac gerontology. The routine assessment of the HF severity may be performed noninvasively by Nohria's profiles rather than other invasive methods. HF is worsened by the interaction with the co-morbidity factors, such as renal dysfunction and anemia. The interaction between HF and kidney disease (and anemia) is called 'cardiorenal (anemia) syndrome.' Recurrent hospitalization due to HF is common, and the period of hospitalization tends to be long in this syndrome. One of the hopeful therapeutic agents is carperitide, a recombinant human atrial natriuretic peptide. In cardiorenal syndrome, much lower initial doses of carperitide, such as 0.0125 microg/kg/min is recommended for treatment of HF in order to avoid possible worsening of renal dysfunction. In cardiorenal anemia syndrome, supplement of iron, careful blood transfusion in severe cases, administration of recombinant human erythropoietin, should be performed if indicated. However, the possibility of anemia unrelated to HF, such as due to gastrointestinal carcinoma, is also considered in the elderly. In such cases, finding a decrease of serum ferritin preceding that of hemoglobin may contribute to a differential diagnosis of anemia in elderly HF patients. Thus, the therapies considering several features of HF in elderly will contribute to improving quality of life and outcome.

Scintigraphic assessment of the effects of bone marrow-derived mononuclear cell transplantation combined with off-pump coronary artery bypass surgery in patients with ischemic heart disease.

UNLABELLED: Myocardial SPECT may be useful for assessment of the therapeutic effects and the mechanisms of cardiac regeneration medicine. We aimed to assess first the feasibility and the short-term safety of autologous bone marrow-derived mononuclear cell transplantation (BMCT) into the ischemic myocardium in patients who undergo off-pump coronary artery bypass surgery (OPCAB). In addition, we aimed to assess our hypothesis that the BMCT may help ameliorate myocardial perfusion in patients with ischemic heart disease (IHD) using myocardial perfusion scintigraphy. METHODS: We performed BMCT in 10 patients with IHD during OPCAB. Cells for BMCT were collected by intraoperative bone marrow aspiration or by preoperative cellular apheresis after pretreatment with granulocyte colony-stimulating factor. After OPCAB was performed in all graftable ischemic areas, a total of 3.4 +/- 1.2 x 10(9) mononuclear cells, including 5.2 +/- 1.6 x 10(6) CD34-positive (CD34(+)) cells, were injected into ungraftable ischemic myocardial areas. Dipyridamole-stress and resting (99m)Tc myocardial SPECT was performed before and 1 mo after the procedures. RESULTS: BMCT was performed safely in all patients. Compared with before treatment, myocardial (99m)Tc tracer uptake on the dipyridamole-stress image increased similarly in BMCT- and OPCAB-treated areas, whereas tracer accumulation at rest did not change in all myocardial areas. The improvement of myocardial perfusion was not correlated with the total number of mononuclear cells transplanted. However, it was positively correlated with the number of transplanted CD34(+) cells: (99m)Tc tracer uptake after/before BMCT (ratio) = 1.091 x (CD34(+) cell number [x10(6)])(0.074) (r(2) = 0.48, P < 0.05), although new development of coronary vessels was not documented cineangiographically. Myocardial histopathology in 2 of 3 autopsy cases revealed coronary angiogenesis in the areas corresponding to the sites of BMCT. CONCLUSION: The present study demonstrates the feasibility of BMCT combined with OPCAB. This therapy improves myocardial perfusion possibly via CD34-related development of coronary microvessels.