scholarly journals Bone marrow mononuclear cells induce beneficial remodeling and reduce diastolic dysfunction in the left ventricle of hypertensive SS/MCWi rats

2012 ◽  
Vol 44 (19) ◽  
pp. 925-933 ◽  
Author(s):  
Sarah J. Parker ◽  
Daniela N. Didier ◽  
Jamie R. Karcher ◽  
Timothy J. Stodola ◽  
Bradley Endres ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Heart Disease ◽  
Diastolic Dysfunction ◽  
Mononuclear Cells ◽  
Diastolic Pressure ◽  
Interstitial Fibrosis ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Lower Percentage ◽  
Bone Marrow Mononuclear Cells

Bone marrow mononuclear cells (BMMNCs) increase capillary density and reduce fibrosis in rodents after myocardial infarction, resulting in an overall improvement in left ventricular function. Little is known about the effectiveness of BMMNC therapy in hypertensive heart disease. In the current study, we show that delivery of BMMNCs from hypertension protected SS-13BN/MCWi donor rats, but not BMMNC from hypertension susceptible SS/MCWi donor rats, resulted in 57.2 and 83.4% reductions in perivascular and interstitial fibrosis, respectively, as well as a 60% increase in capillary-to-myocyte count in the left ventricles (LV) of hypertensive SS/MCWi recipients. These histological changes were associated with improvements in LV compliance and relaxation (103 and 46.4% improvements, respectively). Furthermore, improved diastolic function in hypertensive SS/MCWi rats receiving SS-13BN/MCWi derived BMMNCs was associated with lower clinical indicators of heart failure, including reductions in end diastolic pressure (65%) and serum brain natriuretic peptide levels (49.9%) with no improvements observed in rats receiving SS/MCWi BMMNCs. SS/MCWi rats had a lower percentage of endothelial progenitor cells in their bone marrow relative to SS-13BN/MCWi rats. These results suggest that administration of BMMNCs can prevent or reverse pathological remodeling in hypertensive heart disease, which contributes to ameliorating diastolic dysfunction and associated symptomology. Furthermore, the health and hypertension susceptibility of the BMMNC donor are important factors influencing therapeutic efficacy, possibly via differences in the cellular composition of bone marrow.

scholarly journals Profoundly Reduced Neovascularization Capacity of Bone Marrow Mononuclear Cells Derived From Patients With Chronic Ischemic Heart Disease

Circulation ◽  
2004 ◽  
Vol 109 (13) ◽  
pp. 1615-1622 ◽  
Author(s):  
Christopher Heeschen ◽  
Ralf Lehmann ◽  
Jörg Honold ◽  
Birgit Assmus ◽  
Alexandra Aicher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Mononuclear Cells ◽  
Ischemic Heart ◽  
Bone Marrow Mononuclear Cells ◽  
Chronic Ischemic Heart Disease

Abstract 20556: Safety and Efficacy of Intracoronary Hypoxia-PrecondItioned Bone Marrow Mononuclear Cells Administration for Acute Myocardial Infarction Patients

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Xin Yang Hu ◽  
Xin Huang ◽  
Qian Yang ◽  
Lihan Wang ◽  
Jianzhong Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Bone Marrow ◽  
Primary Endpoint ◽  
Perfusion Defect ◽  
Mononuclear Cells ◽  
Left Ventricular ◽  
Bone Marrow Mononuclear Cells ◽  
Safety And Efficacy ◽  
Intracoronary Infusion

IMPORTANCE: Cell therapy has been a potential approach for ST-segment elevation acute myocardial infarction (STEMI). To improve the therapeutic oucome, the safety and efficacy of hypoxia-preconditioned (H-) bone marrow mononuclear cells (BMCs) in AMI patients need further evaluation. OBJECTIVE: To investigate the safety and efficacy of H-BMCs therapy in AMI patients. DESIGN: A phase 1, randomized and blinded study (February, 2011~ March, 2012) with one-year of follow-up. SETTING: A single center for hospitalized care. PARTICIPANTS: 22 Patients with an acute ST elevation myocardial infarction were recruited and randomized to two groups: normoxia BMCs (N-, n=11) and H-BMCs (n=11). INTERVENTIONS: Intracoronary infusion of H-BMCs or N-BMCs within 5-7 days after treatment with percutaneous transluminal coronary intervention (PCI). Patients were similarly treated by a stop-flow technique through an over-the-wire balloon catheter. MAIN OUTCOMES AND MEASURES: Primary endpoint was Treatment-emergent 30-day serious adverse event rate defined as a composite of death, MI, sustained ventricular tachycardia, stroke, hospitalization for worsening heart failure and revascularization. Secondary endpoints were change of myocardium perfusion, global left ventricular ejection fraction and left ventricular volumes. RESULTS: The primary endpoint events was none for N-BMCs and 9.1% (95% CI, 0.2%-41.3%) for H-BMCs. There was significant increase in the change of LVEF of H-BMCs group at 6 month. The change of end diastolic volume (EDV) and end systolic volume (ESV) in H-BMCs at 12 month were significantly decreased. Ratio of myocardium perfusion defect by Single-Photon Emission Computed Tomography (SPECT) was significantly reduced in H-BMCs group at 6 months, and score of myocardium perfusion defect by SPECT was significantly reduced than that of baseline in H-BMCs group at 6 and 12 months, unlike N- group. CONCLUSIONS AND RELEVANCE: Intracoronary infusion with H-BMCs appeared to be safe and effective for patients with AMI. Although the sample size precludes a definitive statement about safety and efficacy, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach.

scholarly journals Functional recovery of patients with ischemic cardiomyopathy treated with coronary artery bypass surgery and concomitant intramyocardial bone marrow mononuclear cell implantation: A long term follow-up study

2015 ◽  
Vol 72 (3) ◽  
pp. 225-232 ◽  
Author(s):  
Zoran Trifunovic ◽  
Slobodan Obradovic ◽  
Bela Balint ◽  
Radoje Ilic ◽  
Zoran Vukic ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ischemic Cardiomyopathy ◽  
Mononuclear Cells ◽  
Artery Bypass ◽  
Left Ventricular ◽  
Bone Marrow Mononuclear Cells ◽  
Cabg Surgery ◽  
To Receive

Background/Aim. Intramyocardial bone marrow mononuclear cells (BMMNC) implantation concomitant to coronary artery bypass grafting (CABG) surgery as an option for regenerative therapy in chronic ischemic heart failure was tested in a very few number of studies, with not consistent conclusions regarding improvement in left ventricular function, and with a follow-up period between 6 months and 1 year. This study was focused on testing of the hypothesis that intramyocardial BMMNC implantation, concomitant to CABG surgery in ischemic cardiomyopathy patients, leads to better postoperative long-term results regarding the primary endpoint of conditional status-functional capacity and the secondary endpoint of mortality than CABG surgery alone in a median follow-up period of 5 years. Methods. A total of 30 patients with ischemic cardiomyopathy and the median left ventricular ejection fraction (LVEF) of 35.9 ? 4.7% were prospectively and randomly enrolled in a single center interventional, open labeled clinical trial as two groups: group I of 15 patients designated as the study group to receive CABG surgery and intramyocardial implantation of BMMNC and group II of 15 patients as the control group to receive only the CABG procedure. All the patients in both groups received the average of 3.4 ? 0.7 implanted coronary grafts, and all of them received the left internal mammary artery (LIMA) to the left anterior descending (LAD) and autovenous to other coronaries. Results. The group with BMMNC and CABG had the average of 17.5 ? 3.8 injections of BMMNC suspension with the average number of injected bone marrow mononuclear cells of 70.7 ? 32.4 ? 106 in the total average volume of 5.7 ? 1.5 mL. In this volume the average count of CD34+ and CD133+ cells was 3.96 ? 2.77 ? 106 and 2.65 ? 1.71 ? 106, respectively. All the patients were followed up in 2.5 to 7.5 years (median, 5 years). At the end of the follow-up period, significantly more patients from the group that received BMMNC were in the functional class I compared to the CABG only group (14/15 vs 5/15; p = 0.002). After 6 months the results on 6-minute walk test (6-MWT) were significantly different between the groups (435 m in the BMMNC and CABG group and 315 m in the CABG only group; p = 0.001), and continued to be preserved and improved on the final follow-up (520 m in the BMMNC and CABG group vs 343 m in the CABG only group; p < 0.001). Cardiovascular mortality was also significantly reduced in the BMMNC and CABG group (p = 0.049). Conclusion. Implanatation of BMMNC concomitant to CABG is a safe and feasible procedure that demonstates not only the improved functional capacity but also a reduced cardiac mortality in a 5-year follow-up in patients with ischemic cardiomyopathy scheduled for CABG surgery.

Abstract 705: The Difference in Left Ventricular Twisting Behavior Between Patients With Hypertensive Heart Disease and Hypertrophic Cardiomyopathy

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kazuhisa Nishimura ◽  
Hideki Okayama ◽  
Makoto Saito ◽  
Katsuji Inoue ◽  
Toyofumi Yoshii ◽  
...  
Keyword(s):  
Heart Disease ◽  
Hypertrophic Cardiomyopathy ◽  
Diastolic Dysfunction ◽  
Systolic Function ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Control Group ◽  
Control Groups ◽  
The Difference ◽  
And Control

(Background) Left ventricular (LV) untwisting behavior is a novel index of LV diastolic function since it is a powerful determinant of LV diastolic suction. The LV of patients with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) has diastolic dysfunction despite normal systolic function. However, the role of untwisting behavior in HCM and HHD in the pathophysiology of diastolic dysfunction is unknown. The aim of this study was to investigate the difference of LV twisting behavior between patients with HCM and HHD. (Methods) Forty-four patients with HCM (mean age, 63+/−15 y, 34 males), 30 patients with HHD (mean age, 62+/−12 y, 20 males), and 20 age and sex-matched control subjects were evaluated. After a standard echocardiographic examination, LV twist and twisting velocity profiles from apical and basal short-axis images were analyzed using two-dimensional speckle tracking imaging. All temporal parameters were normalized by R-R intervals. (Results) LV diastolic and systolic dimensions, and ejection fraction were not significantly different among the groups. LV mass index and early diastolic mitral annular velocity were not significantly different between the HCM and HHD groups. The peak torsion in the HCM and HHD groups was significantly greater than that in the control group (Table ). The peak untwisting velocity in the HCM group was comparable to that in the control group. However, when the peak untwisting velocity was corrected by peak torsion, the value in the HCM group was significantly decreased compared with that in the HHD and control groups. The time to peak untwisting velocity from aortic valve closure in the HCM group was significantly longer than that in the HHD and control groups. (Conclusion) These results suggest that enhanced peak torsion in HCM might compensate for untwisting behavior, but this mechanism fails to fully compensate for untwisting behavior compared with HHD. Left ventricular twisting behavior

Abstract WP207: Ethnic Disparities in Hypertensive Heart Disease Among Young Adults with Ischemic Stroke in Hawaii

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Alap R Jani ◽  
Cherisse Ito ◽  
Todd Seto ◽  
Kazuma Nakagawa
Keyword(s):  
Young Adults ◽  
Heart Disease ◽  
Ischemic Stroke ◽  
Diastolic Dysfunction ◽  
Ethnic Disparities ◽  
Hypertensive Heart Disease ◽  
Left Ventricular ◽  
Admission Diagnosis ◽  
Lv Mass ◽  
Echocardiographic Findings

A recent study showed that Native Hawaiians and Other Pacific Islanders (NHOPI) with ischemic stroke are younger and have a higher burden of cardiovascular risk factors compared to whites and Asians. However, a detailed assessment of the degree of hypertensive heart disease using echocardiogram data among this multi-ethnic young adult population has not been studied. The objective of this study was to assess ethnic differences in the echocardiographic findings of hypertensive heart disease among young adults who were hospitalized for ischemic stroke. We hypothesized that NHOPI young adults with ischemic stroke have a higher prevalence of echocardiographic findings of hypertensive heart disease compared to whites and Asians. We conducted a retrospective study of all young adults (age ≤ 55 years) who were hospitalized at the Queen’s Medical Center in Honolulu, HI between 2008 and 2012 with an admission diagnosis of ischemic stroke. Patients with an ethnicity other than white, Asian, or NHOPI were excluded. Echocardiograms for each patient were reviewed. Left ventricular mass was estimated by the Devereux formula. Early (E) and late (A) transmitral diastolic flow, and mitral medial annulus early diastolic velocities (E’) were recorded; and E/A and E/E’ were calculated as measures of diastolic dysfunction and LV filling pressures. A total of 259 patients (44% NHOPI, 36% Asians, and 19% whites) were included in the study. The overall mean age was 47.1 ± 7.7 years with 34% women. NHOPIs had a higher LV mass (248.9 ± 94.8 g), LV mass index (121.5 ± 41.4 g/m 2 ), and mitral E/E’ values (15.5 ± 9.3) compared to whites (218.6 ± 74.6 g, 107.9 ± 34.2 g/m 2 , 11.5 ± 4.6, all P <0.05) and Asians (191.3 ± 61.5 g, 106 ± 32.2 g/m 2 , 12.4 ± 5.8, all P <0.01). NHOPIs had more severe diastolic dysfunction and relative wall thickness (all P <0.05) compared to Asians but not whites. Overall, NHOPIs compared to whites and Asians had 8% compared to 10% and 10.6% with normal geometry, 39% compared to 50% and 47.9% with concentric remodeling, 53% compared to 40% and 41.5% with hypertrophy. Left atrial enlargement was seen in 24% of the total population. In conclusion, this study shows that among young adults with ischemic stroke, NHOPIs have a higher burden of hypertensive heart disease compared to whites and Asians.

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