scholarly journals Postischemic functional recovery in immature hearts is influenced by performance index and assessment technique

2001 ◽  
Vol 281 (6) ◽  
pp. H2446-H2455 ◽  
Author(s):  
Shona M. Torrance ◽  
Carin Wittnich
Keyword(s):  
Functional Recovery ◽  
Performance Index ◽  
Systolic Pressure ◽  
Assessment Technique ◽  
Variable Volume ◽  
Assessment Techniques ◽  
Developed Pressure ◽  
Immature Heart ◽  
Contractile Performance

In the in vivo immature heart, conflicting results are reported for postischemic functional recovery. This study determines whether interpretations of functional recovery are influenced by the contractile performance index (systolic pressure, developed pressure, and maximum rate of systolic pressure increase per unit time) reported or the assessment technique (isovolumetric and variable-volume) utilized. In neonatal pigs ( n = 6) on cardiopulmonary bypass, each performance index was examined using both assessment techniques before myocardial ischemia and at 15, 30, and 60 min of reperfusion. With the use of the isovolumetric technique, all performance indexes had significantly different recovery. With the use of the variable-volume assessment technique, recovery of systolic pressure was significantly better than the other indexes. When recovery was compared between the two assessment techniques, systolic pressure recovered significantly better when assessed using the variable-volume technique. For each performance index, the correlation between isovolumetric and variable-volume techniques was positive before ischemia but negative during reperfusion, suggesting that the assessment techniques identified conflicting postischemic contractile performances. Thus both the contractile performance index reported and the assessment technique employed are ultimately important in interpreting postischemic functional recovery in the immature heart.

Abstract P293: Endogenous Lats2 Plays an Important Role in Mediating Myocardial Injury Caused by Ischemia/Reperfusion Through Inhibition of FoxO3

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Dan Shao ◽  
Peiyong Zhai ◽  
Junichi Sadoshima
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Dominant Negative ◽  
Area At Risk ◽  
Perfused Heart ◽  
Developed Pressure

Lats2 is a tumor suppressor and a serine/threonine kinase, acting downstream of mammalian sterile 20 like kinase1 (Mst1), which stimulates apoptosis and inhibits hypertrophy in cardiomyocytes (CM). We investigated the role of Lats2 in mediating myocardial injury after ischemia/reperfusion (IR). Phosphorylation of YAP, an in vivo substrate of Lats2, was increased after 45 minutes ischemia followed by 24 hours reperfusion in control mouse hearts compared with sham, but not in dominant negative (DN) Lats2 transgenic mouse (Tg) hearts, suggesting that Lats2 is activated by IR. The size of myocardial infarction (MI)/area at risk was significantly smaller in Tg mice than in NTg mice (19% and 49%, p<0.01). And there were fewer TUNEL positive cells in Tg than in NTg mice (0.04% and 0.11%, p<0.05). Following 30 min of global ischemia and 60 min of reperfusion in Langendorff perfused heart preparations, left ventricular (LV) systolic pressure (100 vs 71mmHg, p<0.05) and LV developed pressure (79 vs 47 mmHg, p<0.05) were significantly greater in Tg than in NTg mice, indicating that suppression of Lats2 induces better functional recovery after IR. Oxidative stress, as evaluated by 8-OHdG staining, was attenuated in Tg mice. In cultured CMs, DN-Lats2 significantly decreased H 2 O 2 -induced cell death. Overexpression of Lats2 significantly downregulated (51% and 75%, p<0.05), whereas that of DN-Last2 upregulated (100 and 70%, p<0.05), MnSOD and catalase, suggesting that Lats2 negatively regulates expression of antioxidants. Reporter gene assays showed that overexpression of Lats2 significantly inhibits (−70%), whereas knocking down Lats2 by sh-Lats2 increases (+60%), FoxO3-mediated transcriptional activity. Overexpression of Lats2 in CMs inhibited FoxO3 expression, whereas that of DN-Lats2 significantly inhibited FoxO3 downregulation after IR in vivo, suggesting that Lats2 negatively regulates FoxO3 protein expression, which may lead to the downregulation of MnSOD and catalase. Taken together, these results suggest that endogenous Lats2 plays an important role in mediating myocardial injury in response to IR, In part through downregulation of FoxO3 and consequent downregulation of antioxidants and increased oxidative stress in the heart.

scholarly journals Grafts Derived from an α-Synuclein Triplication Patient Mediate Functional Recovery but Develop Disease-Associated Pathology in the 6-OHDA Model of Parkinson’s Disease

2020 ◽  
pp. 1-14
Author(s):  
Shelby Shrigley ◽  
Fredrik Nilsson ◽  
Bengt Mattsson ◽  
Alessandro Fiorenzano ◽  
Janitha Mudannayake ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Lines ◽  
Functional Recovery ◽  
Embryonic Stem ◽  
Hesc Line ◽  
Alternative Source ◽  
And Function

Background: Human induced pluripotent stem cells (hiPSCs) have been proposed as an alternative source for cell replacement therapy for Parkinson’s disease (PD) and they provide the option of using the patient’s own cells. A few studies have investigated transplantation of patient-derived dopaminergic (DA) neurons in preclinical models; however, little is known about the long-term integrity and function of grafts derived from patients with PD. Objective: To assess the viability and function of DA neuron grafts derived from a patient hiPSC line with an α-synuclein gene triplication (AST18), using a clinical grade human embryonic stem cell (hESC) line (RC17) as a reference control. Methods: Cells were differentiated into ventral mesencephalic (VM)-patterned DA progenitors using an established GMP protocol. The progenitors were then either terminally differentiated to mature DA neurons in vitro or transplanted into 6-hydroxydopamine (6-OHDA) lesioned rats and their survival, maturation, function, and propensity to develop α-synuclein related pathology, were assessed in vivo. Results: Both cell lines generated functional neurons with DA properties in vitro. AST18-derived VM progenitor cells survived transplantation and matured into neuron-rich grafts similar to the RC17 cells. After 24 weeks, both cell lines produced DA-rich grafts that mediated full functional recovery; however, pathological changes were only observed in grafts derived from the α-synuclein triplication patient line. Conclusion: This data shows proof-of-principle for survival and functional recovery with familial PD patient-derived cells in the 6-OHDA model of PD. However, signs of slowly developing pathology warrants further investigation before use of autologous grafts in patients.

Treatment of type 2 diabetic db/db mice with a novel PPARγ agonist improves cardiac metabolism but not contractile function

2004 ◽  
Vol 286 (3) ◽  
pp. E449-E455 ◽  
Author(s):  
Andrew N. Carley ◽  
Lisa M. Semeniuk ◽  
Yakhin Shimoni ◽  
Ellen Aasum ◽  
Terje S. Larsen ◽  
...  
Keyword(s):  
Contractile Function ◽  
Ex Vivo ◽  
Metabolic Changes ◽  
Pparγ Agonist ◽  
Perfused Hearts ◽  
Type 2 Diabetic ◽  
Contractile Performance ◽  
Exogenous Substrates

Hearts from insulin-resistant type 2 diabetic db/db mice exhibit features of a diabetic cardiomyopathy with altered metabolism of exogenous substrates and reduced contractile performance. Therefore, the effect of chronic oral administration of 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid (COOH), a novel ligand for peroxisome proliferator-activated receptor-γ that produces insulin sensitization, to db/db mice (30 mg/kg for 6 wk) on cardiac function was assessed. COOH treatment reduced blood glucose from 27 mM in untreated db/db mice to a normal level of 10 mM. Insulin-stimulated glucose uptake was enhanced in cardiomyocytes from COOH-treated db/db hearts. Working perfused hearts from COOH-treated db/db mice demonstrated metabolic changes with enhanced glucose oxidation and decreased palmitate oxidation. However, COOH treatment did not improve contractile performance assessed with ex vivo perfused hearts and in vivo by echocardiography. The reduced outward K+ currents in diabetic cardiomyocytes were still attenuated after COOH. Metabolic changes in COOH-treated db/db hearts are most likely indirect, secondary to changes in supply of exogenous substrates in vivo and insulin sensitization.

scholarly journals Transgenic Overexpression of the Ca2+-binding Protein S100A1 in the Heart Leads to Increased in Vivo Myocardial Contractile Performance

2003 ◽  
Vol 278 (36) ◽  
pp. 33809-33817 ◽  
Author(s):  
Patrick Most ◽  
Andrew Remppis ◽  
Sven T. Pleger ◽  
Eva Löffler ◽  
Philipp Ehlermann ◽  
...  
Keyword(s):  
Binding Protein ◽  
Myocardial Contractile ◽  
Contractile Performance

scholarly journals Subthreshold electrical stimulation as a low power electrical treatment for stroke rehabilitation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyungsoo Kim ◽  
Seung-Jun Yoo ◽  
So Yeon Kim ◽  
Taeju Lee ◽  
Sung-Ho Lim ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Energy Consumption ◽  
Functional Recovery ◽  
Stroke Rehabilitation ◽  
Brain Regions ◽  
Implantable Devices ◽  
Rehabilitation Process ◽  
Neural Excitability ◽  
Spike Firing

AbstractAs a promising future treatment for stroke rehabilitation, researchers have developed direct brain stimulation to manipulate the neural excitability. However, there has been less interest in energy consumption and unexpected side effect caused by electrical stimulation to bring functional recovery for stroke rehabilitation. In this study, we propose an engineering approach with subthreshold electrical stimulation (STES) to bring functional recovery. Here, we show a low level of electrical stimulation boosted causal excitation in connected neurons and strengthened the synaptic weight in a simulation study. We found that STES with motor training enhanced functional recovery after stroke in vivo. STES was shown to induce neural reconstruction, indicated by higher neurite expression in the stimulated regions and correlated changes in behavioral performance and neural spike firing pattern during the rehabilitation process. This will reduce the energy consumption of implantable devices and the side effects caused by stimulating unwanted brain regions.

Subthreshold Electrical Stimulation as A Low Power Electrical Treatment for Stroke Rehabilitation

2021 ◽  
Author(s):  
Kyungsoo Kim ◽  
Seung-Jun Yoo ◽  
So Yeun Kim ◽  
Taeju Lee ◽  
Sung-Ho Lim ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Energy Consumption ◽  
Functional Recovery ◽  
Stroke Rehabilitation ◽  
Brain Regions ◽  
Implantable Devices ◽  
Rehabilitation Process ◽  
Neural Excitability ◽  
Spike Firing

Abstract As a promising future treatment for stroke rehabilitation, researchers have developed direct brain stimulation to manipulate the neural excitability. However, there has been less interest in energy consumption and unexpected side effect caused by electrical stimulation to bring functional recovery for stroke rehabilitation. In this study, we propose an engineering approach with subthreshold electrical stimulation (STES) to bring functional recovery. Here, we show a low level of electrical stimulation boosted causal excitation in connected neurons and strengthened the synaptic weight in a simulation study. We found that STES with motor training enhanced functional recovery after stroke in vivo. STES was shown to induce neural reconstruction, indicated by higher neurite expression in the stimulated regions and correlated changes in behavioral performance and neural spike firing pattern during the rehabilitation process. This will reduce the energy consumption of implantable devices and the side effects caused by stimulating unwanted brain regions.

Effects of ATP precursors on ATP and free ADP content and functional recovery of postischemic hearts

1989 ◽  
Vol 256 (2) ◽  
pp. H560-H566 ◽  
Author(s):  
G. Ambrosio ◽  
W. E. Jacobus ◽  
M. C. Mitchell ◽  
M. R. Litt ◽  
L. C. Becker
Keyword(s):  
Functional Recovery ◽  
Adenine Nucleotide ◽  
Mean Value ◽  
Global Ischemia ◽  
Stunned Myocardium ◽  
Base Line ◽  
Atp Content ◽  
Atp Levels ◽  
Developed Pressure

It has been proposed that administration of adenine nucleotide precursors might accelerate replenishment of myocardial ATP and "free" ADP, thus improving recovery of depressed contractility of postischemic hearts. To test this hypothesis, Langendorff-perfused rabbit hearts were subjected to 20 min of global ischemia and reperfused for 2 h with normal perfusate (n = 8) or perfusate containing 100 mumol/l of the ATP precursors adenosine (n = 8) or 5-amino-4-imidazolecarboxamide riboside (AICAriboside; n = 8). After reperfusion, developed pressure in untreated hearts averaged 70-80% of base line, whereas ATP content was reduced to approximately 70% of preischemic values. AICAriboside administration did not increase tissue ATP levels or contractility. However, in every heart that received adenosine during reperfusion, ATP content increased from a mean value of 65 +/- 4% of base line to 84 +/- 5% at the end of reperfusion (P less than 0.001). Free ADP also increased in adenosine-treated hearts from 40 to 50% of base line at the beginning of reperfusion, to normal levels by 60 min. However, no improvement in contractility was observed in the hearts that received adenosine. These results support the hypothesis that decreased availability of nucleotide precursors is responsible for depressed ATP levels in postischemic hearts; however, reduced ATP and free ADP levels may not be directly responsible for the depressed function of stunned myocardium.

Transplantation of Neural Stem/Progenitor Cells at Different Locations in Mice with Spinal Cord Injury

2014 ◽  
Vol 23 (11) ◽  
pp. 1451-1464 ◽  
Author(s):  
Hiroki Iwai ◽  
Satoshi Nori ◽  
Soraya Nishimura ◽  
Akimasa Yasuda ◽  
Morito Takano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cells ◽  
Functional Recovery ◽  
Control Group ◽  
Cord Injury ◽  
Neural Stem Progenitor Cells ◽  
Neurotropic Factor ◽  
Transplantation Site

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

Inhibition of PKC phosphorylation of cTnI improves cardiac performance in vivo

2004 ◽  
Vol 286 (6) ◽  
pp. H2089-H2095 ◽  
Author(s):  
Brian B. Roman ◽  
Paul H. Goldspink ◽  
Elyse Spaite ◽  
Dalia Urboniene ◽  
Ron McKinney ◽  
...  
Keyword(s):  
Troponin I ◽  
Cardiac Contraction ◽  
Phosphorylation Sites ◽  
Developed Pressure ◽  
Contraction And Relaxation ◽  
Intracellular Targets ◽  
Camp Levels

Protein kinase C (PKC) modulates cardiomyocyte function by phosphorylation of intracellular targets including myofilament proteins. Data generated from studies on in vitro heart preparations indicate that PKC phosphorylation of troponin I (TnI), primarily via PKC-ε, may slow the rates of cardiac contraction and relaxation (+dP/d t and −dP/d t). To explore this issue in vivo, we employed transgenic mice [mutant TnI (mTnI) mice] in which the major PKC phosphorylation sites on cardiac TnI were mutated by alanine substitutions for Ser43 and Ser45 and studied in situ hemodynamics at baseline and increased inotropy. Hearts from mTnI mice exhibited increased contractility, as shown by a 30% greater +dP/dt and 18% greater −dP/d t than FVB hearts, and had a negligible response to isoproterenol compared with FVB mice, in which +dP/d t increased by 33% and −dP/d t increased by 26%. Treatment with phenylephrine and propranolol gave a similar result; FVB mouse hearts demonstrated a 20% increase in developed pressure, whereas mTnI mice showed no response. Back phosphorylation of TnI from mTnI hearts demonstrated that the mutation of the PKC sites was associated with an enhanced PKA-dependent phosphorylation independent of a change in basal cAMP levels. Our results demonstrate the important role that PKC-dependent phosphorylation of TnI has on the modulation of cardiac function under basal as well as augmented states and indicate interdependence of the phosphorylation sites of TnI in hearts beating in situ.

Effect of human urotensin-II infusion on hemodynamics and cardiac function

2003 ◽  
Vol 81 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Ghada S Hassan ◽  
Fazila Chouiali ◽  
Takayuki Saito ◽  
Fu Hu ◽  
Stephen A Douglas ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diastolic Pressure ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Urotensin Ii ◽  
Ventricular Systolic Pressure ◽  
Wide Range ◽  
Dose Dependent Decrease

Recent studies have shown that the vasoactive peptide urotensin-II (U-II) exerts a wide range of action on the cardiovascular system of various species. In the present study, we determined the in vivo effects of U-II on basal hemodynamics and cardiac function in the anesthetized intact rat. Intravenous bolus injection of human U-II resulted in a dose-dependent decrease in mean arterial pressure and left ventricular systolic pressure. Cardiac contractility represented by ±dP/dt was decreased after injection of U-II. However, there was no significant change in heart rate or diastolic pressure. The present study suggests that upregulation of myocardial U-II may contribute to impaired myocardial function in disease conditions such as congestive heart failure.Key words: urotensin-II, rat, infusion, heart.

Sign in / Sign up

Export Citation Format

Share Document