IU Indianapolis ScholarWorks :: Browsing by Subject "Cardiac"

Browsing by Subject "Cardiac"

Now showing 1 - 10 of 12

Absence of cardiomyocyte differentiation following transplantation of adult cardiac-resident Sca-1+ cells into infarcted mouse hearts
(American Heart Association, 2018-12-18) Soonpaa, Mark H.; Lafontant, Pascal J.; Reuter, Sean; Scherschel, John A.; Srour, Edward F.; Zaruba, Marc-Michael; Rubart-von der Lohe, Michael; Field, Loren J.; Medicine, School of Medicine
Although several lines of evidence suggest that the glycosyl phosphatidylinositol-anchored cell surface protein Sca-1 marks cardiac-resident stem cells, a critical analysis of the literature raises some concerns regarding their cardiomyogenic potential.1 Here, isolated adult cardiac-resident Sca-1+ cells were engrafted into infarcted hearts and monitored for cardiomyogenic differentiation. Donor cells were prepared from ACT-EGFP; MHC-nLAC double-transgenic mice ([C57/Bl6J x DBA/2J]F1 genetic background; all procedures followed were in accordance with Institutional Guidelines). The ACT-EGFP transgene targets ubiquitous expression of an enhanced green fluorescent protein reporter, and the MHC-nLAC transgene targets cardiomyocyte-restricted expression of a nuclear-localized β-galactosidase reporter. Donor cell survival was monitored via EGFP fluorescence, while cardiomyogenic differentiation was monitored by reacting with the chromogenic β-galactosidase substrate 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-GAL), which gives rise to a blue product.2 Double-transgenic hearts were dispersed with Blendzyme and the resulting cells reacted with an APC-conjugated anti-Sca-1 antibody and a PE-conjugated cocktail of antibodies recognizing hematopoietic lineage markers.3 Sca-1+, EGFP+, lineage- cells were then isolated via fluorescence-activated cell sorting (FACS; characterization of the donor cells is provided in Figure 1A), and 100,000 cells were injected into the infarct border zone of non-transgenic [C57/Bl6J x DBA/2J]F1 mice immediately following permanent coronary artery occlusion.
Adipose stem cell secretome markedly improves rodent heart and human induced pluripotent stem cell-derived cardiomyocyte recovery from cardioplegic transport solution exposure
(Oxford University Press, 2021) Ellis, Bradley W.; Traktuev, Dmitry O.; Merfeld-Clauss, Stephanie; Can, U. Isik; Wang, Meijing; Bergeron, Ray; Zorlutuna, Pinar; March, Keith L.; Surgery, School of Medicine
Heart transplantation is a life-saving therapy for end-stage organ failure. Organ deterioration during transportation limits storage to 4 hours, limiting hearts available. Approaches ameliorating organ damage could increase the number of hearts acceptable for transplantation. Prior studies show that adipose-derived stem/stromal cell secretome (ASC-S) rescues tissues from postischemic damage in vivo. This study tested whether ASC-S preserved the function of mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes (iCM) exposed to organ transportation and transplantation conditions. Hearts were subjected to cold University of Wisconsin (UW) cardioplegic solution ± ASC-S for 6 hours followed by analysis using the Langendorff technique. In parallel, the effects of ASC-S on the recovery of iCM from UW solution were examined when provided either during or after cold cardioplegia. Exposure of hearts and iCM to UW deteriorated contractile activity and caused cell apoptosis, worsening in iCM as a function of exposure time; these were ameliorated by augmenting with ASC-S. Silencing of superoxide dismutase 3 and catalase expression prior to secretome generation compromised the ASC-S cardiomyocyte-protective effects. In this study, a novel in vitro iCM model was developed to complement a rodent heart model in assessing efficacy of approaches to improve cardiac preservation. ASC-S displays strong cardioprotective activity on iCM either with or following cold cardioplegia. This effect is associated with ASC-S-mediated cellular clearance of reactive oxygen species. The effect of ASC-S on the temporal recovery of iCM function supports the possibility of lengthening heart storage by augmenting cardioplegic transport solution with ASC-S, expanding the pool of hearts for transplantation.
Cardiac Troponin I-interacting Kinase impacts cardiomyocyte S-phase activity but not cardiomyocyte proliferation
(American Heart Association, 2023) Reuter, Sean P.; Soonpaa, Mark H.; Field, Dorothy; Simpson, Ed; Rubart-von der Lohe, Michael; Lee, Han Kyu; Sridhar, Arthi; Ware, Stephanie M.; Green, Nick; Li, Xiaochun; Ofner, Susan; Marchuk, Douglas A.; Wollert, Kai C.; Field, Loren J.; Pediatrics, School of Medicine
Background: Identifying genetic variants that affect the level of cell cycle reentry and establishing the degree of cell cycle progression in those variants could help guide development of therapeutic interventions aimed at effecting cardiac regeneration. We observed that C57Bl6/NCR (B6N) mice have a marked increase in cardiomyocyte S-phase activity after permanent coronary artery ligation compared with infarcted DBA/2J (D2J) mice. Methods: Cardiomyocyte cell cycle activity after infarction was monitored in D2J, (D2J×B6N)-F1, and (D2J×B6N)-F1×D2J backcross mice by means of bromodeoxyuridine or 5-ethynyl-2'-deoxyuridine incorporation using a nuclear-localized transgenic reporter to identify cardiomyocyte nuclei. Genome-wide quantitative trait locus analysis, fine scale genetic mapping, whole exome sequencing, and RNA sequencing analyses of the backcross mice were performed to identify the gene responsible for the elevated cardiomyocyte S-phase phenotype. Results: (D2J×B6N)-F1 mice exhibited a 14-fold increase in cardiomyocyte S-phase activity in ventricular regions remote from infarct scar compared with D2J mice (0.798±0.09% versus 0.056±0.004%; P<0.001). Quantitative trait locus analysis of (D2J×B6N)-F1×D2J backcross mice revealed that the gene responsible for differential S-phase activity was located on the distal arm of chromosome 3 (logarithm of the odds score=6.38; P<0.001). Additional genetic and molecular analyses identified 3 potential candidates. Of these, Tnni3k (troponin I-interacting kinase) is expressed in B6N hearts but not in D2J hearts. Transgenic expression of TNNI3K in a D2J genetic background results in elevated cardiomyocyte S-phase activity after injury. Cardiomyocyte S-phase activity in both Tnni3k-expressing and Tnni3k-nonexpressing mice results in the formation of polyploid nuclei. Conclusions: These data indicate that Tnni3k expression increases the level of cardiomyocyte S-phase activity after injury.
Efficient In Vivo Homology-Directed Repair Within Cardiomyocytes
(American Heart Association, 2022) Zheng, Yanjiang; VanDusen, Nathan J.; Butler, Catalina E.; Ma, Qing; King, Justin S.; Pu, William T.; Pediatrics, School of Medicine
Events Due to Snowblower Use Seen in US Emergency Departments From 2003 Through 2018
(Cureus, 2020-12-01) Loder, Randall T.; Solanki, Dhruv; Orthopaedic Surgery, School of Medicine
Objective To comprehensively analyze emergency department (ED) visits associated with snowblower use in the United States. Methods Data on National Electronic Injury Surveillance System ED visits due to snow blowers from 2003 through 2018 were analyzed by age, sex, diagnosis, anatomic location of the injury, and year, month, or weekday. The mechanism of injury and alcohol use were noted. Statistical analyses were performed, accounting for the weighted, stratified nature of the data. Results There were an estimated 91,451 patients with an average age of 51 years; 91.2% were male. Amputation, fracture, or laceration accounted for 43,524 (47.6%) of the ED visits. The mechanism of injury was placing the hand into the chute (44.5%), a fall/slip (13.3%), medical events (6.1%), and miscellaneous (33.8%). Most (68.9%) occurred at home. Alcohol was rarely involved (0.4%). There were 648 deaths; 647 were due to cardiac events. The five major injury diagnoses were fracture (25.9%), laceration (20.2%), strain/sprain (15.0%), amputation (11.2%), and contusion/abrasion (10.2%); 99.8% of the amputations involved fingers. The incidence of ED snowblower visits was 1.845 per 100,000 US population with no change over time. There was a general correlation between the number of visits and the annual snow cover. Conclusions Ample opportunity for injury prevention exists, as there was no change in the incidence over time. Cardiac events accounted for essentially all of the deaths.
In situ three-dimensional reconstruction of mouse heart sympathetic innervation by two-photon excitation fluorescence imaging
(2014-02-25) Freeman, Kim Renee; Rubart-von der Lohe, Michael; Atkinson, Simon; Hurley, Thomas D., 1961-; Gattone II, Vincent H.
The sympathetic nervous system strongly modulates the contractile and electrical function of the heart. The anatomical underpinnings that enable a spatially and temporally coordinated dissemination of sympathetic signals within the cardiac tissue are only incompletely characterized. In this work we took the first step of unraveling the in situ 3D microarchitecture of the cardiac sympathetic nervous system. Using a combination of two-photon excitation fluorescence microscopy and computer-assisted image analyses, we reconstructed the sympathetic network in a portion of the left ventricular epicardium from adult transgenic mice expressing a fluorescent reporter protein in all peripheral sympathetic neurons. The reconstruction revealed several organizational principles of the local sympathetic tree that synergize to enable a coordinated and efficient signal transfer to the target tissue. First, synaptic boutons are aligned with high density along much of axon-cell contacts. Second, axon segments are oriented parallel to the main, i.e., longitudinal, axes of their apposed cardiomyocytes, optimizing the frequency of transmitter release sites per axon/per cardiomyocyte. Third, the local network was partitioned into branched and/or looped sub-trees which extended both radially and tangentially through the image volume. Fourth, sub-trees arrange to not much overlap, giving rise to multiple annexed innervation domains of variable complexity and configuration. The sympathetic network in the epicardial border zone of a chronic myocardial infarction was observed to undergo substantive remodeling, which included almost complete loss of fibers at depths >10 µm from the surface, spatially heterogeneous gain of axons, irregularly shaped synaptic boutons, and formation of axonal plexuses composed of nested loops of variable length. In conclusion, we provide, to the best of our knowledge, the first in situ 3D reconstruction of the local cardiac sympathetic network in normal and injured mammalian myocardium. Mapping the sympathetic network connectivity will aid in elucidating its role in sympathetic signal transmisson and processing.
Myocardial injuries among patients with COVID-19: a systematic review
(University of Salerno, 2021-09-10) Alali, Alaa Hasan; Smaisem, Mustafa Samir; Alsheikh, Ahmed Mohammed; Alshareef, Aljohara Abdullah; Smaisem, Fatema Samir; Alnahar, Batool Wael; Hassouneh, Amal Khalil; Al-Tawfiq, Jaffar A.; Memish, Ziad A.; Medicine, School of Medicine
This is a systematic review of the literature specifically aimed to explore myocardial injury in coronavirus disease-19 (COVID-19) patients who were hospitalized with severe complicated infections. The medical literature was examined through the large medical databases, including Medline, Ovid, PubMed, and Embase, over the last year between January 2020 and May 2021. The search terms used were a combination of "myocardial injury" AND "COVID-19" AND "Hospitalization". Then we applied a step to filter the results to select original research articles only evaluating the myocardial injuries in severe COVID-19 hospitalized patients. Selected trials mentioned the type of myocardial injury detected with the infection. A total of 245 articles were extracted. Considering the exclusion of ineligible articles, 42 articles appeared. A total of 42 articles were eligible and were included in the review. These studies included a total of 4326 COVID-19 patients. The 30-day mortality was found to be associated with increased cardiac troponin and myocardial infarction could be a systemic reaction rather than the direct action of COVID-19. Patients with myocardial injury were significantly older and with co-morbid conditions. Studies also found a correlation of higher concentrations of cardiac enzymes with disease severity and increased in-hospital mortality. Myocardial injury was a significant predictor for severe COVID-19 infection and in-hospital mortality. Cardiac enzymes should be monitored in hospitalized patients with severe COVID-19 infections.
Na+, K+-Pump/Phospholemman Are Concentrated at Intercalated Discs for Conduction
(American Heart Association, 2022) Chen, Zhenhui; Sung, Yen-Ling; Chen, Peng-Sheng; Li, Xiaochun; Guo, Jin; Biostatistics and Health Data Science, School of Medicine
Obesity alters global response to ischemia and GLP-1 agonism
(2016-05-13) Sassoon, Daniel Jay; Tune, Johnathan; Mather, Kieren
Glucagon-like peptide 1 (GLP-1) receptor agonists are a class of incretin based therapeutics which aid in blood glucose management in Type II diabetes mellitus (T2DM). Recent studies have demonstrated direct cardiovascular benefits conferred by these agents including protection in ischemia and heart failure. Despite these observations, human clinical trials fail to support improvements in cardiovascular outcomes independent of glucose lowering effects in the T2DM populations. Prior data from our lab demonstrate that obesity impairs GLP-1 associated increases in myocardial glucose uptake. However, the reasons for this impairment/resistance to cardiac effects of GLP-1 in the setting of obesity remain ill defined. This investigation tested the hypothesis that underlying differences in the cardiac proteome and microRNA (miR) transcriptome could contribute to distinct cardiac responses to ischemia and activation of GLP-1 signaling in the setting of obesity. To identify whether obesity modulated cardiac functional responses to GLP 1 related drugs, we first examined the effects of obesity on cardiac function, miR transcriptome, and proteome in response to short duration ischemia-reperfusion (I/R). We observed divergent physiologic responses (e.g. increased diastolic volume and systolic pressure in lean, decreased diastolic volumes in obese) to regional I/R in obese vs lean hearts that were associated with significant molecular changes as detected by protein mass spectrometry and miR microarray. Molecular changes were related to myocardial calcium handling (SERCA2a, histidine-rich Ca2+ binding protein), myocardial structure and function (titin), and miRs relating to cardiac metabolism, hypertrophy, and cell death, including miR-15, miR-30, miR-199a, miR-214. Importantly, these effects were modified differently by GLP-1 agonism in lean vs obese swine. Additional studies investigated the functional effects of 30 days of treatment with the GLP-1 analogue liraglutide on a model of slowly-developing, unrelieved coronary ischemia. Liraglutide failed to reduce infarct size or collagen deposition. However, analysis of left ventricular pressure-volume relationships support that liraglutide improved diastolic relaxation/filling, load-dependent indices of cardiac function, and cardiac efficiency in response to sympathetic stimulation in obese swine. Taken together, these findings support that miR and proteomic differences underlie distinct changes in functional cardiac responses to I/R and pharmacologic activation of GLP-1 signaling in the setting of obesity.
Perioperative Multimodal General Anesthesia Focusing on Specific CNS Targets in Patients Undergoing Cardiac Surgeries: The Pathfinder Feasibility Trial
(Frontiers Media, 2021-10-14) Shanker, Akshay; Abel, John H.; Narayanan, Shilpa; Mathur, Pooja; Work, Erin; Schamberg, Gabriel; Sharkey, Aidan; Bose, Ruma; Rangasamy, Valluvan; Senthilnathan, Venkatachalam; Brown, Emery N.; Subramaniam, Balachundhar; Anesthesia, School of Medicine
Multimodal general anesthesia (MMGA) is a strategy that utilizes the well-known neuroanatomy and neurophysiology of nociception and arousal control in designing a rational and clinical practical paradigm to regulate the levels of unconsciousness and antinociception during general anesthesia while mitigating side effects of any individual anesthetic. We sought to test the feasibility of implementing MMGA for seniors undergoing cardiac surgery, a high-risk cohort for hemodynamic instability, delirium, and post-operative cognitive dysfunction. Twenty patients aged 60 or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries were enrolled in this non-randomized prospective observational feasibility trial, wherein we developed MMGA specifically for cardiac surgeries. Antinociception was achieved by a combination of intravenous remifentanil, ketamine, dexmedetomidine, and magnesium together with bupivacaine administered as a pecto-intercostal fascial block. Unconsciousness was achieved by using electroencephalogram (EEG)-guided administration of propofol along with the sedative effects of the antinociceptive agents. EEG-guided MMGA anesthesia was safe and feasible for cardiac surgeries, and exploratory analyses found hemodynamic stability and vasopressor usage comparable to a previously collected cohort. Intraoperative EEG suppression events and postoperative delirium were found to be rare. We report successful use of a total intravenous anesthesia (TIVA)-based MMGA strategy for cardiac surgery and establish safety and feasibility for studying MMGA in a full clinical trial.

Browsing by Subject "Cardiac"

Results Per Page

Sort Options