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From the Literature

2019; Lippincott Williams & Wilkins; Volume: 140; Issue: 16 Linguagem: Inglês

10.1161/circulationaha.119.043556

1524-4539

Tracy Hampton,

Cardiovascular Function and Risk Factors

HomeCirculationVol. 140, No. 16From the Literature Free AccessNewsPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessNewsPDF/EPUBFrom the Literature Tracy Hampton, PhD Tracy HamptonTracy Hampton Originally published14 Oct 2019https://doi.org/10.1161/CIRCULATIONAHA.119.043556Circulation. 2019;140:1352–1353Noninvasive Test Monitors Myocardial OxygenationIschemic heart disease, the leading cause of death in the Western world, often stems from atherosclerotic narrowing of the coronary arteries, which causes reduced delivery of oxygen to the heart muscle. In a Science Translational Medicinestudy, researchers report that they have developed a noninvasive imaging platform that can effectively assess the health and function of the blood vessels of the heart in a canine model of ischemic heart disease."Efforts to attain noninvasive methods for ascertaining myocardial oxygenation have not yet been realized. Instead, the current diagnosis of ischemic heart disease still relies on surrogate metrics that are either non-specific, operator dependent, or require ionizing radiation or contrast agents," said senior author Dr Rohan Dharmakumar, of Cedars-Sinai Medical Center and the University of California, Los Angeles.The imaging platform developed by Dr Dharmakumar and his colleagues, referred to as cardiac functional magnetic resonance imaging, monitors heart oxygenation by repeatedly altering carbon dioxide levels in the blood, rapidly acquiring magnetic resonance images of the associated changes in blood oxygenation, and analyzing the images using computational tools.When the platform was tested in dogs with controlled coronary artery stenosis, the team could objectively identify healthy and affected heart muscle with >90% sensitivity, specificity, and accuracy."cfMRI [cardiac functional magnetic resonance imaging] permits monitoring of myocardial oxygenation to enhance our current understanding of cardiac physiology and pathophysiology. This has the potential to broaden our ability to noninvasively identify those at risk for ischemic heart disease and a diverse spectrum of heart diseases related to myocardial ischemia," said Dr Dharmakumar.Yang HJ et al. Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using magnetic resonance imaging. Sci Transl Med. 2019;11:eaat4407. doi: 10.1126/scitranslmed.aat4407Multiorgan-on-a-Chip System Evaluates Drug ToxicityA newly developed multiorgan-on-a-chip system can determine the efficacy and off-target toxic effects of different chemotherapies. The system contains 5 chambers that can house different populations of human cancer and organ cells in a recirculating medium that mimics blood circulation.In a Science Translational Medicinestudy, investigators tested their device in 2 configurations. In the first, the effects of 2 drugs, diclofenac and imatinib, were assessed on cancer-derived human bone marrow cell lines and on healthy liver cells. Liver viability was not affected by imatinib, but it was reduced by 30% with diclofenac.The second configuration housed a multidrug-resistant vulvar cancer line, a non–multidrug-resistant breast cancer line, liver cells, and induced pluripotent stem cell–derived cardiomyocytes. The anti–breast cancer drug tamoxifen reduced viability of the breast cancer cells only after being processed by the liver, and it did not affect the vulvar cancer cells except when coadministered with verapamil, a permeability glycoprotein inhibitor. Both tamoxifen alone and tamoxifen coadministered with verapamil produced off-target cardiac effects, as indicated by a reduction of contractile force, beat frequency, and conduction velocity, but they did not affect viability. The cardiac toxicity of tamoxifen and verapamil together was greater than the toxicity of either drug by itself.The new system may help establish the therapeutic window of investigational drugs before any animal studies and may be useful for personalized medicine applications using cultured patient-derived cells."Our system will allow testing of different therapies on small samples of a specific cancer patient's tissue to help inform doctors about which treatment works best for each individual," said senior author Dr James Hickman, of Hesperos, Inc, and the University of Central Florida. "In addition, for preclinical drug discovery applications medicinal chemists can test multiple variations of a drug candidate with milligram quantities of the compound, at the pre-animal stage."McAleer CW et al. Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics. Sci Transl Med. 2019;11:eaav1386. doi: 10.1126/scitranslmed.aav1386Parental Diet May Affect the Cardiovascular Health of Several GenerationsResearchers have found that mice that consumed a high-fat, high-sugar diet passed on risk of poor cardiovascular health to the next 3 generations of offspring. Despite being lean and eating a healthy diet, the offspring had enlarged hearts with contractile abnormalities and disrupted metabolism. The findings are published in the American Journal of Physiology–Heart and Circulatory Physiology.Even when the investigators isolated oocytes from mice on the diet, fertilized them in vitro, and implanted them into surrogate mice on a healthy diet, the offspring exhibited cardiovascular problems. In addition, sperm from male offspring could transmit the increased risk of heart problems. Because the oocyte and sperm provide equal amounts of genomic DNA to the offspring but the oocyte provides all of the mitochondria, the findings suggest that the effects of poor maternal diet are passed through the nucleus.Additional studies are needed to uncover the mechanisms involved and whether the findings apply to humans. "If the same effects occur in humans as in mice, then the current obesity epidemic may be harming the cardiac health of future generations," said lead author Dr Jeremie Ferey, of Washington University School of Medicine in St Louis. "Additionally, our findings could be used to help patients in various ways." Dr Ferey noted that parental obesity could be used in risk assessments of cardiovascular disease. In addition, just as parents who smoke or drink alcohol are counseled about the potential health risks to their children, potential parents who are obese could be counseled on the possible health risks to their children.Ferey JLA et al. A maternal high-fat, high-sucrose diet induces transgenerational cardiac mitochondrial dysfunction independently of maternal mitochondrial inheritance. Am J Physiol Heart Circ Physiol. 2019;316:H1202–H1210. doi: 10.1152/ajpheart.00013.2019Download figureDownload PowerPointResearchers have developed a noninvasive method for ascertaining myocardial oxygenation in a canine model of ischemic heart disease.Footnoteshttps://www.ahajournals.org/journal/circ Previous Back to top Next FiguresReferencesRelatedDetails October 15, 2019Vol 140, Issue 16 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.119.043556 Originally publishedOctober 14, 2019 PDF download Advertisement