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K. Francis Lee

Bio: K. Francis Lee is an academic researcher from VCU Medical Center. The author has contributed to research in topics: Afterload & Cardiac output. The author has an hindex of 8, co-authored 9 publications receiving 425 citations.

Papers
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Journal ArticleDOI
TL;DR: The detailed evaluation of left ventricular chamber mechanics suggests that dynamic cardiomyoplasty may have a role in ameliorating the functional and mechanical derangements associated with progression of dilatedCardiomyopathy both by augmenting cardiac performance and by diminishing determinants of myocardial oxygen consumption.

94 citations

Journal ArticleDOI
TL;DR: Prevention of platelet-, adrenergic-, or potassium-induced contraction may be more important when the gastroepiploic artery is used as an alternate conduit for coronary artery bypass, reinforcing consideration of nitrovasodilators and platelet inhibitors in the perioperative interval.

63 citations

Journal ArticleDOI
TL;DR: Chronic stimulation of a predominantly fast skeletal muscle enhanced the expression of type I (slow muscle) Ca‐ATPase and suppressed the expression in the type II (fast muscle), and Ca‐ ATPase isozyme distribution in isolated SR confirmed this effect of chronic stimulation.

62 citations

Journal ArticleDOI
TL;DR: The results indicate that, when combined with cardioplegic ischemic arrest, rapid myocardial cooling in the unarrested state results in significant damage, and the mechanism may be related to the cytosolic calcium loading effect of hypothermia that is not relieved during the subsequent period of cardioleongic arrest.

59 citations

Journal ArticleDOI
TL;DR: The expression of the major protein components of the triad junction involved in excitation-contraction coupling is suppressed, while the expression of other muscle membrane proteins is not affected in chronically stimulated muscle.
Abstract: The chronic stimulation of predominantly fast-twitch mammalian skeletal muscle causes a transformation to physiological characteristics of slow-twitch skeletal muscle. Here, we report the effects of chronic stimulation on the protein components of the sarcoplasmic reticulum and transverse tubular membranes which are directly involved in excitation-contraction coupling. Comparison of protein composition of microsomal fractions from control and chronically stimulated muscle was performed by immunoblot analysis and also by staining with Coomassie blue or the cationic carbocyanine dye Stains-all. Consistent with previous experiments, a greatly reduced density was observed for the fast-twitch isozyme of Ca2+-ATPase, while the expression of the slow-twitch Ca2+-ATPase was found to be greatly enhanced. Components of the sarcolemma (Na+/K+-ATPase, dystrophin-glycoprotein complex) and the free sarcoplasmic reticulum (Ca2+-binding protein sarcalumenin and a 53-k Da glycoprotein) were not affected by chronic stimulation. The relative abundance of calsequestrin was slightly reduced in transformed skeletal muscle. However, the expression of the ryanodine receptor/Ca2+-release channel from junctional sarcoplasmic reticulum and the transverse tubular dihydropyridine-sensitive Ca2+ channel, as well as two junctional sarcoplasmic reticulum protiens of 90 kDa and 94 kDa, was greatly suppressed in transformed muscle. Thus, the expression of the major protein components of the triad junction involved in excitation-contraction coupling is suppressed, while the expression of other muscle membrane proteins is not affected in chronically stimulated muscle.

57 citations


Cited by
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Journal ArticleDOI
TL;DR: Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Starlings R: University of Chicago, Chicago, Illinois,USA; Chan M: university of Alberta, Edmonton, Alberta, Canada ; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA.
Abstract: Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.

1,346 citations

Book ChapterDOI
TL;DR: A simple transition scheme has emerged from the multitude of data collected on fiber type conversions under a variety of conditions, and it is now clear that fiber type transitions do not proceed in immediate jumps from one extreme to the other, but occur in a graded and orderly sequential manner.
Abstract: Mammalian skeletal muscle is an extremely heterogeneous tissue, composed of a large variety of fiber types. These fibers, however, are not fixed units but represent highly versatile entities capable of responding to altered functional demands and a variety of signals by changing their phenotypic profiles. This adaptive responsiveness is the basis of fiber type transitions. The fiber population of a given muscle is in a dynamic state, constantly adjusting to the current conditions. The full range of adaptive ability spans fast to slow characteristics. However, it is now clear that fiber type transitions do not proceed in immediate jumps from one extreme to the other, but occur in a graded and orderly sequential manner. At the molecular level, the best examples of these stepwise transitions are myofibrillar protein isoform exchanges. For the myosin heavy chain, this entails a sequence going from the fastest (MHCIIb) to the slowest (MHCI) isoform, and vice-versa. Depending on the basal protein isoform profile and hence the position within the fast-slow spectrum, the adaptive ranges of different fibers vary. A simple transition scheme has emerged from the multitude of data collected on fiber type conversions under a variety of conditions.

651 citations

Journal ArticleDOI
TL;DR: The molecular responses of neutrophils to ischemia-reperfusion are described, the cellular and tissue damage inflicted either directly or indirectly by these white cells are discussed, and the physiological impact of interdiction ofNeutrophil-mediated interactions with myocardial cells at various levels on lethal post-ischemic injury are discussed.
Abstract: Neutrophils respond to myocardial ischemia-reperfusion in a manner similar to the bacterial invasion of a host. The inflammatory-like response that follows the onset of reperfusion involves intense interactions with the coronary vascular endothelium, arterial wall, and cardiomyocytes in a very well-choreographed manner. Neutrophils have been implicated as primary and secondary mediators of lethal injury after reperfusion to coronary vascular endothelium and cardiomyocytes. The involvement of neutrophils in the pathogenesis of lethal myocardial injury has been inferred from (1) their presence and accumulation in reperfused myocardium in temporal agreement with injury induced, (2) the armamentarium of toxic agents such as oxidants and proteases that are released by neutrophils in reperfused myocardium, (3) responsivity to (recruitment by and/or activation by) inflammatory factors released by reperfused myocardium, and (4) inhibition of lethal post-ischemic myocyte or endothelial cell injury by strategies that interdict neutrophil interactions at any number of stages. However, whether neutrophils are directly involved in the pathogenesis of lethal reperfusion injury in the myocardium, are just pedestrian (first) responders to inflammatory signals released after the onset of reperfusion, or are important to an early but not clinically important phase of pathology are still points of controversy. As with the general area of myocardial protection itself, the failure to reproduce the salubrious effects of anti-neutrophil therapeutic strategies and to successfully translate these strategies into clinical practice has not only fueled the debate, but has jeopardized the further pursuit of myocardial protection therapeutics to improve post-ischemic outcomes. This review will describe the molecular responses of neutrophils to ischemia-reperfusion, discuss the cellular and tissue damage inflicted either directly or indirectly by these white cells, and discuss the physiological impact of interdiction of neutrophil-mediated interactions with myocardial cells at various levels on lethal post-ischemic injury. In addition, it will discuss the arguments for and against the involvement of neutrophils in responses to ischemia-reperfusion in experimental models, and the failure to translate experimentally successful therapy into clinical practice.

636 citations

Journal ArticleDOI
TL;DR: The understanding of the molecular processes regulating actions of neutrophils in ischemic-reperfusion injury may be applicable to other clinical situations, such as trauma, shock and organ or tissue (i.e. vascular conduits) transplantation.
Abstract: Reperfusion of ischemic myocardium is necessary to salvage tissue from eventual death. However, reperfusion after even brief periods of ischemia is associated with pathologic changes that represent either an acceleration of processes initiated during ischemia per se, or new pathophysiological changes that were initiated after reperfusion. This 'reperfusion injury' shares many characteristics with inflammatory responses in the myocardium. Neutrophils feature prominently in this inflammatory component of postischemic injury. Ischemia-reperfusion prompts a release of oxygen free radicals, cytokines and other proinflammatory mediators that activate both the neutrophils and the coronary vascular endothelium. Activation of these cell types promotes the expression of adhesion molecules on both the neutrophils and endothelium, which recruits neutrophils to the surface of the endothelium and initiate a specific cascade of cell-cell interactions, leading first to adherence of neutrophils to the vascular endothelium, followed later by transendothelial migration and direct interaction with myocytes. This specific series of events is a prerequisite to the phenotypic expression of reperfusion injury, including endothelial dysfunction, microvascular collapse and blood flow defects, myocardial infarction and apoptosis. Pharmacologic therapy can target the various components in this critical series of events. Effective targets for these pharmacologic agents include: (a) inhibiting the release or accumulation of proinflammatory mediators, (b) altering neutrophil or endothelial cell activation and (c) attenuating adhesion molecule expression on endothelium, neutrophils and myocytes. Monoclonal antibodies to adhesion molecules (P-selectin, L-selectin, CD11, CD18), complement fragments and receptors attenuate neutrophil-mediated injury (vascular injury, infarction), but clinical application may encounter limitations due to antigen-antibody reactions with the peptides. Humanized antibodies and non-peptide agents, such as oligosaccharide analogs to sialyl Lewis, may prove effective in this regard. Both nitric oxide and adenosine exhibit broad spectrum effects against neutrophil-mediated events and, therefore, can intervene at several critical points in the ischemic-reperfusion response, and may offer greater benefit than agents that interdict at a single point in the cascade. The understanding of the molecular processes regulating actions of neutrophils in ischemic-reperfusion injury may be applicable to other clinical situations, such as trauma, shock and organ or tissue (i.e. vascular conduits) transplantation.

592 citations

Journal ArticleDOI
TL;DR: A comprehensive discussion is presented of advances in understanding the structure and function of phospholamban, the principal regulator of the Ca2+-ATPase of cardiac sarcoplasmic reticulum.
Abstract: Simmerman, Heather K. B., and Larry R. Jones. Phospholamban: Protein Structure, Mechanism of Action, and Role in Cardiac Function. Physiol. Rev. 78: 921–947, 1998. — A comprehensive discussion is p...

570 citations