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  • 1
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 60, No. 6 ( 2015-03-15), p. 976-977
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2002229-3
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 1997
    In:  Irish Journal of Medical Science Vol. 166, No. 3 ( 1997-7), p. 157-194
    In: Irish Journal of Medical Science, Springer Science and Business Media LLC, Vol. 166, No. 3 ( 1997-7), p. 157-194
    Type of Medium: Online Resource
    ISSN: 0021-1265 , 1863-4362
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1997
    detail.hit.zdb_id: 2275855-0
    detail.hit.zdb_id: 2468506-9
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  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 1979
    In:  Circulation Vol. 60, No. 2 ( 1979-08), p. 141-146
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 60, No. 2 ( 1979-08), p. 141-146
    Abstract: To assess the potential benefit of pulsatile perfusion inthe hypertrophied heart during fibrillation, 10 dogs with left ventricular hypertrophy, produced by previous supravalvular aortic banding, were used to compare linear and pulsatile perfusion in the fibrillating heart during total cardiopulmonary bypass. The mass spectrometer was used to measure subendocardial PCO2 and PO2 (PmCO2 and PmO2), and radioactive microspheres were utilized to measure myocardial blood flow in the same layers. Pulsatile perfusion was established using the recently develop "bubble tubing," which produces a pulse pressure of at least 20 mm Hg and can be used in a standard roller-pump apparatus. Both linear and pulsatile flows were compared at mean aortic root pressures of 80 and 50 mm Hg, and these four combinations of aortic root pressure and type of flow were employed for periods of 30 minutes each. Myocardial ischemia developed during linear coronary perfusion at 50 mm Hg, as evidenced by an elevation of PmCO2. Ischemia was not evident during pulsatile perfusion at the same mean pressure. Reversal ischemia was a result of increased myocardial blood flow and pulsatile perfusion, and this increase was shown to occur maximally in the deeper subendocardial layer. Ischemia was not eviden during linear or pulsatile perfusion at an mean perfusion pressure 80 mm Hg. Thus, if lower perfusion pressures are to be tolerated in patients with left ventricular hypertrophy, pulsatile perfusion with the bubble tubing technique may prevent the development of subendocardial ischemia or infarction.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1979
    detail.hit.zdb_id: 1466401-X
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  • 4
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 1989
    In:  Circulation Vol. 79, No. 4 ( 1989-04), p. 776-782
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 79, No. 4 ( 1989-04), p. 776-782
    Abstract: Recognition that myocardial infarction is caused by coronary thrombosis has stimulated a search for a safe, rapidly acting, and effective thrombolytic regimen. Tissue plasminogen activator (t-PA) can provide relatively clot-selective thrombolysis, but one quarter of patients fail to achieve reperfusion, lysis speed is not optimal, and higher doses have been associated with an increased incidence of hemorrhagic stroke. We report the results of a multicenter study of pro-urokinase, a second naturally occurring plasminogen activator that has structural similarities to t-PA but has a different mechanism of action. Pro-urokinase was administered 3.9 +/- 1.1 hours after the onset of chest pain to 40 patients with acute myocardial infarction with angiographically confirmed complete coronary occlusion (TIMI grade 0). After a 90-minute intravenous infusion of pro-urokinase (4.7-9 million units, 36-69 mg) 51% (20 of 39) of the patients demonstrated reperfusion (TIMI grade 2 or 3) occurring 64.8 +/- 22.3 minutes after initiation of therapy. Fibrinogen levels fell only 10 +/- 17% from baseline, confirming the fibrin specificity of pro-urokinase. As with t-PA, however, this specificity was only relative. alpha 2-Antiplasmin decreased to 39% and plasminogen decreased to 64% of initial values. Fibrinogen degradation products increased 63% and the fibrin-specific D-dimer increased 8.7-fold. Thus, pro-urokinase produces relatively clot-selective coronary thrombolysis similar to that produced by t-PA, but the use of either pro-urokinase or t-PA alone in higher doses would be likely to produce more nonspecific effects.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1989
    detail.hit.zdb_id: 1466401-X
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  • 5
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 1979
    In:  Circulation Vol. 60, No. 2 ( 1979-08), p. 151-157
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 60, No. 2 ( 1979-08), p. 151-157
    Abstract: Nifedipine, a slow-channel calcium blocker, is thought to provide useful myocardial protection during prolonged total ischemia and reperfusion. An isolated, isovolumic, feline heart model was used to asses the effectiveness of nifedipine in both cardioplegic (100 microgram/10 ml) and noncardioplegic (10 microgram/10 ml) doses for providing myocardial preservation during 90 minutes of hypothermic ischemic arrest and 45 minutes of normothermic reperfusion. Use of nifedipine was compared to hypothermia (27 degrees C) alone and to hypothermia with potassium cardioplegia. Ventricular function was assessed by recovery of isovolumic left ventricular developed pressure and dP/dt. Myocardial carbon dioxide tension (PCO2) and myocardial oxygen tension (PO2) were measured by mass spectrometry. Potassium cardioplegia and the higher dose of nifedipine resulted in immediate asystole. The rates of rise of PCO were greatest in the group receiving 10 microgram nifedipine and in the control group. The rates of rise in the two cardioplegic groups were significantly lower. Recovery of ventricular function was significantly lower with low-dose nifedipine than with potassium cardioplegia. Higher dose nifedipine resulted in a return of function, which was no different than with potassium cardioplegia. Morphologic protection was better with higher dose nifedipine and potassium cardioplegia than with either low-dose cardioplegia or hypothermia alone. These results demonstrate that nifedipine in a cardioplegic dose results in preservation of myocardial structure and function that is similar to that obtained with potassium cardioplegia. In lower noncardioplegic dose, nifedipine does not appear to offer additional protection compared to hypothermia alone. Whether persistent depression of ventricular contractility will limit nifedipine's clinical usefulness as a myocardial protection agent will require further study.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1979
    detail.hit.zdb_id: 1466401-X
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  • 6
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 1984
    In:  Circulation Vol. 69, No. 3 ( 1984-03), p. 585-592
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 69, No. 3 ( 1984-03), p. 585-592
    Abstract: We used phosphorus-31 nuclear magnetic resonance to test the ability of a perfluorocarbon blood substitute that has been shown in previous studies to improve oxygen delivery to hypothermic myocardium to maintain aerobic high-energy phosphate metabolism during total global ischemia. Twenty-three isolated perfused rabbit hearts were subjected to 180 min of hypothermic (23 degrees C) global ischemia followed by 45 min of normothermic reperfusion. Hearts received multiple doses of a cardioplegic solution that contained either oxygenated perfluorocarbon (Fluosol O2), nonoxygenated perfluorocarbon (Fluosol N2), or standard crystalloid hyperkalemic cardioplegic solution (STD-KCl) at 30 min intervals. Recovery of isovolumic left ventricular developed pressure (LVDP) was used to assess preservation of contractile function. Recovery of LVDP was 84 +/- 19% of preischemic control values with Fluosol O2, 68 +/- 16% with Fluosol N2, and 67 +/- 17% with STD-KCl (p = .058 vs Fluosol N2 and p = .056 vs STD-KCl). During 3 hr of ischemia intracellular pH (pHi) fell to 6.68 +/- 0.20 with STD-KCl and to 6.71 +/- 0.14 with Fluosol N2 but remained above 7.00 throughout the ischemic period with Fluosol O2 (p less than .0001 vs Fluosol N2 or STD-KCl). Myocardial ATP content was better preserved at 107 +/- 14% of control values with Fluosol O2 compared to 60 +/- 18% of control with Fluosol N2 and 75 +/- 21% of control with STD-KCl (p less than .001 vs Fluosol N2, p = .002 vs STD-KCl). Phosphocreatine (PCr) was also better preserved with Fluosol O2.(ABSTRACT TRUNCATED AT 250 WORDS)
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1984
    detail.hit.zdb_id: 1466401-X
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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 1982
    In:  Circulation Vol. 65, No. 3 ( 1982-03), p. 561-570
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 65, No. 3 ( 1982-03), p. 561-570
    Abstract: Phosphorus-31 nuclear magnetic resonance (31P NMR) can estimate tissue intracellular pH as well as the content of high-energy phosphate metabolites in isolated perfused hearts. We used 31P NMR to examine mechanisms associated with the recovery of ventricular function in hearts subjected to global ischemia and reperfusion, with special emphasis on intracellular pH, a previously unreported variable. Single-dose and multiple-dose administration of a hyperkalemic cardioplegic solution were compared with hypothermia alone in 18 isolated perfused rabbit hearts. Hearts in group 1 were subjected to 24 degrees C hypothermia during 60 minutes of global ischemia; group 2 hearts received a single injection of 37-mM KCL cardioplegic solution at 10 degrees C at the onset of ischemia; and group 3 hearts received a similar initial cardioplegic injection followed by two subsequent 24 degrees C injections at 20-minute intervals during the ischemic period. Using an intraventricular balloon, maximal dP/dt provided a quantitative index of left ventricular performance before and after ischemia. Return of ventricular function expressed as a percentage of control was 54 +/- 11% for group 1, 84 +/- 6% for group 2, and 101 +/- 18% for group 3. Differences in the rate of development of intracellular acidosis were noted during the 60-minute ischemic period. Intracellular pH fell to 6.09 +/- 0.12 in group 1, 6.31 +/- 0.09 in group 2, an 6.79 +/- 0.03 in group 3. In all three groups intracellular pH returned to control (pH 7.20) within 10 minutes of reflow. The metabolic correlates of functional recovery appeared to be the tissue content of ATP at the end of ischemia and after reflow. ATP content at the end of ischemia was 22 +/- 2% of control in group 1 hearts, 31 +/- 4% in group 2 and 64 +/- 2% in group 3. After 45 minutes of reperfusion, ATP levels recovered to 33 +/- 9% of control in group 1, to 71 +/- 9% in group 2 and to 86 +/- 6% in group 3. Although there were no differences between groups in the content of creatine phosphate after 60 minutes of ischemia, the rates of creatine phosphate decline were dissimilar. Further, during the early reflow period, a marked overshoot in tissue creatine phosphate was detected, especially in groups 1 and 2. Histologic damage assessed by light microscopy correlated with the metabolic data, confirming that multidose cardioplegia provided the best preservation of cellular morphology. These results demonstrate that the magnitude of intracellular acidosis and the associated increase in inorganic phosphate correlate inversely with recovery of postischemic ventricular structure and function. ATP, but not creatine phosphate, content correlates with return of contractile performance after reperfusion. The overshoot in creatine phosphate during early reperfusion might impede optimal restoration of ATP content and, as a result, optimal recovery of cell functions.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1982
    detail.hit.zdb_id: 1466401-X
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  • 8
    In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Abstract: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    RVK:
    RVK:
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 9
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 68, No. 3 ( 1983-09), p. 576-588
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1983
    detail.hit.zdb_id: 1466401-X
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  • 10
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 89, No. 5 ( 1994-05), p. 1982-1991
    Abstract: Animal studies have demonstrated a burst of oxygen free radical generation after reperfusion of ischemic myocardium that could be blocked by administration of the free radical scavenger recombinant human superoxide dismutase (h-SOD). A multicenter, randomized, placebo-controlled clinical trial was designed to test the hypothesis that free radical-mediated reperfusion injury could be reduced by intravenous administration of h-SOD begun before percutaneous transluminal coronary angioplasty (PTCA) in patients with acute transmural myocardial infarction. METHODS AND RESULTS One hundred twenty patients were randomized to receive placebo (n = 59) or h-SOD (n = 61) given as a 10-mg/kg intravenous bolus followed by a 60-minute infusion of 0.2 mg.kg-1.min-1. Left ventricular function was analyzed via paired contrast left ventriculograms performed before PTCA and after 6 to 10 days and paired radionuclide ventriculograms performed within 24 hours of PTCA and after 4 to 6 weeks. Both h-SOD- and placebo-treated patients showed improvement in global and regional left ventricular function after successful reperfusion. Compared with the placebo group, no additional improvement was observed in the patients treated with h-SOD. CONCLUSIONS The results of this clinical trial failed to demonstrate a beneficial effect of h-SOD on global or regional left ventricular function in patients who underwent successful PTCA for treatment of acute myocardial infarction.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1994
    detail.hit.zdb_id: 1466401-X
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