The Experts below are selected from a list of 408 Experts worldwide ranked by ideXlab platform
Eugene Morkin - One of the best experts on this subject based on the ideXlab platform.
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response to letter regarding article ditpa 3 5 diiodothyropropionic acid a Thyroid Hormone Analog to treat heart failure phase ii trial veterans affairs cooperative study
Circulation, 2010Co-Authors: Madeline Mccarren, Paul W. Ladenson, Eugene Morkin, Robert Edson, Janet Ohm, Hoang Thai, Lori Churby, Steven A Goldman, Meichiung Shih, Phil LavoriAbstract:We are glad that Dr Pingitore and his colleagues share our interest in use of thyromimetic agents to enhance cardiac performance. Inasmuch as a negative finding with respect to heart failure benefit with a low dose would have been an inconclusive study, we elected to administer the presumed maximum tolerated dose. In retrospect, we agree that the DITPA dose we …
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ditpa 3 5 diiodothyropropionic acid a Thyroid Hormone Analog to treat heart failure phase ii trial veterans affairs cooperative study
Circulation, 2009Co-Authors: Steven Goldman, Paul W. Ladenson, Madeline Mccarren, Eugene Morkin, Robert Edson, Stuart R Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie G BarnhillAbstract:Background—In animal studies and a pilot trial in patients with congestive heart failure, the Thyroid Hormone Analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. Methods and Results—This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n57 to DITPA, n29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failure–specific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (20%), low-density lipoprotein cholesterol (30%), and body weight (11 lb). Thyroid-stimulating Hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypoThyroidism or thyrotoxicosis were seen. Conclusions—DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure. (Circulation. 2009;119:3093-3100.)
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ditpa a Thyroid Hormone Analog to treat heart failure phase ii trial va cooperative study
Journal of Cardiac Failure, 2008Co-Authors: Steven Goldman, Paul W. Ladenson, Madeline Mccarren, Eugene Morkin, Robert Edson, Stuart R Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie G BarnhillAbstract:DITPA, a Thyroid Hormone Analog to Treat Heart Failure: Phase II Trial VA Cooperative Study Steven Goldman*, Madeline McCarren*, Eugene Morkin, Paul Ladenson, Robert Edson, Stuart Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie Barnhill, Terrence O’Brien, Inder Anand, Alberta Warner, Mark Dunlap, Brack Hattle, John Erikson, Mei-Chiung Shih, Phil Lavori; Southern Arizona VA Health Care System, Tucson, AZ; VA Center for Medication Safety, Hines, IL; University of Arizona Health Sciences, Tucson, AZ; Johns Hopkins University, Baltimore, MD; Palo Alto CSP Coordinating Center, Palo Alto, CA; CSP Clinical Research Pharmacy Coordinating Center, Albuquerque, NM; VA Medical Center, Charleston, SC; Minneapolis VA Medical Center, Minneapolis, MN; Greater Los Angeles Healthcare System, Los Angeles, CA; Louis Stokes VA Healthcare System, Cleveland, OH; VA Eastern Colorado Health Care System, Denver, CO; South Texas Veterans Health Care System, San Antonio, TX
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regulation of gene expression in rats with heart failure treated with the Thyroid Hormone Analog 3 5 diiodothyropropionic acid ditpa and the combination of ditpa and captopril
Journal of Cardiovascular Pharmacology, 2007Co-Authors: Niranjan Maitra, Steven A Goldman, Joseph J Bahl, Cynthia Adamson, Kevin A Greer, Scott E Klewer, James B Hoying, Eugene MorkinAbstract:We have used an oligonucleotide microarray to identify genes that are affected by congestive heart failure and those influenced by treatment with DITPA and DITPA in combination with captopril using a rat postinfarction model. The most striking result when comparing heart failure to sham operation was that all of the mitochondrial and metabolic enzymes affected were down regulated. When comparing heart failure with DITPA treatment, most of the down regulated metabolic genes were returned toward normal. When comparing heart failure with heart failure animals treated with DITPA and captopril, metabolic enzymes were no longer significantly downregulated. DITPA treatment and the combination of DITPA and captopril show that the metabolic enzymes were no longer down regulated. This represents a substantial improvement in the energy- generating capacity of the heart. These results indicate that the actions of DITPA and the combination of DITPA and captopril in heart failure can be partially explained by differences in gene activation.
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pilot studies on the use of 3 5 diiodothyropropionic acid a Thyroid Hormone Analog in the treatment of congestive heart failure
The Cardiology, 2002Co-Authors: Eugene Morkin, Gregory D Pennock, Peter H Spooner, Joseph J Bahl, Katherine Underhill Fox, Steven A GoldmanAbstract:After an initial safety study in 7 normal volunteers, a randomized double-blind comparison was made between 3,5-diiodothyropropionic acid (DITPA) and placebo in 19 patients with moderately severe congestive failure. In heart failure patients receiving the drug for 4 weeks, cardiac index was increased (p = 0.04) and systemic vascular resistance index was decreased (p = 0.02). Systolic cardiac function was unchanged but isovolumetric relaxation time was decreased significantly, suggesting improvement in diastolic function. Total serum cholesterol (p = 0.005) and triglycerides (p = 0.01) also were decreased significantly. DITPA could represent a useful new agent for treatment of congestive heart failure.
Steven Goldman - One of the best experts on this subject based on the ideXlab platform.
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ditpa 3 5 diiodothyropropionic acid a Thyroid Hormone Analog to treat heart failure phase ii trial veterans affairs cooperative study
Circulation, 2009Co-Authors: Steven Goldman, Paul W. Ladenson, Madeline Mccarren, Eugene Morkin, Robert Edson, Stuart R Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie G BarnhillAbstract:Background—In animal studies and a pilot trial in patients with congestive heart failure, the Thyroid Hormone Analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. Methods and Results—This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n57 to DITPA, n29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failure–specific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (20%), low-density lipoprotein cholesterol (30%), and body weight (11 lb). Thyroid-stimulating Hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypoThyroidism or thyrotoxicosis were seen. Conclusions—DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure. (Circulation. 2009;119:3093-3100.)
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ditpa a Thyroid Hormone Analog to treat heart failure phase ii trial va cooperative study
Journal of Cardiac Failure, 2008Co-Authors: Steven Goldman, Paul W. Ladenson, Madeline Mccarren, Eugene Morkin, Robert Edson, Stuart R Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie G BarnhillAbstract:DITPA, a Thyroid Hormone Analog to Treat Heart Failure: Phase II Trial VA Cooperative Study Steven Goldman*, Madeline McCarren*, Eugene Morkin, Paul Ladenson, Robert Edson, Stuart Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie Barnhill, Terrence O’Brien, Inder Anand, Alberta Warner, Mark Dunlap, Brack Hattle, John Erikson, Mei-Chiung Shih, Phil Lavori; Southern Arizona VA Health Care System, Tucson, AZ; VA Center for Medication Safety, Hines, IL; University of Arizona Health Sciences, Tucson, AZ; Johns Hopkins University, Baltimore, MD; Palo Alto CSP Coordinating Center, Palo Alto, CA; CSP Clinical Research Pharmacy Coordinating Center, Albuquerque, NM; VA Medical Center, Charleston, SC; Minneapolis VA Medical Center, Minneapolis, MN; Greater Los Angeles Healthcare System, Los Angeles, CA; Louis Stokes VA Healthcare System, Cleveland, OH; VA Eastern Colorado Health Care System, Denver, CO; South Texas Veterans Health Care System, San Antonio, TX
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a Thyroid Hormone Analog stimulates angiogenesis in the post infarcted rat heart
Journal of Molecular and Cellular Cardiology, 1998Co-Authors: Robert J Tomanek, Steven Goldman, Eugene Morkin, Bridget M Zimmerman, Padma R Suvarna, Gregory D PennockAbstract:Abstract In view of the evidence that Thyroid Hormone administration has angiogenic effects on the hypertrophic myocardium, we tested the hypothesis that the capillary supply in the hypertrophic myocardium surviving infarction would be improved by administration of the Thyroid Hormone Analog, diiodothyroproprionic acid (DITPA). We administered DITPA (MI-DITPA) or saline (MI-saline), s.c., to rats for 10 days following experimental infarction of the left ventricle (LV). Morphometric methods were used to assess capillarity and myocyte cross-sectional area in three regions of the left ventricle: (1) border (next to the scar of infarction); (2) adjacent (next to the border); and (3) remote (interventricular septum). Infarct size ranged from 20–85% of the LV free-wall, and both groups had similar mean infarct size. Capillary length density (L v ) was significantly higher in the remote region of the treated group than in the MI-saline rats. L v in the border region, which experienced the most marked increase in cardiocyte cross-sectional area, was not significantly lower than in the other regions, indicating a more marked angiogenic response. In hearts with large infarcts (≥40%) L v in the border region was higher in the DITPA group than in the non-treated rats. In the MI-DITPA group, cardiocyte size in the border region was positively correlated with that of the other regions, which contrasts with the negative correlations noted for the MI-saline rats. These data suggest that DITPA therapy (1) may improve maximal perfusion potential of the hypertrophied myocardium surviving a myocardial infarction, and (2) is selectively effective in the border region of hearts with large infarcts.
Paul W. Ladenson - One of the best experts on this subject based on the ideXlab platform.
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response to letter regarding article ditpa 3 5 diiodothyropropionic acid a Thyroid Hormone Analog to treat heart failure phase ii trial veterans affairs cooperative study
Circulation, 2010Co-Authors: Madeline Mccarren, Paul W. Ladenson, Eugene Morkin, Robert Edson, Janet Ohm, Hoang Thai, Lori Churby, Steven A Goldman, Meichiung Shih, Phil LavoriAbstract:We are glad that Dr Pingitore and his colleagues share our interest in use of thyromimetic agents to enhance cardiac performance. Inasmuch as a negative finding with respect to heart failure benefit with a low dose would have been an inconclusive study, we elected to administer the presumed maximum tolerated dose. In retrospect, we agree that the DITPA dose we …
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ditpa 3 5 diiodothyropropionic acid a Thyroid Hormone Analog to treat heart failure phase ii trial veterans affairs cooperative study
Circulation, 2009Co-Authors: Steven Goldman, Paul W. Ladenson, Madeline Mccarren, Eugene Morkin, Robert Edson, Stuart R Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie G BarnhillAbstract:Background—In animal studies and a pilot trial in patients with congestive heart failure, the Thyroid Hormone Analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. Methods and Results—This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n57 to DITPA, n29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failure–specific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (20%), low-density lipoprotein cholesterol (30%), and body weight (11 lb). Thyroid-stimulating Hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypoThyroidism or thyrotoxicosis were seen. Conclusions—DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure. (Circulation. 2009;119:3093-3100.)
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ditpa a Thyroid Hormone Analog to treat heart failure phase ii trial va cooperative study
Journal of Cardiac Failure, 2008Co-Authors: Steven Goldman, Paul W. Ladenson, Madeline Mccarren, Eugene Morkin, Robert Edson, Stuart R Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie G BarnhillAbstract:DITPA, a Thyroid Hormone Analog to Treat Heart Failure: Phase II Trial VA Cooperative Study Steven Goldman*, Madeline McCarren*, Eugene Morkin, Paul Ladenson, Robert Edson, Stuart Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie Barnhill, Terrence O’Brien, Inder Anand, Alberta Warner, Mark Dunlap, Brack Hattle, John Erikson, Mei-Chiung Shih, Phil Lavori; Southern Arizona VA Health Care System, Tucson, AZ; VA Center for Medication Safety, Hines, IL; University of Arizona Health Sciences, Tucson, AZ; Johns Hopkins University, Baltimore, MD; Palo Alto CSP Coordinating Center, Palo Alto, CA; CSP Clinical Research Pharmacy Coordinating Center, Albuquerque, NM; VA Medical Center, Charleston, SC; Minneapolis VA Medical Center, Minneapolis, MN; Greater Los Angeles Healthcare System, Los Angeles, CA; Louis Stokes VA Healthcare System, Cleveland, OH; VA Eastern Colorado Health Care System, Denver, CO; South Texas Veterans Health Care System, San Antonio, TX
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augmented hepatic and skeletal thyromimetic effects of tiratricol in comparison with levothyroxine
The Journal of Clinical Endocrinology and Metabolism, 1997Co-Authors: Steven I Sherman, Matthew D Ringel, Michele J Smith, Helen A Kopelen, William A Zoghbi, Paul W. LadensonAbstract:A Thyroid Hormone Analog with organ-selective effects could have therapeutic application for disorders such as hyperlipidemia and osteoporosis. We performed a randomized clinical trial to determine the specific thyromimetic effects of tiratricol. Twenty-four athyreotic patients underwent detailed metabolic and physiological evaluation after a 2-month baseline period, taking TSH-suppressive doses of L-T4. They were then randomized to blinded treatment with either tiratricol (24 micrograms/kg twice daily) or L-T4 (1.9 micrograms/kg daily). The dose of Hormone was increased until the TSH level was less than 0.1 mU/L, and the metabolic and physiological testing was repeated. Comparing the change from baseline to the study drug periods, when serum TSH levels were equivalently suppressed, there were no significant differences between the two groups in resting metabolic rate, weight, urea nitrogen excretion, or symptom score. Plasma total and low density lipoprotein cholesterol levels declined 13 +/- 4% and 23 +/- 6% in the tiratricol group compared with 2 +/- 2% and 5 +/- 3% in the L-T4 group (P = 0.015 and P = 0.0066, respectively). Serum sex Hormone-binding globulin levels increased 55 +/- 13% with tiratricol compared with a 1.7 +/- 4% decline with L-T4 (P = 0.0006), indicating an augmented hepatic response to tiratricol. Skeletal metabolic activity was enhanced, with increased levels of serum osteocalcin and urinary excretion of calcium and pyridinium cross-links. Tiratricol and L-T4 had comparable effects on cardiovascular function. Tiratricol has distinct augmented hepatic and skeletal thyromimetic actions of potential therapeutic value.
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Organ-specific effects of tiratricol: A Thyroid Hormone Analog with hepatic, not pituitary, superagonist effects
Journal of Clinical Endocrinology and Metabolism, 1992Co-Authors: Steven I Sherman, Paul W. LadensonAbstract:Tiratricol has been used to suppress pituitary TSH secretion, with reported attenuation of extrapituitary thyromimetic effects. A randomized, double-blind trial was performed to define precisely the tissue-specific thyromimetic actions of tiratricol. Ten athyreotic patients, treated for Thyroid carcinoma, were randomly assigned to receive L-T4 sodium 0.7 micrograms/kg daily and either tiratricol 10 micrograms/kg or placebo twice daily. The daily dose of L-T4 was increased by 25-50 micrograms increments until the TRH-stimulated TSH level was less than 0.1 mU/L. After measurement of biochemical and physiological parameters of Thyroid Hormone actions, patients crossed treatment groups. Patients required 46% less L-T4 to achieve equivalent TSH suppression when taking tiratricol. Hepatic effects were enhanced by tiratricol administration, with significant increases in sex Hormone binding globulin and ferritin concentrations, 14% and 37%, respectively. Levels of serum cholesterol, LDL cholesterol, and apolipoprotein B were reduced by 7%, 10%, and 13%, respectively, during tiratricol therapy. Triglyceride levels also declined, but there were no changes of high density lipoprotein cholesterol or apolipoproteins AI and AII. Resting metabolic rate, body weight, urea nitrogen excretion, and symptoms did not differ between the two treatment regimens. Cardiovascular function, as reflected by mean arterial pressure and pulse wave arrival time, was not different during tiratricol therapy. Skeletal metabolic activity was affected by tiratricol, with marked elevation of osteocalcin without significant change in serum calcium, PTH, and urinary calcium and hydroxyproline excretion. Tiratricol has increased hepatic and skeletal actions of potential therapeutic value, but does not have enhanced thyromimetic activity specific to the pituitary gland.
Jamie G Barnhill - One of the best experts on this subject based on the ideXlab platform.
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ditpa 3 5 diiodothyropropionic acid a Thyroid Hormone Analog to treat heart failure phase ii trial veterans affairs cooperative study
Circulation, 2009Co-Authors: Steven Goldman, Paul W. Ladenson, Madeline Mccarren, Eugene Morkin, Robert Edson, Stuart R Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie G BarnhillAbstract:Background—In animal studies and a pilot trial in patients with congestive heart failure, the Thyroid Hormone Analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. Methods and Results—This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n57 to DITPA, n29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failure–specific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (20%), low-density lipoprotein cholesterol (30%), and body weight (11 lb). Thyroid-stimulating Hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypoThyroidism or thyrotoxicosis were seen. Conclusions—DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure. (Circulation. 2009;119:3093-3100.)
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ditpa a Thyroid Hormone Analog to treat heart failure phase ii trial va cooperative study
Journal of Cardiac Failure, 2008Co-Authors: Steven Goldman, Paul W. Ladenson, Madeline Mccarren, Eugene Morkin, Robert Edson, Stuart R Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie G BarnhillAbstract:DITPA, a Thyroid Hormone Analog to Treat Heart Failure: Phase II Trial VA Cooperative Study Steven Goldman*, Madeline McCarren*, Eugene Morkin, Paul Ladenson, Robert Edson, Stuart Warren, Janet Ohm, Hoang Thai, Lori Churby, Jamie Barnhill, Terrence O’Brien, Inder Anand, Alberta Warner, Mark Dunlap, Brack Hattle, John Erikson, Mei-Chiung Shih, Phil Lavori; Southern Arizona VA Health Care System, Tucson, AZ; VA Center for Medication Safety, Hines, IL; University of Arizona Health Sciences, Tucson, AZ; Johns Hopkins University, Baltimore, MD; Palo Alto CSP Coordinating Center, Palo Alto, CA; CSP Clinical Research Pharmacy Coordinating Center, Albuquerque, NM; VA Medical Center, Charleston, SC; Minneapolis VA Medical Center, Minneapolis, MN; Greater Los Angeles Healthcare System, Los Angeles, CA; Louis Stokes VA Healthcare System, Cleveland, OH; VA Eastern Colorado Health Care System, Denver, CO; South Texas Veterans Health Care System, San Antonio, TX
Steven A Goldman - One of the best experts on this subject based on the ideXlab platform.
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response to letter regarding article ditpa 3 5 diiodothyropropionic acid a Thyroid Hormone Analog to treat heart failure phase ii trial veterans affairs cooperative study
Circulation, 2010Co-Authors: Madeline Mccarren, Paul W. Ladenson, Eugene Morkin, Robert Edson, Janet Ohm, Hoang Thai, Lori Churby, Steven A Goldman, Meichiung Shih, Phil LavoriAbstract:We are glad that Dr Pingitore and his colleagues share our interest in use of thyromimetic agents to enhance cardiac performance. Inasmuch as a negative finding with respect to heart failure benefit with a low dose would have been an inconclusive study, we elected to administer the presumed maximum tolerated dose. In retrospect, we agree that the DITPA dose we …
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regulation of gene expression in rats with heart failure treated with the Thyroid Hormone Analog 3 5 diiodothyropropionic acid ditpa and the combination of ditpa and captopril
Journal of Cardiovascular Pharmacology, 2007Co-Authors: Niranjan Maitra, Steven A Goldman, Joseph J Bahl, Cynthia Adamson, Kevin A Greer, Scott E Klewer, James B Hoying, Eugene MorkinAbstract:We have used an oligonucleotide microarray to identify genes that are affected by congestive heart failure and those influenced by treatment with DITPA and DITPA in combination with captopril using a rat postinfarction model. The most striking result when comparing heart failure to sham operation was that all of the mitochondrial and metabolic enzymes affected were down regulated. When comparing heart failure with DITPA treatment, most of the down regulated metabolic genes were returned toward normal. When comparing heart failure with heart failure animals treated with DITPA and captopril, metabolic enzymes were no longer significantly downregulated. DITPA treatment and the combination of DITPA and captopril show that the metabolic enzymes were no longer down regulated. This represents a substantial improvement in the energy- generating capacity of the heart. These results indicate that the actions of DITPA and the combination of DITPA and captopril in heart failure can be partially explained by differences in gene activation.
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Thyroid Hormone Analog ditpa improves endothelial nitric oxide and beta adrenergic mediated vasorelaxation after myocardial infarction
Journal of Cardiovascular Pharmacology, 2004Co-Authors: Peter H Spooner, Hoang M Thai, Steven A Goldman, Mohamed A GaballaAbstract:This study was designed to determine if the Thyroid Hormone Analog 3,5 diiodothyropropionic acid (DITPA), now in clinical trials for heart failure, alters endothelial function after myocardial infarction (MI). Three weeks after MI, adult Sprague-Dawley rats were randomly assigned to DITPA (375 microg/100 g subcutaneous) or no treatment of 3 weeks. In MI rats, left ventricular (LV) end-diastolic pressure and LV dP/dt decreased (P < 0.05). DITPA did not change MAP (87 +/- 10 versus 90 +/- 7 mm Hg) or LV end-diastolic pressure (23 +/- 3 versus 19 +/- 9 mm Hg) but did lower (P < 0.05) LV dP/dt (4,633 +/- 797 versus 3,650 +/- 1,236 mm Hg/s). In aortic segments from MI rats, DITPA enhanced the acetylcholine dependent vasorelaxation (59 +/- 11% at 10(-4) M, P < 0.05) and isoproterenol induced vasorelaxation (57 +/- 13% at 10(-4) M, P < 0.05). The increases in vasorelaxation were blocked with l-NAME and restored with L-arginine. Treatment with DITPA increased (P < 0.05) eNOS protein content in aortic tissue from sham rats (3.8 +/- 2.8 to 44.5 +/- 7.1 integrated intensity units (II)/microg) and in MI rats (5.3 +/- 3.4 to 28.3 +/- 8.9 II/microg). In endothelial cells, 24 hours' treatment with DITPA (10 microM) increased (P < 0.01) eNOS protein expression from 22.1 +/- 4.8 to 52.7 +/- 16.8 II/microg protein and DITPA (20 microM) increased eNOS to 49.1+/- 15.2 II/microg protein. The Thyroid Analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.
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pilot studies on the use of 3 5 diiodothyropropionic acid a Thyroid Hormone Analog in the treatment of congestive heart failure
The Cardiology, 2002Co-Authors: Eugene Morkin, Gregory D Pennock, Peter H Spooner, Joseph J Bahl, Katherine Underhill Fox, Steven A GoldmanAbstract:After an initial safety study in 7 normal volunteers, a randomized double-blind comparison was made between 3,5-diiodothyropropionic acid (DITPA) and placebo in 19 patients with moderately severe congestive failure. In heart failure patients receiving the drug for 4 weeks, cardiac index was increased (p = 0.04) and systemic vascular resistance index was decreased (p = 0.02). Systolic cardiac function was unchanged but isovolumetric relaxation time was decreased significantly, suggesting improvement in diastolic function. Total serum cholesterol (p = 0.005) and triglycerides (p = 0.01) also were decreased significantly. DITPA could represent a useful new agent for treatment of congestive heart failure.