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Article ; Online: Nitric Oxide Is the Cause of Nitroglycerin Tolerance: Providing an Old Dog New Tricks for Acute Heart Failure.

Kaesemeyer, Wayne / Suvorava, Tatsiana

Journal of cardiovascular pharmacology and therapeutics

2022 Volume 27, Page(s) 10742484221086091

Abstract: Our paper highlights the past 50 years of research focusing solely on tolerance involving nitroglycerin (glyceryl trinitrate, GTN). It also identifies and discusses inconsistencies in previous mechanistic explanations that have failed to provide a way to ...

Abstract	Our paper highlights the past 50 years of research focusing solely on tolerance involving nitroglycerin (glyceryl trinitrate, GTN). It also identifies and discusses inconsistencies in previous mechanistic explanations that have failed to provide a way to administer GTN continuously, free of limitations from tolerance and without the requirement of a nitrate-free interval. We illustrate, for the first time in 135 years, a mechanism whereby nitric oxide, the mediator of vasodilation by GTN, may also be the cause of tolerance. Based on targeting superoxide from mitochondrial complex I, uncoupled by glutathione depletion in response to nitric oxide from GTN, a novel unit dose GTN formulation in glutathione for use as a continuous i.v. infusion has been proposed. We hypothesize that this will reduce or eliminate tolerance seen currently with i.v. GTN. Finally, to evaluate the new formulation we suggest future studies of this new formulation for the treatment of acute decompensated heart failure.
MeSH term(s)	Glutathione ; Heart Failure/diagnosis ; Heart Failure/drug therapy ; Humans ; Nitric Oxide ; Nitroglycerin ; Vasodilator Agents/adverse effects
Chemical Substances	Vasodilator Agents ; Nitric Oxide (31C4KY9ESH) ; Nitroglycerin (G59M7S0WS3) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2022-03-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1329372-2
ISSN	1940-4034 ; 1074-2484
ISSN (online)	1940-4034
ISSN	1074-2484
DOI	10.1177/10742484221086091
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Zs.A 4895: Show issues

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Article ; Online: Treating Acute Decompensated Heart Failure in Patients with COVID-19 Using Intravenous Nitroglycerin in 5% Glutathione.

Kaesemeyer, Wayne / Suvorava, Tatsiana

American journal of cardiovascular drugs : drugs, devices, and other interventions

2021 Volume 21, Issue 6, Page(s) 589–593

Abstract: The purpose of this current opinion article is to illustrate a novel approach to the treatment of acute decompensated heart failure (ADHF) in coronavirus disease 2019 (COVID-19) patients. The approach described herein relies on a reformulation of ... ...

Abstract	The purpose of this current opinion article is to illustrate a novel approach to the treatment of acute decompensated heart failure (ADHF) in coronavirus disease 2019 (COVID-19) patients. The approach described herein relies on a reformulation of intravenous nitroglycerin in 5% glutathione, itself novel, and is felt to have the potential to not only improve the rate of resolution of ADHF, but also reduce the risk of complications of heart failure seen in patients with COVID-19.
MeSH term(s)	Administration, Intravenous ; COVID-19/complications ; Drug Compounding ; Glutathione/chemistry ; Heart Failure/diagnosis ; Heart Failure/etiology ; Humans ; Infusions, Intravenous ; Nitroglycerin/chemistry ; Nitroglycerin/therapeutic use ; Vasodilator Agents/chemistry ; Vasodilator Agents/therapeutic use
Chemical Substances	Vasodilator Agents ; Nitroglycerin (G59M7S0WS3) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2021-03-22
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2052547-3
ISSN	1179-187X ; 1175-3277
ISSN (online)	1179-187X
ISSN	1175-3277
DOI	10.1007/s40256-021-00474-w
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Zs.A 5487: Show issues

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Article ; Online: Targeting the Vascular Endothelium in the Treatment of COVID-19.

Suvorava, Tatsiana / Kaesemeyer, Wayne

Journal of cardiovascular pharmacology

2020 Volume 77, Issue 1, Page(s) 1–3

Abstract: Abstract: The involvement of the vascular endothelium in the complications of coronavirus disease 2019 is now recognized. Chief among these are pulmonary endotheliitis, cytokine storm, endotoxic shock, and cardiovascular collapse. This Perspectives ... ...

Abstract	Abstract: The involvement of the vascular endothelium in the complications of coronavirus disease 2019 is now recognized. Chief among these are pulmonary endotheliitis, cytokine storm, endotoxic shock, and cardiovascular collapse. This Perspectives article is focused on therapeutical strategies to reduce the risk of these complications by targeting the vascular endothelium as a part of the overall treatment of coronavirus disease 2019.
MeSH term(s)	Angiotensin II/administration & dosage ; Angiotensin-Converting Enzyme 2/antagonists & inhibitors ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/metabolism ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/metabolism ; Drug Delivery Systems/methods ; Drug Delivery Systems/trends ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Humans ; COVID-19 Drug Treatment
Chemical Substances	Angiotensin II (11128-99-7) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-10-19
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	391970-5
ISSN	1533-4023 ; 0160-2446
ISSN (online)	1533-4023
ISSN	0160-2446
DOI	10.1097/FJC.0000000000000932
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Zs.A 1471: Show issues

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Article ; Online: TARGETING THE VASCULAR ENDOTHELIUM IN THE TREATMENT OF COVID-19

Suvorava, Tatsiana / Kaesemeyer, Wayne

Journal of Cardiovascular Pharmacology

2020 Volume Publish Ahead of Print

Keywords	Pharmacology ; Cardiology and Cardiovascular Medicine ; covid19
Language	English
Publisher	Ovid Technologies (Wolters Kluwer Health)
Publishing country	us
Document type	Article ; Online
ZDB-ID	391970-5
ISSN	1533-4023 ; 0160-2446
ISSN (online)	1533-4023
ISSN	0160-2446
DOI	10.1097/fjc.0000000000000932
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Article: Targeting the Vascular Endothelium in the Treatment of Covid-19

Suvorava, Tatsiana / Kaesemeyer, Wayne

J. cardiovasc. pharmacol

Abstract: Involvement of the vascular endothelium in the complications of COVID-19 is now recognized. Chief among these are pulmonary endotheliitis, cytokine storm, endotoxic shock and cardiovascular collapse. This Perspectives paper is focused on therapeutical ... ...

Abstract	Involvement of the vascular endothelium in the complications of COVID-19 is now recognized. Chief among these are pulmonary endotheliitis, cytokine storm, endotoxic shock and cardiovascular collapse. This Perspectives paper is focused on therapeutical strategies to reduce the risk of these complications by targeting the vascular endothelium as a part of the overall treatment of COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #880843
Database	COVID19

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Article ; Online: Statin drug eluting stent (DES) for early stent thrombosis.

Kaesemeyer, Wayne

Atherosclerosis

2009 Volume 207, Issue 2, Page(s) 343

MeSH term(s)	Acute Coronary Syndrome/therapy ; Angioplasty, Balloon, Coronary/adverse effects ; Angioplasty, Balloon, Coronary/instrumentation ; Animals ; Drug-Eluting Stents ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Thrombosis/etiology ; Thrombosis/prevention & control
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2009-12
Publishing country	Ireland
Document type	Comment ; Letter
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2009.05.026
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Zs.A 226: Show issues

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Article ; Online: Bioresorbable polystatin fourth-generation stents.

Kaesemeyer, Wayne H / Sprankle, Kelly G / Kremsky, Jon N / Lau, Wing / Helmus, Michael N / Ghatnekar, Gautam S

Coronary artery disease

2013 Volume 24, Issue 6, Page(s) 516–521

Abstract: Objective: Stents have evolved through three generations, the latest of which are totally bioresorbable to include drugs targeting restenosis, the surface polymer eluting those drugs, and scaffolds on which those drugs are coated. These scaffolds, ... ...

Abstract	Objective: Stents have evolved through three generations, the latest of which are totally bioresorbable to include drugs targeting restenosis, the surface polymer eluting those drugs, and scaffolds on which those drugs are coated. These scaffolds, however, thus far, have been pharmacologically inactive and remain a potential site for delivering a second drug. Therefore, we sought to evaluate the possibility of modifying a bioresorbable polymer so that it can double as a scaffold for both a stent and a drug targeting impaired re-endothelialization and stent thrombosis. Methods and results: We successfully modified a standard bioresorbable terpolymer in a way found to be consistent with the covalent incorporation of lovastatin, as seen on NMR, into a backbone comprised of lactide, glycolide, ε-caprolactone, and lovastatin (60 : 15 : 10 : 15 parts by weight), respectively. This was accomplished through a reaction of the four components of the polymer at 100°C for 18 h in the presence of an alcohol initiator and a scandium catalyst. The resulting terpolymer was fabricated into a scaffold using a novel RSF system developed by 3D Biotek. Conclusion: It preliminarily appears feasible to fabricate a fourth-generation bioresorbable stent that has the potential to deliver two drugs to the site of the procedure-related vessel lumen injury.
MeSH term(s)	Absorbable Implants ; Drug Carriers ; Drug-Eluting Stents ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Lovastatin/administration & dosage ; Magnetic Resonance Spectroscopy ; Materials Testing ; Polymers/chemical synthesis ; Prosthesis Design
Chemical Substances	Drug Carriers ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Polymers ; Lovastatin (9LHU78OQFD)
Language	English
Publishing date	2013-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1047268-x
ISSN	1473-5830 ; 0954-6928
ISSN (online)	1473-5830
ISSN	0954-6928
DOI	10.1097/MCA.0b013e3283643a4a
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Zs.A 3039: Show issues

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Article: Interactions of L-arginine, isosorbide mononitrate, and angiotensin II inhibitors on arterial pulse wave.

Stokes, Gordon S / Barin, Edward S / Gilfillan, Kerry L / Kaesemeyer, Wayne H

American journal of hypertension

2003 Volume 16, Issue 9 Pt 1, Page(s) 719–724

Abstract: Background: Deficiency of nitric oxide (NO) production has been implicated in the pathogenesis of increased pulse wave reflection associated with systolic hypertension. We investigated the effects on systolic blood pressure (BP) and pulse wave contour ... ...

Abstract	Background: Deficiency of nitric oxide (NO) production has been implicated in the pathogenesis of increased pulse wave reflection associated with systolic hypertension. We investigated the effects on systolic blood pressure (BP) and pulse wave contour of two nitrate donors, isosorbide mononitrate (ISMN) and L-arginine. Methods: The subjects were 14 elderly patients chronically treated with antihypertensive agents. In seven of the subjects, agents causing angiotensin II (AII) inhibition (angiotensin-converting enzyme [ACE] inhibitor or AT(1) receptor antagonist, or both) were used. Study entry required systolic BP of 150 to 200 mm Hg, and aortic pulse wave augmentation more than 15 mm Hg. Pharmacodynamic responses to ISMN, L-arginine, and ISMN plus L-arginine, were assessed in double-blind crossover studies by standard sphygmomanometry and applanation tonometry. Results: Peripheral systolic BP, aortic systolic BP, and the aortic augmentation index were decreased (P <.001) by ISMN, irrespective of AII inhibition. L-arginine enhanced these effects (P <.001) in the subjects without AII inhibition, but not in those receiving AII inhibitors. Given without ISMN or AII inhibitors, L-arginine decreased peripheral systolic BP, but to a lesser extent than ISMN. Conclusions: L-arginine has potential value as an adjunct to ISMN in combination with antihypertensive therapy in elderly patients with systolic hypertension. However, when given with single-dose ISMN, its vasodilator activity may overlap with that of AII inhibitors. Future studies of L-arginine in conjunction with chronic continuous ISMN dosing are warranted.
MeSH term(s)	Aged ; Aged, 80 and over ; Angiotensin II/antagonists & inhibitors ; Angiotensin II/therapeutic use ; Arginine/therapeutic use ; Arteries/drug effects ; Arteries/physiopathology ; Blood Pressure/drug effects ; Circadian Rhythm/drug effects ; Cross-Over Studies ; Diastole/drug effects ; Double-Blind Method ; Drug Interactions/physiology ; Drug Therapy, Combination ; Female ; Heart Rate/drug effects ; Humans ; Hypertension/drug therapy ; Hypertension/physiopathology ; Isosorbide Dinitrate/analogs & derivatives ; Isosorbide Dinitrate/therapeutic use ; Male ; Middle Aged ; Nitric Oxide Donors/therapeutic use ; Posture ; Pulse ; Systole/drug effects ; Time Factors ; Treatment Outcome ; Vasoconstrictor Agents/therapeutic use
Chemical Substances	Nitric Oxide Donors ; Vasoconstrictor Agents ; Angiotensin II (11128-99-7) ; Arginine (94ZLA3W45F) ; Isosorbide Dinitrate (IA7306519N) ; isosorbide-5-mononitrate (LX1OH63030)
Language	English
Publishing date	2003-05-16
Publishing country	United States
Document type	Clinical Trial ; Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	639383-4
ISSN	1879-1905 ; 0895-7061
ISSN (online)	1879-1905
ISSN	0895-7061
DOI	10.1016/s0895-7061(03)00979-8
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Zs.A 2329: Show issues

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Article: The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy.

Parker, John O / Parker, John D / Caldwell, Robert W / Farrell, Bernice / Kaesemeyer, Wayne H

Journal of the American College of Cardiology

2002 Volume 39, Issue 7, Page(s) 1199–1203

Abstract: Objectives: This study was designed to assess the effect of oral L-arginine on the development of tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy.: Background: Continuous TD-GTN therapy leads to complete tolerance within 24 to ... ...

Abstract	Objectives: This study was designed to assess the effect of oral L-arginine on the development of tolerance during continuous transdermal nitroglycerin (TD-GTN) therapy. Background: Continuous TD-GTN therapy leads to complete tolerance within 24 to 48 h. The mechanism(s) responsible for nitrate tolerance are unclear, but there is increasing evidence that nitroglycerin (GTN) leads to superoxide anion production. The trigger for this is unknown, but there is evidence that GTN alters nitric oxide synthase (NOS) function and also leads to reduced L-arginine availability at its site of action with NOS. Methods: Fourteen patients with stable angina pectoris and reproducible treadmill walking time (TWT) until the onset of moderate angina were studied in a placebo-controlled, crossover study. Transdermal GTN (0.4 mg/h) was applied daily for two periods of 5 to 10 days with the patch left in place for 24 h each day. Capsules containing L-arginine (700 mg) or placebo were administered four times daily during a period of TD-GTN therapy. Treadmill walking time was determined before and 4 h after study capsules on day 1 before TD-GTN to assess the effect of L-arginine on exercise performance. On the last day, TWT was determined at 0 h (24 h after TD-GTN and 9 h after study capsule) and 4 h after TD-GTN reapplication and study capsule. After a 5 to 10 day washout period, the study was repeated with the opposite study capsule. Results: Treadmill walking time until the onset of moderate angina was not influenced by the short-term administration of L-arginine. During continuous TD-GTN, the administration of L-arginine increased TWT 4 h and 24 h after patch application. This was significantly greater than TWT during administration of placebo capsules (p < 0.05). Conclusions: The administration of L-arginine modified or prevented the development of nitrate tolerance during continuous TD-GTN therapy.
MeSH term(s)	Administration, Cutaneous ; Administration, Oral ; Angina Pectoris/drug therapy ; Angina Pectoris/physiopathology ; Arginine/administration & dosage ; Arginine/therapeutic use ; Cross-Over Studies ; Double-Blind Method ; Drug Administration Schedule ; Drug Tolerance ; Exercise Test ; Humans ; Nitric Oxide Synthase/metabolism ; Nitroglycerin/administration & dosage ; Nitroglycerin/therapeutic use ; Time Factors ; Vasodilator Agents/administration & dosage ; Vasodilator Agents/therapeutic use
Chemical Substances	Vasodilator Agents ; Arginine (94ZLA3W45F) ; Nitric Oxide Synthase (EC 1.14.13.39) ; Nitroglycerin (G59M7S0WS3)
Language	English
Publishing date	2002-04-03
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/s0735-1097(02)01729-1
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Zs.A 1846: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 196: Show issues

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Article: Rofecoxib decreases renal injury in obese Zucker rats.

Dey, Aparajita / Maric, Christine / Kaesemeyer, Wayne H / Zaharis, Constantine Z / Stewart, Janet / Pollock, Jennifer S / Imig, John D

Clinical science (London, England : 1979)

2004 Volume 107, Issue 6, Page(s) 561–570

Abstract: The present study tested the hypothesis that altered vascular regulation of arachidonic acid enzymes in obese Zucker rats contributes to renal damage. Protein expression of CYP450 (cytochrome P450) and COX (cyclo-oxygenase) enzymes in renal microvessels ... ...

Abstract	The present study tested the hypothesis that altered vascular regulation of arachidonic acid enzymes in obese Zucker rats contributes to renal damage. Protein expression of CYP450 (cytochrome P450) and COX (cyclo-oxygenase) enzymes in renal microvessels was studied in obese and lean Zucker rats at 20-21 weeks of age. Body weight and blood glucose averaged 649+/-13 g and 142+/-10 mg/dl in obese Zucker rats compared with 437+/-10 g and 111+/-5 mg/dl in age-matched lean Zucker rats. Renal microvascular CYP4A and COX-2 protein levels were increased and CYP2C protein levels decreased in obese Zucker rats. TX (thromboxane) B2 excretion was 2-fold higher and PG (prostaglandin) E2 excretion significantly lower in obese Zucker rats. Additional studies investigated the ability of the COX-2 inhibitor, rofecoxib, to slow the progression of renal injury in obese Zucker rats. Rofecoxib treatment decreased urinary PGF2alpha and 8-isoprostane levels in obese Zucker rats. Renal microvessel mRNA expression of pro-inflammatory chemokines was decreased in COX-2-inhibitor-treated obese Zucker rats. Urinary albumin excretion, an index of kidney damage, averaged 95+/-11 mg/day in vehicle-treated and 9+/-1 mg/day in rofecoxib-treated obese Zucker rats. Glomerulosclerosis, characterized by mesangial expansion, tubulo-interstitial fibrosis and extracellular matrix accumulation, was prominent in obese Zucker rats compared with a lack of damage in age-matched lean Zucker rats and rofecoxib-treated obese Zucker rats. These results suggest that altered vascular arachidonic acid enzymes contribute to the renal damage, and that COX-2 inhibition decreases glomerular injury in obese Zucker rats.
MeSH term(s)	Animals ; Chemokines/biosynthesis ; Chemokines/genetics ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors/therapeutic use ; Cytochrome P-450 Enzyme System/metabolism ; Gene Expression Regulation/drug effects ; Isoenzymes/antagonists & inhibitors ; Isoenzymes/metabolism ; Kidney/blood supply ; Kidney Diseases/etiology ; Kidney Diseases/pathology ; Kidney Diseases/prevention & control ; Kidney Glomerulus/pathology ; Lactones/therapeutic use ; Microcirculation/enzymology ; Obesity/complications ; Obesity/metabolism ; Obesity/pathology ; Prostaglandin-Endoperoxide Synthases/metabolism ; RNA, Messenger/genetics ; Rats ; Rats, Zucker ; Sulfones/therapeutic use
Chemical Substances	Chemokines ; Cyclooxygenase 2 Inhibitors ; Cyclooxygenase Inhibitors ; Isoenzymes ; Lactones ; RNA, Messenger ; Sulfones ; rofecoxib (0QTW8Z7MCR) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1)
Language	English
Publishing date	2004-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	760216-9
ISSN	0143-5221 ; 0144-9664
ISSN	0143-5221 ; 0144-9664
DOI	10.1042/CS20040125
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