John D Parker

John D Parker
Mount Sinai Hospital, Toronto · Medical Departments

MD

About

266
Publications
13,900
Reads
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12,853
Citations
Additional affiliations
July 1992 - present
Mount Sinai Hospital, Toronto
Position
  • Clinician Scientist
July 1992 - present
University of Toronto
Position
  • Clinician Scientist, Professor
July 1992 - present
University Health Network
Position
  • Clinician Scientist

Publications

Publications (266)
Article
Full-text available
The ANTHEM-HF, INOVATE-HF, and NECTAR-HF clinical studies of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) systems have collectively provided dose-ranging information enabling the development of several working hypotheses on how stimulation frequency can be utilized during VNS for tolerability and improving cardiovascular o...
Article
Introduction: Understanding cardiorenal pathophysiology in heart failure (HF) is of clinical importance. Objective: To characterize renal hemodynamic function and the transrenal gradient of the renin-angiotensin-aldosterone system (RAAS) markers in patients with HF and non-HF matched controls. Methods: In this post-hoc analysis, glomerular fil...
Article
Importance Heart failure with preserved ejection fraction (HFpEF) is often characterized by nitric oxide deficiency. Objective To evaluate the efficacy and adverse effects of praliciguat, an oral soluble guanylate cyclase stimulator, in patients with HFpEF. Design, Setting, and Participants CAPACITY HFpEF was a randomized, double-blind, placebo-c...
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Aims Patients with sleep apnoea (SA) and heart failure (HF) are less sleepy than SA patients without HF. HF and SA both increase sympathetic nervous system activity (SNA). SNA can augment alertness. We previously showed that in HF patients, the degree of daytime sleepiness was not related to the severity of SA but was inversely related to SNA. Elev...
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Aims: Clinical studies of vagal nerve stimulation (VNS) for heart failure with reduced ejection fraction have had mixed results to date. We sought to compare VNS delivery and associated changes in symptoms and function in autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure (ANTHEM-...
Article
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We investigated the impact of short-acting and extended release nifedipine on sympathetic activity using radiotracer methodology in patients with stable coronary artery disease in order to more accurately document the response of the sympathetic nervous system to different formulations of this dihydropyridine calcium channel antagonist. Participant...
Article
Poorly controlled type 2 diabetes mellitus is associated with the development of cardiovascular and renal complications, resulting in significant morbidity and mortality. Intensive glycemic control has been a major focus for clinical trials and novel drug development. However, narrow treatment strategies developed strictly for glycemic control did...
Article
Background: Evidence of a circadian rhythm in endothelium-dependent vasomotor function, with a nadir in Flow-Mediated Dilation (FMD) in the early morning hours, has been previously reported. These changes have been proposed to be one of the mechanisms explaining the circadian pattern in the incidence of cardiovascular events. We set out to investi...
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The mechanism of the bioactivation of nitroglycerin has long been controversial, with a number of suggested enzymatic pathways. More recently, aldehyde dehydrogenase-2 (ALDH-2) has been reported as the important enzyme involved in the bioactivation of nitroglycerin at therapeutically relevant concentrations. Other previously described enzyme system...
Article
Aim: Nitroglycerin (or glyceryl trinitrate, GTN) has been long considered as an endothelium-independent vasodilator since GTN vasodilation is intact in the absence of the endothelium and in the presence of endothelial dysfunction. However, in animal and in vitro models, GTN has been shown to stimulate the release of certain endothelium-derived vas...
Article
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Background: Hypertensive disorders complicating pregnancy are a major cause of maternal death. Our objective was to evaluate maternal clinical, hemodynamic, and placental prognostic indicators in a consolidated manner to identify women who develop hypertension in pregnancy. Methods and results: Twenty-six normotensive pregnant women from a speci...
Article
Background: The phosphodiesterase-5 (PDE5) inhibitors that have been available for nearly 20 years are highly effective in treating erectile dysfunction and have been consistently shown to be safe when used according to package insert instructions. Aim: To review the cardiovascular (CV) safety of PDE5 inhibitors used to treat erectile dysfunctio...
Article
Background: Nitrates and nitrate-containing compounds are vasodilators used for the treatment of angina and heart failure. Phosphodiesterase type 5 inhibitors used for the treatment of erectile dysfunction are also vasodilators, and when taken together with nitrates, synergistic effects that enhance hypotensive effects may occur. Phosphodiesterase...
Article
The maternal cardiovascular system undergoes critical anatomic and functional adaptations in order to achieve a successful pregnancy outcome which, if disrupted, can result in complications that significantly impact maternal and fetal health. Complications that involve the maternal cardiovascular system are amongst the most common disorders of preg...
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Low molecular weight heparin has been extensively evaluated for the prevention of preeclampsia in high-risk pregnant women, however, the results from these trials have been conflicting. This review discusses the potential mechanisms of action of low molecular weight heparin for the prevention of severe preeclampsia, how to optimize the selection of...
Article
Aims: Changes in systolic blood pressure (SBP) during an admission for acute heart failure (AHF), especially those leading to hypotension, have been suggested to increase the risk for adverse outcomes. Methods and results: We analysed associations of SBP decrease during the first 24 h from randomization with serum creatinine changes at the last...
Article
The beneficial effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AII) receptor antagonists in patients with heart failure secondary to reduced ejection fraction (HFrEF) are felt to result from prevention of the adverse effects of AII on systemic afterload and renal homeostasis. However, AII can activate the sympathetic n...
Article
Reperfusion in the setting of acute ischemia is essential in limiting tissue necrosis. However, reperfusion itself is associated with significant adverse effects. There is animal evidence that platelets play a role in the adverse effects of ischemia and reperfusion (IR) injury. We examined whether clopidogrel would have favorable effects on endothe...
Article
Objective Non-invasive hemodynamic monitoring has the potential to be a valuable clinical tool for the screening and management of hypertensive disorders of pregnancy. The objective of this study was to validate the clinical utility of the non-invasive cardiac output monitoring (NICOM) system in pregnant women. Methods Twenty healthy pregnant wome...
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Background— The therapeutic potential of renal denervation (RDN) for arrhythmias has not been fully explored. Detailed mechanistic evaluation is in order. The objective of the present study was to determine the antiarrhythmic potential of RDN in a postinfarct animal model and to determine whether any benefits relate to RDN-induced reduction of symp...
Article
Objective: Plasma concentrations of B-type natriuretic peptide (BNP) and troponin are often measured for diagnostic purposes when patients are admitted with heart failure, but their prognostic value when measured soon after admission is uncertain. We aimed to investigate the added prognostic value of admission measurements of BNP and troponins in...
Article
Introduction: Flow-mediated dilation (FMD) quantifies endothelium-dependent vasomotor responses to short-term increases in blood flow. Low-flow mediated vasoconstriction (L-FMC) has been more recently introduced as additional measure of endothelial function, and its relationship with changes in blood flow, cardiovascular risk factors and FMD ha∧s...
Article
Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant...
Article
In premenopausal women, ovarian steroids are felt to play a role in the prevention of cardiovascular disease. We aimed to assess whether menstrual cycle variations in estrogen can modify the response to ischemia-reperfusion (IR) injury in humans. In an investigator-blinded crossover study, 10 healthy premenopausal women with regular menstrual cycle...
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Background: There is limited evidence that the use of nitrates in acute decompensated heart failure early after presentation to a hospital can improve clinical outcomes. We aimed to determine whether early nitrate exposure is associated with improved survival in a large retrospective cohort study. Methods and results: We examined 11 078 acute de...
Article
Background: The length of hospital stay (LOS) is important in patients admitted for acute heart failure (AHF) as it prolongs an unpleasant experience for the patients and adds substantially to health care costs. Methods and results: We examined the association between LOS and baseline characteristics, 10-day post-discharge HF readmission, and 90...
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Abnormal renal function is common in acute and chronic CHF and is related to the severity of congestion. However, treatment of congestion often leads to worsening renal function. Our objective was to explore basal determinants of renal function and their response to hemodynamic interventions. Thirty-seven patients without CHF and 59 patients with c...
Article
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During normal pregnancy, the maternal cardiovascular system undergoes important anatomic and functional modifications to establish a low-resistance, high-volume state to support fetal demands for nutrients and gas exchange.1 Cardiac output increases by as much as 30% to 40%, resulting from increases in stroke volume and, to a lesser extent, heart r...
Article
The 3-hydroxy-3-methyglutaryl coenzyme A (HMG Co-A) reductase inhibitors have preconditioning effects involving up-regulation of cyclooxygenase (COX)-2. We investigated the effect of selective and non-selective COX inhibition on rosuvastatin-mediated protection against ischemia reperfusion (IR)-induced endothelial dysfunction in the human forearm....
Article
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Objectives and background: We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Methods: Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass g...
Article
Acute heart failure (HF) is common in the elderly, but the association of age with clinical outcomes and prognostic factors has not been examined thoroughly. We have analyzed the clinical and laboratory characteristics and the outcomes of 1347 patients with acute HF enrolled in the VERITAS trial. Subjects were subdivided based on their median age o...
Article
Chronic stable angina remains an important cause of morbidity in patients with coronary artery disease (CAD). Although dramatic improvements in surgical and percutaneous revascularization techniques have occurred, many patients continue to have symptoms of angina and benefit from pharmacologic therapy. Traditional pharmacologic approaches to angina...
Article
Aims: Worsening heart failure (WHF) in the first 7 days after an admission for acute HF (AHF) has been proposed as a therapeutic target in several recent AHF studies and was a co-primary endpoint of the VERITAS studies. Methods and results: Patients were randomized within 24 h of admission for AHF. WHF was defined as worsening or persistent sign...
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Background. Sildenafil and nitroglycerin (GTN) are effective pharmacologic preconditioning agents, protecting from the adverse effects of ischemia and reperfusion (IR). Objectives. To determine whether repeated, daily administration of sildenafil or GTN provides sustained preconditioning from IR in the human forearm vasculature. Methods. Thirty-six...
Article
Flow mediated dilatation (FMD) is an accepted, non-invasive measure of endothelial function. FMD measures the capacity of the endothelium to respond to a stimulus but does not assess resting vascular tone. Prior to the measurement of FMD, the radial artery constricts as blood flow to the hand is interrupted, a phenomenon termed low-flow mediated co...
Article
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It is well established that acute ischemic preconditioning (IPC) protects against ischemia-reperfusion (IR) injury; however, the effectiveness of repeated IPC exposure has not been extensively investigated. We aimed to determine whether daily IPC episodes provide continued protection from IR injury in a human forearm model, and the role of cyclooxy...
Article
Unlabelled: Conventional coronary angiography (CCA) is the standard diagnostic for coronary artery disease (CAD), but multi-detector computed tomography coronary angiography (CTCA) is a non-invasive alternative. Methods: A multi-center coverage with evidence development study was undertaken and combined with an economic model to estimate the cos...
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Purpose: Cardiac resynchronisation therapy (CRT) is associated with acute haemodynamic improvement in patients with intrinsic bundle branch block and the magnitude of improvement has been correlated with QRS duration. The acute haemodynamic effect of CRT in patients with chronic right ventricular (RV) pacing is unclear. We investigated the magnitud...
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Purpose: Acute haemodynamic improvement with cardiac resynchronisation therapy (CRT) is often used to guide optimization of device function, and may predict long term response to therapy. QRS duration reportedly correlates with acute haemodynamic response to CRT but other predictors are not known. We investigated whether baseline invasive haemodyna...
Article
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To examine the relationship between acoustic characteristics of the first and second heart sounds (S1 and S2) and underlying cardiac structure and haemodynamics in patients with isolated pulmonary arterial hypertension (PAH) and controls. Prospective multicentre cohort study. Tertiary referral and community hospitals. We prospectively evaluated 40...
Article
Purpose: We set out to investigate whether the oxidative stress associated with acute, short-term exposure to cigarette smoking could induce a paradoxical protection similar to the phenomenon known as ischemic preconditioning. Background: Cigarette smoking is a well-accepted risk factor for myocardial infarction, stroke, and mortality. Paradoxicall...
Article
This study examined the effect of acute and sustained transdermal glyceryl trinitrate (GTN) therapy on insulin and glucose regulation. Totally, 12 males (18-30 years) underwent a glucose tolerance test at baseline (visit 1), 90 minutes after acute transdermal GTN 0.6 mg/h (visit 2), following 7 days of continuous GTN (visit 3), and 2 to 3 days afte...
Article
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Background: Coronary (micro)vascular resistance is regulated by the complex interplay of several factors. Two potentially important determinants include endothelial function and the rheological properties of blood. However, their impact on the control of the coronary resistance vasculature is poorly understood. Methods: The corrected Thrombolysi...
Article
Previous studies from our and other laboratories have demonstrated the existence of a clear relationship between different measures of endothelial function and the extent of coronary atherosclerosis. The relationship between endothelial function and carotid intima-media thickness has not been extensively investigated. Endothelial function using rad...
Article
While the role of physical forces on the control of atherogenesis and the modulation of endothelial function is well known, studies investigating the impact of shear stress on the extent of central atherosclerosis and flow-mediated dilation in humans produced controversial results. We investigated the relationship between viscosity, coronary athero...
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Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to recei...
Article
Patients with congestive heart failure (CHF) due to left ventricular (LV) dysfunction have sympathetic activation specifically directed to the myocardium. Although pulmonary arterial hypertension (PAH) is associated with increased systemic sympathetic activity, its impact on sympathetic drive to ventricular myocardium is unknown. Fifteen patients w...
Article
Coronary artery disease (CAD) remains an important cause of morbidity and mortality and is a serious public health problem. Over the last 4 decades there have been dramatic advances in the both the prevention and treatment of CAD. The management of CAD was revolutionized by the development of effective surgical and percutaneous revascularization te...
Article
Introduction: Ischemic and pharmacologic preconditioning have great clinical potential, but it remains unclear whether their effects can be maintained over time during repeated exposure.We have previously demonstrated that the acute protective effect of nitroglycerin (GTN) is attenuated during repeated daily administration. Pentaerythrityl tetrani...
Article
Inflammation plays an important role in the pathophysiology of atherosclerosis and endothelial dysfunction, and occurs after percutaneous coronary intervention (PCI). We evaluated whether endothelial function is attenuated after PCI and if inhibition of secretory phospholipase A2 (sPLA2) activity augments endothelial function and coronary flow rese...
Article
Full-text available
Studies have demonstrated that the acute administration of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has protective effects in the setting of ischemia-reperfusion (IR). Previously, we demonstrated that a single dose of rosuvastatin prevented IR-induced endothelial dysfunction in humans through a cyclooxygenase-2-dependent...
Article
We explored the impact of rosiglitazone on endothelial function in normal volunteers and its interaction with glyceryl trinitrate (GTN)-induced abnormalities in endothelial function. We hypothesized that rosiglitazone would have a neutral effect on endothelial function in normal volunteers and would favorably modify endothelial dysfunction induced...
Article
Full-text available
A number of risk factors for atherosclerosis have been identified, but it remains difficult, on an individual patient basis, to predict how these factors interact in determining the development of coronary artery disease (CAD). It also remains unclear whether the study of endothelial function provides information that is additive to that of traditi...