Delayed Preconditioning-Mimetic Actions of Nitroglycerin in Patients Undergoing Exercise Tolerance Tests

Jneid, Hani; Chandra, Mukul; Alshaher, Motaz; Hornung, Carlton A.; Tang, Xian Liang; Leesar, Massoud A.; Bolli, Roberto

doi:10.1161/circulationaha.104.515445

Cited by 43 publications

(35 citation statements)

References 33 publications

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“…Short-term continuous nitroglycerin delivery by the intravenous or transdermal route for only 2 to 4 hours protects the endothelium from experimental ischemia in healthy volunteers and reduces ischemia during coronary angioplasty and physical exercise in IHD patients. [863][864][865] Oxygen free radical release seems to be associated with these protective outcomes. Nitroglycerin causes dilation of the artery wall not affected by plaque, but independent of an intact endothelium, leading to reduced resistance across the obstructed lumen.…”

Section: Nitratesmentioning

confidence: 99%

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease

Fihn¹,

Gardin²,

Abrams³

et al. 2012

Circulation

736

441

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Section: Nitratesmentioning

confidence: 99%

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease

Fihn¹,

Gardin²,

Abrams³

et al. 2012

Circulation

736

441

View full text Add to dashboard Cite

“…Furthermore, Jneid and co-workers [187] have shown that a 4 h infusion of nitroglycerin (a NOdonor) had a preconditioning-like effect 24 h later during exercise testing with increased exercise tolerance, less STsegment depression, faster recovery of ST segments, despite a greater workload. Symptoms and ST-segment ECG changes in response to sequential coronary angioplasty balloon inflations during elective percutaneous coronary Fig.…”

Section: Surrogate Human Models Of Delayed Preconditioningmentioning

confidence: 99%

The Second Window of Preconditioning (SWOP) Where Are We Now?

Hausenloy

Yellon

2010

Cardiovasc Drugs Ther

142

118

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A standard ischemic preconditioning (IPC) stimulus of one or more brief episodes of non-lethal myocardial ischemia and reperfusion elicits a bi-phasic pattern of cardioprotection. The first phase manifests almost immediately following the IPC stimulus and lasts for 1-2 h, after which its effect disappears (termed classical or early IPC). The second phase of cardioprotection appears 12-24 h later and lasts for 48-72 h (termed the Second Window of Protection [SWOP] or delayed or late IPC). The cardioprotection conferred by delayed IPC is robust and ubiquitous but is not as powerful as early IPC. Although there are some similarities in the mechanisms underlying early and delayed IPC, one of the major distinctions between the two is the latter's requirement for de novo protein synthesis of distal mediators such as iNOS and COX-2 which mediate the cardioprotection 24 h after the IPC stimulus. The phenomenon of delayed IPC has been demonstrated in man using a variety of experimental models. However, its clinical application has been limited by the same factors which affect early IPC- i.e. the need to intervene before the onset of myocardial ischemia, thereby restricting its potential clinical utility to planned settings of acute myocardial ischemia-reperfusion injury such as coronary artery bypass graft surgery, cardiac transplantation and percutaneous coronary intervention. In this article, the focus will be on the origins of delayed IPC, the mechanisms underlying its delayed cardioprotective effect, and the potential areas for its clinical application.

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“…In addition to drugs inhibiting Precon or Postcon responses, patients are often exposed to agents that may actually trigger the same signaling pathways, including anesthetics (54,241), opioid-based analgesics (69,164), and vasodilators (83,103,131). While such effects may provide acute benefit, they will simultaneously exclude further protection from therapy targeting Precon or Postcon mechanisms.…”

Section: Drug and Environmental Interactionsmentioning

confidence: 99%

Clinical cardioprotection and the value of conditioning responses

Peart

Headrick²

2009

American Journal of Physiology-Heart and Circulatory Physiology

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Adjunctive cardioprotective strategies for ameliorating the reversible and irreversible injuries with ischemia-reperfusion (I/R) are highly desirable. However, after decades of research, the promise of clinical cardioprotection from I/R injury remains poorly realized. This may arise from the challenges of trialing and effectively translating experimental findings from laboratory models to patients. One can additionally consider whether features of the more heavily focused upon candidates could limit or preclude therapeutic utility and thus whether we might shift attention to alternate strategies. The phenomena of preconditioning and postconditioning have proven fertile in identification of experimental means of cardioprotection and are the most intensely interrogated responses in the field. However, there is evidence these processes, which share common molecular signaling elements and end effectors, may be poor choices for clinical exploitation. This includes evidence of age dependence, limiting efficacy in target aged or senescent hearts; refractoriness to conditioning stimuli in diseased myocardium; interference from a variety of relevant pharmaceuticals; inadvertent induction of these responses by prior ischemia or commonly used drugs, precluding further benefit; and sex dependence of protective signaling. This review focuses on these features, raising questions about current research strategies, and the suitability of these widely studied phenomena as rational candidates for clinical translation.

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Delayed Preconditioning-Mimetic Actions of Nitroglycerin in Patients Undergoing Exercise Tolerance Tests

Cited by 43 publications

References 33 publications

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease

The Second Window of Preconditioning (SWOP) Where Are We Now?

Clinical cardioprotection and the value of conditioning responses

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