Inducible Nitric Oxide Synthase Expression and Cardiomyocyte Dysfunction During Sustained Moderate Ischemia in Pigs

Heinzel, Frank R.; Gres, Petra; Boengler, Kerstin; Duschin, Alexej; Konietzka, Ina; Rassaf, Tienush; Snedovskaya, Julia; Meyer, Steven De; Skyschally, Andreas; Kelm, Malte; Heusch, Gerd; Schulz, Rainer

doi:10.1161/circresaha.108.186015

Cited by 55 publications

(29 citation statements)

References 65 publications

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“…This may be explained by an undiscovered endothelial mediator(s) that improved myocardial microcirculation in the group P. in group P. v. Reperfusion injury syndrome to be deleted, interestingly the study results showed that immediate myocardial reperfusion might be unnecessary. The procedure, provides stabilization as well as myocardial and hemodynamic recoveries without the urgent need of reperfusion with the well known consequences of the reperfusion injury syndrome (Heinzel, et al, 2008). This was confirmed with our ongoing study, using an intrapulmonary catheter device induced percutaneously through the jugular vein.…”

Section: Commentsupporting

confidence: 75%

“Flow and Rate”: Concept and Clinical Applications of a New Hemodynamic Theory

Nour¹

2012

Biophysics

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Section: Commentsupporting

confidence: 75%

“Flow and Rate”: Concept and Clinical Applications of a New Hemodynamic Theory

Nour¹

2012

Biophysics

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“…For example, compared with normal controls, left ventricular biopsy samples from explanted failing human hearts express elevated levels of S-nitrosylated tropomyosin (18). Although the effect of tropomyosin S-nitrosylation on actomyosin ATPase function has not been fully characterized, these observational data raise speculation that S-nitrosylation of tropomyosin may modulate the adverse downstream actions of iNOS-derived NO on myocyte contractility that has been observed previously in certain animal models of coronary ischemia (57).…”

Section: S-nitrosylation In Cardiovascular Diseasesmentioning

confidence: 85%

S-Nitrosothiols and theS-Nitrosoproteome of the Cardiovascular System

Maron

Tang²,

Loscalzo³

2013

Antioxidants & Redox Signaling

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Significance: Since their discovery in the early 1990's, S-nitrosylated proteins have been increasingly recognized as important determinants of many biochemical processes. Specifically, S-nitrosothiols in the cardiovascular system exert many actions, including promoting vasodilation, inhibiting platelet aggregation, and regulating Ca 2+ channel function that influences myocyte contractility and electrophysiologic stability. Recent Advances: Contemporary developments in liquid chromatography-mass spectrometry methods, the development of biotin-and His-tag switch assays, and the availability of cyanide dye-labeling for S-nitrosothiol detection in vitro have increased significantly the identification of a number of cardiovascular protein targets of S-nitrosylation in vivo. Critical Issues: Recent analyses using modern S-nitrosothiol detection techniques have revealed the mechanistic significance of S-nitrosylation to the pathophysiology of numerous cardiovascular diseases, including essential hypertension, pulmonary hypertension, ischemic heart disease, stroke, and congestive heart failure, among others. Future Directions: Despite enhanced insight into S-nitrosothiol biochemistry, translating these advances into beneficial pharmacotherapies for patients with cardiovascular diseases remains a primary as-yet unmet goal for investigators within the field. Antioxid. Redox Signal. 18, 270-287.

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“…10 With increasing duration of ischemia, perfusion-contraction matching is progressively lost. 9,11 The pathophysiological concept of perfusion-contraction matching coincided with the clinical observation of hibernating myocardium by Shahbudin Rahimtoola, 12 and the idea emerged that indeed perfusion-contraction matching permits adaptation of the myocardium to ischemia and, in consequence, maintenance of its viability and eventual recovery after revascularization. 13 Indeed, perfusion-contraction matching is a hallmark of hibernation.…”

Section: T His Pioneering Article Was the First To Quantitatively Relmentioning

confidence: 90%

The Regional Myocardial Flow–Function Relationship

Heusch

2013

Circulation Research

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T his pioneering article was the first to quantitatively relate regional myocardial blood flow (microspheres) to regional contractile function (sonomicrometry).Regional flow and function were more or less proportionately reduced during acute ischemia in conscious dogs.The notion that myocardial ischemia arises from an imbalance between oxygen demand and supply goes originally back to the characterization of hemodynamic determinants of myocardial oxygen consumption in the whole heart and the observation that decreases or increases, respectively, in heart rate or ventricular function decrease or increase, respectively, the severity of ischemic injury.1 However, myocardial ischemia is in most instances a regional event. It was not until into the 1970s that experimental techniques became available to measure myocardial blood flow and contractile function on a regional level, notably the microsphere technique 2 and sonomicrometry. 3 Stephen Vatner in his classic article 4 was the first to use both techniques simultaneously and quantitatively relate subendocardial segment shortening to subendocardial blood flow. He characterized the flow-function relationship as exponential during acute coronary stenosis in conscious dogs, with a more steep and almost linear part at more severe stenosis. Admittedly, the measurements were restricted to only the subendocardial layer, and segment length measurements are somewhat technically limited by the alignment of piezocrystals with respect to myofiber direction. Nevertheless, flow-function relationships were subsequently reported from other groups for transmural flow and function, using more chronic coronary stenosis 5,6 and extending the data from rest to exercise.5 Whereas initially there were heated debates on the exact shape of the flow-function plot and the potential meaning of its deviation from linearity, 7 the prevailing view emerged that in (sub)acute ischemia regional myocardial blood flow and function are proportionately reduced ( Figure) and not in imbalance, contrary to the above notion that ischemia is characterized by an imbalance of oxygen supply and demand. John Ross developed the concept of perfusion-contraction matching in which the observed reduction in contractile function is not the energetic consequence of reduced blood flow but an adaptive response.8 Perfusion-contraction matching can be maintained over hours of (sub)acute ischemia, 9 and all drugs that attenuate ischemia operate along the flowfunction relationship.10 With increasing duration of ischemia, perfusion-contraction matching is progressively lost. 9,11The pathophysiological concept of perfusion-contraction matching coincided with the clinical observation of hibernating myocardium by Shahbudin Rahimtoola, 12 and the idea emerged that indeed perfusion-contraction matching permits adaptation of the myocardium to ischemia and, in consequence, maintenance of its viability and eventual recovery after revascularization.13 Indeed, perfusion-contraction matching is a hallmark of hibernation. In shortterm hi...

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Inducible Nitric Oxide Synthase Expression and Cardiomyocyte Dysfunction During Sustained Moderate Ischemia in Pigs

Cited by 55 publications

References 65 publications

“Flow and Rate”: Concept and Clinical Applications of a New Hemodynamic Theory

“Flow and Rate”: Concept and Clinical Applications of a New Hemodynamic Theory

S-Nitrosothiols and theS-Nitrosoproteome of the Cardiovascular System

The Regional Myocardial Flow–Function Relationship

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