Oxidative Stress as a Mechanism of Cardiac Failure in Chronic Volume Overload in Canine Model

Prasad, Kailash; Gupta, Jang B.; Kalra, Jawahar; Lee, P.; Mantha, Subrahmanyam V.; Bharadwaj, B

doi:10.1006/jmcc.1996.0035

Cited by 86 publications

(59 citation statements)

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“…Three SOD isozymes have been identified in the heart: Cu/Zn-SOD, which is primarily cytosolic in location, mitochondrial Mn-SOD, and EC-SOD (13). A decrease in SOD activity and an increase in lipid peroxides have been reported in volume-overload heart failure in dogs (30), pressure-overload heart failure in guinea pigs (11), and myocardial infarct-induced heart failure in rats (18). Up to one-half of the total SOD in vessels is EC-SOD, and EC-SOD has been implicated as a regulator of endothelium-derived NO bioavailability (13,14).…”

Section: Endothelial Dysfunction and Vascular Omentioning

confidence: 99%

Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart

Chen

Hou

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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This study examined whether increased superoxide (O2−·) production contributes to coronary endothelial dysfunction and decreased coronary blood flow (CBF) in congestive heart failure (CHF). To test this hypothesis, the effects of the low-molecular-weight SOD mimetic M40401 on CBF and myocardial oxygen consumption (MV̇o2) were examined in dogs during normal conditions and after CHF was produced by 4 wk of rapid ventricular pacing. The development of CHF was associated with decreases of left ventricular (LV) systolic pressure, maximum first derivative of LV pressure, MV̇o2, and CBF at rest and during treadmill exercise as well as endothelial dysfunction with impaired vasodilation in response to intracoronary acetylcholine. M40401 increased CBF (18 ± 5%, P < 0.01) and MV̇o2 (14 ± 6%, P < 0.01) in CHF dogs and almost totally reversed the impaired CBF response to acetylcholine. M40401 had no effect on acetylcholine-induced coronary vasodilation, CBF, or MV̇o2 in normal dogs. Western blot analysis demonstrated that extracellular SOD (EC-SOD) was significantly decreased in CHF hearts, whereas mitochondrial Mn-containing SOD was increased. Cytosolic Cu/Zn-containing SOD was unchanged. Both increased O2−· production and decreased vascular O2−· scavenging ability by EC-SOD could have contributed to endothelial dysfunction in the failing hearts.

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Section: Endothelial Dysfunction and Vascular Omentioning

confidence: 99%

Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart

Chen

Hou

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…It is important to accurately evaluate cardiac function in children with SCA, as it may be compromised from iron overload [3][4][5], chronic volume overload [6,7], or micro-infarcts [8]. The problem with commonly used indices of cardiac systolic function, like shortening fraction, ejection fraction, and V cfc , is that they are dependent on left ventricular loading conditions.…”

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confidence: 99%

Cardiac abnormalities in children with sickle cell anemia

et al. 2002

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Sickle cell anemia (SCA) results in chronic volume overload of the heart due to hemodilution. Previous echocardiographic studies of cardiac function in children with SCA have not accounted for these abnormal loading conditions. The objectives of this study were to (1) determine how the degree of anemia and transfusion status relate to cardiac findings and (2) evaluate cardiac function using load-independent parameters of function. We evaluated 77 patients with SCA, ages 2 to 22 years (mean ± SD = 11.7 ± 4.7), using physical examination, electrocardiography, and echocardiography. We compared two groups of patients. Group 1 consisted of 57 non-transfused patients, and Group 2 consisted of 20 patients on a chronic transfusion protocol. Group 1 patients exhibited a significantly lower hemoglobin, higher cardiac output, and larger left ventricular (LV) end-diastolic dimension and LV mass than groups 2 (P < 0.05). However, the velocity of circumferential fiber shortening-wall stress index (a load-independent measure of systolic function) was normal and not statistically different between the two groups. Conversely, the LV myocardial performance index (a measure of combined systolic and diastolic function) was significantly higher in Group 2 (P < 0.001), possibly indicating impaired myocardial diastolic function. SCA in children results in a volume-overloaded heart with a significant increase in LV dimensions and mass, both proportional to the degree of anemia. Despite these abnormal loading conditions, systolic function is preserved. Patients on a chronic transfusion protocol may develop diastolic dysfunction despite iron chelation therapy. Am.

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“…The endothelium supplies oxygen and is also responsible for the generation of nitric oxide (NO) for relaxation of underlying cardiac muscle. The increase in pulse pressure during chronic volume overload may develop protracted cycles of ischemia-reperfusion (6,37). The high oxygen concentration produces oxyradical: 2O 2 ϩ 2H 2 O ϭ 2H 2 O 2 ϩ O 2 Ϫ (toxic oxygen), dependent or independent of NADH/NAD oxidase (4), and masks the activity of superoxide dismutase and catalase (25,28,41).…”

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confidence: 99%

Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats

Cox¹,

Sood²,

Hunt³

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats. Am J Physiol Heart Circ Physiol 282: H1197-H1205, 2002. First published November 29, 2001 10.1152/ajpheart.00483.2001.-The hypothesis is that chronic increases in left ventricular (LV) load induce oxidative stress and latent matrix metalloproteinase (MMP) is activated, allowing the heart to dilate in the absence of endothelial nitric oxide (NO) and thereby reduce filling pressure. To create volume overload, an arteriovenous (A-V) fistula was placed in male Sprague-Dawley rats. To decrease oxidative stress and apoptosis, 0.08 mg/ml nicotinamide (Nic) was administered in drinking water 2 days before surgery. The rats were divided into the following groups: 1) A-V fistula, 2) A-V fistula ϩ Nic, 3) sham operated, 4) sham ϩ Nic, and 5) control (unoperated); n ϭ 6 rats/group. After 4 wk, hemodynamic parameters were measured in anesthetized rats. The heart was removed and weighed, and LV tissue homogeneates were prepared. A-V fistula caused an increase in heart weight, lung weight, and end-diastolic pressure compared with the sham group. The levels of malondialdehyde (MDA; a marker of oxidative stress) was 6.60 Ϯ 0.23 ng/mg protein and NO was 6.87 Ϯ 1.21 nmol/l in the LV of A-V fistula rats by spectrophometry. Nic treatment increased NO to 13.88 Ϯ 2.5 nmol/l and decreased MDA to 3.54 Ϯ 0.34 ng/mg protein (P ϭ 0.005). Zymographic levels of MMP-2 were increased, as were protein levels of nitrotyrosine and collagen fragments by Western blot analysis. The inhibition of oxidative stress by Nic decreased nitrotyrosine content and MMP activity. The levels of tissue inhibitor of metalloproteinase-4 mRNA were decreased in A-V fistula rats and increased in A-V fistula rats treated with Nic by Northern blot analysis. TdT-mediated dUTP nick-end labeling-positive cells were increased in A-V fistula rats and decreased in fistula rats treated with Nic. Acetylcholine and nitroprusside responses in cardiac rings prepared from the above groups of rats suggest impaired endothelial-dependent cardiac relaxation. Treatment with Nic improves cardiac relaxation. The results suggest that an increase in the oxidative stress and generation of nitrotyrosine are, in part, responsible for the activation of metalloproteinase and decreased endocardial endothelial function in chronic LV volume overload. nitric oxide; malondialdehyde; collagen degradation; tissue inhibitor of metalloproteinase; arteriovenous fistula; nicotinamide; NADH oxidase; nitrotyrosine; TUNEL; cardiac ring; acetylcholine; nitroprusside; stretch; contraction; relaxation; heart failure THE EXTRACELLULAR MATRIX (ECM), particularly type I fibrillar collagen surrounding the cardiomyocytes, helps the cardiac muscle to synchronize contraction and relaxation during systole and diastole, respectively (22,53,62). To compensate for the increase in workload and to reduce the wall stress, the cardiac muscle undergoes hypertrophy. This leads to remodeling of the ECM (54). Remodelin...

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Oxidative Stress as a Mechanism of Cardiac Failure in Chronic Volume Overload in Canine Model

Cited by 86 publications

References 0 publications

Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart

Increased superoxide production causes coronary endothelial dysfunction and depressed oxygen consumption in the failing heart

Cardiac abnormalities in children with sickle cell anemia

Apoptosis in the left ventricle of chronic volume overload causes endocardial endothelial dysfunction in rats

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