High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

Kashioulis, Pavlos; Hammarsten, Ola; Marcussen, Niels; Shubbar, Emman; Saeed, Aso; Guron, Gregor

doi:10.1159/000446547

Cited by 4 publications

(4 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, using careful morphometrical analyses we did not detect a significant difference between groups in LV fibrosis in the present study. This is in agreement with our previous results in ACRF rats on a normal dietary NaCl intake [13]. In line with the histological data, LV protein expression of COL1A1 was not significantly increased in ACRF rats.…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction

Kashioulis

Lundgren

Shubbar

et al. 2018

Kidney Blood Press Res

Self Cite

View full text Add to dashboard Cite

Background/Aims: Cardiovascular disease is the major cause of death in patients with chronic kidney disease (CKD). Rats with adenine-induced chronic renal failure (ACRF) develop severe renal insufficiency and metabolic abnormalities that closely resemble those in patients with uremia. The aim of the present study was to determine left ventricular (LV) morphology and function in rats with ACRF. Methods: Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls, C). After 9-13 weeks animals were anesthetized with isoflurane and cardiac function was assessed both by echocardiography and by LV catheterization. Results: Rats with ACRF showed increases in serum creatinine (323±107 vs. 33±5 µM, P< 0.05), mean arterial pressure (115±6 vs. 106±7 mmHg, P< 0.05) and LV weight (3.4±0.3 vs. 2.5±0.2 mg/kg, P< 0.05) vs. controls. Rats with ACRF had reduced early diastolic tissue Doppler velocities in the LV, enlarged left atrial diameter (4.8±0.8 vs. 3.5±0.4 mm, P< 0.05) and elevated LV end-diastolic pressure (15±5 vs. 8±1 mmHg, P< 0.01). Cardiac output was increased in ACRF rats (211±66 vs. 149±24 ml/min, P< 0.05) and systolic function preserved. In the LV of ACRF rats there were statistically significant (P< 0.05) increases in cardiomyocyte diameter, proliferation and apoptosis, while there was no difference between groups in fibrosis. Conclusion: Rats with ACRF develop LV hypertrophy and diastolic dysfunction while systolic performance was preserved. There was an increased hypertrophy and apoptosis of cardiomyocytes in the LV of ACRF rats. The cardiac abnormalities in ACRF rats resemble those in patients with CKD in which heart failure with preserved ejection fraction is common. Hence, this experimental model is well suited for studying pathophysiological mechanisms in chronic renocardiac syndromes.

show abstract

Section: Discussionsupporting

confidence: 93%

“…Morphometric analyses of LV fibrosis were performed as previously described in detail [13]. In brief, images of sections stained with Picrosirius red were derived using an Olympus BX60 microscope (camera Olympus DP72) and the imaging software cellSens (Olympus).…”

Section: Kashioulis Et Al: Left Ventricular Function In Rats With Admentioning

confidence: 99%

Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction

Kashioulis

Lundgren

Shubbar

et al. 2018

Kidney Blood Press Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…These mechanisms provide some pathophysiological bases for the increased risk of stroke [56,57], stroke mortality [58], coronary heart disease mortality [57], and overall cardiovascular risk [57] associated with increased sodium consumption. Even in experimental models, a high sodium diet produces left ventricular injury and probably causes myocardial ischemia [59].…”

Section: Sodium Intake and Cardiovascular Eventsmentioning

confidence: 99%

Sodium Intake and Target Organ Damage in Hypertension—An Update about the Role of a Real Villain

Nista

Gatto

Albertelli

et al. 2020

IJERPH

View full text Add to dashboard Cite

Salt intake is too high for safety nowadays. The main active ion in salt is sodium. The vast majority of scientific evidence points out the importance of sodium restriction for decreasing cardiovascular risk. International Guidelines recommend a large reduction in sodium consumption to help reduce blood pressure, organ damage, and cardiovascular risk. Regulatory authorities across the globe suggest a general restriction of sodium intake to prevent cardiovascular diseases. In spite of this seemingly unanimous consensus, some researchers claim to have evidence of the unhealthy effects of a reduction of sodium intake, and have data to support their claims. Evidence is against dissenting scientists, because prospective, observational, and basic research studies indicate that sodium is the real villain: actual sodium consumption around the globe is far higher than the safe range. Sodium intake is directly related to increased blood pressure, and independently to the enlargement of cardiac mass, with a possible independent role in inducing left ventricular hypertrophy. This may represent the basis of myocardial ischemia, congestive heart failure, and cardiac mortality. Although debated, a high sodium intake may induce initial renal damage and progression in both hypertensive and normotensive subjects. Conversely, there is general agreement about the adverse role of sodium in cerebrovascular disease. These factors point to the possible main role of sodium intake in target organ damage and cardiovascular events including mortality. This review will endeavor to outline the existing evidence.

show abstract

“…Our previous studies have established that cTnT is cleared, in part, by glomerular filtration 20,21 , but also that low kidney function can only explain a 2-3-fold elevation of cTnT. As many patients with stable cTnT elevation due to kidney failure sometimes have levels ten times higher than expected 18 , decreased kidney clearance cannot be the only mechanism behind stable cTn elevations in patients with impaired kidney function.…”

Section: Discussionmentioning

confidence: 95%

The Liver and Kidneys mediate clearance of cardiac troponin in the rat

Muslimović

Fridén

Tenstad

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Cardiac-specific troponins (cTn), troponin T (cTnT) and troponin I (cTnI) are diagnostic biomarkers when myocardial infarction is suspected. Despite its clinical importance it is still not known how cTn is cleared once it is released from damaged cardiac cells. The aim of this study was to examine the clearance of cTn in the rat. A cTn preparation from pig heart was labeled with fluorescent dye or fluorine 18 (18 F). The accumulation of the fluorescence signal using organ extracts, or the 18 F signal using positron emission tomography (PET) was examined after a tail vein injection. The endocytosis of fluorescently labeled cTn was studied using a mouse hepatoma cell line. Close to 99% of the cTnT and cTnI measured with clinical immunoassays were cleared from the circulation two hours after a tail vein injection. The fluorescence signal from the fluorescently labeled cTn preparation and the radioactivity from the 18F-labeled cTn preparation mainly accumulated in the liver and kidneys. The fluorescently labeled cTn preparation was efficiently endocytosed by mouse hepatoma cells. In conclusion, we find that the liver and the kidneys are responsible for the clearance of cTn from plasma in the rat. Cardiac troponin (cTn) is a ternary complex consisting of three distinct subunits: cardiac troponin T (cTnT), cardiac troponin I (cTnI) and cardiac troponin C (cTnC). cTn binds thin filaments within the cardiomyocyte sarcomere and, with tropomyosin, makes muscular contraction dependent on calcium ions 1. Both cTnT and cTnI are released into the circulation following cardiac damage 2 and are the preferred cardiac biomarkers when myocardial infarction (MI) is suspected 3. The use of cTn assays with low diagnostic cutoffs improve diagnostic accuracy for MI on the emergency departments 4,5 and reduce hospital spending 6. However, low diagnostic cutoffs have been accompanied by an accumulation of patients presenting with stable cTn levels above the accepted cutoff point without MI 7,8. A third of older emergency department patients without MI on emergency departments have stable cTn elevations 7 , often for unknown reasons 9 , and are generally admitted to have their workup done 6,10. Even if MI can be excluded during the hospital stay, patients with stable cTn elevations still constitute a significant health care problem, as a stable cTn elevation is a strong risk factor for the development of heart disease and death 11-14. The reason behind stable cTn elevations, where sample-to-sample variation is often 10% 7 but can be as large as 40-50% 15 , is still unclear but is typically found at old age, in patients with decreased renal function or with comorbidities 10. It is possible that, in addition to necrosis, cTnT and cTnI are also released from living cardiomyocytes under ischemic stress 16 and possibly from normal cardiomyocytes as well 17. To understand the possible mechanisms that link stable cTn elevations to mortality, we need to know how cTn is released and cleared from the circulation 10,18,19. Surprisingly little is know...

show abstract

High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

Cited by 4 publications

References 25 publications

Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction

Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction

Sodium Intake and Target Organ Damage in Hypertension—An Update about the Role of a Real Villain

The Liver and Kidneys mediate clearance of cardiac troponin in the rat

Contact Info

Product

Resources

About