A Clinically Relevant Functional Model of Type-2 Cardio-Renal Syndrome with Paraventricular Changes consequent to Chronic Ischaemic Heart Failure

Autor: Emma Maria Hinemoa Besley, Scott Duncan George Smart, Jessica Renee Kelly, Ivan A. Sammut, Morgayn I. Read, Joanne C. Harrison, Yimin Yao
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Angiotensin receptor
Fractional excretion of sodium
Heart Ventricles
Cardiology
Myocardial Infarction
Myocardial Ischemia
lcsh:Medicine
Cardiorenal syndrome
030204 cardiovascular system & hematology
Kidney
Article
Ventricular Function
Left

03 medical and health sciences
Ventricular Dysfunction
Left

0302 clinical medicine
Medical research
Cardio-Renal Syndrome
Internal medicine
Medicine
Animals
Ventricular remodeling
lcsh:Science
Multidisciplinary
Ventricular Remodeling
business.industry
lcsh:R
Troponin I
Hemodynamics
medicine.disease
Angiotensin II
Rats
Disease Models
Animal

Oxidative Stress
030104 developmental biology
Renal pathology
Rats
Inbred Lew

Heart failure
lcsh:Q
business
Glomerular Filtration Rate
Paraventricular Hypothalamic Nucleus
Zdroj: Scientific Reports
Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
ISSN: 2045-2322
Popis: Cardiorenal syndrome, de novo renal pathology arising secondary to cardiac insufficiency, is clinically recognised but poorly characterised. This study establishes and characterises a valid model representative of Type 2 cardiorenal syndrome. Extensive permanent left ventricular infarction, induced by ligation of the left anterior descending coronary artery in Lewis rats, was confirmed by plasma cardiac troponin I, histology and cardiac haemodynamics. Renal function and morphology was assessed 90-days post-ligation when heart failure had developed. The involvement of the paraventricular nucleus was investigated using markers of inflammation, apoptosis, reactive oxygen species and of angiotensin II involvement. An extensive left ventricular infarct was confirmed following coronary artery ligation, resulting in increased left ventricular weight and compromised left ventricular diastolic function and developed pressure. Glomerular filtration was significantly decreased, fractional excretion of sodium and caspase activities were increased and basement membrane thickening, indicating glomerulosclerosis, was evident. Interestingly, angiotensin II receptor I expression and reactive oxygen species levels in the hypothalamic paraventricular nucleus remained significantly increased at 90-days post-coronary artery ligation, suggesting that these hypothalamic changes may represent a novel, valuable pharmacological target. This model provides conclusive morphological, biochemical and functional evidence of renal injury consequent to heart failure, truly representative of Type-2 cardiorenal syndrome.
Databáze: OpenAIRE