Physiopathological Mechanisms of Type 1 Cardiorenal Syndrome Induced by Acute Myocardial Infarction

Abstract

Objectives: Cardiovascular diseases are the leading global cause of mortality. Approximately 20 to 31% of acute myocardial infarction (AMI) cases progress to renal dysfunction, indicating concurrent cardiac and renal alterations, characterizing Cardiorenal Syndrome Type 1 (CS1). Therefore, this study evaluates the CS1 onset and progression three days after AMI by examining renal and cardiac function and their inflammatory responses. The study hypothesizes that inflammatory mediators are a key component contributing significantly to the onset and progression of CS1 pathophysiology. Methods: Male Sprague-Dawley rats (250-300g) were divided into AMI-SHAM (undergoing sham surgery for AMI) and AMI (left coronary artery ligation) groups. Samples were collected three days post-AMI from blood, urine, heart, and renal tissues. Assessments included osmolality (plasma and urine), creatinine (plasma and urine), glomerular filtration rate (GFR), and tissue cytokine levels. Left ventricular end-diastolic pressure (LVEDP) represented cardiac function. Results are presented as mean ± standard error. Results: LVEDP measurements (mmHg) demonstrated similar results from SHAM (5.89 ± 0.61, n=14) and AMI groups (6.38 ± 0.43, n=6). Tumor Necrosis Factor-Alpha (TNF-α) levels (pg/mg of tissue) from the heart [SHAM (2.74 ± 0.50, n=10) vs AMI (5.05 ± 0.83, n=8)] and renal tissue [SHAM (2.37 ± 0.69, n=7) vs AMI (5.53 ± 0.41, n=5)] were significantly different (p<0.05) concerning their respective groups. Of note, molecular biochemical analyses revealed similar results. Plasma Osmolality (kgH2O): SHAM (310.8 ± 5, n=13) vs AMI (310.4 ± 2.57, n=10); Urinary Osmolality: SHAM (1653 ± 140, n=14) vs AMI (2054 ± 166.9, n=9); Plasma Creatinine (mg/dL): SHAM (0.35 ± 0.21, n=14) vs AMI (0.39 ± 0.25, n=10); Urinary Creatinine: SHAM (118.9 ± 12.35, n=14) vs AMI (126.5 ± 18.90, n=10). GFR (mL/min/100g) was also similar: SHAM (1.22 ± 0.18, n=14) vs AMI (1.22 ± 0.12, n=9). Conclusions: The study shows that the increase of TNF-α is contributing to the onset and progression of the pathophysiology of CS1, in line with the original hypothesis. On the other hand, because the three-day post-surgery timeframe addressed the primary mechanisms triggering the CS1, it seems that the functional impairment of the heart and kidneys was not manifest yet. Support or Funding Information: FAPESP Process 2020/06043-7. CNPq Processes 306994/21-6 and 423999/21-4; FAEPA; CAPES/PROEX. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.