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Updated: Aug 18, 2026
Acute Myocardial Infarction in Rats
Published on: February 16, 2011
Effect of amiloride on age-dependent cardiac dysfunction after ischemia/reperfusion in the isolated, perfused rat
1Department of Pediatrics, Rhode Island Hospital, Brown University School of Medicine, Providence 02903, USA.
Insights
Amiloride treatment attenuated ischemia/reperfusion injury in adult and juvenile rat hearts but worsened it in immature hearts, suggesting age-dependent mechanisms. This highlights differential cardiac responses to amiloride based on age.
Area of Science:
- Cardiology
- Physiology
- Pharmacology
Background:
- Ischemia/reperfusion (I/R) injury is a significant concern in cardiovascular medicine.
- Understanding age-dependent responses to cardiac injury and potential therapeutic interventions is crucial.
Purpose of the Study:
- To compare the cardiac consequences of ischemia/reperfusion and amiloride treatment across different age groups of rats (immature, juvenile, adult).
- To investigate the age-dependent effects of amiloride on cardiac function following ischemia/reperfusion injury.
Main Methods:
- Isolated, perfused rat hearts from immature, juvenile, and adult male rats were subjected to normothermic ischemia followed by reperfusion.
- Hearts were reperfused with either Krebs-Henseleit-Bicarbonate (KHB) solution alone or KHB with amiloride.
- Left ventricular pressure was measured to assess cardiac function and quantify ischemia/reperfusion injury.
Main Results:
- Immature hearts showed relative resistance to ischemia/reperfusion injury compared to juvenile and adult hearts.
- Amiloride attenuated ischemia/reperfusion injury in juvenile and adult hearts.
- Amiloride worsened ventricular dysfunction in immature hearts during reperfusion.
Conclusions:
- Cardiac responses to amiloride during reperfusion are age-dependent.
- Differential mechanisms of sarcolemmal ion exchange likely underlie these age-dependent effects.
- These findings suggest that amiloride's efficacy in treating cardiac injury varies with age.
Abstract:
This study was intended to compare the cardiac consequences of ischemia/reperfusion and amiloride treatment in immature (2-3 wk), juvenile (4-6 wk), and adult (3-5 mo) rats using an isolated, perfused heart model. Male immature, juvenile, and adult rats were anticoagulated and anesthetized. Hearts were harvested and coronary arteries were perfused on a Langendorff apparatus via retrograde perfusion of the aorta at a constant coronary flow (initially determined by perfusing the heart at 50 mm Hg perfusion pressure) with oxygenated Krebs-Henseleit-Bicarbonate (KHB) solution. Left ventricular peak systolic (LVPSP) and end diastolic (LVEDP) pressures were measured via a balloon-tipped catheter placed in the left ventricle through the mitral valve. Following a 20-30 min stabilization period, hearts underwent 30 min of normothermic ischemia and were then reperfused with Krebs-Henseleit-Bicarbonate alone for 30 min, or Krebs-Henseleit-Bicarbonate containing 500 microM amiloride for 5 min followed by Krebs-Henseleit-Bicarbonate alone for 25 min (n = 6/age group). Left ventricular generated pressure was calculated (left ventricular peak systolic-left ventricular end diastolic) and used as a measure of ventricular function. All hearts demonstrated a decrease in generated pressure, respectively, from preischemic levels at 15 and 30 min of reperfusion, although this decrease was significantly less for the immature hearts. Ischemia/reperfusion injury was attenuated by amiloride in adult and juvenile hearts, whereas ischemia/reperfusion injury was worsened by amiloride in immature hearts. Although immature hearts were relatively resistant to ischemia/reperfusion injury compared with adult and juvenile hearts, the presence of amiloride during reperfusion resulted in more severe ventricular dysfunction in immature hearts. These data suggest a differential age-dependent mechanism of sarcolemmal ion exchange in response to ischemia/reperfusion.
