Effect of amiloride on age-dependent cardiac dysfunction after ischemia/reperfusion in the isolated, perfused rat heart.
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.
Linakis
J G
JG
Department of Pediatrics, Rhode Island Hospital, Brown University School of Medicine, Providence 02903, USA.
Raymond
R M
RM
D000367:Age Factors; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D004232:Diuretics / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects*
D004232:Diuretics; D000584:Amiloride