Effects of Specific Sodium/Hydrogen Exchange Inhibitor During Cardioplegic Arrest

• Published in: The Annals of thoracic surgery Vol. 64; no. 1; pp. 94 - 99
• Main Authors: Choy, Isaac O, Schepkin, Victor D, Budinger, Thomas F, Obayashi, Derek Y, Young, J.Nilas, DeCampli, William M
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-07-1997; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Cardioplegic Solutions; Cardiovascular system; Disease Models, Animal; Guanidines - pharmacology; Heart Arrest, Induced; Hemodynamics; In Vitro Techniques; intracellular sodium; Magnetic Resonance Spectroscopy; Male; Medical sciences; Miscellaneous; Myocardial Contraction; myocardial ischemia; Myocardial Ischemia - physiopathology; Myocardial Reperfusion Injury - prevention & control; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; reperfusion injury; Sodium - metabolism; Sodium-Hydrogen Exchangers - antagonists & inhibitors; Sulfones - pharmacology; Ventricular Function, Left; intracellular sodium; myocardial ischemia; reperfusion injury; Cardioplegic solution; Rat; Rodentia; Induced cardiocirculatory arrest; Isolated organ; Prevention; Vertebrata; Chemotherapy; Mammalia; Treatment; Sodium; Animal; Myocardium; Complication; Inhibitor; Ion exchange; Potassium; Protection
• ISSN: 0003-4975; 1552-6259
• DOI: 10.1016/S0003-4975(97)00245-2

Background. The accumulation of intracellular sodium during myocardial ischemia couples an inappropriate calcium influx and depressed cardiac recovery during subsequent reperfusion. The effects of the selective sodium/hydrogen exchange inhibitor HOE 694 are evaluated during myocardial ischemia and reperfusion.
Methods. Ten isolated rat hearts were subjected to a 2-minute infusion of St. Thomas’ cardioplegia ± 1 μmol/L HOE 694 followed by 50 minutes’ normothermic (37°C) global ischemia. Intracellular sodium accumulation was continuously measured using triple quantum filtered
23Na nuclear magnetic resonance spectroscopy without chemical shift reagents. Hemodynamic variables were assessed before and after ischemia.
Results. The addition of 1 μmol/L HOE 694 to St. Thomas’ cardioplegic solution (n = 5) attenuated the accumulation of intracellular sodium after 50 minutes’ ischemia (160.5% ± 9.1% versus 203.4% ± 10.9% [mean ± standard error], HOE 694 versus control, respectively;
p = 0.014) and after the initial reperfusion period (first 30 minutes) (288.7% ± 10.2% versus 335.9% ± 10.3%;
p = 0.008). HOE 694–treated hearts showed significantly improved postischemic recovery of left ventricular developed pressure (53.5% ± 8.4% versus 26.4% ± 6.6%;
p = 0.036) and rate–pressure product (40.2% ± 6.9% versus 13.2% ± 5%;
p = 0.014). Postischemic recovery of coronary flow was not significantly different between the two groups (68.6% ± 5.9% versus 55.5% ± 4.6%, HOE 694 versus control, respectively;
p = 0.11).
Conclusions. The addition of 1 μmol/L HOE 694 to cardioplegic solution attenuates the increase of intracellular sodium during myocardial ischemia and early reperfusion. This is coupled with an improved recovery of contractile function, possibly as a result of decreased sodium and calcium overload of ischemic myocardium.