Effect of sodium aspartate on the recovery of the rat heart from long-term hypothermic storage.
We have investigated the reported ability of aspartate to enhance greatly the cardioprotective properties of the St. Thomas' Hospital cardioplegic solution after prolonged hypothermic storage. Rat hearts (n = 8 per group) were excised and subjected to immediate arrest with St. Thomas' Hospital cardioplegic solution (2 minutes at 4 degrees C) with or without addition of monosodium aspartate (20 mmol/L). The hearts were then immersed in the same solution for 8 hours (4 degrees C) before heterotopic transplantation into the abdomen of homozygous rats and reperfusion in vivo for 24 hours. The hearts were then excised and perfused in the Langendorff mode (20 minutes). Addition of aspartate to St. Thomas' Hospital cardioplegic solution gave a small but significant improvement in left ventricular developed pressure, which recovered to 82 +/- 3 mm Hg compared with 70 +/- 2 mm Hg in control hearts (p less than 0.05). However, coronary flow and high-energy phosphate content were similar in both groups. In subsequent experiments hearts (n = 8 per group) were excised, arrested (2 minutes at 4 degrees C) with St. Thomas' Hospital cardioplegic solution containing a 0, 5, 10, 20, 30, 40, or 50 mmol/L concentration of aspartate, stored for 8 hours at 4 degrees C, and then reperfused for 35 minutes. A bell-shaped dose-response curve was obtained, with maximum recovery in the 20 mmol/L aspartate group (cardiac output, 48 +/- 5 ml/min versus 32 +/- 5 ml/min in the aspartate-free control group; p less than 0.05). However, additional experiments showed that a comparable improvement could be achieved simply by increasing the sodium concentration of St. Thomas' Hospital cardioplegic solution by 20 mmol/L. Similarly, if sodium aspartate (20 mmol/L) was added and the sodium content of the St. Thomas' Hospital cardioplegic solution reduced by 20 mmol/L, no significant protection was observed when recovery was compared with that of unmodified St. Thomas' Hospital cardioplegic solution alone. In still further studies, hearts (n = 8 per group) were perfused in the working mode at either high (greater than 80 ml/min) or low (less than 50 ml/min) left atrial filling rates. Under these conditions, if functional recovery was expressed as a percentage of preischemic function, artifactually high recoveries could be obtained in the low-filling-rate group. In conclusion, assessment of the protective properties of organic additives to cardioplegic solutions requires careful consideration of (1) the consequences of coincident changes in ionic composition and (2) the characteristics of the model used for assessment.
Galiñanes
M
M
Department of Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London, United Kingdom.
Chambers
D J
DJ
Hearse
D J
DJ
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D001639:Bicarbonates / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D016027:Heart Transplantation; D006439:Hemodynamics / Q000187:drug effects; D007036:Hypothermia, Induced; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
D001639:Bicarbonates; D002314:Cardioplegic Solutions; C041711:St. Thomas' Hospital cardioplegic solution; D001224:Aspartic Acid; D012965:Sodium Chloride; D011189:Potassium Chloride; D008274:Magnesium; D002122:Calcium Chloride