A Novel Anti-Oxidative Agent Improves Recovery of the Heart After Cardiac Arrest

Summary

Experiments were designed to determine whether adding a synthetic anti-oxidative agent H 290/51 (cis-7mcthyl-9-methoxy-5,5 a,6,10 b-tetrahydroindeno [2,1-b] indole), to a crystalloid cardioplegic Solution was beneficial for myocardial recovery and coronary reactivity in isolated rat hearts after six hours cold arrest. Two groups of hearts were single-flush perfused using the Langendorff technique (10 ml at 4 °C) with either Plegisol® (St. Thomas' Hospital Solution) (n = 6) or Plegisol® with H 290/51 (n = 6) added to a final concentration of 1 μmmol/L. The heart were then stored for six hours in the respective Solution at 4 °C. A third group of hearts (n = 6) were single-flush with Plegisol® and reperfusion was immediately started (the 'non-stored' group). Before and after the arrest phase the hearts were perfused at constant pressure with Krebs-Henseleit bicarbonate buffer. To evaluate coronary vascular function, endothelium-dependent vasodilatation was induced with 5-hydroxy-tryptamine (5-HT) and smooth-muscle relaxation with nitroglycerin (GTN). Myocardial contractility after 30 min reperfusion, measured as left-ventricular developed pressure (LVDP), was significantly improved in hearts in the Plegisol + H 290/51 group compared to hearts in the Plegisol group (LVDP 89. ± 8.5 % vs 57.2 ± 10.7 % of prearrest values; p < 0.05). LVDP in hearts receiving Plegisol + H 290/51 was comparable to non-stored hearts (88.2 ±1.3%). The vasodilatory response to GTN was significantly reduced in hearts perfused with piain Plegisol (p < 0.05) but not in hearts reeeiving Plegisol + H 290/51 or in the non-stored hearts. The release of creatine-kinase from the hearts in the Plegisol + H 290/51 group was 16.0 ± 2.6 IU 30 min, 37.1 ± 14.0 IU/ 30 min (p = 0.098) from the hearts in the Plegisol group, and 0.8 ± 0.30 IU/30 min from hearts in the non-stored group. Addition of an anti-oxidative agent, H 290/51 to a cardioplegic storage Solution improves functional recovery and preserves the coronary vascular funetion in rat hearts after storage and reperfusion which implies further improvement in the technique of heart preservation.

Zusammenfassung

Mittels der Langendorff-Technik wurde an Rattenherzen in einer Reihe von Experimenten die myokardiale Erholung nach längerem Herzstillstand geprüft, wobei in einem Teil der Fälle der kardioplegischen Lösung eine synthetische antioxidative Substanz H 290/51 (cis-7 methyl-9-methoxy-5,5 a,6,l 0 b-tetra-hydroindeno [2,1-b] indole) zugefügt wurde. In diesen Fällen zeigte sich eine verbesserte myokardiale Erholung der Herzen.

Key words

Cardiac preservation - Endothelium - Antioxidant - Nitric oxide - Vasodilatation