Effect of combining phosphodiesterase III inhibitors with St Thomas Hospital's solution used as transplantation preservative solution in isolated rat hearts.
Improved preservation of the harvested heart with attenuation of the reperfusion injury is important for successful outcomes of cardiac transplantations. The most commonly used cardioplegic solution, to prevent ischemic changes has been St Thomas' Hospital cardioplegic solution (STHCS). However, it is neither ideal nor sufficient to prevent myocardial ischemia and reperfusion injury. Phosphodiesterase inhibitors can attenuate the damage due to the injuries of ischemia and reperfusion. In this study we sought to enrich STHCS with a phosphodiesterase inhibitor to improve preservation of cardiac functions. The harvested hearts of 24 rats were divided into four groups. All hearts were mounted on a Langendorff perfusion system. After a stabilization period, cardiac arrest was maintained by STHCS. The hearts were stored in STHCS alone or with milrinone, amrinone, or enoximone for 6 hours. The reperfusion was maintained using a modified Tyrode's solution. All hearts were compared for their preischemic and postischemic left ventricular developed pressure, +dp/dtmax, -dp/dtmax, duration of systole, ejection time, and time to reach peak systolic pressure. Coronary effluent was collected for lactate dehydrogenase (LDH) measurements. The initial values for all metrics were comparable between the groups. During the postreperfusion period, all hearts showed lower peak systolic pressures than the initial values. Although the amrinone group seemed to have higher values, the 25-minute result was at the border of significance and the 30-minute value, significantly higher. All hearts showed far lower results of maximum changes in contractility during the time period (+dp/dtmax) versus the initial values; comparisons between groups were not significant. For the parameter of maximum changes in relaxation during the time period (-dp/dtmax), while other hearts showed lower results, the amrinone group displayed values comparable to the initial ones after 20 minutes. Comparisons between groups were insignificant. While other hearts had comparable values for time of systole, the hearts applied with milrinone reached these values after 15 minutes. Group comparison for time of ejection revealed that the results at 5-minute postreperfusion were higher in the enoximone and the amrinone groups than the milrinone group. Postreperfusion 5-minute results were higher in the enoximone and the amrinone groups than the milrinone group for time to reach peak systolic pressure. LDH levels were lowest in the amrinone group. In conclusion, our study revealed that adding phosphodiesterase inhibitors to STHCS improved peak systolic pressure and maximum changes in relaxation during the time period (-dp/dtmax, mm Hg/s). It also decreased the LDH leakage, which corresponded to the degree of ischemic tissue damage. Amrinone seemed to result in more favorable results, which may be attributed to its additional effects on inflammation, including those on cytokines and leukocyte aggregation.
Besirli
K
K
Department of Cardiovascular Surgery, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. kazimbesirli@yahoo.com
Burhani
S M
SM
Arslan
C
C
Suzer
O
O
Sayin
A G
AG
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002314:Cardioplegic Solutions; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D003971:Diastole; D006321:Heart; D006334:Heart Function Tests; D066298:In Vitro Techniques; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008274:Magnesium / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D012965:Sodium Chloride / Q000494:pharmacology; D013599:Systole; D020858:Tissue and Organ Harvesting / Q000379:methods
D001639:Bicarbonates; D002314:Cardioplegic Solutions; D010726:Phosphodiesterase Inhibitors; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D011189:Potassium Chloride; D007770:L-Lactate Dehydrogenase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D008274:Magnesium; D002122:Calcium Chloride