title: Adding ROS quenchers to cold K+ cardioplegia reduces superoxide emission during 2-hour global cold cardiac ischemia.
abstract: We reported that the combination of reactive oxygen species (ROS) quenchers Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), catalase, and glutathione (MCG) given before 2 hours cold ischemia better protected cardiac mitochondria against cold ischemia and warm reperfusion (IR)-induced damage than MnTBAP alone. Here, we hypothesize that high K(+) cardioplegia (CP) plus MCG would provide added protection of mitochondrial bioenergetics and cardiac function against IR injury. Using fluorescence spectrophotometry, we monitored redox balance, ie reduced nicotinamide adenine dinucleotide and flavin adenine dinucleotide (NADH/FAD), superoxide (O(2)               (•-)), and mitochondrial Ca(2+) (m[Ca(2+)]) in the left ventricular free wall. Guinea pig isolated hearts were perfused with either Krebs Ringer's (KR) solution, CP, or CP + MCG, before and during 27°C perfusion followed immediately by 2 hours of global ischemia at 27°C. Drugs were washed out with KR at the onset of 2 hours 37°C reperfusion. After 120 minutes warm reperfusion, myocardial infarction was lowest in the CP + MCG group and highest in the KR group. Developed left ventricular pressure recovery was similar in CP and CP + MCG and was better than in the KR group. O(2)               (•-), m[Ca(2+)], and NADH/FAD were significantly different between the treatment and KR groups. O(2)               (•-) was lower in CP + MCG than in the CP group. This study suggests that CP and ROS quenchers act in parallel to improve mitochondrial function and to provide protection against IR injury at 27°C.
authors.affiliation: Department of Anesthesiology, The Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Aldakkak
authors.forename: David F
authors.initials: DF
authors.lastname: Stowe
authors.forename: James S
authors.initials: JS
authors.lastname: Heisner
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Riess
authors.forename: Amadou K S
authors.initials: AK
authors.lastname: Camara
mesh_terms: D000818:Animals; D002314:Cardioplegic Solutions / Q000627:therapeutic use; D050377:Cold Ischemia / Q000379:methods*; D006168:Guinea Pigs; D006324:Heart Arrest, Induced / Q000379:methods*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006982:Hypertonic Solutions / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000378:metabolism / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D017680:Potassium Compounds / Q000627:therapeutic use*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
chemical_list: D002314:Cardioplegic Solutions; D006982:Hypertonic Solutions; D017680:Potassium Compounds; D017382:Reactive Oxygen Species; C018369:potassium cardioplegic solution; D013481:Superoxides