The isolated post ischaemic rat heart is more vulnerable to protamine sulphate than the non-ischaemic heart

Halpern, Pinchas; Hochhauser, Edith; Puzhevsky, A.; Rudick,; Sorkine, Patrick; Vidine, B

doi:10.1016/s0967-2109(96)00091-9

Cited by 4 publications

(1 citation statement)

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“…application resulted in impaired mitochondrial respiration (Popinigis, 1974;Kossekova et al, 1975). Similar results were obtained with in vivo studies performed with dogs (Wakefield et al, 1989), as well as rabbit and rat hearts (Wakefield et al, 1990(Wakefield et al, , 1992Halpern et al, 1997). A rapid decline in ATP levels particularly in the presence of heparin occurred within minutes after application of PS to the cultured bovine pulmonary artery endothelial cells (Wakefield et al, 1989).…”

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confidence: 73%

Protamine Sulfate Induces Mitochondrial Hyperpolarization and a Subsequent Increase in Reactive Oxygen Species Production

Ramzan

Michels

Weber

et al. 2019

J Pharmacol Exp Ther

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Protamine sulfate (PS) is widely used in heart surgery as an antidote for heparin, albeit its pharmacological effects are not fully understood and applications are often accompanied by unwanted side effects. Here we show the effect of PS on mitochondrial bioenergetics profile resulting in mitochondrial reactive oxygen species (ROS) production. Polarographic measurements were performed in parallel to membrane potential and ROS measurements by FACS analyzer using tetramethylrhodamine ethyl ester and MitoSOX fluorescent dyes, respectively. PS inhibited intact rat heart mitochondrial respiration (stimulated by ADP) to 76% (P , 0.001) from the baseline of 51.6 6 6.9 to 12.4 6 2.3 nmol O 2 ×min 21 ×ml 21 . The same effect was found when respiration was inhibited by antimycin A (101.0 6 8.9 vs. 38.0 6 9.9 nmol O 2 ×min 21 ×ml 21 , P , 0.001) and later stimulated by substrates of cytochrome oxidase (CytOx) i.e., ascorbate and tetramethyl phenylene diamine, suggesting that PS exerted its effect through inhibition of CytOx activity. Furthermore, the inhibition of mitochondrial respiration by PS was concentration dependent and accompanied by hyperpolarization of the mitochondrial membrane potential (Dc m ), i.e., 18% increase at 50 mg/ml and an additional 3.3% increase at 250 mg/ml PS compared with control. This effect was associated with a strong consequent increase in the production of ROS, i.e., 85% and 88.6% compared with control respectively. We propose that this excessive increase in ROS concentrations results in mitochondrial dysfunction and thus might relate to the "protamine reaction," contributing to the development of various cardiovascular adverse effects.

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