The effect of some proton conducting systems on protamine inhibited respiration

Popinigis, Jerzy; Rzeczycki, W; Świerczyński, Julian

doi:10.1016/0014-5793(70)80249-6

Cited by 21 publications

(6 citation statements)

References 14 publications

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“…These include systemic hypotension, bradycardia, thrombocytopenia, leukopenia, and pulmonary artery hypotension, as well as pulmonary hypertension associated with pulmonary vasoconstriction, leading to noncardiogenic pulmonary edema and occasional ", death. 19 thousands of vascular procedures accompanied by protamine sulfate usage each year, the potential number of untoward protamine-related events represents an important threat to patient welfare. The present investigation demonstrates that protamine sulfate reversal of heparin activity results not only in adverse cardiovascular responses but also in major reductions in systemic oxygen consumption, which is evident by a 50% to 60% decrease during the time of maximal hemodynamic changes.…”

Section: Discussionmentioning

confidence: 99%

Decreased oxygen consumption as a toxic manifestation of protamine sulfate reversal of heparin anticoagulation

Wakefield¹,

Ucros²,

Kresowik³

et al. 1989

Journal of Vascular Surgery

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Protamine sulfate has been observed to interfere with the control of isolated mitochondrial respiration in vitro. This study was designed to determine if oxygen consumption changes in intact animals occur in vivo during protamine administration. Oxygen consumption was assessed in seven dogs anticoagulated with heparin (150 IU/kg) and reversed 30 minutes later with protamine sulfate (1.5 mg/kg). Oxygen saturations measured included arterial (SaO2 arterial), mixed venous (SvO2 systemic), jugular (SvO2 jugular), portal (SvO2 portal), and coronary (SvO2 coronary). Cardiac output (CO) and carotid artery flow determinations allowed calculation of systemic oxygen consumption (VO2 systemic) and cerebral oxygen consumption VO2 cerebral. Hemodynamic measurements included arterial blood pressure (BP), pulmonary artery systolic and diastolic pressures (PAS, PAD), and heart rate (HR). Protamine sulfate administration resulted in hypotension (delta BP -64 mm Hg), pulmonary hypertension (delta PAS + 13 mm Hg, delta PAD + 11 mm Hg), and bradycardia (delta HR -30). Shortly after protamine administration, CO fell 54% and carotid artery flow fell more than 50%, yet declines in SvO2 systemic and SvO2 jugular were not observed. In fact these parameters increased 3% and 2%, respectively. VO2 systemic fell 55% and VO2 cerebral fell 57%. Similarly, SvO2 portal and SvO2 coronary increased 6% and 9%, respectively. Significant correlations existed between changes in VO2 systemic and BP (r = 0.05, p less than 0.001), HR (r = 0.3, p less than 0.01, PAD (r = -0.3, p less than 0.05, and CO (r = 0.8, p less than 0.001). Impaired oxygen utilization was most evident during the first 5 minutes after protamine administration. This investigation, for the first time, establishes that protamine sulfate decreases in vivo oxygen consumption, a finding that may account for certain of the drug's adverse side effects.

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Section: Discussionmentioning

confidence: 99%

Decreased oxygen consumption as a toxic manifestation of protamine sulfate reversal of heparin anticoagulation

Wakefield¹,

Ucros²,

Kresowik³

et al. 1989

Journal of Vascular Surgery

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“…It is possible that progesterone reacts with the mitochondrial membrane at the locus where back diffusion of protons take place, thereby preventing back diffusion of protons. Popinigis et al [5] suggested that citrate and isocitrate, in the presence of protamine -which probably prevents back diffusion of protons into mitochondrion -penetrate the mitochondrion only in the nonionlsed form (A-/H + symport of Mitchell [6]) thereby conducting the protons into mitochondrion. These protons react with OH-ions generated by respiration or by ATP hydrolisis.…”

Section: Discussionmentioning

confidence: 99%

“…According to Popinigis et al [5 ] tricarboxylic anions require protons from ATP hydrolysis and respiration for their output from mitochondria. This view is also supported by our experiments with oligomycin.…”

Section: North-holland Publishing Company -Amsterdammentioning

confidence: 99%

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The effect of some anions on respiration inhibited by progesterone

Świerczyński

Aleksandrowicz

1970

FEBS Letters

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“…I n this respect the effect of progesterone on succinate oxidation is similar to that of protarnine. Popinigis et al [18,20] reported that inhibition of succinate oxidation by protamine waa reversed by citrate. I n this paper the effect of citrate on succinate (+ rotenone) oxidation inhibited by progesterone has been studied.…”

Section: Effect Of Progesterone On Succinate Oxidation By Mitochondrimentioning

confidence: 99%

Effect of Progesterone on Respiration and Oxidative Phosphorylation

Aleksandrowicz¹,

Świerczyński²,

Zelewski³

1972

European Journal of Biochemistry

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1.Progesterone inhibited oxidation of succinate by intact rat liver mitochondria in metabolic state 3. The degree of inhibition did not depend on succinate and ADP concentration. Inhibition was less pronounced in the presence of EDTA. The respiration has been slightly inhibited by progesterone if mitochondria were damaged by sonication.2. Inhibition of succinate (f rotenone) oxidation by progesterone in intact rat liver mitochondria in metabolic state 3 was reversed by 2,4-dinitrophenol, calcium ion, gramicidin + NH,Cl, EDTA, some anions and partially by gramicidin + K+. The degree of reversal by anions was pH-dependent.3. Progesterone inhibited ATP synthesis with succinate (+ rotenone) as substrate. This inhibition has not been observed in the presence of citrate and other anions (in contrast to inhibition caused by oligomycin). 4.Progesterone was without effect on ATPase activity stimulated by 2,4-dinitrophenol.Under nonrespiring conditions progesterone did not induce ATPase activity. 5. The experiments described suggest that inhibition of succinate oxidation by progesterone in the intact rat liver mitochondria is exerted by interference with the uptake of protons into the mitochondrion.Hormonal steroids and related substances have been shown to inhibit electron transfer with both mitochondrial and submitochondrial systems [ 1-41. Steroids are capable of interacting with respiratory chain a t two different sites, the more sensitive located in the NADH-flavoprotein region and less sensitive located in the cytochrome b and cytochrome c region [l-41. Wade and Jones reported that progesterone uncouples oxidative phosphorylation by activating the mitochondrial ATPase activity [5]. Vallejos and Stoppani [2] claimed that progesterone affects the energy conserving mechanism a t the second phosphorylation site. Chance et al. [6,7] suggested that steroids affect energy transfer system preferentially a t the first phosphorylation site.Trivial Names. Androstendione, androst-4-ene-3,17-dione; androsterone, androstane-3a-ol-17-one; corticosterone, pregn-4-ene-11/?,21-diol-3,2O-dione; cortisone, pregn-4-ene-17a,21-diol-3,1l,2O-trione ; deoxycorticosterone, pregn-4-ene-21-01-3,20-dione; 17a-hydroxyprogesterone, 17a-hydroxypregn-4-ene-3,2O-dione ; oestradiol, oestra-1,3,5-triene-3,178 -diol ; oestra -1,3,5 -triene -3,16a,17/? -triol;pregnanolone, pregnane-3a-ol-20-one; pregnanediol, 58-pregnane-3a,20a-diol; pregnenolone, 3/3-hydroxypregn-5-ene-20-one; progesterone, pregn-4-ene-3,20-dione; testosterone, 17t9-hydroxyandrost-4-ene-3-one. Enzymes. Hexokinase or ATP : D-hexose 6-phosphotransferase (EC 2.7.1.1); ATPase or ATP phosphohydrolase (EC 3.6.1.3). oestriol, These contradictory observations inspired the present study, the aim of which is to obtain more information on the mechanism of progesterone action on mitochondrial respiration and oxidative phosphorylation. I n this paper the effects of classical uncouplers, gramicidin, calcium ion, and some anions on mitochondrial respiration inhibited by progesterone have been studie...

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The effect of some proton conducting systems on protamine inhibited respiration

Cited by 21 publications

References 14 publications

Decreased oxygen consumption as a toxic manifestation of protamine sulfate reversal of heparin anticoagulation

Decreased oxygen consumption as a toxic manifestation of protamine sulfate reversal of heparin anticoagulation

The effect of some anions on respiration inhibited by progesterone

Effect of Progesterone on Respiration and Oxidative Phosphorylation

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