Organotoxic effects of excessive doses of sodium nitroprusside in the rabbit

Höbel, M; Kreye, V. A. W.; Nemes, Zoltán; Pill, Johannes

doi:10.1007/bf01477467

Cited by 5 publications

(1 citation statement)

References 2 publications

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“…drastic lowering of systemic blood pressure). In addition, the infusion concentrations of L-arg, [12][13][14] NLA, [15][16][17] and SNP 18,19 were readily used by other investigators.…”

Section: Protein Kinase C Delta Modulates L-arginine-induced Enhancemmentioning

confidence: 99%

Protein Kinase C Delta Modulates Endothelial Nitric Oxide Synthase after Cardiac Arrest

Lin

Gresia

Stradecki

et al. 2014

J Cereb Blood Flow Metab

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We previously showed that inhibition of protein kinase C delta (PKCd) improves brain perfusion 24 hours after asphyxial cardiac arrest (ACA) and confers neuroprotection in the cortex and CA1 region of the hippocampus 7 days after arrest. Therefore, in this study, we investigate the mechanism of action of PKCd-mediated hypoperfusion after ACA in the rat by using the two-photon laser scanning microscopy (TPLSM) to observe cortical cerebral blood flow (CBF) and laser Doppler flowmetry (LDF) detecting regional CBF in the presence/absence of dV1-1 (specific PKCd inhibitor), nitric oxide synthase (NOS) substrate (L-arginine, L-arg) and inhibitor (N o -Nitro-L-arginine, NLA), and nitric oxide (NO) donor (sodium nitroprusside, SNP). There was an increase in regional LDF and local (TPLSM) CBF in the presence of dV1-1 þ L-arg, but only an increase in regional CBF under dV1-1 þ SNP treatments. Systemic blood nitrite levels were measured 15 minutes and 24 hours after ACA. Nitrite levels were enhanced by pretreatment with dV1-1 30 minutes before ACA possibly attributable to enhanced endothelial NOS protein levels. Our results suggest that PKCd can modulate NO machinery in cerebral vasculature. Protein kinase C delta can depress endothelial NOS blunting CBF resulting in hypoperfusion, but can be reversed with dV1-1 improving brain perfusion, thus providing subsequent neuroprotection after ACA. Keywords: asphyxial cardiac arrest; middle cerebral artery occlusion; neuroprotection; palmitic acid methyl ester; stearic acid methyl ester INTRODUCTIONWe previously showed that inhibition of protein kinase C delta (PKCd) via dV1-1 can increase perfusion 24 hours after asphyxial cardiac arrest (ACA). Global cerebral ischemia (via ACA) causes derangement of cerebral blood flow (CBF) responsible for neuronal cell death in the CA1 region of the hippocampus as well as the cortex.1 Owing to the overall decrease in CBF after ischemia, neuronal cell death 1 can occur in major regions of the brain responsible for learning, memory, and cognitive function.2 It is thought that during global ischemia, PKCd (a novel PKC) levels are elevated causing PKCd to translocate to the nucleus (activation) resulting in cellular damage. In the normal brain, PKCd levels are nominal whereas global ischemia can cause activation/translocation of PKCd.3 Inhibition of PKCd (via specific inhibitor of PKCd, dV1-1) can cause a revival of CBF 24 hours after ischemia to counteract hypoperfusion or low CBF found to be suppressed after cardiac arrest from 38% to 65%. 1,4 We previously showed that pretreatment of dV1-1 before ACA can enhance perfusion 24 hours after ischemia, resulting in improved neuronal survival in the hippocampal CA1 and cortex regions in our rat model of ACA.1 Here, we sought out to define the specific mechanism(s) of how inhibition of PKCd can alleviate these pathologies. The possible endothelium and endothelial-mediated nitric oxide synthase (eNOS) involvement as a target for PKCd relating to general circulation was first reported by Monti et al.

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“…drastic lowering of systemic blood pressure). In addition, the infusion concentrations of L-arg, [12][13][14] NLA, [15][16][17] and SNP 18,19 were readily used by other investigators.…”

Section: Protein Kinase C Delta Modulates L-arginine-induced Enhancemmentioning

confidence: 99%

Protein Kinase C Delta Modulates Endothelial Nitric Oxide Synthase after Cardiac Arrest

Lin

Gresia

Stradecki

et al. 2014

J Cereb Blood Flow Metab

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The antidote effect of thiosulphate and hydroxocobalamin in formation of nitroprusside intoxication of rabbits

et al. 1980

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Sodium nitroprusside (SNP) and hydroxocobalamin (HC) - in molar ratios of 1:4, 1:5, and 1:8, respectively - were infused simultaneously during 4 h into two veins of separate ears of conscious rabbits. Controls received HC only. Sodium thiosulphate (ST) was infused with SNP at molar ratios of 1:4, 1:5, and 1:10. The observation period was 48 h. With the lowest dose of HC (1:4), SNP produced a severe metabolic acidosis; three of ten animals died during the infusion, an additional six within 24 h. When the 1:5 ratio was administered, the acidosis was less marked, but still three of seven animals succumbed within 24 h. The highest dose (1:8) prevented acidosis, however three of eight animals died. All doses of HC caused histological changes in the liver, the myocardium, and the kidney, independently if given alone or with SNP. In contrast to this, ST had a complete antidote effect, if administered in a 1:5 ratio; no acidosis was demonstrable and death did not occur. In neither dosage ST could prevent histological changes in the liver, but the kidney and the heart were not affected. In contrast to HC ST alone did not cause histological alterations. Consequently, ST is the preferable antidote and is superior to HC for preventing or treating intoxications with SNP.

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Counteraction of cyanide poisoning by thiosulphate when administering sodium nitroprusside as a hypotensive treatment

Schulz

Bonn²,

Kämmerer

et al. 1979

Klin Wochenschr

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A 42-year old patient received a continuous infusion of sodium nitroprusside (SNP) at a dosage rate of 600 microgram/min for approximately four days. On the third day of treatment a dangerous high level of cyanide was measured in the blood. When an additional continuous infusion of sodium thiosulphate at five times the molar concentration of the SNP was given, this cyanide level dropped over a period of 7h to one-seventh of its initial value. The thiosulphate did not reduce the effectiveness of the SNP in lowering the blood pressure.

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Organotoxic effects of excessive doses of sodium nitroprusside in the rabbit

Cited by 5 publications

References 2 publications

Protein Kinase C Delta Modulates Endothelial Nitric Oxide Synthase after Cardiac Arrest

Protein Kinase C Delta Modulates Endothelial Nitric Oxide Synthase after Cardiac Arrest

The antidote effect of thiosulphate and hydroxocobalamin in formation of nitroprusside intoxication of rabbits

Counteraction of cyanide poisoning by thiosulphate when administering sodium nitroprusside as a hypotensive treatment

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