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Biomedical subjects

H Kruszyna

Publications and source records attributed to H Kruszyna.

32 records · Page 2Linked to original sources
PubMed1984

Hypotensive effects of hydroxylamine in intact anesthetized dogs and cats.

When given IV in bolus doses to intact anesthetized dogs or cats, hydroxylamine hydrochloride produced transient but precipitous falls in the mean arterial blood pressure in a dose-related manner, as well as a significant methemoglobinemia. The half-time for recovery of the mean arterial pressure was also dose-related. These effects were very similar to those elicited by comparable doses of sodium nitrite, except that the half-recovery time for return to normal blood pressure was somewhat longer with nitrite. Although hydroxylamine has long been known to relax vascular smooth muscle in vitro, we are not aware of previous demonstrations of hypotensive effects in vivo. Acute poisoning by either nitrite or hydroxylamine is apt to result in both an anemic hypoxia due to methemoglobinemia and a stagnat (hypokinetic) hypoxia due to direct vasodilation. Hydroxylamine, but not nitrite, also appeared to stimulate respiration possibly through an effect on the chemoreceptors of the carotid body.

Anesthesia↗
PubMed1982

Nitroprusside increases cyclic guanylate monophosphate concentrations during relaxation of rabbit aortic strips and both effects are antagonized by cyanide.

The authors have confirmed previous observations that sodium cyanide (CN-) partially reverses the vasodilator effects of sodium nitroprusside (SNP) on vascular smooth muscle. As tested on rabbit aortic strips contracted by norepinephrine (NE), the final tension is independent of the order of addition of reagents. In the same concentration, CN- alone had no effect on tension also as reported by others. The ED50 values for relaxation of aortic strips for a series of directly acting agonists ("nitric oxide vasodilators") were: sodium azide (N-3) 2.1 X 10(-7) M; SNP 2.7 X 10(-7) M; hydroxylamine (H2NOH) hydrochloride 2.5 X 10(-6) M; human nitric oxide hemoglobin (HbNO) 3.5 X 10(-6) M; and sodium nitrite (NO-2) 1.2 X 10(-4) M. In addition to SNP, CN- antagonized the vasodilator effects of N-3 and H2NOH, but it failed to reverse relaxation by HbNO, NO gas, NO-2 (as observed by us), glyceryl trinitrate, adenosine, or papaverine (as observed by others). The only change noted in cyclic-adenosine monophosphate (c-AMP) concentrations in aortic strips exposed to 1) NE, 2) NE + NO-2 or SNP, or 3) NE + NO-2 or SNP + CN- was an increase due to NE. The only statistically significant change noted in cyclic-guanosine monophosphate (c-GMP) concentrations exposed to 1) NE, 2) NE + NO-2 or 3) NE + NO-2 + CN- was also an increase due to NE. In contrast, SNP resulted in further increases in c-GMP after NE, and when cyanide was added, a significant decrease in c-GMP followed. These results are only partially consistent with a role for c-GMP in relaxation of vascular smooth muscle, but cyanide may become a useful tool for the study of mechanisms of action of the nitric oxide vasodilators.

Animals↗
PubMed1980

Toxicology and pharmacology of some ruthenium compounds: Vascular smooth muscle relaxation by nitrosyl derivatives of ruthenium and iridium.

A series of compounds were synthesized from ruthenium trichloride, and their ip LD50s were determined in mice: pentamminenitrosylruthenium(II) chloride, 8.9; chloronitrobis(2,2'-dipyridyl)ruthenium(II), 55;dichlorobis(2,2'-dipyridyl)ruthenium(II), 63; ruthenium trichloride, 108; and potassium pentachloronitrosylruthenate(II), 127 mg/kg. The two bis-bipyridyl complexes produced death in convulsions within minutes, whereas the remaining compounds resulted in long, debilitating courses with death occurring in 4-7d. When given in massive overdoses, however, the compounds with inorganic ligands also produced rapid convulsive death in mice, and when given iv to anesthetized cats, they produced respiratory arrest. The major toxic effects of all the complexes appeared to be due to the metal and not to its associated ligands. Only complexes having nitrosyl ligand specifically relaxed vascular smooth muscle. Potassium pentabromoiridate(III) also relaxed rabbit aortic strips that had been contracted by adrenergic agonists, but potassium pentachloroiridate(III) did not. None of the complexes was as active as nitroprusside in relaxing aortic strips or in decreasing arterial blood pressure in cats. No compound tested was as potent as cisplatin in antitumor activity. The pentamminenitrosylruthenium(II) complex also relaxed guinea pig ileum and frog rectus abdominus when these isolated muscles had been contracted by acetylcho line. It appears that these organoruthenium compounds may produce death in central respiratory arrest, as do the inorganic complexes when given iv or ip in massive overdoses. In minimally lethal doses, the complexes with inorganic ligands may affect a variety of contractile tissues, perhaps by a general mechanism involving Ca. These complexes are apt to be generally cytotoxic as well.

Animals↗
PubMed1976

Toxicology of some inorganic antihypertensive anions.

Sodium nitroprusside reacts with hemoglobin in vitro and in vivo to cause the formation of cyanmethemoglobin and the liberation of excess free cyanide. The latter is responsible for the typical signs of acute cyanide poisoning in mice after lethal doses of nitroprusside. Differences in the reactivity of the red cells of various species toward nitroprusside are due to differences in the permeability of the red cell membranes to nitropruside. In vivo thiocyanate results in the formation of methemoglobin in an elevation of blood cyanide levels in mice. The latter, however, does not result in cyanide poisoning since it is bound in the biologically inert form of cyanmethemoglobin. Thus, both nitroprusside and thiocyanate generate their own antidote in mice, but an excess of cyanide is released in the case of nitroprusside whereas excess methemoglobin is generated in the case of thiocyanate. Acute poisoning with thiocyanate salts apparently involves direct excitatory effects on the central nervous system. In vitro the reaction between thiocyanate and hemoglobin proceeds only in the presence of hydrogen peroxide. Chronic administration of nitroprusside results in the elevation of blood thiocyanate levels presumably because of continuous, endogenous cyanide metabolism via rhodanese (thiosulfate sulfurtransferase). When one includes these previously unrecognized effects of nitroprusside and thiocyanate, there appears to be some correlation between the ability of a chemical to oxidize hemoglobin and its ability to activate nonadrenergic receptors for the relaxation of vascular smooth muscle.

Animals↗
PubMedDate not supplied

Effect of cyanide on the reaction of nitroprusside with hemoglobin: relevance to cyanide interference with the biological activity of nitroprusside.

The reaction of sodium nitroprusside (SNP) with deoxyhemoglobin (Hb) results in two distinct EPR-detectable species, the one-electron-reduced nitroprusside ion [(CN)5FeNO]3- and nitrosylhemoglobin (HbNO). In the presence of excess cyanide (CN-) only the signal for [(CN)5FeNO]3- is observed. Thus, while free CN- does not interfere with Hb reduction of SNP, it prevents transfer of the NO moiety to Hb. Electrolytic reduction of SNP under similar conditions, however, leads to [(CN)5FeNO]3- and a small amount of [(CN)4FeNO]2- resulting from loss of the CN- trans to the NO. Excess free CN- shifts the equilibrium between these two species toward [(CN)5FeNO]3-, thereby reducing the concentration of [(CN)4FeNO]2-. Thus, [(CN)4FeNO]2- appears to be responsible for the transfer of NO to Hb. Consistent with this mechanism, both [(CN)5FeNO]3- and [(CN)4FeNO]2- are observed when SNP is added to erythrocyte lysates. Under these conditions HbNO is formed more rapidly due to the higher concentration of the latter species with the labile NO. This observation suggests that red blood cell constituents capable of binding CN- shift the equilibrium between the reduced SNP ions toward [(CN)4FeNO]2-. In the reaction of reduced glutathione (GSH) with SNP, [(CN)5FeNO]3- is formed as well as low concentrations of an EPR-detectable GSH-SNP adduct. Excess free CN- introduces a lag in the appearance of these signals, suggesting that GSH mediates SNP reduction by a different mechanism from that of Hb, although it too is inhibited by CN-.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMedDate not supplied

Management of acute sulfide poisoning. Effects of oxygen, thiosulfate, and nitrite.

Oxygen (100% at 1 atmosphere) did not protect mice against death from acute sulfide poisoning as compared with animals maintained under air at 1 atmosphere. Sodium thiosulfate had a small, but statistically significant (P less than .05) protective effect against death due to sodium sulfide, whether the mice were maintained under air or oxygen. Pretreatment with sodium nitrite, however, increased the acute intraperitoneal lethal dose for 50% survival of the group (LD50) of sodium sulfide 2.5 times. Neither oxygen, thiosulfate, nor the combination potentiated the protective effects of nitrite against sulfide poisoning. Antidotal effects of nitrite in acute sulfide poisoning were demonstrated in rats. The therapeutic efficacy of nitrite in acute poisoning is clearly superior to that of oxygen, which is the more widely recommended antidote.

Acute Disease↗