Effects of 4-dimethylaminophenol,Co2EDTA,or NaNO2 on cerebral blood flow and sinus blood homeostasis of dogs in connection with acute cyanide poisoning

The effects of the cyanide antidotes DMAP, Co₂EDTA, and NaNO₂ on cerebral blood flow (CBF) and cerebral blood gases were investigated in connection with acute poisoning of dogs by cyanide. The substances were injected intravenously. Local CBF as measured with thermocouples in the cingulum increased by 100–200% after a non-lethal dose of KCN (1 mg/kg) and by 50% after injection of NaNO₂ (15 mg/kg), that oxidized some 20% of the total hemoglobin to ferrihemoglobin. Co₂EDTA (10 mg/kg) induced a decrease in local CBF of 30% and in brain temperature of 0.5°C. The temperature diminished also after poisoning by KCN, but it rose by 0.15°C after the administration of NaNO₂. Local CBF and sinus sagittalis blood flow increased by 60–160% for about 15 min, and the brain temperature decreased by 0.4–0.5°C when DMAP (3.25 mg/kg) or Co₂EDTA (15 mg/kg) was injected 1 min after poisoning by cyanide (4 mg/kg), a dose that always caused respiratory arrest. Immediately after injection of DMAP the brain temperature rose transiently by 0.1–0.2°C. Co₂EDTA did not exert such an effect. In the sinus sagittalis blood of artificially ventilated animals pCO₂ decreased rapidly by 10–20 mmHg after poisoning and approached the initial level after treatment with DMAP or Co₂EDTA. The highest value of pO₂ was about 80 mmHg and 50 mmHg after injection of DMAP and Co₂EDTA, respectively; thereafter pO₂ declined to 20 mmHg or 40 mmHg at 20 min. The lactate concentration increased by 60–70% without tendency to return to normal.     

Effects of amyl nitrite on circulation,respiration and blood homoeostasis in cyanide poisoning

The effects of intravenously (i.v.) administered or inhaled amyl nitrite (AN) were followed under chloralose anaesthesia in intact and cyanide-poisoned, spontaneously breathing beagles. The i.v. doses of AN were 0.03 and 0.15 mmol/kg and the i.v. dose of KCN was 0.06 mmol/kg. AN was inhaled in a closed system at 0.15 mmol/kg without previous poisoning and, in addition, at 0.074 mmol/kg (two ampoules at 0.3 ml AN) during artificial ventilation after poisoning with 0.045 mmol KCN/kg i.v., Mean arterial pressure decreased by 15 and 40 mmHg, respectively, after i.v. injection of AN, associated with bradycardia and lowered peripheral blood flow. Respiratory minute volume rose by 65% with the higher dose. Arterial pO₂ decreased by 20 mmHg while pCO₂ rose by 6 mmHg. Within 30 min of injection, these changes were only partially reversible. Similar results were obtained following inhalation of AN in a closed system. Lactic acidosis and lowering of pH were produced by the i.v. route, but not by inhalation. Total haemoglobin increased. The lethality of KCN was abolished with AN doses that produced 10–30% ferrihaemoglobin. Artificial ventilation and simultaneous inhalation of AN after poisoning with lethal doses of KCN turned out to be ineffective therapeutic measures. The findings are compared with those of other papers dealing with cyanide poisoning and AN. It is pointed out that, for the present, there is no experimental proof for another antidotal mechanism of action of AN than ferrihaemoglobin formation.     

Circulation,respiration, and blood homeostasis in cyanide-poisoned dogs after treatment with 4-dimethylaminophenol or cobalt compounds

The effects of intravenously injected 4-dimethylaminophenol-HCl (DMAP), Co₂EDTA, and Co(histidine)₂ on the survival rate and several physiological parameters were studied on dogs after acute intravenous poisoning with the double lethal dose of potassium cyanide.All dogs survived when the antidotes were administered 1 min after poisoning. When the therapy began 4 min after poisoning more dogs were rescued in the DMAP group than in the cobalt groups. DMAP, Co₂EDTA, and Co(histidine)₂ restored circulation and respiration of the surviving animals in a similar manner.The increase in the plasma concentrations of glucose and lactate was much higher in the Co₂EDTA group than in the DMAP group. The injection of Co₂EDTA produced a sharp rise in the lactate-to-pyruvate ratio. The lactate-to-pyruvate ratio stayed unchanged for some 15 min after injection of DMAP before also rising. The total dose of KCN (4 mg/kg) was bound to the ferrihemoglobin formed by DMAP. The arterial pO₂ increase, caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin, was less when the cyanide could act on the tissues for a longer period of time before the therapy with DMAP began.DMAP is more appropriate for the therapy of cyanide poisoning than Co₂EDTA, since the latter adds its inhibitory effects on the metablism to those of cyanide.     

Renal and femoral venous blood flows are regulated by different mechanisms dependent on α-adrenergic receptor subtypes and nitric oxide in anesthetized rats

Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injection of different doses of vasoactive drugs which act in arterial vascular beds. Anesthetized adult male Wistar rats underwent to right femoral artery and vein cannulation for hemodynamic recordings and infusion of drugs. Doppler flow probes were placed around the left renal artery and vein, and left femoral artery and vein to evaluate the changes in flood flow. Phenylephrine (PHE) injection (α₁-adrenergic receptor agonist) elicited vasoconstriction in all arteries and veins. Intravenous prazosin (PZS) (1 mg/kg, α₁-adrenergic receptor blocker) caused renal artery vasodilation, but not in the other beds. Vasoconstrictor effect of PHE was abolished by PZS in all vascular beds, except in femoral vein. Phentolamine (PTL) injection (1 mg/kg, α₁/α₂-adrenergic receptor blocker) produced renal artery vasodilation with no change in other beds. After PTL, the vasoconstriction evoked by PHE was abolished in all vascular beds. Sodium Nitroprusside (SNP), a nitric oxide donor, elicited vasodilation in all beds, and after PTL but not post PZS injection, SNP enhanced the vasodilatory effect in femoral vein. Our findings suggest that the vasoconstriction in renal and femoral veins is mediated by different subtypes of α-adrenoceptors. The nitric oxide-dependent vasodilation in femoral vein enhances when α₂-adrenoceptors are not under stimulation, but not in the other vascular beds investigated.     

Cardiopulmonary effects of cannabidiol in anesthetized mongrel dogs.

Seventeen artificially ventilated, pentobarbital-anesthetized dogs were treated with 0.5 mg/kg of cannabidiol (CBD), 1.0 mg/kg CBD, or control vehicle (50% propylene glycol) by iv injection. Lung resistance (R_L), lung compliance (C_L), heart rate (HR), mean systemic arterial blood pressure (BP), cardiac output (C.O.) and arterial blood pO₂, pCO₂, and pH were measured. The higher dose of CBD was followed by a persistent decrease in C_L and the lower dose by a transitory decrease. Neither dose of CBD was followed by significant alteration in R_L, arterial blood pO₂, pCO₂, or pH. Both groups of dogs treated with CBD showed a trend toward increased HR and decreased C.O.     

Acute phencyclidine poisoning in the unanesthetized dog: Pathophysiologic profile of acute lethality

Phencyclidine HCl was infused intravenously (1.0 mg/kg/min) to unanesthetized mongrel dogs until death. All animals experienced tonic-clonic convulsions (mean convulsive dose: 4.7± 0.3 mg/kg) which lasted until shortly before death (mean lethal dose: 49.8 ± 2.5 mg/kg). Significant increases in heart rate, arterial blood pressures, cardiac output, body temperature, and arterial pCO₂ were observed in all animals. Significant reductions from pre-drug control values were observed in total peripheral resistance, arterial pH, arterial pO₂, and respiratory minute volume. Blood lactate, oxygen uptake, and plasma glucose levels rose to values significantly higher than pre-drug control values then declined during the latter phase of the experiment, glucose levels decreased to final values lower than control. Animals appeared to die of primary respiratory failure, which was exacerbated by hyperthermia, and which resulted in final cardiovascular collapse.     

Effects of intravenous infusion of ouabain on respiration

Effect of continuous infusion of ouabain (2 μg/kg/min) on respiration and on pH, pCO₂ and electrolytes in arterial plasma and CSF were investigated in anesthetized dogs. In most experimental animals, hyperventilation developed about 15 min after ouabain infusion, and cardiac arrhythmia was observed 5–10 min later. During the hyperventilatory phase, arterial blood pH was increased and pCO₂ decreased. CSF pH revealed changes paralleling those in arterial blood. However, the pH values of CSF were lower than those of arterial blood. Arterial plasma potassium concentration was increased after ouabain infusion, but CSF potassium concentration was not affected. Concentrations of sodium and chloride in both plasma and CSF did not alter during the experiment. Results of this study suggest that hyperventilation after ouabain infusion is not due to the changes of chemical constituent in CSF.     

Effect of increased cardiac output on liver blood flow,oxygen exchange and metabolic rate during longterm endotoxin-induced shock in pigs

1. We investigated hepatic blood flow, O₂ exchange and metabolism in porcine endotoxic shock (Control, n=8; Endotoxin, n=10) with administration of hydroxyethylstarch to maintain arterial pressure (MAP)>60 mmHg.
2. Before and 12, 18 and 24 h after starting continuous i.v. endotoxin we measured portal venous and hepatic arterial blood flow, intracapillary haemoglobin O₂ saturation (Hb-O₂%) of the liver surface and arterial, portal and hepatic venous lactate, pyruvate, glyercol and alanine concentrations. Glucose production rate was derived from the plasma isotope enrichment during infusion of [6,6-²H₂]-glucose.
3. Despite a sustained 50% increase in cardiac output endotoxin caused a progressive, significant fall in MAP. Liver blood flow significantly increased, but endotoxin affected neither hepatic O₂ delivery and uptake nor mean intracapillary Hb-O₂% and Hb-O₂% frequency distributions.
4. Endotoxin nearly doubled endogenous glucose production rate while hepatic lactate, alanine and glycerol uptake rates progressively decreased significantly. The lactate uptake rate even became negative (P<0.05 vs Control). Endotoxin caused portal and hepatic venous pH to fall significantly concomitant with significantly increased arterial, portal and hepatic venous lactate/pyruvate ratios.
5. During endotoxic shock increased cardiac output achieved by colloid infusion maintained elevated liver blood flow and thereby macro- and microcirculatory O₂ supply. Glucose production rate nearly doubled with complete dissociation of hepatic uptake of glucogenic precursors and glucose release. Despite well-preserved capillary oxygenation increased lactate/pyruvate ratios reflecting impaired cytosolic redox state suggested deranged liver energy balance, possibly due to the O₂ requirements of gluconeogenesis.

     

MICROCYSTIN-LR DECREASES HEPATIC AND RENAL PERFUSION,AND CAUSES CIRCULATORY SHOCK,SEVERE HYPOGLYCEMIA,AND TERMINAL HYPERKALEMIA IN INTRAVASCULARLY DOSED SWINE

Cross-bred, anesthetized female swine were given intravascularly a lethal (72 µg/kg; n = 6) or toxic-sublethal (25 µg/kg; n = 6) dose of microcystin-LR (MCLR), from Microcystis aeruginosa, or the vehicle (n = 4). At the high dose, from 12 to 18 min after administration, central venous pressure and hepatic perfusion were significantly lower, and shortly thereafter, portal venous pressure was significantly higher and aortic mean pressure was significantly lower than controls. By 45 min postdosing, serum bile acids, lactate, potassium, and total bilirubin, as well as blood pO₂, were significantly higher, while hematocrit, platelet count, and blood bicarbonate, pCO₂, and base excess were significantly lower than controls. By 90 min, serum arginase, urea nitrogen, inorganic phosphorus, and creatinine were significantly higher, while glucose and blood pH were significantly     

Effect of 3-aminopicolinic acid on renal ammoniagenesis in the rat

The effects of 3-aminopicolinate, a known activator of phosphoenolpyruvate carboxykinase (PEPCK), on renal ammoniagenesis were studied in normal rats and in rats allowed to recover for 2 days from ammonium chloride induced metabolic acidosis. The administration of 3-aminopicolinate (5 mg/100 g body wt) did not affect glomerular filtration rate, renal blood flow, arterial blood pH, pO₂ or pCO₂ in either normal or “recovered” rats. A significant increase in renal glutamine extraction and total ammonia production was observed in recovered rats, but not in normal rats, after 3-aminopicolinate treatment. Although this compound activated partially purified renal PEPCK, the profile of metabolites from freeze-clamped kidneys was not consistent with an activation of the enzyme. Thus, the enhancement of renal ammoniagenesis in vivo by 3-aminopicolinate was probably due to an effect other than activation of PEPCK.     

Biochemical indexes accompanying functional decay of working muscle in hyperbaric helium-oxygen-carbon dioxide environments

Innervated rat diaphragm tissues incubated in bicarbonate buffers saturated at high pressure with He/O₂/CO₂ gas mixtures have been subjected to isometric work stresses. The muscles have then been analyzed for content of creatine phosphate (CP), total creatine (TC), adenosine triphosphate, glycogen and lactate, as indicators of biochemical state. At 15.8–18 atm total pressure and at adequate pCO₂ (0.05 atm), pO₂ (≥0.95 atm) and pH (approx. 7.4), the CP content of the stressed tissue rises by a factor of about 2 above control, the TC content falls to about 80% of control and remains constant, and the remaining biochemical indexes are essentially unchanged. At lower pO₂ (0.22 atm) the initial increments in CP decay rapidly with extended incubation/work time, and a rise in tissue lactate is noted. Very high levels of pCO₂ (0.54–0.90 atm) in the hyperbaric gas phase accompanied by drops in buffer pH also lead to transient rise and then decay in the CP content of the muscle. At moderate pCO₂ levels (0.016-0.16 atm) the hyperbarically worked muscle is functionally and biochemically stable to changes in pCO₂ and buffer bicarbonate concentration, within the buffer pH range 7.4–6.9, but loses twitch function capability as the pH falls to 6.4 and below. These findings are interpreted in terms of tissue responses to pressure and work stresses involving anoxia and the direct action of increased acidity on the tissue.     

Arterial-venous blood alcohol concentration gradients

Arterial and venous blood alcohol concentration (BAC)-time courses were completely defined in the peripheral circulations, both during and after the constant rate infusions of ethanol via the cephalic vein or hepatic artery in the dog. These BAC data were characterized by the following trends. (1) A much faster rise in the blood alcohol curve, as well as a higher peak BAC was found using the shorter infusion time. (2) During infusion, the alcohol concentration was higher in arterial or arterialized blood than venous blood when infusion was via the cephalic vein. (3) Peak BAC was higher in the femoral artery than the femoral vein whether infusion was via the cephalic vein or hepatic artery. (4) Peak BAC was higher in the hepatic artery or portal vein than the hepatic vein when infusion was via the cephalic vein. When administration was directly into the liver, the peak BAC in the hepatic vein was higher than the portal vein. (5) After infusion ceased, there was an arterial-venous inversion; peripheral arterial ethanol concentrations were significantly less (p<0.001)than corresponding venous concentrations; with cephalic vein administration, a hepatic vein-portal crossover was observed, the reverse being true when ethanol was administered via the hepatic artery. In either case, the BAC was observed to be higher in the hepatic artery than the portal vein or hepatic vein throughout the sampling period. (6) BAC was observed to be higher for the same sampling times at the respective sites when ethanol was administered directly into the liver. While the methodology in this study is prohibitive for human experimentation, correlations may be extended to man. The elaboration of the arterial-venous concentration differences for ethanol should prove beneficial in revealing the relationships among the doses of alcohol, the circulating blood ethanol concentrations, and physiological and psychomotor test parameters in man.This work was supported in part by a grant from The University of Connecticut Research Foundation.Abstracted in part from a dissertation by J. L. Rheingold submitted to The University of Connecticut in partial fulfillment of the Doctor of Philosophy degree requirements.     

Significance of acid base status,respiration, Na+-and K+-concentrations and plasma glucose for acute toxicity of TRIS (hydroxymethyl-)aminomethane in rats

The mechanism of acute toxicity of TRIS-buffer was investigated in pentobarbital-anaesthetized Wistar-rats. An infusion of 0.5 mmol/kg · min TRIS, either pH 10.9 or pH 7.4, was tolerated for 60–70 min before death. TRIS concentration in plasma increased linearly to 53.7±9.09 mmol/l after 60 min (¯x±s_x), indicating slow uptake of the drug into tissues. Blood pressure, heart rate, ECG and Na⁺- and K⁺-concentrations in plasma and erythrocytes were not influenced by TRIS. A small rise of plasma osmolarity by 39±4.7 mosmol/l after 30 min seemed unimportant for toxicity. With alkaline TRIS a metabolic alkalosis developed and the compensatory arrest of ventilation caused a sudden drop of arterial pO₂ to 48±9 mm Hg after 50 min. A similar, though more gradual, decline of pO₂ was observed with neutralized TRIS without concomitant changes of acid-base status. Artificially ventilated rats, with constant arterial pO₂, tolerated an infusion of neutralized TRIS for at least 90 min. With TRIS of either pH plasma glucose concentration was nearly halved after 30 min. Addition of glucose (50 mg/ml) to the infusion neither prevented this effect nor increased the survival time. From these results we conclude that the main lethal action of TRIS is a depression of ventilation that, in the case of neutralized TRIS, may be related to an intracellular alkalosis.     

Effects of carvedilol on cerebral blood flow and its autoregulation in previous stroke patients with hypertension

We studied the effects of oral carvedilol (20 mg/day) on cerebral blood flow (CBF) and CBF autoregulation in ten previous stroke patients with hypertension. Measurement of CBF was done by the argon inhalation method. CBF autoregulation was also studied by the (A-V)O₂ method after stepwise reduction in systemic blood pressure. After 1 week of carvedilol administration, the mean arterial blood pressure showed an 18% decrease, with no significant changes in CBF, CBF autoregulation, or other cerebral circulation parameters. From these findings, it can be said that carvedilol is a potent anti-hypertensive agent that does not affect cerebral circulation parameters.     

Verapamil enhances brain function tolerance against severe hypoxia without enhancing cerebral blood flow in the rat

In spontaneously breathing, lightly anesthetized rats with chronically implanted epicortical electrodes, tolerance times were measured from onset of progressive hypoxia, anoxia or decapitation, until ultimate apnea and subsequent cessation of brain electrical activities. Arterial and cerebrovenous blood was collected initially and during progressive hypoxia, starting 5 min after intravenous verapamil or NaCl (controls). Verapamil induced significant hyperpnea, arterial alkalosis, slight bradycardia and brain venous acidosis. During progressive hypoxia, hyperpnea persisted and heart rate remained stable for a longer period than in controls. Tolerance times were significantly prolonged. Time courses of arterial PO2 and PCO2 and of cerebrovenous PO2 were hardly influenced. However, arterial alkalosis and brain venous acidosis became highly significant versus control courses. This raised the O2 saturation in arterial and O2 extraction in cerebral venous blood. Sinus sagittalis puncture needle outflow (as a measure of CBF) tended to be below the control rat courses throughout. This led to a higher O2 supply to the brain in verapamil rats only during severe hypoxia. Verapamil did not prolong tolerance times in anoxia or ischemia. It is concluded that the verapamil-induced increase of tolerance to hypoxia is primarily due to the acid-base (Bohr) effects observed in response to hyperpnea and prolonged cerebral metabolic activity.     

Indirect sympathomimetic agents and cerebral blood flow and metabolism.

The effects upon cerebral blood flow (CBF) and oxygen consumption (CMRO2) of the infusion into the internal carotid artery of tyramine and amphetamine were investigated in 24 anaesthetized baboons. The infusion of tyramine was without effect upon CBF and CMRO2 at normocapnia, even at concentrations which significantly raised arterial blood pressure. However, marked reductions in cerebral blood flow were noted at hypercapnia during the infusion of tyramine (2.5 X 10(-7) moles/kg/min). The infusion of amphetamine (7.5 X 10(-10) moles/kg/min) resulted in significant increases in CBF (32%) and CMRO2 (37%). However, an increased concentration of amphetamine (2.5 X 10(-7) moles/kg/min) significantly reduced CBF (22%) and CMRO2 (20%). It is suggested that amphetamine, by virtue of being able to cross the blood--brain barrier and interact with the cerebral monoamine systems, is able to influence cerebral blood flow by inducing changes in cerebral metabolism, and that the minimal reactivity of the cerebral circulation to the infusion of tyramine is the result of the inability of tyramine to cross the blood--brain barrier.     

Liver blood flow measurement in the rat the electromagnetic versus the microsphere and the clearance methods

This study describes the simultaneous measurement of hepatic arterial and portal venous blood flow in the pentobarbital anesthetized rat by means of electro-magnetic flowmeters. Hepatic arterial flow was 0.21 ± 0.02 mL/min/g liver, and portal venous flow was 1.53 ± 0.19 mL/min/g liver (n = 20). Flows remained stable for more than 3 hr. A clear advantage of the electromagnetic technique is that it allows the continuous simultaneous separate measurement of hepatic arterial and portal venous blood flow. Simultaneous measurement of hepatic blood flow by the electromagnetic method and the microsphere method yielded almost identical results. Adenosine infusion (100 μg/min) did not affect hepatic blood flow measured electromagnetically nor via the microsphere technique. The suitability of indocyanine green (ICG) as an indicator of hepatic blood flow was evaluated by comparing the ICG clearance at steady-state conditions to the values of liver flow obtained by direct electromagnetic measurement. ICG clearance was only 30% of the electromagnetically measured blood flow. These data strongly suggest that ICG clearance does not reflect liver flow in the rat.Intravenous infusion of the vasoactive agents phenylephrine (2, 4, 10 μg/min during 5 min) and adenosine (20, 40, 200 μg/min) did not affect portal venous nor hepatic arterial flow, measured by the electromagnetic method, although brisk effects on mean arterial blood pressure were observed. This suggests autoregulatory responses of the hepatic vascular bed.The data suggest that electromagnetic flowmeters may be used to measure portal venous and hepatic arterial flow simultaneously in anesthetized rats. The continuous measurement of both flows simultaneously offers a clear advantage over other methods of hepatic flow measurement.     

Effects of propranolol and tertatolol on cardiac output and regional blood flows in the rat

Tertatolol (±)-1-(tert-butylamino)-3(thiochroman-8-yloxy)-2-propanol, hydrochloride is a noncardioselective beta-adrenoceptor antagonist that is devoid of partial agonist activity. The effects of this substance on regional blood flows (RBF) in the rat were studied in comparison with those of propranolol. Rats were artificially ventilated with a mixture of 70% nitrous oxide and 30% oxygen. RBFs were assessed using radioactive microspheres of 15 ± 5 μm diameter, injected into the left ventricle. An initial injection of microspheres (⁵⁷Co) was carried out 5 min before intravenous administration of propranolol (500 μg·kg^?1), tertatolol (50 μg·kg^?1) or physiological serum. A second microsphere administration (¹¹³Tin) was performed 10 min after injection of the test substances. The animals were sacrificed 3 min after the second injection of microspheres. Neither modifications in arterial pH, pO₂, pCO₂, nor in the arterial blood pressure were observed with either propranolol or tertatolol. In contrast, a decrease in heart rate was observed (?22% with propranolol and ?14% with tertatolol). The reduction in cardiac output was 33% with propranolol and 29% with tertatolol. Propranolol reduced blood flow to the majority of structures and organs examined; such a reduction was 39% in the cerebral hemispheres, 31% in the brainstems and of greater than 20% in all the renal zones studied. With tertatolol, no significant modifications of RBF were observed in any of the cortical or medullary renal zones investigated, nor in any of the cerebral areas studied; only in several colonic areas and in the skin of the abdomen and back, were reductions in RBF observed. These results demonstrate a difference in the effects of these two substances on renal and cerebral haemodynamics.     

CEREBROVASCULAR AND METABOLIC EFFECTS OF BRADYKININ, ATP AND HYPERCAPNIA IN THE GOAT

1. Cerebral blood flow (CBF) and cerebral O₂ metabolism (CMRO₂) changes were measured in these studies during treatment with three reputed cerebral vasodilators: bradykinin, adenosine triphosphate (ATP) and increased arterial Pco₂. 2. Intracerebrovascular bradykinin infusions increased CMRO₂ and CBF to a similar degree. Intramaxillary ATP infusions increased CBF to an extent greater than that required for increases seen in CMRO₂. Hypercapnia increased CBF without a significant change in CMRO₂. 3. Results suggest that increases in cerebral metabolism may mediate most, some and none of the cerebrovascular changes produced by bradykinin, ATP or hypercapnia, respectively.     

Effects of 4-dimethylaminophenol and Co2EDTA on circulation,respiration, and blood homeostasis in dogs

The effects of intravenously injected 4-dimethylaminophenol and Co₂EDTA on peripheral circulation, respiration, acid-base balance, and several other physiological and biochemical parameters were studied on dogs. DMAP increased the respiratory minute volume and mean arterial pressure, diminished the lactate-to-pyruvate ratio, and induced an increase in arterial oxygen pressure caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin.A study in vitro of the fate of the oxygen during the reaction between DMAP and oxyhemoglobin showed that only 30–40% of the oxygen released by the formation of ferrihemoglobin appeared in the gas phase.Co₂EDTA caused circulatory depression, hyperventilation, and metabolic acidosis resulting in a decrease in base-excess and pH. The concentrations of lactate, pyruvate, potassium, and urea nitrogen and the hemoglobin content were increased by Co₂EDTA. The side effects of Co₂EDTA in therapeutic doses were more serious than those of DMAP. Thus the latter is superior in the therapy of cyanide poisoning, all the more since it detoxifies more cyanide.