Administration Of Potassium Chloride Research Articles

Antagonism by endothelin of centrally mediated cardiovascular effects of potassium in anaesthetized rats.

1. We have previously demonstrated that cerebroventricular administration of potassium chloride (KCl) solutions produces dose-dependent reductions in blood pressure and heart rate in anaesthetized rats and that these effects are significantly attenuated by ouabain, a selective inhibitor of the Na(+)-pump. These observations suggest an important relationship between Na+,K(+)-ATPase activity in the central nervous system (CNS) and neural mechanisms involved in the regulation of cardiovascular function. 2. Since endothelin-1 (ET-1) has been shown to affect various ion transport mechanisms, including the Na(+)-pump, the present studies were conducted to evaluate whether this peptide would antagonize central effects of KCl. 3. The present studies demonstrate that cumulative doses of ET-1 (0.8-3.2 pmol, intracerebrolateral ventricular administration, i.c.v.) produced significant attenuation of hypotension and bradycardia produced by i.c.v. injections of KCl (0.75 mumol/5 microL, i.c.v.); in a separate series, a single high dose of ET-1 (4.0 pmol, i.c.v.) significantly reduced cardiovascular responses to various doses of KCl (0.375, 0.75, 1.25 mumol/5 microL, i.c.v.). 4. These studies suggest that endothelin may be involved in the regulation of arterial pressure since it is present in CNS and possesses a ouabain-like effect. However, it is not conclusive that ET-1 inhibits neuronal Na(+)-pump, since alternative mechanisms can also account for the efficacy of the peptide to antagonize central effects of potassium chloride.

Myotonic and repetitive discharges in hypokalemic myopathy associated with glycyrrhizin-induced hypochloremia

Electromyographic studies were performed in two patients with hypokalemic myopathy induced by the administration of glycyrrhizin, 270–273 mg per day for a period of two and eight months, respectively. Myotonic and repetitive discharges were observed when the serum chloride level fell below 90 mEq/l. Following the administration of potassium chloride, when the chloride level rose above 90 mEq/l, these discharges disappeared. These findings support the causal role of hypochloremia in myotonic discharges. A serum chloride level below 90 mEq/l appears to be critical in producing the myotonic and repetitive discharges.

Contrasting Effects of Various Potassium Salts on Renal Citrate Excretion*

Mechanisms for the citraturic response to potassium citrate treatment were sought by assessing renal citrate clearance and acid-base status after oral administration of potassium citrate, potassium bicarbonate, and potassium chloride. After 2 weeks of treatment of eight patients with stones at a dose of 80 meq/day, urinary citrate rose significantly from 2.5 +/- 1.6 mmol/day (no drug) to 5.1 +/- 1.7 mmol/day with potassium citrate and to 4.5 +/- 1.5 mmol/day with potassium bicarbonate (P less than 0.05), but did not change significantly with potassium chloride. Citrate clearance increased from 8.0 to 27.4 mL/min with potassium citrate and 25.8 mL/min with potassium bicarbonate (P less than 0.05), but did not increase with potassium chloride. Both potassium citrate and potassium bicarbonate significantly raised urinary bicarbonate and decreased urinary ammonium, titratable acid, and net acid excretion. Potassium chloride was without effect. Effects of potassium citrate on urinary citrate, citrate clearance, and acid-base status tended to be more prominent than those of potassium bicarbonate, but these changes were not significant. Thus, the citraturic action of potassium citrate is largely accountable for by provision of an alkali load. Potassium itself had no effect in the absence of potassium deficiency.

Hyperkalemic periodic paralysis in horses

Summary Eleven horses (3 mares, 7 stallions, 1 gelding) with clinical and biochemical evidence of hyperkalemic periodic paralysis were studied. Each horse had history of episodic weakness, muscular tremors, or collapse, which lasted for periods of a few minutes to hours. Diagnosis was based on hyperkalemia in association with a spontaneous episode of paralysis or by precipitation of an episode by oral administration of potassium chloride. Clinical and biochemical events were documented during spontaneous and induced episodes of muscular weakness. During episodes, electrocardiographic findings were consistent with hyperkalemia. Electromyography performed between episodes revealed fibrillation potentials and positive sharp waves, complex repetitive discharges, and myotonic discharges. Histologic changes in muscle biopsy specimens varied from no overt changes in some horses to vacuolation in type-2B fibers with mild degenerative changes in other horses. Electron microscopy of myofibers revealed dilatations of the sarcoplasmic reticulum. Analysis of blood samples taken serially during induced attacks in 5 horses revealed marked hyperkalemia (5.5 to 9.0 mEq/L), with normal acid-base status, hemoconcentration, and modest changes in muscle-derived enzymes. Close correlation (r2 = 0.882) between total plasma protein and plasma potassium concentrations was observed and indicated a shift of fluid out of the extracellular fluid compartment. Treatment of either spontaneous or induced episodes by iv administration of calcium, glucose, or bicarbonate resulted in rapid recovery. Dietary management or daily administration of acetazolamide effectively controlled episodes. An affected mare was bred to an affected stallion, and 3 affected offspring were produced by embryo transfer. Blood samples from another extended family of affected horses were analyzed for identification of a genetic marker. Blood typing, including 22 loci, revealed no linkage with erythrocytic or serum markers. Lymphocyte typing for equine lymphocytic antigen markers also failed to reveal any linkage.

A comparison of the effects of central ν peripheral bolus injections of potassium chloride on aortic root potassium concentrations in swine

Clinically relevant doses of potassium chloride (equivalent to 2 mEq/60 kg of body weight) were administered as rapid intravenous (IV) boluses to healthy halothane-anesthetized pigs. Potassium was given either peripherally through a standard IV ear catheter or centrally through the central venous port of a pulmonary artery catheter. Multiple injections were made in each pig, and cardiac output was varied by changing end-tidal halothane concentration. The aortic root potassium concentration was measured every three to six seconds for 90 seconds following potassium administration in each pig. Monitored variables included end-tidal halothane, end-tidal carbon dioxide, pulmonary artery pressure, mean arterial blood pressure, cardiac output, electrocardiogram, and temperature. Following both peripheral and central administration of potassium chloride, aortic root potassium increased significantly. However, the time required to achieve the peak aortic root potassium concentration was significantly less after central administration. In addition, the change in aortic root potassium concentration was greater following central administration compared with peripheral. The change in aortic root potassium concentration correlated inversely with cardiac output only after central, but not peripheral injection. Despite marked transient hyperkalemia in all animals, no electrocardiographic evidence of hyperkalemia could be demonstrated. It is concluded that small bolus doses of potassium chloride (2 mEq/60 kg) can be given safely either peripherally or centrally in normal, hemodynamically stable swine.

Effect of nimodipine on canine cerebrovascular responses to 5-hydroxytryptamine and potassium chloride after exposure to blood.

The stainless steel cannula inserting method was used to investigate the blocking effects of nimodipine on vascular responses to intraluminal administration of 5-hydroxytryptamine (5-HT) or potassium chloride (KCl) before and after application of abluminal blood containing thrombin in isolated and perfused canine basilar arteries. A transient elevation of perfusion pressure was observed initially, and during the course of the experiment the perfusion pressure gradually increased. Nimodipine significantly depressed both transient and prolonged changes of perfusion pressure. Dose-dependent vasoconstriction induced by 5-HT was significantly enhanced, while that evoked by KCl was significantly attenuated for up to 8 hours after the application of blood. Pretreatment with nimodipine inhibited vasoconstriction to 5-HT less effectively than to KCl both before and after application of blood. The proportion of the 5-HT-induced vasoconstriction, which was sensitive to nimodipine, was reduced after application of blood, while no such change was observed in the responses to KCl. It is suggested that the augmentation of cerebrovascular responses to 5-HT in the early stage of subarachnoid hemorrhage may be mediated mainly by changes in intracellular calcium utilization rather than by the increase of calcium influx through nimodipine-sensitive channels.

Thyrotoxic Periodic Paralysis in a Hispanic Man

Thyrotoxic periodic paralysis occurs much more frequently in Orientals than in whites, and has rarely been reported in patients of Hispanic descent. A 28-year-old Mexican man presented with acute onset of bilateral lower extremity weakness after ingestion of a large carbohydrate meal. Laboratory investigation revealed severe hypokalemia, with a serum potassium level of 2.1 mmol/L (2.1 mEq/L), and hyperthyroidism. Administration of potassium chloride resulted in normalization of the serum potassium level and resolution of muscle weakness. Treatment with propranolol, and subsequent restoration of a euthyroid state with iodine 131, was effective in preventing further episodes of paralysis. Thyrotoxic periodic paralysis, although rare, may occur in Hispanic patients, and should be considered in the differential diagnosis of muscle weakness in this population.

Hydrochloric acid infusion for treatment of metabolic alkalosis

The effects of hydrochloric acid (HCl) administration were studied in 15 critically ill patients whose metabolic alkalosis caused a significant alkalemia (pH 7.50 to 7.58) unresponsive to sodium and potassium chloride administration. Arterial pH and bicarbonate and chloride concentrations normalized after a 6- to 12-h mean infusion of 200 +/- 54 mmol of .25 N HCl. There were no deleterious vascular, hematologic, or metabolic side-effects. HCl administration was associated with an increase in mean PaO2 from 94 +/- 21 to 121 +/- 31 torr (p less than .001). This increase was comparable in patients breathing spontaneously and those treated with controlled mechanical ventilation, and was attributed at least in part to a decrease in pulmonary shunt. These results indicate that .25 N HCl, infused at the rate of 100 ml/h into the superior vena cava, can correct metabolic alkalosis safely and rapidly. The persistence of the beneficial effects of this treatment on arterial oxygenation remains to be confirmed.

Modulation of aldosterone secretion in frusemide-induced hypokalaemia.

To study the effect of hypokalaemia in the regulation of aldosterone secretion, repeated injections of frusemide (3 mg/kg) plus saline with or without simultaneous infusion of potassium chloride (1 mEq/kg/h) were performed in 24 conscious female rabbits for 7 h. Without potassium supplementation, the plasma renin activity (PRA) remained elevated throughout the study, while an initial increase (1 h to 3 h) in plasma aldosterone (PA) gradually returned to normal with reduction of the serum potassium. In rabbits on potassium supplements to prevent the development of hypokalaemia, both PRA and PA remained elevated. The incremental aldosterone response to administration of potassium chloride, angiotensin II or ACTH, was considerably smaller in potassium-depleted rabbits than in potassium-repleted rabbits. These results suggest that serum potassium modulates the effects of angiotensin II or ACTH on aldosterone secretion, and that a certain level of potassium is necessary to maintain the aldosterone secretory capacity of the adrenal gland.

Effect of dietary sodium intake on the metabolism of prostaglandins in the kidney in hypertensive patients

To investigate the role of renal prostaglandins (PGs) in the renal handling of sodium, urinary excretion of PGE, PGF 2α and PGF 2αMUM (main urinary metabolite of PGF 2α) were measured after various manipulations of dietary sodium intake in 8 hypertensive patients. A low sodium intake increased urinary excretion of PGF 2αMUM (p<0.05), but failed to change urinary excretion of PGE and PGF 2α. In contrast, a high sodium intake increased urinary excretion of PGE (p<0.01) and decreased urinary excretion of PGF 2αMUM (p<0.02). A low sodium intake decreased the ratio of urinary PGE/PGF 2αMUM and a high sodium increased it (both p<0.001). There was a significant positive correlation between urinary excretion of sodium and that of PGE (p<0.001). Additional oral administration of potassium chloride did not change urinary excretion of PGs. These results may suggest that dietary sodium intake may be one of the regulators of the metabolism of PGs in the kidney, supporting the hypothesis that renal PGE has a natriuretic action in humans.

Effects of nerve stimulation and of administration of noradrenaline or potassium chloride upon the release of prostaglandins, I2, E2, and F2 alpha from te perfused mesenteric arterial bed of the rabbit.

1 The release of prostaglandin I2 (PGI2), PGE2 and PGF2 alpha from the perfused mesenteric arterial bed of the rabbit was examined at rest, following nerve stimulation and following noradrenaline (NA) or potassium chloride (KCl) administration. 2 Stimulation of adrenergic nerves at 10 Hz caused a significant increase in the release of both PGI2, (assayed in terms of 6-oxo-PGF1 alpha) and PGE2 but a significant decrease in the release of PGF2 alpha. 3 Exogenous Na (2 micrograms) increased the output of PGI2 and PGE2 but left the output of PGF2 alpha unaffected. 4 KCl (15 mg) significantly increased the output of PGF2 alpha but left the output of PGF2 unaffected. 5 It is concluded that PGI2 and PGE2 output from the mesenteric arterial bed of the rabbit increases following stimulation of adrenoceptors. The sympathetic nervous system may therefore modulate PGI2/platelet interaction. 6 Prostaglandins released from the blood vessels by sympathetic nerve stimulation may also modulate adrenergic transmission to the blood vessels.

塩化カリウムの経口投与がめん羊の血漿中マグネシウム,インスリン,グルコース濃度に及ぼす影響

塩化カリウムの経口投与がめん羊の血漿中マグネシウム,インスリン,グルコース濃度に及ぼす影響

Contrasting reflexes evoked by chemical activation of cardiac afferent nerves.

Afferent neurons within cardiac sympathetic nerves can reflexly excite central sympathetic outflow. However, their contribution to cardiovascular control remains unclear because they are potentially opposed by inhibitory reflexes of cardiac vagal or arterial baroreceptor afferent origin. It was considered that sympathetically mediated, excitatory responses might be more prominent when initiated by chemical stimulation. In chloralose-anesthetized, vagotomized, sinoaortic-denervated cats, epicardial or intracoronary administration of bradykinin or potassium chloride evoked renal nerve excitation and pressor responses mediated by cardiac sympathetic afferent nerves. When upper thoracic sympathetic nerves were severed, and vagal afferent nerves remained intact, bradykinin and potassium chloride produced inhibition of renal nerve activity and depressor responses. When sympathetic and vagal components of cardiac innervation remained intact, these substances produced excitation, inhibition, or no change in sympathetic outflow. Excitation occurred as often as inhibition. A similar pattern was observed when arterial baroreceptor nerves remained intact. These data illustrate that cardiac sympathetic afferent neurons can have significant excitatory influences on the cardiovascular system in spite of opposition by inhibitory afferent groups.

Effects of social isolation on memory formation

Memory formation for a single-trial passive avoidance task in day-old chicks was inhibited by intracranial administration of potassium chloride, ouabain, or cycloheximide when the chicks were trained in pairs. If chicks were isolated during training the onset of amnesia resulting from potassium chloride or ouabain was delayed, while amnesia due to cycloheximide was prevented. It is suggested that the counteractive effect of isolation on cycloheximide-induced amnesia was due to isolation extending some phase of memory preceding the cycloheximide-sensitive protein synthesis-dependent phase, until cycloheximide inhibition of protein synthesis starts to dissipate. A possible mechanism is the release of noradrenaline associated with isolation-induced changes in hormonal levels. A similar mechanism may underlie the delay of onset of ouabain-induced amnesia. The mechanism for the delay of potassium chloride-induced amnesia as a result of isolation is not clear.

Bartter's syndrome with normal urinary excretion of prostaglandin E: therapeutic effects of propranolol, spironolactone, indomethacin and potassium chloride.

Urinary excretion of prostaglandin E (PGE) in 8 patients with Bartter's syndrome measured by the radioimmunoassay method was not augmented over the normal values. In one of them, urinary excretion of sodium, potassium, chloride and PGE, serum sodium, potassium and chloride, plasma renin activity and plasma aldosterone concentration were studied before and after the administration of propranolol, spironolactone, indomethacin and potassium chloride. Neither propranolol nor spironolactone affected any of these parameters. Indomethacin promptly reduced urinary excretion of sodium, potassium, chloride and PGE, and markedly suppressed the renin-aldosterone system. Serum potassium was elevated, but remained still in hypokalemic range. Potassium chloride was most effective in raising the serum potassium level during the first 4 weeks of administration. These results suggest that overproduction of renal PGs is not the primary cause of Bartter's syndrome, and that the renal potassium wastage is one of the etiological factors in this syndrome. It has also been suggested that hyperreninemia in this syndrome was associated in some way with renal PGs, not PGE but other series of PGs.

Regulation of urinary prostaglandins in Bartter's syndrome

Enhanced prostaglandin production, possibly stimulated by hypokalemia, may mediate the manifestations of Bartter's syndrome. To investigate the cause of increased urinary prostaglandin excretion, we measured urinary immunoreactive prostaglandin E (iPGE) during the oral administration of potassium and the parenteral administration of magnesium, and during water restriction and oral water loading in two subjects with Bartter's syndrome. In one patient (Case 1), iPGE was 0.91 μg/day (normal 0.50 ± 0.20 μg/day, SD). Following the administration of indomethacin, 200 mg/day, iPGE, plasma renin activity (PRA), plasma aldosterone and angiotensin pressor sensitivity returned to normal but serum potassium did not. The oral administration of potassium citrate, acetate, bicarbonate, (Potassium Triplex), 240 meq/day for four days, increased iPGE to 2:3 μg/day and PRA from 47 to 73 ng/ml/hour (normal 1 to 3 ng/ml/hour). In the second patient (Case 2), iPGE was 1.4 μg/day. Therapy with ibuprofen, 1,600 mg/day, and indomethacin, 200 mg/day, again resulted in the return of iPGE, PRA, plasma aldosterone and angiotensin pressor sensitivity to normal, but serum potassium increased only transiently from 2.1 to 3.1 meq/liter. The oral administration of potassium chloride, 240 meq/day for four days, increased potassium to 3.0 meq/liter and increased iPGE to 8.0 μg/day. The administration of potassium triplex, 240 meq/day for four more days, further increased potassium to 3.4 meq/liter and iPGE to 9.3 μg/day, and PRA increased from 7.1 to 13.8 ng/ml/hour. This patient (Case 2) was hypomagnesemic (1.0 meq/liter, normal 1.5 to 2.4 meq/liter), and the intravenous administration of magnesium transiently increased iPGE by 15-fold. Following water restriction iPGE returned to normal (0.35 μg/day), and water loading increased iPGE to 3.0 μg/day, but neither maneuver altered PRA, aldosterone or serum electrolytes. The findings that potassium administration failed to reduce iPGE excretion and that water restriction renormalized iPGE excretion suggest that hypokalemia is not the primary stimulus to prostaglandin excretion.

Impaired renal tubular potassium secretion in sickle cell disease.

We examined renal tubular function in six patients with sickle cell hemoglobin. All had normal inulin and para-aminohippurate clearances and impaired urinary concentrating and acidifying abilities. After intravenous potassium chloride administration, maximum excretion of potassium (U,V) was significantly lower in sickle cell patients than in control subjects, and the percentage of potassium load excreted in 5 h was markedly reduced. Urinary potassium excretion after sodium sulfate infusion was also markedly reduced in sickle cell patients compared to control subjects. After 40 mg of oral furosemide, U,V was also diminished in sickle cell patients. Plasma aldosterone response to ACTH and intravenous potassium was similar to that of control subjects. Plasma renin activity increased normally after volume contraction. We conclude that sickle cell patients have a defect in their ability to excrete an acute potassium load that cannot be attributed to abnormal renin or aldosterone secretion. Overall potassium homeostasis is maintained by extrarenal mechanisms during acute potassium loading.

Factors related to potassium transport in chronic stable renal disease in man.

1. The inter-relationships between plasma aldosterone, plasma renin activity, potassium excretion and plasma potassium were evaluated in subjects with normal and decreased glomerular filtration rate. 2. In seven studies of healthy control subjects and 12 studies of patients with renal disease, daily urine collections, plasma aldosterone and plasma renin activity were measured on a free diet for 5–10 days and subsequently during the addition of 50 mmol of potassium chloride daily for 5 days. Plasma aldosterone was also measured in 22 hospital patients with normal glomerular filtration rate and 24 patients with reduced glomerular filtration rate. 3. Plasma aldosterone was similar in base-line conditions in patients with or without renal disease and increased similarly during the administration of potassium chloride, suggesting that potassium excretion in patients with reduced glomerular filtration rate probably does not depend primarily upon increased aldosterone. 4. Plasma renin activity increased similarly in control subjects and patients with renal disease during the administration of 50 mmol of potassium chloride/day, but plasma renin activity did not increase when 100 mmol of potassium chloride/day was given to control subjects. 5. With the administration of 50 mmol of potassium chloride/day mean daily potassium excretion increased similarly in control subjects and patients with renal disease but plasma potassium increased significantly (4·7 to 5·4 mmol/l) only in patients with renal disease, suggesting that their uptake of potassium into cells was impaired.

Digoxin, whole body potassium and the electrocardiogram.

Previous studies have shown a significant linear relationship between the PTQ-index (a combination function of the PR-interval, corrected QT-time and T-wave depression in the ECG) and serum digoxin level in chronically treated patients. The relationship was confirmed in the present study and it was shown that it could be changed by concomitant administration of potassium chloride or furosemide, and that there was marked interindividual variation in response. An inverse linear relationship between PTQ-index and whole body potassium was found during chronic administration of a constant daily dose of digoxin, but no such relationship was found for serum potassium.

Healing of burn wounds depending on the dose and time of potassium chloride administration

Healing of burn wounds depending on the dose and time of potassium chloride administration