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Biomedical subjects

D Malcolm

Publications and source records attributed to D Malcolm.

At least 19 recordsLinked to original sources
PubMed1992

Diaspirin cross-linked hemoglobin solution as a resuscitative fluid following severe hemorrhage in the rat.

The effect of diaspirin cross-linked hemoglobin (DCLHb) on mean arterial pressure (MAP) and heart rate (HR) was compared to Ringer's lactate (RL) and shed blood in a 70% lethal model of hemorrhage (35 cc/kg blood loss) in conscious rats. All animals resuscitated with DCLHb regardless of dose (17.5 and 35 cc/kg) and concentration (7% and 10% solution) exhibited complete restoration of MAP and HR which was maintained for at least 5 hrs. Hemodynamic responses in DCLHb-treated animals were not significantly different from 35 cc/kg blood-treated animals. In RL (105 cc/kg) treated animals the MAP was restored to 60-70% of baseline. 24 hr survival in animals resuscitated with fluids ranged between 88-100% and was not significantly different between treatment groups.

Animals↗
PubMed1992

Dissociation between prostaglandin levels and blood flow to the retina and choroid in the newborn pig after nonsteroidal antiinflammatory drugs.

To assess whether prostaglandins contribute to the control of basal retinal and choroidal hemodynamics, retinal (RBF) and choroidal blood flow (ChBF) were measured by a microsphere technique in 1- to 4-day-old pigs before and after (at 20 and 60 min) administration of indomethacin (0.3 mg/kg, n = 6 or 10 mg/kg, n = 5), ibuprofen (40 mg/kg, n = 7), naproxen (20 mg/kg, n = 5) or vehicle (n = 8). In 40 other animals, PGF2 alpha, PGE2, and 6-keto-PGF1 alpha were measured in the retina and choroid at times corresponding to blood flow measurements. Mean arterial blood pressure and blood gases and pH were not altered by any of the agents. Except for the lower dose of indomethacin (0.3 mg/kg), which did not change retinal and choroidal prostaglandin concentrations, the prostaglandin levels were decreased similarly (P < 0.01) by the three drugs. However, RBF and ChBF were not changed by ibuprofen and naproxen, but decreased to the same extent after low and high doses of indomethacin. The data suggest that the effects of indomethacin on RBF and ChBF cannot be simply attributed to prostaglandin synthesis inhibition, and that prostaglandins may not play a significant role in controlling basal blood flow to the retina and choroid.

Animals↗
PubMed1988

Endotoxin-induced hypocalcemia results in defective calcium mobilization in rats.

Hypocalcemia is common in critically ill patients with sepsis; however, its etiology remains unclear. We have previously reported that hypocalcemia occurs in approximately 20% of patients with gram-negative septicemia. Based upon this finding, we evaluated the effect of endotoxin on calcium homeostasis in laboratory animals. We report here that endotoxin produces a dose-related decrease in circulating ionized calcium levels and impairs calcium mobilization during ethylenebis (oxyethylenenitrilo)-tetraacetic acid infusion. We conclude that endotoxin or its products can cause ionized hypocalcemia during sepsis by impairing calcium mobilization.

Animals↗
PubMed1988

Hypercalcemia attenuates blood pressure response to epinephrine.

The potent alpha and beta adrenergic actions of epinephrine are probably mediated through an increase in free intracellular calcium concentration. Despite an absence of experimental evidence, many clinicians administer epinephrine with calcium to augment its cardiovascular effects. We evaluated the effects of calcium on epinephrine's pressor response in both normal and endotoxin-treated rats by administering epinephrine to animals made hypercalcemic with calcium chloride or hypocalcemic with the calcium chelator EGTA. EPI, given in incremental doses of 10, 20 and 50 micrograms/kg, produced incremental increases in mean arterial pressure. Calcium chloride infused i.v. at a rate of 50 mg/ml/hr significantly (P less than .05) blunted (50% decrease) the hypertensive response to 50 micrograms/kg epinephrine in normal animals. In endotoxin-treated rats, calcium chloride at 50 mg/ml/hr significantly blunted the hypertensive response to 10 micrograms/kg (73% decrease), 20 micrograms/kg (62% decrease) and 50 micrograms/kg (50% decrease) epinephrine. Endotoxemia plus calcium chloride at 25 mg/ml/hr also significantly blunted (30% decrease) the hypertensive response to 50 micrograms/kg EPI. By contrast, hypocalcemia produced by EGTA (30 mg/ml/hr) had no effect on epinephrine's hypertensive effects in normal or endotoxemic rats. Since calcium chloride significantly diminishes epinephrine's hypertensive effects in both normal and endotoxin-treated rats, the clinical use of calcium chloride along with epinephrine may not have a sound experimental basis.

Animals↗
PubMed1987

Verapamil reverses calcium cardiotoxicity.

High circulating concentrations of calcium are toxic to the heart and may cause cardiac arrhythmias and arrest. To investigate the therapeutic use of calcium antagonists in hypercalcemia, we evaluated the efficacy of verapamil hydrochloride and magnesium chloride in the treatment of experimental calcium-induced cardiac arrest in laboratory rats. Verapamil rapidly reversed the experimental calcium-induced arrest and improved survival (83% survival versus 0% in controls). Magnesium failed to reverse this toxic event. We conclude from these experimental studies that verapamil may be useful in the treatment of hypercalcemic cardiac toxicity.

Animals↗
PubMed1987

Glucagon's chronotropic action is calcium dependent.

Evidence is increasing that many anesthetics and cardiovascular agents alter cellular Ca kinetics and flux. In prior work we demonstrated that the tachycardic effects of glucagon were significantly blunted by Ca channel blockade, but not by beta adrenergic receptor blockade. Thus, the chronotropic effects of glucagon may be dependent upon extracellular Ca levels. Based upon these observations, we tested the hypothesis that changes in circulating ionized Ca concentrations may alter glucagon's ability to increase heart rate in rats. In conscious normocalcemic rats, glucagon's tachycardic actions were dose related with peak effects obtained at 1 to 2 min and persisting approximately 10 min after 1.0 mg/kg of glucagon. The effects of altered Ca levels on glucagon tachycardia were evaluated in three groups of rats: 1) rats rendered hypercalcemic by the infusion of Ca chloride (10, 50 or 100 mg/ml/hr); 2) rats rendered hypocalcemic by infusion of the Ca chelator EDTA (15 or 30 mg/ml/hr); and 3) normocalcemic rats infused with saline. Normocalcemic rats had a mean ionized Ca level of 4.73 mg/dl. In rats, increasing Ca chloride doses resulted in increasing mean serum ionized Ca levels (5.24, 8.35 and 15.2 mg/dl, respectively), whereas increasing doses of EDTA produced progressive decreases in mean ionized Ca (3.62 and 2.13 mg/dl, respectively). Severe hypo (2.13 mg/dl)- or hypercalcemia (15.2 mg/dl) significantly blunted glucagon's chronotropic action (51 and 44%, respectively). From these data, we conclude that glucagon has its maximal tachycardic action at physiologic Ca levels (being blunted by both hyper- and hypocalcemia), indicating that this effect of glucagon is Ca dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

Glucagon is an antagonist of morphine bradycardia and antinociception.

Glucagon and its receptors have been identified within the mammalian brain, and their anatomical distribution correlates well with the distribution of opioid peptides and their receptors. To evaluate possible physiological interactions between these two peptidergic systems, we examined the effects of glucagon on two opioid responses - bradycardia and antinociception. Glucagon administered either intravenously (iv) (100-1000 micrograms/kg) or intracerebroventricularly (icv) (5 micrograms) significantly attenuated morphine-induced (200 micrograms/kg, iv) bradycardia without producing any alterations in cardiovascular parameters when given alone. Furthermore, glucagon did not antagonize the bradycardia produced by phenyldiguanide (10 micrograms/kg, iv), a non-opioid substance. Peripheral (1 mg/kg, iv) and central (5 micrograms, icv) glucagon pretreatment antagonized morphine-induced (7.5 mg/kg, intraperitoneal) antinociception by 67% and 86%, respectively, at 30 minutes (as determined by the hot plate test). Glucagon treatment alone at these doses did not alter baseline response latencies. In both cases, central injections of glucagon were more effective than iv injections in antagonizing morphine's effects. These findings demonstrate a central action for glucagon and provide the first evidence that this neuropeptide may function as an endogenous antagonist of opioid actions.

Analgesia↗
PubMed1982

A mortality study of lead workers 1925-76.

The principal causes of mortality of 754 individuals from a population of 1898 pensioners from four lead acid battery factories during the period 1 January 1925 to 31 December 1976 were studied. In addition the causes of 553 deaths occurring before retirement was also studied. All subjects were placed into one of three groups according to their history of lead exposure. Group 1 had no occupational lead exposure, group 2 low, and group 3 the highest. Mortality was studied in 16 principal disease groups as well as all causes combined. A significant excess of deaths from cerebrovascular accidents was found among pensioners dying between 1925 and 1976 in group 3 but not among men in the same exposure group dying in employment. There was also a significant excess of deaths from renal disease among this group. After 1958, however, the causes of most of the deaths from renal disease were not those likely to be associated with exposure to lead. There was no significant excess of deaths from all causes, nor was there a significant excess of deaths in any of the exposure groups from cancer, hypertensive disease, nor any other circulatory disease. There was no excess of observed to expected deaths among any of the three groups of women in any of the cause groups examined. After the introduction of regular blood lead analysis in 1964 the blood lead distribution in men in group 3 had by 1976 come down to roughly the same level as group 2 in 1965-7. Since there was no excess of deaths in any of the 16 categories studied among group 2 subjects present conditions are probably now adequate to prevent any excess of mortality in any of the three groups.

Aged↗
PubMed1982

Dissociation between hepatosplenic and marrow iron in liver cirrhosis.

Histochemical study of tissue iron in the various parts of the reticuloendothelial system in 15 subjects with cirrhosis was performed. Stainable iron in the liver and spleen sections, generally in large quantities, was found in 13 of 15 cases. Paradoxical association of hepatosplenic siderosis with depletion of marrow iron reserves was observed in seven subjects. In all seven, gross gastrointestinal blood loss had occurred during life and the source of bleeding from one or more anatomic lesions was identified at the time of autopsy. Depletion of marrow iron reserves in these seven subjects can be attributed to two factors: first, the available marrow iron stores were used for erythropoiesis; second, the ample hepatosplenic iron deposits could not be mobilized for transport to the bone marrow. Thus, hepatosplenic iron in cases of cirrhosis seems to be sequestered from its normal metabolic pathways.

Adult↗
PubMed1980

Hemosiderosis in hemodialysis patients. An autopsy study of 50 cases.

The distribution of stainable iron stores was investigated in various organs of 50 hemodialysis patients with chronic renal disease. Massive iron deposits were found in the liver and spleen. Among 18 patients with severe hepatosplenic siderosis, iron deposits were abundant in the adrenal glands, lymph nodes, and lungs and were sparse in the heart, kidneys, and pancreas. There was an absence or scarcity of stainable iron in bone marrow of 19 pats. In five of these marrow-iron-depleted patients, serum concentrations of ferritin were high. In long-term hemodialysis patients, a variety of factors make massive iron overloads of various organs a likely occurrence, severe hepatosplenic siderosis may occur in marrow-iron-depleted patients, and serum ferritin levels in this setting may not always accurately reflect the status of marrow iron store.

Adult↗