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Biomedical subjects

R D Olson

Publications and source records attributed to R D Olson.

At least 73 records · Page 4Linked to original sources
PubMed1986

Lesions in ventromedial hypothalamus or amygdala do not affect naloxone's suppression of water consumption.

Rats received lesions in the ventromedial hypothalamus (VMH) or amygdala, or were sham operated, and then were tested for two-hour intake of water after injections of naloxone (2 mg/kg), MIF-1 (2, 4, or 8 mg/kg), or diluent. There was a significant effect of test compound, with naloxone reducing consumption relative to the diluent control and the largest dose of MIF-1. Although MIF-1 tended to suppress drinking, the effect did not reach significance. There was no main effect for lesions, indicating that the amygdala and the VMH do not play a critical role in the effect of naloxone or MIF-1 on water consumption. A significant lesion by time interaction occurred, however, with amygdala-lesioned rats drinking the most in the first 30 min but much less after that. The VMH rats drank the most in the 30-60 min interval, but there were no differences in groups after 60 min. Thus, it appears that the intact VMH and basolateral amygdala are not necessary for naloxone's suppression of water consumption in the rat.

Amygdala↗
PubMed1986

Prostaglandin synthetase inhibition in group B streptococcal shock: hematologic and hemodynamic effects.

A rabbit model of group B Streptococcal (GBS) shock was used to study the effects of prostaglandin synthetase inhibition on the hemodynamic and hematologic response to GBS shock. The infusion of heat-killed GBS in groups I and II produced significant decreases in mean arterial pressure, neutrophil counts, and platelet counts (p less than 0.05), and significant rises in concentrations of thromboxane B2 and 6-Keto-PGF1 alpha, the stable metabolites of thromboxane A2 and prostacyclin (p less than 0.05). Administration of indomethacin (4 mg/kg) after GBS infusion (group II) was associated with a significant rise in mean arterial pressure and a significant decline in thromboxane B2 and 6-Keto-PGF1 alpha concentrations (p less than 0.05) but had no effect on GBS-induced hematologic alterations. Indomethacin administration before GBS infusion (group III) prevented alterations in mean arterial pressure and was associated with a decrease in thromboxane B2 and 6-Keto-PGF1 alpha concentrations. Indomethacin in group III did not prevent neutropenia and thrombocytopenia and may have exacerbated neutropenia. Alteration of experimental GBS shock with prostaglandin synthetase inhibition produces disparate hemodynamic and hematologic response.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

The comparison of myocardial dysfunction in three forms of experimental septic shock.

A rabbit model of septic shock was used to determine if myocardial dysfunction is a common component of shock due to diverse neonatal pathogens, and prostaglandins modulate septic myocardial dysfunction. The infusion of heat-killed Escherichia coli (group I), Haemophilus influenzae (group II), or Staphylococcus epidermidis (group III) produced significant decreases in the first derivative of left ventricular pressure with respect to time (p less than 0.05). Each organism also produced significant changes in mean arterial pressure, cardiac output, and heart rate, while pulmonary artery pressure was altered in groups I and III. Saline-infused control animals (group IV) exhibited no significant changes in any hemodynamic variable. Blood gas variables were not significantly changed in any group. These cardiovascular changes appeared dependent on arachidonic acid metabolism since indomethacin pretreatment prevented the cardiovascular changes induced by bacterial infusion. These results suggest that septic myocardial dysfunction is a common component of gram-negative and gram-positive septic shock, and that myocardial dysfunction is modulated by prostaglandin products.

Animals↗
PubMed1986

Doxorubicin and doxorubicinol-induced alterations in human polymorphonuclear leukocyte oxygen metabolite generation.

The effects of doxorubicin and its primary metabolite doxorubicinol on the polymorphonuclear leukocyte (PMNL) respiratory burst were studied using lucigenin and luminol for detection of oxygen metabolite generation. Although both anthracyclines inhibited PMNL activation at concentrations achieved with therapeutic administration of doxorubicin, doxorubicinol was much more potent than doxorubicin. Preincubation of PMNL with either drug caused a persistent inhibition of cell function after drug washout that was not prevented by inclusion of either free radical scavengers or iron chelators in the incubation medium. Although complete suppression of the PMNL respiratory burst occurred with concentrations of doxorubicinol greater than 0.3 microgram/ml, a marked potentiation of the response was observed at lower concentrations (0.01 or 0.03 microgram/ml) of the same drug. Potentiation occurred only when albumin was present in the reaction medium, was eliminated by iron chelators, was not observed after PMNL incubation with drug and was dependent upon the activating agent. In contrast to doxorubicinol, doxorubicin did not potentiate the PMNL respiratory burst. These results demonstrate potent effects of doxorubicinol on PMNL oxygen metabolite generation that are markedly greater in degree and different in character than those of doxorubicin. Because both inhibitory and enhancing effects are apparent at concentrations of doxorubicinol achieved in vivo, this metabolite may be important in the clinically observed toxicity of doxorubicin.

Adult↗
PubMed1985

Beneficial effects of perfluorochemical artificial blood on cardiac function following coronary occlusion.

This study compares the effects of perfluorochemical artificial blood versus whole blood on the systolic and diastolic function of regionally ischemic myocardial preparations. Regional ischemia was produced by ligation of the circumflex coronary artery in isolated, blood-perfused rabbit hearts. Three minutes after occlusion, half the hearts were switched from the blood perfusate to perfluorochemical artificial blood; the other half continued to be perfused with blood. Isovolumic left ventricular (LV) developed pressure, dP/dt and resting pressure were monitored before, and for 2 hours after coronary occlusion. After 90 minutes of regional ischemia, perfluorochemical-treated hearts exhibited significantly greater developed pressure than those perfused with blood (78 +/- 6% versus 61 +/- 5% of preligation values; P less than 0.05). At the end of the experiment, LV dP/dt was 21% greater in the perfluorochemical-perfused group than in the blood-perfused group (74 +/- 8% versus 53 +/- 10%; P less than 0.01). Perfluorochemical perfusion also preserved diastolic function by preventing the 58% increase in left ventricular chamber stiffness (i.e., resting pressure; P less than 0.01) associated with circumflex ligation. Thus, in the present model of regional ischemia, perfluorochemical artificial blood is significantly better than blood at maintaining both systolic and diastolic myocardial function after a major coronary artery has been occluded.

Animals↗
PubMed1985

Naloxone and fluid consumption in rats: dose-response relationships for 15 days.

Rats were given daily intraperitoneal injections of 10.0, 1.0, 0.1, 0.01, 0.001 or 0.0 mg/kg naloxone for 15 days. Each day after the injections, animals were allowed access to a 20% sucrose solution for two hours and to tap water for the subsequent 10 hours. Consumption of the sucrose solution by the group that received 1.0 mg/kg was reliably decreased on Day 1 and 2, reflecting the suppressive effect of naloxone at that dose. By Day 3 until the end of the experiment, however, the suppression was no longer significant, suggesting that tolerance had developed. A similar effect was seen with the group given the highest dose, 10.0 mg/kg; although drinking was significantly less than the control in each of the 15 sessions, this group showed a trend to increase intake over the days of the experiment, thus also indicating possible tolerance to the effect of naloxone. Drinking patterns of the other groups did not differ statistically from the control. Thus, the low doses had no ability to suppress consumption, and the lowest dose that did lower it soon lost that ability; the highest dose continued to suppress drinking throughout the study but with decreasing efficacy. High performance liquid chromatography (HPLC) demonstrated that the naloxone remained intact over the 15 days of the experiment, supporting the suggestion that tolerance to naloxone might have developed.

Animals↗
PubMed1985

Pharmacokinetic calculator program for generation of initial parameter estimates from a three-compartment infusion model.

A polyexponential curve-stripping program, KIN, is described for use on the HP-41CV programmable calculator. The program may be used in the analysis of plasma-concentration-time curves for a three-compartment intravenous bolus or infusion model with linear elimination processes. The coefficients and hybrid rate constants of the exponential function are then used to compute pharmacokinetic parameters (volume of the central compartment, intercompartmental rate transfer constants), which may be used as initial estimates of model parameters in non-linear regression curve-fitting procedures.

Computers↗
PubMed1985

Depression of cardiac function by bisantrene.

Bisantrene is a newer anthracycline derivative currently being investigated in phase 2 trials. One presumed advantage of bisantrene is that it is purportedly free of cardiotoxic effects. However, bisantrene apparently precipitated congestive heart failure after a single intravenous infusion in a young boy, prompting our study of a second child who remained asymptomatic but had transient declines in cardiac function after receiving bisantrene. Since bisantrene may acutely depress myocardial contractile function, further investigation is necessary.

Anthracenes↗
PubMed1985

Myocardial dysfunction in group B streptococcal shock.

A rabbit model of group B Streptococcal (GBS) shock was used to determine if myocardial dysfunction contributes to GBS shock and, if so, to ascertain if prostaglandins modulate this dysfunction. The infusion of heat-killed GBS (group I) produced a dramatic decrease in the first derivative of left ventricular pressure with respect to time (LVdP/dt) from baseline values (p less than 0.05). LVdP/dt remained stable in rabbits pretreated with indomethacin (group II) and in saline-infused control rabbits (group III), and was significantly different at 30 min from LVdP/dt in group I (p less than 0.05). Values for group I mean arterial pressure, cardiac output, pulmonary vascular resistance, and heart rate and for pH and pO2 after GBS infusion were all significantly different from baseline values and from postinfusion values for groups II and III (p less than 0.05). Systemic vascular resistance and left ventricular end diastolic pressure did not change significantly in any group at any time interval. These results indicate a primary role for myocardial dysfunction in the pathogenesis of GBS shock, and suggest strongly that prostaglandins modulate GBS-induced myocardial dysfunction.

Animals↗
PubMed1985

Efficacy of sulfhydryl compounds as inhibitors of iron-dependent doxorubicin-enhanced lipid peroxidation.

The ability of sulfhydryl compounds to inhibit doxorubicin enhanced lipid peroxidation in the presence of added iron was evaluated. Optimal conditions for doxorubicin-enhanced lipid peroxidation were 25 microM doxorubicin, 2 mM ADP and 250 microM ferric chloride at pH 8.0. Lipid peroxidation was inhibited by EDTA (500 microM), SKF 525 A (100 microM) and vitamin E (0.1 unit/ml). Cysteamine (1 mM) stimulated basal lipid peroxidation but produced net inhibition of lipid peroxidation with doxorubicin. Cysteamine (10 mM) was more efficacious at inhibiting lipid peroxidation. N-acetylcysteine at 1 and 10 mM was a potent stimulator of lipid peroxidation and was ineffective at inhibiting lipid peroxidation in the presence of doxorubicin either at optimal or suboptimal concentrations of iron. In contrast, glutathione (1 mM) was a potent inhibitor of lipid peroxidation. The data suggests that N-acetylcysteine protects against doxorubicin by prior conversion to glutathione.

Acetylcysteine↗
PubMed1984

Depression of contractility in isolated rabbit myocardium following exposure to iron: role of free radicals.

The mechanism of acute iron cardiotoxicity was investigated in isometrically contracting left atrial strips and right ventricular papillary muscles isolated from rabbit hearts. A 90-min exposure to iron (1.8 mM; as ferrous sulfate) reduced the peak-developed tension and the maximal rate of tension development. The presence of either N-acetylcysteine (20 mM), superoxide dismutase (2000 units/ml), or mannitol (5 mM) prevented this depression of contractility. Catalase (30,000 units/ml) was not protective against the effects of iron. Iron did not decrease myocardial adenosine triphosphate or creatine phosphate contents. The force-frequency relationship (positive staircase phenomenon) was examined in the absence and presence of iron. Iron did not reduce the positive inotropic response evoked by increasing the stimulation frequency, but at higher frequencies iron prolonged the time from peak tension to 90% relaxation. We conclude that acute iron cardiotoxicity may be mediated by free radical generation and does not involve impairment of myocardial high energy phosphate production.

Adenosine Triphosphate↗
PubMed1984

MIF-1 (Pro-Leu-Gly-NH2) decreases activity in Siamese fighting fish (Betta splendens).

The effects of MIF-1 (Pro-Leu-Gly-NH2) on activity and aggression of male Siamese Fighting Fish ( Betta splendens) were considered. Animals were given intraperitoneal injections of 0.0 or 10.0 mg/kg MIF-1. After a 10-minute delay, they were placed in a 10 gallon aquarium and their activity was monitored for 60 minutes. Although aggressive responses in the presence of suitable opponents were not reliably affected, as significant decrease in general activity was produced. This is compatible with differential effects of MIF-1 across species.

Aggression↗
PubMed1984

Acute effects of iron on contractile function in isolated rabbit myocardium.

Changes in contractile function following exposure to iron (Fe) salts were evaluated in isolated isometrically contracting rabbit left atrial strips and right ventricular papillary muscles. Fe acutely depressed myocardial contractility as evidenced by dose-related declines in developed force and maximal rate of force development. There were no significant changes in duration of contraction or resting force. The tissue Fe content was increased nearly 3-fold after a 60 min exposure to Fe and subsequently was not decreased by repeated washing or by treatment with deferoxamine. Isoproterenol, but not deferoxamine, reversed the Fe-mediated impairment of myocardial contractility. These findings suggest that in cases of severe acute iron poisoning, depression of cardiac contractility might occur which may be improved by treatment with isoproterenol.

Animals↗
PubMed1984

Comparative effects of verapamil, nifedipine, and diltiazem on contractile function in the isolated immature and adult rabbit heart.

The effects of postnatal development on the systolic and diastolic responses to pharmacologic blockade of the slow inward calcium current were investigated in blood-perfused hearts isolated from immature (14-21-day-old) and adult rabbits. Isovolumic left ventricular developed pressure, resting pressure, and maximal rate of pressure development (+dP/dt) at cumulative doses of either verapamil, nifedipine, or diltiazem were determined by means of an intracavitary balloon. Myocardial contractile function in the immature heart was more sensitive to pharmacologic blockade of the slow inward calcium current than is the adult heart. Doses of verapamil, or nifedipine, that comparably reduced pretreatment developed pressure and +dP/dt were approximately 10-fold less in immature as compared to the adult heart. The dose of diltiazem which reduced developed pressure and dP/dt by 50% was 3-fold less in immature as compared to the adult heart. Verapamil and nifedipine decreased resting pressure in the adult but not in the immature heart. Conversely, diltiazem decreased resting pressure in the immature while not affecting resting pressure in adult hearts. Thus, postnatal cardiac development affects both the systolic and diastolic responses to calcium channel blockade. In addition, diltiazem appears to be qualitatively and quantitatively different from verapamil and nifedipine with respect to the age-related cardiac effects of calcium channel blockade.

Aging↗
PubMed1983

Behavioral effects of melanocyte stimulating hormone release-inhibiting factor-1 (MIF-1).

Consideration of the isolation, structure, localization, and behavioral effects of melanocyte stimulating hormone release inhibiting factor (MIF-1) is followed by a review of its opiate antagonistic and clinical effects. Evidence pertaining to various hypotheses offered in explanation of these behavioral effects is examined and evaluated. It is concluded that MIF-1 affects behavior in many instances with possible antagonistic effects as well as clinical possibilities.

Animals↗
PubMed1983

Tyr-MIF-1 affects passive avoidance behavior but not motor activity in rats.

The effects of the brain peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) were tested with several behavioral tests after peripheral injection in rats. In a passive avoidance test, Tyr-MIF-1 (1 mg/kg SC) resulted in significantly faster entry into the second compartment of a two-chamber shuttle box than was found with MIF-1 or diluent. Tyr-MIF-1 also resulted in flinch and escape responses that occurred at reliably lower amperage than the control. No significant effects were obtained on measures of ambulation, rearing, or defecation. The results demonstrate that Tyr-MIF-1 can affect behavior and that this action can differ from that of the same dose of MIF-1.

Animals↗
PubMed1983

Catecholamine-induced renin release in the anesthetized mongrel dog is due to both alpha and beta adrenoceptor stimulation: evidence that only the alpha adrenoceptor component is prostaglandin mediated.

The role of renal alpha and beta adrenoceptor activation and prostaglandin synthesis in mediating renin release to intrarenal infusions of the natural neurotransmitters, norepinephrine and epinephrine, was assessed in anesthetized mongrel dogs. Intrarenal infusions of norepinephrine and epinephrine at doses adjusted to reduce renal blood flow by 20 and 50% of baseline values elicited renin release that was not completely blocked by either alpha adrenoceptor blockade with phentolamine or beta adrenoceptor blockade with propranolol. The renin release that persisted during propranolol administration was abolished by the alpha adrenoceptor antagonist, phentolamine, and by the prostaglandin synthetase inhibitor, indomethacin. The beta adrenergic component of renin release, elicited in the presence of phentolamine, was not blocked by indomethacin but abolished by propranolol. These data are consistent with the hypothesis that norepinephrine and epinephrine stimulate renin release by activation of both the renal beta and renal alpha adrenoceptors. The beta adrenoceptor-stimulated renin release appears to be direct and independent of the prostaglandin system, whereas the alpha adrenoceptor-stimulated renin release appears to be indirect and dependent on the generation of endogenous prostaglandins.

Animals↗