Biomedical subjects

R W Caldwell

Publications and source records attributed to R W Caldwell.

At least 19 recordsLinked to original sources

PubMed1995

Effect of diterpenoid alkaloids on cardiac sympathetic efferent and vagal afferent nerve activity.

The diterpenoid alkaloid, lappaconitine, at a dose of 150 micrograms/kg (i.v.) increased cardiac vagal afferent nerve activity (16.2%) and reduced cardiac sympathetic efferent nerve activity (12.5%). A polar analog, N-deacetyllappaconitine, at this same dose, increased cardiac vagal afferent nerve activity (40%) and reduced cardiac sympathetic efferent nerve activity (23.5%). Both of these agents also reduced arterial blood pressure and heart rate. A larger dose of lappaconitine (300 micrograms/kg i.v.) produced the same changes in nerve activities and cardiac function as the lower dose. Two other structurally related agents, lycoctonine and aconine, failed to alter these variables in doses up to 300 micrograms/kg. These data suggest that certain diterpenoid alkaloids activate autonomic reflex receptors, including cardiac reflex receptors. The polar agent, N-deacetyllappaconitine, appears to be more effective on cardiac reflex receptors than the non-polar agent, lappaconitine. Such agents may be useful in the treatment of hypertension.

Aconitine↗

PubMed1995

Local cardiac effects of substance P: roles of acetylcholine and noradrenaline.

1. The local cardiac actions of substance P were examined in isolated perfused hearts and atria of the guinea-pig. 2. In both hearts and right atria, substance P caused negative inotropic and chronotropic effects. 3. Atropine (10(-6) M) or depletion of acetylcholine, by electrical stimulation and hemicholinium-3 perfusion, significantly attenuated the negative inotropic and chronotropic effects of substance P. alpha- and beta-adrenoceptor blockade by nadolol and phentolamine (10(-6) M each) did not prevent the negative inotropic and chronotropic effects of substance P. This indicates that cholinergic neurones, but not adrenergic neurones, partially mediate the effects of substance P. 4. There was no significant difference in the effects of substance P observed between groups with acetylcholine depletion and with cholinoceptor blockade. This suggests that substance P elicits its effects mainly through release of acetylcholine. 5. These results indicate that substance P has negative inotropic and chronotropic effects in guinea-pig hearts and right atria mediated partly by release of acetylcholine. Substance P also appears to have direct effects on cardiac tissue.

Acetylcholine↗

PubMed1995

Contraction-induced cell wounding and release of fibroblast growth factor in heart.

The heart hypertrophies in response to certain forms of increased mechanical load, but it is not understood how, at the molecular level, the mechanical stimulus of increased load is transduced into a cell growth response. One possibility is that mechanical stress provokes the release of myocyte-derived autocrine growth factors. Two such candidate growth factors, acidic and basic fibroblast growth factor (aFGF and bFGF, respectively), are released via mechanically induced disruptions of the cell plasma membrane. In the present study, we demonstrate that transient, survivable disruption (wounding) of the cardiac myocyte plasma membrane is a constitutive event in vivo. Frozen sections of normal rat heart were immunostained to reveal the distribution of the wound event marker, serum albumin. Quantitative image analysis of these sections indicated that an average of 25% of the myocytes contained cytosolic serum albumin; ie, this proportion had suffered a plasma membrane wound. Wounding frequency increased approximately threefold after beta-adrenergic stimulation of heart rate and force of contraction. Heparin-Sepharose chromatography, enzyme-linked immunosorbent assay, growth assay coupled with antibody neutralization, and two-dimensional SDS-PAGE followed by immunoblotting were used to demonstrate that both aFGF and bFGF were released from an ex vivo beating rat heart. Importantly, beta-adrenergic stimulation of heart rate and force of contraction increased FGF release. Cell wounding is a fundamental but previously unrecognized aspect of the biology of the cardiac myocyte. We propose that contraction-induced cardiac myocyte wounding releases aFGF and bFGF, which then may act as autocrine growth-promoting stimuli.

Animals↗

PubMed1995

HP-228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro.

alpha-Melanocyte stimulating hormone has been shown to prevent endotoxin shock. A heptapeptide analog (HP-228) has recently been synthesized and shown to be an even more potent protective agent. Because the hypotensive and toxic actions of lipopolysaccharide (LPS) appear to involve the induction of type II nitric oxide synthase (iNOS), we have examined the actions of HP-228 on nitric oxide production using an endotoxemia model in conscious rats given E. coli LPS (5 mg/kg i.v.) and monitored for 6 h. A group of rats received HP-228 (30 micrograms/kg) 30 min before LPS. Using nitro L-arginine methyl ester-sensitive cGMP production as an estimate of nitric oxide synthase activity in aortic segments, ex vivo, we determined that LPS increases iNOS activity and that HP-228 pretreatment markedly reduces this response. Additionally, the rate of conversion of 3[H]-arginine to 3[H]-citrulline was significantly reduced in lung homogenates from HP-228-treated rats. HP-228 did not alter the activity of the constitutive nitric oxide synthase in aortic rings or in cerebella. In isolated rat aortic smooth muscle cells, LPS or interleukin-1 beta caused prominent rises in nitric oxide generated by iNOS. HP-228 did not antagonize the effect of these inducing agents. However, in these cells, plasma obtained from rats 1 h after administration of HP-228 prevented the induction of iNOS by both LPS and interleukin-1 beta. In conclusion, HP-228 prevents the in vivo induction of nitric oxide synthase by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effect of halothane on in vivo and in vitro cardiotoxicity of an aminocardenolide.

Halothane opposes cardiotoxicity of neutral-sugar digitalis compounds in intact animals, presumably by depressing a sympathetic component of arrhythmogenesis. However, halothane also produces a dose-related reduction in arrhythmogenicity of ouabain in isolated canine Purkinje fibers, suggesting that the anesthetic may oppose direct mechanisms of cardiotoxicity as well. The present study examined in vivo and in vitro the effect of halothane on the arrhythmogenicity of ASI-222 (3-beta-O[4-amino-4-6-dideoxy-beta-D-galactopyranosyl] digitoxigen in HCl), a highly polar aminocardenolide with no sympathetic component to cardiotoxicity. For in vivo studies, ASI-222 was infused at a rate of 1 microgram/kg/min until appearance of third-degree atrioventricular (AV) block or sustained ventricular arrhythmias in 5 conscious (control) and 6 halothane-anesthetized (1.4% end-tidal) dogs. For in vitro studies, standard microelectrode techniques were used to measure action potentials (AP) in seven excised canine Purkinje fibers superfused with oxygenated Krebs-Henseleit buffer. AP were recorded during control superfusion, after induction of toxicity with 10(-7) M ASI-222, and during exposure to 0.5, 1.0, and 2.0% halothane. Purkinje fibers were paced at 500-ms cycle lengths (CL) for 20 beats, and the amplitude of delayed afterdepolarizations (DAD) were recorded. Pacing at 250 ms CL was used to trigger ectopy. In vivo studies showed no difference in the cardiotoxic dose of ASI-222 between control dogs and those anesthetized with 1.4% halothane. However, in 4 of 6 anesthetized dogs, acutely increasing the inspired halothane concentration suppressed arrhythmias once end-tidal concentration were >2.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

PubMed1994

Integrative cardiovascular actions of a novel catecholamine, GP-2-128.

Systematic modification in the chemical structure of dobutamine resulted in production of a long-acting, highly potent catecholamine, GP-2-128 [(1-(3,4-dihydroxyphenyl)-2-[3-(4-carbamyl phenyl)-1-methylpropylamino] ethanol)]. The cardiovascular actions of GP-2-128 were compared with those of isoproterenol (ISO) and dobutamine (DOB) in anesthetized dogs. GP-2-128 significantly increased left ventricular pressure (LVdP/dtmax), cardiac output (CO), and heart rate (HR). It also reduced total peripheral vascular resistance (TPVR). For a given increase in contractility, changes in HR were greater after ISO than after GP-2-128 administration. DOB did not change HR significantly. Both GP-2-128 and DOB reduced TPVR, but ISO was more effective than GP-2-128 and DOB in reducing TPVR. GP-2-128 was 18,000 and 52 times more potent than DOB and ISO, respectively, in increasing LVdP/dtmax. For a given increase in contractility, the cardiovascular actions of GP-2-128 lasted significantly longer than those of DOB or ISO. A 50% mixture of the RR and RS distereoisomer forms of GP-2-128 (GP-2-114) have the same pharmacologic profile as the pure RR distereoisomer. Both GP-2-128 and GP-2-114 produced current-dependent cardiovascular actions when administered by transdermal iontophoresis. The inotropic and chronotropic effects of GP-2-128 are both largely due to stimulation of beta-adrenoceptors, as shown by receptor blockade with propranolol. GP-2-128 is a very potent, long-acting catecholamine that can be administered by other than intravenous (i.v.) route.

Adrenergic beta-Antagonists↗

PubMed1994

Interactions of a novel catecholamine, GP-2-128, with adrenoceptors.

GP-2-128 is a novel catecholamine designed for transdermal iontophoretic delivery in patients with limited mobility to prevent deconditioning and muscular wasting. We characterized the interactions of this agent with alpha- and beta-adrenoceptors in vitro. In electrically stimulated rat left atria, GP-2-128 produced a concentration-dependent increase in contractile force. pD2 values for GP-2-128, isoproterenol (ISO), and dobutamine (DOB) were 10.6 +/- 0.12, 8.55 +/- 0.02, and 7.0 +/- 0.20, respectively. Metoprolol caused a shift in the concentration-effect curves for the three agonists. In spontaneously beating rat right atria, pD2 values of GP-2-128, ISO, and DOB are 10.4 +/- 0.24, 8.82 +/- 0.18, and 6.92 +/- 0.18, respectively. The affinity constant (KA) of GP-2-128, ISO, and DOB for cardiac beta 1-adrenoceptors was determined by competition binding assays to be 8.09, 6.04 and 4.49, respectively. In guinea pig trachea precontracted with histamine, GP-2-128 and ISO produced a concentration-dependent relaxation. pD2 values were 10.0 +/- 0.1 and 8.2 +/- 0.1, respectively. DOB was more potent than GP-2-128 in contracting isolated rat aortic rings (alpha 1 effect) and in displacing [3H]rauwolscine (alpha 2 effect). We also studied the interactions of GP-2-128 and ISO with the atypical beta-adrenoceptors (beta 3) in guinea pig ilea and rat and hamster adipocytes. Both agents inhibited twitches produced by transmural nerve stimulation in the presence of 10(-5) M nadolol. The EC30 for GP-2-128 and ISO at this atypical receptor site were 4.25 x 10(-10) and 5.05 x 10(-8) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipocytes↗

PubMed1992

Effects of sinoaortic denervation on the reflex actions of digoxin and a polar aminocardenolide.

To determine the role of carotid sinus and aortic arch baroreceptors in the reflex cardiac sympathetic nerve activity (SNA) responses to administration of ASI-222, a polar aminocardenolide, and to digoxin, a neutral cardenolide, we used anesthetized dogs from which these reflex receptor areas had been removed. The SNA was measured in postganglionic fibers from the stellate ganglion. After we made baseline measurements, we infused either ASI-222 or digoxin intravenously (i.v.) at dose rates that produce cardiac arrhythmias in approximately 100 min (0.7 and 1.2 micrograms/kg/min), respectively. Our data indicate that with sinoaortic baroreceptors removed, progressive infusion of digoxin increases cardiac SNA. In contrast, cardiac SNA decreases progressively during continuous infusion of ASI-222. In saline-treated dogs, SNA was not significantly altered. In another series of experiments, we examined the effects of these drugs and saline on cardiac vagal afferent nerve activity (VANA). ASI-222 (50 micrograms/kg i.v. in 10 min) caused a progressive increase in cardiac VANA in a 60-min observation period. Neither digoxin, at less than or equal to 120 micrograms/kg i.v. in 100 min, nor saline altered VANA. Digoxin appears to reduce SNA by interacting with the carotid sinus and aortic arch baroreceptors, which are myelinated. It does not affect VANA acutely. In contrast, ASI-222 appears to decrease cardiac SNA by interacting with other reflex receptor areas--the unmyelinated cardiopulmonary afferent nerve endings, particularly cardiac mechanoreceptors.

Animals↗

PubMed1992

Effect of transient vagal cold blockade upon reflex actions of a polar and nonpolar cardiac glycoside.

To determine the role of vagal afferent fibers in expressing the actions of a polar aminosugar digitalis agent [ASI-222 (4-amino-galactose beta-D-digitoxigenin HCl)] and a nonpolar neutral sugar agent (digoxin) on cardiac sympathetic nerve activity (CSNA), we utilized a period of vagal cooling to block traffic in that nerve. Anesthetized dogs were prepared to measure CSNA in efferent fibers from the right stellate ganglion. Both vagi were exposed midcervically and fitted with water-filled glass coils. The vagi were cooled (approximately 4 degrees C) and then either ASI-222 or digoxin was infused i.v. at dose rates which produce cardiac arrhythmias after about 100 min. Saline was infused in a third group. After 50 min of drug infusion, the vagi were rewarmed. During vagal cooling and infusion of saline or ASI-222, CSNA rose by 25 to 30%. Within 10 min after rewarming, CSNA returned to base line values in the saline group but nerve activity in the ASI-222 group promptly fell about 45% below base line and remained depressed. This dose rate of ASI-222 depresses CSNA in neurally intact dogs within 30 min. In contrast, during vagal cooling digoxin caused a slow but progressive fall in CSNA (approximately 20%); with rewarming and higher doses, CSNA began to rise above base-line levels. This profile of changes in CSNA to digoxin is similar to that observed in neurally intact animals. In other dogs given atropine to block the effects of efferent vagal nerve traffic, ASI-222 produced a prompt decline in CSNA like that observed previously in neurally intact dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effect of a prostaglandin F2 alpha injection 96 hours after introduction of intact bulls on estrus and calving distribution of beef cows.

Most estrus synchronization schemes facilitate the use of artificial insemination; however, combining estrus synchronization with natural service also offers several benefits to beef producers. This experiment was designed to study the effectiveness of one injection of prostaglandin F2 alpha (PGF2 alpha) 96 h after introduction of intact bulls on estrus synchronization and calving distribution of beef cows and heifers. Three hundred sixty beef cows and 45 beef heifers in seven trials were allotted by age, breed, and prior calving date to one of two treatments. Within each subclass, one group was injected with an appropriate dose of PGF2 alpha and the second group at each location received 5 ml of saline (SAL). Cows were classified as estrual or anestrual at the start of breeding based on serum progesterone levels and were observed for behavioral estrus regularly during the first 25 d of the breeding season in two of the trials (d 0 = day before bull turn-in). Pregnancy data and calving dates were recorded in each of the studies. All cows were palpated per rectum for pregnancy approximately 70 d after the introduction of bulls. During d 5 to 9 after treatment, the percentage of cows exhibiting behavioral estrus (P = .02) and the pregnancy rate (P = .02) obtained was greater for PGF2 alpha-treated cows than for SAL-treated cows. There were 6.5% more (P = .05) calves born during the overall calving period from animals treated with PGF2 alpha compared with those in the SAL group. In summary, treatment of cows and heifers with PGF2 alpha 96 h after bull turn-in was effective in synchronizing behavioral estrus of beef cows and heifers and increasing the calving rate during the subsequent calving season.

Animals↗

PubMed1990

The cardiovascular response to digoxin in conscious dogs with left atrial obstruction.

In addition to positive inotropic and atrioventricular conduction-blocking properties, digoxin is capable of producing systemic and pulmonary vasoconstriction. However, whether chronic digoxin treatment exacerbates the pulmonary hypertension that results from left atrial (LA) outflow obstruction has not been specifically examined. This study assessed the vascular and inotropic responses to 5 days of digoxin treatment in six conscious dogs before and after filling a permanently implanted LA balloon. Dogs were also instrumented to measure left ventricular (LV) pressure, LV dP/dt, mean systemic arterial (MAP), right atrial (RAP), pulmonary arterial, and pulmonary capillary wedge pressures, as well as cardiac output (CO). Under normal conditions with the balloon empty, digoxin treatment (40 micrograms/kg loading dose and 12 micrograms/kg/d for 5 days) reduced CO (-17%) and increased systemic (SVR) and pulmonary (PVR) vascular resistances 27% and 37%, respectively; heart rate (HR) and LV dP/dt were not changed. Filling the balloon with enough saline to double PVR also increased SVR (52%), HR (42%), and RAP (92%), and reduced CO (-24%). During LA outflow obstruction, 5 days of digoxin reduced HR (-17%), SVR (-29%), and RAP (-23%), but did not alter PVR, CO, or LV dP/dt. This study demonstrates that although systemic and pulmonary vasoconstriction result from chronic digoxin treatment under normal conditions, the drug produces systemic vasodilation and no change in PVR during LA outflow obstruction.

Animals↗

PubMed1990

Actions of the opioid antagonist, nalmefene, and congeners on reperfusion cardiac arrhythmias and regional left coronary blood flow.

Opioid antagonists have been shown to prevent the occurrence of lethal arrhythmias following coronary reperfusion. In this study, we have examined the effect of a new, long-lasting, potent opioid antagonist, nalmefene, and congeners in the prevention of reperfusion arrhythmias in dogs. Nalmefene given at a dose of 1 mg/kg i.v. reduced the incidence of reperfusion arrhythmias significantly when compared to the saline control. Neither N-methyl nalmefene, a quaternary analog that does not cross the blood brain barrier, nor (+) nalmefene, an isomer with no anti-opioid actions, provided any protection against reperfusion arrhythmias. Regional myocardial blood flow profiles, during and after coronary occlusion, were not different between the nalmefene- and saline-treated groups. We conclude that nalmefene prevents the occurrence of reperfusion-induced arrhythmias by blocking opioid receptors in the brain.

Animals↗

PubMed1990

Administration of pig relaxin to beef heifers 4 or 7 days pre partum.

Crossbred beef heifers (N = 36) were assigned to one of three treatment groups: untreated controls (C; N = 15); Group R4, treated with pig relaxin (1.0 mg i.m.) 4 days pre partum (N = 11); or Group R7, treated with pig relaxin (1.0 mg i.m.) 7 days pre partum (N = 10). Bioactivity of the pig relaxin (UMC-R-P8) was determined by the mouse interpubic ligament assay to be greater than or equal to 3000 U/mg, both before and after the experiment was conducted. Peripheral serum immunoreactive relaxin values were 7.5, 3.4, 2.5, and 1.5 ng/ml at 2, 4, 6 and 8 h after injection of relaxin, respectively. Gestation lengths were 282.9 +/- 1.1, 285.5 +/- 1.3 and 285.6 +/- 1.5 days for Groups C, R4 and R7 (C vs R4 + R7; P congruent to 0.08). Calving difficulty score (1 to 4) tended to be greater (P congruent to 0.08) for Group R4 and R7 heifers (C vs R4 + R7; 1.3 +/- 0.24 vs 1.75 +/- 0.28 + 2.04 +/- 0.32), but the incidences of dystocia and retained placentae were not influenced by treatment (P greater than or equal to 0.10). The mean concentration and concentration profile of daily serum progesterone, oestradiol-17 beta, dihydroprostaglandin F-2 alpha and relaxin were not affected by treatment from 6 days pre partum through 2 days post partum. Cervical diameter, cervical softness score, pelvic measurements, and vulva opening length during the periparturient period were not affected (P greater than or equal to 0.10) by treatment, but all of these characteristics changed over time (P less than or equal to 0.01), relative to calving. We conclude that i.m. administration of pig relaxin (greater than or equal to 3000 U) does not effectively alter periparturient characteristics of beef heifers. Discrepancies between these results and those reported for intracervical administration cannot be readily explained.

Animals↗

PubMed1990

Different patterns of autonomic nerve activity produced by a polar vs. a neutral cardiac glycoside.

Digitalis agents react with various peripheral reflex receptor areas (i.e., carotid artery baroreceptors and cardiac mechanoreceptors) to alter autonomic nerve activity. Physical characteristics of these reflex receptors differ and thus they may respond differently to polar and neutral cardenolides. Our purpose was to determine the effect of progressive i.v. infusion of either ASI-222, a polar aminocardenolide agent, or digoxin, a neutral cardenolide, on cardiac sympathetic, efferent vagal, and carotid sinus nerve activity. Digoxin or ASI-222 were infused into anesthetized dogs at dose rates which caused cardiac arrhythmias in about 2 hr. Nerve activities were monitored and recorded by a system of differential amplifiers and by a digital storage oscilloscope. Infusion of ASI-222 progressively reduced sympathetic nerve activity (approximately 55%) through the toxic dose; sympathetic nerve activity remained depressed even through the onset of cardiac arrhythmias. Digoxin also depressed cardiac sympathetic nerve activity but only at intermediate dose levels; sympathetic activity rose near the toxic dose. Digoxin increased both carotid sinus and vagal efferent nerve activity with progressive doses. In contrast, ASI-222 did not alter carotid sinus and efferent vagal nerve activity. In summary, digoxin activates carotid sinus baroreceptors; ASI-222 does not. Digoxin and ASI-222 produce different profiles of changes in cardiac autonomic nerve activity and appear to differ in autonomic reflex receptor interactions.

Animals↗

PubMed1989

Comparative ability of digoxin and an aminosugar cardiac glycoside to bind to and inhibit Na+,K+-adenosine triphosphatase. Effect of potassium.

We compared the abilities of digoxin and aminogalactose digitoxigenin (ASI-222) to bind to, or inhibit, purified dog heart Na+,K+-ATPase in the presence of 1, 10, or 80 mM potassium chloride. Changing the potassium concentration from 1 to 10 mM increased the dose producing 50% inhibition of enzyme activity (IC50) by 9- and 2.5-fold for digoxin and ASI-222 respectively. Raising the potassium concentration to 80 mM increased the IC50 for digoxin 3-fold but did not alter significantly the IC50 for ASI-222. Equilibrium binding studies showed that this enzyme exhibited a single class of specific binding sites for both digoxin and ASI-222. Raising the potassium concentration did not affect the maximum number of binding sites (Bmax) but increased the apparent dissociation constant (KD) for digoxin. Potassium differentially affected the affinity and number of binding sites for ASI-222; raising the potassium concentration from 1 to 10 mM did not affect the Bmax or the KD, but raising it to 80 mM increased both. The effect of i.v. infusion of potassium chloride upon cardiac upon cardiac arrhythmias produced by i.v. infusion of digoxin or ASI-222 in anesthetized dogs was also determined. Infusion of potassium chloride reversed the cardiac arrhymias due to digoxin to normal rhythm, but not those due to ASI-222. In conclusion, the interaction of digoxin and the polar digitalis agent, ASI-222, with dog heart Na+,K+-ATPase was differentially affected by potassium. These agents also also produced cardiac arrhythmias, which were differentially affected by potassium.

Animals↗

PubMed1989

Interactions of pyridostigmine with cardiopulmonary systems and their relationships to plasma cholinesterase activity.

Three dose levels of pyridostigmine (0.5, 2, and 5 mg/kg) were given iv to dogs anesthetized with sodium pentobarbital. Hemodynamic measurements made were cardiac output, blood pressure, left ventricular dP/dT, and heart rate. Pulmonary function data obtained were airway resistance, respiratory rate, and tidal volume. Activity of blood cholinesterase was also measured. Increasing doses of pyridostigmine promptly and progressively lowered the acetylcholinesterase activity of blood to a minimum of 40% of control at the 5 mg/kg dose. Airway resistance was most sensitive to the drug. Resistance increased significantly with 2 mg/kg, and the 5 mg/kg dose resulted in more than a 10-fold increase, which persisted for more than 2 hr. Tidal volume was decreased and minute volume was increased due to an increase in respiratory rate. With the higher doses, heart rate decreased and stroke volume rose sufficiently to compensate so that cardiac output was unchanged. The lowest dose produced minimal effects on both cardiovascular and respiratory systems, and since this dose is greater than that proposed for organophosphate poisoning in humans, it seems likely that this drug would not cause important effects in normal humans when used as a protective agent.

Acetylcholinesterase↗

PubMed1989

The mechanism of nitrous oxide-induced changes in pulmonary vascular resistance in a dog model of left atrial outflow obstruction.

Nitrous oxide has been reported to increase pulmonary vascular resistance (PVR) in patients with pulmonary hypertension secondary to mitral stenosis. Additional data suggest this response involves sympathetic stimulation because the increase in PVR can be prevented by alpha-adrenergic and ganglionic blockade. Whether or not active pulmonary vasoconstriction occurs remains unclear. This study was designed to more fully characterize the influence of N2O on pulmonary hemodynamics during left atrial outflow obstruction (LAO). Responses in an in situ blood-perfused lung lobe were compared with those in the remaining intact lung of six dogs anesthetized with pentobarbital, 30 mg/kg, and morphine, 1.5 mg/kg, and prepared for measurement of peak left ventricular (LV) pressure, LV end-diastolic pressure (LVEDP), LV dP/dt, systemic arterial and pulmonary arterial (PA) pressures, and cardiac output (CO). The pulmonary artery branch supplying the left middle lung lobe was cannulated and perfused at a constant rate with warmed blood. LAO was produced by filling the balloon of a Foley catheter positioned in the left atrium (LA) with enough saline to increase PA pressure by 50%; the balloon was subsequently left filled for the entire protocol. Measurements were first obtained during ventilation with 67% N2, and 33% O2. The inspired gas was then changed to 67% N2O and 33% O2 for 10 minutes, and then returned to the N2/O2 mixture. Once baselines had been reestablished (about 10 minutes), phentolamine, 0.75 mg/kg, was administered, and the response to 10 minutes of N2O again observed. N2O did not change vascular resistance in the isolated lobe, but increased intact-lung PVR.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

PubMed1988

Mechanisms of altered sodium excretion after preoptic hypothalamic lesions.

These experiments investigated cardiovascular and hormonal responses during the natriuresis and subsequent sodium retention following electrolytic lesions of the periventricular tissue surrounding the anteroventral third ventricle (AV3V-X) in the rat. Four hours following treatment, AV3V-X resulted in a significant increase in blood pressure (18 +/- 3 mmHg), bradycardia (-68 +/- 20 beats/min), and natriuresis (212 +/- 36 mu eq/h), compared with control-operated (control: 2 +/- 4 mmHg, -14 +/- 18 beats/min, 89 +/- 34 mu eq/h) and unanesthetized control (UC) animals (-1 +/- 3 mmHg, -5 +/- 12 beats/min, 74 +/- 25 mu eq/h). Preventing the hypertensive response in AV3V-X rats abolished the natriuresis. Twenty-four hours after treatment, blood pressure, heart rate, urine flow, and sodium excretion were similar between experimental groups. However, sodium excretion by AV3V-X rats was significantly smaller than control 24-48 h following treatment. AV3V-X rats had significantly elevated plasma concentrations of aldosterone and corticosterone 4, 24, and 48 h and increased plasma renin 24 and 48 h after treatment. These data suggest that the acute natriuresis following AV3V-X is mediated by increased arterial blood pressure, whereas the subsequent sodium retention could be due to activation of the renin-aldosterone system.

Aldosterone↗