Reduction In HR Research Articles

Antagonism of morphine analgesia by intracerebroventricular naloxonazine.

Intravenous pretreatment with naloxonazine, an irreversible and selective antagonist of mu-1 sites for over 24 hr, reduces analgesia induced by morphine as well as a series of opiates and enkephalins. The present study evaluated whether intracerebroventricular (ICV) administration of naloxonazine produces similar long-term (24 hr) reductions in morphine analgesia on the tail-flick and jump tests. Naloxonazine failed to alter baseline tail-flick latencies or jump thresholds, but antagonized in a dose-dependent manner morphine analgesia for 24 hr. Naloxone had no effect at 24 hr. Morphine actions in the jump test were quite sensitive to doses of naloxonazine as low as 1 microgram/rat. Although tail-flick assays also revealed naloxonazine effects, far greater doses (30 micrograms/rat) were needed. Naloxonazine also shifted full morphine dose-response curves to the right. Again, naloxonazine antagonized morphine in the jump test more effectively than in the tail-flick assay. These data provide support for the involvement of the mu-1 opioid binding site in the central mediation of morphine analgesia and point out the differing sensitivities of two analgesiometric assay systems to naloxonazine.

Enhanced retention of biofeedback-assisted HR slowing due to training context

Abstract Visual biofeedback was administered for HR reduction while the subject listened to music or to nothing. On the next day, half of the music group was tested with music and half without music; likewise, half of the group trained without music were tested with and half without music. Twenty-eight subjects were run in this 2×2 factorial design. During the test period, no feedback was given. Significant HR reduction (3.5 BPM) occurred in both auditory contexts. In the test session on the next day there was a tendency for the two subgroups trained with music to continue to have reduced HR, while the HR of the two subgroups trained without music increased. This tendency was not quite statistically significant; it did not interact with testing context, nor did testing context itself have any effect on HR.

Comparative efficacy and tolerance of esmolol to propranolol for control of supraventricular tachyarrhythmia

This multicenter, double-blind, randomized, parallel study compared the effectiveness and tolerance of intravenous esmolol with intravenous propranolol in patients with supraventricular tachyarrhythmia (heart rate [HR] > 120 beats/min). Efficacy was evaluated in 53 patients receiving esmolol and in 57 patients receiving propranolol. Patients randomized to esmolol received infusions of various doses of esmolol ranging from 50 to 300 μg/kg/min (each dose infused for 5 minutes) over a 30-minute titration period with intermittent placebo boluses of propranolol. Those randomized for propranolol received 1 mg/min for the first 3 minutes, and then another 3 mg from minutes 5 to 8 with continuous placebo esmolol infusion during the 30-minute titration period. A therapeutic response, defined by 20% or greater reduction in HR, HR < 100 beats/min or conversion to normal sinus rhythm, was achieved in 72% of patients on esmolol compared with 69% of patients on propranolol (difference not significant). The therapeutic response was maintained in 67% of patients on esmolol and 58% of patients on propranolol (difference not significant) during a 4-hour maintenance period. Conversion to normal sinus rhythm occurred in 14% of esmolol patients and 16% of propranolol patients during titration and 10% of esmolol and 8% of propranolol patients during maintenance. After discontinuation of study drugs, a more rapid reversal of the reduction in HR was observed in esmolol patients compared with those patients receiving propranolol. Adverse reactions were seen in 29 (45%) patients on esmolol and 11 (18%) patients on propranolol. The principle adverse reaction was hypotension, which was predominantly asymptomatic and found in 23 patients receiving esmolol and 4 receiving propranolol. Hypotension resolved quickly after discontinuation of esmolol and did not cause any significant consequences. This study demonstrates that esmolol is comparable in safety and efficacy to propranolol, and unlike propranolol, it has a much faster termination of β blocking because of its short half-life. Esmolol, therefore, has marked theoretical advantages in its use in the intensive care unit for the control of supraventricular tachyarrhythmia.

Splanchnic vasomotor and metabolic adjustments to hypoxia and exercise in humans.

To determine whether hypoxia increases splanchnic vasoconstriction and impedes splanchnic metabolism during exercise, 11 subjects were exercised for 72 min at O2 uptake (VO2) of 1.8 1/min; 11% O2 was breathed during 30-50 min. Splanchnic blood flow (SBF), arterial and hepatic venous concentrations of indocyanine green (ICG), O2, CO2, metabolites, and catecholamines were determined in seven subjects; complete sets of all measurements were obtained from four. Arterial O2 content and tension fell from normal values to 12.3 ml/100 and to 32.2 Torr, respectively, during hypoxia; heart rate rose to 159 from 117 beats/min, arterial blood pressure was unchanged, and plasma norepinephrine (NE) and epinephrine (E) concentrations rose from 0.79 (NE) and 0.2 (E) ng/ml (normoxia) to 2.7 and 0.72, respectively, during hypoxia. SBF rose insignificantly from 1.14 (normoxia) to 1.35 l/min during hypoxia and fell significantly to 1.01 1/min after return to normoxia. Splanchnic VO2 was maintained at normal levels by increased extraction as hepatic venous O2 fell to 1.7 ml/100 ml and hepatic venous O2 tension to 7.5 Torr. Hepatic glucose release rose from 642 (normoxia) to 1,164 mg/min (hypoxia); lactate uptake increased from 0.26 to 2.1 mM/min; NE uptake rose from 417 to 1,508 ng/min, but hypoxia reduced ICG extraction by 28%. Thus hypoxia did not cause splanchnic vasoconstriction normally accompanying increases in HR and NE concentration or reductions in maximum VO2. SBF was maintained at a level sufficient to maintain all metabolic functions except ICG extraction.

Biofeedback for HR reduction in different contexts

Abstract Binary visual biofeedback was administered for HR reduction while the subject was listening to music, a pure tone, or nothing. All 27 subjects received all 3 contexts in a completely counterbalanced order. Immediately following the biofeedback training, HR was recorded during each of the 3 contexts with no biofeedback. Significant HR reduction (over 4 BPM) occurred in all 3 contexts. This effect was also observed during the test without feedback immediately following training. But 24 hours later, HR was no longer significantly below baseline in any of the contexts. HR variability (between subjects) increased significantly in the second test. There was no difference due to context, either in training or transfer. ∗Now at University of Padua.

Prizidilol, a combined vasodilatory and beta-adrenoceptor blocking drug, in primary hypertension. A long-term efficacy, tolerance and pharmacokinetic study.

After an initial placebo period of four weeks 24 patients with primary hypertension were treated with prizidilol, a hydrazinopyridazine derivative with combined vasodilator and non-selective beta-adrenoceptor blocking actions, for a dose titration period of 14 weeks. Prizidilol 200 to 800 mg was given once daily to achieve a target supine diastolic blood pressure (BP) less than 90 mmHg. Supine and standing BP recorded 24-27 h after drug intake decreased from 172 +/- 17/106 +/- 6 mmHg (mean +/- SD) and 167 +/- 18/111 +/- 8 mmHg, respectively, after placebo to 159 +/- 16/99 +/- 8 and 154 +/- 18/101 +/- 9 mmHg after active treatment for six weeks (mean dose 447 mg), and to 154 +/- 16/97 +/- 7 and 148 +/- 14/97 +/- 7 mmHg after treatment for 14 weeks (mean dose 687 mg/day). A slight reduction in HR was seen after treatment for six weeks and in plasma renin activity and urinary methoxycatecholamine excretion after treatment for 14 weeks. A sustained decrease in BP was observed for 10 h after prizidilol 800 mg (n = 9), with a maximum antihypertensive effect (mean reduction in supine BP 33/18 mmHg) 2.5 h after dosing, which coincided with the mean peak plasma concentration. The plasma elimination half-life of the drug was 3.9 h (range 2.0-8.9 h). Changing to a twice daily regimen in 17 patients (mean daily dose 748 mg at six months) did not produce any further reduction in the BP (recorded 12-15 h after dosing) as compared to the once daily regimen at 14 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

High‐Dose Analgesic Anesthesia with Morphine or Sufentanil in Propranolol‐Treated Dogs

In propranolol-pretreated dogs (2 mg . kg -1) the immediate cardiovascular effects of sufentanil (0.01 mg . kg -1) or morphine (4 mg . kg -1) were compared. Besides a 40% decrease in cardiac index (CI), sufentanil and morphine initiated quite different hemodynamic changes. Sufentanil did not significantly change mean arterial pressure (MAP), central venous pressure (CVP) and mean pulmonary artery pressure (MPAP), while the pulmonary capillary wedge pressure (PCWP) increased by 50%. After morphine, MAP declined significantly by about 65%, and significant decreases in MPAP (14%) and PCWP (33%) were also observed. Propranolol reduced heart rate by 16%, and morphine caused no further reduction in HR. A significant decrease of about 30% was seen in HR after sufentanil. Sufentanil significantly raised systemic vascular resistance index (SVRI) by 15%, whereas morphine decreased it by 32%. Pulmonary vascular resistance index (PVRI) was unchanged after sufentanil, but significantly increased after morphine. Right ventricular stroke work index (RVSWI) was unaffected by both analgesics, and morphine decreased left ventricular work index (LVSWI) significantly by 80%. Oxygen transport index declined significantly after both analgesics. Sufentanil reduced oxygen consumption by 20%, while morphine left this parameter unaffected. We conclude that the administration of high-dose sufentanil leads to a stable circulation, even when a total beta-blockade exists.

Reduction of Methemerythrin-Anion Adducts by Dithionite Ion

The reduction by dithionite ion (in excess) of methemerythrin-anion adducts, Hr +X −, to deoxyhemerythrin, Hr°, has been examined at 25° and pH 6.3 and 8.2. The results accord with the scheme: ▪ With X − = Br −, HCO 2 −, CNO −, and F −, k 2[SO 2 −] 〉 k 1[X −], and the pseudo first-order rate constant, k obs (= k −1), is independent of [X −] and [S 2O 4 2−]. Only with X − = NCS − is k 2[SO 2 −] ∼ k 1[X −] and k obs = a[S 2O 4 2−] sol1 2 ( b[NCS −] + [S 2O 4 2−] sol1 2 ) −1. Values at pH 6.3 of k −1 (sec −1) and k 1 (M −1 sec −1), obtained by anation and anion displacement reactions, are 2.3 × 10 −3, 1.6 × 10 −2 (Br −); 1.5 × 10 −3, 1.2 × 10 −2 (HCO 2 −); 1.3 × 10 −4, 0.52 (CNO −) and ∼2 × 10 −4, 3.3 × 10 −3 (CN −, pH 7.0). Values of k −1 from reduction and displacement methods are in good agreement with each other. The value of k 2 (1.6 × 10 5 M −1 sec −1, pH 6.3) is somewhat smaller than that for reduction of the met form of hemoproteins. There is only a small effect of pH on rates. Direct reduction of Hr +CN − does not occur, in contrast with Mb +CN −.

Abrupt propranolol withdrawal in angina pectoris: Effects on platelet aggregation and exercise tolerance

Data collected before the initial reports of myocardial infarction following sudden withdrawal of propranolol are presented here to evaluate possible mechanisms for this phenomenon. Twenty patients with angina pectoris were randomized into placebo and propranolol (160 mg./day) treated groups and followed for 50 weeks at which time treatment was abruptly discontinued. Measurements of exercise tolerance, the product of heart rate and blood pressure at exercise end-point (HR × BP), and platelet aggregation thresholds in response to ADP and epinephrine were made before, during, and after treatment. Prior to propranolol, mean total work performance was 765 ± 125 k.p.m., HR × BP (heart rate-blood pressure product) was 16,800 ± 1,535. Mean platelet aggregation threshold with ADP was 1.32 μM ∗ ∗ Geometric mean. ; with epinephrine 1.26 μM ∗ . Patients treated with propranolol demonstrated significant improvement in exercise performance (1,790 ± 285 k.p.m., p < .01), reduction in HR × BP (12,000 ± 895, p < .01), and an elevation in platelet aggregation threshold; with ADP 3.43 μM ∗ (p < .01); with epinephrine 12.9 μM ∗ (p < .01). Following abrupt cessation of propranolol, exercise tolerance and HR × BP fell below pretreatment levels (630 ± 117 k.p.m. and 15,500 ± 513, respectively). Similarly platelet aggregation threshold fell to 1.0 μM ∗ with ADP and 0.57 μM ∗ with epinephrine. In six patients platelets were significantly more hyperaggregable than prior to therapy. Anginal frequency increased in all, but no acute infarction was observed. Abrupt withdrawal of propranolol may be deleterious in patients, sometimes causing “rebound” platelet hyperaggregability associated with increasing anginal frequency and decreasing exercise tolerance.

Heart rate and oxygen uptake response to angiotensin in the squirrel monkey at 10 degrees C

Unanesthetized squirrel monkeys exposed to an ambient temperature of 10 degrees C showed elevations in total body oxygen consumption (VO2), systemic arterial blood pressure (BP), and heart rate (hr) above values recorded at 28 degrees C. Further elevation of BP in the cold by intravenous infusion of phenylephrine (5-50 microgram/kg-min) was accompanied by reduction in both VO2 and HR, and the changes in VO2 were proportional to those in HR. When BP was raised by intravenous infusion of angiotensin (0.05-1.0 microgram/kg-min), large elevations in BP were again accompanied by reductions in HR and VO2. However, for equivalent elevations in BP, the depressions in both HR and VO2 were much smaller with angiotensin than they were with phenylephrine. Previous studies in this laboratory have demonstrated that in response to experimental elevation of BP, reflexes originating at the sinoaortic baroreceptors depress not only HR but also VO2. The present results suggest that angiotensin modulates baro-reflexive responses to elevation in BP. The reductions in HR and VO2 that ordinarily occur in response to baroreceptor stimulation may be modified by an action of angiotensin on the central nervous system.

Autonomic correlates of meditation and hypnosis.

Abstract Peripheral autonomic responses during meditation and autohypnosis are compared with controls. HR, Resp, and GSR were assessed during a meditation/hypnosis period and compared to both pre- and post-baseline conditions for three groups of 10 Ss each: Transcendental Meditators, Ss trained in autohypnosis, and control Ss. All Ss were selected for high susceptibility to hypnosis. There were no significant differences between groups on any initial baseline measures. All groups showed a marked reduction of all autonomic measures during the experimental period. Meditators showed a more persistent reduction of HR extending into the post-baseline condition. The results suggest that, at least for the measures investigated, meditation and hypnosis do not differ markedly from each other nor from instructed relaxation.

Analysis of Interphase Chromosome Damage by Means of Premature Chromosome Condensation after X- and Ultraviolet-Irradiation

Sendai virus-mediated fusion between mitotic and interphase mammalian cells causes the rapid condensation of the interphase chromosomes into distinct structures, a process termed premature chromosome condensation. This phenomenon has been used to assess the immediate action of x-rays and ultraviolet light on the chromosomes of HeLa cells irradiated in the G1 phase of the life cycle. X-irradiation produces fragmented chromosomes; but even the most finely chopped fragments retain the condensed morphology characteristic of the premature chromosome condensation of unirradiated G1 cells. For doses up to about 1800 rads, the increase in the number of fragments is linearly related to the dose. One mean lethal dose (about 100 rads) yields a net increase of 10-15 fragments per G1 cell, which is considerably larger than previous estimates based on scoring of mitotic chromosomes. Incubation of irradiated cells produces a rapid (within 2 hr) reduction in the number of fragments, indicative of a rejoining process. The decrease in the number of pieces is not accompanied by unscheduled DNA synthesis detectable by radioautography. G1 chromosomes of cells irradiated with UV light in G1 phase are not appreciably fragmented but are elongated and attenuated so that they resemble the premature-chromosome-condensation chromosomes of unirradiated S-phase cells. Both the degree of "S-like" character attained by the G1 chromosomes in a cell and the percentage of the cell population displaying the G1 --> S transition increase with the dose and incubation time after irradiation. Thus, in contrast to the immediate manifestation of damage from x-rays, the maximum induction of the "S-like" state does not occur until about 2 hr after irradiation. The "S-like" chromosomes are capable of unscheduled DNA synthesis. We suggest that the difference in chromosome morphology found after UV- and x-irradiation underlies the reason why the former, but not the latter, induces unscheduled DNA synthesis in G1 cells.

Chemical states and thermal annealing of the 131I, 133I and 135I formed by 235U fission during thermal neutron irradiation of uranyl nitrate at room and liquid nitrogen temperatures

By means of an ion exchange method, using KNO 3 solutions as eluant, the species IO 4 −, IO 3 −, I − and I 0 have been separated, after dissolution of uranyl nitrate crystals irradiated with thermal neutrons. The average percentages as iodide are: 35·22 for 131I, 41·82 for 133I and 70·6 for 135I when the uranyl nitrate crystals were irradiated at 10 11 n cm −2 sec −1 (CT-2 channel of VVRS Reactor) and reactor channel temperature. With an 8·8 × 10 8 n cm −2 sec −1 (CT-3 channel) thermal neutron flux, the same average values are: 34·55 for 131I, 47·45 for 133I and 88·33 for 135I at reactor channel temperature, and 41·57, 50·48, 86·01 respectively at liquid nitrogen temperature. The dehydration temperature of the uranyl nitrate crystals before irradiation seems not to have an important effect on the initial values of the percentage of reduced form. In the case of the 131I and 133I isotopes (CT-2 channel) on heating the irradiated crystals at 100°C, oxidised forms increase during the first 2–4 hr. Then reduction becomes the predominant process and the red/ox ratio reaches a higher steady value for the samples pre-heated at 51°C, than those pre-heated at 100°C. On heating the irradiated crystals at 150°C, oxidation processes are always predominant for all three 131I, 133I and 135I isotopes. With the uranyl nitrate crystals irradiated in the CT-3 channel at liquid nitrogen temperature, thermal annealing at 100°C favours the reduction of both 131I and 133I forms. At 130°C, in the first 10 hr reduction of iodine occurs, but after this period oxidation becomes predominant. At 150°C only oxidation was observed. The 135I isotope behaved differently. The species formed oxidise at all temperatures studied.

Effect of fixatives on silver impregnation of plant cells.

The kind of fixative and duration of fixation modify the affinity of plant cell structures, as shown by a 10-15 hr impregnation at 70 C in 2% aqueous AgNO2, and a 1-2 hr reduction at room temperature by a 1:1 mixture of 10% formalin and 1% hydroquinone. Cytoplasmic staining was enhanced by fixing in salts of heavy metals, in buffered 6.5% glutaraldehyde, and in 0.5% picric acid. Nuclear staining was prominent after mixtures of glutaraldehyde and hydroquinone, after formalin and pyrogallol, and after acetone, propylene glycol or ether. Nucleolar staining was favored by fixing in 10% formalin, in 5% formalin containing 0.5% hydroquinone, in 50% ethanol containing 0.5% pyrogallol, or in ethylene glycol. Chromosome staining was favored by fixation in 50% acetic or propionic acid, in 2% trichloroacetic acid, and in methanol or ethanol. The best morphological preservations were seen after 50% acetic acid, 6.5% glutaraldehyde, or the 5% formalin-0.5% hydroquinone mixture.

ACUTE REDUCTION OF PLASMA NONESTERIFIED FATTY ACID BY GROWTH HORMONE IN HYPOPHYSECTOMIZED AND HOUSSAY RATS.

Intraperitoneal administration of 1 or 3 mg of bovine growth hormone (GH, NIH-916) to hypophysectomized Sprague-Dawley rats evoked a diminution of plasma nonesterified fatty acids (NEFA) at 30 and 60 min. These effects were clearly distinct from the commonly observed elevation at 2–6 hr. Hypoglycemia and hypoaminoacidemia were associated temporally with the decline in plasma NEFA, Epididymal fat pads at 6 hr showed increased relative water content, as indirect evidence of intense lipid mobilization. Subtotal (95 %) pancreatectomy 3–5 days prior to removal of the hypophysis failed to prevent the 1 hr reduction of plasma NEFA in response to GH. A dose of ACTH 3 times greater than that calculated as a maximum contaminant in the larger of the GH doses used failed to elicit the 1 hr NEFA decline. The acute diminution of plasma NEFA strongly suggests, from temporal relations alone, that the adipokinetic response is not a primary effect of GH. (Endocrinology 76: 665, 1965)

SILVER IMPREGNATION OF THE GOLGI APPARATUS WITH SUBSEQUENT NITROCELLULOSE EMBEDDING.

The appearance of silver impregnation of the Golgi apparatus can be enhanced by the use of nitrocellulose as an embedding medium. Fixation of 1.5 mm thick pieces of fresh tissue for 8 hr in: glycine, 1.7 gm; 15% formalin, 100 ml; HNO3, conc., 0.5 ml, at pH 2.6 followed by rinsing in water, 4 hr in 1.5% AgNO3, another rinse, and 2 hr reduction in 1.5% hydroquinone in 15% formalin. This staining procedure yields consistently good results for rat, rabbit, and human tissues. Low-viscosity nitrocellulose embedding is done by infiltrating at 56 C in 7% nitrocellulose for 0.5 hr, 15% for 4 hr, and 27% for 1 hr. The nitrocellulose is hardened 2 hr in chloroform, after which, sections as thin as 5 μ can be cut on a sliding microtome. Gold toning and counterstaining can be done with the tissue affixed to the slide. The Golgi apparatus is stained dark brown to black, and there is better preservation of cellular detail than in tissues processed in paraffin.

Ferrimagnetic Resonance and Torque Measurements on Ytterbium-Substituted Yttrium Iron Garnet

It is pointed out that the comparison of microwave resonance and static torque measurements on single-crystal samples may enable relaxation effects in the former to be identified. Such a comparison is made for a crystal of nominal composition (Yb0.021Y0.979)3Fe5O12 in the temperature range 4.2–250°K. It is shown that for this crystal, as in Yb3Fe5O12, the anisotropy in Hr, the field for resonance, is not due only to magnetocrystalline energy in a range of temperatures below 220°K. It is suggested that the extra reduction in Hr observed,which occurs most strongly in the [111] directions, is associated with the heavily damped motion of the magnetization of the ytterbium ion. Both types of measurement show that between 20 and 4.2°K, the magnetocrystalline energy surface of the ytterbium ion changes very rapidly and develops sharp curvature.