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Biomedical subjects

M J Miller

Publications and source records attributed to M J Miller.

At least 343 records · Page 19Linked to original sources
PubMed1989

Assessment of right atrial pressure-volume relations in patients with and without an atrial septal defect.

Assessment of the complex relations between pressure and volume in the right atrium has been hampered in the past by difficulties in the measurement of atrial volume. Accordingly, in the present study the dynamics of right atrial pressure-volume relations were examined (with the use of an impedance catheter to measure right atrial volume) in patients with and without an atrial septal defect. Right atrial pressure and impedance volume were measured in 16 patients at the time of cardiac catheterization with the use of a multi-electrode impedance catheter to provide continuous, on-line, pressure-volume data. Eleven patients without evidence of an interatrial shunt were examined during normal respiration and during the Valsalva maneuver and contrasted with five patients with an atrial septal defect documented by oxygen saturation step-up and echocardiographic studies. Right atrial pressure-volume diagrams in patients without an atrial septal defect exhibited the normal figure eight pattern, with an A loop (atrial contraction) and a V loop (passive filling), corresponding to the A wave and V wave of right atrial pressure, respectively. During inspiration, mean right atrial pressure decreased and mean right atrial volume increased, consistent with augmented venous return. With the Valsalva maneuver, right atrial pressure increased and both right atrial stroke volume and mean right atrial volume decreased compared with baseline. Patients with an atrial septal defect demonstrated baseline pressure-volume diagrams similar to those of patients without an interatrial shunt. However, no change in mean right atrial volume occurred with either respiration or the Valsalva maneuver despite changes in right atrial pressure similar to those seen inpatients without an atrial septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Mutations in the conserved proline 43 residue of the uncE protein (subunit c) of Escherichia coli F1F0-ATPase alter the coupling of F1 to F0.

The conserved Pro43 residue of the uncE protein (subunit c) of the Escherichia coli F1F0-ATPase was changed to Ser or Ala by oligonucleotide-directed mutagenesis, and the mutations were incorporated into the chromosome. The resultant mutant strains were capable of oxidative phosphorylation as indicated by their ability to grow on succinate and had growth yields on glucose that were 80-90% of wild type. Membrane vesicles from the mutants were slightly less efficient than wild type vesicles in ATP-driven proton pumping as indicated by ATP-dependent quenching of quinacrine fluorescence. The decreased quenching response was not due to increased H+ leakiness of the mutant membranes or to loss of F1-ATPase activity from the membrane. These results indicate that the mutant F1F0-ATPases are defective in coupling ATP hydrolysis to H+ translocation. The membrane ATPase activity of the mutants was inhibited less by dicyclohexylcarbodiimide than that of wild type. The decrease in sensitivity to inhibition by dicyclohexylcarbodiimide was caused primarily by dissociation of the F1-ATPase from the mutant F0 in the ATPase assay mixture. These results support the idea that Pro43, and neighboring conserved polar residues play an important role in the binding and functional coupling of F1 to F0. Although a Pro residue is found at position 43 in all species of subunit c studied, surprisingly, it is not absolutely essential to function.

Dicyclohexylcarbodiimide↗
PubMed1989

Effects of respiration and vasodilation on venous volume in animals and man, as measured with an impedance catheter.

Venous return determines cardiac preload and is in turn affected by respiration and vasodilation. The purpose of the present study was to examine the dynamics of venous return and venous volume, using impedance volume measurements in the venous system. In order to develop a methodology for the assessment of venous volume and venous return in man, we first studied 17 endotracheally intubated and ventilated anesthetized closed-chest dogs. We measured central venous and inferior vena cava (IVC) pressure (micromanometer) and volume (impedance catheter). Studies were done above and below the diaphragm with normal ventilation, with positive end-expiratory pressure (PEEP), and with beta-adrenergic blockade and i.v. nitroglycerin. Intrathoracic IVC volume fell and extrathoracic IVC volume rose with lung inflation, while PEEP raised extrathoracic IVC volume and lowered intrathoracic IVC volume. Nitroglycerin lowered intrathoracic IVC volume. Beta blockade did not affect IVC volume, ventilatory variation, or response to PEEP and nitroglycerin. We performed similar studies in 14 human subjects during normal quiet respiration, with measurements above and below the diaphragm, and with interventions including Valsalva maneuver and i.v. nitroglycerin. Intrathoracic IVC volume fell and extrathoracic IVC volume rose with expiration and Valsalva maneuver. Nitroglycerin again lowered intrathoracic IVC volume. We conclude that venous volume and the dynamics of venous return can be assessed in animals and man with an impedance catheter. Specifically, we show the divergent effects of respiration, ventilation, PEEP, and nitroglycerin on IVC volumes above and below the diaphragm. Beta-adrenergic blockage does not appear to play a role in altering any of these effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1989

Effect of nifedipine on the contractile function of the rat diaphragm in vitro.

The isometric contractile response of the directly-stimulated rat diaphragm was studied before and following addition of the calcium channel blocker, nifedipine. Nifedipine (10 micrograms/ml and 30 micrograms/ml bath concentrations) significantly increased isometric force output during twitch and unfused tetanic stimulation. Force potentiation during unfused tetanic stimulation was equivalent during either high or low voltage stimulation. Nifedipine had no effect on the time to peak force, half relaxation time, or relaxation time during twitch stimulation; thus, both activation and relaxation rates were increased. The force potentiating actions of nifedipine persisted in a calcium-free bathing solution and were enhanced by d-tubocurarine. In contrast to the force enhancing effects found with twitch and unfused tetanic stimulation, nifedipine caused a small but significant reduction in isometric force during maximal fused tetanic stimulation. It is concluded that the force potentiating effects of nifedipine on rat diaphragm are not due to fiber recruitment, enhancement of neuromuscular excitation, or altered inward trans-sarcolemmal calcium flux, but may result from a direct effect of the drug on the rate of activation of the contractile apparatus.

Animals↗
PubMed1989

Inhibition by nifedipine of the indirectly induced contractile response of the rat diaphragm.

The effects of nifedipine (30 micrograms/ml) on isometric force production of in-vitro rat diaphragm were studied during direct and indirect modes of muscle activation. During direct muscle stimulation, nifedipine potentiated isometric force during twitch and unfused tetanic stimulation. Indirectly elicited responses, evoked by stimulation of the phrenic nerve, were uniformly depressed following nifedipine. Inhibition of indirect force production increased with time, while force potentiation with direct activation remained constant. We conclude that inhibitory effects of nifedipine on the phrenic nerve-diaphragm preparation are specific for nerve or neuromuscular junction.

Animals↗
PubMed1989

Spermexatin and spermexatol: new synthetic spermidine-based siderophore analogues.

Syntheses of hexanediamine-based dihydroxamate (Hexamate), spermidine-based trihydroxamate (Spermexatins), and spermidine-based mixed siderophore analogues (Spermexatols) are described. Key intermediates include the N-hydroxysuccinimide esters of various hydroxamic acids, e.g., malonohydroxamate, succinohydroxamate, and glutarohydroxamate. These intermediates were synthesized, characterized, and incorporated as the ligating chains on spermidine. Also, mixed iron chelating compounds (Spermexatols) with both catechol and hydroxamic acid side chains were synthesized. The reagent carbobenzoxyimidazole was employed to distinguish between the primary and secondary amino groups of spermidine. The ability of these iron chelators to stimulate microbial growth is also described.

Iron Chelating Agents↗
PubMed1989

Effects of unilateral nasal occlusion on ventilation and pulmonary resistance in infants.

Because neonates are vulnerable to spontaneous nasal obstruction, this study was designed to evaluate the ventilatory consequences of obstructing a single nasal passage in preterm infants. We employed a nasal pneumotachograph that separately quantified airflow between the two nasal passages and permitted unilateral nasal mask occlusions. Changes in minute ventilation (VI) and total (RT) and inspiratory pulmonary resistance (RI) were measured in response to 30-s unilateral occlusions during quiet and active sleep in 11 subjects. Unilateral nasal obstruction caused VI to fall significantly in both sleep states, because of a fall in both tidal volume and respiratory rate, without alteration in transcutaneous blood gases. RT and RI increased by 27 and 24 cmH2O.1-1.s, respectively, during unilateral nasal occlusion; this increase was greater than would be expected solely from elimination of one nasal passage. In 7 of the 11 infants a single dominant side could be identified as contributing 56-67% to tidal volume. The effect of occlusion on VI, RT, or RI did not differ whether the dominant or nondominant side was occluded. We conclude that unilateral nasal mask occlusion increases RT and RI and decreases VI in preterm infants. The larger than expected increase in resistance suggests that unilateral nasal loading predisposes to narrowing of the extrathoracic airway, and this may explain the comparable ventilatory responses to occluding the dominant and nondominant nasal passage.

Airway Obstruction↗
PubMed1989

Theophylline does not increase maximal tetanic force or diaphragm endurance in vitro.

These experiments tested the capacity of theophylline to improve diaphragm strength (maximal force development) and endurance (maintenance of force output during repeated contractions). Rodent diaphragm strips were mounted at optimal length in oxygenated Krebs-Ringer solution (37 degrees C, pH 7.37). Direct stimuli used supramaximal current density, 0.2-ms pulses, and 250-ms tetanic trains. Theophylline (500 mg/ml) increased force development at low stimulation frequencies but did not increase maximal force [25.7 +/- 0.5 for theophylline vs. 26.0 +/- 0.4 (SE) N/cm2 for control (n = 34)]. During repeated submaximal (25-36 Hz) tetanic contractions, theophylline did not affect endurance. During repeated maximal (160 Hz) tetanic contractions theophylline reduced endurance, accelerating the fall of developed force. Theophylline also inhibited recovery of force after endurance trials ended. We conclude that theophylline does not increase maximal tetanic force and can reduce diaphragm endurance in vitro.

Animals↗
PubMed1989

Diaphragm atrophy and weakness in cortisone-treated rats.

Despite frequent therapeutic use, the potential of corticosteroids to produce respiratory muscle myopathy is unknown. We studied effects of chronic steroid treatment on diaphragm mass and function. Eleven Sprague-Dawley rats were treated with cortisone acetate (100 mg.kg-1.day-1 im) for 10 days. Controls (injected with vehicle) included 11 freely eating rats and 11 animals pair fed to match food intake of cortisone rats. Steroid treatment depressed body weight 30% compared with controls. Mass of diaphragm, gastrocnemius, and extensor digitorum longus showed significant atrophy (30%); heart and soleus were unaffected. Isometric contractile properties of costal diaphragm strips were studied in vitro using direct stimulation. The force-frequency relationship was markedly depressed by steroid treatment, both at low and high frequencies. However, force developed per unit cross-sectional area was similar among all three groups, as were twitch characteristics. When stimulated every minute, forces developed by control strips fell progressively, whereas the forces of cortisone-treated strips remained unchanged. When stimulated every 5 s, the fall in force was not different between groups. We conclude that cortisone weakened the diaphragm by decreasing muscle mass but made the diaphragm more resistant to one form of fatigue in vitro.

Animals↗
PubMed1989

Alcohol consumption and chronic obstructive pulmonary disease.

This study examined the relationship between lifetime alcohol consumption and respiratory symptoms in 195 subjects (including 111 alcoholics) and FEV1 level in 165 subjects (including 91 alcoholics). After adjustment for age and cigarette smoking status, using multiple logistic regression, lifetime alcohol consumption was a significant predictor of chronic cough and chronic phlegm, but not of any wheeze or persistent wheeze. Multiple linear regression analysis indicated that lifetime alcohol consumption was also a predictor of lower levels of FEV1 in a model that included age, pack-years of cigarette smoking, and an interaction between alcohol consumption and pack-years. The interaction between smoking and alcohol consumption was in a direction opposite to the independent effects of alcohol and smoking, suggesting a protective effect of alcohol with heavier amounts of smoking. Additional study is needed to further assess the relationship between respiratory symptoms and alcohol consumption, and between pulmonary function and alcohol consumption.

Adult↗
PubMed1989

Genioglossus and diaphragm activity during obstructive apnea and airway occlusion in infants.

To document mechanisms contributing to upper airway collapse, we compared the electromyographic activity of the genioglossus (GG) and diaphragm (DIA) during spontaneous mixed and obstructive apnea and during induced end-expiratory airway occlusion in 11 premature infants. In addition to ventilation and esophageal pressure measurements, we obtained DIA and GG electromyograms (EMG) from subcostal and sublingual surface electrodes, respectively. Amplitude of the DIA EMG and the frequency of occurrence of the GG EMG were determined for: 1) the breath preceding apnea or occlusion, 2) the initial and last obstructed inspiratory efforts, and 3) the first breath at resolution of both apnea and occlusion. During spontaneous apnea with airway obstruction amplitude of the DIA, EMG decreased on the initial obstructed inspiratory effort and did not exceed that of the breath preceding apnea until reestablishment of flow. In contrast, during end-expiratory airway occlusion, the amplitude of the DIA EMG increased both during and at release of occlusion. In 18 +/- 6% of the spontaneous apneic episodes, GG EMG was present with the breath preceding apnea and this frequency did not increase significantly until resolution of the apnea. During induced airway occlusion, GG EMG was not present with the breath preceding occlusion but its frequency did increase to 58 +/- 8 and 42 +/- 8% with the last occluded inspiratory effort and the first breath after release of occlusion, respectively. The decreased presence of the GG EMG from the last occluded effort to the breath at release of occlusion (58 +/- 8 versus 42 +/- 8%, p less than 0.05) was probably due to the greater mechanoreceptor-mediated inhibition associated with reestablishment of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗
PubMed1989

The use of nitroprusside to characterize aortic pressure-diameter relationships.

The viscoelastic properties of the wall of the ascending aorta can be determined by calculating the relationship between pressure and diameter of the vessel. Because of potential nonlinearities in aortic pressure-diameter relationships, however, pressure-diameter curves are more accurate than compliance expressed as a single value in measuring aortic viscoelastic properties. To determine whether nitroprusside could be used to obtain aortic pressure-diameter curves over a wide range, we measured simultaneous aortic pressure and diameter in anesthetized dogs. The inferior vena cava (IVC) of each animal was briefly occluded to generate a baseline series of pressure-diameter points over a wide range of pressure and diameter. We found that moderate lowering of systolic arterial pressure (30 mmHg) with nitroprusside did not significantly affect the aortic pressure-diameter relationship in comparison with control measurements during brief IVC occlusions at similar pressures and diameters. Prolonged inferior vena caval occlusion and a more profound lowering of arterial pressure with nitroprusside or IVC occlusion resulted in a leftward and upward shift of the aortic pressure-diameter relationship, with higher pressures at comparable diameters and lower diameters at comparable pressures. However, with more profound changes in arterial pressure, possible reflex-mediated mechanisms that alter the baseline aortic pressure-diameter relationship may be activated. We conclude that nitroprusside can be used to obtain aortic pressure-diameter data over a wider range than that possible from a single cardiac cycle.

Journal Article↗
PubMed1989

Strategies and techniques for testing the precision, reliability and reproducibility of computerized two-dimensional gel electrophoresis analysis systems.

A set of test procedures is described for evaluating the reliability, precision and reproducibility of computer systems designed to analyze two-dimensional gel electrophoretograms. The Elsie 4 gel analysis system (Analyt. Biochem., 169, 49-70 (1988) is used to demonstrate the use of these tests. Three major groups of tests are described: analysis of the scanner; analysis of mathematically constructed model gels; and analysis of real gel images. Scanner tests involve evaluating the stability and reproducibility of the scanner. The tests consist primarily of measuring the output of the scanner over a time period to determine its stability, and evaluating the consistency of the scanner at different points in the scanning field. Commonly encountered real gel situations are simulated and analyzed by arranging computer-generated 'ideal spots' in different ways. With such gels we can determine such things as the ability of the computer system to separate closely resolved and/or shoulder spots; whether or not streaks and/or smears are handled correctly; how random noise affects measurements; and, in idealized situation, the accuracy of the quantitation. The idealized spots are generated using the two-dimensional Gaussian as a model of density distribution; other spot models can be used. The Elsie 4 system is capable of finding virtually any spot (if detection parameters are set low enough), and of resolving different-sized spots whose peaks are separated by one and one-half their mean half width). The most significant tests are done on a set of actual gels.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoradiography↗
PubMed1989

Rat vascular tissue contains a neutral endopeptidase capable of degrading atrial natriuretic peptide.

Neutral endopeptidase (NEP, EC 3.4.24.11), purified from renal brush border, cleaves the Cys7-Phe8 amide bond of rat atrial natriuretic peptide (ANP), to generate the inactive metabolite (ANP cleaved at the Cys7-Phe8 bond; x-ANP). To determine if NEP contributes to the inactivation of circulating ANP, we investigated the degradation of rat ANP (rANP, 1-28) in the vasculature. Formation of x-ANP from exogenous ANP was studied in a mesenteric arterial preparation by perfusion in a single pass system in the presence and absence of the NEP inhibitors, thiorphan or phosphoramidon. In addition, a purified membrane fraction was prepared from mesenteric arterial homogenate and compared with an equivalent renal membrane fraction. Formation of x-ANP was quantified by a specific immunoassay (ELISA). Renal and vascular membranes shared the same pH optima for x-ANP formation (pH 7.5), although x-ANP generation was considerably greater in renal vs. vascular membranes (31.6 and 0.4 nmol min-1 mg-1 of protein, respectively). Both preparations were inhibited in a similar, dose-dependent manner by phosphoramidon, thiorphan or a polyclonal antibody to NEP. In perfused mesenteric arteries, 1.6 +/- 0.8 pmol of x-ANP were generated from 1 microgram of ANP; this formation was inhibited 51% by 10 microM phosphoramidon or thiorphan. Plasma levels of x-ANP after bolus i.v. administration of rANP in rats, were inhibited (70-80%) by thiorphan at comparable doses to those used in perfused mesenteric arteries. These studies indicate that ANP is degraded in the vasculature by NEP or an "NEP-like" enzyme(s).

Animals↗