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Biomedical subjects

J D Allen

Publications and source records attributed to J D Allen.

At least 91 records · Page 5Linked to original sources
PubMed1989

Cardiac injury with damped sine and trapezoidal defibrillator waveforms.

To assess defibrillator-induced cardiac damage, 49 anaesthetized greyhounds received either no shocks (control group) or five shocks from a defibrillator delivering one of five waveforms (Lown, Edmark, Belfast damped sine waveforms: 5 and 20 ms trapezoidal waveforms). At 3 days the hearts of the 36 surviving dogs were examined for macroscopic damage. The Belfast and Edmark waveforms caused significantly more damage (mean 21.1 +/- SEM 2.9 g and 16.0 +/- 3.7 g) respectively than the Lown waveform (3.5 +/- 1.3 g) P less than 0.01. The 20 ms trapezoid caused significantly more damage (8.1 +/- 3.1 g) than the 5 ms pulse (0.7 +/- 1.3 g) P less than 0.05). The ventricular ectopic counts per minute were not significantly different in the three sine wave and 20 ms trapezoidal groups at 24 and 48 h (P greater than 0.05), but at 2 and 72 h were significantly greater in the Belfast and Edmark groups than in the Lown group (2 h, Belfast P less than 0.01, Edmark P less than 0.05: 72 h P less than 0.05). At 15 min there was more right chest ST-segment elevation in the Belfast than in the Lown, Edmark and 20 ms trapezoid groups (P less than 0.01), while left chest ST elevation was greater in the Belfast and Edmark than in the Lown (P less than 0.05) and 20 ms trapezoid groups (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Metabolic changes and mitochondrial dysfunction early following transthoracic countershock in dogs.

The mechanisms of myocardial injury and necrosis following transthoracic shocks from a direct current cardiac defibrillator were investigated in adult greyhounds. Myocardial lactate extraction became negative maximally at 1 minute, following two (mean -22% +/- SEM23) or five (-193% +/- 135) shocks and returned to baseline in 6-15 minutes. Myocardial necrosis assessed at 4 hours following the shock period was 0.05 g (+/- 0.03) after two shocks, 6.69 g (+/- 1.76) after five shocks and zero in controls. In further experiments, dogs received five or zero (dummy) shocks and mitochondria were isolated from their hearts following excision within 1 minute of receiving the final shock. Maximal oxygen consumption in right ventricular mitochondria was lower than the unshocked controls with both glutamate (66.9 +/- 9.4 nanoatoms of oxygen/mg per minute, n = 9 vs 86.6 +/- 13.6 nanoatoms/mg per minute, n = 7) and succinate (96.2 +/- 8.7 nanoatoms/mg per minute, n = 9 vs 119.5 +/- 14.4 nanoatoms/mg per minute, n = 7) as substrates. Using electron spin resonance spectroscopy, an increase in a peroxyl-free radical with g = 2.031 was detected in myocardial tissue after two internal shocks (50 joules stored energy, 0.5-minute intervals). We conclude that mitochondrial dysfunction and free-radical generation are likely contributors to cellular injury following multiple countershocks.

Animals↗
PubMed1988

Fourier analysis of ventricular fibrillation and synchronization of DC countershocks in defibrillation.

Spectral analysis of the first 40 seconds of ventricular fibrillation confirmed the presence of a large periodic component in fibrillation, with a dominant frequency of 9.9 +/- 0.7 Hz and a narrow bandwidth. To determine whether less energy was required for defibrillation at any particular phase of the ventricular fibrillation cycle, the authors studied the effect of synchronization of the countershock to the peaks and troughs of the ventricular fibrillation waveform in 12 dogs anesthetized with sodium pentobarbitone (35 mg/kg iv). There was no significant difference in threshold-delivered energy or threshold-delivered current between shocks synchronized to the peaks of ventricular fibrillation, shocks synchronized to the troughs of ventricular fibrillation, and unsynchronized shocks.

Animals↗
PubMed1988

The effects of apomorphine on the acquisition of schedule-induced polydipsia in rats.

Injections of the dopamine agent, apomorphine, at the doses of 0.05, 0.50 and 1.0 mg/kg were given to three different groups of rats while a fourth group received an injection of the drug vehicle. The injections preceded each of 15 schedule-induced polydipsia (SIP) acquisition sessions in which the subjects bar-pressed for food pellets on a fixed interval 60-sec schedule of reinforcement. The vehicle-injected group developed SIP over sessions while each dose of apomorphine suppressed the acquisition of SIP. Bar-press rates were also depressed at the higher doses, while response patterning was affected at the lower dose. The results support the contention that a normally functioning dopamine system is necessary for the acquisition of SIP, but they do not support the view that this neurotransmitter system is specifically involved in the generation of SIP.

Animals↗
PubMed1988

Death and damage caused by multiple direct current shocks: studies in an animal model.

Patients who require multiple defibrillator shocks have a poor prognosis. In healthy greyhounds the acute mortality increased as the number of transthoracic shocks (400 J) applied increased (one shock 0/6: five shocks 8/18: 10 shocks 12/17 dogs died acutely from asystole or electromechanical dissociation). The appearance on electron microscopy of the myocardium of these dogs showed few specific abnormal features to account for the total contractile failure that occurs in these dogs. In the survivors, significant ST segment elevation was recorded from the precordial leads of the dogs receiving five and 10 shocks, but not those receiving a single shock. At three days there was significantly more macroscopic cardiac damage in the 10-shock (13.1 +/- 1.8 g) than in the five-shock (7.2 +/- 2.0) group (P less than 0.05). One shock caused little damage. Hence a single high-energy shock was well tolerated in this model. Multiple shocks caused cardiac injury and acute pump failure. These studies indicate the need to reassess why patients die following multiple shocks, and re-emphasise the need for optimized first-shock effectiveness.

Animals↗
PubMed1988

Effects of tocainide enantiomers on experimental arrhythmias produced by programmed electrical stimulation.

The enantiomers of tocainide, a Class Ib antiarrhythmic agent, have recently been shown to exhibit differences in antiarrhythmic activity and pharmacokinetic characteristics. The present study examined the antiarrhythmic and electrophysiological effects of SR tocainide, S tocainide, and R tocainide on arrhythmias in a conscious canine arrhythmia model and compared the results with placebo. Using up to three extrastimuli, programmed electrical stimulation was performed in conscious dogs, 7-30 days after coronary artery ligation. Each treatment was assessed for its ability to abolish sustained ventricular tachycardia, prevent nonsustained ventricular tachycardia, and protect against death (ventricular fibrillation), in groups of six dogs. In the placebo group, arrhythmias in four of six dogs remained unchanged, and two dogs died. SR tocainide prevented the arrhythmia in three of six dogs (mean effective dose, 21.3 mg/kg), one remained unchanged, and two died. S tocainide prevented the arrhythmia in four of six dogs (mean effective dose, 7.1 mg/kg), one remained unchanged, and one died (p less than 0.05 compared with placebo). R tocainide prevented the arrhythmia in five of six dogs (mean effective dose, 9.0 mg/kg), one remained unchanged, and none died (p less than 0.01 compared with placebo). PR intervals, QRS durations, and corrected QT intervals were unaffected by any treatment and there was no change in effective or functional refractory periods. These results indicate that the enantiomers of tocainide are more effective than the racemic mixture in abolishing ventricular arrhythmias and in preventing death in this model; no additive antiarrhythmic effect occurs with the racemic mixture, and adverse effects may be potentiated.

Animals↗
PubMed1987

Effect of dopamine agents on schedule- and deprivation-induced drinking in rats.

The dopamine agonist, apomorphine, or its antagonist, haloperidol, was administered to rats whose drinking was induced by fixed-interval schedules of pellet delivery or by water deprivation. The first study revealed that both drugs produced dose-dependent decreases in bar-pressing and schedule-induced polydipsia (SIP). At higher doses, haloperidol also depressed the rate of pellet delivery. The second study demonstrated that the suppression in SIP obtained in the first study was primarily due to the direct effect of the drugs and not to changes they produced on the underlying food reinforcement schedule. The third study showed that both drugs suppressed water deprivation-induced drinking during a ten-minute session. Apomorphine delayed the onset of drinking, while haloperidol accelerated the cessation of drinking. The results indicated that apomorphine produced motor deficits that interfered with consummatory behavior, and that haloperidol interfered with the sensory feedback necessary to sustain consummatory behavior.

Animals↗
PubMed1987

Effect of molybdenum treatments on the distribution of Cu and metallothionein in tissue extracts from rats and sheep.

An examination was made of the effects of tetrathiomolybdate (TTM), ammonium molybdate (AM), sodium sulphide, and two molybdo amino acids (cysteine-Mo, cysteine-Mo-S) on the distribution of Cu and Zn among proteins in extracts of the livers and kidneys of rats and sheep. Tetrathiomolybdate caused a shift in the chromatographic distribution of Cu from low molecular weight proteins such as metallothionein (MT) to proteins of higher molecular weight (greater than 100,000 daltons). This was not due to polymerization or cross-linking of metallothionein with the latter, but to the formation of protein-TTM complexes that had a strong affinity for Cu. There was a concomitant redistribution of Zn towards proteins of low molecular weight. Pretreatment of high molecular weight proteins from rat liver with TTM greatly increased the capacity of the proteins to remove Cu from MT. When AM or sodium sulphide were added together to extracts of rat liver, changes similar to those induced by TTM were observed in the chromatographic distribution of Cu and Zn. Individually, these compounds had no significant effect on the distribution of the metals. Of the two molybdo amino acids, only cysteine-Mo-S altered the chromatographic distribution of Cu in extracts of rat liver. The redistribution was in the same direction as that induced by TTM, but was not as pronounced.

Animals↗
PubMed1987

Involvement of the solid phase of rumen digesta in the interaction between copper, molybdenum and sulphur in sheep.

1. Merino sheep fed on a diet of chopped wheaten hay, chopped lucerne (Medicago sativa) hay and oat grain were the source of rumen contents for the study. The diet contained (mg/kg dry weight) 3.3 copper, 0.24 molybdenum and 2.8 sulphur. The effects of adding between 5 and 25 mg Mo/kg as ammonium molybdate (AM) or tetrathiomolybdate (TTM) on the distribution and forms of Cu and Mo in rumen contents were investigated in vivo and in vitro. 2. Approximately 88% of the Cu and 94% of the Mo in rumen contents were associated with the solid phase. When AM or TTM was added to rumen contents in vivo or in vitro the proportion of these elements in the solid phase was increased at the expense of the fluid phase. 3. The addition of AM and TTM to rumen contents also decreased the proportion of Cu that was soluble in trichloroacetic acid (50 g/l; TCA) and increased the proportion of Cu that was not extractable by sequential treatment with TCA and neutral detergent. 4. Column chromatography of neutral-detergent extracts of rumen contents revealed that TTM treatment caused Cu to be strongly bound to proteins of high molecular weight. 5. Addition of sulphide to rumen contents did not result in significant changes in the distribution of Cu between the fluid and solid phases, or in the solubility of Cu in TCA. 6. It is postulated that constant removal of TTM from the fluid phase via reaction with proteins and other macromolecules in the solid phase results in greater formation of TTM in vivo than would be expected from solution chemistry. The molybdo-proteins so formed are strong chelators of Cu and may be the agents responsible for the decrease in Cu absorption in animals that consume diets containing high concentrations of Mo.

Animals↗
PubMed1987

Factors influencing the ascending limb of the sarcomere length-tension relationship in rabbit skinned muscle fibres.

1. The length dependence of Ca2+-activated tension within the ascending limb of the length-tension relationship, corresponding to sarcomere lengths below about 2.25 micron, was investigated in skinned fibres from rabbit psoas muscle. At high [Ca2+] a shallow phase and then a steep phase of tension decline were observed as sarcomere length was reduced, while at low [Ca2+] tension decreased monotonically with decreases in sarcomere length. The sarcomere length at which the ascending limb intersected zero tension was greater for lower concentrations of Ca2+. 2. The length tension relationship from maximally activated fibres changed when filament lattice spacing was reduced by osmotic compression. Relationships obtained in the presence of 5% (w/v) dextran T500 more distinctly demonstrated both the shallow and steep portions of the ascending limb than did relationships from untreated fibres. 3. As striation spacing was decreased a progressive decline in the Ca2+ sensitivity of tension development was observed. Tension-pCa relationships from both control and dextran-treated fibres underwent a rightward shift (i.e. to a higher [Ca2+]) by 0.23 pCa units as sarcomere length was reduced between 2.46 and 1.54 microns. 4. Fibre stiffness was studied by applying a 3.3 kHz sinusoidal length change at one end of the fibre and measuring the resultant tension change. At submaximal activation (pCa 5.8), stiffness increased relative to tension as sarcomere length was decreased below approximately 2.4 microns, suggesting that there is an activation-related internal load at low [Ca2+]. At maximal activation, a significant increase in this ratio occurred only at sarcomere lengths less than approximately 1.8 microns, and presumably involved collision of the thick filaments with the Z-lines. 5. Length-dependent changes in the Ca2+ sensitivity of tension development do not appear to be the result of shortening-induced dissociation of Ca2+ from troponin-C, the Ca2+ binding subunit of troponin. Fibres activated in the absence of Ca2+, by the partial removal of whole troponin complexes, produced length-tension relationships similar to those observed in the same fibres before troponin removal at a submaximal [Ca2+] yielding similar active tensions.

Animals↗
PubMed1986

Human schedule-induced cardiovascular response.

Sixty-six students were randomly assigned to a vigilance task during which observing responses produced targets according to either a fixed-interval or random-interval 90-sec schedule. During the task, interbeat interval, masseter (EMG) activity, blood pressure and digital blood volume pulse were monitored. Vasoconstriction was initiated within a 4 to 6-sec period following target detection for the majority of subjects assigned to each schedule. Vasomotor tone returned to prechange levels approximately 16 sec after target detection. Transient heart rate increases also occurred during the post-event period, but were more prevalent with subjects in the fixed than in the random-interval group. Post-event masseter activity was exhibited infrequently and only by subjects assigned to the fixed-interval group. The involvement of cardiovascular responsiveness with human schedule-induced behavior and the implications of this involvement for arousal theories of schedule-induced behavior are discussed.

Adolescent↗
PubMed1986

Involvement of organic molybdenum compounds in the interaction between copper, molybdenum, and sulfur.

The effect on Cu metabolism of two organic Mo compounds, cysteine-Mo (CM) and cysteine-Mo-S (CMS), and of an inorganic compound, tetrathiomolybdate (TTM), was investigated in sheep. Intravenous administration of CMS or TTM increased total plasma Cu concentrations and promoted the appearance of trichloroacetic acid (TCA)-insoluble Cu in plasma. Plasma Mo was increased by both compounds. Column chromatography of plasma showed that CMS caused the accumulation of TCA-insoluble Cu in high-MW fractions, whereas TTM increased the Cu content of low-MW fractions, mainly albumin. CMS and TTM increased the concentration of Cu and Mo in kidney. In liver, Mo concentrations were elevated by both CMS and TTM, and Cu concentrations were reduced by TTM when it was given at a low dose rate. The subcellular distribution of Cu and Mo in liver and kidney was investigated. The findings are discussed in relation to the proposal that Mo-containing, organic compounds are intermediaries in the interaction between Cu, Mo, and S in ruminants.

Animals↗
PubMed1986

Effects of partial extraction of troponin complex upon the tension-pCa relation in rabbit skeletal muscle. Further evidence that tension development involves cooperative effects within the thin filament.

Partial extraction of troponin C (TnC) decreases the Ca2+ sensitivity of tension development in mammalian skinned muscle fibers (Moss, R. L., G. G. Giulian, and M. L. Greaser. 1985. Journal of General Physiology. 86:585), which suggests that Ca2+-activated tension development involves molecular cooperativity within the thin filament. This idea has been investigated further in the present study, in which Ca2+-insensitive activation of skinned fibers from rabbit psoas muscles was achieved by removing a small proportion of total troponin (Tn) complexes. Ca2+-activated isometric tension was measured at pCa values (i.e., -log[Ca2+]) between 6.7 and 4.5: (a) in control fiber segments, (b) in the same fibers after partial removal of Tn, and (c) after recombination of Tn. Tn removal was accomplished using contaminant protease activity found in preparations of LC2 from rabbit soleus muscle, and was quantitated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and scanning densitometry. Partial Tn removal resulted in the development of a Ca2+-insensitive active tension, which varied in amount depending on the duration of the extraction, and concomitant decreases in maximal Ca2+-activated tensions. In addition, the tension-pCa relation was shifted to higher pCa values by as much as 0.3 pCa unit after Tn extraction. Readdition of Tn to the fiber segments resulted in the reduction of tension in the relaxing solution to control values and in the return of the tension-pCa relation to its original position. Thus, continuous Ca2+-insensitive activation of randomly spaced functional groups increased the Ca2+ sensitivity of tension development in the remaining functional groups along the thin filament. In addition, the variation in Ca2+-insensitive active tension as a function of Tn content after extraction suggests that only one-third to one-half of the functional groups within a thin filament need to be activated for complete disinhibition of that filament to be achieved.

Animals↗
PubMed1984

Lack of effect of bretylium tosylate on electrical ventricular defibrillation in a controlled study.

The threshold stored energy and transthoracic current for electrical defibrillation were determined in dogs anaesthetised with pentobarbitone. Groups were randomly allocated to pre-treatment with either saline or bretylium. The intravenous administration of bretylium tosylate (10 to 30 mg . kg-1) did not significantly alter either measurement. The drug caused large changes in heart rate and arterial blood pressure.

Animals↗
PubMed1984

The long term efficacy of a hardjo-pomona vaccine in preventing leptospiruria in cattle exposed to natural challenge with Leptospira interrogans serovar hardjo.

The long term efficacy of a commercially prepared bivalent vaccine against Leptospira interrogans serovar hardjo and L. interrogans serovar pomona was evaluated in a group of 82 dairy heifers exposed to natural challenge with L. interrogans serovar hardjo for up to 55 weeks after calfhood vaccination. Nineteen heifers were vaccinated twice with a one-month interval, at calfhood (9 to 10 months). A further 18 heifers received a similar calfhood vaccination regimen plus a third injection at adulthood (22 to 23 months), while 19 heifers were vaccinated twice at adulthood only and finally 22 heifers were used as unvaccinated controls. At 55 weeks after calfhood vaccination and prior to adulthood vaccination, only 2.7% of the vaccinated heifers were found to have leptospiruria compared with 58.5% of the unvaccinated heifers (p less than 0.0001). Microscopic agglutination (MA) titres at the same time in the unvaccinated heifers ranged from 32 to 4096 while those vaccinated at calfhood ranged from 32 to 64. Adult vaccination of infected animals did not significantly reduce leptospiruria . Prior to adulthood vaccination, 9 of 19 heifers had leptospiruria , in comparison to 4 of 15 after adulthood vaccination. At the same sampling periods 15 of 22 controls had leptospiruria in comparison to 4 of 9 subsequently tested.

Animals↗
PubMed1984

The effects of shock energy, propranolol, and verapamil on cardiac damage caused by transthoracic countershock.

Myocardial damage by transthoracic countershocks was assessed by observation for electrocardiographic loss of R waves and elevation of ST segments, creatine kinase depletion, and histologic evidence of necrosis in damaged areas, and by excision and examination, 3 days later, of all tissue macroscopically observed to be damaged. When 4000 J of stored energy was passed across the chest of dogs anesthetized with pentobarbital sodium (30 mg/kg), more damage was caused when the energy was divided among 10 shocks than when it was applied in 20 or 40 shocks (at intervals of 0.5 min). The prior intravenous administration of verapamil (1 mg/kg) reduced the weight of damaged shocks. Propranolol (0.4 mg/kg) had no effect. These results give further evidence for the role of calcium accumulation in cardiac necrosis after direct current countershocks. Multiple low-energy shocks cause less cardiac damage than do a few high-energy shocks of similar total energy.

Animals↗
PubMed1984

Bedside evaluation of respiratory distress.

Observations made at the time of the first trial of independent ventilation in 112 episodes of mechanical ventilatory support led to identification of a group of indicators, each of which, when present, was significantly associated (p less than 0.05) with a need for continued mechanical ventilation and/or with death. Six of these were potentially suitable for use in a format for clinical assessment of the risk of respiratory failure: pulse over 120 or under 70 beats per minute, respiratory rate of over 30, palpable scalene muscle recruitment in inspiration, palpable abdominal tensing in expiration, presence of irregular irregularity of respiratory rhythm with apneic pauses of varying duration, and coma or any condition preventing a patient from responding appropriately to commands aimed at producing ventilatory movements like those needed for vital capacity testing. When none of the six signs was present, there was a 90 percent chance of a favorable outcome. With one or two indicators positive, more than 50 percent of the subjects required further ventilatory support or died. There were no favorable outcomes when three or more of the signs were present together.

Adult↗