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Biomedical subjects

D G Allen

Publications and source records attributed to D G Allen.

At least 145 records · Page 8Linked to original sources
PubMed1989

Comparison of the effects of inotropic interventions on isometric tension and shortening in isolated ferret ventricular muscle.

In this study, we have compared the effects of a range of positive and negative inotropic interventions on isometric tension and shortening at low load in isolated ferret papillary muscles. It was found that the majority of interventions produced broadly similar effects on tension and shortening. Positive inotropic interventions which behaved in this way included increasing extracellular calcium and increasing frequency at moderate stimulation rates. Acidosis, the addition of cyanide, and metabolic blockade produced by the addition of iodoacetic acid and cyanide, all produced negative inotropic effects which showed a similar pattern. For all these interventions, it was noted that the fractional effect on tension was 1.5-2 times larger than the fractional effect on shortening. This was attributed to the shape of the tension-length relation for cardiac muscle in different inotropic states. When frequency was increased to a high rate, tension rose to an initial peak, but then showed a marked decline, while shortening rose to a new level and was then well maintained. When protocols consisting of varying amounts of isometric and isotonic contraction were applied, the amount of the secondary decline for both tension and shortening was related to the period spent doing isotonic contractions, and hence to the energy consumption of the muscle. Thus the difference in the behaviour of tension and shortening under these conditions can be accounted for by the lower energy requirements of shortening, rather than by other factors. Over the range of inotropic interventions studied, peak shortening velocity was a more sensitive index of contractility than shortening, being roughly comparable to isometric tension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The consequences of simulated ischaemia on intracellular Ca2+ and tension in isolated ferret ventricular muscle.

1. In order to study cellular events occurring in ischaemia, we have developed a method for simulating ischaemia in an isolated papillary muscle. Muscles were suspended in a chamber and changed from conventional superfusion with Tyrode solution to gas perfusion with 95% N2/5% CO2 (N2 gas perfusion), thus simultaneously stopping oxygenation and flow. Surface cells of the preparation were injected with the photoprotein aequorin in order to monitor intracellular free calcium concentration [( Ca2+]i). 2. Gas perfusion with 95% O2/5% CO2 (O2 gas perfusion) had little effect on the tension or Ca2+ transients. Superfusion with Tyrode solution equilibrated with 95% N2/5% CO2 (N2 Tyrode) caused tension to decline to 30-40% of control, but had little effect on the amplitude of the Ca2+ transients. N2 gas perfusion caused tension to fall more rapidly and to a lower level than superfusion with N2 Tyrode. Ca2+ transients showed a small initial decline followed by a slowly developing increase in magnitude and duration. 3. Long exposures to N2 gas perfusion caused tension to decline to very low levels and Ca2+ transients to increase to a maximum. After a variable length of time, resting tension began to increase. At approximately the same time, Ca2+ transients began to decrease and eventually disappeared. Resting Ca2+ increased during N2 gas perfusion and remained elevated when the Ca2+ transients had declined. These changes could be reversed by restarting superfusion with standard Tyrode or by perfusion with O2 gas. 4. N2 gas perfusion caused a depolarization of the resting potential and an abbreviation of the action potential. In a long exposure the action potential eventually failed. These changes could be reversed by restarting superfusion with standard Tyrode or by perfusion with O2 gas. 5. Many of the effects of N2 gas perfusion could be mimicked by the addition of 20 mM-lactic acid to the superfusing solution, which caused a profound reduction of tension and also an increase in the amplitude and duration of the Ca2+ transients. Calculation of the changes in intracellular pH caused by the addition of lactic acid suggest that the fall in intracellular pH produced by lactic acid was similar to that occurring in ischaemia. 6. Repeated exposures to N2 gas perfusion caused tension to fall more rapidly and an increased resting tension to develop more rapidly. The slowly developing rise in Ca2+ transients was abolished and a rise in resting Ca2+ occurred more quickly. 7. When muscles were quiescent, exposure to N2 gas perfusion caused an increase in resting light.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

Intracellular calcium and tension during fatigue in isolated single muscle fibres from Xenopus laevis.

1. Single muscle fibres were dissected from Xenopus lumbrical muscles and microinjected with the photoprotein aequorin in order to measure the myoplasmic free calcium concentration ([Ca2+]i). Fatigue was produced by repeated intermittent tetanic stimulation continued until tension had declined to approximately 50% of the initial level. Fibres were then allowed to recover by giving tetani at less frequent intervals. Aequorin light (a measure of [Ca2+]i) and tension were measured during fatiguing stimulation and recovery. 2. During fatiguing stimulation, tetanic tension declined steadily, but peak aequorin light first increased before declining substantially. The largest light signal was about 155% of initial control while at the end of fatiguing stimulation the tetanic light fell to about 14% of control. 3. Fibres showed a characteristic slowing of relaxation in the fatigued state. This was associated with a slowing of the rate of decline of the aequorin light signal. 4. Intracellular acidosis produced by equilibrating the Ringer solution with either 5 or 15% CO2 caused an increase in the light signal associated with a tetanus. Carbon dioxide also caused a reduction of tension and a slowing of relaxation. 5. In vivo pCa-tension curves were constructed by exposing the fibres to a series of K+ concentrations which produced contractures of different sizes. Light and tension were measured during periods when both were relatively stable and the light signal was subsequently converted to pCa. 6. Exposure of fibres to 5 or 15% CO2 caused the pCa-tension curve to be shifted to the right of the control curve. This indicates a reduced Ca2+ sensitivity of the contractile proteins, which is in agreement with results from skinned fibre studies. 7. The pCa-tension points obtained from tetani during the early part of fatiguing stimulation also deviated to the right of the control pCa-tension curve, suggesting a reduced Ca2+ sensitivity of the contractile proteins. At the end of fatiguing stimulation, however, pCa-tension points did not differ greatly from the control pCa-tension curve, suggesting that Ca2+ sensitivity was approximately normal. Thus the reduced [Ca2+]i during tetani at the end of fatiguing stimulation (when tension was reduced to approximately 50%) could explain all of the reduction in tension. 8. After fatiguing stimulation, tension and light recovered monotonically in some fibres; however, in the majority of fibres, tension and light showed a secondary decline followed by a slower recovery (post-contractile depression). 9. During post-contractile depression, caffeine contractures or tetani in the presence of caffeine gave increased aequorin light signals and the tension developed was close to that produced in an unfatigued tetanus.(ABSTRACT TRUNCATED AT 400 WORDS)

Aequorin↗
PubMed1989

Simultaneous measurements of action potential duration and intracellular ATP in isolated ferret hearts exposed to cyanide.

Shortening of the cardiac action potential during ischemia and anoxia is likely to contribute to the decline in contractility that occurs under such conditions. It has been hypothesized that a decrease in the intracellular ATP concentration ([ATP]i) underlies the changes in the action potential. The recently discovered potassium channel activated at low ATP concentrations might provide the link between action potential shortening and low [ATP]i. However, it has yet to be shown that [ATP]i falls to the range required for channel activation at the time when action potential shortening occurs. We have measured action potentials and [ATP]i simultaneously in isolated ferret hearts during inhibition of both oxidative phosphorylation and anaerobic glycolysis (metabolic blockade). Metabolic blockade caused a rapid decline in cardiac contractility, accompanied by a rapid fall in action potential duration. [ATP]i fell only slightly and remained well above the range where activation of the ATP-sensitive K+ channel would be expected to occur. Moreover, reintroduction of glucose to the perfusate led to a substantial recovery in both contraction and in action potential duration, again in the absence of any great change in [ATP]i. These results suggest that the action potential shortening observed in metabolic blockade cannot be explained by the simple hypothesis of K+ channel opening as a consequence of a decrease in bulk [ATP]i unless the Km for suppression of channel activity by ATP is very much higher in intact cells than in any of the patch configurations studied. An alternative explanation is that the channel may be regulated under these conditions by mechanisms other than a change in [ATP]i.

Action Potentials↗
PubMed1989

Writing to learn: a reconceptualization of thinking and writing in the nursing curriculum.

The connection between writing and thinking has been radically reconceptualized in recent years. Whereas the previous view saw writing as recording thought, the new perspective sees writing as developing thinking. The change in views about writing is discussed and implications of the "Writing to Learn" paradigm for instructional and curricular issues in nursing are explored.

Curriculum↗
PubMed1988

Plasma volume expansion in pregnancy hypertension.

Stabilised human serum 500 ml was infused intravenously over 90 minutes in 14 hypertensive women in late pregnancy, and the haemodynamic changes were investigated and compared with those in 7 similar women who were not treated. There was a significant mean increase of 1,85 l in plasma volume, a decrease in diastolic and systolic blood pressure, and an increase in central venous pressure (CVP), pulse pressure and pulse rate in the treated group at 2 hours but not in the control group. After 24 hours most of the observations were not significantly different from the pretreatment levels except the CVP and pulse rate measurements which were still significantly raised. The CVP measurements in the hypertensive women before treatment were relatively low compared with those reported in normal women in late pregnancy. It is suggested that there may be an under-filling of the circulation in pregnancy hypertension and that plasma volume expansion may have an important therapeutic effect by increasing cardiac output and renal and uterine blood flow.

Blood Pressure↗
PubMed1988

Takayasu's arteritis in pregnancy. A report of 4 cases.

Four cases of Takayasu's arteritis in association with pregnancy are described. These patients are at high risk of pregnancy hypertension. Measurement of the blood pressure in the arms may be impossible or unreliable and is often more accurately obtained in the legs.

Adult↗
PubMed1988

The effects of repeated exposure to anoxia on intracellular calcium, glycogen and lactate in isolated ferret heart muscle.

Isolated cardiac tissue from the ferret was repeatedly exposed to anoxia while perfused with glucose-containing Tyrode solution. In one series of experiments, papillary muscles were injected with aequorin to measure intracellular Ca2+. On the first exposure to anoxia, the Ca2+ transients often increased, but on subsequent exposures this increase disappeared and eventually the Ca2+ transients declined on exposure to anoxia. This decline in the Ca2+ transients could be converted back to an increase by a 1 h exposure to an elevated (x5) glucose concentration. Exposure of aerobic muscles to 10 mM lactic acid caused a similar increase in the Ca2+ transients to that seen in early exposures to anoxia. In a second series of experiments, performed on Langendorff-perfused hearts, measurements were made of glycogen concentration preceding, and lactate production during, exposures to anoxia. At a constant level of glucose, glycogen concentration and lactate production were found to decline on repeated exposures to anoxia, and both were increased after a period of elevated glucose and reduced stimulation frequency. These results suggest that the response of the Ca2+ transients to anoxia is dependent on the metabolic status of the muscle. The increase in the Ca2+ transients during an early exposure to anoxia may be a consequence of lactic acid production due to accelerated glycolysis. Repeated exposures to anoxia reduce glycogen concentration and lactate production and this reduces the rise in the Ca2+ transients.

Animals↗
PubMed1988

Effects of rapid application of caffeine on intracellular calcium concentration in ferret papillary muscles.

In this paper we investigate the effects of caffeine (5-20 mM) on ferret papillary muscle. The intracellular Ca2+ concentration ( [Ca2+]i) was measured from the light emitted by the photoprotein aequorin, which had previously been microinjected into superficial cells. Isometric tension was measured simultaneously. The rapid application of caffeine produced a transient increase of [Ca2+]i, which decayed spontaneously within 2-3 s and was accompanied by a transient contracture. The removal of extracellular Na+ or an increase in the concentration of intracellular Na+ (produced by strophanthidin) increased the magnitude of the caffeine response. Cessation of stimulation for several minutes or stimulation at low rates decreased the magnitude of the stimulated twitch and Ca2+ transient. These maneuvers also decreased the size of the caffeine response. These results are consistent with the hypothesis that the caffeine-releasable pool of Ca2+ (sarcoplasmic reticulum) is modulated by maneuvers that affect contraction. Ryanodine (10 microM) decreased the magnitude of the caffeine response as well as that of the stimulated twitch. In contrast, the rapid removal of external Ca2+ abolished the systolic Ca2+ transient within 5 s, but had no effect on the caffeine response. From this we conclude that the abolition of twitch by Ca2+-free solutions is not due to depletion of the sarcoplasmic reticulum of Ca2+, but may be due to a requirement of Ca2+ entry into the cell to trigger Ca2+ release from the sarcoplasmic reticulum.

Aequorin↗
PubMed1988

Primary postpartum haemorrhage in Tasmania 1982-1986.

Primary postpartum haemorrhage remains a significant problem in modern obstetric practice. The incidence and factors associated with postpartum haemorrhage in Tasmania over a 5-year period were studied. The mode of delivery, anaesthesia, birth-weight, induction and augmentation of labour, multiple pregnancy, antepartum haemorrhage and hypertension were found to be important factors. The incidence of retained placenta was not considered in this study.

Birth Weight↗
PubMed1988

The effects of changes in muscle length during diastole on the calcium transient in ferret ventricular muscle.

1. Ferret papillary muscles were isolated and injected with aequorin to measure intracellular Ca2+ concentration [( Ca2+]i). Developed tension and [Ca2+]i were measured in response to length changes. 2. A maintained reduction in muscle length produced an immediate decrease in developed tension followed by slow decline over 10-20 min. This slow decline in tension was accompanied by a slow decline in the amplitude of the systolic [Ca2+]i rise (the Ca2+ transient). The immediate decrease in tension was accompanied by a prolongation of the Ca2+ transient and an abbreviation of the twitch. 3. Repeated reductions in muscle length timed to occur only during the period of contraction (systolic shortening) produced an immediate decrease of developed tension but the subsequent slow decline was substantially smaller. The slow decline in the amplitude of the Ca2+ transients was also smaller. The prolongation of the Ca2+ transient and abbreviation of the twitch were similar to those observed with a maintained reduction of length. 4. Repeated reductions in muscle length during the period between contractions (diastolic shortening) did not produce the immediate decrease of tension but the slow decline of tension was present. The slow decline in the amplitude of the Ca2+ transients was also present. However no change in the duration of the Ca2+ transient or the twitch was present under these conditions. 5. These results suggest that diastolic muscle length can influence the amplitude of the Ca2+ transients achieved during systole. This conclusion was confirmed by experiments in which the recovery of tension and Ca2+ transients was observed after periods of rest. Both developed tension and Ca2+ transients on recovery from a rest were reduced when the rest occurred at a short length in comparison with a long length. 6. We suggest that muscle length influences resting [Ca2+]i and this in turn affects the Ca2+ transients and developed tension.

Action Potentials↗
PubMed1988

Calcium concentration in the myoplasm of skinned ferret ventricular muscle following changes in muscle length.

1. Ferret ventricular muscles were skinned by prolonged application of Triton X-100. Aequorin was allowed to diffuse into the myoplasmic space and the resulting light emission was used to monitor the myoplasmic [Ca2+]. The muscle was then activated with a lightly buffered Ca2+ solution and the changes in myoplasmic [Ca2+] and tension in response to length changes were investigated. 2. A sudden reduction in muscle length led to a rapid increase in myoplasmic [Ca2+] to a new level which was maintained as long as muscle length was reduced and which was reversed when the muscle was stretched back to the control length. The rate of increase of [Ca2+] when the muscle length was reduced was greater than the rate of decrease in [Ca2+] when the muscle was stretched. 3. Increasing the concentration of EGTA in the activating solution, so as to increase its Ca2+-buffering capacity, eliminated the changes in myoplasmic [Ca2+] in response to a length change but had little effect on developed tension. 4. On stretching the muscle there was a slow component of recovery of tension with a time course broadly similar to the rate of decrease of myoplasmic [Ca2+]. The time course of tension redevelopment and of the accompanying reduction in myoplasmic [Ca2+] both decreased to a similar extent when the [Ca2+] used to activate the muscle was increased. 5. Step reductions of length of increasing amplitude caused increases in myoplasmic [Ca2+] which were larger in proportion to the size of the step. 6. Step reductions of length of equal size but from different starting lengths caused changes in myoplasmic [Ca2+] the amplitude of which correlated with the change in tension rather than the change in length. 7. The increase in myoplasmic [Ca2+] when muscle length is reduced suggests that Ca2+ is released from a site in the muscle, probably troponin C. The time course and magnitude of the changes in myoplasmic [Ca2+] correlate more closely with the changes in developed tension than muscle length.

Aequorin↗
PubMed1988

Effects of metabolic blockade on intracellular calcium concentration in isolated ferret ventricular muscle.

Tension and intracellular free calcium concentration [( Ca2+]i) were measured in isolated ferret papillary muscles. When both anaerobic glycolysis and oxidative phosphorylation were prevented (metabolic blockade), there was a rapid decline of both developed tension and systolic [Ca2+]i signals. Subsequently, resting tension increased, and after a further delay, resting [Ca2+]i also rose. When oxidative metabolism was restarted after a period of metabolic blockade that was sufficient to elevate both resting tension and [Ca2+]i, a variable recovery of mechanical function occurred. In preparations that showed recovery, resting tension declined toward control level, and there was considerable recovery of developed tension. [Ca2+]i initially fell, but it then rose to a level similar to that at the end of the preceding period of metabolic blockade and exhibited large variations in amplitude with frequency components in the range 0.2-1 Hz. This elevated [Ca2+]i gradually declined. Arrhythmias were often present during this recovery period and appeared to be triggered by the spontaneous increases in [Ca2+]i. In preparations that failed to recover, resting tension remained elevated or increased, and developed tension showed little recovery. Such preparations showed larger rises in [Ca2+]i both during and after metabolic blockade, and [Ca2+]i continued to rise when oxidative metabolism was restarted. In experiments in which Na-Ca exchange was inhibited (by replacement of sodium by lithium or by the application of nickel), the rise of [Ca2+]i when oxidative metabolism was restarted was reduced, but recovery of mechanical function was improved. The correlation between elevated [Ca2+]i on reactivation of oxidative metabolism and failure of recovery of mechanical function suggests that elevated [Ca2+]i has a direct role in preventing the recovery of mechanical function.

Animals↗
PubMed1988

Effects of acidosis on ventricular muscle from adult and neonatal rats.

We compared the response of ventricular muscle from adult and neonatal rats to hypercapnic acidosis. In adult muscle, acidosis caused an initial rapid fall of developed tension to 30 +/- 5% of control (mean +/- SEM, n = 6). However, tension recovered slowly to a steady state that was 56 +/- 6% of control. In neonatal muscle, acidosis caused a significantly smaller initial fall in tension to 43 +/- 3% (n = 8, p less than 0.05), but the tension then showed a subsequent slower fall to a steady state that was 29 +/- 4% of control, significantly less than in the adult (p less than 0.01). We have attempted to identify the mechanisms underlying these differences in response. In detergent-skinned myofibrils, reducing the pH from 7.0 to 6.5 caused a reduction in the pCa50 of 0.61 units in the adult muscle, but only 0.27 units in the neonatal ventricular muscle. Myofibrillar Ca2+ sensitivity in neonatal ventricular muscle is thus less susceptible to the effects of acidic pH than that of adult muscle. Since intracellular pH decreases rapidly on application of increased external CO2, these results are consistent with the finding that, initially, developed tension in neonatal muscles is less sensitive to the effects of acidosis. Sodium dodecylsulfate gel electrophoresis of myofibrillar preparations from adult and neonatal rats demonstrated differences in thin filament proteins, including troponin I, which may underlie the observed differences in Ca2+ sensitivity. In adult rat ventricular muscles, the slow recovery of tension during acidosis is associated with an increase in the amplitude of the Ca2+ transients to 263 +/- 34% of control (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗
PubMed1988

Cardiopulmonary effects of a ketamine hydrochloride/acepromazine combination in healthy cats.

The effect of a ketamine hydrochloride/acepromazine combination on the cardiopulmonary function of 11 healthy cats was studied. Test parameters included cardiac output, measured by thermodilution, heart rate, respiratory rate, arterial blood pressure (systolic, diastolic and mean) and arterial blood gas analysis. Values for systemic vascular resistance, cardiac index and stroke volume were calculated. The cardiac output, cardiac index, stroke volume, arterial blood pressure and arterial blood pH decreased significantly (p less than 0.006). The arterial CO2 increased significantly (p less than 0.006). All changes occurred during the five to 45 minute postinduction time period. The heart rate, respiratory rate, arterial O2 and systemic vascular resistance were not significantly altered. The anesthetic regime maintained an adequate plane of surgical anesthesia for 30-45 minutes.

Acepromazine↗
PubMed1988

Cardiopulmonary effects of a halothane/oxygen combination in healthy cats.

The effects of a halothane/oxygen combination on the cardiopulmonary function of 11 healthy cats were studied. Test parameters included cardiac output, measured via thermo-dilution, heart rate, respiratory rate, arterial blood pressure (systolic, diastolic and mean) and blood gas analysis. Values for systemic vascular resistance, cardiac index and stroke volume were calculated from these data. Cardiac output, cardiac index, heart rate, stroke volume, arterial blood pressure (systolic, diastolic and mean) and arterial blood pH were significantly decreased (p less than 0.001). Respiratory rate was also significantly decreased (p less than 0.007) with arterial CO2 tension being significantly increased (p less than 0.001). Statistically significant changes, where seen, persisted for the duration of the anesthetic period. Arterial O2 tension and systemic vascular resistance remained unchanged. All parameters returned to near pretest values within 30 minutes following cessation of halothane anesthesia.

Animals↗