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Biomedical subjects

D J Paterson

Publications and source records attributed to D J Paterson.

At least 73 records · Page 4Linked to original sources
PubMed1994

Effect of physical training on exercise-induced hyperkalemia in chronic heart failure. Relation with ventilation and catecholamines.

BACKGROUND: The exercise-induced rise in arterial potassium concentration ([K+]a) may contribute to exercise hyperpnea and could play a role in exertional fatigue. This study was designed to determine whether the exercise-induced rise in [K+]a is altered in patients with chronic heart failure (CHF) and whether physical training affects K+ homeostasis. METHODS AND RESULTS: We evaluated 10 subjects with CHF (ejection fraction, 23 +/- 3.9%) and 10 subjects with normal left ventricular function (NLVF) who had undergone previous coronary artery graft surgery (ejection fraction, 63 +/- 8.6%). Subjects performed an incremental cycle ergometer exercise test before and after a physical training or detraining program. Changes in [K+]a and ventilation (VE) during exercise were closely related in both groups. Subjects with CHF did less absolute work and had reduced maximal oxygen consumption (VO2max) compared with subjects with NLVF (P < .01). Exercise-induced rises in [K+]a, VE, norepinephrine, lactate, and heart rate were greater at matched absolute work rates in subjects with CHF than in subjects with NLVF (P < .01). However, when the rise in [K+]a was plotted against percentage of VO2max to match for relative submaximal effort, there were no differences between the two groups. Physical training resulted in reduced exercise-induced hyperkalemia at matched submaximal work rates in both groups (P < .01) despite no associated change in the concentration of arterial catecholamines. At maximal exercise when trained, peak increases in [K+]a were unaltered, but peak concentrations of catecholamines were raised (P < .05). The decrease in VE at submaximal work rates after training was not significant with this incremental exercise protocol, but both groups had an increased peak VE when trained (P < .01). CONCLUSIONS: Exercise-induced rises in [K+]a, catecholamines, and VE are greater at submaximal work rates in subjects with CHF than in subjects with NLVF. Physical training reduces the exercise-induced rise in [K+]a but does not significantly decrease VE during submaximal exercise with this incremental cycle ergometry protocol. The reduction in exercise-induced hyperkalemia after training is not the result of altered concentrations of arterial catecholamines. The pathophysiological significance of the increased exercise-induced hyperkalemia in CHF and the mechanisms of improved K+ homeostasis with training have yet to be established.

Epinephrine↗
PubMed1993

The effect of tolbutamide on cerebral blood flow during hypoxia and hypercapnia in the anaesthetized rat.

The increase in blood flow in the cerebral cortex of the anaesthetized rat during hypoxia and hypercapnia was investigated. Cerebral blood flow (CBF) was measured using the hydrogen clearance method with acutely implanted platinum electrodes. Hypoxia (PaO2 35.3 +/- 2.4 Torr) and hypercapnia (PaCO2 68.1 +/- 5.1 Torr) increased basal CBF from 76.3 +/- 9.0 ml/100g/min to 168.1 +/- 20.1 ml/100g/min and 162.4 +/- 31.9 ml/100g/min respectively. The sulphonylurea tolbutamide (1mM in 1%DMSO) had no significant effect on CBF in hyperoxia or in hypercapnia. However, it attenuated the increase of CBF during hypoxia by 66 +/- 11% (p < 0.01). This suggests that opening of tolbutamide-sensitive potassium channels may be involved in the process of hypoxic vasodilation in the rat cerebral cortex.

Anesthesia↗
PubMed1993

Effect of catecholamines on the ventricular myocyte action potential in raised extracellular potassium.

We describe the relationship between catecholamines and raised extracellular potassium ([K+]o) on action potential parameters and calcium currents in isolated ventricular myocytes of the guinea-pig and relate these findings to the problem of understanding how the heart is protected from exercise-induced hyperkalaemia ([K+]a up to 8.5 mM). Action potential duration (APD90), amplitude and upstroke velocity were recorded in stimulated (2Hz) guinea-pig ventricular myocytes using whole-cell patch electrode recordings (37 degrees C). Cells were superfused with normal K+ Tyrode and with raised K+ Tyrode in the presence of either noradrenaline, adrenaline or raised calcium. Inward calcium current was measured using voltage clamp. Raised K+ (8, 12, 16 mM K+ Tyrode) caused a significant (P < 0.01) depolarisation, shortened the APD90 and decreased the action potential amplitude and upstroke velocity. In raised K+ Tyrode addition of noradrenaline (0.08-0.1 microM) or adrenaline (0.1-0.2 microM) increased action potential amplitude (P < 0.01), APD90 (P < 0.01) and upstroke velocity (P < 0.01) (measured only in 16 mM K+ Tyrode). In 12 mM K+ Tyrode raised Ca2+ (5-6 mM) increased action potential amplitude (P < 0.05) and shortened APD90 (P < 0.05). Addition of NA (0.08-0.1 microM) increased the inward Ca2+ current. All effects were fully reversible. In raised [K+]o increases in catecholamines and [Ca2+]o cause changes in action potential parameters that would be expected to maintain propagation of the cardiac action potential in the whole heart. Thus, in the ventricular myocyte the increase in conductance to Ca2+ caused by catecholamines may be one factor that is important in minimising the potentially adverse effects of exercise-induced hyperkalaemia.

Action Potentials↗
PubMed1993

Cardiac sympathetic nerve stimulation enhances cardiovascular performance during hyperkalaemia in the anaesthetized pig.

A rapid increase in arterial plasma potassium concentration to values seen during intense exercise depresses cardiac function at rest. Increasing the cardiac concentration of noradrenaline by right-sided sympathetic stimulation in eleven anaesthetized pigs significantly augmented cardiovascular performance during hyperkalaemia, while electrical pacing of the right atrium at equivalent rates to sympathetic stimulation afforded no protection against the deleterious effects of hyperkalaemia. We conclude that the inotropic effect of sympathetic activation may be important in sustaining cardiac function during exercise-induced hyperkalaemia.

Animals↗
PubMed1993

Potassium loss from skeletal muscle during exercise in man: a radioisotope study.

Muscle potassium (K+) content decreases during exercise. Previous studies, in humans, have used measurements of arteriovenous plasma potassium concentration differences (AV delta[K+]) and/or muscle biopsy to measure the loss of muscle K+ during exercise. In the current study a non-invasive method was developed to measure skeletal muscle K+ before and after exercise, using an isotope of K+, potassium-43 (43K+). Twelve subjects performed single-leg extension exercise for 2 h at 50% of their maximum predicted heart rate. The level of radioactivity from the quadriceps femoris was determined before exercise and during two periods post-exercise. After correction for counts arising outside the exercised muscle, we estimate a decrease in muscle K+ content of 3.2 +/- 1.55% (mean +/- S.E.M.) following exercise. The muscle K+ was not restored following 75 min of recovery. The decrease in muscle K+ following exercise in our study is considerably less than that suggested by previous studies using AV delta[K+] measurements but not so dissimilar from results obtained using muscle biopsy. We conclude that a small but significant loss of K+ occurs following prolonged dynamic exercise, and that complete recovery of muscle K+ is slow.

Adult↗
PubMed1992

Effect of potassium on ventilation in the rhesus monkey.

Increasing the concentration of arterial plasma K+ to 6-8 mM increased ventilation in two sedated analgesic-treated rhesus monkeys who had their end-tidal CO2 held constant during euoxia (arterial oxygen pressure, Pa,O2, ca 100 Torr) and hypoxia (Pa,O2, ca 40 Torr). During euoxia and hypoxia, hyperkalaemia increased ventilation up to 40 and 250%, respectively. This effect was reduced in euoxia and virtually abolished in hypoxia following an abrupt switch to 100% oxygen. Thus the ventilatory response of this primate to hyperkalaemia is at least as sensitive as that of the cat and if hypoxia is added the two stimuli generate a powerful drive to breathing.

Animals↗
PubMed1992

Potassium and ventilation in exercise.

The drive to breathe in exercise is thought to result from a combination of neural and humoral factors, but the exact nature of the controlling signals is controversial. This review examines evidence suggesting that potassium could be a signal that drives ventilation (VE) in exercise. Potassium is lost from working muscle, which results in a marked hyperkalemia in the arterial plasma. The rise in potassium is directly proportional to the increase in carbon dioxide production during exercise and is also well correlated with VE in normal subjects and in subjects who do not produce acid (McArdle's syndrome). In the anesthetized and decerebrate cat, physiological levels of hyperkalemia stimulate VE by direct excitation of the peripheral arterial chemoreceptors, because surgical and chemical denervation of the chemoreceptors abolishes the increase in VE caused by potassium. The effect of hyperkalemia on chemoreceptor activity is further enhanced by hypoxia, but an abrupt switch to hyperoxia removes this effect. From these studies, it is suggested that potassium fulfills many of the criteria of being the special substance or "work factor" that was postulated over a century ago to stimulate VE in exercise. Although there is no direct proof that potassium causes an increase in breathing during exercise, circumstantial evidence strongly supports the idea that it should be considered as a stimulus to exercise hyperpnea.

Animals↗
PubMed1992

Effects of catecholamines and potassium on cardiovascular performance in the rabbit.

Resting subjects risk cardiac arrest if plasma potassium ([K+]p) is raised rapidly to 7-9 mM, but brief bouts of exhaustive exercise in healthy subjects can give similar [K+]p without causing cardiac problems. We investigated the effects of [K+]p and catecholamines on systolic blood pressure (SBP) and mean aortic flow (MAF) in anesthetized rabbits and on maximum output pressure (MOP) in isolated working rabbit hearts. In six rabbits, hyperkalemia (11.4 +/- 0.4 mM) caused a fall in SBP from 116 +/- 6 to 49 +/- 6 mmHg and in MAF from 373 +/- 30 to 181 +/- 53 ml/min (P < 0.01). Raising [K+]p (11.6 +/- 0.3 mM) with norepinephrine (NE) (1.3 micrograms.kg-1.min-1 iv), however, increased SBP from 108 +/- 7 to 150 +/- 6 mmHg (P < 0.01) and MAF from 347 +/- 42 to 434 +/- 35 ml/min (P < 0.01). In 19 isolated working hearts, perfusion with 8 mM K+ Tyrode and then 12 mM K+ Tyrode reduced MOP from 87 +/- 3 (control 4 mM K+) to 67 +/- 3 (8 mM K+) and 51 +/- 2 cmH2O (12 mM K+) (P < 0.01); 12 mM K+ Tyrode with 0.08 microM NE or epinephrine, however, increased MOP from 67 +/- 6 (in 8 mM K+) to 85 +/- 6 cmH2O (NE) and from 58 +/- 2 to 76 +/- 5 cmH2O (epinephrine) (P < 0.01). Catecholamines may therefore play a key role in protecting the heart from exercise-induced hyperkalemia.

Anesthesia↗
PubMed1992

The effect of acute hypoxia on the latency of the human auditory brainstem evoked response.

Recent studies have shown a decrease in the amplitude and an increase in the threshold of the cat's auditory brainstem evoked response (ABER) during severe hypoxia (PaO2 of 20 to 30 Torr). In this study we have examined the effects of euoxia (end tidal PO2 100 Torr) and mild hypoxia (end tidal PO2 of 45 to 50 Torr) on the latency of the ABER in 6 human subjects. Hypoxia resulted in a blood O2 saturation of between 75 to 85% and caused a significant prolongation of the latency of wave V of the ABER by 0.185 +/- 0.045 ms (Mean +/- S.D; p < 0.01). The prolongation of the ABER during severe hypoxia has previously been attributed to a change in peripheral sensitivity. Using the stimulus level/response latency relationship obtained for each subject under normal breathing conditions, the change in latency produced by mild hypoxia can be interpreted as a mean shift in auditory sensitivity of 5.1 +/- 3.4 dB. These results suggest that the auditory system is sensitive to much smaller changes in blood O2 saturation than previously thought.

Adult↗
PubMed1992

The effects of chronic hypoxia on human auditory system sensitivity.

We have examined the effects of prolonged periods of hypoxia produced at high altitudes on the latency of the auditory brain-stem evoked response (ABER) in 9 subjects at around sea level, 3,500 m, and 4,370 m. Following an ascent from 1,300 m to 3,500 m over 24 h, the mean blood O2 saturation fell to 86.5 +/- 1.2% (+/- S.E.M.) and was associated with a mean prolongation of latency of wave V of the ABER of 0.34 +/- 0.10 ms (p = 0.011 two-tailed paired t-test). Using the stimulus-level/response latency relation determined at around sea-level for each subject, this prolongation of wave V corresponded to a mean reduction in sensitivity of 9.1 dB +/- 1.6 dB. Over a period of 72 h, blood O2 saturation improved slightly (mean 88.1% +/- 1.8%) and mean wave V latency returned to control values. A second rapid ascent to 4,370 m reduced blood O2 to below prerecovery levels (82.5% +/- 1.7%), but in this case there were no significant changes in auditory sensitivity (p = 0.79 two-tailed paired t-test). These data show that mild hypoxia results in an initial decrease in auditory sensitivity. However, the recovery of sensitivity with more prolonged exposure suggests that the auditory system can compensate for chronic mild hypoxia.

Adult↗
PubMed1991

Effect of oxygen on potassium-excited ventilation in the decerebrate cat.

Raising arterial potassium ([K+]a) from ca. 3.5 to 6.5 mM, as occurs in heavy exercise, excites the arterial chemoreceptors and ventilation (VE) in anaesthetised cats. We have previously shown that the excitation of chemoreceptors by potassium is enhanced by hypoxia and abolished by hyperoxia, and here we show, in decerebrate cats, that the potassium-induced increase in VE is also abolished by hyperoxia. 100% oxygen was given abruptly in hypoxia (PETO2 ca. 50 Torr), with inspired gas tensions adjusted to give the same PETO2 and PETCO2 values before all tests on a given animal. Intravenous infusions of 150 mM KCl, which raised [K+]a from 3.9 +/- 0.3 mM to 7.4 +/- 0.3 mM (mean +/- SE), always excited hypoxic VE (42 +/- 8%; P less than 0.01). Hyperoxia, given during KCl infusion, reduced VE to a value not significantly greater (P greater than 0.27) than the hyperoxic value obtained before infusion. These results show that: (i) VE reflects the responses of chemoreceptors to K+, (ii) that abrupt hyperoxia removes the potassium-induced ventilatory drive, and (iii) that, in our experiments, K+ appears to have excited VE only via the peripheral chemoreceptors.

Animals↗
PubMed1991

Initiation and evolution of interstitial leukocytic infiltration in experimental glomerulonephritis.

Most forms of glomerulonephritis have a significant interstitial leukocytic infiltrate which is associated with disease progression. However, there is little data concerning the timing, initial location, and development of this interstitial component. Therefore, we have addressed these issues in a study of passive accelerated anti-GBM glomerulonephritis in the rat. In this model, interstitial leukocytic infiltration was an early event in the disease process with a significant infiltrate apparent at 12 hours after administration of nephrotoxic serum (NTS). This initial infiltrate was restricted to a perivascular sheath surrounding the hilar arterioles. The sheath infiltrate then spread to include the whole hilar area by day 1, the entire periglomerular area by day 3, and became widespread throughout the cortical tubulointerstitium by day 7. The early sheath infiltrate was composed of macrophages and T cells. Both cell types continued to increase as the infiltrate expanded, and a significant accumulation of activated cells (IL-2R+) was evident from day 7 onwards. There was a highly significant correlation between interstitial macrophage infiltration and renal function impairment, proteinuria, and histologic damage. Interstitial T cell infiltration correlated with proteinuria and histologic damage, while the appearance of immune-activated mononuclear cells (IL-2R+) exhibited a highly significant correlation with all disease parameters. This study demonstrates the importance of the glomerular hilar arteriolar region as a focus for mononuclear leucocytic migration and accumulation which not only affects the structure and function of the glomerulus but subsequently the entire tubulointerstitium.

Animals↗
PubMed1991

Leukocyte involvement in the pathogenesis of pulmonary injury in experimental Goodpasture's syndrome.

To investigate the role of leukocytes in the pathogenesis of pulmonary injury after antibody deposition on the alveolar basement membrane, we have induced experimental Goodpasture's syndrome in the rat using passive accelerated anti-glomerular basement membrane (GBM) disease. Animals were immunized with normal rabbit IgG and given either rabbit anti-rat GBM serum or normal rabbit serum (control) 5 days later. In this model, leukocytic infiltration, severe hemorrhage, and granulomatous-like lesions developed in the lung, while a rapidly progressive glomerulonephritis was evident in the kidney. Within 30 minutes of injection of anti-GBM serum, strong linear deposition of antibody on both glomerular and alveolar basement membranes was evident. In the lung, a transient influx of polymorphonuclear cells during the first 12 hours was closely followed by macrophage infiltration, with T cell infiltration not evident until day 3. Pulmonary hemorrhage correlated with ED1+ macrophage infiltration (p less than 0.001), but not with OX-19+ T cell accumulation. Many activated mononuclear cells were found in the lung infiltrate from day 14 onward and were associated with areas of tissue damage. This study demonstrates the feasibility of using passive accelerated anti-GBM disease as a model of Goodpasture's syndrome, and suggests that inflammatory macrophages are the major cellular participants in progressive pulmonary injury after antibody deposition.

Animals↗
PubMed1990

Changes in arterial K+ and ventilation during exercise in normal subjects and subjects with McArdle's syndrome.

1. We have examined the relationship between ventilation (VE), lactate (La) and arterial plasma K+ concentrations [( K+]a) during incremental exercise in six normal subjects and in four subjects with McArdle's syndrome (myophosphorylase deficiency) who do not become acidotic during exercise. 2. In normal subjects, [K+]a rose to ca 7 mM at the point of exhaustion. The time courses of the increases in VE, La and [K+]a were all similar during the exercise period. La reached its peak concentration during the recovery from exercise when both VE and [K+]a were returning to resting levels. 3. McArdle's subjects, like normal subjects, had a non-linear ventilatory response during incremental exercise. Their [K+]a was closely related to VE throughout exercise and recovery. 4. The arterial pH of McArdle's subjects, rather than remaining constant, actually rose from the onset of exercise. 5. For a given level of exercise, the levels of VE and [K+]a were greater in the McArdle's subjects than in normal subjects. 6. These findings are consistent with the idea that hyperkalaemia may contribute significantly to the drive to breathe, especially during heavy exercise.

Adult↗
PubMed1990

A comparison of indirect methods for continuous estimation of arterial PCO2 in men.

Four different measures (PETCO2, PACO2, PADCO2, and PJCO2) for indirectly estimating arterial PCO2 (PaCO2) from respired gas at the mouth have been investigated. PETCO2 was the end-tidal PCO2. PACO2 was calculated using a reconstruction of the alveolar oscillation of PCO2 obtained from the end-tidal "plateau" in PCO2. PADCO2 was calculated as for PACO2 except that the effects of dead space were incorporated. PJCO2 was calculated from an empirical relationship involving PETCO2 and tidal volume. Six subjects were studied at rest and during cycle ergometry at 50 and 100 W while breathing a variety of gas mixtures. Arterial samples were drawn for determination of true PaCO2. The differences for each method between estimated and true PaCO2 at rest and at 50 and 100 W were as follows: PETCO2, -1.35 +/- 2.64, 1.67 +/- 2.31, and 2.67 +/- 2.02 (SD) Torr; PaCO2, -2.15 +/- 2.73, -0.80 +/- 2.18, and -0.35 +/- 2.31 (SD) Torr; PADCO2, -1.55 +/- 2.54, 0.25 +/- 2.16, and 0.63 +/- 2.26 (SD) Torr; and PJCO2, -1.41 +/- 2.30, 0.12 +/- 1.79, and 0.08 +/- 1.96 (SD) Torr. It is concluded that, at rest, all methods significantly underestimate true PaCO2 and during exercise PETCO2 significantly overestimates PaCO2, but no bias was detected for any of the other methods.

Adolescent↗