Biomedical subjects

W Snedden

Publications and source records attributed to W Snedden.

At least 19 recordsLinked to original sources

PubMed1996

Repetitive inhalation endotracheal anaesthesia for cobalt radiotherapy in a child.

PURPOSE: Provision of general anaesthesia in areas remote from the operating room creates many difficult challenges especially if required for repeated radiotherapy in the prone position. This case illustrates these problems and some innovative solutions. CLINICAL FEATURES: A nine-year-old girl with medulloblastoma became extremely distressed whenever cobalt radiotherapy was attempted. Sedation with midazolam and high dose propofol infusion failed to achieve satisfactory conditions and caused concerns regarding airway management. The patient received a total of 37 endotracheal anaesthetics in the prone position using isoflurane in oxygen. Activated charcoal was used to scavenge anaesthetic vapors and adequate gas supplies were assured by connecting an "H' size tank to the oxygen pipeline inlet of the anaesthesia machine. Measurement of isoflurane in exhaust gases using gas chromatography confirmed the effectiveness of scavenging. No serious complications occurred related to repeated anaesthesia. CONCLUSION: The methods and equipment described permitted safe delivery of repeated inhalation general anaesthesia for radiotherapy. The same methods could be applied to anaesthesia in other remote locations.

Anesthesia, Inhalation↗

PubMed1996

A new method for the measurement of gas solubility.

A novel technique for the measurement of gas solubility and gas content in liquids and suspensions is described. Saturation of the liquid and subsequent extraction of the test gas both took place in a specially modified gastight syringe. The test gas was extracted from the saturated liquid by bubbling an inert carrier gas through the liquid ("sparging"). All gas exiting the apparatus was directed toward a mass spectrometer that measured the volume of extracted test gas in the presence of the carrier. The technique was used to measure the solubilities of nitrogen, oxygen, carbon monoxide, carbon dioxide, and nitrous oxide in olive oil at 37 degrees C. The Bunsen solubility coefficients so obtained are in good agreement with those obtained by classic techniques.

Carbon Dioxide↗

PubMed1996

A new method for measuring nitrogen and gases in blood.

The authors developed a new apparatus for extracting nitrogen or other inert gases from blood by flushing (sparging) the specimen with another gas. To investigate the utility of the new methodology, the apparatus was used in conjunction with a mass spectrometer to measure the blood N2 content of healthy normobaric, non-smoking, adult volunteers; the mean was found to be 11.7 microliters/ml +/- 0.9 microliter. This compares closely with values cited in the literature. The within-subject variation for repeat samples taken several weeks apart was significantly (P < 0.003) less than the variation between different subjects, suggesting that there may be true differences in N2 content between different individuals. These data must be considered preliminary, a larger study is needed to investigate population differences in detail. The advantages of the new method are discussed.

Adult↗

PubMed1992

The pharmacodynamic responses of hypertensive patients to quinapril therapy.

HYPOTHESIS: Impaired baroreflex-induced release of noradrenaline during angiotensin converting enzyme (ACE) inhibition may interfere with orthostatic responses of blood pressure. OBJECTIVE: To compare blood pressure and heart rate responses of hypertensive patients to upright posture over a 12 h period before and after quinapril therapy. DESIGN: Four weeks of placebo was given to all patients. If subject's sitting diastolic blood pressure was between 100 and 115 mmHg, patients received 2.5, 5, 10 or 20 mg quinapril bid for four more weeks in a double-blind randomized fashion. SETTING: Ambulatory hypertension clinic with admission to clinical investigation unit overnight for interventions. PATIENTS: Uncomplicated essential hypertensives of English or Irish ancestry. Twenty-five eligible patients completed the study while three withdrew early. INTERVENTIONS: Supine and erect blood pressures and heart rates were recorded for each patient at 1 to 2 h intervals over a 12 h period following ingestion of placebo capsule and again after initial acute dose of quinapril the next day. Blood was sampled for quinapril and quinaprilat concentrations. Procedure was repeated after four weeks of quinapril therapy following morning dose of drug. MAIN RESULTS: Orthostatic response of diastolic pressure was reduced while maintenance of systolic was impaired 1 to 4 h following an acute dose of quinapril. Orthostatic cardioacceleration was maintained. Responses were largely restored after four weeks of chronic therapy. CONCLUSIONS: A possible initial impairment of baroreflex-mediated peripheral vasoconstriction by ACE inhibition may be offset by compensatory changes to vascular reactivity.

Antihypertensive Agents↗

PubMed1991

Converting enzyme inhibition attenuates the noradrenaline response to the Valsalva maneuvre.

HYPOTHESIS: Reduction of plasma angiotensin II inhibits release of noradrenaline in response to a sympathetic nervous system stimulus. OBJECTIVE: To compare heart rate and plasma catecholamine responses to the Valsalva maneuvre before and after inhibition of angiotensin converting enzyme. DESIGN: Four weeks of placebo (all patients). If sitting diastolic blood pressure was found to be between 100 and 115 mmHg, then double-blind randomization to receive 2.5, 5, 10 or 20 mg of quinapril bid for a further four weeks. SETTING: Ambulatory hypertension clinic with admission to clinical investigation unit overnight for interventions. PATIENTS: Uncomplicated essential hypertensives of English-Irish ancestry. Twenty-five eligible patients completed the study, while three additional patients withdrew early. INTERVENTIONS: Blood pressure and heart rate were monitored weekly during placebo, and biweekly during active treatment. Patients were rehearsed in performance of the Valsalva maneuvre. At the end of the placebo and active therapy phases, each patient performed standard Valsalva maneuvres immediately before and 2 h after the morning dose of placebo or active drug. Heart rate was recorded continuously throughout the maneuvre, while blood was sampled for catecholamine determinations prior to the start of straining and again approximately 10 s following the end of straining. MAIN RESULTS: Heart rate responses to the Valsalva maneuvre were not affected by acute administration of quinapril, but a slight attenuation of the tachycardic response was seen after four weeks of therapy (P less than 0.05). An increase in plasma noradrenaline concentration associated with the straining phase of the Valsalva maneuvre was markedly attenuated after both acute and chronic quinapril therapy (P less than 0.01). CONCLUSION: By blocking biosynthesis of angiotensin II, converting enzyme inhibition may attenuate baroreceptor-stimulated release of noradrenaline.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

Bevantolol attenuates thiazide stimulated renin secretion and catecholamine release in diuretic resistant hypertensives.

An attempt was made to establish whether cardioselective beta-blockade could counteract the stimulation by hydrochlorothiazide of the renin-angiotensin and sympathetic nervous systems and to what extent such actions contributed to the antihypertensive effect of bevantolol. The hemodynamic and neurohumoral responses of 21 thiazide resistant hypertensives who had received sequential chronic therapy with hydrochlorothiazide, hydrochlorothiazide combined with bevantolol and bevantolol monotherapy were compared. In these patients, bevantolol had a negative chronotropic effect and appeared, when administered alone, to induce an overall lowering of sympathetic nervous system activity without inhibiting the reflex responses of peripheral vascular resistance to postural change or lowered heart rate. When bevantolol and hydrochlorothiazide were administered together, sympathetic activity appeared to be maintained, possibly as a reflex response to volume depletion but vascular resistance did not appear to be responsive to baroreceptor stimulation. Diminished vascular reactivity induced by the hydrochlorothiazide is suspected to be a contributory factor. Inhibition of thiazide stimulated renin release by bevantolol may contribute to the antihypertensive effect of the combined therapy.

Adrenal Glands↗

PubMed1988

Modulation of left ventricular hypertrophy by dietary salt and inhibition of angiotensin converting enzyme.

The interactions of blood pressure, salt intake and angiotensin converting enzyme (ACE) inhibition were investigated in the Dahl salt-sensitive (DS) and salt-resistant (DR) strains of rats. Eight-week-old DS and DR (40 of each) were separately randomized to receive a low- (0.4% NaCl) or a high- (8% NaCl) salt diet for 3 weeks. Thereafter the rats were further separated randomly to receive the ACE inhibitor lisinopril (3-8 mg/kg per day) or no drug treatment for 11 weeks. In untreated DS rats blood pressure rose, paralleled by a higher left ventricular mass (ratio left ventricular weight/body weight) irrespective of salt intake. Lisinopril lowered blood pressure to normotensive levels in all groups except DS rats on a high-salt diet, despite doses of up to 100 mg/kg per day, although there was a significant fall in blood pressure. Lisinopril reduced left ventricular mass significantly on the low- but not on the high-salt diet. Plasma renin activity increased on lisinopril treatment in all groups except DS rats on the high-salt diet. Regression of an increased left ventricular mass by ACE inhibition seemed to be impaired by a high salt intake, even when blood pressure was lowered. Therefore, although for regression of left ventricular hypertrophy, reduction of afterload was the leading factor, this might be adversely affected by a high salt intake.

Aldosterone↗

PubMed1988

Can plasma catecholamine levels be a useful index of sympathetic nervous system activity?

The hemodynamic responses of the sympathetic nervous system to the Valsalva maneuver were related to changes in circulating levels of catecholamines, aldosterone and plasma renin activity. Fourteen healthy normotensives (aged 27 +/- 8 years) took part. A catheter was inserted in the forearm then the subject was rested quietly (supine) for 30 mins. The Valsalva maneuver was performed (duration 40 s, intrathoracic pressure 40 mmHg) with continuous recording of supine heart rate. Blood was sampled before the maneuver (basal state) and at the bradycardic post maneuver phase for measurement of plasma noradrenaline, adrenaline, renin activity and aldosterone. In six subjects the procedure was repeated for durations of 10, 20, 30 and 40 s with a 30-min rest between each maneuver. Plasma catecholamines increased consistently (P less than 0.001) from pre- to post bradycardic phases of the maneuver. No changes in plasma renin activity or aldosterone were observed. The maximum tachycardia observed during each maneuver and the increments in catecholamine concentrations were each linearly related to the duration of straining but there was no overall correlation between the tachycardia and catecholamine concentrations. In conclusion under controlled conditions, plasma catecholamine concentrations can be useful indices of the stimulation of the sympathetic nervous system; the Valsalva maneuver does not appear to affect significantly the peripheral renin-angiotensin system; and the heart rate response to the Valsalva maneuver does not appear to be mediated solely by the sympathetic nervous system.

Adult↗

PubMed1987

The blood pressure responses of thiazide-resistant hypertensives to a once-a-day bevantolol regimen.

The antihypertensive efficacy of a single daily dose of bevantolol (200 mg) alone or in combination with hydrochlorothiazide (25 mg) has been compared against conventional twice daily propranolol (80 mg) therapy in a group of 22 hypertensive patients whose blood pressures did not respond to thiazide monotherapy. Addition of bevantolol to the diuretic resulted in a significant (P less than 0.001) fall in sitting blood pressures (144/97 to 137/90 mmHg), supine blood pressures (147/100 to 141/92 mmHg) and heart rate (83 to 73 beats/min) 24 h after administration. When the diuretic was withdrawn, heart rate and diastolic pressures remained unchanged and within normotensive limits but systolic pressures increased to pre-treatment levels. Substitution of propranolol for bevantolol gave results comparable to the combined bevantolol-diuretic regimen except that heart rate was still lower (66 beats/min). No significant adverse reactions were reported. In thiazide-resistant hypertensives, a once daily dose of 200 mg bevantolol effectively reduced diastolic blood pressures towards normotensive limits and to an extent comparable with twice daily propranolol therapy.

Adrenergic beta-Antagonists↗

PubMed1987

Hemodynamic and neurohumoral factors in the response of hypertensives to hydrochlorothiazide therapy.

We investigated the roles of the renin-angiotensin-aldosterone axis, the sympathetic nervous system, and the responses of the forearm vascular bed in the antihypertensive action of hydrochlorothiazide. Plasma renin activity, aldosterone, catecholamines, blood pressure, and forearm blood flow were measured before and after 8 weeks of hydrochlorothiazide therapy in 21 hypertensive patients whose blood pressures responded to the diuretic, and were then compared to a similar group of 19 hypertensives who did not respond to the thiazide therapy. Dietary salt intake was stable and comparable for the two groups. In the responsive patients, administration of the diuretic caused a significant fall in supine systolic and diastolic blood pressure and forearm vascular resistance, with constant forearm blood flow. No significant changes were noted in these parameters in the non-responsive group. Plasma renin activity and aldosterone concentration was increased in both groups to a comparable extent but plasma norepinephrine and epinephrine concentrations were increased to a greater extent (p less than 0.01) in the responsive group. Heart rate did not change significantly in either group in spite of significant increases in circulating epinephrine. The results are consistent with minimal thiazide-induced volume and salt depletion in either study group. The reduction in blood pressure and forearm vascular resistance observed in the responsive group appears to be the result of diminished target-organ sensitivity towards catecholamines and possibly angiotensin II.

Aldosterone↗

PubMed1986

Increased metabolic heat production following chronic alpha-methyldopa therapy in hypertensives.

The objective of this study was to measure metabolic heat production in mild-moderate hypertensives when given chronic alpha-methyldopa for control of hypertension and to compare this with hydrochlorothiazide. Four men and one woman, age range 29-55 years, euthyroid, and not previously on alpha-methyldopa, had their drugs replaced by placebo for 4 weeks, and then alpha-methyldopa or hydrochlorothiazide was randomized single blindly to patients. The dose of each drug was increased until the ambulatory diastolic blood pressure was less than 95 mmHg (1 mmHg = 133.322 Pa), and then the dose was maintained for 20-24 weeks. The two active drugs were then crossed over, and each medication was again titrated to attain diastolic normotension (less than 95 mmHg). Maintenance was for a comparable 20-24 weeks. At week 4 (end of placebo period), weeks 20-24 (for hydrochlorothiazide or alpha-methyldopa monotherapy), and again at week 40-48 (end of cross-over period), metabolic heat production (watts), heart rate (beats per minute), and blood pressure (millimetres of Hg) were measured in a resting sitting position for 1 h in a whole body calorimeter (air temperature 28 degrees C and a dew point temperature less than 5 degrees C) for 15 experimental sessions. In four out of five patients, metabolic heat production was significantly (P less than 0.05) higher when patients were treated with alpha-methyldopa. We speculate from our data that alpha-methylnorepinephrine, the major metabolite of alpha-methyldopa, may be thermogenic and that this should be considered when the drug is prescribed.

Aged↗

PubMed1986

High performance liquid chromatography analysis of nifedipine and some of its metabolites in hypertensive patients.

Techniques are described for the analysis of nifedipine and three of its metabolites; dehydronifedipine (I), dehydronifedipinic acid (II), and dehydronifedipinolactone (III) in human serum and urine. The analytes are extracted at pH 9 or 3 with ethyl acetate and chromatographed on a C8 reverse-phase column. Recoveries from spiked control serum and urine ranged from 70 to 95% depending on the polarity of the analyte. The coefficient of variation ranged from 10 to 15% (nifedipine, I, and III at 50-200 ng/mL) and 15-20% (II at 200-2000 ng/mL). Accuracy was always within the limits of precision. The metabolism of nifedipine in a group of hypertensive patients receiving long-term nifedipine therapy was compared with that reported for acute administration. Serum nifedipine levels were comparable in both cases, but contrary to previous reports, dehydronifedipine was consistently found in significant amounts. Serum levels of II were considerably elevated but III was not detected either in serum or in urine. Thus, prolonged nifedipine therapy in conjunction with other antihypertensive medications appears to be associated with significant alterations in the metabolism of nifedipine compared with acute administration.

Aged↗

PubMed1986

The metabolism of nifedipine during long-term therapy.

The serum concentrations and urinary excretion of nifedipine and 3 of its metabolites have been compared in two groups of hypertensive patients, one receiving prolonged (1-2 years) nifedipine monotherapy, the second receiving the same dosage of nifedipine in conjunction with a variety of other antihypertensive and cardioactive drugs. It was found that prolonged administration of nifedipine was associated with an eight-fold reduction in serum nifedipine concentration, one hour following a 10 mg dose, compared with the levels observed at the same time after an acute 10 mg dose. The serum concentration of the metabolite dehydronifedipinic acid was concomitantly increased, but no evidence for dehydronifedipinolactone, derived from hydroxylation of dehydronifedipinic acid, was found. When the nifedipine was administered as part of polytherapy, there was a marked (p less than 0.001) increase in the serum concentration of the drug as compared with monotherapy, together with a significant (p less than 0.05) increase in the serum concentration of its metabolites. The results suggest that while a significant enhancement of nifedipine metabolism occurs during long-term monotherapy, chronic administration of nifedipine as part of polytherapy appears to be associated with significant inhibition of the initial oxidation of nifedipine to dehydronifedipine, which may be attributable to the actions of the co-administered drugs. The subsequent hydrolysis of dehydronifedipine to dehydronifedipinic acid and the excretion of the latter metabolite appear to be much less affected, but subsequent oxidation of dehydronifedipinic acid may also be inhibited.

Chemical Phenomena↗

PubMed1985

A novel therapeutic approach for reversal of left ventricular hypertrophy and blood pressure control in hypertensive patients treated with alpha-methyldopa or propranolol.

A recently added goal in the control of primary hypertension is the reversal of left ventricular hypertrophy which may occur early in the disease and which can have serious consequences. We have attempted to define the hemodynamic parameters which distinguish most sensitively between the long-term effects of two antihypertensive drugs, alpha-methyldopa and propranolol, with a view to determining the optimal conditions under which each of the drugs may be used therapeutically. Twenty matched hypertensive patients, all with established left ventricular hypertrophy, were divided at random into two groups who received either alpha-methyldopa or propranolol as monotherapy. Dosage was titrated until blood pressures were normalized (diastolic blood pressure (DBP) less than or equal to 95 mmHg) (1 mmHg = 133.322 Pa); then therapy was maintained for 48-52 weeks. Supine and erect blood pressures, heart rates, and eight echocardiographic indices were recorded before commencement of therapy and at the 48- to 52-week period. Stepwise discriminant analysis identified erect DBP, erect heart rate, and posterior wall thickness of the left ventricle as being the parameters which distinguished most clearly the therapeutic effects of the chosen drugs. Using these three parameters, all 20 patients were correctly classified into their respective drug groups. We propose that these results may form the basis of a more rational choice of antihypertensive therapy with alpha-methyldopa or propranolol for hypertensive patients based on the initial determination of these three parameters.

Adult↗

PubMed1985

Modulation of right and left ventricular wall thicknesses in experimental hypertension.

Enalapril maleate and hydrochlorothiazide were administered over an 8-week period to groups of Dahl salt-sensitive and Dahl salt-resistant rats receiving either a high (8%) or low (0.4%) salt diet. Regional differences of interventricular septal thickness, left ventricular free wall thickness, right ventricular free wall thickness, right ventricular weight/body weight ratio, left ventricular weight/body ratio, and heart weights were determined. For salt-sensitive rats of both diet groups, lowering of blood pressure induced by either drug was associated with a reduction in cardiac weight which was localized to the left ventricle. For salt-resistant rats, irrespective of diet, the associated reduction of cardiac mass induced by enalapril maleate was largely confined to the right ventricle. Regional changes in tissue thickness were, however, not always associated with corresponding changes in tissue mass or blood pressure. These regional modulations appeared to be quite dependent on salt intake and the nature of the antihypertensive drug, for a given animal type, suggesting that pressure afterload is not the only factor in the pathogenesis of left and right ventricular hypertrophy. The responses of the right ventricle were not necessarily the same as those of the left ventricle to identical dietary and drug regimens. In all animal groups, ventricular mass and tissue thickness did not always change in the same sense, suggesting that alterations in the nature and packaging of the cellular constituents may be induced by the combined actions of the dietary salt and antihypertensive medications.

Animals↗

PubMed1985

Forearm vascular responses in normotensives and hypertensives after sublingual nifedipine.

Some hemodynamic variables of ten untreated hypertensives and nine normotensives were compared before and at 10, 30, and 60 min after nifedipine 10 mg sublingually. Serum nifedipine concentration was measured at each of these times, and was similar between groups. Resting forearm venous compliance did not differ between groups, and did not change after nifedipine. Nifedipine did not change mean arterial pressure significantly, but heart rate was increased in both groups. Resting forearm blood flow was significantly higher in hypertensives than normotensives and forearm vascular resistance was correspondingly lower. Forearm blood flow increased and vascular resistance fell after nifedipine in normotensives, but did not change significantly in hypertensives. Our data do not suggest any effect of nifedipine on peripheral venous compliance. We do not confirm the reported decrease in forearm venous compliance in hypertensives, but the characteristics of blood flow, vascular resistance, and lack of effect of nifedipine on blood pressure likely reflect a predominance of early hypertensives in our study population.

Administration, Oral↗

PubMed1984

Left ventricular changes after chronic therapy with enalapril maleate in moderate to severe hypertensive patients.

A randomized double-blind trial was carried out to determine the relationship of the changes in blood pressure and heart rate with changes in echocardiographic left ventricular indices in moderate to severe hypertensive patients with established left ventricular hypertrophy who were being treated chronically with enalapril or hydrochlorothiazide plus propranolol for 26 weeks. After a 2-week period on placebo, drug dosages in the two groups were adjusted to individual needs until blood pressure was normalized (diastolic less than 90 mmHg). Patients in Group I received 10 to 40 mg enalapril/day; those in Group II received 50 mg hydrochlorothiazide plus 80 to 240 mg propranolol/day. Echocardiographic measurements were made at the end of the placebo and 26-week active treatment periods. Significant correlations were observed between the changes in four pairs of variables in each group. In the 8 patients receiving enalapril, there were negative correlations between interventricular septal thickness and supine systolic blood pressure, erect and supine heart rates, and a positive correlation between relative wall thickness and erect diastolic blood pressure. In the 7 patients on hydrochlorothiazide plus propranolol, there were negative correlations between relative wall thickness and erect and supine heart rate, and positive correlations between left ventricular mass and erect diastolic blood pressure, and the percentage change in internal diameter of the left ventricle and supine systolic blood pressure. Possible explanations for and implications of these regional changes are discussed.

Adult↗

PubMed1984

The reversal of left ventricular hypertrophy with control of blood pressure in experimental hypertension.

The precise mechanisms of hypertensive left ventricular hypertrophy and reversal with antihypertensive drugs are unclear and complex. Enalapril maleate (MK421) and hydrochlorothiazide (HTZ) were used to assess the control of hypertension, and reversal of left ventricular hypertrophy in Dahl sensitive (DS) and Dahl resistant (DR) rats given either a high (8% NaCl), or a low (0.4% NaCl) salt diet. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), left ventricular weight/body weight (LVwt/Bwt) ratio were determined. Both drugs were effective in reducing blood pressure and left ventricular mass in DS rats placed on a high salt diet. For DR rats under the same conditions, only MK421 induced significant lowering of blood pressure. Neither drug caused significant change in ventricular mass. Both DS and DR rats on a low salt diet underwent significant blood pressure reduction with MK421 but not HTZ. Significant regression of the left ventricle was observed only in DS rats treated with MK421. Regression was not observed in DR rats even though MK421 reduced blood pressure to distinctly hypotensive levels. The dissociation of left ventricular mass and blood pressure control observed with both MK421 and HTZ suggests that pressure afterload is not the only factor involved in the pathophysiology of hypertensive cardiac hypertrophy. The mechanisms of anti-hypertensive drug action and salt intake both appear to play a significant if unexplained role.

Animals↗