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Biomedical subjects

D G Shand

Publications and source records attributed to D G Shand.

155 records · Page 9Linked to original sources
PubMedDate not supplied

Effect of verapamil on left ventricular function at rest and during exercise in normal men.

Verapamil is a calcium channel blocking agent used primarily for treatment of arrhythmias and coronary artery disease. It may also depress myocardial contractility. The purpose of this study was to assess the effect of verapamil on left ventricular function. Twelve normal men, 22-29 years of age, were studied at rest and during exercise, with and without verapamil, using first-pass radionuclide angiocardiography. Verapamil was administered by continuous intravenous infusion to produce steady-state blood levels of 106-123 ng/ml. The heart rate, ejection fraction, stroke volume index, and end-diastolic volume index were measured with and without the drug. Verapamil increased the mean resting heart rate from 74 to 78 beats/min (p = 0.001), decreased the mean stroke volume index from 48 to 42 ml/m2 (p = 0.01), and decreased the mean end-diastolic volume index from 77 to 71 ml/m2 (p less than 0.05). No changes in cardiac index, ejection fraction, end-systolic volume index, or peak systolic pressure/end-systolic volume ratio were observed at rest. No differences occurred in exercise hemodynamics. Thus verapamil at therapeutic dose levels did not significantly depress contractility or have other clinically important hemodynamic effects at rest or during exercise in normal subjects.

Adult↗
PubMedDate not supplied

Alterations in the responses of the sympathetic nervous system and renin in borderline hypertension.

We investigated the effect of stimuli activate the sympathetic nervous system on plasma catecholamines, renin activity, urinary metanephrine and normetanephrine, and various hemodynamic parameters in normal subjects (NIs) and borderline hypertensive (BH) subjects. No differences were observed in sympathetic nervous system activity or renin activity when the subjects were in the resting state on a 150 mEq sodium diet. However, the BH group exhibited greater responses in terms of plasma catecholamines and plasma renin activity in response to sodium deprivation and treadmill exercise. Although hemodynamic differences in the cold pressor test and handgrip exercise did not emerge, the radio of atrial size decrement to venous tone increment during the Valsalva maneuver was significantly reduced in the BH group. The investigations suggest that in the basal state, BH subjects have appropriate levels of activation of the sympathetic and renin systems for a normal level of pressure but that perturbations of pressure and volume factors lead to unmasking of abnormalities in regulation of both systems. The data are also consistent with the suggestion that venous compliance is reduced in these patients.

Adolescent↗
PubMedDate not supplied

Plasma norepinephrine in the evaluation of baroreceptor function in humans.

The value of plasma norepinephrine measurement in assessing baroreceptor-mediated changes in sympathetic vasomotor activity was studied in seven healthy normotensive volunteers. Blood pressure was decreased by graded steady-state infusions of sodium nitroprusside (25-100 micrograms/min) and increased by infusions of phenylephrine (25-100 micrograms/min) at rates producing a 10% to 20% change in diastolic blood pressure. Sodium nitroprusside produced significant decreases in diastolic blood pressure (p less than 0.01) and calculated mean arterial blood pressure (p less than 0.005), and increases in heart rate (p less than 0.001) and plasma norepinephrine (p less than 0.001). Phenylephrine administration produced increases in systolic (p less than 0.005), diastolic (p less than 0.005), and mean blood pressure (p less than 0.001). Heart rate (p less than 0.001) and plasma norepinephrine (p less than 0.05) fell. The absolute changes in diastolic and mean pressure and heart rate were not significantly different for the two drugs, but were of opposite sign; however, the increase in plasma norepinephrine during hypotension was greater than the decrease during hypertension (p = 0.02). We conclude that plasma norepinephrine changes appropriately in response to altered blood pressure and that the response is greater to a given fall than to a rise in blood pressure, consistent with known changes in sympathetic vasomotor outflow.

Adult↗
PubMedDate not supplied

Clinical pharmacokinetics of propranolol.

Propranolol is completely absorbed after oral administration and widely distributed throughout tissues. Elimination occurs almost wholly by metabolic transformation in the liver and excretion of the resultant products in the urine. An active metabolite, 4-hydroxypropranolol and possibly other active compounds have been identified; the former only after oral administration. After intravenous administration, hepatic extraction is so efficient that drug clearance is dependent on liver blood flow. After oral administration, propranolol kinetics depend on both dose and duration of therapy, but hepatic extraction remains relatively high and leads in presystemic ('first-pass') elimination and low systemic availability. During continued administration, plasma concentrations vary quite widely due to genetic differences superimposed on which are certain constitutional factors, such as age, and environmental factors such as smoking, other drugs, and perhaps diet. Hepatic, renal, thyroid and some gastrointestinal diseases as well as hypertension, malnutrition and hypothermia may be associated with alterations in propranolol disposition, all of which are consistent with the pathophysiology of these diseases.

Administration, Oral↗
PubMedDate not supplied

A re-evaluation of intersubject variation in enzyme induction in man.

It has previously been suggested that subjects who are initially slow metabolisers of drugs have a greater potential for induction of their drug metabolising enzymes than subjects with initial high rates of metabolism. This inference is based on observations made of changes in half-life of antipyrine. The purpose of this presentation is to reanalyse data previously presented in the literature with reference to clearance, a more precise estimate of drug metabolising activity, and half-life a parameter derived from both clearance and distribution. In one study in non-obese subjects, approximately 80% of intersubject variation in the change of total antipyrine clearance can be explained by differences in body size, particularly differences in liver volume. Furthermore, the relationship between initial antipyrine half-life and the percentage change in antipyrine half-life following induction can be explained by the association between each parameter and body weight. These observations imply that the potential for enzyme induction, and therefore for drug interactions based on enzyme induction, is present in all subjects and that intersubject variance in steady-state drug concentrations are as wide following induction as before induction.

Antipyrine↗
PubMedDate not supplied

Disposition of carbamazepine and its 10,11-epoxide metabolite in the isolated perfused rat liver.

The disposition of carbamazepine and its metabolite, the 10,11-epoxide, was investigated in isolated perfused livers from control and phenobarbital-pretreated rats. The mean hepatic clearance of carbamazepine was 0.28 ml per min per g of liver corresponding to a mean extraction ratio of 0.16 and a mean intrinsic clearance of 0.33 ml per min g of liver. In phenobarbital-pretreated rats, there was an approximately 40% increase in the hepatic clearance due to a concomitant increase in the mean extraction ratio from 0.16 to 0.26. The carbamazepine-10,11-epoxide generated in the liver approached and attained its peak concentration more rapidly in pretreated than in control rat livers. In the latter group there was virtually no disappearance of the epoxide from the perfusate, whereas in the pretreated rat livers the perfusate concentrations declined after 90 min. The extremely low clearance of the epoxide generated by metabolism in control rat liver was confirmed by administration of the epoxide per se to the perfusion system. The mean extraction ratio of the epoxide in this situation was only 0.016 and it was unaffected by prior treatment of the rats with phenobarbital. However, the epoxids exhibited dose-dependent kinetics with a 3-fold increase in the extraction ratio when the administered dose was reduced from 500 to 166 microng. The observed induction of the hepatic clearance of carbamazepine is supportive of the involvement of this mechanism in the interaction of this drug with various other anticonvulsants in both children and adults.

Animals↗