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Biomedical subjects

C Hartley

Publications and source records attributed to C Hartley.

At least 73 records · Page 4Linked to original sources

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. II. Verapamil, enflurane, and isoflurane.

The effects of enflurane and isoflurane on the cardiovascular system and cellular calcium kinetics are somewhat different. Consequently, the interaction with the calcium channel blocking drug, verapamil, may also differ. In order to compare the anesthetics, the authors studied the effects of two infusion doses of verapamil (which produced plasma levels of 90 and 180 ng X ml-1) on cardiovascular dynamics and regional blood flow in awake dogs. On two other days, in the same dogs, the effects of approximately 1.1 and 2 MAC enflurane and isoflurane were first studied and then the same verapamil dose regimens while the same anesthetic concentrations were maintained. Verapamil produced only increases in heart rate and the P-R interval in the awake animal. The high dose of both anesthetics markedly decreased mean aortic pressure and left ventricular rate of tension development (dP/dt), and increased heart rate. However, only enflurane also decreased myocardial segment length shortening and increased left atrial pressure. Neither anesthetic alone affected coronary or renal blood flow, while both increased carotid blood flow at the low dose. Verapamil infusion during 1.2 MAC enflurane was more depressant than during 1.2 MAC isoflurane, but the combination of verapamil with 2 MAC concentration of both anesthetics was equally depressant. Both doses of both anesthetics increased plasma verapamil levels compared with the same verapamil dosing regimen awake. When these results are compared with those previously reported for halothane, the effects of verapamil during all three anesthetics are more similar than different.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Endotracheal↗

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. III. Nicardipine and isoflurane.

To assess the interaction between isoflurane and the new calcium channel blocker, nicardipine, mongrel dogs were chronically instrumented to allow the following measurements: aortic, left ventricular and left atrial pressures; heart rate; cardiac output; and carotid, coronary, and renal blood flows. The hemodynamic effects of intravenous nicardipine 5, 10, 30, and 50 micrograms/kg were measured in awake dogs and during 1.6 and 3.0 per cent (end-tidal) isoflurane anesthesia. Nicardipine induced a dose-dependent fall in mean arterial pressure in both awake dogs and during 1.6 and 3.0 per cent isoflurane anesthesia. Heart rate and cardiac output were increased in proportion to the nicardipine dose in the awake dogs and, to a lesser degree, in the dogs anesthetized with 1.6 per cent isoflurane, but did not change during 3.0 per cent isoflurane anesthesia. Left atrial pressure was unchanged by nicardipine in awake dogs and during anesthesia. Left ventricular maximum rate of tension development (dP/dt) increased in awake dogs and decreased during anesthesia. Coronary blood flow increased dose dependently without anesthesia, and, to a smaller degree, during anesthesia. Nicardipine increased carotid blood flow without anesthesia, whereas it was unchanged during anesthesia. Renal blood flow was unchanged in awake dogs and decreased during anesthesia. The authors conclude that nicardipine is a potent vasodilator that minimally affects cardiac function and regional blood flow in the presence of isoflurane. The interactions between nicardipine and isoflurane are mainly the result of the isoflurane-induced inhibition of the reflex tachycardia elicited by nicardipine.

Animals↗

Effects of alpha and beta adrenergic blockade on hepatic glucose balance before and after oral glucose. Role of insulin and glucagon.

In conscious dogs, phentolamine infusion significantly increased fasting portal vein insulin, glucagon, and decreased net hepatic glucose output and plasma glucose. Propranolol significantly decreased portal vein insulin, portal flow, and increased hepatic glucose production and plasma glucose. Phentolamine, propranolol, and combined blockade reduced glucose absorption after oral glucose. alpha, beta, and combined blockade abolished the augmented fractional hepatic insulin extraction after oral glucose. Despite different absolute amounts of glucose absorbed and different amounts of insulin reaching the liver, the percent of the absorbed glucose retained by the liver was similar for control and with alpha- or beta blockade, but markedly decreased with combined blockade. Our conclusions are: (a) phentolamine and propranolol effects on basal hepatic glucose production may predominantly reflect their action on insulin and glucagon secretion; (b) after oral glucose, alpha- and beta-blockers separately or combined decrease glucose release into the portal system; (c) net hepatic glucose uptake is predominantly determined by hyperglycemia but can be modulated by insulin and glucagon; (d) direct correlation does not exist between hepatic delivery and uptake of insulin and net hepatic glucose uptake; (e) alterations in oral glucose tolerance due to adrenergic blockers, beyond their effects on glucose absorption, can be, to a large extent, mediated by their effects on insulin and glucagon secretion reflecting both hepatic and peripheral glucose metabolism.

Administration, Oral↗

Control of herpes simplex virus infections of the genital tract by vaccination.

The apparent increasing incidence of herpes simplex virus infections of the genital tract has focused attention on the efficacy of vaccination in preventing infection or modifying established disease. Results of an 'open trial' using a DNA-free inactivated virus subunit vaccine have shown that vaccination of subjects at risk of contracting infection from their sexual partner reduced the transmission rate from 34% in unvaccinated controls to 0.5%. In a separate study, vaccination of patients who had experienced their first overt attack of herpes genitalis (the initial clinical episode) had significantly fewer recurrences over the follow-up period of 12 months than the unvaccinated control group. The results, we feel, justify a placebo controlled trial.

Adolescent↗

Effects of atropine and gastric inhibitory polypeptide on hepatic glucose uptake and insulin extraction in conscious dogs.

Previous studies comparing the effects of oral, intraportal, and peripheral venous administration of glucose in conscious dogs demonstrated a significant increase in hepatic extraction of insulin only after oral glucose, but similar hepatic uptake of glucose after oral and intraportal glucose, which was greater than that after peripheral intravenous glucose infusion. This study evaluated the effect of atropine blockade of the parasympathetic nervous system on the increased fractional hepatic extraction of insulin and the role of gastric inhibitory polypeptide (GIP) on augmented hepatic uptake of oral glucose in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery, and catheters in the portal and hepatic veins and carotid artery. Since atropine infusion decreased absorption of glucose, and in order to achieve comparable portal vein levels of glucose and insulin, the dogs receiving atropine were given 1.9 +/- 0.1 g/kg glucose, compared with the control dogs who received 1.1 +/- 0.1 g/kg. The percentage of the glucose load that was absorbed was greater in the dogs not given atropine (80 +/- 4 vs. 44 +/- 7%), but because of the different loads, the absolute amount of glucose absorbed was similar in both groups (20.2 +/- 1.6 vs. 21.7 +/- 4.1 g). Although delayed by atropine, the peak portal vein glucose and insulin concentrations and the amounts presented to the liver were similar in both groups. However, the increased portal vein plasma flow and fractional hepatic extraction of insulin observed after oral glucose was not observed in the dogs infused with atropine. The net hepatic glucose uptake after oral glucose was significantly less at 10, 20, and 45 min in the atropine-treated dogs, and the area under the curve over the 180-min period was 44% less. However, the latter was not statistically significant. Infusion of GIP with peripheral intravenous glucose did not increase hepatic uptake of glucose or the fractional hepatic extraction of insulin compared with peripheral intravenous glucose alone. These results indicate an important role for parasympathetic innervation in the augmented fractional hepatic extraction of insulin, and increased portal vein plasma flow after oral glucose. Although a relationship between the augmented fractional extraction of insulin and the net hepatic glucose uptake may exist, it does not necessarily indicate that the former is required for the latter. Such parasympathetic innervation may be involved in the greater removal of glucose by the liver after oral compared with peripheral glucose administration. The augmented hepatic uptake of glucose and fractional hepatic extraction of insulin after oral glucose doesn not appear to be mediated by gastric inhibitory polypeptide.

Administration, Oral↗

Adaptation of canine saphenous veins to grafting. Correlation of contractility and contractile protein content.

Saphenous veins are used extensively to replace stenotic coronary arteries. However, the contractile and biochemical adaptations of grafted veins are unknown. The three purposes of this work were to characterize the contractile properties of grafted veins, to determine whether altered contractile characteristics were associated with quantitative changes in actin, myosin and collagen, and to determine which changes were associated with the surgical procedure and which with placement in the arterial circulation. Canine saphenous veins were removed and returned to their original location (venous autograft), while others were used to replace a segment of femoral artery (arterial graft). The grafts were removed 1, 4, and 8 weeks later and compared with the contralateral saphenous vein. Both graft types exhibited an increase in sensitivity to norepinephrine but not to potassium chloride. The venous autograft exhibited a reversible reduction in myosin content and in maximum contractile response (force/cross-sectional area) to potassium chloride and norepinephrine. In contrast, the arterial graft exhibited increased wall thickness and content of all measured proteins and decreased maximum contractile response. The latter occurred even though there was an increase in the net production of actin and myosin. Expressing the maximum contractile response in terms of the myosin content did not normalize the contractile response. These results suggest that, except for the elevated sensitivity to norepinephrine, the vein is capable of recovering from the effects of surgery within 8 weeks; however, placement of the vein in the arterial circulation delays this recovery and initiates a hypertrophic response that includes an attenuation of contractile function.

Adaptation, Physiological↗

Efficacy of vaccine Ac NFU1 (S-) MRC 5 given after an initial clinical episode in the prevention of herpes genitalis.

A subunit antigenoid vaccine, Ac NFU1 (S-) MRC 5, was used in patients who had had a clinical episode of herpes genitalis. The rate of recurrence was compared with that in unvaccinated patients to determine the efficacy of vaccination in preventing recurrence and spread of the virus in the community. Seven of 22 (31%) vaccinated patients had eight recurrences after the initial clinical episode; in contrast there were 51 recurrences in 17 of 20 (85%) unvaccinated patients. Although further studies are needed, the results indicate that the vaccine may prevent recurrent episodes of herpes genitalis and thereby reduce the dissemination of this virus in the population.

Adolescent↗

Differential effects of oral, peripheral intravenous, and intraportal glucose on hepatic glucose uptake and insulin and glucagon extraction in conscious dogs.

The effect of equal (1.1 +/- 0.1 g/kg body wt) amounts of glucose administered orally, or by peripheral intravenous or intraportal infusion on hepatic glucose uptake and fractional hepatic extraction of insulin and glucagon was studied in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery and catheters in the portal vein, hepatic vein, carotid artery, and superior mesenteric vein. Portal vein and hepatic vein plasma flow increased only after oral glucose administration. Arterial plasma glucose increased equally to 150-160 mg/100 ml after all three routes of glucose administration. Portal vein glucose was similar after oral (195 +/- 15 mg/100 ml) and intraportal glucose infusion (215 +/- 11 mg/100 ml) and significantly higher than after peripheral intravenous glucose. Hepatic glucose uptake after oral (68 +/- 4%) and intraportal glucose administration (65 +/- 7%) significantly exceeded that after peripheral intravenous glucose infusion (23 +/- 5%). The amount of insulin above basal presented to the liver during the 180 min after oral glucose was 7.6 +/- 1.3 U, 4.3 +/- 0.6 U after intraportal glucose, and 4.1 +/- 0.6 U after peripheral intravenous glucose. Hepatic extraction of insulin increased significantly after oral glucose (42 +/- 3 to 61 +/- 4%), but was unchanged after intraportal and peripheral intravenous glucose administration. When the portal vein glucose levels achieved during peripheral intravenous glucose infusion for 90 min were maintained by a subsequent 90-min intraportal glucose infusion, hepatic glucose uptake was significantly greater during the intraportal glucose infusion. Glucagon secretion was suppressed equally after oral glucose, intraportal glucose, and peripheral intravenous glucose administration; fractional hepatic extraction of that hormone, which was significantly less than that of insulin, was unchanged. These results indicate that hepatic glucose uptake is significantly greater after oral and intraportal glucose administration than after peripheral intravenous glucose infusion. This difference is not simply related to the amount of glucose or insulin presented to the liver and the increased hepatic glucose uptake did not depend solely upon the augmented fractional hepatic extraction of insulin. Hepatic extraction of insulin and hepatic glucose uptake appear to be regulated independently.

Administration, Oral↗

Early experience with "antigenoid" vaccine Ac NFU1(S-) MRC towards prevention or modification of herpes genitalis.

The preparation and early clinical experience with "antigenoid" vaccine Ac NFU1(S-) MRC is described. A neutralising antibody response against both type 1 and type 2 herpes simplex virus was stimulated in 19 of 21 and 25 of 60 patients who received the high and low dosage of vaccine, respectively: immunoprecipitating antibody against type-common virus antigen "band II", a virus antigen of major importance in neutralization of herpes simplex virus, was detected in 12 of 19 and 2 of consorts who received the high and low dosage vaccine, respectively. To date, after a mean follow-up period of one year, none of the 42 consorts have contracted herpes genitalis: following a mean follow-up period of 6 months, only 1 patient vaccinated after the initial clinical episode has reported a recurrence of herpetic disease. These results compare favourably with the rates of consort transmission and first year recurrences in unvaccinated subjects. Seventeen of 24 patients with recurrent herpetic disease reported an "improvement" in terms of modification of the frequency, severity or extent of herpetic lesions. There were no important side-effects from vaccination: most patients experienced a degree of minor local reaction at the vaccination site for 24-72 hours and 3 patients reported a mild transient "flu-like" syndrome which disappeared within 48 hours of vaccination. It is intended to subject these data to the scrutiny of a placebo-controlled trial with an objective system of clinical assessment.

Animals↗

Noninvasive pulsed Doppler blood velocity measurements and calculated flow in human digital arteries.

Few quantitative studies of blood velocities and calculated flow measurements in the human digital arteries have been reported due to resolution limitations of existing Doppler instruments. Under carefully controlled conditions, we transcutaneously measured blood flow velocities in the ten digital arteries in the right hand of five male adults (BSA 1.83-2.19m2) with a high resolution 20MHz pulsed Doppler instrument which was calibrated in vitro. A 1.0mm2 ultrasonic transducer was mounted on a 16 gage needle in a stereotaxic apparatus at a known Doppler angle to the vessel flow axis. The sample volume (SV) was adjustable in both range (1 - 13 mm) and length (0.3 - 4.0 mm). In order to obtain a more uniform acoustic field in the SV, the transmitted pulse was attenuated exponentially at a rate consistent with acoustic attenuation in blood. This permitted measurement of velocity profiles and spatially averaged velocities along the sound beam. Deconvoluted calculations of vessel internal diameter (D) and volume flow rates (Q) were made in the 10 different digital vessels. Velocity waveforms were triphasic with positive diastolic flow. In the digital vessels, the average D varied from 0.78 +/- 0.11 to 1.04 +/- 0.05 mm and the average Q from 2.03 +/- 0.92 to 3.71 +/- 0.69 ml/min. For each vessel, Q correlated with body surface area r = 0.80 to 0.91 (p less than .05) with a coefficient of variance calculated from the normalized flow rate (Q/BSA) ranging from 10% to 38%. Flows in parallel vessels of the middle digits were not significantly different. These studies suggest that noninvasive, spatially averaged blood velocity and calculated flow measurements, which are accurate and reproducible, can be made in human digital arteries.

Adult↗

The comparative electrophysiologic and hemodynamic effects of verapamil in puppies and adult dogs.

Verapamil has been studied extensively in adult animals. However, there is limited data about the effects of this antiarrhythmic agent in young animals. We studied the electrophysiologic and hemodynamic effects of verapamil in 5 awake, chronically instrumented puppies and in 6 anesthetized, acutely instrumented puppies. We compared the responses in puppies to those in 7 awake, chronically instrumented adult dogs and in 6 anesthetized, acutely instrumented adult dogs. In the awake, chronically instrumented animals, we measured heart rate and the effective refractory period of the atrio-ventricular specialized conduction system (ERP-AVSCS). In the anesthetized, acutely instrumented preparation, we measured heart rate, ERP-AVSCS, mean right atrial and systemic arterial blood pressure, and velocity of blood flow in the aorta, carotid and femoral arteries. We infused verapamil intravenously at doses of 50, 100, 200 and 400 microgram/kg. Verapamil (400 micrograms/kg) increased the ERP-AVSCS by 64% in awake, chronically instrumented puppies; 62% in awake, chronically instrumented adult dogs; 125% in anesthetized, acutely instrumented puppies, and 120% in anesthetized, acutely instrumented adult dogs. The effect of verapamil upon heart rate and ERP-AVSCS was more pronounced in anesthetized animals than in awake animals. Mean systemic arterial blood pressure was reduced by verapamil in anesthetized, acutely instrumented puppies and adult dogs. Verapamil reduced the velocity of aortic, femoral and carotid artery blood flow in anesthetized, acutely instrumented puppies.

Aging↗

The effect of lithium chloride on the replication of herpes simplex virus.

Lithium chloride inhibited the replication of type 1 and type 2 Herpes simplex virus at concentrations which permitted host cell replication. Virus polypeptide and antigen synthesis were unaffected while viral DNA synthesis was inhibited. The replication of two other DNA viruses, pseudorabies and vaccinia virus, was inhibited but there was no inhibition of two RNA viruses, namely, EMC and influenze virus.

Antigens, Viral↗