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Biomedical subjects

P R Knight

Publications and source records attributed to P R Knight.

At least 55 records · Page 3Linked to original sources
PubMed1990

Alterations in influenza A virus specific immune injury in mice anesthetized with halothane or ketamine.

CD-1 mice infected with a sublethal dose of influenza A virus were anesthetized for 2 h with halothane. These mice were compared to a control group which was similarly infected using ketamine sedation. Mice anesthetized with halothane showed less physical signs of illness and demonstrated less lung histopathology than the control group of mice. Virus titers were reduced in the group of animals exposed to halothane 12 h after infection, but were the same as the infected controls at all other times measured (1-12 days after infection). Morphometric analysis of lung tissue demonstrated a delayed appearance of both neutrophils and monocytes in the halothane-exposed mice. These results suggest that the halogenated volatile anesthetic halothane decreases the pulmonary pathogenesis of influenza A virus by altering the recruitment of immunological effector cells during the course of the infection.

Animals↗
PubMed1989

Characterization of a halothane-resistant strain of measles virus.

A strain of measles virus (MVr) whose replication demonstrated increased resistance to halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) exposure compared with the susceptible parental strain (MVs) is described. After exposure to a 1.2% halothane concentration, substantial amounts of the measles virus H protein were detected in MVr-infected Vero cell lysates by immunoprecipitation and polyacrylamide gel electrophoresis or by quantitative immunofluorescence staining. The protein was barely detectable in identically treated MVs-infected lysates, however. The recovery of all other measles virus proteins studied was the same in MVr- and MVs-infected cells at this anesthetic concentration. Thus, the altered expression of a single gene product appears to be responsible for the observed halothane resistance.

Animals↗
PubMed1989

Alterations of cytosolic calcium in LLC-PK1 cells induced by vasopressin and exogenous purines.

The regulation of cytosolic calcium in LLC-PK1 cells by various agonists was characterized. Arginine vasopressin (AVP, 100 nM) rapidly increased cytosolic calcium (Caf) measured with fura-2 from a basal level of 65 +/- 5 to 516 +/- 102 nM followed by a return to a plateau level of 128 +/- 18 nM. Similar responses to 100 nM lysine vasopressin were seen. AVP also increased adenosine 3',5'-cyclic monophosphate (cAMP) as previously documented for these cells. A V2-selective AVP analogue increased cAMP without affecting Caf, whereas two V1-receptor antagonists prevented the Caf response to AVP without altering the cAMP response. Increasing cellular cAMP with forskolin, cholera toxin, or stable cAMP analogues did not affect Caf or the response of Caf to AVP. Both adenosine and ATP produced large Caf transients at concentrations of 1-10 microM in both calcium-containing media and after acute chelation of medium Ca with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The A1-selective adenosine analogue, (R-phenyl-isopropyl)-adenosine, and the A2-selective analogue, 5'-(N-ethyl)-carboxamido-adenosine, both produced Caf responses similar to adenosine. The Caf responses to adenosine and its analogues but not to ATP were blocked by the adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine. Islet-activating protein, pertussis toxin, inhibited the Caf response to adenosine and enhanced the cAMP response to AVP. Responses to all agonists were demonstrable in greater than 80% of single cells studied by microfluorometry, and individual cells responded to multiple agonists. These studies indicate that the Caf and cAMP responses to AVP in the LLC-PK1 cell line involve separate receptors, and they document the presence in this cell line of at least two types of receptors for exogenous purines.

Arginine Vasopressin↗
PubMed1989

Acute acid aspiration lung injury in the rat: biphasic pathogenesis.

The purpose of this study was to develop a reproducible model of acute acid aspiration-induced lung injury in the rat to explore the pathophysiology of aspiration pneumonitis. A biphasic injury pattern was observed with injury peaks at 1 hr and 4 hr. Histologic studies at 4 hr revealed significant increases in neutrophils in the alveolar interstitial space. These studies suggest that acid aspiration results in a biphasic acute injury. We hypothesize that the first phase results from a direct physiochemical process or is mediated via afferent (capsaicin sensitive) nerves or both. The second phase, occurring 2-3 hr later, is mediated by neutrophils and is consistent with an acute inflammatory response.

Animals↗
PubMed1988

Effects of the volatile anesthetic agents on sinus node function and atrioventricular conduction in dogs: a comparison with chloralose anesthesia.

The effects of equipotent concentrations (1.5 times minimum alveolar concentration) of the inhalational agents halothane, enflurane, and isoflurane on sinus node function, and atrioventricular (A-V) conduction and refractoriness were compared with chloralose anesthesia in 49 mongrel dogs. Sinus node function was assessed using corrected sinus node recovery time. Atrial-His and His-ventricular conduction times were measured at paced heart rates of 150, 180, and 200 beats/min, and A-V refractoriness was assessed by Wenckebach periodicity. There was no evidence that sinus node function was impaired by any of the inhalational agents. Enflurane anesthesia was associated with a significant prolongation of atrial-His conduction at paced heart rates of 180 and 200 beats/min when compared to chloralose anesthesia and the other two inhalational agents (P < .001). Atrioventricular refractoriness was impaired by enflurane (P < .001) and halothane (P < .05), but not isoflurane, when compared with chloralose anesthesia. Ventricular-His conduction was not altered by any of the agents. The authors conclude that enflurane is associated with a greater impairment of A-V conduction and refractoriness than halothane or isoflurane, and that these changes are related to the anesthetic agent and not the anesthetic state.

Anesthetics, Inhalation↗
PubMed1988

Cardiac electrophysiologic interactions of bepridil, a new calcium antagonist, with enflurane, halothane, and isoflurane.

Bepridil is an investigational calcium antagonist that also has fast sodium channel blocking and antidysrhythmic properties. In the present study, the potential interactions of bepridil with volatile anesthetics on cardiac electrophysiologic parameters were evaluated in open-chest dogs. Twenty-four dogs anesthetized with enflurane (n=6), halothane (n=6), isoflurane (n=6), or chloralose (n=6) received 2.5 mg/kg of bepridil intravenously (IV). Twenty-five additional dogs anesthetized with enflurane (n=7), halothane (n=6), isoflurane (n=6), or chloralose (n=6), received bepridil, 5.0 mg/kg, IV. Dogs anesthetized with cloralose served as controls. Cardiac electrophysiologic parameters were measured after the dogs were anesthetized and were repeated 5, 15, 30, 45, and 60 minutes after bepridil infusion. Plasma bepridil concentrations were also determined at the above time points. Synergy between bepridil and enflurane was demonstrated in the following cardiac electrophysiologic parameters: depression of sinus node function as evidenced by severe depression of sinus node automaticity and conduction; depression of atrioventricular function as evidenced by prolongation of the atrial-His bundle interval and the Wenckebach R-R interval; and, prolongation of the atrial effective refractory period. No synergy was demonstrated between bepridil and halothane or isoflurane when compared to bepridil's effects during chloralose anesthesia. It is concluded that significant synergistic cardiac electrophysiologic effects exist between bepridil and enflurane in dogs. It is recommended that caution be used when anesthetizing patients receiving bepridil with enflurane until human data on the use of this combination of pharmacologic agents is available.

Anesthetics, Inhalation↗
PubMed1988

The effect of trimethaphan-induced hypotension on canine spinal cord blood flow. Measurement at different cord levels using radiolabelled microspheres.

Controlled hypotension which is used during scoliosis surgery to improve operating conditions and minimize transfusion requirements may decrease spinal cord blood flow (SCBF). Previous studies using hydrogen washout, an invasive technique, have shown that trimethaphan-induced hypotension is associated with a decrease in SCBF, whereas hypotension induced with sodium nitroprusside or nitroglycerin is not. To determine whether the decrease seen with trimethaphan represented a generalized rather than regional spinal cord phenomenon, SCBF was measured at three separate cord levels (T2-3, 7-8, L2-3) using a noninvasive radionuclide-labelled microsphere technique. When the mean arterial pressure was reduced by 50%, SCBF decreased 35 to 45% at all levels of the cord examined, and remained at this reduced level during the period of hypotension. The results confirm that trimethaphan-induced hypotension is associated with a significant reduction in SCBF and that this occurs throughout the spinal cord during the period of hypotension.

Animals↗
PubMed1988

Alterations in the course of and histopathologic response to influenza virus infections produced by enflurane, halothane, and diethyl ether anesthesia in ferrets.

Alterations in the course of and histopathologic response to influenza viral infections by halothane, enflurane, and diethyl ether anesthesia were evaluated in ferrets. There were no significant differences in the incidence and duration of lethargy, pyrexia, rhinorrhea, or sneezing in infected animals given one of the three anesthetic agents under investigation, compared with those receiving no anesthesia. There were no differences in lung pathology in infected animals given one of the three anesthetic agents, or no anesthesia, though histopathologic changes in the nasal turbinates were significantly greater in ferrets given enflurane. This study suggests that general anesthesia administered to ferrets infected with influenza virus carries minimal morbidity, although enflurane anesthesia was found to produce greater histopathologic changes than the other agents.

Anesthesia, Inhalation↗
PubMed1987

Intraoperative respiratory complications in patients with upper respiratory tract infections.

A retrospective survey of 3,585 patients aged newborn to 20 years was performed to investigate the prevalence of intraoperative respiratory complications in patients with symptoms of upper respiratory tract infections (URIs). There were no significant differences in complication rates between asymptomatic patients (1.61 per 100) and those with symptoms (1.64 per 100); however, patients who were asymptomatic but had a recent history of an URI had a significantly higher complication rate (5.31 per 100; p less than 0.05) than the asymptomatic patients. There were no significant differences in intraoperative complications between patients managed with and without tracheal intubation, nor was there any association between the type of anaesthetic agent used and the development of intraoperative respiratory complications. Results from the study suggest no increased risk of respiratory complications for patients presenting with uncomplicated URIs. However, patients who were asymptomatic but had a recent history of an URI showed a significantly increased risk for the development of intraoperative complications.

Adolescent↗
PubMed1987

Effect of nitroglycerine-induced hypotension on canine spinal cord blood flow.

Twenty-four mongrel dogs were anaesthetized with pentobarbitone and morphine sulphate. Neuromuscular blockade was achieved using pancuronium. Spinal cord blood flow was measured using the radionuclide microsphere and hydrogen washout methods before, during, and following nitroglycerine-induced hypotension. Heart rate, mean arterial pressure, cardiac output, pulmonary capillary wedge pressure, and acid-base balance were determined with each measurement. Mean arterial pressure was reduced by 50%. Spinal cord blood flow, as measured by the microsphere method, increased during the period of hypotension, whereas values obtained using the hydrogen washout method were not significantly different from those at normotension. No significant change in spinal cord blood flow was detected by either method after the application of spinal distraction. Nitroglycerine acts predominantly on venous capacitance vessels and it is postulated that perfusion pressure, and therefore flow, is maintained despite a reduction in arterial pressure.

Anesthesia, General↗
PubMed1987

The effects of general anesthesia on upper respiratory tract infections in children.

A prospective cohort study of 489 pediatric patients was performed to investigate the prevalence of perioperative respiratory complications and symptomatology in children presenting for myringotomy with upper respiratory tract infections (URIs). All children undergoing myringotomy received halothane N2O/O2 anesthesia administered via face mask. Information on complications and respiratory symptoms was obtained from the anesthesia and recovery room records, and by standardized questionnaire. There were no significant differences in perioperative complications between asymptomatic children (1.23%), symptomatic children fulfilling predetermined URI criteria (1.28%), and symptomatic children that did not fulfill the URI criteria (2.38%). In addition, the prevalence and duration of respiratory symptoms was significantly less in children having received anesthesia and surgery than in a matched group of non-anesthetized controls who did not have surgery. Results from this study suggest that there is no increased morbidity for children presenting at minor surgery with acute uncomplicated URIs and who did not require tracheal intubation. In addition, the administration of general anesthesia and surgery to this group of patients was followed by a decrease in both the appearance and duration of a number of respiratory symptoms.

Anesthesia, Inhalation↗
PubMed1987

The effects of calcium-blocking agents on sympathetic responses to acute haemorrhagic shock in dogs.

The effects of three calcium channel-blocking agents, verapamil, nifedipine and diltiazem, given intravenously, have been studied on the cardiovascular and sympathetic responses to acute haemorrhagic shock in anaesthetized dogs. Following acute haemorrhage, cardiac output, mean pulmonary artery pressure, mean right atrial pressure, and pulmonary capillary wedge pressure all fell, and adrenaline, noradrenaline and plasma renin activity rose. In the presence of each calcium antagonist the fall in cardiac output, mean pulmonary artery pressure, central venous pressure and pulmonary capillary wedge pressure was similar, and the rise in catecholamine levels unaffected. The rise in plasma renin activity following diltiazem 0.02 mg kg-1 or 0.1 mg kg-1 or nifedipine 0.01 mg kg-1 was similar to values in a control group, whereas in those receiving verapamil 0.15 mg kg-1 or 0.6 mg kg-1, or nifedipine 0.05 mg kg-1, the rise was greater.

Animals↗
PubMed1987

Effects of isoflurane on myocardial blood flow, function, and oxygen consumption in the presence of critical coronary stenosis in dogs.

Because isoflurane has been reported to produce coronary steal, we studied 12 open chest, anesthetized (pentobarbital) dogs with critical stenosis (CS) of the left circumflex coronary artery (LCA). Sonomicrometers were implanted to measure systolic wall thickening, myocardial blood flow (MBF) was measured with microspheres (15 microns diameter), and regional venous sampling was performed to estimate regional oxygen extraction and myocardial oxygen consumption (MVO2). Anesthetic concentrations of isoflurane reduced arterial blood pressure dramatically, resulting in a maldistribution of MBF distal to the CS consistent with the pattern characterizing a transmural coronary steal effect. Elevation of arterial blood pressure with phenylephrine during high concentration isoflurane (1.7 +/- 0.1%) augmented MBF, but the maldistribution distal to the CS persisted. Despite the maldistribution, however, there was no indication of ischemia in the LCA region because systolic wall thickening, oxygen extraction, and MVO2 were not significantly different between the LCA and left anterior descending coronary artery (LAD) (control) areas. Because wall thickening, oxygen extraction, and MVO2 were markedly reduced by isoflurane in both the LCA and control areas, it was concluded that isoflurane substantially reduced myocardial oxygen requirements by inducing myocardial depression, reducing heart rate, and decreasing afterload. Consequently, the apparent maldistribution of LCA blood flow (coronary steal) was due to the hemodynamic and vasodilatory effects of isoflurane, but did not result in ischemia because the level of blood flow was at or above the requirements of the myocardium.

Animals↗
PubMed1986

Enhanced capillary blood flow in rapidly expanded random pattern flaps.

We have quantitatively examined the effect of rapid sequential skin expansion on capillary blood flow in the porcine random flap model in order to determine the relation between the increased survivability of expanded random flaps and capillary blood flow. Three 6 X 20 cm random flaps were tattooed on the backs of six small (20-kg) pigs. One flap was not manipulated (control). A 450-ml expander was inserted at the base of the second flap and left in place (sham). At the base of the third flap a 450-ml expander was inserted and each day for 5 days sequentially filled to the limits of skin viability as determined by vital dye staining (expanded). Capillary blood flow was measured on day 8 by measurement of radioactivity after injection of 15-microns radiolabeled microspheres. Samples were taken at 4-cm intervals from the base of each flap. Rapid expansion led to significant increases in capillary blood flow in expanded skin and to enhanced preservation of capillary flow after elevation of random pattern flaps based on expanded skin compared to sham and to control tissues. This correlates with and explains at least in part our previous observation of improved length of survival of flaps raised on expanded skin.

Animals↗
PubMed1986

The influence of trimethaphan (Arfonad)-induced hypotension with and without spine distraction on canine spinal cord blood flow.

Controlled hypotension is used in scoliosis surgery to reduce the need for transfusion and to improve operating conditions, but there is concern that deliberate hypotension may decrease spinal cord blood flow (SCBF) and predispose the spinal cord to injury, particularly when it is distracted during Harrington instrumentation. To study the effect of deliberate hypotension on SCBF, the mean arterial pressure (MAP) was reduced to 50% of its normotensive value with trimethaphan (Arfonad) in dogs and the SCBF measured using the hydrogen washout technique with and without spine distraction. The SCBF was significantly reduced to half its normotensive value of 23.2 ml/min/100 gm to 11.4 ml/min/100 gm after hypotension was established. The SCBF remained significantly decreased compared with controls when measured at 30, 45, and 60 minutes following the induction of hypotension and also when hypotension was terminated. SCBF was not further reduced when 2 cm of spine distraction was added. These results show that induction of hypotension with trimethaphan is associated with a similar decrease in SCBF, which is maintained as long as the drug is used and that this effect continues after the drug is terminated and the MAP increases. Cautiously extrapolating these findings clinically would suggest that trimethaphan may not be the drug of choice for controlled hypotension during scoliosis surgery, despite its apparently favorable hemodynamic and hormonal responses.

Animals↗
PubMed1986

Inhibition of herpes simplex virus type 1 replication by halothane.

Halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) inhibited herpes simplex virus type 1 (HSV-1) replication, although HSV-1 DNA was synthesized at normal levels in Vero cells. Viral capsids and extracellular virions were inhibited, and HSV-1 protein synthesis decreased by 50%, although no specific HSV-1 protein failed to be synthesized. Hyperbaric pressure failed to reverse the halothane-induced inhibition of HSV-1 replication.

Capsid↗