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Biomedical subjects

P R Knight

Publications and source records attributed to P R Knight.

At least 73 records · Page 4Linked to original sources

Hyperbaric pressure of 51 atmospheres is without effect on the depression of oxygen uptake in kidney tissue culture produced by halothane.

Although anesthetized animals are awakened when subjected to increased pressure, compression does not result in antagonism of all phenomena associated with these drugs. It has recently been demonstrated that halothane's inhibition of respiration of isolated rat liver mitochondria is not reversed by hydraulic compression to 51 atmospheres. In order to determine whether this phenomenon can be extrapolated to the whole cell, we have investigated the effect of hydraulic compression of intact renal cells equilibrated with halothane, and conclude that pressure does not overcome the inhibitory effect of this anesthetic.

Animals↗

Response of random skin flaps to rapid expansion.

We studied the physiologic accommodation of tissues to 5-day expansion in a porcine random flap model to assess the time taken to expand skin to provide early coverage of traumatic defects. Three 6 X 20 cm random flaps were outlined but not elevated on the backs of 12 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 sequentially filled to the limits of skin viability each day for 5 days (expanded). Skin tension produced by the pressure of expansion and tissue oxygen (TpO2) in each flap were measured before and after each manipulation. Flaps were raised on day 8, and survival determined on day 15. Creation of the pocket reduced TpO2 to 55% of control values, expansion to 17.5% of control. Within 24 hours both sham and expanded had recovered to 80% of control values. After the second expansion, recovery from hypoxia was again almost complete after 24 hours. Recovery after subsequent expansions was less complete, but 3 days after the final expansion there was no statistical difference between TpO2 values in expanded, sham, and control groups. High pressures generated in the flap by expansion also returned to near normal within 24 hours. Flaps utilizing expanded skin survived to greater length (14.2 cm) than did sham (11.6 cm) or control (7.2 cm) flaps (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The influence of induced hypotension and spine distraction on canine spinal cord blood flow.

Deliberate hypotension is used in scoliosis surgery to reduce the need for blood transfusion and to improve operating conditions. There are concerns, however, that hypotension may decrease spinal cord blood flow (SCBF) and thereby predispose the spinal cord to ischemic injury, particularly when it is distracted during Harrington instrumentation. In a canine model, the mean arterial pressure (MAP) was reduced to 50% of the normotensive value with sodium nitroprusside and halothane to study its effects, with and without spinal distraction, on spinal cord blood flow measured by the hydrogen clearance technique. The induction of systemic hypotension resulted in a significant decrease in spinal cord blood flow from 15.7 +/- 1.1 ml/min/100 g (control) to 10.7 +/- 4.7 ml/min/100 g. This initial decrease in spinal cord blood flow returned to normotensive values by 35 minutes following the induction of hypotension, suggesting an autoregulatory effect. This indicates that the induction of deliberate hypotension to half its normotensive mean arterial pressure is associated with a significant decrease in spinal cord blood flow that returns to normotensive levels by 35 minutes. One and two centimeters of longitudinal distraction applied during systemic hypotension did not reduce spinal cord blood flow when it was applied at least 45 minutes after the hypotension was induced. Thus, when longitudinal stretch of a magnitude approximating that used clinically during Harrington instrumentation is applied in the presence of systemic hypotension, the normal SCBF is not reduced when the autoregulating system is functioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intravenous nitroglycerin administration during infrarenal aortic clamping.

Twenty-five patients requiring infrarenal abdominal aortic clamping were studied during halothane, nitrous oxide anaesthesia. Aortic clamping caused reductions in cardiac index (CI), stroke volume index (SVI) and left ventricular stroke work index (LVSWI). Systemic vascular resistance (SVR) increased. In seven patients CI was less than 1.81 X min-1 X m-2. Intravenous administration of nitroglycerin, 1 microgram X kg-1 X min-1, for 20 minutes, accompanied by volume loading to maintain pulmonary capillary wedge pressure, resulted in a significant improvement in haemodynamic parameters. CI increased 24 per cent as a result of a 14 per cent increase in SVI and an eight per cent increase in heart rate. LVSWI increased 13 per cent and SVR decreased 21 per cent. The plasma nitroglycerin concentration at the time of these measurements was 2.9 +/- 1.0 ng X ml-1. Aortic unclamping resulted in a mean maximum decrease of 14 +/- 2 torr mean arterial pressure. Epinephrine, norepinephrine and plasma renin activity gradually increased during the period of the anaesthetic.

Aged↗

Antifibrillatory effects of volatile anesthetics in acute occlusion/reperfusion arrhythmias.

Halothane, enflurane, and isoflurane were evaluated for antifibrillatory efficacy and compared with lidocaine, propranolol, procainamide, and verapamil in a canine acute left anterior descending (LAD) coronary artery occlusion/reperfusion model with basal pentobarbital anesthesia. Of the antiarrhythmic drugs, only verapamil prevented ventricular fibrillation during occlusion and reperfusion. Halothane 1% inspired after 15 min showed similar protection. Enflurane 2.5% inspired after 15 min resulted in significant protection but caused hypotension after occlusion in 4 of 17 dogs. Isoflurane 1.7% inspired after 15 min showed intermediate results. At inspired concentrations of 0.5% and 1.25%, respectively, halothane and enflurane protected against ventricular fibrillation without hypotension. It is concluded that the volatile anesthetics have antifibrillatory effects in this canine model but differ in their ability to cause hypotension in the presence of proximal LAD coronary artery occlusion.

Anesthesia, Inhalation↗

Effect of halothane on the replication of animal viruses.

Five RNA- and two DNA-containing viruses were propagated in Vero cells and tested for their ability to replicate in the presence of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane), a commonly used inhalational anesthetic. Halothane did not affect poliovirus replication at any anesthetic concentration tested, but all other viruses were either partially or totally inhibited by clinical doses of the anesthetic. Replication of Sendai virus, simian virus 40, vesicular stomatitis virus, and herpes simplex virus type 1 were moderately inhibited by halothane exposure. At concentrations of 2.2% (vol/vol) halothane, peak virus titers were reduced by ca. 2 orders of magnitude for vesicular stomatitis virus and simian virus 40, 3.5 orders of magnitude for Sendai virus, and 4 orders of magnitude for herpes simplex virus. Newcastle disease virus and measles virus were the most susceptible to exposure to halothane. Total inhibition of the replication of these viruses occurred at 1.6 to 2.0% halothane. All of the viruses whose replication was susceptible to the action of halothane were inhibited in a concentration-dependent manner. Furthermore, with the exception of simian virus 40, the inhibition of the replication of all viruses was reversible after halothane removal, although total recovery of virus synthesis was not observed unless the culture medium was changed or the pH was adjusted after anesthetic removal.

Animals↗

Effect of general anesthetics and pressure on aerobic metabolism of monkey kidney cells.

The authors examined the inhibition of aerobic metabolism in monkey kidney cell cultures exposed to halothane, enflurane, and isoflurane. The ability of hyperbaric pressure to reverse the halothane-induced metabolic inhibition also was examined. Incubation of two monkey kidney cell lines for 24 h with clinically equipotent concentrations (2.6 MAC) of halothane, enflurane, or isoflurane vapors increased the concentration of lactate in the media by 126 to 244% relative to nonexposed control cultures. The increased rate of lactate accumulation was proportional to the concentration of halothane and was accompanied by a decrease in media pH. Removal of halothane restored the normal rate of lactate production. Hyperbaric pressures of 25, 50, and 100 atmospheres did not alter the halothane-stimulated rate of lactate production relative to non-anesthetic-treated controls, although pressure alone did depress the rate of lactate accumulation in all cultures. The stimulation of lactate production likely reflects the known ability of halothane to inhibit mitochondrial respiration. The failure of pressure to reverse the stimulation of lactate production by halothane suggests that inhibition of mitochondrial metabolism cannot be reversed by pressure.

Aerobiosis↗

Alterations in influenza virus pulmonary pathology induced by diethyl ether, halothane, enflurane, and pentobarbital anesthesia in mice.

Three-week-old CD-1 mice infected with the PR-8 (mouse-adapted) strain of influenza virus while exposed to enflurane demonstrated a decrease in virus titers from the lungs of infected animals, less abnormality of lung histology, and an increase in survival in animals as compared with those receiving the other anesthetics tested. Greater than 90% mortality occurred in groups of mice which inhaled aerosolized virus and received no anesthesia, pentobarbital, diethyl ether, or halothane anesthesia 96 h following infection. Infected mice anesthetized with enflurane 96 h post-infection had significantly lower mortality rate (68%) when compared with the other groups. Halothane-anesthetized mice receiving intranasal influenza virus during anesthesia demonstrated increased survival and a delay in the mean day of death when compared with animals receiving either diethyl ether of pentobarbital anesthesia. Animals receiving enflurane during virus inoculation had an even lower mortality rate and a later mean day of death when compared with infected animals receiving day of the other three anesthetics. Examination of lungs from animals infected during anesthesia demonstrated influenza virus titers significantly less in the animals that received enflurane anesthesia when compared with the other groups. Histologic sections of lungs revealed extensive spread of the disease process into the alveoli and interstitium of the lungs of animals infected while receiving pentobarbital or diethyl ether anesthesia. Animals infected during halothane demonstrated pathologic characteristics similar to pentobarbital- and diethyl-ether-treated groups; however, the changes were not as extensive. Mice infected during exposure to enflurane revealed only a mild bronchopneumonia.

Anesthesia↗

Pressure reversal of halothane's antiviral effect.

The authors have studied the effects that hyperbaric pressure and halothane had on measles virus replication. Two per cent halothane at one atmosphere of air (ATA) reduced the number of infectious measles virus particles produced in cultured Vero cells by greater than four orders of magnitude (P less than 0.001) relative to virus produced in untreated cultures at 1 ATA. The same concentration of halothane at 100 ATA still reduced the amount of virus synthesized but only by 1 1/2 orders of magnitude (P less than 0.01) as compared with control cultures. Pressure (100 ATA) alone reduced virus production insignificantly. Thus, it appears that the antiviral effects of halothane on measles virus replication in cultured Vero cells is reversible at least partially by pressure.

Animals↗

Intracavitary radiation for rectal carcinoma.

Thirty-five patients with low-lying rectal adenocarcinoma have been treated with intracavitary radiation (Papillon's technique). Twenty-three were treated for cure and 12 for palliation. The indications for curative intracavitary radiation were mobile polypoid tumors, less than 3 cm in diameter, with Broder's Grades I and 2 differentiation lying less than 11 cm from the anal verge. Doses between 2 000 and 4 000 cGy were delivered to a total of 7 000 to 20 000 cGy with complete resolution of the tumors. Eighty-seven per cent in the curative group are alive and well up to 42 months after treatment with a minimum follow-up of six months. Of the 23 patients treated for cure, three patients had recurrences within 18 months of therapy. Two of the three patients are alive following surgery. The third patient died in the postoperative period. The results of intracavitary radiation are comparable to ablative surgery and avoid a permanent colostomy. Age, frailty, or other medical conditions do not preclude this treatment. Anesthesia and hospitalization are not required. This method can also be used for palliation of recurrent tumors and in patients who are unsuitable for surgery.

Adenocarcinoma↗

Use of pentolinium in postoperative hypertension resistant to sodium nitroprusside.

Five patients with systemic arterial hypertension occurring in the postoperative period and resistant to sodium nitroprusside are described. The hypertension was associated with evidence of increased activity of the autonomic and renin-angiotensin systems. Sympathetic blockade using the ganglion blocking agent, pentolinium, enabled the arterial pressure to be controlled adequately in all patients. This was associated with a decrease in catecholamine concentrations, plasma renin activity and angiotensin II concentrations.

Adult↗

Termination of cardiopulmonary bypass facilitated by insulin.

A 61-year old woman with severe coronary artery disease underwent three-vessel coronary bypass surgery. Difficulty was encountered in terminating cardiopulmonary bypass, but there was dramatic improvement following the administration of intravenous insulin. The use of insulin to facilitate termination of cardiopulmonary bypass is discussed.

Anesthesia, General↗