Tumor oxygen tension during photodynamic therapy.
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Biomedical subjects
Publications and source records attributed to S J Barker.
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In a recent study, we compared a new intraarterial fiberoptic "optode" probe to continuously measure arterial oxygen and carbon dioxide tensions and pH with intermittently drawn blood samples in patients undergoing surgery. In one patient with a diagnosis of Arnold-Chiari type I malformation with outflow obstruction of the fourth ventricle, a major pulmonary air embolism occurred while the patient was undergoing suboccipital craniectomy and cervical laminectomy in the prone position. Three hours after the incision the optode-displayed oxygen tension decreased from a stable value of 225 +/- 8 mm Hg to 63 mm Hg over a 10-minute period. During the same interval, carbon dioxide tension increased and end-tidal carbon dioxide decreased; shortly thereafter, transcutaneous oxygen tension decreased also. Within 20 minutes after the inspired gas mixture was changed to 100% oxygen, the patient's respiratory variables returned to near baseline. No further complications ensued. This is the first time continuously monitored arterial oxygen tension values during a pulmonary embolism have been reported. With further refinement, intraarterial optode probes will add another valuable method of detecting pulmonary air embolism.
Among the sequence of events which occur during photodynamic therapy (PDT) are depletion of oxygen and disruption of tumor blood flow. In order to more clearly understand these phenomena we have utilized transcutaneous oxygen electrodes to monitor tissue oxygen disappearance. These results provide, for the first time, non-invasive real-time information regarding the influence of light dose on tissue oxygenation during irradiation. Measurements were conducted on transplanted VX-2 skin carcinomas grown in the ears of New Zealand white rabbits. Rabbits were treated with Photofrin II and tumors were irradiated with up to 200 kJ/m2 (500 W/m2) of 630-nm light. Substantial reductions in tumor oxygen tension were observed upon administration of as little as 20 kJ/m2. For a series of brief irradiations, oxygen tension was modulated by the appearance of laser light. Tissue oxygen reversibility appeared to be dependent upon PDT dose. Long-term, irreversible tissue hypoxia was recorded in tumors for large (200 kJ/m2) fluences. These results suggest that transcutaneous oxygen tension may be useful as a general indicator of the effectiveness of PDT and as an in situ predictor of the energy required to elicit tumor damage.
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The performance of three commercially available pulse oximeters was assessed in five anesthetized dogs in which increasing levels of methemoglobin were induced. Hemoglobin oxygen saturation in each dog was monitored with three pulse oximeters (Nellcor N-100, Ohmeda 3700, and Novametrix 500) and a mixed venous saturation pulmonary artery catheter (Oximetrix Opticath). Arterial and mixed venous blood specimens were analyzed for PaO2, PaCO2, and pHa using standard electrodes. An IL-282 Co-oximeter was used on the same specimens to determine oxyhemoglobin and methemoglobin as percentages of total hemoglobin. Methemoglobin levels of up to 60% were induced by intratracheal benzocaine. As MetHb gradually increased while the dogs were breathing 100% inspired oxygen, the pulse oximeter saturation (SpO2) overestimated the fractional oxygen saturation (SaO2) by an amount proportional to the concentration of methemoglobin until the latter reached approximately 35%. At this level the SpO2 values reached a plateau of 84-86% and did not decrease further. When, at fixed methemoglobin levels, additional hemoglobin desaturation was induced by reducing inspired oxygen fraction, SpO2 changed by much less than did SaO2 (regression slopes from 0.16 to 0.32). Thus, at high methemoglobin levels SpO2 tends to overestimate SaO2 by larger amounts at low hemoglobin saturations. Plots of SpO2 versus functional saturation (oxyhemoglobin/reduced hemoglobin plus oxyhemoglobin) show an improved but still poor relationship (regression slopes from 0.32 to 0.46). The Oximetrix Opticath pulmonary artery catheter behaves similarly but provides somewhat better agreement with functional saturation than do the pulse oximeters in the presence of methemoglobinemia. Pulse oximetry data (SpO2) should be used with caution in patients with methemoglobinemia.
Transcutaneous PO2 (PtcO2) and liver surface PO2 (PIO2) were measured in six mongrel dogs during hemorrhagic shock, normotensive shock, and volume resuscitation. Normotension was produced during extreme hypovolemia by an infusion of phenylephrine. PtcO2 and PlO2 were compared to each other and to hemodynamic and oxygen transport variables. PtcO2 and PlO2 correlated well with cardiac index (CI) r = .71 and .86, respectively; n = 60) and with each other (r = .79; n = 60). Heart rate, mean arterial pressure (MAP), and PaO2) correlated less with PtcO2 or PlO2. During the normotensive shock period, PtcO2, PIO2, CI, oxygen delivery (DO2), and oxygen consumption (VO2) were all severely decreased, while PaO2 and MAP were normal and lactic acid concentrations were elevated. It was concluded that PtcO2 follows changes in PlO2 during hypotensive and normotensive low cardiac output shock in mongrel dogs. Low PtcO2 values are associated with low values of PlO2, DO2, VO2, and rising lactic acid concentrations in dogs. These animal data imply that low PtcO2 values encountered in clinical monitoring during anesthesia and surgery may correspond to decreased blood volume, blood flow, and PlO2.
We investigated the chromosomal organization and developmental regulation of soybean beta-conglycinin genes. The beta-conglycinin gene family contains at least 15 members divided into two major groups encoding 2.5-kilobase and 1.7-kilobase embryo mRNAs. beta-Conglycinin genes are clustered in several DNA regions and are highly homologous along their entire lengths. The two groups differ by the presence or absence of specific DNA segments. These DNA segments account for the size differences in beta-conglycinin mRNAs. The 2.5-kilobase and 1.7-kilobase beta-conglycinin mRNAs accumulate and decay at different times during embryogenesis. By contrast, genes encoding these mRNAs are transcriptionally activated and repressed at the same time periods. Our studies indicate that the beta-conglycinin family evolved by both duplication and insertion/deletion events, and that beta-conglycinin gene expression is regulated at both the transcriptional and posttranscriptional levels.
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Rapid and reliable detection of inadvertent endobronchial intubation is an essential function of oxygen monitoring. We have studied the detection of this event by using three oxygen monitoring techniques: pulse oximetry, transcutaneous measurement of oxygen tension, and intraarterial fiberoptic measurement of oxygen tension. Four dogs were anesthetized, intubated, and monitored with these three techniques and with arterial and central venous cannulas. Endotracheal tubes were moved from the trachea into the right mainstem bronchi at several inspired oxygen fraction (FIO2) values for each dog, and the responses of the oxygen monitors were recorded for 20 minutes thereafter. The pulse oximeter showed little change in oxygen saturation (SpO2) during endobronchial intubation at FIO2 values above 0.3. SpO2 decreased by an average of 1.3 +/- 2.1% at an FIO2 of 1.0 and by 4.0 +/- 4.1% at an FIO2 of 0.5. Simultaneously measured transcutaneous oxygen tensions decreased by 42 to 64% and the optode reading decreased by 64 to 79%. At lower FIO2 values, the changes in SpO2 were more significant: a decrease of 6.0 +/- 6.3% at an FIO2 of 0.3 and of 9.8 +/- 6.1% at an FIO2 of 0.2. The transcutaneous oxygen and optode readings decreased by 31 to 45% under these conditions. Endobronchial intubations at FIO2 values greater than 0.3 may not yield immediate decreases in arterial saturation and hence may go undetected by pulse oximetry. Transcutaneous oxygen tension decreases significantly with endobronchial intubation at any FIO2. The experimental, intraarterial optode consistently yielded the greatest changes with the fastest time response.
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We transformed tobacco plants with a soybean beta-conglycinin gene that encodes the 1.7-kilobase beta-subunit mRNA. We showed that the beta-conglycinin mRNA accumulates and decays during tobacco seed development and that beta-conglycinin mRNA is undetectable in the tobacco leaf. We utilized in situ hybridization to localize beta-conglycinin mRNA within the tobacco seed. beta-Conglycinin mRNA is not detectable within the endosperm but is localized within specific embryonic cell types. The highest concentration of beta-conglycinin mRNA is found in cotyledon storage parenchyma cells. We conclude that sequences required for embryo expression, temporal control, and cell specificity are linked to the beta-conglycinin gene, and that factors regulating beta-conglycinin gene expression are compartmentalized within analogous soybean and tobacco seed regions.
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An experimental study using a new fiberoptic sensor for the continuous intraarterial measurement of oxygen tension is described. This "optode" sensor uses the phenomenon of fluorescence quenching to determine the oxygen tension of the surrounding medium. To assess the accuracy of this device, we anesthetized 4 dogs and monitored them continuously with arterial catheters and an intraarterial optode probe, and intermittently with arterial blood gas analysis. The inspired oxygen fraction was varied from 1.0 to 0.1, and arterial blood gases were measured for comparison with the optode reading. Two hundred ninety data sets yielded a correlation coefficient of 0.96, with a linear regression slope of 0.98 and intercept of 5.1 mm Hg. In the 72 data sets from the last dog, the bias and precision of the optode arterial oxygen tension values were -10.3 mm Hg and 20.0 mm Hg, respectively. The optode probe was easily inserted through a 20-gauge catheter and did not interfere with continuous arterial pressure measurement or blood sampling. This study suggests that the optode has great potential as a continuous, real-time monitor of arterial oxygen tension.
This study compares two noninvasive techniques for monitoring the partial pressure of carbon dioxide (PCO2) in 24 anesthetized adult patients. End-tidal PCO2 (PetCO2) and transcutaneous PCO2 (PtcCO2) were simultaneously monitored and compared with arterial PCO2 (PaCO2) determined by intermittent analysis of arterial blood samples. PETCO2 and PtcCO2 values were compared with PaCO2 values corrected to patient body temperature (PaCO2T) and PaCO2 values determined at a temperature of 37 degrees C (PaCO2). Linear regression was performed along with calculations of the correlation coefficient (r), bias, and precision of the four paired variables: PETCO2 versus PaCO2 and PaCO2T (n = 211), and PtcCO2 versus PaCO2 and PaCO2T (n = 233). Bias is defined as the mean difference between paired values, whereas precision is the standard deviation of the difference. The following values were found for r, bias, and +/- precision, respectively. PETCO2 versus PaCO2: 0.67, -7.8 mm Hg, +/- 6.1 mm Hg; PETCO2 versus PaCO2T: 0.73, -5.8 mm Hg, +/- 5.9 mm Hg; PtcCO2 versus PaCO2: 0.87, -1.6 mm Hg, +/- 4.3 mm Hg; PtcCO2 versus PaCO2T: 0.84, +0.7 mm Hg, +/- 4.8 mm Hg. Although each of these PCO2 variables is physiologically different, there is a significant correlation (P less than 0.001) between the noninvasively monitored values and the blood gas values. Temperature correction of the arterial values (PaCO2T) slightly improved the correlation, with respect to PETCO2, but it had the opposite effect for PtcCO2. In this study, the chief distinction between these two noninvasive monitors was that PETCO2 had a large negative bias, whereas PtcCO2 had a small bias. We conclude from these data that PtcCO2 may be used to estimate PaCO2 with an accuracy similar to that of PETCO2 in anesthetized patients.
Five dogs were anesthetized, intubated, and ventilated with various mixtures of oxygen, nitrogen, and carbon monoxide. Each dog was monitored with arterial and pulmonary artery catheters, a transcutaneous PO2 analyzer, and two pulse oximeters. An IL-282 Co-oximeter was used to periodically measure arterial oxyhemoglobin (O2Hb) and carboxyhemoglobin (COHb) as percentages of the total hemoglobin. The PaO2, PaCO2, and pHa were measured in the same blood specimens using standard electrodes. When the inspired oxygen concentration was reduced in the absence of COHb, the pulse oximeter saturation (SpO2) estimated O2Hb with reasonable accuracy. COHb levels were then varied slowly from 0-75% in each dog. As the COHb level increased and oxyhemoglobin decreased, both pulse oximeters continued to read an oxygen saturation of greater than 90%, while the actual O2Hb fell below 30%. In the presence of COHb, the SpO2 is approximately the sum of COHb and O2Hb, and, thus, may seriously overestimate O2Hb. The pulse oximeter, as the sole indicator of blood oxygenation, should, therefore, be used with caution in patients with recent carbon monoxide exposure. On the other hand, transcutaneous PO2 falls linearly as COHb increases, and reaches about one-fifth of its initial value at the highest COHb levels despite the maintenance of constant arterial PO2.
Transcutaneous PO2 sensors have been developed over the past ten years from the same basic electrodes used in conventional blood-gas machines. The skin is heated to enable the skin surface sensors to respond quickly to the gas tensions beneath them. PtcO2 is a variable that reflects the PO2 in the peripheral tissue. PtcO2 has its own range of normal values, and it responds to cardiopulmonary changes that affect tissue oxygenation. In most patients, those without decreased cardiac output, PtcO2 follows the trend of PaO2 and decreases relative to PaO2 with increasing patient age (see Table 2). In the presence of severely reduced cardiac output and peripheral perfusion, the PtcO2 values will deviate from their relationship with the arterial tensions and become blood flow dependent, thus providing quantitative information regarding blood flow. The technique of PtcO2 monitoring likely will gain wider acceptance because it is a noninvasive and continuous monitor that provides useful information regarding tissue oxygenation.
The pulse oximeter estimates arterial hemoglobin saturation by measuring the light absorbance of pulsating vascular tissue at two wavelengths. The relationship between measured light absorbances and saturation was developed empirically and is built into the oximeter software. Studies in human volunteers have shown good performance of the device in healthy adults for saturations in the range of 70 to 100%. Studies in the operating room and intensive care unit have established its clinical accuracy and usefulness. The pulse oximeter has already found a number of clinical applications outside of the operating room, such as monitoring during patient transport, respiratory monitoring during narcotic administration, and evaluation of home-oxygen therapy. To use this monitor to its full potential, we must be aware of its limitations as well as its advantages. Because of the nature of the HbO2 dissociation curve, saturation measurements will not be sensitive to changes in PaO2 when the PaO2 is greater than 100 torr. This also implies that the pulse oximeter may fail to detect an inadvertent endobronchial intubation in the operating room. It may take minutes to detect an esophageal intubation in a well-preoxygenated patient. When desaturation does occur, the pulse oximeter detects it quickly, accurately, and reliably. Since the pulse oximeter uses two wavelengths of light, it cannot distinguish more than two hemoglobin species. Thus, COHb and MetHb will cause errors in SpO2 if present in large amounts. Intravenously administered dyes can also cause errors because of their absorbance properties, particularly methylene blue and indocyanine green. The pulse oximeter may be unable to detect an adequate signal during abnormal hemodynamic conditions. The pulse oximeter is one of the most important advances in noninvasive monitoring because it provides a means of continuously and quickly assessing arterial blood oxygenation. It is easy to use and interpret, requires little setup time, and poses no additional risks to the patient. Pulse oximetry may soon be a standard of practice for routine monitoring in any clinical setting in which the patient is at risk of hypoxemia.