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Oxygen delivery modulates intracellular hydrogen peroxide generation during initial reperfusion of the isolated ischemic rat heart
RESEARCH FORUM ABSTRACTS
of the b-fibrinogen G/A-455, the rate-limiting region of the blood coagulation cascade, has been reported to be associated with the development of ischemic stroke. The aim of this study is to determine the relationship between the b-fibrinogen G/A-455 single nucleotide polymorphisms and the risk of ischemic stroke in Korea because there are racial differences in polymorphisms and Koreans have never been studied before. Methods: From March to September 2003, we compared 96 (male:female=1.2:0.8) patients who were diagnosed with ischemic stroke at the Kyung Hee University hospital emergency department and 129 control subjects, men or women, between the ages of 50 and 70 years. The genotypes of b-fibrinogen G/A-455 polymorphisms were confirmed by polymerase chain reaction followed by Hae III restriction enzyme digestion. The ischemic stroke patients were divided into 3 groups (large-vessel disease, lacuna stroke, and other reasons [unknown, aortic dissection]) by computed tomography and magnetic resonance imaging diagnosis by a radiologist. They were compared, and the statistics were done using 1-sample t test, x2 test, and analyses of variance, and the statistical significance was defined as P value less than .05. Results: The results showed that the patient group had a much higher rate of heterozygotism (GA or AG). We analyzed the genotype frequency of 80 patients, and the percentage of homozygote of the cut type (GG type) was 58.7%, and the uncut type (AA type) was 7.5%, whereas the control group showed 73.3% of the uncut type and 2.7% of the cut type. For allele frequency in the patient group, A allele was 81.3% and G allele was 18.7% in comparison with that of the control group, which was 85.3% for A allele and 14.7% for G allele. The analysis of the statistics of genome frequency showed x2 to be 6.24, resulting in a significant difference between the patient and the control group (P\.05). For allele frequency, the x2 was 1.88 (95% confidence interval 1.16 to 3.04; P\.01), also showing significant difference between the 2 groups. These results suggest that the polymorphism of b-fibrinogen G/A-455 is associated with ischemic stroke. Conclusion: The high rate of polymorphisms of AA genotype of b-fibrinogen G/A455 in large-vessel atherosclerosis of cerebrovascular disease in Koreans leads us to believe that the prognosis of men with b-fibrinogen G/A-455 AA–type polymorphism and a smoking history, if these were found in advance, could be improved by early diagnosis and preventive management, and clinical expenses could be reduced.
170
Feasibility and Utility of Infrared Thermography as a Thermometer: Comparison With Oral and Tympanic Thermometry
Haldeman LA, Allen TL, Chan KJ, Snow GL/LDS Hospital, Salt Lake City, UT Study objectives: We determine the relationship between infrared thermography (IRT) acquired body surface temperature (BST) values and temperature values obtained by conventional measures (oral and tympanic). Methods: IRT images using a ThermaCAM P60 (FLIR Systems, North Billerica, MA) were obtained for 20 consecutive adult emergency department (ED) patients, regardless of complaint, in a tertiary care center. Patients also had their oral and tympanic temperature measured within 1 minute of IRT imaging. The camera has a spatial resolution of 320 3 240 pixels in focal plane array, scan integration rate of 60 Hz, and thermal sensitivity of 0.08°C per pixel. Focal distance was 1 m, with a set emissivity of 0.98. Images are acquired in JPEG format. The mean BST using IRT over an area 4 cm2 was collected and recorded for each patient in 3 distinct anatomic areas using specialized software. Body areas imaged with IRT were the glabella, the abdomen centered at the umbilicus, and the dorsum of a hand. The skin of the abdomen was exposed and allowed to equilibrate with the environment for 2 minutes before IRT, and the imaged hand was contralateral to any intravenous line. The temperature difference (DT) for tympanic thermometry and IRT was calculated against oral temperatures (where DT=oral temperature – mean BST by IRT for each body region per patient), and the mean DT6SD are reported. The coefficient of determination (R2) was also calculated for each IRT region data set. The institutional review board approved the study, and informed consent was obtained on all patients. All temperatures were recorded in °C. Results: For DT-tympanic, the mean was –0.260.5°C (SD), the DT-glabella mean was 2.260.7°C, the DT-abdomen mean was 3.361.6°C, and for DT-hand the mean was 4.461.7°C. R2 values were tympanic 0.629, glabella 0.405, abdomen 0.163, and hand 0.035. Conclusion: With the exception of IRT images of the glabellar region, IRT regional mean BST values appear to correlate poorly with oral thermometry. Some of the variance may be due to technique and environmental temperature interference. Because IRT is fast and easy to obtain, is not associated with radiation, and may convey other important information, additional study to refine IRT technique is warranted.
OCTOBER 2004
44:4
ANNALS OF EMERGENCY MEDICINE
EMF-3
Myocardial Contractile Function During Post-Ischemic Low Flow Reperfusion: Critical Thresholds of Nicotinamide Adenine Dinucleotide and Oxygen Delivery
Stoner J, Angelos M, Claton T/Ohio State University, Columbus, OH Study objectives: The degree of myocardial oxygen delivery necessary to reestablish functional contractile activity after short-term global ischemia in the heart is unknown. To determine the relationship of oxygen delivery and recovery of contractile and metabolic function, we use tissue nicotinamide adenine dinucleotide (NADH) fluorometric changes to characterize adequacy of reperfusion flow. Methods: Isolated perfused rat hearts were subjected to global ischemia and reperfused at variable flow rates ranging from 1% to 100% of baseline flow. Myocardial function and tissue NADH changes were continuously measured. NADH fluorescence rapidly increased and plateaued during ischemia. Results: A strong inverse logarithmic correlation between NADH fluorescence and reperfusion oxygen delivery (DO2) was demonstrated (r=–0.952). Left ventricle function (rate-pressure product) was inversely related to NADH fluorescence at reperfusion flows from 25% to 100% of baseline (r=–0.922) but not at lower reperfusion flow levels. An apparent reperfusion threshold of 25% baseline DO2 was necessary to resume contractile function. At very low reperfusion flows (1% of baseline), another threshold flow was identified at which NADH levels increased beyond that observed during global ischemia (3.4%63.0% mean6SEM, n=9), suggesting further reduction of the cellular redox state. This NADH increase at 1% baseline reperfusion flow was blocked by removing glucose from the perfusate. Conclusion: NADH fluorescence is a sensitive indicator of myocardial cellular oxygen use over a wide range of reperfusion DO2. Although oxygen is used at very low flow, as indicated by changes in NADH, a critical threshold of approximately 25% of baseline DO2 is necessary to restore contractile function after short-term global ischemia.
EMF-4
Oxygen Delivery Modulates Intracellular Hydrogen Peroxide Generation During Initial Reperfusion of the Isolated Ischemic Rat Heart
Stoner J, Angelos M, Claton T/Ohio State University, Columbus, OH Study objectives: Reactive oxygen species (ROS) generated during reperfusion of the ischemic heart play a major role in myocyte injury and may be dependent on changes in O2 delivery (DO2). We hypothesize that during low-flow reperfusion (eg, cardiopulmonary resuscitation after cardiac arrest), DO2 modulates ROS formation and affects contractile recovery in the postischemic period. Methods: Isolated perfused rat hearts were loaded with 25 mM of dihydrofluorescein-diacetate (HFLUOR) and then subjected to 5 minutes of global ischemia. Controlled reperfusion consisted of 5 minutes of variable DO2, ranging from 437.8 to 70.7 mL O2/min before restoration of full baseline perfusion. Intracellular ROS was quantitated using surface fluorometry at the left ventricle to measure the oxidation of HFLUOR to fluorescein, reflecting H2O2 generation. Cellular NADH changes and contractile function were simultaneously measured. Results: At reperfusion, a burst of H2O2 was observed, which was significantly reduced by lowering DO2 (354.4, 22.8 to 84.7; 4.2 mL O2/min) during 5 minutes of controlled reperfusion (n=8/group, 0.47, 0.05 AU, versus 0.88; 0.14 AU, P=.035). However, this reduction did not correlate with improved functional recovery. Hearts reperfused with transient lower DO2 before full reperfusion had a lower percentage of recovery of left ventricular–developed pressure (39.2%, 7.6% versus 73.5%; 6.3, P\.01), and rate-pressure product (84.8%, 13.7 versus 27.4%; 4.9, P\.01). Conclusion: Controlled reperfusion using an initial lower DO2 reduces the intracellular ROS burst but does not improve recovery of postischemic contractile function.
EMF-5
Collective Behavior in Populations of Coupled Stochastic Oscillators
Roberts SB, Ermentrout GB/University of Pittsburgh, Pittsburgh, PA Study objectives: Theoretical studies of coupled oscillators have potential implications for such diverse fields as physics, chemistry, mathematics, and biology. One crucial question about the collective behavior of such populations is whether or
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of the b-fibrinogen G/A-455, the rate-limiting region of the blood coagulation cascade, has been reported to be associated with the development of ischemic stroke. The aim of this study is to determine the relationship between the b-fibrinogen G/A-455 single nucleotide polymorphisms and the risk of ischemic stroke in Korea because there are racial differences in polymorphisms and Koreans have never been studied before. Methods: From March to September 2003, we compared 96 (male:female=1.2:0.8) patients who were diagnosed with ischemic stroke at the Kyung Hee University hospital emergency department and 129 control subjects, men or women, between the ages of 50 and 70 years. The genotypes of b-fibrinogen G/A-455 polymorphisms were confirmed by polymerase chain reaction followed by Hae III restriction enzyme digestion. The ischemic stroke patients were divided into 3 groups (large-vessel disease, lacuna stroke, and other reasons [unknown, aortic dissection]) by computed tomography and magnetic resonance imaging diagnosis by a radiologist. They were compared, and the statistics were done using 1-sample t test, x2 test, and analyses of variance, and the statistical significance was defined as P value less than .05. Results: The results showed that the patient group had a much higher rate of heterozygotism (GA or AG). We analyzed the genotype frequency of 80 patients, and the percentage of homozygote of the cut type (GG type) was 58.7%, and the uncut type (AA type) was 7.5%, whereas the control group showed 73.3% of the uncut type and 2.7% of the cut type. For allele frequency in the patient group, A allele was 81.3% and G allele was 18.7% in comparison with that of the control group, which was 85.3% for A allele and 14.7% for G allele. The analysis of the statistics of genome frequency showed x2 to be 6.24, resulting in a significant difference between the patient and the control group (P\.05). For allele frequency, the x2 was 1.88 (95% confidence interval 1.16 to 3.04; P\.01), also showing significant difference between the 2 groups. These results suggest that the polymorphism of b-fibrinogen G/A-455 is associated with ischemic stroke. Conclusion: The high rate of polymorphisms of AA genotype of b-fibrinogen G/A455 in large-vessel atherosclerosis of cerebrovascular disease in Koreans leads us to believe that the prognosis of men with b-fibrinogen G/A-455 AA–type polymorphism and a smoking history, if these were found in advance, could be improved by early diagnosis and preventive management, and clinical expenses could be reduced.
170
Feasibility and Utility of Infrared Thermography as a Thermometer: Comparison With Oral and Tympanic Thermometry
Haldeman LA, Allen TL, Chan KJ, Snow GL/LDS Hospital, Salt Lake City, UT Study objectives: We determine the relationship between infrared thermography (IRT) acquired body surface temperature (BST) values and temperature values obtained by conventional measures (oral and tympanic). Methods: IRT images using a ThermaCAM P60 (FLIR Systems, North Billerica, MA) were obtained for 20 consecutive adult emergency department (ED) patients, regardless of complaint, in a tertiary care center. Patients also had their oral and tympanic temperature measured within 1 minute of IRT imaging. The camera has a spatial resolution of 320 3 240 pixels in focal plane array, scan integration rate of 60 Hz, and thermal sensitivity of 0.08°C per pixel. Focal distance was 1 m, with a set emissivity of 0.98. Images are acquired in JPEG format. The mean BST using IRT over an area 4 cm2 was collected and recorded for each patient in 3 distinct anatomic areas using specialized software. Body areas imaged with IRT were the glabella, the abdomen centered at the umbilicus, and the dorsum of a hand. The skin of the abdomen was exposed and allowed to equilibrate with the environment for 2 minutes before IRT, and the imaged hand was contralateral to any intravenous line. The temperature difference (DT) for tympanic thermometry and IRT was calculated against oral temperatures (where DT=oral temperature – mean BST by IRT for each body region per patient), and the mean DT6SD are reported. The coefficient of determination (R2) was also calculated for each IRT region data set. The institutional review board approved the study, and informed consent was obtained on all patients. All temperatures were recorded in °C. Results: For DT-tympanic, the mean was –0.260.5°C (SD), the DT-glabella mean was 2.260.7°C, the DT-abdomen mean was 3.361.6°C, and for DT-hand the mean was 4.461.7°C. R2 values were tympanic 0.629, glabella 0.405, abdomen 0.163, and hand 0.035. Conclusion: With the exception of IRT images of the glabellar region, IRT regional mean BST values appear to correlate poorly with oral thermometry. Some of the variance may be due to technique and environmental temperature interference. Because IRT is fast and easy to obtain, is not associated with radiation, and may convey other important information, additional study to refine IRT technique is warranted.
OCTOBER 2004
44:4
ANNALS OF EMERGENCY MEDICINE
EMF-3
Myocardial Contractile Function During Post-Ischemic Low Flow Reperfusion: Critical Thresholds of Nicotinamide Adenine Dinucleotide and Oxygen Delivery
Stoner J, Angelos M, Claton T/Ohio State University, Columbus, OH Study objectives: The degree of myocardial oxygen delivery necessary to reestablish functional contractile activity after short-term global ischemia in the heart is unknown. To determine the relationship of oxygen delivery and recovery of contractile and metabolic function, we use tissue nicotinamide adenine dinucleotide (NADH) fluorometric changes to characterize adequacy of reperfusion flow. Methods: Isolated perfused rat hearts were subjected to global ischemia and reperfused at variable flow rates ranging from 1% to 100% of baseline flow. Myocardial function and tissue NADH changes were continuously measured. NADH fluorescence rapidly increased and plateaued during ischemia. Results: A strong inverse logarithmic correlation between NADH fluorescence and reperfusion oxygen delivery (DO2) was demonstrated (r=–0.952). Left ventricle function (rate-pressure product) was inversely related to NADH fluorescence at reperfusion flows from 25% to 100% of baseline (r=–0.922) but not at lower reperfusion flow levels. An apparent reperfusion threshold of 25% baseline DO2 was necessary to resume contractile function. At very low reperfusion flows (1% of baseline), another threshold flow was identified at which NADH levels increased beyond that observed during global ischemia (3.4%63.0% mean6SEM, n=9), suggesting further reduction of the cellular redox state. This NADH increase at 1% baseline reperfusion flow was blocked by removing glucose from the perfusate. Conclusion: NADH fluorescence is a sensitive indicator of myocardial cellular oxygen use over a wide range of reperfusion DO2. Although oxygen is used at very low flow, as indicated by changes in NADH, a critical threshold of approximately 25% of baseline DO2 is necessary to restore contractile function after short-term global ischemia.
EMF-4
Oxygen Delivery Modulates Intracellular Hydrogen Peroxide Generation During Initial Reperfusion of the Isolated Ischemic Rat Heart
Stoner J, Angelos M, Claton T/Ohio State University, Columbus, OH Study objectives: Reactive oxygen species (ROS) generated during reperfusion of the ischemic heart play a major role in myocyte injury and may be dependent on changes in O2 delivery (DO2). We hypothesize that during low-flow reperfusion (eg, cardiopulmonary resuscitation after cardiac arrest), DO2 modulates ROS formation and affects contractile recovery in the postischemic period. Methods: Isolated perfused rat hearts were loaded with 25 mM of dihydrofluorescein-diacetate (HFLUOR) and then subjected to 5 minutes of global ischemia. Controlled reperfusion consisted of 5 minutes of variable DO2, ranging from 437.8 to 70.7 mL O2/min before restoration of full baseline perfusion. Intracellular ROS was quantitated using surface fluorometry at the left ventricle to measure the oxidation of HFLUOR to fluorescein, reflecting H2O2 generation. Cellular NADH changes and contractile function were simultaneously measured. Results: At reperfusion, a burst of H2O2 was observed, which was significantly reduced by lowering DO2 (354.4, 22.8 to 84.7; 4.2 mL O2/min) during 5 minutes of controlled reperfusion (n=8/group, 0.47, 0.05 AU, versus 0.88; 0.14 AU, P=.035). However, this reduction did not correlate with improved functional recovery. Hearts reperfused with transient lower DO2 before full reperfusion had a lower percentage of recovery of left ventricular–developed pressure (39.2%, 7.6% versus 73.5%; 6.3, P\.01), and rate-pressure product (84.8%, 13.7 versus 27.4%; 4.9, P\.01). Conclusion: Controlled reperfusion using an initial lower DO2 reduces the intracellular ROS burst but does not improve recovery of postischemic contractile function.
EMF-5
Collective Behavior in Populations of Coupled Stochastic Oscillators
Roberts SB, Ermentrout GB/University of Pittsburgh, Pittsburgh, PA Study objectives: Theoretical studies of coupled oscillators have potential implications for such diverse fields as physics, chemistry, mathematics, and biology. One crucial question about the collective behavior of such populations is whether or
S 5 3