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PubMed1999

Gender differences in the relation between ST-T-wave abnormalities at baseline electrocardiogram and stress myocardial perfusion abnormalities in patients with suspected coronary artery disease.

The presence of ST-T-wave abnormalities in the resting electrocardiogram was reported as a predictor of coronary artery disease (CAD) and increased morbidity and mortality. However, the independent value of ST-T abnormalities for predicting the presence and severity of perfusion abnormalities during stress testing has not been studied in a homogenous patient group without known CAD. We evaluated the relation between resting ST-T abnormalities and myocardial perfusion abnormalities in 246 patients (age 59 +/- 13 years, 114 men and 132 women) without known CAD or previous myocardial infarction referred for evaluation of possible myocardial ischemia by dobutamine (up to 40 microg/kg/min) stress sestamibi or tetrofosmin single-photon emission computed tomographic imaging. Resting ST-T abnormalities were present in 123 patients, whereas 123 patients with normal resting electrocardiograms served as a matched control group. Abnormal myocardial perfusion (fixed or reversible perfusion defects) was detected in 72% of men with and in 35% of men without resting ST-T abnormalities (p <0.0001), whereas the prevalence of myocardial perfusion abnormalities was not different in women with and without resting ST-T abnormalities (27% vs 23%, p = NS). In the entire population, independent predictors of an abnormal perfusion by multivariate analysis of clinical characteristics and risk factors were male gender (p <0.001, chi-square 10.5) and resting ST-T abnormalities (p <0.05, chi-square 3). Separate analysis of patients based on gender revealed resting ST-T abnormalities as independent predictors of abnormal perfusion in men (p <0.05, chi-square 4) but not in women. Stress perfusion defect score was higher in men with than without ST-T abnormalities (887 +/- 545 vs 207 +/- 180, p <0.001). It is concluded that resting ST-T wave abnormalities are associated with a higher prevalence and severity of resting and dobutamine-induced myocardial perfusion abnormalities in men but not in women. Resting ST-T wave abnormalities are powerful predictors of compromised myocardial perfusion independent of other clinical risk factors of CAD in men.

Cardiotonic Agents↗
PubMed2002

Renal perfusion during thoracoabdominal aortic operations: cold crystalloid is superior to normothermic blood.

BACKGROUND: Renal failure remains a common complication of thoracoabdominal aortic aneurysm repair. The purpose of this randomized clinical trial was to compare two methods of selective renal perfusion--cold crystalloid perfusion versus normothermic blood perfusion--and determine which technique provides the best kidney protection during thoracoabdominal aortic aneurysm repair. METHODS: Thirty randomized patients undergoing Crawford extent II thoracoabdominal aortic aneurysm repair with left heart bypass had renal artery perfusion with either 4 degrees C Ringer's lactate solution (14 patients) or normothermic blood from the bypass circuit (16 patients). Acute renal dysfunction was defined as an elevation in serum creatinine level exceeding 50% of baseline within 10 postoperative days. RESULTS: One death occurred in each group. One patient in the blood perfusion group experienced renal failure requiring hemodialysis. Ten patients (63%) in the blood perfusion group and 3 patients (21%) in the cold crystalloid perfusion group experienced acute renal dysfunction (p = 0.03). Multivariable analysis confirmed that the use of cold crystalloid perfusion was independently protective against acute renal dysfunction (p = 0.02; odds ratio, 0.133). CONCLUSIONS: When using left heart bypass during repair of extensive thoracoabdominal aortic aneurysms, selective cold crystalloid perfusion offers superior renal protection when compared with conventional normothermic blood perfusion.

Aged↗
PubMed1996

The effects of pulsatile and nonpulsatile systemic perfusion on renal sympathetic nerve activity in anesthetized dogs.

It is still controversial whether to pulse or not to pulse for the establishment of ideal extracorporeal circulation. We directly measured the renal sympathetic nerve activity in mongrel dogs (n = 10, weighing from 13 to 21 kg) to determine the effects of pulsatile and nonpulsatile systemic perfusion on the control of the sympathetic nerve activity during left ventricular assistance. Pulsatile perfusion was generated with an air-driven, diaphragm-type blood pump, and nonpulsatile perfusion was generated with a centrifugal pump. Renal sympathetic nerve activity and the blood flow of the descending aorta were then recorded during pulsatile and nonpulsatile systemic perfusion. Other variables, such as mean arterial pressure, central venous pressure, left atrial pressure, and blood gas levels, were kept constant. At the same mean arterial pressure, renal sympathetic nerve activity during pulsatile perfusion decreased significantly to 80% of renal sympathetic nerve activity during nonpulsatile perfusion (26.8 +/- 2.4 vs 33.4 +/- 2.9 spikes/sec, p < 0.01). Total systemic vascular resistance during pulsatile perfusion decreased significantly to 85% of that during nonpulsatile perfusion (5700 +/- 580 vs 6667 +/- 709 dynes.sec.cm-5, p < 0.05). These results suggest that pulsatile systemic perfusion, compared with nonpulsatile systemic perfusion, reduces sympathetic nerve activity and peripheral vascular resistance and thus may improve both microcirculation and organ function.

Animals↗
PubMed2003

Poor agreement between dipyridamole-stress technetium-99m-tetrofosmin myocardial perfusion single photon emission computed tomography and two-dimensional echocardiography in Kawasaki disease.

To establish a noninvasive diagnostic method for early assessment of cardiac involvement in Kawasaki disease (KD), 28 children with KD were included in this study. Two-dimensional echocardiography (2D-Echo) to detect the aneurysms of coronary arteries (CA), as well as rest and dipyridamole-stress technetium-99m tetrofosmin (Tc-TF) myocardial perfusion single photon emission computed tomography (SPECT) to detect abnormal myocardial perfusion were performed in all of the 28 children with KD and to compare each other. The results showed that (1). 42.9% of cases had no aneurysm and 57.1% had significant aneurysms detected by 2D-Echo; (2). 42.9% of cases had normal perfusion and 57.1% of cases had abnormal myocardial perfusion assessed by Tc-TF myocardial perfusion SPECT; (3). 25.0% of cases showed both normal 2D-Echo and Tc-TF myocardial perfusion SPECT findings and 39.3% of cases showed both abnormal 2D-Echo and Tc-TF myocardial perfusion SPECT findings; and (4). there was poor agreement between 2D-Echo and Tc-TF myocardial perfusion SPECT findings (P>0.05). We concluded that poor agreement exists between aneurysms and abnormal myocardial perfusion detected by 2D-Echo and Tc-TF myocardial perfusion SPECT findings in patients with KD.

Adolescent↗
PubMed2003

Evaluation of myocardial perfusion with grey-scale ultra-harmonic and multiple-frame triggering. The need for quantification.

BACKGROUND AND OBJECTIVE: Contrast echocardiography has been recently introduced as a new technique for evaluating myocardial perfusion in a qualitative basis. The objective of this study was to test whether a visual subjective evaluation of myocardial perfusion by myocardial contrast echocardiography adequately matches the data obtained with an off-line quantification of myocardial perfusion. METHODS: Sixty-one myocardial segments were evaluated by myocardial contrast echocardiography with Ultra-harmonic and Multiframe Triggering in 11 patients 3-7 days after an anterior myocardial infarction, using SH-U 563A (Levovistâ, Schering AG, Berlin, Germany) as contrast agent. Myocardial perfusion was classified as grade 1 (absent), 2 (patchy or incomplete) and 3 (complete) in each segment. The quantitative analysis was performed off-line by a different investigator blinded to the qualitative evaluation, using a commercially available software. The quantitative data on grey-scale obtained were compared between grade 1, 2 and 3 segments. RESULTS: Of the 61 segments, 45 (73.8%) were classified as grade 3, whereas the remaining 16 (26.2%) were considered to be abnormally perfused (grade 2: n=12, 19.6%; grade 1: n=4, 6.6%). Segments with grade 1 perfusion had a significantly higher grey-scale value (123.6 +/- 41.3 vs. 70.1 +/- 34.3, p=0.004). However, there were no significant differences between segments with perfusion grade 2 and 3 (76.8 +/- 33.2 vs. 68.3 +/- 34.8, p=0.452). CONCLUSION: Qualitative assessment of myocardial perfusion by Ultra-harmonic and Multiframe Triggering is of limited value, since only myocardial segments with absent perfusion may be reliably identified. This findings support the need of quantification in the evaluation of myocardial perfusion by contrast echocardiography.

Aged↗
PubMed2000

Radiation dose-effect relations and local recovery in perfusion for patients with non-small-cell lung cancer.

PURPOSE: To determine local dose-effect relations for lung perfusion and density changes due to irradiation for patients with non-small-cell lung cancer (NSCLC) and to quantify the effect of reperfusion. METHODS AND MATERIALS: For 25 NSCLC patients and a reference group of 81 patients with healthy lungs, registered single photon emission computed tomography (SPECT) lung perfusion and CT scans were made, before and after radiotherapy. Average dose-effect relations for perfusion and CT-density changes were calculated and compared with the dose-effect relation of the reference group. On the basis of these dose-effect relations, the post-RT perfusion was predicted for each patient and compared to the measured post-RT perfusion. RESULTS: Well-perfused lung regions of the NSCLC patients showed the same dose-effect relation as the reference patients. By comparing predicted and measured post-treatment perfusion scans, regions of reperfusion could be determined for 18 of 25 NSCLC patients but for none of the reference patients. CONCLUSION: Well-perfused lung tissue of patients with NSCLC behaves like healthy lung tissue with respect to radiation. The dose-effect relation for perfusion and CT density was extended for doses up to 80 Gy. Radiation damage in poorly perfused lung regions was less than predicted as a consequence of local reperfusion.

Algorithms↗
PubMed2000

Spatial relationship between hypoxia and the (perfused) vascular network in a human glioma xenograft: a quantitative multi-parameter analysis.

PURPOSE: To quantitatively study the spatial distribution of tumor hypoxia in relation to the perfused vasculature. METHODS AND MATERIALS: Using a human glioma xenograft model, nude mice were administered two different hypoxia markers (NITP or pimonidazole) and the perfusion marker Hoechst 33342. Frozen tumor sections were sequentially scanned for perfusion, hypoxia, and vasculature, respectively, to quantitate perfusion, vasculature, and hypoxia parameters in the same section. RESULTS: All tumors showed incomplete perfusion. Both NITP and pimonidazole stained the same hypoxic tumor areas. No statistically significant differences between the two markers were observed. The density of the perfused vessels was inversely related to the hypoxic fraction. At critical distances from perfused vessels, hypoxia occurred. These data suggest that predominantly diffusion-limited hypoxia was detected, based on the spatial distribution of nearby vessels. Also, the proportion of hypoxia distributed over arbitrary zones of 50 microm around perfused vessels was calculated. The largest proportion of hypoxia was found at distances beyond 100 microm from perfused vessels. CONCLUSION: With the multiple staining and functional microscopic imaging technique described here, the spatial relationship between perfused vessels and hypoxia was quantified in whole tumor cross-sections. The usefulness of this histologically-based method to quantitate morphological and physiological aspects of the tumor microenvironment was evaluated.

Animals↗
PubMed2000

Cerebral perfusion SPECT in transient ischemic attack.

PURPOSE: The purpose of our study is to evaluate the efficacy of cerebral perfusion single photon emission computerized tomography (SPECT) in patients with transient ischemic attack (TIA). METHODS: Thirty-seven patients with TIA were collected for study. All patients had transient focal neurological symptoms or signs with complete recovery within 24 h after onset. The patients underwent cerebral perfusion SPECT between 6 h and 11 days after onset, with 10 cases performed within 24 h (group A), nine cases performed between 1 and 3 days (group B), 11 cases performed between 3 and 5 days (group C), and seven cases performed after more than 5 days (group D). A semi-quantitative method was used for analyzing the SPECT data, and the difference ratios between lesion side and contralateral normal side were calculated on each pair of regions of interest. RESULTS: In total, 78.4% (29/37) of patients had reduced perfusion in the cerebral cortical regions or deep nuclei, and the regions with reduced perfusion corresponded with clinical presentations of the patients. The abnormal rate with reduced perfusion was 90.0% in group A, 77.8% in group B, 72.7% in group C and 71.4% in group D. Cross cerebellar diaschisis (CCD) was present in seven patients, and all of the primary cerebral perfusion defects of these patients were located at the territory of left or right middle cerebral artery. CONCLUSION: Cerebral perfusion SPECT is a potential tool to detect cerebral perfusion defects and CCD in patients with TIA. Although the perfusion defect may persist more than 5 days after onset, we suggest cerebral perfusion SPECT should be performed as soon as possible.

Adult↗
PubMed1999

Assessment of myocardial perfusion using multisection first-pass MRI and color-coded parameter maps: a comparison to 99mTc Sesta MIBI SPECT and systolic myocardial wall thickening analysis.

The most recently reported magnetic resonance first-pass myocardial perfusion studies were restricted to single slice imaging or a data analysis based on interactively placed regions of interest. This study was designed to investigate a new saturation recovery TurboFLASH sequence for multisection myocardial perfusion imaging and to develop a pixel-based software tool to calculate qualitative perfusion parameters. The findings of perfusion imaging were compared to percent systolic myocardial wall thickening analysis and 99mTc Sesta MIBI SPECT. Six healthy volunteers and twelve patients with proven coronary artery disease (CAD) or chronic myocardial infarction were examined. Diagnostic images were acquired for all volunteers and patients with the multisection saturation recovery TurboFLASH sequence. Perfusion defects could be visualized on parameter maps for signal intensity increase over baseline and signal intensity upslope. Sensitivity and specificity were 76.9% and 97.1% for first-pass perfusion MRI, and respectively 84.6% and 94.3% for CINE imaging. All perfusion defects determined with 99mTc Sesta MIBI SPECT were identified by the combined analysis of myocardial perfusion and wall thickening. The presented software demonstrated a pixel-based analysis of first-pass perfusion studies and simplified image interpretation in a clinical setting. The combination of perfusion and wall motion imaging provided complementary information for the treatment of patients suffering from CAD.

Adult↗
PubMed1997

Evaluation of patterns of perfusion and metabolism in dobutamine-responsive myocardium.

OBJECTIVES: We investigated the patterns of perfusion and metabolism in dysfunctional myocardium whose contractility improved with dobutamine. BACKGROUND: Clinical studies have suggested that dobutamine echocardiography can identify hibernating myocardium, but laboratory studies suggest that reduced perfusion limits the response to dobutamine. METHODS: Twenty-five patients with coronary disease and ventricular dysfunction underwent low (5 and 10 micrograms/kg body weight per min) and high dose (maximum of 50 micrograms/kg per min) dobutamine echocardiography and positron emission tomography (PET) using nitrogen-13 (N-13) ammonia and fluorine-18 fluorodeoxyglucose (FDG) for imaging of perfusion and metabolism. Wall motion and tracer uptake were scored in 16 left ventricular segments. RESULTS: Perfusion and metabolism were normal in 56.4%, mildly reduced in 29.1% and mismatched (reduced perfusion, preserved FDG uptake) in 14.5% of dysfunctional segments viable on PET. Wall motion improved with dobutamine in 89 dysfunctional segments (62 at low dose, 27 only at peak dose), and 86 of these (97%) were viable on PET. Improvement in wall motion with dobutamine was more common in segments with normal perfusion and metabolism (56.5%) than in those with mildly reduced tracer uptake (28.5%, p < 0.001) and those with mismatch (32%, p = 0.03). All the segments with a biphasic response were supplied by vessels with > or = 70% stenosis, and 88% had normal perfusion and metabolism. CONCLUSIONS: The majority of viable segments with rest dysfunction had normal perfusion and metabolism, suggesting that myocardial stunning was common. Improvement of wall motion at low and high doses of dobutamine was highly correlated with myocardial viability on PET and was more common in myocardium with normal perfusion. A biphasic response to dobutamine identified segments with normal perfusion and metabolism supplied by severely diseased vessels.

Ammonia↗
PubMed1997

Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain.

OBJECTIVES: This study sought to determine the ability of early perfusion imaging using technetium-99m sestamibi to predict adverse cardiac outcomes in patients who present to the emergency department with possible cardiac ischemia and nondiagnostic electrocardiograms (ECGs). BACKGROUND: Evaluation of patients presenting to the emergency department with possible acute coronary syndromes and nondiagnostic ECGs is problematic. Accurate risk stratification is necessary to prevent serious adverse outcomes. Initial results suggest that early perfusion imaging using technetium-99m sestamibi enables reliable risk stratification. METHODS: Patients presenting to the emergency department with a low to moderate probability of acute coronary syndromes underwent rapid sestamibi injection with gated single-photon emission computed tomographic imaging. Studies showing perfusion defects with associated wall motion abnormalities were considered positive. RESULTS: A total of 532 consecutive patients underwent serial myocardial marker analysis and rest perfusion imaging. Of these patients, perfusion imaging was positive in 171 (32%). Positive perfusion imaging was the only multivariate predictor of myocardial infarction (MI) (p < 0.0001, odds ratio [OR] 33, 95% confidence interval [CI] 7.7 to 141) and was the most important independent predictor of MI or revascularization (p < 0.0001, OR 14, 95% CI 7.3 to 25), followed by diabetes (p < 0.01, OR 2.8, 95% CI 1.5 to 5.1), typical angina (p = 0.01, OR 2.1, 95% CI 1.2 to 3.7) and male gender (p = 0.03, OR 1.9, 95% CI 1.1 to 3.5). The sensitivity of positive perfusion imaging for MI was 93% (95% CI 77% to 98%), and for MI or revascularization it was 81% (95% CI 71% to 88%), with negative predictive values of 99% (95% CI 98% to 100%) and 95% (95% CI 92% to 97%), respectively. CONCLUSIONS: Positive rest perfusion imaging accurately identified patients at high risk for adverse cardiac outcomes, whereas negative perfusion imaging identified a low risk patient group. Early perfusion imaging allows for rapid and accurate risk stratification of emergency department patients with possible cardiac ischemia and nondiagnostic ECGs.

Aged↗
PubMed1999

Intraoperative scanning laser Doppler flowmetry in the assessment of gastric tube perfusion during esophageal resection.

BACKGROUND: Ischemia from tissue hypoperfusion in the gastric tube after esophagectomy is believed to contribute significantly to postoperative complications associated with anastomotic failure. This study assessed the ability of the new technique of laser Doppler flowmetry to measure differential levels of blood flow in human gastric tubes during esophagectomy. STUDY DESIGN: Gastric perfusion was measured in 16 patients undergoing esophagectomy by making laser Doppler scans of the stomach before mobilization and after formation of the gastric tube. Mean perfusion was calculated within the whole anterior surface of the stomach or tube and within 1 cm2 regions of interest, each of which contained 1,750 individual measurements of perfusion. These regions represented the cephalic end of the gastric tube, 10 adjacent 1 cm2 regions distally along the tube, and the proposed anastomosis site. Results were expressed as mean perfusion units, and tissue blood flow from each scan in each region was compared. RESULTS: There were significant decreases in gastric perfusion measured with the scanning laser Doppler in all patients after formation of the gastric tube. Mean perfusion of the stomach fell 41% (p<0.0005) after mobilization. In all patients there was a gradient of perfusion from the proximal end of the tube where flow was poor, to more distal areas where it was higher. At the proximal end of the tube perfusion fell by a mean of 72%, 5 cm distally the mean fall was 44%, and 10 cm from the proximal end of the tube the mean fall was 28%. At the anastomosis site mean perfusion fell 55%. CONCLUSIONS: This new technique can be used intraoperatively and appears to overcome the limitations of single point laser Doppler flowmetry. It has measured large differences in perfusion at different sites within the gastric tubes and could therefore have widespread clinical applications.

Adult↗
PubMed2002

Development of perfusion CT software for personal computers.

RATIONALE AND OBJECTIVES: The authors developed software for creating quantitative maps of arterial and portal perfusion in the upper abdominal organs on personal computers. The image quality of these perfusion computed tomographic (CT) images was visually evaluated. MATERIALS AND METHODS: In 58 patients (38 men, 20 women; mean age, 63.9 years +/- 11.9; range, 22-85 years) with various diseases of the upper abdomen, 91 single-section dynamic CT studies were obtained. The data were transferred on-line to a personal computer, and quantitative maps of arterial and portal perfusion were created by means of the maximum-slope method. Perfusion CT images were reviewed by a radiologist and a radiation technologist, and image quality was rated according to a four-category scoring system (1 = good quality, 2 = moderate, 3 = poor, 4 = images could not be created). RESULTS: Arterial perfusion CT images could be created in 81 (89%) of 91 examinations, and 74 images (81%) were scored as 1 or 2. Portal perfusion CT images could be created in 60 (68%) of 88 examinations, in which a portal trunk was included in the section, and 33 of them (38%) were scored as 1 or 2. Patient motion during dynamic CT sequences resulted in poor image quality in seven arterial and 27 portal perfusion images. CONCLUSION: Perfusion CT can combine quantitative perfusion maps with good anatomic detail in one image, although patient movement frequently degrades image quality in portal perfusion CT.

Abdomen↗
PubMed1996

Effect of pulmonary volume loss on the size and appearance of experimentally produced scintigraphic perfusion defects.

RATIONALE AND OBJECTIVES: Atelectasis is a frequent concomitant of pulmonary embolism (PE) and other conditions that mimic PE. Accordingly, we developed an animal model to study the effect of regional loss of pulmonary volume on the size and configuration of experimentally induced perfusion defects that simulated PE. METHODS: After baseline anteroposterior and lateral chest radiographs were taken, 11 pulmonary vascular occlusions were created in 10 anesthetized, intubated mongrel dogs. Three were created by balloon occlusions of segmental pulmonary arteries, and eight were created by release of autologous PE. The size and shape of the affected lung zones were determined by perfusion scintigraphy (technetium-99m-macroaggregrated albumin [99mTc-MAA]) and the results recorded. A balloon-tip Fogarty catheter then was passed through the trachea and inflated at preselected endobronchial sites to produce bronchial occlusion and volume loss, which were documented radiographically. Because one animal had two such occlusions sequentially, a total of 12 volume reduction experiments were performed. After inducing volume loss, perfusion imaging was repeated without reinjection of 99mTc-MAA to allow any changes in the perfusion defects to be recorded, measured, and compared with the degree of volume loss visualized radiographically. RESULTS: Volume loss did not alter the shape of ipsilateral scintigraphic perfusion defects, but it did result in the expansion of eight of the 12 perfusion defects (range = 18-137% increase in area, Mdn = 33%) and a 28% decrease in the size of one defect located within a lobe that lost volume. Despite these quantitative changes, only three of the perfusion defects appeared substantially larger. When independently interpreted radiographs demonstrated large volume losses, quantitative changes in perfusion defects were no greater on average than when radiographic volume loss was modest. CONCLUSION: Loss of pulmonary volume is occasionally associated with considerable ipsilateral alterations in the size of scintigraphic perfusion defects. It is probably advisable to consider the effects of anatomic distortions such as volume loss when interpreting the significance of scintigraphic perfusion defects in patients suspected of having PE.

Animals↗
PubMed2003

Continuous plant cell perfusion culture: bioreactor characterization and secreted enzyme production.

Culture perfusion is widely practiced in mammalian cell processes to enhance secreted antibody production. Here, we report the development of an efficient continuous perfusion process for the cultivation of plant cell suspensions. The key to this process is a perfusion bioreactor that incorporates an annular settling zone into a stirred-tank bioreactor to achieve continuous cell/medium separation via gravitational sedimentation. From washout experiments, we found that under typical operating conditions (e.g., 200 rpm and 0.3 vvm) the liquid phase in the entire perfusion bioreactor was homogeneous despite the presence of the cylindrical baffle. Using secreted acid phosphatase (APase) produced in Anchusa officinalis cell culture as a model we have studied the perfusion cultures under complete or partial cell retention. The perfusion culture was operated under phosphate limitation to stimulate APase production. Successful operation of the perfusion process over four weeks has been achieved in this work. When A. officinalis cells were grown in the perfusion reactor and perfused at up to 0.4 vvd with complete cell retention, a cell dry weight exceeding 20 g/l could be achieved while secreted APase productivity leveled off at approximately 300 units/l/d. The culture became extremely dense with the maximum packed cell volume (PCV) surpassing 70%. In comparison, the maximum cell dry weight and overall secreted APase productivity in a typical batch culture were 10-12 g/l and 100-150 units/l/d, respectively. Operation of the perfusion culture under extremely high PCV for a prolonged period, however, led to declined oxygen uptake and reduced viability. Subsequently, cell removal via a bleed stream at up to 0.11 vvd was tested and shown to stabilize the culture at a PCV below 60%. With culture bleeding, both specific oxygen uptake rate and viability were shown to increase. This also led to a higher cell dry weight exceeding 25 g/l, and further improvement of secreted APase productivity that reached a plateau fluctuating around 490 units/l/d.

Journal Article↗
PubMed2001

Relationship between function and perfusion early after acute myocardial infarction.

To assess the relationship between baseline left ventricle function, functional reserve and resting myocardial perfusion in patients with acute myocardial infarction (AMI). After AMI the presence of dysfunctioning but viable myocardium plays a determinant role in clinical outcome. Regional ventricular function was evaluated by echocardiography both in resting conditions and during dobutamine infusion (10 microg/kg/min). Perfusion was assessed by magnetic resonance imaging in a single slice approach where the first pass of an intravenously injected bolus of gadolinium-based contrast agent was followed through six regions of interest within the myocardium. In each patient a region with normal function was used as reference and the cross-correlation coefficient (CCC), which described the myocardial perfusion relatively to the reference region (CCC = 1 means equivalent perfusion), was obtained for the other five myocardial regions. Twenty-two patients were enrolled into the study. Sixty-one segments had normal function and normal perfusion (CCC = 0.92+/-0.23). The perfusion deficit was more marked in the 29 regions with resting akinesia-dyskinesia than in the 20 hypokinetic regions (CCC = 0.71+/-0.45 vs. 0.84+/-0.23; p < 0.05). Out of the 29 regions with resting akinesia-dyskinesia the 13 segments which showed functional improvement following dobutamine had a higher resting perfusion than the 16 segments which were unresponsive to dobutamine (CCC = 0.83+/-0.32 vs. 0.61+/-0.52, p < 0.05). Similarly, out of the 20 regions with resting hypokinesia the 11 segments having functional reserve showed an higher resting perfusion than the segments which did not (0.96+/-0.21 vs. 0.69+/-0.19; p < 0.05). Early after AMI, the perfusion deficit reflects the severity of the mechanical dysfunction. In regions with baseline dyssynergy resting perfusion is, in general, higher when contractile reserve can be elicited by stress-echo.

Adrenergic beta-Agonists↗
PubMed1997

Modulation of c-fos and egr-1 expression in the isolated perfused kidney by agents that alter tubular work.

The isolated perfused rat kidney provides a model of selective hypoxia to the medullary thick ascending limb. To investigate the relationship between immediate early gene expression and the extent of hypoxic damage, we determined expression of the immediate early genes (IEG) c-fos and egr-1 in isolated perfused kidneys during standard perfusion and after various measures shown previously to be protective. mRNA levels of c-fos and egr-1 were markedly increased in kidneys after 90 minutes of standard perfusion with Krebs-Henseleit buffer containing albumin. Gene expression was most prominent in the outer medulla followed by papilla and cortex, a pattern reflected by the immunohistochemical demonstration of a prominent accumulation of both egr-1 and c-fos polypetides mainly in the medullary thick ascending limb (mTAL). Protective measures known to minimize morphological damage to the mTAL, including hyperoncotic perfusion, perfusion with glycine, or perfusion with a mixture of amino acids, decreased mRNA levels of c-fos and egr-1 in the outer medulla (by 50% and 35%, respectively) and the papilla (by 60 and 30%, respectively). Renal cortex showed only minor changes. In contrast, prevention of tubular transport by perfusion with 1 mM ouabain increased mRNA levels of c-fos and egr-1 in the outer medulla by 100% and 60%, respectively. Ouabain also dramatically increased mRNA levels of both IEGs in two lines of cultured renal epithelial cells. Changes in the level and distribution of the protein products of these IEGs were not detectable in perfused kidneys by immunohistochemistry. Hypoxic injury of the kidney stimulates IEG expression even in the absence of reperfusion. Protection against hypoxic injury in the mTAL correlates with suppression of IEG mRNA levels when protection is provided by amino acids or hyperoncotic perfusion, but not when provided by inhibition of Na,K-ATPase, which stimulates IEG expression. We conclude that diminished IEG expression is not a necessary concomitant of protection against hypoxic injury.

Amino Acids↗
PubMed2003

Measurement of renal tumour and normal tissue perfusion using positron emission tomography in a phase II clinical trial of razoxane.

Measurement of tumour and normal tissue perfusion in vivo in cancer patients will aid the clinical development of antiangiogenic and antivascular agents. We investigated the potential antiangiogenic effects of the drug razoxane by measuring the changes in parameters estimated from H(2)(15)O and C(15)O positron emission tomography (PET) to indicate alterations in vascular physiology. The study comprised 12 patients with primary or metastatic renal tumours >3 cm in diameter enrolled in a Phase II clinical trial of oral razoxane. Perfusion, fractional volume of distribution of water (VD) and blood volume (BV) were measured in tumour and normal tissue before and 4-8 weeks after treatment with 125 mg twice-daily razoxane. Renal tumour perfusion was variable but lower than normal tissue: mean 0.87 ml min(-1) ml(-1) (range 0.33-1.67) compared to renal parenchyma: mean 1.65 ml min(-1) ml(-1) (range 1.16-2.88). In eight patients, where parallel measurements were made during the same scan session, renal tumour perfusion was significantly lower than in normal kidney (P=0.0027). There was no statistically significant relationship between pretreatment perfusion and tumour size (r=0.32, n=13). In six patients scanned before and after razoxane administration, there was no statistically significant change in tumour perfusion: mean perfusion pretreatment was 0.81 ml min(-1) ml(-1) (range 0.46-1.26) and perfusion post-treatment was 0.72 ml min(-1) ml(-1) (range 0.51-1.15, P=0.15). Tumour VD and BV did not change significantly following treatment: mean pretreatment VD=0.66 (range 0.50-0.87), post-treatment VD=0.71 (range 0.63-0.82, P=0.22); pretreatment BV=0.18 ml ml(-1) (range 0.10-0.25), post-treatment BV=0.167 ml ml(-1) (range 0.091-0.24, P=0.55). Tumour perfusion, VD and BV did not change significantly with tumour progression. This study has shown that H(2)(15)O and C(15)O PET provide useful in vivo physiological measurements, that even highly angiogenic renal cancers have poor perfusion compared to surrounding normal tissue, and that PET can provide valuable information on the in vivo biology of angiogenesis in man and can assess the effects of antiangiogenic therapy.

Antineoplastic Agents↗