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Regional heterogeneity of myocardial perfusion in healthy human myocardium: assessment with magnetic resonance perfusion imaging.

The knowledge of myocardial perfusion in healthy volunteers is fundamental for evaluation of patients with ischemic heart disease. The study was conducted to determine range, regional variability, and transmural gradient of myocardial perfusion in normal volunteers with Magnetic Resonance Perfusion Imaging (MRPI). Perfusion was assessed in 17 healthy volunteers (age: 20-47 yr, 11 males) at rest and adenosine-induced hyperemia using a 1.5 T MR scanner. Perfusion was quantified (mL/g/min) for the transmural myocardium and separately for the endo- and epimyocardium in the anterior, lateral, posterior, and septal left ventricular wall using the Fermi model for constrained deconvolution. Regional variabilities for resting, hyperemic perfusion, and perfusion reserve were 22 +/- 8%, 21 +/- 10%, and 35 +/- 18%. Mean resting, hyperemic perfusion, and perfusion reserve were 1.1 +/- 0.4 mL/g/min, 4.2 +/- 1.1 mL/g/min, and 4.1 +/- 1.4. Perfusion in the septum was higher at rest (1.3 +/- 0.3 mL/g/min vs. 1.0 +/- 0.3 mL/g/min, p < 0.05) and lower during hyperemia (3.6 +/- 0.8 mL/g/min vs. 4.5 +/- 1.1 mL/g/min, p < 0.03), resulting in a reduced perfusion reserve (PR) (3.2 +/- 0.9 vs. 4.5 +/- 1.4, p < 0.01) in the septum vs. the combined anterior, lateral, and posterior segments. Resting (0.9 +/- 0.3 mL/g/min vs. 1.4 +/- 0.5 mL/g/min, p < 0.01), but not hyperemic perfusion, was lower in the epi- vs. endomyocardium, resulting in a higher epimyocardial PR (4.8 +/- 1.8 vs. 3.5 +/- 1.4, p < 0.01) in all regions but the septum, where endo- and epimyocardial perfusion and perfusion reserve were not different. A considerable regional variability of myocardial perfusion was confirmed with MRPI. The exceptional anatomical position of the septum is reflected by the lack of a perfusion gradient, which was demonstrated in all other regions but the septum.

Adult↗

Decreased pulmonary perfusion in pulmonary vein stenosis after radiofrequency ablation: assessment with dynamic magnetic resonance perfusion imaging.

STUDY OBJECTIVES: The functional impact of pulmonary vein (PV) stenosis on pulmonary perfusion after radiofrequency ablation (RFA) for atrial fibrillation (AF) has not been systematically evaluated previously. Therefore, we correlated magnetic resonance (MR) pulmonary perfusion imaging with single-photon emission CT (SPECT) perfusion and with the degree of PV stenosis (PVS) apparent on MR angiography (MRA) after RF ablation. SETTING: Joint radiology-cardiology collaborative magnetic resonance unit at the Kerckhoff Heart Center. DESIGN AND PATIENTS: This was a cohort study of 110 patients who were routinely examined by MRA after RFA for AF, whereby 51 patients with a PV diameter reduction of > 25% or with clinical symptoms (ie, dyspnea and cough) were enrolled into the study. Patients were examined at follow-up by MR perfusion imaging and MRA, and the results were compared to those from patients who underwent SPECT scanning and from a control group of 26 untreated patients. Twelve patients underwent PVS dilatation as well as 22 sequential follow-up examinations. METHODS: Pulmonary perfusion was evaluated using a dynamic contrast-enhanced three-dimensional MR perfusion sequence (1.5 T, 2.5-s temporal resolution, and 0.05 cm spatial resolution), and high-resolution, contrast-enhanced MRA was performed to measure PV diameter. PV dilatation was performed using an angioplasty catheter that was 8 to 10 mm in diameter. RESULTS: The localization and extent of perfusion defects measured by MRI or SPECT scanning were precisely matched. MR perfusion imaging detected 20 of 21 perfusion defects (sensitivity, 95.2%; specificity, 100%). PVSs and perfusion deficits correlated closely and showed the following threshold: perfusion decreased substantially in PVs 6 mm in diameter. After PVS dilatation, perfusion was restored partially after weeks, and complete normalization was seen in 4 of 12 patients (33%). CONCLUSIONS: PVSs caused severe perfusion deficits, which were reliably demonstrated by MR perfusion imaging. Clinical symptoms correlated better with MR perfusion than they did with MRA. The combination with MRA to assess underlying PVS allowed a "one-stop-shopping" MRI procedure to be carried out. The results led to alterations of RFA techniques, and therefore MRA and MR perfusion imaging may be beneficial in patient follow-up and in evaluating new ablation techniques.

Atrial Fibrillation↗

Detection of regional myocardial perfusion deficit using rest and stress perfusion MRI: a feasibility study.

OBJECTIVE: Providing high temporal and spatial resolution, perfusion MRI is an attractive alternative to traditional radionuclide methods like SPECT and PET. Although first-pass perfusion MRI examinations have gained increasing attention during the past years, this technique still exhibits relatively low signal-to-noise ratio and cardiac coverage. Previous studies have suggested that refocused gradient sequence technology (e.g., true fast imaging with steady-state precession [FISP]) should improve perfusion MRI examinations. The aim of this study was to assess myocardial perfusion deficits in patients with proven coronary artery disease using a saturation recovery true FISP perfusion sequence. SUBJECTS AND METHODS: Rest and stress perfusion MRI studies were performed in 22 patients with coronary artery disease at 1.5 T using a multislice saturation recovery true FISP sequence after the bolus injection of 0.025 mmol/kg of body weight of gadopentetate dimeglumine. The myocardium of each slice was divided into 12 radial segments with subdivision into subendocardial and subepicardial subregions. Myocardial perfusion was assessed semiquantitatively and independently for each subregion. The standard of reference for myocardial perfusion was SPECT. Delayed enhancement images were acquired after the injection of 0.15 mmol/kg of body weight of gadopentetate dimeglumine. RESULTS: Sensitivity and specificity of perfusion MRI examinations for the detection of perfusion deficits were 81% and 89%, respectively, for the semiquantitative perfusion parameter upslope and 78% and 86% for the parameter peak signal intensity. More specifically, rest perfusion examinations were able to detect areas of infarction, whereas stress examinations increased the perfusion differences between normal and ischemic myocardial areas. Excellent correlation was observed between rest perfusion and late enhancement findings (r = 0.90). CONCLUSION: In patients with single-vessel coronary artery disease, perfusion deficits can reliably be detected using a saturation recovery true FISP sequence. Semiquantitative perfusion parameters upslope and peak signal intensity yielded similar results.

Adult↗

Isolated hindlimb perfusion in dogs: the effect of perfusion pressures on the oxygen supply (ptO2 histogram) to the skeletal muscle.

During regional isolated perfusion, neoplasms in extremities are treated with high doses of chemotherapeutic drugs by means of an extracorporeal circuit. The question is whether optimal tissue perfusion, which is essential for the therapy, is obtained by regulation of the extracorporeal circuit on an adequate perfusion flow or on an adequate perfusion pressure. To determine which perfusion pressure is needed to maintain adequate tissue perfusion, hindlimbs of six dogs were perfused at perfusion pressures 0, 15, 25, and 50 mm Hg below systemic mean arterial pressure. A multiwire polarographic oxygen electrode placed on the sartorius muscle permitted quantitative evaluation of tissue oxygenation by means of ptO2 histograms. Our results indicated that the perfusion pressure must be equal to or within 15 mm Hg below systemic mean arterial pressure to obtain optimal tissue perfusion. To maintain this perfusion pressure, high perfusion flows of about five to 10 times control femoral flows were needed. At a perfusion pressure 50 mm Hg below systemic mean arterial pressure, perfusion flow was normal, but tissue perfusion was severely impaired.

Animals↗

Tissue and perfusate pharmacokinetics of melphalan in isolated perfused rat hindlimb.

Melphalan is commonly used as a cytotoxic agent in isolated limb perfusion for locally recurrent malignant melanoma. The time course of melphalan concentrations in perfusate and tissues during a 60-min melphalan perfusion and 30-min drug-free washout in the single-pass perfused rat hindlimb was examined using a physiologically based pharmacokinetic model. The rat hindlimbs were perfused with Krebs-Heinseleit buffer containing 4.7% bovine serum albumin (BSA) or 2.8% dextran 40 at a constant rate of 3.8 ml/min. The concentration of melphalan in perfusate and tissues was determined by high-performance liquid chromatography. The tissue concentrations of melphalan were significantly higher with the perfusate containing dextran than BSA during the 60-min perfusion. During the washout period, the melphalan concentration in the perfusates decreased rapidly in first few minutes, followed by a slower monoexponential decline. The estimated half life (t1/2) for melphalan removal from skin and fat was 59 +/- 2 min for both BSA and dextran perfusates. However, the estimated t1/2 for melphalan removal from muscle was 79 and 96 min for BSA and dextran washout perfusates, respectively. The predicted concentration-time profiles obtained for melphalan with BSA and dextran perfusates appear to correspond closely to the observed data. This study showed that the uptake of melphalan into perfused tissues is impaired by the use of perfusates in which melphalan is highly bound. Melphalan washout from muscle, but not skin and fat, was facilitated by the use of perfusates in which melphalan is highly protein bound.

Adipose Tissue↗

The response to ischemia in blood perfused vs. crystalloid perfused isolated rat heart preparations.

With a research hypothesis that the behavior of blood perfused hearts was different from that of crystalloid perfused hearts, we tested the null hypothesis that the functional and metabolic status of blood-perfused (paracorporeal oxygenation) and Krebs-Henseleit (bubble oxygenation) perfused Langendorff isolated rat hearts is the same before, during and after global myocardial ischemia. Thirty isolated rat hearts were studied under identical conditions except that in equal numbers they were randomly assigned to either blood or crystalloid perfusion. In the blood perfused and crystalloid perfused hearts subjected to 22 min of normothermic ischemia and 30 min of reperfusion, mean systolic recovery was 72 +/- 3.9% (S.E.) and 20 +/- 10% (P = 0.001), respectively; coronary resistance increased 21 +/- 16% and 158 +/- 27% (P = 0.0003) (unadjusted for viscosity); mean water content after reperfusion was 82.0 +/- 0.43% and 86.7 +/- 0.42% (P < 0.0001), ATP content was 8.4 +/- 1.9 and 4.3 +/- 0.5 mumol/g dry wt (P = 0.08), and energy charge was 0.74 +/- 0.114 and 0.59 +/- 0.048 (P = 0.3). A major qualitative difference during reperfusion was spontaneous relaxation of contracture and rapid resumption of sinus rhythm in blood perfused hearts, in contrast to continued contracture and rise in intraventricular pressure in 9 of 10 crystalloid perfused hearts. One crystalloid perfused heart did not develop contracture, and its phenomena during reperfusion were similar to those of blood perfused hearts. The data support the research hypothesis, and suggest caution in extrapolating to blood perfused systems inferences from crystalloid perfused models. Better preservation of reactive hyperemia early in reperfusion may explain the better performance of blood perfused hearts.

Adenosine Triphosphate↗

Mechanism by which renin secretion from perfused rat kidneys is stimulated by isoprenaline and inhibited by high perfusion pressure.

1. Rat kidneys were completely isolated and perfused to determine the ionic mechanism whereby isoprenaline stimulates and high perfusion pressure inhibits renin secretion. 2. Isoprenaline (2.43 microM) stimulated renin secretion, but K-free medium and ouabain also reduced perfusate flow. 3. Removing Ca from the perfusion medium increased renin secretion threefold when perfusion pressure was 100 mmHg and fourfold when pressure was raised to 150 mmHg. Simultaneously raising the perfusion pressure to 150 mmHg and the Ca concentration to 5 mM inhibited renin secretion. Verapamil (50 microM) prevented this inhibition. Raising Ca also caused vasoconstriction at a pressure of 150 mmHg, but verapamil partially prevented the vasoconstriction. 4. High concentration of K (50 mM) in the perfusion medium also stimulated renin secretion when Ca was removed and inhibited secretion when Ca concentration was raised to 5 mM. Verapamil (50 microM) prevented this inhibition. High K induced vasoconstriction in the presence of high Ca, but verapamil partially prevented the constriction. 5. High concentration of K (50 mM) and high perfusion pressure (150 mmHg) stimulated renin secretion in the absence of Ca and 20 mM-Mg potentiated this effect. This suggests that both sets of stimuli activate renin secretion by different cellular mechanisms, but that both act to lower cytoplasmic Ca in the juxtaglomerular cell. This is discussed. 6. High perfusion pressure inhibited renin secretion and reduced perfusate flow when Na was lowered from 145 to 14.5 or 0 mM whether or not Ca was present. 7. K-free medium and ouabain blocked the elevated renin secretion and reduced the high flow stimulated by high perfusion pressure when Ca was removed from the perfusion medium. 8. These observations suggest that isoprenaline stimulates renin secretion by a mechanism coupled to the Na-K pump. These observations are also consistent with the hypothesis that high renal perfusion pressure inhibits renin secretion by promoting Ca movement into the juxtaglomerular cell and stimulates secretion by a mechanism coupled to the Na-K pump. High perfusion pressure also causes renal vasoconstriction by increasing the Ca permeability of the smooth muscle cells in the afferent arteriole.

Animals↗

Low-pressure perfusion results in effective microvascular perfusion of isolated rabbit hearts during hypothermic preservation for twenty-four hours.

Hypothermic, low-pressure coronary artery perfusion with oxygenated electrolyte solutions containing oncotic agents has resulted in successful orthotopic transplantation of hearts after extended preservation periods. Coronary flow may not, however, be consistently maintained during preservation. Previous research has demonstrated that coronary flow during preservation is related to contractile function after preservation. Specific mechanisms leading to reduced coronary flow during preservation remain undefined. This study was designed to determine whether low-pressure perfusion is a mechanism for decreased coronary flow and decreased microvascular perfusion during preservation. With India ink used as a marker of flow, microvascular perfusion was measured in rabbit hearts immediately after isolation (controls) or after 24 hours of hypothermic perfusion at 13 mm Hg (preserved hearts). There were no differences in the percentage of perfused microvessels in the control hearts perfused at either 13 or 80 mm Hg (94% +/- 2% and 99% +/- 1%, respectively). Nor was there a difference in the percentage of perfused microvessels in hearts perfused at either 13 or 80 mm Hg after 24 hours of hypothermic, low-pressure perfused preservation (67% +/- 9% and 74% +/- 6%, respectively). There was a significant difference, however, between the percentage of perfused microvessels in control hearts and in hearts preserved for 24 hours. These differences were independent of the pressure at which the India ink solution was administered. A perfusion pressure of 13 mm Hg is as effective as is 80 mm Hg in providing perfusion of the coronary microvascular beds during long-term hypothermic perfused preservation.

Analysis of Variance↗

Comparison of ischemic vulnerability and responsiveness to cardioplegic protection in crystalloid-perfused versus blood-perfused hearts.

The possibility of differences between crystalloid-perfused and blood-perfused hearts in their vulnerability to ischemia and responsiveness to protective interventions has been investigated in isolated rabbit hearts perfused with bicarbonate buffer or arterial blood. In preliminary studies with 165 minutes of aerobic perfusion at constant perfusion pressure (55 +/- 3 mm Hg), the stability of left ventricular developed pressure was significantly better in blood-perfused hearts. In subsequent studies, hearts were subjected to 20 minutes of aerobic perfusion (coronary flow, 2.0 +/- 0.3 ml/min/gm wet weight in blood-perfused hearts versus 11.3 +/- 3.0 ml/min/gm wet weight in crystalloid-perfused hearts; left ventricular developed pressure, 90 +/- 4 and 91 +/- 2 mm Hg, respectively) followed by 30, 45, 60, 75, 90, or 105 minutes of normothermic global ischemia and 40 minutes of reperfusion (n = 4 per group). In the buffer-perfused groups the postischemic recoveries of left ventricular developed pressure were 74% +/- 6%, 45% +/- 7%, 39% +/- 6% 32%, +/- 5%, 27% +/- 4%, and 12% +/- 3% of preischemic control, respectively. In blood-perfused groups they were consistently greater (91% +/- 3%, 55% +/- 5%, 46% +/- 5%, 45% +/- 1%, 33% +/- 2%, and 19% +/- 3%, respectively). In further studies, hearts (n = 5 per group) were perfused with buffer (groups 1 and 2) or blood (groups 3 and 4), and each was subjected to 60 minutes of normothermic global ischemia, with (groups 2 and 4) or without (groups 1 and 3) a 3-minute preischemic infusion of St. Thomas' Hospital cardioplegic solution. After 60 minutes of reperfusion, the postischemic recoveries of left ventricular developed pressure in groups 1, 2, 3, and 4 were 32% +/- 3%, 44% +/- 4%, 43% +/- 7%, and 72% +/- 6%, respectively, with coronary flow recovering to 64% +/- 7%, 82% +/- 4%, 82% +/- 4%, and 110% +/- 5%, respectively. Left ventricular end-diastolic pressures were 20 +/- 5, 24 +/- 7, 15 +/- 4, and 4 +/- 3 mm Hg, and tissue water contents were 4.76 +/- 0.11, 4.87 +/- 0.55, 3.93 +/- 0.05, and 3.68 +/- 0.02 ml/gm dry weight, respectively. In conclusion, compared with crystalloid perfusion, the blood-perfused rabbit heart has a greater resistance to ischemia, a superior response to cardioplegic protection, and a lower tissue water content.

Animals↗

[Myocardial perfusion scintigraphy with Tc-99m MIBI in patients with left bundle branch block: Visual quantification of the anteroseptal perfusion imaging for the diagnosis of left anterior descending artery stenosis].

INTRODUCTION: The non-invasive detection of myocardial ischaemia in patients with left bundle branch block (LBBB) remains a challenge. It is often associated with coronary artery disease or hypertension, but frequently there is no indication of cardiovascular pathology at presentation. Exercise-induced electrocardiographic ST segment changes are non-diagnostic. Confirming coronary artery disease has obvious implications for management. Several studies have shown greater cardiac mortality in the presence of LBBB. Generally, a good prognosis has been found in patients with LBBB and normal or near-normal myocardial perfusion scintigraphy (MPS). Various investigators report frequent anteroseptal defects with MPS in patients with LBBB in the absence of significant left anterior descending (LAD) coronary artery disease. Several mechanisms have been proposed to explain this false-positive phenomenon. Various interpretative methods and stress techniques have been evaluated in an attempt to improve the specificity of noninvasive studies for detecting LAD disease. A number of software packages for quantifying myocardial perfusion are commercially available. Quantification is recommended to improve diagnostic accuracy and intra- and inter-observer reproducibility.41 METHODS: Patients with LBBB on ECG, who were referred to our institution (February 2002 to September 2003) for myocardial perfusion scintigraphy, were included in the study. Patients with previous myocardial infarction were excluded, unless the location was confirmed to be not anteroseptal before the onset of LBBB. Patients who did not undergo coronary angiography within six months were also excluded, unless a LAD lesion of > or = 50% was diagnosed more than six months prior to MPS without subsequent intervention, or angiography more than six months later showed a LAD lesion of < or = 50%. Treadmill exercise, dipyridamole or dobutamine infusion were used according to standard protocols and imaging commenced 15-60 minutes later. QPS quantitative software, used to reconstruct the images and quantify perfusion, is described in detail elsewhere. Three experienced nuclear physicians interpreted the studies. Stress and rest perfusion, as well as reversibility, to the anteroseptal wall (excluding the apex), anteroseptal wall and apex, and apex only, were graded on a scale of 0 (normal) to 4 (absent perfusion), where 1 represents mild, 2 moderate, and 3 severe impairment of perfusion. A final decision was made by consensus. Using QPS, summed stress, rest and difference scores were obtained for the same regions. Angiographic correlation was obtained by reviewing the patients' records. Stenosis of the LAD or graft vessel to the LAD of > or =50% was regarded as significant. The Kruskal-Wallace non-parametric test was used to compare the groups with and without significant LAD stenosis. A Bonferroni correction was applied to make provision for multiple testing. Receiver operating characteristic (ROC) analysis was utilised to determine the optimal threshold of the significant measurements to distinguish between the two groups; for this threshold, the sensitivity and specificity were calculated. RESULTS: Nine men and nine women (42-78 years) satisfied the inclusion criteria and were included in the study. Dipyridamole was used in nine patients, exercise in seven, dobutamine in one, and one patient was injected during a period of typical chest pain. Ten patients had a LAD stenosis of < 50% and eight > or = 50%. The only measurement that yielded a significant difference between the groups was visual improvement in perfusion to the anteroseptal wall and apex between the stress and rest study (p < 0.0096). Even after applying a Bonferroni correction, the value tended towards significance (p = 0.16). A ROC curve was calculated and an optimal threshold of 0.5 determined, which in turn had a sensitivity of 88% and specificity of 67%. DISCUSSION: Our findings suggest that visual reversibility in the anteroseptal wall and apex gives an indication of significant LAD stenosis in patients with LBBB. This finding agrees with that of Mairesse et al. Wackers argues that cardiomyopathic changes cause anteroseptal perfusion defects in LBBB. It is possible that irreversible perfusion defects in the anteroseptal wall and apex are caused by a constant, stress-independent mechanism, whereas reversible defects indicate underlying ischaemia. Interestingly, quantitative analysis was not helpful in predicting LAD disease. The quantitative software we used is well validated. On the other hand, Svenssson et al. compared three myocardial perfusion quantification software packages and found considerable variation, especially in the presence of perfusion defects. The state of perfusion to the apex was not helpful to detect significant LAD disease. It is known that the LAD usually supplies the apex. Matzer et al. found that requiring the presence of an apical defect improved specificity. This could not be confirmed by Lebtahi et al. or Vaduganathan et al. LIMITATIONS: A definite limitation of our study was that treadmill stress testing was performed in seven patients. It is currently recommended by most authors that pharmacological stress be performed in patients with LBBB Selection bias is also a limitation because only patients who also had angiography were included in the study (18 out of 91). CONCLUSION: A visual improvement in anteroseptal and apical myocardial perfusion between stress and rest with Tc-99m MIBI in patients with LBBB probably indicates significant LAD stenosis. In our hands, quantitative software did not aid in the diagnosis. A well-designed, prospective study using a standardized stress protocol (probably dipyridamole or adenosine), which specifically evaluates visual reversibility in the anteroseptal wall and apex, will obviate the need for a Bonferroni correction, and could confirm these findings.

Adult↗

Cytostatic lung perfusion results in heterogeneous spatial regional blood flow and drug distribution: evaluation of different cytostatic lung perfusion techniques in a porcine model.

OBJECTIVES: Comparison of doxorubicin uptake, leakage and spatial regional blood flow, and drug distribution was made for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), as opposed to intravenous administration in a porcine model. METHODS: White pigs underwent single-pass lung perfusion with doxorubicin (320 mug/mL), labeled 99mTc-microspheres, and Indian ink. Visual assessment of the ink distribution and perfusion scintigraphy of the perfused lung was performed. 99mTc activity and doxorubicin levels were measured by gamma counting and high-performance liquid chromatography on 15 tissue samples from each perfused lung at predetermined localizations. RESULTS: Overall doxorubicin uptake in the perfused lung was significantly higher (P = .001) and the plasma concentration was significantly lower (P < .0001) after all isolated lung perfusion techniques, compared with intravenous administration, without differences between them. Pulmonary artery infusion (blood flow occlusion) showed an equally high doxorubicin uptake in the perfused lung but a higher systemic leakage than surgical isolated lung perfusion (P < .0001). The geometric coefficients of variation of the doxorubicin lung tissue levels were 175%, 279%, 226%, and 151% for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), respectively, compared with 51% for intravenous administration (P = .09). 99mTc activity measurements of the samples paralleled the doxorubicin level measurements, indicating a trend to a more heterogeneous spatial regional blood flow and drug distribution after isolated lung perfusion and blood flow occlusion compared with intravenous administration. CONCLUSIONS: Cytostatic lung perfusion results in a high overall doxorubicin uptake, which is, however, heterogeneously distributed within the perfused lung.

Animals↗

3'-azido-3'-deoxythymidine (AZT) transplacental perfusion kinetics and DNA incorporation in normal human placentas perfused with AZT.

Vertical transmission of the human immunodeficiency virus 1 (HIV-1) is reduced from approximately 25% to approximately 7% as a result of 3'-azido-3'-deoxythymidine (AZT) therapy given during pregnancy; however, the consequences of transplacental AZT exposure to the fetus remain unknown. To address the extent and kinetics of AZT transfer across the human placenta, perfusion studies have been performed with fresh uninfected human placentas perfused with 0.5, 1. 0 and 5.0 mg AZT/ml for 2 h using a dual recirculating single cotyledon perfusion apparatus [T.I. Ala-Kokko, P. Pienimaki, R. Herva, A.I. Hollmen, O. Pelkonen, K. Vähäkangas, Transfer of lidocaine and bupivacaine across the isolated perfused human placenta, Pharmacol. Toxicol. 77 (1995) 142-148]. For two placentas, samples of perfusion effluent were taken every 15 min from the maternal and fetal sides of the apparatus and AZT levels were determined by AZT radioimmunoassay (RIA). At the end of the perfusion, AZT-DNA incorporation into placental DNA was determined by AZT-RIA. The concentration of AZT in the fetal perfusate increased with time, along with a concomitant slow decrease in the concentration of AZT in the maternal perfusates. For three different placentas, at 2 h after the start of perfusion, AZT-DNA incorporation values (molecules of AZT/10(6) nucleotides) were 11.8 for the 0.5 mg AZT/ml perfusate, 13.7 for the 1.0 mg AZT/ml perfusion, and 42.0 for the 5 mg AZT/ml perfusion. An additional placenta perfused with 1 mg AZT/ml did not have detectable values of AZT incorporated into DNA (data not shown). The data show that AZT crosses the human placenta and becomes rapidly incorporated into DNA of placental tissue in a dose-dependent fashion, suggesting that even short exposures to this drug might induce fetal genotoxicity and might also inhibit maternal-fetal viral transmission.

Anti-HIV Agents↗

Ventilation-perfusion-chest radiography match is less likely to represent pulmonary embolism if perfusion is decreased rather than absent.

PURPOSE: The authors' goal was to determine whether the prevalence of pulmonary embolism in patients with matching ventilation-perfusion (V-Q) defects and chest radiographic opacities differs depending on the degree of perfusion deficit (absent versus decreased). METHODS: The authors performed a retrospective analysis of the data obtained from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study. In 233 patients, angiograms were of diagnostic quality for 275 lung zones that showed matching V-Q defects and chest radiographic opacities (triple matches). Of these, V-Q scans and chest radiographs from 217 patients with triple matches in 255 lung zones were retrieved and reviewed. Areas corresponding to chest radiographic opacities were scored as having either decreased perfusion or absent perfusion by consensus. Information regarding the presence or absence of pulmonary embolism in corresponding lung zones was obtained from the PIOPED database. RESULTS: The overall prevalence of pulmonary embolism in all lung zones with triple matches was 27% (69 of 255). Of the 255 areas of triple matches, the perfusion was decreased in 153 (60%) and absent in 102 (40%). The prevalence of pulmonary embolism in areas of triple matches with decreased perfusion and triple matches with absent perfusion was 13% (20 of 153) and 48% (49 of 102), respectively (P = 0.0001 by the chi-square test). When these were divided further by lung zones, triple matches with decreased perfusion and triple matches with absent perfusion in the upper-middle lung zone were associated with a prevalence of 0% (O of 44), and 25% (9 of 36), respectively. The prevalence of pulmonary embolism in areas of triple matches with decreased perfusion and triple matches with absent perfusion in the lower lung zone was 18% (20 of 109), and 61% (40 of 66), respectively. CONCLUSIONS: A V-Q/chest radiographic match is less likely to represent pulmonary embolism if perfusion is decreased rather than absent. The overall prevalence of pulmonary embolism associated with all triple matches in all lung zones varied from very low (0% in this series) to upper intermediate (61 %), depending on whether perfusion was decreased or absent and also on the location of the triple match.

Databases, Factual↗

Importance of perfusate hematocrit for insulin- and glucagon-induced choleresis in the perfused rat liver.

Insulin and glucagon stimulate bile production in the intact rat without affecting the biliary excretion rate of bile acids. This effect was not demonstrable in rat liver perfused with human erythrocytes suspended in a Krebs-Henseleit-bicarbonate buffer at a hematocrit of about 18%. The present experiments demonstrate that the choleretic effect of insulin and glucagon observed in the intact rat is reproducible in perfused rat liver if the hematocrit of the perfusate is raised to about 35%. An increase in perfusate hematocrit is also accompanied by a 65% rise in hepatic oxygen consumption and a 27% rise in the basic production of bile, due to an increase in bile acid-independent bile formation. The mechanism by which these changes in perfusate hematocrit influence the function of the perfused liver is obscure. The difference in oxygen content of the perfusates appears to be without importance. Judged from lactate-pyruvate and beta-hydroxybutyrate-acetoacetate ratios of perfusate as well as electron microscopy, maldistribution of perfusate flow and local hypoxia were not evident in perfusions with low hematocrit. A part of the increase in hepatic oxygen consumption seen with a rise in perfusate hematocrit can, however, be explained by an increase in lactate supply from erythrocyte glycolysis. The results stress the importance of perfusate hematocrit for optimal bile production of the perfused rat liver.

Animals↗

Comparison between the use of whole blood versus a diluted perfusate in regional isolated perfusion by continuous monitoring of transcutaneous oxygen tension: a pilot study.

In 12 successive women (median age, 58 [39-89] years) who were treated with regional isolated perfusion for melanoma of the lower extremities, peroperative continuous monitoring of the transcutaneous oxygen tension (PtcO2) was performed as an indicator for tissue oxygenation and (sub)cutaneous perfusion. Regional perfusion started using whole blood as perfusate with a hematocrit of 40.7 +/- 4.9. After 40 min of drug circulation the perfusate was diluted to a hematocrit of 25.3 +/- 4.9, a value usually applied in perfusion. Flow rates (mean 51.2 +/- 14.4 mL/min/L perfused tissue) were kept at a level that caused no systemic leakage and no more than 10-cm increase above starting venous pressure. Oxygen supply was set at one half of the flow of the perfusate (in mL/min). The mean PtcO2 during the first part of perfusion, in which seven patients could achieve preperfusion levels for at least some of the time, was significantly higher than during the last part, in which no patient reached the preperfusion level (30.8 mm Hg vs 23.5 mm Hg; p = .0019). The mean maximal decrease in PtcO2 after dilution was 21.3 +/- 11.6 mm Hg. Venous blood gases of the perfusate also deteriorated after dilution. Two patients encountered a grade III and two a grade IV toxicity reaction after perfusion. We conclude that increasing the hematocrit of the perfusate to physiologic levels by using whole blood can guarantee a physiologic tissue oxygenation at relatively low flow rates. However, physiologic tissue oxygenation on its own is not enough to prevent toxicity after perfusion.

Adult↗

Cerebral perfusion abnormalities in children with Sturge-Weber syndrome shown by dynamic contrast bolus magnetic resonance perfusion imaging.

OBJECTIVE: Sturge-Weber syndrome is characterized by leptomeningeal angiomatosis and a facial naevus that is usually unilateral. Magnetic resonance imaging is the cornerstone of confirming the disease and judging the extent of the abnormalities. It has been shown, however, that brain perfusion abnormalities on nuclear medicine imaging often are more extensive than the abnormal leptomeningeal enhancement on magnetic resonance. In this article, we assess the utility of magnetic resonance perfusion in demonstrating perfusion abnormalities in pediatric cases of Sturge-Weber syndrome. METHODS: Magnetic resonance perfusion studies were performed on 7 consecutive children who presented to our department with clinically suspected Sturge-Weber syndrome. The extent of time to peak abnormality on dynamic gadolinium bolus magnetic resonance perfusion imaging was compared with the extent of leptomeningeal enhancement and the presence of venous abnormalities. RESULTS: Good magnetic resonance perfusion data were obtained in all 7 cases. Perfusion abnormalities were closely anatomically related to meningeal enhancement on postcontrast T1-weighted imaging. However, perfusion abnormalities were found consistently in the vicinity of developmental venous anomalies that were present in 4 of 7 cases. In 1 child, there was a perfusion deficit in the cerebellar lobe contralateral to the leptomeningeal angiomatosis, consistent with crossed cerebellar diaschisis. CONCLUSIONS: Magnetic resonance perfusion is a sensitive indicator of perfusion abnormalities in Sturge-Weber syndrome and can be performed easily at the same time as the diagnostic scan. Magnetic resonance perfusion imaging therefore is useful in the assessment of this disease. This approach has the extra advantage of correlating the perfusion abnormalities with the high-resolution imaging that is provided from magnetic resonance imaging.

Adolescent↗

The significance of perfusion defect at myocardial perfusion MR imaging in a cat model of acute reperfused myocardial infarction.

OBJECTIVE: To determine whether the size of a perfusion defect seen at myocardial perfusion MR imaging represents the extent of irreversibly damaged myocardium in acute reperfused myocardial infarction. MATERIALS AND METHODS: In nine cats, reperfused myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 90 minutes and subsequent reperfusion for 90 minutes. At single-slice myocardial perfusion MR imaging at the midventricular level using a turbo-FLASH sequence, 60 short-axis images were sequentially obtained with every heart beat after bolus injection of gadomer-17. The size of the perfusion defect was measured and compared with both the corresponding unstained area seen at triphenyl tetrazolium chloride (TTC) staining and the hyperenhanced area seen at gadophrin-2- enhanced MR imaging performed in the same cat six hours after myocardial perfusion MR imaging. RESULTS: The sizes of perfusion defects seen at gadomer-17-enhanced perfusion MR imaging, unstained areas at TTC staining, and hyperenhanced areas at gadophrin-2-enhanced MR imaging were 20.4+/-4.3%, 29.0+/-9.7%, and 30.7+/- 10.6% of the left ventricular myocardium, respectively. The perfusion defects seen at myocardial perfusion MR imaging were significantly smaller than the unstained areas at TTC staining and hyperenhanced areas at gadophrin-2- enhanced MR imaging (p < .01). The sizes of both the perfusion defect at myocardial perfusion MR imaging and the hyperenhanced area at gadophrin-2- enhanced MR imaging correlated well with the sizes of unstained areas at TTC staining (r = .64, p = .062 and r = .70, p = .035, respectively). CONCLUSION: In this cat model, the perfusion defect revealed by myocardial perfusion MR imaging underestimated the true size of acute reperfused myocardial infarction. The defect may represent a more severely damaged area of infarction and probably has prognostic significance.

Animals↗

Acute brain perfusion disorders in children assessed by quantitative perfusion computed tomography in the emergency setting.

OBJECTIVE: Perfusion computed tomography (CT) is a simple imaging technique that allows accurate quantitative assessment of brain perfusion. Perfusion CT is an ideal imaging technique to be used in the emergency setting and has thus gained recognition in the early management of adult acute stroke patients. Perfusion CT can be applied to children successfully by using adequate imaging protocols. The goal of this article is to provide a pictorial essay of the perfusion CT features of diseases that affect brain perfusion as depicted in a population of children who were evaluated in the emergency CT unit of our institution. METHODS: During the period of September 2001 to October 2002, all the children, who were evaluated in the emergency CT unit of our institution and who were prescribed with a cerebral CT and an intravenous administration of iodinated contrast material, underwent a perfusion-CT examination. Perfusion-CT maps were reviewed in the patients diagnosed as abnormal on the basis of follow-up clinical/radiological examinations and correlated with the results of these tests. RESULTS: Brain perfusion-CT examinations have been performed in 77 children. Fifty-three patients were considered as normal, based on normal conventional cerebral CT and normal clinical/radiological follow-up. Perfusion-CT results showed major abnormalities in 14 cases among the 24 remaining patients, related to brain ischemia in 2, head trauma in 9, brain infection in 2, and sickle cell disease in 1. These abnormalities consisted in low regional cerebral blood flow and volume values, and in high mean transit time values. They demonstrated typical anatomical distribution, depending on the considered pathological condition. CONCLUSIONS: Perfusion CT provides quantitative assessment of child brain perfusion disorders. Its ability to be easily performed upon admission makes it an ideal emergency tool that advantageously competes with other imaging techniques such as perfusion-weighted magnetic resonance imaging, despite its limited spatial coverage. Its usefulness with respect to the impact on treatment and outcome, however, remains to be established in further studies.

Adolescent↗