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Effect of the number of projections collected on quantitative perfusion and left ventricular ejection fraction measurements from gated myocardial perfusion single-photon emission computed tomographic images.

BACKGROUND: Gated myocardial perfusion single-photon emission computed tomographic (SPECT) imaging is currently performed by step-and-shoot detector rotation, resulting in acquisition dead time and lengthened study duration compared with nongated SPECT imaging with continuous or pseudocontinuous rotation. Dead time is particularly undesirable in new fast-gated SPECT imaging protocols with inotropic pharmacologic stress. METHODS AND RESULTS: This article evaluated the influence of projections' angular spacing on quantitative measurements of left ventricular ejection fraction (LVEF) and perfusion from postexercise 99mTc-labeled sestamibi images. Gated 60-projection data sets from 30 patients were compacted into 30- and 15-projection sets. The three sets (corresponding to 3-, 6-, and 12-degree spacing over 180 degrees) were reconstructed into gated and ungated short-axis image sets. LVEFs were measured from the gated images according to a previously described automatic algorithm, whereas perfusion was assessed from the ungated images by a 20-segment division of their maximal pixel polar maps. LVEF values were essentially unchanged between 60- and 30-projection images (y = 0.37 + 0.996x; r = 0.999; standard error of the estimate = 0.56) and 60- and 15-projection images (y = 1.35 + 0.987x; r = 0.999; standard error of the estimate = 0.77) in the 30 patients. Overall, 30- and 15-projection polar maps differed by 1.87% +/- 1.24% and 4.38% +/- 2.25% from the 60-projection polar maps, respectively. Segmental perfusion score agreement between 60- and 30-projection images and between 60- and 15-projection images was 93% (kappa = 0.92; p < 0.001) and 83% (kappa = 0.81; p < 0.001), respectively. Sixty- and 30-projection images were visually undistinguishable, whereas loss of image resolution was noticed in many 15-projection gated and ungated images. CONCLUSIONS: Thirty-projection gated SPECT imaging is a practical, accurate, and time-saving approach in standard gated protocols and, potentially, fast-gated protocols. Fifteen-projection gated SPECT imaging is not generally recommended and should be considered only for LVEF assessment in conjunction with fast-gated protocols.

Aged↗

A reverse perfusion pattern during Technetium-99m stress myocardial perfusion imaging does not predict flow limiting coronary artery disease.

BACKGROUND: A reverse redistribution pattern during myocardial perfusion imaging is most widely described using thallium (Tl-201), when stress images exhibit greater perfusion than rest. Technetium (Tc-99 m) radiopharmaceuticals may also yield a reverse perfusion (RP) pattern, but its significance is uncertain. This study tested the hypothesis that RP correlates with the presence and location of flow limiting coronary stenosis(es). METHOD: We reviewed 842 consecutive Tc-99 m tetrofosmin SPECT stress studies performed at a cardiothoracic centre over a 15 month period. 69 (8.2%) demonstrated RP. Thirty-three patients (age 32-79 mean 56, 17 female) had undergone cardiac catheterisation within 12 months of the scan. Correlation was sought between the presence and location of angiographic stenoses and RP pattern. RESULTS: 10/33 (30.3%) had significant (>60%) coronary stenosis(es); 5 single-vessel, 2 two-vessel and 3 three-vessel disease (3VD). Stenosis location correlated poorly with the RP territory (LAD/Anterior 5/17, RCA/Inferior 1/10, Cx/lateral 0/4 (p = 0.57)). Of the 6 patients with a lesion in the RP territory, 3 had 3VD; 2 of these had a simultaneous reversible defect. All 5 patients with previous myocardial infarction had a simultaneous fixed defect. However only 3/12 with co-existent reversible defects had significant disease. CONCLUSION: The reverse perfusion pattern is a poor predictor of flow limiting coronary disease, and does not correlate with stenosis location in those with significant lesions. Such patients should not undergo invasive investigation purely on the basis of this result.

Adult↗

Accuracy of the automated assessment of left ventricular function with gated perfusion SPECT in the presence of perfusion defects and left ventricular dysfunction: correlation with equilibrium radionuclide ventriculography and echocardiography.

BACKGROUND: Gated single photon emission computed tomography (SPECT) with automated methods allows the quantitative assessment of left ventricular function and perfusion; however, its accuracy must be defined for patients with large earlier infarctions and severe rest perfusion defects, in whom the estimation of endocardial and epicardial borders might be more difficult, even with automated edge-detection techniques. METHODS AND RESULTS: We prospectively compared the automated measurements of left ventricular ejection fraction (LVEF) and volumes from rest-injected gated Technetium 99m (Tc99m) perfusion SPECT with equilibrium radionuclide angiocardiography (ERNA) in 62 patients and the assessment of regional function with echocardiography in 22 patients. Forty-six patients had an earlier myocardial infarction (mean defect size, 34% of left ventricle; SD, 12.7%; range, 8% to 56%); 27 patients had large defects (> or = 20% of left ventricle; LVEF range, 8% to 75%). LVEF, as determined with Cedars-Sinai software (quantitative gated SPECT), correlated well with ERNA (r = 0.941; y = 1.003x + 1.15; P<.0001; SE of the estimate = 6.3%; mean difference -1.3% for LVEF) in the entire study population and in the subgroups of patients with an earlier infarction, severe defects, and large infarctions (> or = 20% of the left ventricle). A correlation existed between gated SPECT and ERNA volumes (r = 0.882, y = 1.040x - 14.7, P<.0001 for end-diastolic volume; r = 0.954, y = 1.147x - 13.9, P<.0001 for end-systolic volumes with the count-ratio technique), but with wider limits of agreement. The exact segmental score agreement between gated SPECT and echocardiography for regional function was 79.8% (281 of 352, kappa = 0.682). CONCLUSIONS: Automated gated SPECT provides an accurate assessment of ejection fraction and regional function, even in the presence of an earlier myocardial infarction with large perfusion defects and significant left ventricular dysfunction.

Echocardiography↗

Protective effect of aminophylline on renal perfusion changes induced by high-energy shockwaves identified by Gd-DTPA-enhanced first-pass perfusion MRI.

PURPOSE: The purpose of this study was to evaluate regional renal hemodynamics in a noninvasive manner using gadolinium-DPTA magnetic resonance imaging (MRI) before and after extracorporeal shockwave lithotripsy (SWL). In addition, the renoprotective effect of intravenous aminophylline was evaluated on the perfusion on kidneys undergoing SWL. PATIENTS AND METHODS: Ten randomly selected patients were evaluated for regional renal blood flow in the cortex and medulla with Gd-DTPA MRI studies within 2 weeks before and 4 hours after SWL. Five of these patients were treated with 500 mg of intravenous aminophylline 45 minutes prior to SWL. Renal hemodynamics were assessed utilizing relative perfusion indices (PI) calculated from signal intensity-v-time curves obtained from regions of interest (ROI). The ROI choice was based on the contrast-enhanced MRI images. Relative PIs of pre-SWL and post-SWL studies were compared in the first group of patients. Relative PIs of the treated kidney were compared with those of the contralateral kidney in the second group of patients, who received aminophylline. RESULTS: In the group not treated with aminophylline, there was no significant difference in cortical perfusion before SWL (average PI -7+/-3%). However, after lithotripsy, there was a reduction of cortical flow (average PI 31+/-12%) in the treated kidney. In the group treated with aminophylline, renal hemodynamics study after SWL revealed no significant difference in relative perfusion (average PI -8+/-6%). Relative PIs of the medulla were small for all patients, but standard errors were large, indicating a wide range of values. CONCLUSIONS: This study helps to establish reduced cortical flow after SWL and demonstrates that aminophylline attenuated this response in the kidneys subjected to lithotripsy. It appears that aminophylline administration causes no alteration in medullary blood flow.

Aminophylline↗

Effects of feeding high-fat diets to rats: metabolism of erucic acid (C 22:1 n-9) in the perfused liver and secretion of metabolites to the perfusate.

The liver metabolism of erucic acid, 22:1 n-9, was studied in rat livers perfused with 14-14C-labelled erucic acid for 15 and 60 min, determining the distribution of radioactivity in the perfusate and in the lipids of the liver cell organelles. The rats were adapted to a high-fat diet containing either partially hydrogenated marine oil (PHMO) or palm oil (PO), both adjusted to a 10% content of linoleic acid. The results showed an efficient uptake and metabolism of erucic acid with the secretion to the perfusate medium of labelled free fatty acids other than erucic acid, labelled phospholipids as well as water soluble oxidation products. Only minor amounts of secreted labelled triglycerides were found within 60 min of perfusion. In the liver, labelled lipids accumulated in the endoplasmic reticulum, after 15 min mainly as free fatty acids, after 60 min as triglycerides. The esterification pathway, including the erucic acid given as well as chain-shortened fatty acids, seemed to be preferred under the experimental conditions and with adequate linoleic acid in the diet. A chain shortening of erucic acid probably took place in both peroxisomes and mitochondria shown by the presence of labelled 18:1 and 20:1 in the organelle-bound phospholipids. A chain shortening was found in both dietary groups, and is assumed to be an affect of the adaptation to a high-fat diet rather than an effect of dietary very long chain monoenoic fatty acids. Somewhat higher levels were found in the PHMO group, but the difference in the dietary fat was not a major factor in the liver lipid adaptation.

Animals↗

Effects of perfusion pressure and renal flow upon albumin excretion in isolated perfused kidneys.

To explore the effects of renal hemodynamics upon urinary albumin excretion, sequential changes in perfusion pressure and/or flow were performed in isolated perfused rat kidneys. Elevation of perfusion pressure from 90 to 130 mm Hg increased renal flow from 48.9 +/- 1.1 to 54.3 +/- 1.4 ml/min and glomerular filtration rate (GFR) from 0.37 +/- 0.03 to 0.81 +/- 0.06 ml/min (p less than 0.001). Despite more than a doubling in GFR, albumin excretion remained unchanged (from 252 +/- 53 to 167 +/- 36 micrograms/min, p not significant), resulting in a decreased fractional clearance of albumin (theta) from 0.009 +/- 0.002 to 0.004 +/- 0.005 ml/min (p less than 0.01). To dissociate the effects of flow from those of pressure, angiotensin II was infused to decrease renal flow from 49.9 +/- 0.6 to 38.7 +/- 0.6 ml/min (p less than 0.001), while keeping perfusion pressure constant at 96 +/- 1 mm Hg. Although GFR was essentially unchanged (from 0.59 +/- 0.02 to 0.65 +/- 0.05 ml/min, p not significant), albumin excretion increased from 68 +/- 8 to 151 +/- 21 micrograms/min (p less than 0.001) and theta rose from 0.002 +/- 0.000 to 0.005 +/- 0.001 (p less than 0.02). Whole kidney hemodynamics acutely affect renal excretion of albumin in isolated kidneys.

Albuminuria↗

Comparison between echo contrast agent-specific imaging modes and perfusion-weighted magnetic resonance imaging for the assessment of brain perfusion.

BACKGROUND AND PURPOSE: Contrast burst imaging (CBI) and time variance imaging (TVI) are new ultrasonic imaging modes enabling the visualization of intravenously injected echo contrast agents in brain parenchyma. The aim of this study was to compare the quantitative ultrasonic data with corresponding perfusion-weighted MRI data (p-MRI) with respect to the assessment of brain perfusion. METHODS: Twelve individuals with no vascular abnormalities were examined by CBI and TVI after an intravenous bolus injection of 4 g galactose-based microbubble suspension (Levovist) in a concentration of 400 mg/mL. Complementary, a dynamic susceptibility contrast MRI, ie, p-MRI, of each individual was obtained. In both ultrasound (US) methods and p-MRI, time-intensity curves were calculated offline, and absolute time to peak intensities (TPI), peak intensities (PI), and peak width (PW) of US investigations and TPI, relative cerebral blood flow (CBF) and relative cerebral blood volume (CBV) of p-MRI examinations were determined in the following regions of interest (ROIs): lentiform nucleus (LN), white matter (WM), posterior (PT), and anterior thalamus (AT). In addition, the M(2) segment of the middle cerebral artery (MCA) was evaluated in the US, and the precentral gyrus (PG) was examined in the p-MRI examinations. In relation to a reference parenchymal ROI (AT), relative TPIs were compared between the US and p-MRI methods and relative PI of US investigations with the ratio of CBF (rCBF) of p-MRI examinations in identical ROIs. RESULTS: Mean TPIs varied from 18.3+/-5.0 (AT) to 20.1+/- 5.8 (WM) to 17.2+/-4.9 (MCA) seconds in CBI examinations and from 19.4+/-5.3 (AT) to 20.4+/-4.3 (WM) to 17.3+/-4.0 (MCA) seconds in TVI examinations. Mean PIs were found to vary from 581.9+/-342.4 (WM) to 1522.9+/-574.2 (LN) to 3400.9+/- 621.7 arbitrary units (MCA) in CBI mode and from 7.5+/-4.6 (WM) to 17.5+/-4.9 (LN) to 46.3+/-7.1 (MCA) arbitrary units in TVI mode. PW ranged from 7.3+/-4.5 (AT) to 9.1+/-4.0 (LN) to 24.3+/-12.8 (MCA) seconds in CBI examinations and from 7.1+/-3.9 (AT) to 8.7+/-3.5 (LN) to 26.7+/-18.2 (MCA) seconds in TVI examinations. Mean TPI was significantly shorter and mean PI and mean PW were significantly higher in the MCA compared with all other ROIs (P<0.05). Mean TPI of the p-MRI examinations ranged from 22.0+/-6.9 (LN) to 23.0+/-6.8 (WM) seconds; mean CBF ranged from 0.0093+/- 0.0041 (LN) to 0.0043+/-0.0021 (WM). There was no significant difference in rTPI in any ROI between US and p-MRI measurements (P>0.2), whereas relative PIs were significantly higher in areas with lower insonation depth such as the LN compared with rCBF. CONCLUSIONS: In contrast to PI, TPI and rTPI in US techniques are robust parameters for the evaluation of cerebral perfusion and may help to differentiate physiological and pathological perfusion in different parenchymal regions of the brain.

Adult↗

Comparison of perfusion computed tomography and computed tomography angiography source images with perfusion-weighted imaging and diffusion-weighted imaging in patients with acute stroke of less than 6 hours' duration.

BACKGROUND AND PURPOSE: We aimed to determine the diagnostic value of perfusion computed tomography (PCT) and CT angiography (CTA) including CTA source images (CTA-SI) in comparison with perfusion-weighted magnetic resonance imaging (MRI) (PWI) and diffusion-weighted MRI (DWI) in acute stroke <6 hours. METHODS: Noncontrast-enhanced CT, PCT, CTA, stroke MRI, including PWI and DWI, and MR angiography (MRA), were performed in patients with symptoms of acute stroke lasting <6 hours. We analyzed ischemic lesion volumes on patients' arrival as shown on NECT, PCT, CTA-SI, DWI, and PWI (Wilcoxon, Spearman, Bland-Altman) and compared them to the infarct extent as shown on day 5 NECT. RESULTS: Twenty-two stroke patients underwent CT and MRI scanning within 6 hours. PCT time to peak (PCT-TTP) volumes did not differ from PWI-TTP (P=0.686 for patients who did not undergo thrombolysis/P=0.328 for patients who underwent thrombolysis), nor did PCT cerebral blood volume (PCT-CBV) differ from PWI-CBV (P=0.893/P=0.169). CTA-SI volumes did not differ from DWI volumes (P=0.465/P=0.086). Lesion volumes measured in PCT maps significantly correlated with lesion volumes on PWI (P=0.0047, r=1.0/P=0.0019, r=0.897 for TTP; P=0.0054, r=0.983/P=0.0026, r=0.871 for CBV). Also, PCT-CBV lesion volumes significantly correlated with follow-up CT lesion volumes (P=0.0047, r=1.0/P=0.0046, r=0.819). CONCLUSIONS: In hyperacute stroke, the combination of PCT and CTA can render important diagnostic information regarding the infarct extent and the perfusion deficit. Lesions on PCT-TTP and PCT-CBV do not differ from lesions on PWI-TTP and PWI-CBV; lesions on CTA source images do not differ from lesions on DWI. The combination of noncontrast-enhanced CT (NECT), perfusion CT (PCT), and CT angiography (CTA) can render additional information within <15 minutes and may help in therapeutic decision-making if PWI and DWI are not available or cannot be performed on specific patients.

Adult↗

Perfusion measurement in acute pancreatitis using dynamic perfusion MDCT.

OBJECTIVE: Our objective was to determine whether MDCT with perfusion imaging could help in assessing the severity of acute pancreatitis in the initial phase of the disease. One hundred six patients with abdominal pain were prospectively enrolled in this study. CONCLUSION: Patients were separated into two groups: P1 (severe) and P2 (mild) acute pancreatitis. Mean perfusion value was 24.8 mL/100 mL/min in the P1 group and 50.5 mL/100 mL/min in the P2 group (p = 0.0016, significant). Our preliminary data suggest that pancreatic perfusion measurement using MDCT with perfusion imaging could help in assessing the severity of acute pancreatitis.

Acute Disease↗

Magnetic resonance imaging of myocardial perfusion in single-vessel coronary artery disease: implications for transmural assessment of myocardial perfusion.

The purpose of the study was to investigate the potential of magnetic resonance imaging (MRI) to assess transmural differences in myocardial perfusion. Contrast-enhanced MRI was performed at rest and during hyperemia in a dog model and in 22 patients with single-vessel coronary artery disease. From MR signal intensity-versus-time curves, three perfusion parameters were derived: maximum myocardial contrast enhancement (MCE), slope, and inverse mean transit time (1/MTT). In dogs, MCE correlated well (r = 0.87, p < 0.00001) with microsphere-assessed myocardial blood flow. In the patients, the subendocardial MCE decreased during hyperemia (0.89 +/- 0.18 vs. 0.74 +/- 0.15, p < 0.003) and was lower in subendocardium than in subepicardium (0.74 +/- 0.15 vs. 0.84 +/- 0.21, p < 0.02). Parameters slope and 1/MTT paralleled MCE. Contrast-enhanced MRI reflects the transmural redistribution of myocardial perfusion during hyperemia. Perfusion abnormalities can be identified most distinctly in subendocardial myocardium.

Adult↗

Gated spect myocardial perfusion scintigraphy for identifying septal perfusion artifacts in left bundle branch block.

OBJECTIVE: To determine the role of gated Single Photon Emission Computed Tomography (SPECT) for accurate assessment of myocardial perfusion scintigraphy (MPS) of patients with left bundle branch block (LBBB). DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Punjab Institute of Nuclear Medicine (PINUM), Faisalabad, Pakistan, from June 2002 to April 2003. PATIENTS AND METHODS: MPS data of patients with LBBB was analyzed. Resting gated SPECT MPS was performed after an injection of 740 MBq 99mTc-MIBI in 10 normal and 25 subjects with LBBB (with low probability of coronary artery disease). Visual and quantitative analyses were done on non-gated (NG), end diastolic (ED), end systolic (ES) images. Calculations included septal to lateral wall ratio (SLR), myocardial thickening (MT=% increase in counts during systole) at end systolic phase and myocardial thickening at peak level (% peak MT). RESULTS: Septal hypoperfusion was noted in 19 (76%) patients on NG images and in only 1 (4%) patient on gated SPECT ED images. On NG images of LBBB group, SLR was lower than in controls (0.68+/-0.07 vs. 0.87+/-0.05, p<0.001). SLR of LBBB patients approached to that of control group in gated SPECT ED data (0.86+/-0.06 vs 0.88+/-0.06, p=ns). Myocardial thickening at ES for septum was markedly lower in LBBB group than in controls (21.83%+/-10.86 vs. 66.32%+/-20.15, p<0.001). CONCLUSION: In patients with LBBB, reduced septal thickening results in artifactual septal perfusion defects. Gating the perfusion scintigraphy and reporting perfusion status on end diastolic frames in LBBB patients can eliminate these artifacts.

Adult↗

Distinguishing between anterior cerebral artery and middle cerebral artery perfusion by color-coded perfusion direction mapping with arterial spin labeling.

The purpose of this study was to evaluate collateral circulation by describing anterior cerebral artery and middle cerebral artery perfusion areas. Pairs of image sets spin labeled on the medial and lateral side were used. A pixel-by-pixel t test was performed, with blue gradation used to display lateral perfusion (ie, middle cerebral artery) and orange gradation for anterior cerebral artery perfusion. Extensions of anterior cerebral artery perfusion areas in cases of middle cerebral artery stenosis were described. This method may aid in estimation of collateral circulation for stroke treatment.

Cerebral Angiography↗

Perfusion-weighted MR imaging studies in brain hypervascular diseases: comparison of arterial input function extractions for perfusion measurement.

BACKGROUND AND PURPOSE: Brain hypervascular diseases are complex and induce hemodynamic disturbances on brain parenchyma, which are difficult to accurately evaluate by using perfusion-weighted (PWI) MR imaging. Our purpose was to test and to assess the best AIF estimation method among 4 patients with brain hypervascular disease and healthy volunteers. METHODS: Thirty-three patients and 10 healthy volunteers underwent brain perfusion studies by using a 1.5T MR imaging scanner with gadolinium-chelate bolus injection. PWI was performed with the indicator dilution method. AIF estimation methods were performed with local, regional, regional scaled, and global estimated arterial input function (AIF), and PWI measurements (cerebral blood volume [CBV] and cerebral blood flow [CBF]) were performed with regions of interest drawn on the thalami and centrum semiovale in all subjects, remote from the brain hypervascular disease nidus. Abnormal PWI results were assessed by using Z Score, and evaluation of the best AIF estimation method was performed by using a no gold standard evaluation method. RESULTS: From 88% to 97% of patients had overall abnormal perfusion areas of hypo- (decreased CBV and CBF) and/or hyperperfusion (increased CBV and CBF) and/or venous congestion (increased CBV, normal or decreased CBF), depending on the AIF estimation method used for PWI computations. No gold standard evaluation of the 4 AIF estimates found the regional and the regional scaled methods to be the most accurate. CONCLUSION: Brain hypervascular disease induces remote brain perfusion abnormalities that can be better detected by using PWI with regional or regional scaled AIF estimation methods.

Adolescent↗

[Color coded ultrasound--quantification of perfusion in a perfusion model].

This experimental study demonstrates the quantification of perfusion in a phantom-simulating tissue using a computer-assisted interpretation. The parameters flow volumin, velocity (defined by pulse-repetition-frequency-PRF), and the time of adding up peaks were varied. The detected color-coded pixels determine the flow area as a percentage of the ground area and the frequency with the highest pixel density. The width is the area between the highest and lowest detected frequencies. The flow area correlates with the perfusion rate (r > or = 0.97). To detect low perfusions, a slow velocity and extended Peak Hold-function are necessary. Peaks with a high frequency superpose those with lower frequencies, so that these signals are not available for the interpretation. To determine the width or the frequency with highest pixel density a short Peak Hold-function must be chosen. When changing the velocity, these quantities are also changed, so that standards are necessary. This study shows a correlation between a defined perfusion in a phantom-simulating tissue and the flow area. It suggests a possibility to quantify flow in different organs. One aim would be to determine abnormal vascularisation, for example, in tumours of the liver or breast.

Blood Flow Velocity↗

Improved machine perfusion preservation of the non-heart-beating donor rat liver using Polysol: a new machine perfusion preservation solution.

Waiting lists for transplantation have stimulated interest in the use of non-heart-beating donor (NHBD) organs. Recent studies on organ preservation have shown advantages of machine perfusion (MP) over cold storage (CS). To supply the liver with specific nutrients during MP, the preservation solution Polysol was developed. The aim of our study was to compare CS in University of Wisconsin solution (UW) with MP using UW-gluconate (UW-G) or Polysol in an NHBD model. After 30 minutes of warm ischemia, livers were harvested from rats for preservation by either CS, MP-UW-G, or MP-Polysol. After 24 hours of preservation, livers were reperfused with Krebs-Henseleit buffer (KHB). Perfusate samples were analyzed for liver damage and function. Biopsies were examined by hematoxylin and eosin staining and transmission electron microscopy. Liver damage was highest after CS compared with the MP groups. MP using Polysol compared with UW-G resulted in less aspartate aminotransferase (AST) and alanine aminotransferase (ALT) release. Perfusate flow, bile production, and ammonia clearance were highest after MP-Polysol compared with CS and MP-UW-G. Tissue edema was least after MP-Polysol compared with CS and MP-UW-G. In conclusion, preservation of the NHBD rat liver by hypothermic MP is superior to CS. Furthermore, MP using Polysol results in better-quality liver preservation compared with using UW-G.

Animals↗

A comparison of AMP degradation in the perfused rat heart during 2-deoxy-D-glucose perfusion and anoxia. Part I: The release of adenosine and inosine.

AMP degradation is studied in two models of the Langendorff-perfused rat heart which generate a large release of purines: the 2-deoxy-D-glucose (2DG)-perfused heart and the anoxic heart. In the 2DG model, mitochondrial energy generation is quasi-normal, despite a very low ATP concentration. Furthermore, inorganic phosphate (Pi) concentration is low, an important difference with anoxia where Pi is very high, up to 82 mM. Coronary release of purines is measured by high performance liquid chromatography, and myocardial metabolite content by 31P nuclear magnetic resonance spectroscopy. In the 2DG-perfused hearts with glucose or acetate, the purine release consists nearly exclusively of inosine [up to 130 nmol/(min x gww)] while adenosine is less than 1 nmol/(min x gww). A possible interpretation is that AMP degradation proceeds mainly through deamination to inosine monophosphate by AMP deaminase (the IMP pathway). In contrast, the purine release in anoxia (100% N2) contains comparable quantities of adenosine and inosine [respectively 30 and 20 nmol/(min x gww)], indicating that part of AMP is dephosphorylated directly to adenosine. Comparison with the 2DG model suggests that the release of adenosine in the anoxic heart is a result of inhibition of AMP deaminase by Pi.

Adenosine↗

AMP degradation in the perfused rat heart during 2-deoxy-D-glucose perfusion and anoxia. Part II: The determination of the degradation pathways using an adenosine deaminase inhibitor.

Using the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), we determine the contribution of the adenosine pathway to the abundant purine release of two Langendroff-perfused rat heart models which differ particularly in inorganic phosphate (Pi) content: the 2-deoxy-D-glucose (2DG) perfused heart and the anoxic heart. We measure the release of coronary purines by high performance liquid chromatography, and the content of myocardial metabolites by 31P nuclear magnetic resonance spectroscopy. In the 2DG-perfused heart (2 mM for 45 min), the release of inosine [130 nmol/(min.gww)] is much larger than that of adenosine, and EHNA (50 microM) has little effect, showing that the pathway of inosine monophosphate (IMP) accounts for 97% of purine catabolism. In the anoxic heart (100% N2 for 45 min), where inosine and adenosine release are comparable in the absence of EHNA, the inhibitor reduces the release of inosine and catabolites from 50 to 20 nmol/(min.gww) and increases that of adenosine [from 30 to 55 nmol/(min.gww)], showing that the contributions of the IMP and adenosine pathways are 23 and 77%. The difference between the two models has been ascribed to the inhibition of AMP deaminase by Pi in the anoxic heart (Chen W, et al., 1996). We discuss the physiological significance of this heart-specific duality of degradation pathways.

Adenine↗

Renovascular responses to high and low perfusate calcium steady-state experiments in the isolated perfused rat kidney with baseline vascular tone.

Acute hypercalcemia is commonly observed in surgical patients after calcium infusion while acute hypocalcemia is common during rapid citrated blood transfusion. Although high and low ionized calcium ([Ca2+]) within the clinical range produce an increase or decrease in cardiac performance and systemic vessel resistance, respectively, their effects on renal vessels have not been quantified. A possible renal vasoconstriction that might occur with high [Ca2+] is of clinical interest because it is a factor which may contribute to impaired renal circulation and decreased function. In this study we examined the renovascular responses to [Ca2+], which was varied within the clinical range under hemodynamically controlled conditions. We instituted high and low [Ca2+] in the per fusate, which consisted of Krebs-Henseleit buffer containing albumin, 60-65 g/liter. Stable high (n = 10) or low (n = 7) [Ca2+] (1.93 +/- 0.02 and 0.59 +/- 0.01 mM, respectively) was instituted for 10 min and preceded and followed by normal [Ca2+] of the same duration. In a separate protocol (n = 8) verapamil (10(-5) M) was added to the perfusate 10 min before high [Ca2+] was tested. We measured changes in renal flow at a constant perfusion pressure of 110 mm Hg and also characterized the renal vessels over a range of pressures by pressure vs flow plots. High [Ca2+] was associated with a small decrease in flow (from 28.8 +/- 2.4 to 26.9 +/- 2.6 ml/min/g, P < 0.02), indicating a small vasopressor effect. This effect was also shown by a leftward shift in the pressure vs flow plots. These changes were prevented by verapamil. GFR decreased (from 0.35 +/- 0.04 to 0.28 +/- 0.06 ml/min/ g, P < 0.01) without a significant change in sodium excretion or fractional sodium excretion. Low [Ca2+] was associated with increased renal flow (from 30.8 +/- 2.1 to 35.2 +/- 2.7 ml/min/g, P < 0.02), indicating a vasodilator effect. This effect was also shown by a rightward displacement of the pressure vs flow plots. GFR increased from 0.51 +/- 0.03 to 0.56 +/- 0.04 ml/min/ g, P < 0.01, as did sodium excretion (from 2.32 +/- 0.22 to 3.87 +/- 0.49 microEq/min, P < 0.01) and fractional sodium excretion (from 2.33 +/- 0.26 to 3.61 +/- 0.49%, P < 0.01). We conclude, first, that in the isolated perfused rat kidney, high [Ca2+] is a weak vasopressor while low [Ca2+] has vasodilator action. Second, high [Ca2+] effects are abolished by verapamil pretreatment. These findings illuminate mechanisms of high [Ca2+] effects on renovascular tone.

Animals↗