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Myocardial perfusion and perfusion reserve in endurance-trained men.

PURPOSE: This study was undertaken to determine whether endurance training is associated with changes in myocardial perfusion in humans. METHODS: Myocardial perfusion was measured in eleven trained and nine sedentary men at rest and during adenosine-stimulated hyperemia using positron emission tomography (PET). Left ventricular (LV) dimensions and mass were measured using echocardiography. Myocardial work per gram of tissue was calculated as (cardiac output. mean arterial blood pressure)/LV mass. RESULTS: LV mass was significantly higher and myocardial work per gram of tissue lower in the trained than in the untrained subjects. Basal (0.78 +/- 0.10 and 0.76 +/- 0.15 mL. min-1. g-1, P = NS) and adenosine-stimulated perfusion (3.46 +/- 0.91 and 3.14 +/- 0.70 mL. min-1. g-1, P = NS) were similar between trained and untrained men, respectively. Consequently, myocardial perfusion reserve was similar in both groups (4.4 +/- 1.2 and 4.1 +/- 0.7, P = NS). In addition, coronary resistance at baseline (115 +/- 17 vs 119 +/- 22, mm Hg. mL. min-1. g-1, P = NS) and during adenosine infusion (28 +/- 8 vs 30 +/- 8, mm Hg. mL. min-1. g-1, P = NS) were similar in both groups. Resting myocardial work correlated with resting myocardial perfusion in both groups, but the relationship between perfusion and work was different between the groups so that perfusion for a given myocardial work was significantly higher in trained subjects (0.56 +/- 0.04 and 0.34 +/- 0.05 mL. (mm Hg. L)-1, P < 0.001). CONCLUSIONS: These findings suggest that endurance trained subjects do not have different resting or adenosine-stimulated myocardial perfusion. However, the relationship between myocardial perfusion and work appears altered in the athletes.

Adenosine↗

Dynamic perfusion MRI versus perfusion scintigraphy: prediction of postoperative lung function in patients with lung cancer.

OBJECTIVE: The purpose of this study was to determine the capability of dynamic perfusion MRI as an alternative to pulmonary perfusion scintigraphy for prediction of postoperative lung function in patients with lung cancer. SUBJECTS AND METHODS. Sixty patients with lung cancer (35 men, 25 women) underwent dynamic perfusion MRI, perfusion scintigraphy, and preoperative and postoperative pulmonary function tests (forced expiratory volume in 1 sec [FEV(1)]). Perfusion MRIs were obtained with a 3D turbo field-echo sequence (TR/TE, 2.7/0.6; flip angle, 40 degrees; matrix, 128 x 96) using a 1.5-T scanner. Regional blood flow was calculated from the signal intensity-time curves after bolus injection of contrast medium on MRI (Q(MRI)) and uptake ratios of radioisotope on perfusion scintigraphy (Q(PS)). Postoperative lung functions predicted by MRI (FEV(1,MRI)) and perfusion scintigraphy (FEV(1,PS)) were calculated from preoperative FEV(1) and regional Qs. To determine the capability of MRI as an alternative to scintigraphy, we evaluated correlations and the limits of agreement between predicted FEV(1,MRI) and postoperative FEV(1) and between predicted FEV(1,PS) and postoperative FEV(1). RESULTS: The correlation coefficient of postoperative FEV(1) with FEV(1,MRI) (r = 0.93, p < 0.0001) was better than that with FEV(1,PS) (r = 0.89, p < 0.0001). The limits of agreement between postoperative FEV(1) and predicted FEV(1,MRI) (0.9% +/- 10.4%) were smaller than those between postoperative FEV(1) and predicted FEV(1,PS) (2.1% +/- 13.2%). CONCLUSION: Dynamic perfusion MRI is a feasible alternative to pulmonary perfusion scintigraphy for predicting postoperative lung function in patients with lung cancer.

Adult↗

Toward normal perfusion after radiosurgery: perfusion MR Imaging with independent component analysis of brain arteriovenous malformations.

BACKGROUND AND PURPOSE: Brain perfusion is disturbed by cerebral arteriovenous malformations (AVMs). Our study was conducted to determine the radiosurgical effects on this disturbed perfusion. METHODS: MR perfusion imaging with independent component analysis was performed in five healthy subjects and 19 patients with AVM before and after radiosurgery (every 6 months up to 2 years). Perfusion map relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transient time (rMTT) were assessed. Regions of interest (ROIs) on AVM target sections were defined as follows: N, AVM nidus; H, the rest of the ipsilateral hemisphere; P, immediately posterior to the nidus; A, immediately anterior to the nidus; Ar, anterior remote; Pr, posterior remote. Similar ROIs in the contralateral hemisphere (N1, H1, P1, A1, Pr1, and Ar1) served as internal references. Perfusion ratios of ROI-ROI1 were defined. Nonparameteric Mann-Whitney U tests and generalized linear models were used for statistical analysis. RESULTS: Before radiosurgery, patients' H/H1 rCBV and rCBF ratios were significantly higher than those of healthy subjects (P < .005), indicating AVM steal. Three types of perilesional perfusion disturbance were observed. From the first postradiosurgical follow-up at 6 months, N/N1 rCBV and rCBF ratios gradually decreased to 1.0 (both P < .001), whereas rMTT ratios gradually increased to 1.0 (P < .015); H/H1, A/A1, and P/P1 rCBV and rCBF ratios decreased after radiosurgery (P < .005), indicating reversal of steal toward normal perfusion. CONCLUSION: Initial high transnidal flow and perinidal perfusion disturbances were demonstrated. They gradually changed toward normal perfusion after radiosurgery. This explains, in part, the pathophysiologic factors of AVM and therapeutic effects.

Adult↗

Pulmonary perfusion abnormalities and ventilation-perfusion imbalance in children after total repair of tetralogy of Fallot.

The pulmonary perfusion of 25 children who had total surgical correction of tetralogy of Fallot was evaluated by radionuclide perfusion scans. In addition, 18 had 133Xe ventilation studies. Eighteen of the children previously had palliative systemic-pulmonary shunts; 14 had aortic-pulmonary shunts (Waterston or Potts-Smith) and four had Blalock-Taussig shunts. Seven children had single stage total corrections. An asymmetric perfusion pattern was found in 13 of 18 children who previously had systemic-pulmonary shunts, including 12 of 14 with previous aortic-pulmonary shunts (P less than 0.05). The most common finding was relative hypoperfusion of the lung which had received the palliative shunt (P less than 0.001). The distribution of ventilation remained relatively symmetric, even when perfusion was markedly abnormal, and this resulted in ventilation-perfusion imbalance in several patients. Asymmetric perfusion was significantly less common in patients who had undergone single stage corrections (P less than 0.05). The findings document the frequent occurrence of residual abnormalities of pulmonary perfusion and ventilation-perfusion imbalance in patients who have palliative aortic-pulmonary shunts prior to total repair, and support the position that single stage correction is preferable to aortic-pulmonary shunting in the surgical management of tetralogy of Fallot.

Child↗

Combined assessment of technetium-99m SESTAMIBI planar myocardial perfusion images at rest and during exercise with rest/exercise left ventricular wall motion studies evaluated from gated myocardial perfusion studies.

The favorable physical characteristics of technetium-99m-labeled 2-methoxy-2-methylisopropyl-1-isonitril (Tc-SESTAMIBI) enable the combined evaluation of both myocardial perfusion and left ventricular wall motion. To assess the potential of rest and exercise regional myocardial function as an adjunct to planar myocardial perfusion imaging, 60 patients with coronary artery disease and documented arteriographic findings were studied with both protocols during a single study. Exact segmental concordance between myocardial perfusion and wall motion studies was 77% (701/900 segments). Overall sensitivity and specificity to detect hemodynamically significant coronary artery disease with Tc-SESTAMIBI myocardial perfusion imaging were 89% and 79%, respectively, with resting wall motion studies 83% and 71%, respectively, and with rest/exercise wall motion studies, 85% and 71%, respectively. If the results of both perfusion and rest/exercise studies were combined, sensitivity increased to 96% and specificity decreased to 64%. The differences with perfusion studies alone were not statistically significant. Thus despite a good correlation between regional left ventricular function and perfusion, no statistically significant incremental diagnostic value was found when the results of both perfusion and wall motion studies were combined.

Adult↗

Effects of short-term hypothermic perfusion and cold storage on function of the isolated-perfused dog kidney.

The isolated-perfused dog kidney was used as a model to measure the effects of short-term hypothermic preservation on renal function and metabolism. Kidneys were cold-stored in Collins' solution, hypotonic citrate, or phosphate-buffered sucrose for 4 and 24 hr, or were continuously perfused for 4 and 24 hr with a synthetic perfusate. Following preservation kidneys were perfused with an albumin-containing perfusate at 37 degrees C for 60 min for determination of renal function. The results indicate that many of the effects of short-term preservation on renal function in dog kidneys are similar to results reported for rat and rabbit kidneys. Cold storage for 4 hr resulted in a large decrease in GFR (57%), but only a small decrease in Na reabsorption (from 97 to 87%). Cold storage for 24 hr caused a further decline in renal function (GFR = 95% decrease, Na reabsorption = 49-64%). Results were similar for all cold storage solutions tested. Perfusion for 4 hr was less damaging to renal function than cold storage. The GFR decreased only 14% and urine formation and Na reabsorption were practically normal. After 24 hr of hypothermic perfusion, the GFR was reduced by 79%, urine flow was normal, and Na reabsorption was 78%. There were no obvious biochemical correlates (adenine nucleotides, tissue edema, or electrolyte concentration) with the loss of renal function during short-term preservation. The results suggest that the isolated-perfused dog kidney can be used to test the effects of preservation on renal function, and yields results similar to those obtained using small animal models.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antegrade cerebral perfusion with a simplified technique: unilateral versus bilateral perfusion.

BACKGROUND: Selective antegrade cerebral perfusion has been introduced as a strategy of cerebral protection in operations on the aortic arch with hypothermic circulatory arrest. Several techniques of unilateral and bilateral cerebral perfusion have been described with varying results. METHODS: Patients underwent either unilateral cerebral perfusion with a cannula in the right subclavian artery or bilateral cerebral perfusion, with an additional cannula in the left carotid artery. A simplified Seldinger-type technique for subclavian artery cannulation was employed. Results were analyzed with multivariable logistic regression analysis and propensity score analysis to adjust for nonrandomized treatment assignment. RESULTS: Of 65 patients, 17 (26%) had unilateral cerebral perfusion. Mortality was 11% (n = 7); 14% (n = 9) had a stroke. In multivariable analysis, unilateral cerebral perfusion was significantly associated with stroke (odds ratio 6.6 [1.2 to 36]). Age more than 70 years was associated with in-hospital death (odds ratio 12 [1.3 to 113]), and concomitant coronary artery bypass graft surgery was associated with adverse outcome (odds ratio 23 [1.8 to 299]). Balancing variables in a propensity score analysis, stroke remained significantly more common with unilateral brain perfusion (29% versus 0%, p = 0.045). Complications associated with subclavian artery cannulation were encountered in 1 patient (1.5%). CONCLUSIONS: The described cannulation technique is safe and effective. Bilateral cerebral perfusion is easily achieved and is associated with decreased stroke risk, and should be the preferred brain protection strategy.

Aged↗

Single-pass isolated lung perfusion versus recirculating isolated lung perfusion with melphalan in a rat model.

BACKGROUND: Isolated lung perfusion (ILuP) with melphalan (MN) is superior to intravenous infusion for the treatment of pulmonary carcinoma and sarcoma metastases. However, it is unknown whether a bolus injection of MN into the perfusion circuit or ILuP with a fixed concentration of MN will result in the highest lung levels. METHODS: ILuP with 0.5 mg MN was performed in Wag-Rij rats for 30 minutes either by a single-pass system (SP) (fixed concentration) (n = 10) or by reperfusion (RP) (bolus injection) (n = 10). In a separate experiment, rats were perfused with blood as the perfusate. In a third experiment, tumor levels were compared between SP, RP, or intravenous therapy with a dose of 0.5 mg. For induction of pulmonary metastases, 0.5 x 10(6) single adenocarcinoma cells were injected intravenously and therapy was given on day 30. For comparison of drug concentrations, unpaired Student's t test was applied. Statistical significance was accepted at p less than 0.05. RESULTS: Lung perfusion studies were succesfully performed without systemic leakage. Temperature of perfusate and rats was 34 degrees C to 37 degrees C. A significantly higher hematocrit (mean 27.9) compared with buffered starch (mean 2.5) did not result in higher MN lung levels or lower wet-to-dry ratio. Tumor levels were significantly higher after ILuP compared with intravenous therapy. However, no difference in tumor and lung levels was seen between single-pass and reperfusion. CONCLUSIONS: Both ILuP techniques resulted in significantly higher MN lung levels than after intravenous therapy. Because no difference was seen between single-pass and recirculating perfusion, MN can be injected as a bolus into the closed perfusion circuit.

Adenocarcinoma↗

Hydrodynamic and biochemical effects of isolated hypothermic renal perfusion depending on the pump model and perfusion solution.

OBJECTIVES: To evaluate hydrodynamic, biochemical, and histological consequences of hypothermic isolated renal perfusion using a new computerized perfusion system. MATERIALS AND METHODS: The device that allowed us to obtain on renal hydrodynamics during perfusion included multiple parts. The organ was perfused at 4 degrees C with a constant flow either using a classic roller pump or a pump designed in our laboratory to employ vacuum or atmospheric pressure sequentially to achieve a truly pulsatile wave (vacuum-powered tubular pump). The study included 16 minipigs with Eurocollins or Belzer perfusion solutions sampled at predefined interval and histological studies of the organs performed. RESULTS: There was a significant difference in weight increase between the two types of pumps; those perfused with Eurocollins showed greater values than those with Belzer solution. Onset of nitric oxide (NO) in the perfusion solution increased inversely with the renal vascular resistance. The highest NO levels were observed with the Belzer solution and vacuum pump. CONCLUSIONS: Changes in renal hydrodynamics, as induced by perfusion wave form and solution type, may be recorded in real time using a computerized system. A vacuum pump with the Belzer solution achieved the best experimental results.

Animals↗

Reverse cholesterol transport in the rat. Studies using the isolated perfused spleen in conjunction with the perfused liver.

1. A new method combining the use of an isolated perfused extrahepatic tissue with a perfused liver was developed as a model system for the study of reverse cholesterol transport. Rat spleens, initially labelled in vivo with [3H]cholesterol, were perfused for 3 h with whole blood. The spleen was then replaced with an isolated rat liver, whose uptake of cholesterol from the spleen-derived blood and excretion of cholesterol into bile constituents were determined. 2. During spleen perfusion, a net release of cholesterol mass and radioactivity to lipoproteins was observed. 3. During liver perfusion, there was also a rapid exchange or transport of unesterified cholesterol between high-density lipoprotein (HDL) and the liver, in particular with HDL2 (d = 1.085-1.125). 4. The liver showed an increased uptake of cholesteryl ester from serum that had previously been used in spleen perfusion. 5. Approximately half of the [3H]cholesterol released by the spleen was recovered in erythrocytes. During subsequent liver perfusion there was a substantial uptake of radioactivity from the erythrocytes, although less than that recorded from serum lipoproteins. 6. In all experiments there was significant excretion of [3H]cholesterol into bile; most (85%) was in bile acids. Thus the complete process of reverse cholesterol transport is observed in this dual-perfusion system.

Animals↗

The relation between the excretion of sodium and water and the perfusion pressure in the isolated, blood-perfused, rabbit kidney, with special reference to changes occurring in clip-hypertension.

1. The sodium and water excretion rates of rabbit kidneys were studied when isolated and perfused at known pressure with blood from another normal anaesthetized rabbit. Studies at several different perfusion pressures confirmed that a small rise in perfusion pressure caused a large rise in sodium excretion and that the potential sodium-excreting ability of the isolated kidney was high. The curve obtained could be closely fitted by a quadratic equation which allowed an estimate to be made of the blood pressure below which no urine is formed, i.e. the 'theoretical perfusion pressure threshold'. For normal kidneys this was 55-4 mmHg. 2. A group of rabbits had a silver clip applied to the left renal artery and, 3-6 weeks later, the eight most hypertensive animals were selected to provide their kidneys for perfusion. Both kidneys were perfused simultaneously. The clip on the left renal artery was removed immediately before perfusion and the cannula placed distal to the stenosis in the post-stenotic dilatation. The function curves of these kidneys were compared with the curves obtained from normal kidneys. 3. The untouched kidney contralateral to the clip was found to require a significantly higher perfusion pressure (71-7 mmHg) for it to achieve a given sodium excretion rate and, surprisingly, the clipped kidney showed a similar functional change (76-4 mmHg). In other words the positions of both function curves were shifted though their slopes were not much changed. 4. Both kidneys in single-clip-hypertension appear to adapt or reset their sodium excretory behaviour. The resetting in the untouched kidney allows hypertension to be sustained without undue sodium loss. Aldosterone probably contributes little to the resetting. We infer, indirectly, that the normal kidney may, to a significant extent, restrain sodium excretion by virtue of its sympathetic innervation. We also opine that the kidney cannot be assigned fixed intrinsic functional properties on which a renal sodium-handling theory of long-term blood pressure regulation can be firmly based.

Animals↗

Loss of myocardial viability following hypothermic perfusion storage from contaminating trace elements in the perfusate.

Two groups (A and B) of isolated baboon hearts were preserved by continuous hypothermic perfusion storage for 48 hours using perfusates that, according to the manufacturers, differed only in the concentrations of the contaminating trace elements iron, lead, and arsenic. Storage with the perfusate containing the higher concentration of these elements (perfusate B) led to significantly less gain in heart mass, a greater reduction in coronary flow, coronary sinus effluent lactate, and myocardial arteriovenous oxygen difference and a greater increase in coronary sinus effluent lactate dehydrogenase, when compared with perfusate A. Group B hearts totally failed to support the circulation following orthotopic transplantation, whereas group A hearts showed excellent function. Group B hearts had undergone the typical changes of enhanced resting myocardial tension during the storage period (before warm blood reperfusion); we proposed that these changes were brought about by the production of superoxide anions and radicals by the higher relative concentration of iron, or a combination of contaminating trace elements, in perfusate B. To confirm that these perfusates did differ significantly in the concentration of these trace elements, in particular with regard to iron, the superoxide anion activity in both solutions was measured and was found to be significantly higher in perfusate B. The addition of superoxide dismutase to both solutions inhibited superoxide anion activity by more than 80%.

Animals↗

Prevention of initial perfusion failure during xenogeneic ex vivo liver perfusion by selectin inhibition.

BACKGROUND: Endothelial cell activation triggered by xenoreactive antibodies and complement products is the main feature of discordant xenograft rejection. The contribution of early cell-mediated mechanisms to this rejection process is poorly understood, and the function of adhesion molecules in xenogeneic cell interactions in vivo is unclear. The aim of the study was to investigate the role of selectins in mediating cell-dependent initial perfusion failure and functional restrictions in xenoperfused guinea pig (GP) livers. METHODS: Isolated GP livers were hemoperfused in a flow-constant, recirculating perfusion system via the portal vein. Microhemodynamic parameters such as sinusoidal perfusion rate and leukocyte flux were analyzed using intravital fluorescence microscopy. Hepatic oxygen consumption and bile production, as well as liver enzymes, potassium level, and numbers of white blood cells and platelets in the perfusate, were determined. The GP livers were perfused either with GP blood (control perfusion), with unmodified rat blood (xenoperfusion), or with rat blood treated with the selectin-blocking polysaccharide Fucoidin. RESULTS: A significant sinusoidal perfusion failure was observed in the xenoperfusion group, which was accompanied by distinct signs of a functional restriction-like reduced oxygen consumption, bile production, and increased perfusion pressure. However, there were significantly fewer impairments in the Fucoidin group. Furthermore, fewer platelets were trapped and a smaller number of stagnant leukocytes were observed in this group. CONCLUSION: Fucoidin did not suppress complement activation during xenoperfusion. Considering that Fucoidin inhibits the selectin-dependent interactions among white blood cells, platelets, and sulfate-containing proteoglycans on the surface of vascular endothelium, these findings suggest an important role for early cellular interactions in the development of organ failure during xenogeneic rejection.

Animals↗

Effect of perfusion flow rate on the tissue uptake of solutes after dermal application using the rat isolated perfused hindlimb preparation.

The rat perfused hindlimb preparation was investigated as a model to study the dermal clearance and tissue distribution of three solutes with differing physicochemical properties ([3H]water, [3H]diazepam, and [14C]lignocaine). The dermal clearance of each solute increased and the depth of tissue preparation decreased with increasing perfusion flow rate. The half-life for solute efflux from tissues into perfusate, and the peak times for amount of solute in tissue were in the order water > lignocaine > diazepam. Topical iontophoresis, which has previously been shown to achieve similar clearances from topical sites to those seen following passive dermal application, resulted in a clearance of lignocaine in the perfused hindlimb comparable with that obtained in the preparation following passive absorption through exposed dermis. The distribution of capillary blood flow in the perfused hindlimb was quantified using 51Cr-labelled 15-microns microspheres, with greater increases in flow found in deeper muscle tissues with increasing perfusion flow rate compared with superficial layers. Microsphere studies in anaesthetized rats also demonstrate slight differences in the distribution of flow within the hindlimb compared with the perfused preparation. We conclude that the rat perfused hindlimb preparation successfully combines many of the advantages of in-vitro and in-vivo methods and has potential for routine use in the study of solute dermal absorption kinetics.

Animals↗

Effects of perfusion pressure on intracellular calcium, energetics, and function in perfused rat hearts.

Effects of perfusion pressure in a range from 50 to 140 cmH2O on intracellular Ca2+ concentration ([Ca2+]i) were evaluated along with cardiac function, energy metabolism, and left ventricular geometry in a concentration of 2 or 4 mM of extracellular Ca2+ ([Ca2+]o) in isovolumic perfused rat hearts. [Ca2+]i was evaluated with a surface fluorometry technique in hearts loaded with indo-1/AM. The systolic and diastolic values and the amplitude (difference between systolic and diastolic values) of indo-1 fluorescence ratio (an index of [Ca2+]i) were linearly related to perfusion pressure. Changes in the fluorescence ratio were harmonious with rapid changes in left ventricular pressure and stabilized within 30-40 s after changes in perfusion pressure. Developed pressure and O2 consumption were closely, linearly correlated with the fluorescence ratio irrespective of [Ca2+]o. Left ventricular end-diastolic wall thickness, measured by 2-dimensional echocardiography, paralleled perfusion pressure and showed a good correlation with the fluorescence ratio. Diastolic myocardial adenosine 3',5'-cyclic monophosphate significantly decreased only at the lowest perfusion pressure. The ln[phosphocreatine]/[Pi] also changed with altered perfusion pressure. In conclusion, perfusion pressure modulates [Ca2+]i, which in turn regulates myocardial contraction and associated O2 utilization.

Animals↗

Myoelectrical and mechanical activity of isolated canine stomach perfused in vitro with fluorocarbon. Role of glucose, phosphate, calcium and strontium in the perfusate.

Myoelectrical and mechanical activities were recorded from whole isolated canine stomachs perfused, intravascularly, with fluorocarbon emulsion, oxygenated in vitro. The perfusate was composed of an oxygen carrier, fluorcarbon, emulsified with a surfactant added to a simulated physiological solution. Bipolar electrodes and a strain gauge were used for recordings. Stomachs perfused as above for 5 h displayed normal electrical and mechanical activities. 'Normal' meaning identical with those observed under in vivo conditions or during perfusion with homologous blood. Normal response to electrical stimulation of a vagus nerve branch or to intraarterial injection of methacholine or pentagastrin were also observed. These functions of smooth muscles were not altered when glucose-free or glucose-and phosphate-free perfusate were used. In calcium-free perfusate, electrical and mechanical activities were absent and no responses to stimulants used were recorded. When calcium was added to the perfusate, these functions were restored to normal. Strontium was found to be an adequate substitute for calcium in fluorocarbon perfusate. Gastric secretions were alkaline and contained fluorocarbon emulsion.

Animals↗

Comparison of admission perfusion computed tomography and qualitative diffusion- and perfusion-weighted magnetic resonance imaging in acute stroke patients.

BACKGROUND AND PURPOSE: Besides classic criteria, cerebral perfusion imaging could improve patient selection for thrombolytic therapy. The purpose of this study was to compare quantitative perfusion CT imaging and qualitative diffusion- and perfusion-weighted MRI (DWI and PWI) in acute stroke patients at the time of their emergency evaluation. METHODS: Thirteen acute stroke patients underwent perfusion CT and DWI or PWI on admission. The size of infarct and ischemic lesion (infarct plus penumbra) on the admission perfusion CT was compared with that of the MR abnormalities as shown on the DWI trace and on the relative cerebral blood volume, cerebral blood flow, time to peak, and mean transit time maps calculated from PWI studies. RESULTS: The most significant correlation was found between infarct size on the admission perfusion CT and abnormality size on the admission DWI map (r=0.968, P<0.001). A significant correlation was also observed between the size of the ischemic lesion (infarct plus penumbra) on the admission perfusion CT and the abnormality size on the mean transit time map calculated from admission PWI (r=0.946, P<0.001). Information about cerebral infarct and total ischemia (infarct plus penumbra) carried by both imaging techniques was similar, with slopes of 0.913 and 0.905, respectively. CONCLUSIONS: An imaging technique may be helpful in the identification of cerebral penumbra in acute stroke patients and thus in the selection of patients for thrombolytic therapy. Perfusion CT and DWI/PWI are equivalent in this task.

Acute Disease↗

Effect of chlorpromazine on hepatic perfusion and bile secretory function in the isolated perfused rat liver.

The hepatotoxicity of CPZ was studied in the isolated perfused rat liver in order to more closely define possible mechanisms of phenothiazine-induced cholestasis. Perfusate concentrations of CPZ were increased from 5 x 10(-6) M to 5 x 10(-4) M until bile secretion was significantly inhibited. Measurements were then made of determinants of bile secretory function, including the magnitude of lobar distribution of perfusate flow, BAIF, and liver plasma membrane enzyme activity, Na+,K+-ATPase, Mg++-ATPase and 5'-nucleotidase. BAIF diminished significantly from control values of 1.76 +/- 0.07 microliter min-1gm-1 of liver to 1.34 +/- 0.15 and 0.80 +/- 0.09 following 2.5 and 5 x 10(-4) M CPZ, respectively. Perfusate flow also diminished from 5.64 +/- 0.44 to 1.24 +/- 0.12 ml min-1 gm-1 of liver 20 min following 5 x 10(-4) M CPZ and was associated with reduced flow to peripheral areas of the hepatic lobes as demonstrated by Tc-HAM. By 30 min, perfusate flow had returned to baseline values. CPZ also transiently diminished the excretion of bile acids in livers receiving a constant infusion of 40 mumol hr-1 sodium taurocholate. Defects in hepatic perfusion could not account entirely for the impairment in BAIF, since comparable mechanical restriction of perfusate flow in controls only diminished BAIF to 1.49 +/- 0.08 microliter min-1gm-1 of liver. CPZ signofocamt;u rediced tje secofoc actovotu pf Mg++-ATPase and 5'-nucleotidase but did not affect Na+,K+-ATPase in liver plasma membrane isolated 20 min after 5 x 10(-4) M CPZ. CPZ also resulted in a profound shift in the recovery of protein in isolated liver plasma membrane fractions from the light (density = 1.16) to heavier (density = 1.18) fractions. These findings, together with previous observations demonstrating alterations in hepatic ultrastructure, indicate that CPZ interacts in a complex manner with hepatocyte plasma and cytoplasmic membrane components and suggest that these drug-membrane interactions independently result in diminished hepatic perfusion, impairment of bile acid excretion, and inhibition of bile acid-independent bile secretion.

Adenosine Triphosphatases↗