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The effect of acidosis on lactate removal by the perfused rat kidney.

1. The isolated perfused kidneys of fed rats in normal acid-base status showed a constant rate of lactate removal from the perfusate between 5 and 90 min of perfusion at a perfusate pH of 7-4-7-5. 2. Lactate removal by kidneys of rats in normal acid-base status was stimulated within 30 min by a reduction in perfusate pH to 7-1-7-2, but depressed when perfusate pH was reduced further. 3. Kidneys taken from rats previously made acidotic and perfused with media of various pH values showed a progressive fall in the rate of lactate removal during the perfusion. 4. Glucose output by the kidneys of rats in normal acid-base status perfused with lactate as substrate was not affected by an alteration in perfusate pH. The kidneys of acidotic rats generally showed an increased rate of glucose output compared with those of control rats.

Acid-Base Imbalance↗

Perfusate composition influences nitric oxide homeostasis in rat juxtamedullary afferent arterioles.

AIM: Vascular diameters in isolated juxtamedullary nephron preparations perfused with cell-free solutions differ from those perfused with blood. In the present study, the effects of the albumin content of the perfusate on the afferent arteriolar diameter and endothelial nitric oxide were investigated in the isolated juxtamedullary nephron preparation perfused with Krebs-Ringer-bicarbonate buffer containing albumin in different concentrations. METHODS: The endothelium was loaded with DAF-FM DA, a nitric oxide-sensitive fluoroprobe. Perfusion was maintained either with 4% (control group), 10 or 20% albumin in the perfusate or with L-NAME (10-4 m) added to the perfusate. Fluorescent images were obtained and stored for evaluation of DAF-FM fluorescence and vascular diameters (in mid-afferent arterioles) immediately before perfusate change and every 15 min thereafter, for a 2-h period. RESULTS: Increasing the albumin concentration resulted in a decrease in fluorescence. The most rapid decline of fluorescence was obtained following L-NAME administration (relative fluorescence after 2 h: 4% albumin 92.4 +/- 5.3%; 10% albumin 79.5 +/- 4.2%; 20% albumin 66.2 +/- 2.6%; L-NAME 55.4 +/- 3.0%; mean +/- SD, n = 5). A dose-dependent constriction of the afferent arterioles was observed (normalized diameter: 4% albumin 99.8 +/- 3.0%; 10% albumin 80.3 +/- 3.3%; 20% albumin 74.3 +/- 3.2%; L-NAME 70.6 +/- 3.5%). CONCLUSION: We propose that albumin interferes with arteriolar nitric oxide homeostasis, probably by scavenging nitric oxide intra-luminally. In this respect, albumin acts similarly to red blood cells in the circulation. The magnitude of the scavenging determines the effectiveness of autoregulation in the perfused preglomerular vessels. The scavenging properties of the perfusing fluid are important in setting operating levels of endothelial nitric oxide.

Albumins↗

[The isolated perfused rat pancreas - an experimental model for investigation the early events in the pathogenesis of acute pancreatitis].

METHODS: External perfusions of the pancreatic glands of Wistar-rats were done, using a modified Krebs-Ringer-Buffer (KRB). We looked for an elevation of amylase, lipase and lactate-dehydrogenase in the effusion fluid (portal outflow fluid). We investigated a normal perfusion (KRB, 60 minutes), a long term perfusion (KRB, 240 minutes) and a perfusion (60 minutes) including an additive of the detergents triton x-100 or the cholecystokinin analogue ceruletid (10(-8) M). RESULTS: An isolated external perfusion of a rat pancreas is possible without inducing any increase of parameters of damage such as amylase, lipase or lactate-dehydrogenase in the outflow medium. The perfusion time should be limited to 80 minutes including a 20 minutes equilibration period. A damage of pancreatic parenchyma is indicated by increased levels of pancreatic enzymes in the perfusion medium. Such damage can be induced by various noxious substances like detergents or cerulein, which has a significance in the pathophysiology of experimental acute pancreatitis. A significant increase (p < 0.01) of lactate-dehydrogenase, lipase and amylase was found 10, 20 and 30 minutes after an application of triton x-100. During a perfusion with the cholecystokinin analogue ceruletid (10(-8) M) we found an increase of lipase (p < 0.05) after 30 minutes and an increase of amylase (p < 0.05) after 50 minutes perfusion. CONCLUSIONS: The isolated perfused rat pancreas is a valuable experimental model to investigate the early phase of pathophysiology in acute pancreatitis.

Acute Disease↗

Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis.

Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined.

Adult↗

Tissue oxygen tension during regional low-flow perfusion in neonates.

OBJECTIVE: We examined cerebral cortical and peripheral organ tissue Po(2) values in a neonatal piglet model of regional low-flow perfusion. METHODS: Twenty-one neonatal piglets were placed on cardiopulmonary bypass, were cooled to 18 degrees C, then underwent either deep hypothermic circulatory arrest or regional low-flow perfusion at 20 or 40 mL/(kg x min) for 90 minutes. Regional low-flow perfusion was carried out by advancing the aortic cannula into the proximal innominate artery. Tissue mean Po(2) and Po(2) distribution were measured in the cerebral cortex, liver, small bowel, and skeletal muscle through the principle of oxygen-dependent quenching of phosphorescence. Measured quantities were compared by analysis of variance or the Fisher exact test. RESULTS: During regional low-flow perfusion, axillary and femoral arterial pressures, respectively, were 55 +/- 15 and 8 +/- 4 mm Hg at 40 mL/(kg x min) and 37 +/- 10 mm Hg (P =.04) and 17 +/- 5 mm Hg (P =.08) at 20 mL/(kg x min). Venous saturations were 95% +/- 6% at 40 mL/(kg x min) and 84% +/- 6% at 20 mL/(kg x min) (P =.03 at 15, 30, and 45 minutes). Cortical Po(2) was similar to prebypass values during regional low-flow perfusion at 40 mL/(kg x min) (53 +/- 5 mm Hg) but declined during reperfusion and recovery. Cortical Po(2) was lower than before bypass during low-flow perfusion at 20 mL/(kg x min) (38 +/- 7 mm Hg) but increased during reperfusion. Po(2) in liver and bowel was less than 10 mm Hg during low-flow perfusion at both 20 and 40 mL/(kg x min). Fraction of oxygen distribution with Po(2) lower than 15 mm Hg was less during perfusion at 40 mL/(kg x min) than at 20 mL/(kg x min) (P =.001). Three of 6 piglets that received a 40-mL/(kg x min) flow rate had significant upper torso edema, metabolic acidosis, and an unstable recovery period, whereas zero of 6 piglets that received a 20-mL/(kg x min) flow rate did. CONCLUSIONS: In a piglet model, regional low-flow perfusion at 20 mL/(kg x min) resulted in lower cortical tissue oxygenation but better recovery than did perfusion at 40 mL/(kg x min). Neither flow rate adequately oxygenated organs in the lower torso.

Acidosis↗

Continuous monitoring of cerebral perfusion by thermal clearance.

Currently, no commercially available system exists to continuously monitor the effective tissue perfusion within the parenchyma of the brain. While several methods exist for accurately measuring cerebral perfusion; among them: 133xeonon clearance, hydrogen clearance and radiolabeled microsphere injection; none of these methods provides continuous monitoring. The Cook Incorporated VH8500 Volumetric Hyperthermia Treatment System (Bloomington, IN, USA) was initially developed to treat brain tumours by maintaining constant, moderate hyperthermia within a defined tissue volume over an extended duration. The system continuously adjusts the power applied to heating elements in order to maintain a constant temperature within the treatment volume. Because tissue perfusion is a primary factor responsible for removing heat from tissue, monitoring the amount of power applied to the heating elements allows one to continuously estimate tissue perfusion in the vicinity of the heating elements. In the current study, regional blood flow in the vicinity of heater/sensor catheters implanted in the brain parenchyma of three dogs was estimated by the VH8500 tissue perfusion algorithm and directly measured with radioactive labeled microspheres. The accuracy of the perfusion estimate (Thermal Perfusion Index) was evaluated by comparing these values. A range of blood flow was achieved in each animal by infusing nitroprusside. It was found that with the perfusion estimation algorithm of the Cook Incorporated VH8500 Volumetric Hyperthermia Treatment System as it is currently implemented, the Thermal Perfusion Index tended to underestimate regional perfusion as measured with radioactive microspheres, but the relationship was nearly linear. Thus, the system currently tracks changes in regional blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hyperlactacidaemia in isolated hyperthermic perfusion of tumour bearing rat limbs: a study of feasibility using a novel infusion solution.

PURPOSE: In a methodological study the applicability of hyperlactacidaemia in isolated hyperthermic perfusion of tumour-bearing rat limbs was investigated. METHODS: In 50 Sprague Dawley rats, DS-sarcoma growth was initiated on the right food dorsum by subcutaneous injection of 0.5 ml ascites cells. In the anaesthetized animals isolated limb perfusion was performed under steady state conditions for 60min using a miniature equipment. Thereafter tumour volume was measured daily. (a) Investigation of feasability: 40 rats were allocated to four groups. Group I: Normothermic perfusion at 38 degrees C, n = 10; Group II: Hyperthermic perfusion at 40-41 degrees C, n = 10; Group III: Normothermic perfusion at 38 degrees C and hyperlactacidaemia of 10 mmol/l, n = 10; Group IV: Hyperthermic perfusion at 40-41 degrees C and hyperlactacidaemia of 10 mmol/l, n = 10. (b) Investigation of survival and histological changes: In group V hyperthermic perfusion at 40-41 degrees C and hyperlactacidaemia of 10 mmol/l, n = 10 was performed. After the animals had died, hip disarticulation of the tumour-bearing limb was performed for histological examination. RESULTS: Normothermic and hyperthermic perfusion of tumour-bearing rat limbs using miniature equipment was feasible and tolerated by the animals. Regional hyperlactacidaemia of 10 mmol/l could be maintained throughout the perfusions. After combined treatment with hyperthermia and hyperlactacidaemia, tumour volume decreased and extensive tumour necrosis occurred, while in other animals aggressive tumour growth with bone infiltration could be observed. CONCLUSIONS: The present study demonstrates the applicability of hyperlactacidaemia in hyperthermic isolated limb perfusion in the rat and proved a tumour growth delay due to an induction of tumour necrosis thereafter. Further investigations in other tumour entities and experimental models are required to confirm this impressive therapeutic effect of hyperthermia in combination with hyperlactacidaemia.

Animals↗

Comparative effects of combretastatin A-4 disodium phosphate and 5,6-dimethylxanthenone-4-acetic acid on blood perfusion in a murine tumour and normal tissues.

PURPOSE: To compare the ability of combretastatin A-4 disodium phosphate (CA4DP) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) to change tissue blood perfusion. MATERIALS AND METHODS: The tissues were a C3H mouse mammary carcinoma and various murine normal tissues, with perfusion measured using the 86RbCl extraction technique. RESULTS: CA4DP (250mg/kg; i.p.) reduced tumour perfusion to 34% of that seen in controls within 1 h of injection. It was maintained at this for at least 6 h, returning to control levels by 24 h. This decrease was dose-dependent. DMXAA (25mg/kg; i.p.) caused a 79% reduction in tumour perfusion 6h after injection; no recovery was observed even after 24 h. DMXAA showed no changes at doses below 10 mg/kg. Both CA4DP and DMXAA increased perfusion in the gut, kidney, bladder and lung, while decreasing splenic perfusion. CA4DP tended to decrease perfusion in muscle, while DMXAA increased liver perfusion. These changes in normal tissue perfusion were generally less than those changes seen in tumours. No significant changes were seen in skin. CONCLUSIONS: CA4DP and DMXAA produced a selective and significant reduction in tumour perfusion, but the pattern of change was different. These results suggest how these vascular targeting drugs should be combined with more conventional therapies.

Animals↗

Application of perfusion culture system improves in vitro and in vivo osteogenesis of bone marrow-derived osteoblastic cells in porous ceramic materials.

Composites of bone marrow-derived osteoblasts (BMOs) and porous ceramics have been widely used as a bone graft model for bone tissue engineering. Perfusion culture has potential utility for many cell types in three-dimensional (3D) culture. Our hypothesis was that perfusion of medium would increase the cell viability and biosynthetic activity of BMOs in porous ceramic materials, which would be revealed by increased levels of alkaline phosphate (ALP) activity and osteocalcin (OCN) and enhanced bone formation in vivo. For testing in vitro, BMO/beta-tricalcium phosphate composites were cultured in a perfusion container (Minucells and Minutissue, Bad Abbach, Germany) with fresh medium delivered at a rate of 2 mL/h by a peristaltic pump. The ALP activity and OCN content of composites were measured at the end of 1, 2, 3, and 4 weeks of subculture. For testing in vivo, after subculturing for 2 weeks, the composites were subcutaneously implanted into syngeneic rats. These implants were harvested 4 or 8 weeks later. The samples then underwent a biochemical analysis of ALP activity and OCN content and were observed by light microscopy. The levels of ALP activity and OCN in the composites were significantly higher in the perfusion group than in the control group (p < 0.01), both in vitro and in vivo. Histomorphometric analysis of the hematoxylin- and eosin-stained sections revealed a higher average ratio of bone to pore in BMO/beta-TCP composites of the perfusion group after implantation: 47.64 +/- 6.16 for the perfusion group and 26.22 +/- 4.84 for control at 4 weeks (n = 6, p < 0.01); 67.97 +/- 3.58 for the perfusion group and 47.39 +/- 4.10 for control at 8 weeks (n = 6, p < 0.05). These results show that the application of a perfusion culture system during the subculture of BMOs in a porous ceramic scaffold is beneficial to their osteogenesis. After differentiation culture in vitro with the perfusion culture system, the activity of the osteoblastic cells and the consequent bone formation in vivo were significantly enhanced. These results suggest that the perfusion culture system is a valuable and convenient tool for applications in tissue engineering, especially in the generation of artificial bone tissue.

Alkaline Phosphatase↗

Characterization of nascent lipoproteins produced by perfused rat liver: evidence of hepatic secretion and post-secretory modification of nascent lipoproteins.

We characterized the lipoproteins produced by perfused rat liver in recirculating and non-recirculating systems. The apolipoprotein (apo) B of the perfusate very low density lipoprotein (VLDL) and low density lipoprotein (LDL) were labeled with a radioactive precursor amino acid in both systems, suggesting that newly synthesized apo B was secreted in association with VLDL and LDL. When the lipoproteins obtained from the non-recirculating perfusate were injected into rats in vivo, the half life of the VLDL was 13 min and most of it was converted to LDL, while that of the LDL was 5.2 h, indicating that the perfusate LDL was different from the VLDL with respect to its metabolic fate. These observations suggest that both VLDL and LDL are produced as independent primary products in the liver, although the majority of LDL is derived from VLDL in vivo. The nascent lipoproteins in the non-recirculating perfusate were richer in apo E than those in the recirculating perfusate, and a part of the apo E disappeared when the VLDL was added to the recirculating perfusate. The particle sizes of the VLDL and LDL were examined by electron microscopy, which revealed that those in the non-recirculating perfusate were more homogeneous and smaller than the plasma counterparts, while those in the recirculating perfusate were more heterogeneous and their mean diameter was closer to that of the plasma lipoproteins, than in the case of non-recirculating perfusate. These observations suggest that apo E secreted with the nascent lipoproteins may be picked up by the liver just after secretion, causing the heterogeneity in size, as observed in the case of plasma lipoproteins.

Animals↗

Influence of calcium and magnesium deprivation on ovulation and ovum maturation in the perfused rabbit ovary.

The role of calcium (Ca++) and magnesium (Mg++) in the ovulation process was studied using in vitro perfused rabbit ovaries. Ovaries were perfused with or without human chorionic gonadotropin (hCG) in Ca++/Mg++-free medium (M199) alone or combined with standard M199 to yield varying concentrations of Ca++ and/or Mg++. In all ovaries perfused with hCG, ovulatory efficiency was similar regardless of the concentration of Ca++ and/or Mg++. In ovaries perfused in Ca++/Mg++-free medium without hCG, ovulatory efficiency was similar to that in ovaries perfused with hCG. As Ca++/Mg++ levels were increased without hCG, ovulatory efficiency declined. Ovulation time was significantly accelerated in ovaries perfused in Ca++/Mg++-free medium with or without hCG. Most ovulated ova from ovaries perfused without hCG were immature. With hCG, degree of ovum maturity was directly related to ovulation time. Ovarian smooth muscle contractions were undetectable in 3 ovaries perfused in Ca++/Mg++-free M199 despite occurrence of ovulation. Smooth muscle contractions were recorded in 2 of 3 ovaries perfused in standard M199 with hCG. These results indicate: 1) Ca++/Mg++ exclusion results in rapid follicle rupture and immature ova; 2) oocyte maturation appears to be gonadotropin-dependent; 3) ovulation occurs in the absence of ovarian smooth muscle contractions during perfusion with Ca++/Mg++-free medium.

Animals↗

Isolated hypoxic hepatic perfusion with tumor necrosis factor-alpha, melphalan, and mitomycin C using balloon catheter techniques: a pharmacokinetic study in pigs.

OBJECTIVE: To validate the methodology of isolated hypoxic hepatic perfusion (IHHP) using balloon catheter techniques and to gain insight into the distribution of tumor necrosis factor-alpha (TNF), melphalan, and mitomycin C (MMC) through the regional and systemic blood compartments when applying these techniques. SUMMARY BACKGROUND DATA: There is no standard treatment for unresectable liver tumors. Clinical results of isolated limb perfusion with high-dose TNF and melphalan for the treatment of melanoma and sarcoma have been promising, and attempts have been made to extrapolate this success to the isolated liver perfusion setting. The magnitude and toxicity of the surgical procedure, however, have limited clinical applicability. METHODS: Pigs underwent IHHP with TNF, melphalan, and MMC using balloon catheters or served as controls, receiving equivalent dosages of these agents intravenously. After a 20-minute perfusion, a washout procedure was performed for 10 minutes, after which isolation was terminated. Throughout the procedure and afterward, blood samples were obtained from the hepatic and systemic blood compartments and concentrations of perfused agents were determined. RESULTS: During perfusion, locoregional plasma drug concentrations were 20- to 40-fold higher than systemic concentrations. Compared with systemic concentrations after intravenous administration, regional concentrations during IHHP were up to 10-fold higher. Regional MMC and melphalan levels steadily declined during perfusion, indicating rapid uptake by the liver tissue; minimal systemic concentrations indicated virtually no leakage to the systemic blood compartment. During isolation, concentrations of TNF in the perfusate declined only slightly, indicating limited uptake by the liver tissue; no leakage of TNF to the systemic circulation was observed. After termination of isolation, systemic TNF levels showed only a minor transient elevation, indicating that the washout procedure at the end of the perfusions was fully effective. CONCLUSIONS: Complete isolation of the hepatic vascular bed can be accomplished when performing IHHP using this balloon catheter technique. Thus, as in extremities, an ideal leakage-free perfusion of the liver can now be performed, and repeated, without major surgery. The effective washout allows the addition of TNF in this setting.

Animals↗

Cardiac function after eight hour storage by using polyethylene glycol hemoglobin versus crystalloid perfusion.

Efforts to extend myocardial preservation for transplantation by crystalloid perfusion have been limited by edema and compromised function. We hypothesized that hypothermic perfusion preservation with a polyethylene glycol (PEG) conjugated hemoglobin solution may extend preservation times. The purpose of this study was to compare cardiac function after continuous perfusion by using a hypocalcemic, normokalemic crystalloid perfusate with and without the addition of PEG-hemoglobin (Hb). The hearts of 20 anesthetized and ventilated New Zealand White rabbits were harvested after cold cardioplegic arrest. Group I (n = 10) hearts were continuously perfused with a hypocalcemic, normokalemic 3% bovine PEG-Hb solution at 20 degrees C and 30 mm Hg for 8 hours. Group II (n = 10) hearts were continuously perfused with an identical crystalloid solution without PEG-Hb for 8 hours under the same conditions as group I hearts. Cardiac function was measured with a left ventricular force transducer after transfer to a standard crystalloid Langendorff circuit at 37 degrees C and an aortic root pressure of 59 mm Hg. After 8 hours of perfusion preservation, heart rate was similar for groups I and II (p = not significant [NS]). Coronary blood flow after and during preservation was similar between PEG-Hb and crystalloid preserved hearts (p = NS). Left ventricular developed pressure, peak dP/dt, and peak -dP/dt were superior in hearts preserved with PEG-Hb. Percent water of total ventricular weight was 82.0% for group I and 81.6% for group II (p = NS). Continuous perfusion preservation of rabbit hearts for 8 hours with a hypocalcemic normokalemic PEG-Hb based solution at 30 mm Hg and 20 degrees C yields left ventricular function that is superior to perfusion with a similar crystalloid solution without PEG-Hb, despite similar myocardial edema and coronary flow. Extended cardiac perfusion preservation with this PEG-Hb based solution deserves further study, including comparison with traditional cardioplegic preservation solutions.

Animals↗

Liver perfusion studied with ultrafast CT.

OBJECTIVE: Our goal was to quantify absolute hepatic arterial and portal venous perfusion noninvasively in patients with and without liver disease using ultrafast CT. MATERIALS AND METHODS: A single slice through the porta hepatis was repeatedly scanned after bolus injection of 25 ml of iohexol 300 mg I/ml, followed by a 25 ml saline "chaser" intravenously at 10 ml/s. Thirty-nine controls, 7 cirrhotic patients, and 5 patients with known metastases on the slice plane were studied; hepatic arterial perfusion was determined in 41 patients and portal venous perfusion in 24. Time-attenuation curves from regions of interest drawn over the liver, spleen, aorta, and portal vein were analysed. Hepatic arterial perfusion was calculated by dividing the peak gradient of the liver time-attenuation curve prior to the time of peak splenic attenuation by the peak aortic CT number increase. Splenic perfusion was calculated by dividing the peak gradient of the splenic time-attenuation curve by the peak aortic CT number increase. Portal perfusion was derived by scaling the splenic time-attenuation curve by the ratio of hepatic arterial/splenic perfusion. This scaled curve was subtracted from the liver time-attenuation curve to give a portal curve. The peak up-slope of this curve was divided by the peak rise in splenic or portal vein density. RESULTS: Hepatic arterial perfusion averaged 0.19 ml/min/ml (n = 31) in controls and was raised in cirrhosis to 0.25 ml/min/ml (n = 6) and metastases 0.43 ml/min/ml (n = 4). Portal venous perfusion was 0.93 ml/min/ml (n = 19) in controls and 0.43 ml/min/ml (n = 4) in cirrhosis. Reproducibility has been confirmed. CONCLUSION: Dynamic ultrafast CT shows potential in quantifying arterial and portal hepatic perfusion. The technique may be adaptable to dynamic bolus MRI.

Female↗

Three-dimensional surface displays of perfusion SPET in the evaluation of patients with pulmonary emphysema for thoracoscopic lung volume reduction surgery.

A modified, three-dimensional display was applied to 99Tcm-macroaggregated albumin (99Tcm-MAA) SPET to help assess the effect of thoracoscopic lung volume reduction surgery (LVRS) on regional lung perfusion. Surface-rendered three-dimensional images for 99Tcm-MAA and xenon-133 (133Xe) equilibrium (EQ) SPET were obtained in 11 patients with pulmonary emphysema before and after LVRS. A single three-dimensional fusion display of both images was then reconstructed, and the perfused lungs were transparently visible through the lung contours delineated by the three-dimensional 133Xe EQ image. The extent of preserved perfusion in the lung (the perfusion index) was estimated using the ratio (%) of the total pixel numbers of the segmented perfusion data to those of the 133Xe lung volume data. The three-dimensional fusion display provided an overview of the distribution of hypoperfusion in the lungs with geometric realism and enhanced the perception of anatomic size and configuration compared with multiple tomograms and three-dimensional perfusion images without superimposition of three-dimensional 133Xe image. Post-operatively, it displayed restored perfusion in the remaining lungs, and changes in the perfusion index correlated with %FEV1 (r = 0.731, P = 0.0001) more closely than the perfusion data alone (r = 0.593, P < 0.01). This method is useful for directing LVRS and assessing its effectiveness, as it provides precise tomographic information on regional perfusion.

Aged↗

Metabolism of normal and ischemically injured rabbit kidneys during perfusion for 48 hours at 10 C.

We report a study of the effects of perfusate composition on the 5'-adenine nucleotides of rabbit kidneys perfused continuously at 10 C for 24 or 48 hr. It was found that when glucose was the sole energy source and the pO2 was approximately 150 mm Hg, the total high-energy phosphate content was reduced to one-half and total adenine nucleotides to one-third after 48-hr perfusion of freshly isolated kidneys. At this pO2 the supplementation of glucose of additional energy substrates had no effect on adenine nucleotide reserves, but the inclusion of hypoxanthine did have a positive effect, although not sufficient to restore normal levels. Increasing the pO2 to approximately 650 mm Hg however, in combination with the provision of energy substrates and hypoxanthine, produced adenine nucleotide levels very close to normal after 48 hr of perfusion. Study of metabolites in the perfusate suggested that significant glycolysis occurred when the pO2 was 150 mm Hg: it was stimulated by caprylate and inhibited by raising the pO2 to 650 mm Hg. Kidneys exposed to 60 min of warm ischemia before perfusion had severely depleted adenine nucleotide levels (less than one-fifth of normal) but after 48-hr perfusion with hypoxanthine, energy substrates, and a high pO2, the total adenine nucleotides were restored to normal and only the ATP to ADP ratio was significantly less than that observed in kidneys perfused for 48 hr without prior warm ischemia. Study of metabolites in the perfusate suggested that a burst of aerobic respiration occurred after a lag period of 20 hr in these kidneys. It is clear that a remarkable recovery of adenine nucleotides can occur during perfusion, under appropriate conditions, of kidneys damaged by warm ischemia.

Adenosine Diphosphate↗

Hemodynamic and biochemical changes during normothermic and hypothermic sanguinous perfusion of the porcine hepatic graft.

Using an ex vivo liver sanguinous perfusion system, hemodynamic and biochemical changes of the porcine livers were studied, which were preserved cold (4 degrees C) for 24 hr in University of Wisconsin solution and reperfused with normothermic (37 degrees C) (n = 8) or hypothermic (32 degrees C) (n = 8) blood for 3 hr. Six more livers were reperfused with normothermic blood (37 degrees C) immediately after procurement as controls. The total hepatic blood flow was adjusted to 1 ml/min/g liver weight, in which hepatic artery and portal vein flows were administered at a 1:2 ratio. In livers stored cold for 24 hr in UW solution and perfused normothermically, a statistically higher hepatic artery resistance was exhibited at 30 and 60 min after reperfusion (P less than 0.05), and there was lower bile output (P less than 0.05) at 90 and 120 min as compared to the controls. In livers stored cold for 24 hr in UW solution and perfused hypothermically, as compared to ones perfused normothermically, statistically higher hepatic-artery and portal-vein resistances (P less than 0.05) were observed throughout the perfusion period and 60 min after reperfusion, respectively. In addition, bile output and oxygen consumption of these livers were statistically lower than those of ones perfused normothermically (P less than 0.05). In contrast, chemistries of the perfusate of livers perfused hypothermically were comparable to ones perfused normothermically. Histologic examination of the liver perfused hypothermically demonstrated hepatic arterial and/or portal venous congestion and mild-to-moderate hemorrhage in the portal triads. This study suggests that livers preserved for a prolonged period of time demonstrate a high hepatic arterial resistance shortly after revascularization, and that recipient hypothermia after revascularization may be a risk factor for the development of hepatic arterial thrombosis following liver transplantation.

Animals↗

Impact of metabolic syndrome on myocardial perfusion grade after primary percutaneous coronary intervention in patients with acute ST elevation myocardial infarction.

AIMS: Metabolic syndrome with its associated cardiovascular risk factors and prothrombotic, procoagulant and proinflammatory properties and its detrimental effects on coronary microcirculation may play a role in the occurrence of poor myocardial perfusion after primary percutaneous coronary intervention in patients with acute myocardial infarction. Accordingly, this study was designed to evaluate the association between metabolic syndrome and myocardial perfusion grade in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. MATERIAL AND METHODS: The study population included 283 consecutive patients (229 men, mean age=62+/-8 years) admitted to our hospital with ST-elevation myocardial infarction and who underwent primary percutaneous coronary intervention. Thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG) was graded densitometrically on the basis of visual assessment of relative contrast opacification of the myocardial territory subtended by the infarct vessel in relation to epicardial density. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Patients were divided into two groups on the basis of the myocardial perfusion grade determined after percutaneous coronary intervention. Group I consisted of 223 patients with good myocardial perfusion (TMPG 2-3) after successful percutaneous coronary intervention and group II of 60 patients with poor myocardial perfusion (TMPG 0-1). RESULTS: The prevalence of metabolic syndrome was found to be significantly higher in patients with poor myocardial perfusion than in those with good myocardial perfusion (40 vs. 20%, respectively, P=0.002). Moreover, we detected an independent association between metabolic syndrome and the occurrence of poor myocardial perfusion grade (adjusted OR=2.54, 95% CI=1.35-4.75, P=0.003). CONCLUSIONS: We have shown, for the first time, a significant association between metabolic syndrome and impaired myocardial perfusion after percutaneous coronary intervention in patients with acute myocardial infarction. This data may partially explain the poor short and long-term outcomes of acute myocardial infarction in patients with metabolic syndrome.

Aged↗