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Value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin during hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan.

BACKGROUND: The aim of this study was to analyze the value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin (RISA) in patients treated with hyperthermic isolated limb perfusion with tumor necrosis factor-alpha (TNF alpha) and melphalan. METHODS: Forty-eight patients with melanoma (n = 14) or soft tissue sarcoma (n = 34) of an extremity underwent 51 perfusions. Perfusion was performed at the iliac level in 22 cases, at the popliteal level in 16 cases, at the femoral level in 7 cases, and at the axillary level in 6 cases. Leakage rates and perfusion circuit and systemic levels of TNF alpha, interleukin-6, and C-reactive protein were determined, as were systemic hematological and metabolic profiles and tumor response. RESULTS: The mean isotopically measured leakage was 2.9%. Systemic leakage was < or = 2% in 28 perfusions and >2% in 23 perfusions. The correlation between the maximal monitored leakage and maximal systemic TNF alpha levels was.7114. The area under the curve for TNF alpha in the perfusion circuit, indicating the exposure of the perfused limb to TNF alpha, was 18.7% lower in the >2% leakage group. No significant differences in tumor response were found between groups. The area under the curve for systemic TNF alpha, indicating the exposure of the patient to TNF alpha, was 18.1 times higher in the >2% leakage group, resulting in a significant decrease in leukocyte and platelet count, hyperbilirubinemia, hypocholesterolemia, and proteinemia. No beneficial effect of the systemically leaked TNF and melphalan was seen on the occurrence of distant metastasis during follow-up. There was a significant difference between perfusions performed at the iliac and femoral levels compared with leakage values at the popliteal level. CONCLUSIONS: A good correlation between RISA leakage measurement and TNF alpha exposure during and after hyperthermic isolated limb perfusion with TNF alpha and melphalan was demonstrated. RISA leakage measurement serves as a good guide for the effectiveness of isolation during perfusion. If leakage exceeds the 2% limit during perfusion, less exposure of the tumor-bearing limb to TNF alpha, increased exposure of the patient systemic circulation to TNF alpha, and more systemic side effects can be expected.

Adult↗

[An experimental study on the occurrence of brain edema after retrograde cerebral perfusion].

To assess the safety of retrograde cerebral perfusion, the occurrence of brain edema after this procedure was investigated. Twenty-eight adult mongrel dogs were divided into three groups that underwent the following treatments: antegrade perfusion (group 1, n = 9); retrograde perfusion alone (group 2, n = 11); or tetrograde perfusion with drugs (manuitol, thiopental sodium, and methylprednisolone; group 3, n = 8). After 90 minutes of cerebral perfusion at 20 degrees C of the pharyngeal temperature, evans blue (EB) was administered to check for disruptions of the blood-brain-barrier (BBB) and brain tissue water content was measured. Intracranial pressure after cerebral perfusion was markedly higher in group 2 than in group 1 (26.4 +/- 9.4 vs. 11.2 +/- 3.6 mmHg), and brain tissue water content was also significantly higher in group 2 than in group 1 (80.7 +/- 2.0 vs. 77.8 +/- 0.9%). These data suggested that brain edema was more prominent after retrograde perfusion than after antegrade perfusion. The extent of EB to brain tissue was greater in group 2 than in group 1 (169.8 +/- 97.7 vs. 54.7 +/- 31.5 micrograms/dl). The BBB was highly disrupted in group 2 and vasogenic edema appeared after retrograde cerebral perfusion. Maximum intracranial pressure, brain tissue water content and EB concentration were significantly lower in group 3 than in group 2, and did not differ significantly between group 3 and 1. Administration of pharmacologic agents suppressed edema formation and extravasation of EB. We conclude that 90 minutes of retrograde cerebral perfusion at 20 degrees C of the pharyngeal temperature causes brain edema and disrupts the BBB in a manner different from that associated with antegrade perfusion. Mannitol, thiopental sodium, and methylprednisolone prevent these phenomena, indicating that pharmacologic intervention may improve the safety of retrograde cerebral perfusion.

Animals↗

Inhibition by diltiazem of pressure-induced afferent vasoconstriction in the isolated perfused rat kidney.

The renal hemodynamic response to calcium entry blockade depends on the neural, hormonal and physiologic determinants influencing basal renal vascular tone. The effects of perfusion pressure per se on the renal vascular response of the rat kidney to diltiazem were evaluated using normal kidneys and hydronephrotic kidneys perfused extracorporally. In isolated perfused normal kidneys, diltiazem did not alter perfusate flow or glomerular filtration rate (GFR) when administered at a perfusion pressure of 100 mm Hg. In contrast, when diltiazem was administered at a perfusion pressure of 150 mm Hg, the calcium antagonists caused a striking increase in GFR, which was accompanied by an increase in renal perfusate flow. In the isolated perfused hydronephrotic rat kidney, elevation of perfusion pressure was associated with an increase in renal vascular resistance and a reduction in afferent arteriolar diameter. Diltiazem abolished the pressure-induced constriction of afferent arterioles and caused an increase in renal perfusate flow in hydronephrotic kidneys perfused at pressures above 100 mm Hg. These findings suggest that in the setting of increased renal perfusion pressure, diltiazem's effects on GFR are mediated in part by an inhibition of pressure-induced constriction of the afferent arteriole.

Animals↗

Retrograde cerebral perfusion using pulsatile flow under conditions of profound hypothermia.

We investigated the effects of pulsatile flow for retrograde cerebral perfusion under profound hypothermia. Total cardiopulmonary bypass was carried out in adult mongrel dogs to induce hypothermia. One hour of total circulatory arrest was then performed at 20 degrees C in the control group of 6 dogs. In another group of 6 dogs, after cardiac arrest was obtained at 20 degrees C, retrograde cerebral perfusion with nonpulsatile flow was performed through both sides of the internal maxillary vein for 60 minutes; in a third group of 6 dogs, retrograde pulsatile perfusion was continued for 60 minutes. At the end of either retrograde perfusion or total circulatory arrest for 60 minutes, cerebrospinal fluid pressure and blood flow in the cerebral tissues were measured, and cerebral tissues were collected to measure water and adenosine triphosphate content. A significant difference was found for water content between the group undergoing retrograde perfusion with pulsatile flow as opposed to nonpulsatile flow. Cerebral tissues in the group perfused retrogradely with nonpulsatile flow contained more water than in the group perfused with pulsatile flow. Cerebrospinal fluid pressure was lower in the group perfused retrogradely with pulsatile flow when compared with nonpulsatile flow, but no significant difference could be found. As for cerebral flow and adenosine triphosphate content, no significant differences could be found between the groups perfused retrogradely with pulsatile or with non-pulsatile flow. Values were always higher, nonetheless, in the groups perfused with pulsatile flow. We conclude that retrograde cerebral perfusion with pulsatile flow, when used under conditions of profound hypothermia, possesses more cerebroprotective effects than does non-pulsatile perfusion or circulatory arrest.

Adenosine Triphosphate↗

Platelet-vessel wall interactions: effects of platelets and plasma on the antiaggregatory activity and 6 keto-PGF1 alpha production in isolated perfused aortas.

An experimental model for the study of platelet-vessel wall interactions has been developed, based on perfusion of rat platelet rich plasma (PRP) through isolated rat aortas. In the perfused PRP, platelet aggregation was inhibited and levels of 6 Keto PGF1 alpha and cAMP were elevated over the values found in non perfused PRP. When PPP or buffer were perfused through the isolated artery, elevations of 6 Keto PGF1 alpha levels in the perfusate were smaller (in perfused PPP) or of shorter duration (in both perfused PPP and buffer). The presence of platelets in the perfusion fluid thus enhanced the formation of Prostacyclin by the arterial wall. Levels of 6 Keto PGF1 alpha in PRP obtained from aspirin-treated animals and in PRP from normal animals, both perfused through normal aortas, were the same, and also levels of the above metabolite in normal PRP perfused through aortas of aspirin-treated animals did not differ from those found in non perfused PRP. It is concluded, from these data, that PRP does not stimulate PGI2 formation in perfused aortas by providing cyclic endoperoxides. The experimental model developed allows the study of interactions between normal platelets and aortas from experimentally treated animals or viceversa.

6-Ketoprostaglandin F1 alpha↗

Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies.

We evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Initially, groups of rats were injected intravenously (i.v.) with 131I-5G6.4 MoAb (murine IgG2aK reactive with ovarian carcinoma). These animal's radioactivity levels were determined by dose calibrator and they were imaged before and after perfusion which was conducted at 4 or 24 h post-antibody injection. Animals were sacrificed after perfusion, as were controls, and normal organ radioactivity levels determined. In addition, nude mice bearing HTB77 ovarian cancers subcutaneously were injected i.v. with 131I-5G6.4 MoAb and were imaged before and after systemic perfusion with saline 24 h post-5G6.4 injection. Perfusion in rats dropped whole-body 5G6.4 levels significantly at both perfusion times (P less than 0.0005). The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 5G6.4 antibody injection (48.3 +/- 5.1%) than for those perfused at 24 h post i.v. antibody injection (32.9 +/- 2.9%) (P less than 0.025). In the nude mice with ovarian cancer xenografts, gamma camera images of tumors were visually and quantitatively (by computer image analysis) enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor (P less than 0.05). These studies show that (1) much background antibody radioactivity can be removed using whole-body perfusion with saline, (2) that the decline in whole body activity is larger with 4 than 24 h perfusion and (3) tumor imaging can be enhanced by this approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Isolated perfusion of a tubed superficial epigastric flap in a rodent model.

BACKGROUND: Isolated perfusion models can yield important data regarding metabolism of the skin. An effective model must remain stable during perfusion but respond appropriately to metabolic and vascular stimuli. We describe the design and characterization of a tubed superficial epigastric isolated perfusion flap. MATERIALS AND METHODS: Tubed superficial epigastric flaps were created in 20 male Sprague Dawley rats. Forty-eight hours later the femoral vessels were cannulated and the flaps were perfused using a Krebs-Heinseleit buffer containing albumin for a period of 2 h. In five of the flaps norepinephrine and acetylcholine were added sequentially to the perfusate to determine vascular reactivity. In a further four flaps insulin (20 U/liter) and iodoacetate (5 mM) were added to the perfusate to confirm that the flap was metabolically active and reactive. Venous outflow was collected at regular intervals and analyzed for electrolytes, lactate, and glucose content. Vascularity and skin perfusion were characterized using barium microangiography and methylene blue dye injection. RESULTS: This flap model was found to be stable in terms of arterial pressure, electrolyte levels, and lactate production over the perfusion period. Norepinephrine caused a sharp increase in vascular resistance, which was reversed by administration of acetylcholine. Lactate production increased appropriately with the addition of insulin to the perfusate with a rapid decline following addition of the glycolysis inhibitor iodoacetate. There was no leakage of perfusate or significant swelling of the flap during the perfusion. CONCLUSIONS: The tubed superficial epigastric artery flap makes an effective model for isolated perfusion studies of the skin with a wide range of experimental applications.

Acetylcholine↗

Perfusion preservation maintains myocardial ATP levels and reduces apoptosis in an ex vivo rat heart transplantation model.

BACKGROUND: Machine perfusion preservation improves reperfusion function of many solid organs, compared with conventional storage, but has received limited clinical attention in preserving hearts for transplantation. We evaluated representative extracellular (Celsior) and intracellular (University of Wisconsion) storage solutions using static and perfusion protective strategies over a clinically relevant preservation period. METHODS: Rat hearts were preserved for 200 minutes by either static storage or perfusion preservation in Celsior or University of Wisconsin solutions. Three conditions were studied: conventional static storage; static storage using either solution with 5.5 mmol/L glucose added; and perfusion preservation using either solution with 5.5 mmol/L glucose added. Glucose was provided as U-13C-labeled glucose, and glycolysis and oxidative metabolism during preservation were quantified from incorporation of (13)C into glycolytic and tricarboxylic acid cycle intermediates. Adenosine triphosphate levels after preservation, and apoptosis and cardiac function after reperfusion were measured. RESULTS: Both perfusion preservation groups had higher myocardial oxygen consumption during storage and better early graft function, compared with static preservation groups (P < .05). Adenosine triphosphate levels were higher after storage in the perfusion groups (P < .01). Apoptosis was reduced in the perfusion groups (P < .01). Comparing perfusion groups, hearts preserved with Celsior had higher myocardial oxygen consumption and glucose utilization during perfusion storage and exhibited decreased reperfusion coronary vascular resistance and myocardial water content, compared with the UW perfusion group (P < .05). CONCLUSIONS: Perfusion preservation results in greater metabolism during storage and superior cardiac function with improved myocyte survival, compared with static storage. Extracellular preservation solutions appear more effective for perfusion preservation, possibly by augmenting cellular metabolism.

Adenosine Triphosphate↗

Isolated lung perfusion for patients with unresectable metastases from sarcoma: a phase I trial.

BACKGROUND: In patients with unresectable pulmonary metastases from sarcoma, systemic chemotherapy has had limited efficacy possibly because of dose-limiting toxicities. Isolated lung perfusion is an alternative method of delivering high-dose chemotherapy to the lungs while minimizing systemic toxicities. We present the results of our Phase I trial of isolated lung perfusion with doxorubicin hydrochloride in such a group of patients. METHODS: From May 1995 to June 1997, 8 patients with unresectable metastases from sarcoma limited to the lungs underwent isolated lung perfusion with doxorubicin. A dose-escalation schedule starting at 40 mg/m2 was used. Seven patients were treated with a dose of 40 mg/m2 or less, and 1 patient received 80 mg/m2. Blood, tumor, and normal lung samples were obtained at various time points during the operation. Patients were evaluated for cardiac, pulmonary, and other toxicities. RESULTS: The doxorubicin concentrations in both normal lung and tumor correlated directly with the amount of doxorubicin in the perfusate. The tumors took up less doxorubicin than the lung. All patients had minimal or undetectable systemic levels of doxorubicin at the conclusion of the perfusion. There were no cardiac or other systemic toxicities. In the 7 patients perfused with 40 mg/m2 or less of doxorubicin, there was a significant decrease in the forced expiratory volume in 1 second and a trend toward a significant decrease in diffusing capacity. The patient who received 80 mg/m2 underwent lung scanning postoperatively, and scans showed no ventilation or perfusion in the perfused lung. There were no perioperative deaths. Two patients are alive with disease, and 6 patients died of disease. The median follow-up is 11 months and the longest, 31 months. There were no partial or complete responses. One patient had stabilization of disease in the perfused lung, whereas the lesions in the untreated lung progressed markedly. CONCLUSION: Isolated lung perfusion is well tolerated by patients and effectively delivers high doses of doxorubicin to the lung and tumor tissues while minimizing systemic toxicities. A single dose of 80 mg/m2 resulted in substantial injury to the lung. There were no partial or complete responses in patients perfused with doxorubicin at the maximum tolerated dose of 40 mg/m2. Isolated lung perfusion remains a model for testing new and innovative therapies for metastatic sarcoma.

Adult↗

Is maintained cranial hypothermia the only factor leading to improved outcome after retrograde cerebral perfusion? An experimental study with a chronic porcine model.

BACKGROUND: Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcome after prolonged hypothermic circulatory arrest. Here we have compared two temperatures of retrograde cerebral perfusion (15 degrees C and 25 degrees C) with hypothermic circulatory arrest at systemic hypothermia of 25 degrees C to clarify whether the possible benefit of retrograde cerebral perfusion may only be due to improved cooling effect. METHODS: Eighteen pigs (23-27 kg) were randomly assigned to undergo 15 degrees C retrograde cerebral perfusion at systemic hypothermia of 25 degrees C, 25 degrees C retrograde cerebral perfusion at 25 degrees C systemic hypothermia, or hypothermic circulatory arrest at 25 degrees C for 40 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg during retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were performed until 4 hours after the start of rewarming. Daily behavioral assessment was done until death or until the animals were killed on day 7. Histopathologic analysis of the brain was carried out on all animals. RESULTS: Epidural temperatures were lower in the 15 degrees C retrograde cerebral perfusion group during the intervention (P <.05). In the 15 degrees C retrograde cerebral perfusion group, 4 (67%) of 6 animals survived for 7 days compared with 3 (50%) of 6 in both the 25 degrees C retrograde cerebral perfusion and hypothermic circulatory arrest groups. The median total histopathologic score was 5 in the 15 degrees C retrograde cerebral perfusion group and 7 in the 25 degrees C retrograde cerebral perfusion group (P =.04). CONCLUSIONS: These findings suggest that enhanced cranial hypothermia is the major beneficial factor of retrograde cerebral perfusion when careful attention is paid to its implementation.

Animals↗

A controlled clinical trial of machine perfusion of cadaveric donor renal allografts.

Outcome in eighty-eight recipients of cadaveric donor renal allografts preserved before implantation by machine perfusion with a solution of human albumin was compared to that for eighty-three recipients of similar kidneys implanted after simple cold storage. Average total ischaemic intervals for machine-perfused and cold-stored kidneys were 18 and 4 1/4 hours, respectively. Machine-perfused kidneys were implanted regardless of perfusion characteristics. Initial function and 1-month and 1-year graft survivals for the machine-perfused group (58%, 85%, 68%, respectively) were either similar or improved compared to those of cold-stored kidneys (58%, 81%, 52%, respectively). Improved 1-year survival for machine-perfused grafts was dependent upon reduced rejection. Careful donor selection and management ensured good machine perfusion of kidneys on 90% of occasions. In the other 10%, despite poor perfusion characteristics, outcome for kidneys was similar to those with good perfusion characteristics. Antilymphocyte globulin treatment reduced rejection whether allografts were machine perfused or not. In the absence of antilymphocyte globulin treatment, machine-perfused kidneys did much better than cold-stored kidneys. Machine perfusion had important advantages and improved the results in kidney-graft recipients.

Cadaver↗

An examination of whether human placental perfusion allows accurate prediction of placental drug transport: studies with diazepam.

INTRODUCTION: Presently, no well-validated predictive tools are available for human placental transfer. We studied the transplacental passage of diazepam (DZP) in a recirculating dual human placental perfusion and compared the data with in vivo clinical data from the literature. METHODS: Term placentas from healthy mothers without medication were used. The dual, recirculating perfusion technique was used. DZP (2 microg/ml, n = 4; 200 ng/ml, n = 3) and the reference compound antipyrine (100 microg/ml) were added into the maternal circulation simultaneously. The disappearance of drugs from the maternal circulation and appearance into the fetal circulation were followed every 15 min for 2 h. RESULTS: DZP was detectable in the fetal circulation within 15 min in all of the perfusions indicating rapid transfer. DZP concentrations in the maternal circulation were higher than in the fetal circulation throughout the perfusion with both initial concentrations. At the end of the perfusion, the feto-maternal ratio was 0.48 +/- 0.11 (mean +/- S.D.) and the transfer from the maternal to the fetal compartment 18.4 +/- 3.6% with 2 microg/ml of DZP and 0.55 +/- 0.10 and 20.5 +/- 3.1% with 200 ng/ml of DZP, respectively. DZP concentrations in the perfused area of the placenta were in average 2 times higher than in the maternal perfusate and 3.6 times higher than in the fetal perfusate. Total recovery of DZP from samples, perfusion fluid, and perfused tissue was 37.6 +/- 21%. DISCUSSION: Since animal studies in vivo do not accurately predict human placental transfer and it is problematic to study placental transfer of drugs in humans in vivo, the present human placental perfusion system could serve as one part of a test battery for fetotoxicity. However, although our earlier studies and those from the literature indicate a good correlation between in vivo and placental perfusion data, the present study shows this is not the case for all drugs.

Anticonvulsants↗

Development and application of an isolated perfused rat liver model to study the stimulation and inhibition of tumor necrosis factor-alpha production ex vivo.

PURPOSE: To develop an isolated perfused rat liver (IPRL) model with low baseline levels of tumor necrosis factor (TNF)-alpha in the outlet perfusate to study the effects of immunostimulants and immunosuppressants on the release of TNF-alpha from this organ. METHODS: Isolated rat livers were perfused with a buffer containing no albumin or three different bovine serum albumin (BSA) preparations. Using the no-albumin perfusate, the inhibitory effects of methylprednisolone (MP) on lipopolysaccharide (LPS)-stimulated release of TNF-alpha were studied in livers isolated 1 or 5 h after the intravenous administration (5 mg/kg) of MP. The concentrations of TNF-a in the outlet perfusates were measured using enzyme-linked immunosorbent assay. RESULTS: In the absence of albumin, the perfusate levels of TNF-alpha were close to zero. However, when the perfusate contained BSA. the TNF-alpha levels in the perfusate reached as high as 1200 pg/ml at steady state. An injection of LPS into IPRLs perfused with a no-albumin perfusate resulted in mean (+/- SD) TNF-alpha steady-state concentrations of 825 +/- 125 pg/ml. The pretreatment of rats with MP before liver harvest attenuated the LPS-induced TNF-alpha release in the livers. However, the attenuation was substantial (>60%) and was statistically significant only 5 h after pretreatment with MP. CONCLUSIONS: Perfusates containing BSA may result in nonphysiologically high levels of TNF-alpha. An IPRL with a no-albumin perfusate is more suitable for studies of the stimulation and inhibition of TNF-alpha production by this organ.

Adjuvants, Immunologic↗

The venous flaps: an experimental study of the microvascular architecture, the area of perfusion and their correlation.

The aim was to compare the various modes (cephalic, caudal and bidirectional input) of venous-flap perfusion and to relate the area perfused to the microvascular architecture of the venous flaps. Thirty-three flaps harvested from the forearm and dorsal foot regions of 12 fresh cadavers were divided into four groups: Group 1, cephalic input (n = 12); Group 2, caudal input (n = 11); Group 3, bidirectional input (n = 13 - converted from either Group 1 or Group 2); and Group 4, a control group made up of traditional arterial free flaps (n = 10). Perfusion was carried out using a cocktail of vital dye and Roentgen contrast medium, so that the flaps could be studied both for area of perfusion and by microangiography. Perfusion in Groups 1 and 2 was carried out with increasing numbers of injected veins. The numbers of contrasted vessels in the microangiograms were counted and correlated with the areas of perfusion. Statistical comparisons were made between the different groups, between the test groups and the control group, and between the flaps from different anatomical locations. The bidirectional-input flaps showed statistically significantly larger areas of perfusion than both the caudal-input and the cephalic-input groups. The perfusion areas of the cephalic-input flaps were larger than those of the caudal-input flaps. The control flaps had the largest area of perfusion. Forearm flaps had larger areas of perfusion than dorsal foot flaps. There was a significant correlation between the area perfused and the number of vessels contrasted in all the venous flaps, with a significant increase in perfusion area with increasing numbers of veins.

Adult↗

Contamination of perfused donor kidneys by starch from surgical gloves.

Starch induces a variety of inflammatory reactions in humans and may contaminate surgical procedures from surgical gloves. Using polarized microscopy and electron microscopy, the authors observed starch particles in renal perfusate and in glomeruli of perfused donor kidneys. Group 1 consisted of 10 unusable kidneys handled with standard concern of glove sterility. Eight other kidneys (Group 2) were perfused with particular attention toward avoidance of starch contamination. The gloves were rinsed five times, and the cuffs were not dipped into the perfusate. Two kidneys (Group 3), deemed unsuitable for transplantation, were perfused for 24 hours with perfusate swished with unwashed sterile gloves. Group 4 consisted of five transplant biopsies performed within one week after transplantation. Perfusates alone were also circulated through the Waters Perfusion Machine continuously for 24, 72, and 188 hours with and without the use of gloves. The number of birefringent crosses were counted in each of 25 glomeruli per specimen. Group 1 displayed a mean of 1.8 birefringent crosses per glomerulus; Group 2, 0; Group 3, 5.3; and Group 4, 4.4. Groups 1 and 3 also exhibited birefringent crosses in peripheral renal vessels. Perfusate alone, handled without gloves, showed no birefringent crosses; by contrast, perfusate handled with gloves showed numerous birefringent crosses. The authors conclude that starch from surgical gloves can enter the perfusate and lodge in glomeruli and other sites of donor kidneys. Rinsing gloves five times and avoiding contact of the perfusate with the glove cuff effectively eliminates the contamination.

Birefringence↗

The additive value of gated SPET myocardial perfusion imaging in patients with known and suspected coronary artery disease.

In myocardial perfusion scintigraphy, the clinical significance of fixed defects presents some difficulty. In this study, we evaluated whether additional information on left ventricular function assessed by quantitative gated single-photon emission computed tomography (gated SPET) would increase the diagnostic yield of the study in such patients. We studied 55 patients with a previous myocardial infarction and 20 patients without a previous myocardial infarction using gated SPET 99Tc(m)-tetrofosmin myocardial perfusion imaging. Each patient had to have a persistent perfusion defect consisting of at least three contiguous segments in the same vascular territory. The left ventricle was divided into 20 segments which were analysed for perfusion and wall thickening on a 4-point severity scale. Of the 55 patients with myocardial infarction, 19 (35%) patients showed preserved wall thickening in the region of the previous infarction with fixed perfusion abnormalities, which suggested residual myocardial viability. In the 20 patients without myocardial infarction, preserved wall thickening was seen in 10 (50%) patients with fixed perfusion defects, suggesting an attenuation artefact. Conversely, in 16 (29%) patients in the myocardial infarction group and two (10%) patients in the non-myocardial infarction group normal perfusion was associated with severely diminished wall thickening possibly due to stunning. We found an excellent correlation between wall thickening and left ventricular ejection fraction both for the patients with myocardial infarction and the patients without myocardial infarction (r = 0.86 and r = 0.82, respectively, both P<0.0001). A reasonable correlation between perfusion and left ventricular ejection fraction was found for the patients with myocardial infarction (r = 0.41, P = 0.002), and a non-significant correlation for the patients without myocardial infarction (r = 0.37, P = 0.1). Quantitative gated SPET myocardial imaging allows the detection of residual wall thickening in patients with a previous myocardial infarction who show severe fixed perfusion defects. In patients without myocardial infarction, gated SPET imaging allows differentiation between an attenuation artefact and a fixed perfusion defect due to coronary artery disease. In addition, gated SPET may show diminished ventricular function in normally perfused segments possibly due to myocardial stunning. The addition of gated SPET myocardial perfusion imaging increases diagnostic confidence and may have direct clinical implications for optimal patient management.

Aged↗

Oxygen consumption in rabbit Langendorff hearts perfused with a saline medium.

Isolated rabbit hearts were perfused according to Langendorff at a temperature of 38 degrees C and a pressure of 5.9 kPa with gassed Tyrode solution. Gas mixtures containing 5% CO2 and 15, 20, 30, 60, or 95% O2 in N2 were used to saturate the perfusion medium. In some cases lactate (50 or 500 microM) was present in the medium perfusing the heart. Coronary flow (CF), oxygen pressure in the perfusion medium and in the cardiac effluent and lactate in the effluent were analysed in all experiments. The oxygen uptake in the hearts perfused with a medium equilibrated at atmospheric pressure with 95% O2 and 5% CO2 (oxygen pressure approximately 87 kPa, oxygen content 19 ml X 1(-1)), averaged 3 ml X 100 g w.w. -1 X min-1. Reduction of the oxygen pressure in the perfusion medium resulted in an increase in CF and in the fractional extraction of oxygen from the medium, making it possible to maintain the heart's oxygen uptake (VO2) down to an oxygen pressure in the perfusion medium of about 24 kPa (oxygen content approximately 5 ml X 1(-1), the perfusion medium equilibrated with 20% O2 and 5% CO2 in N2). Myocardial lactate production was low during perfusion at pO2 approximately 87 kPa but increased rapidly when the oxygen pressure was lowered. The addition of lactate (500 microM) to the perfusion medium at pO2 approximately 87 kP induced a fractional uptake of about 20%. It is concluded that the VO2 observed during perfusion at pO2 approximately 87 kPa mainly reflects aerobic myocardial metabolism in this preparation. This assumption is based on the facts that coronary flow and fractional oxygen extraction are submaximal and that a considerable uptake of lactate occurs concurrently with a very limited production. However, even moderate reduction of the oxygen pressure in the perfusion medium (to approximately 61 kPa) is followed by a significant increase in lactate production, indicating that myocardial oxygenation is inefficient.

Animals↗

Influence of raising albumin concentration on renin release in isolated perfused rat kidneys.

1. Experiments were conducted in isolated perfused rat kidneys to determine the effect of raising perfusate albumin concentration on renin release.2. Raising albumin concentration in the perfusion fluid from 20 g/l. to 60 g/l. (high albumin concentration) increased renin release and renal perfusate flow rate. The effect was reversible.3. Ureteral occlusion did not prevent the rise in renin release and renal perfusate flow induced by high albumin concentration.4. Propranolol (0.28 mM) did not block the renin release stimulated by high albumin concentration, but it inhibited the release stimulated by isoprenaline (2.43 muM).5. Clonidine (10 muM) and oxymetazoline (10 muM) constricted the renal vasculature and stimulated renin release during high perfusate albumin concentration providing perfusion pressure was kept constant.6. Low renal perfusion pressure (50 mmHg) and isoprenaline (2.43 muM) stimulated renin release in perfusion experiments with both 20 and 60 g/l., but the rate of renin release was substantially greater with 60 g/l.7. On the other hand, perfusion fluid deprived of calcium induced a greater increase in renin release in kidneys perfused with 20 g/l. than in those with 60 g/l.8. We conclude that high albumin concentration stimulates renin release in isolated perfused rat kidneys by a mechanism which does not involve the renal nerve, direct renal vasodilation or sodium excretion. High albumin concentration may increase the sensitivity of the kidney to acute stimulation by a mechanism involving calcium.

Animals↗