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PubMed2000

Detection of false lumen perfusion at the beginning of cardiopulmonary bypass in patients undergoing repair of aortic dissection.

OBJECTIVE: In patients undergoing surgical repair of aortic dissection, false lumen perfusion during cardiopulmonary bypass may produce central nervous system damage, myocardial ischemia, aortic rupture, and death. We describe a method to detect false lumen perfusion at the beginning of retrograde aortic perfusion that may prevent these complications. DESIGN: Sonicated albumin microbubbles (8 mL) were injected through a side branch of the extracorporeal circulation line to detect true lumen and/or false lumen perfusion of the thoracic aorta at the beginning of cardiopulmonary bypass. Transesophageal echocardiography was used to image aortic perfusion. SETTING: The study was performed in a cardiac surgery theater. PATIENTS: A total of 27 consecutive patients undergoing operation for Type I aortic dissection were studied. INTERVENTIONS: All patients underwent surgical repair of aortic dissection and retrograde aortic perfusion through one femoral artery. MEASUREMENTS AND MAIN RESULTS: Patients were divided into three groups: Group I, those having adequate true lumen perfusion: brisk appearance and washout of contrast in the true lumen with no, poor, or delayed opacification of the false lumen; Group II, those having mixed true lumen and false lumen perfusion: simultaneous opacification of both lumens; Group III, those having inappropriate false lumen perfusion: same criteria as for adequate true lumen perfusion applied to the false lumen. The true lumen was perfused in 13 patients, both lumens in 11 patients, and false lumen alone in three patients. In these three patients, cannulation was repeated through the contralateral femoral artery with restoration of true lumen perfusion; the first patient died of diffuse cerebral ischemic damage and renal failure, another one experienced temporary postoperative monoparesis, and the last had no neurologic sequelae. CONCLUSIONS: Contrast echocardiography allows immediate detection of retrograde aortic perfusion during cardiopulmonary bypass and may help prevent neurologic complications and death in patients with Type I dissection.

Adult↗
PubMed2003

Partially parallel three-dimensional magnetic resonance imaging for the assessment of lung perfusion--initial results.

RATIONALE: Contrast-enhanced magnetic resonance imaging (MRI) of lung perfusion requires a high spatial and temporal resolution. Partially parallel MRI offers an improved spatial and temporal resolution. OBJECTIVE: To assess the feasibility of partially parallel MRI for the assessment of lung perfusion. METHODS: Two healthy volunteers and 14 patients were examined with a contrast-enhanced 3D gradient-echo pulse sequence with partially parallel image acquisitions (TE/TR/alpha: 0.8/1.9 milliseconds/40 degrees; voxel size 3.6 x 2.0 x 5.0 mm3, TA: 1.5 seconds). The image analysis included an analysis of the signal-to-noise ratio in the lungs in areas with normal and impaired perfusion. 3D MR perfusion image data were analyzed for perfusion defects and compared with radionuclide perfusion scans, which were available for 10 of 14 patients. RESULTS: The analysis of the 3D perfusion-weighted data allowed a clear differentiation of perfusion abnormalities: MRI showed normal lung perfusion in 9 of 16 cases, whereas perfusion abnormalities were observed in 7 cases. When compared with the radionuclide perfusion scans, a good intermodality agreement was shown (kappa = 0.74). When compared with normally perfused lung a significantly lower signal to noise ratio was observed in hypoperfused lung (7 versus 17; P = 0.02). CONCLUSION: Partially parallel MRI might be used for the assessment of lung perfusion. Future studies are required to further evaluate the diagnostic impact of this technique.

Adult↗
PubMed2005

Pulmonary arterial hypertension: diagnosis with fast perfusion MR imaging and high-spatial-resolution MR angiography--preliminary experience.

PURPOSE: To determine prospectively the accuracy of a magnetic resonance (MR) perfusion imaging and MR angiography protocol for differentiation of chronic thromboembolic pulmonary arterial hypertension (CTEPH) and primary pulmonary hypertension (PPH) by using parallel acquisition techniques. MATERIALS AND METHODS: The study was approved by the institution's internal review board, and all patients gave written consent prior to participation. A total of 29 patients (16 women; mean age, 54 years +/- 17 [+/- standard deviation]; 13 men; mean age, 57 years +/- 15) with known pulmonary hypertension were examined with a 1.5-T MR imager. MR perfusion imaging (temporal resolution, 1.1 seconds per phase) and MR angiography (matrix, 512; voxel size, 1.0 x 0.7 x 1.6 mm) were performed with parallel acquisition techniques. Dynamic perfusion images and reformatted three-dimensional MR angiograms were analyzed for occlusive and nonocclusive changes of the pulmonary arteries, including perfusion defects, caliber irregularities, and intravascular thrombi. MR perfusion imaging results were compared with those of radionuclide perfusion scintigraphy, and MR angiography results were compared with those of digital subtraction angiography (DSA) and/or contrast material-enhanced multi-detector row computed tomography (CT). Sensitivity, specificity, and diagnostic accuracy of MR perfusion imaging and MR angiography were calculated. Receiver operator characteristic analyses were performed to compare the diagnostic value of MR angiography, MR perfusion imaging, and both modalities combined. For MR angiography and MR perfusion imaging, kappa values were used to assess interobserver agreement. RESULTS: A correct diagnosis was made in 26 (90%) of 29 patients by using this comprehensive MR imaging protocol. Results of MR perfusion imaging demonstrated 79% agreement (ie, identical diagnosis on a per-patient basis) with those of perfusion scintigraphy, and results of MR angiography demonstrated 86% agreement with those of DSA and/or CT angiography. Interobserver agreement was good for both MR perfusion imaging and MR angiography (kappa = 0.63 and 0.70, respectively). CONCLUSION: The combination of fast MR perfusion imaging and high-spatial-resolution MR angiography with parallel acquisition techniques enables the differentiation of PPH from CTEPH with high accuracy.

Diagnosis, Differential↗
PubMed1972

Regional myocardial perfusion rates in patient with coronary artery disease.

Regional myocardial perfusion rates were estimated from the myocardial washout of (133)Xenon in 24 patients with heart disease whose coronary arteriograms were abnormal and 17 similar subjects whose coronary arteriograms were judged to be normal. Disappearance rates of (133)Xe from multiple areas of the heart were monitored externally with a multiple-crystal scintillation camera after the isotope had been injected into a coronary artery and local myocardial perfusion rates were calculated by the Kety formula. The mean myocardial perfusion rates in the left ventricle exceeded those in the right ventricle or atrial regions in subjects without demonstrable coronary artery disease. In this group there was a significant lack of homogeneity of local perfusion rates in left ventricular myocardium; the mean coefficient of variation of left ventricular local perfusion rates was 15.8%. In the patients with radiographically demonstrable coronary artery disease, a variety of myocardial perfusion patterns were observed. Local capillary blood flow rates were depressed throughout the myocardium of patients with diffuse coronary disease but were subnormal only in discrete myocardial regions of others with localized occlusive disease. Local myocardial perfusion rates were similar to those found in the group with normal coronary arteriograms in patients with slight degrees of coronary disease and in those areas of myocardium distal to marked coronary constrictions or occlusions which were well supplied by collateral vessels. In subjects with right coronary disease, the mean right ventricular perfusion rates were significantly subnormal; in seven subjects of this group perfusion of the inferior left ventricle by a dominant right coronary artery was absent or depressed. The average mean left ventricular perfusion rate of 12 subjects with significant disease of two or more branches of the left coronary artery was significantly lower than that of the group with normal left coronary arteriograms. In the patients with abnormal left coronary arteriograms, the average coefficient of variation of local left ventricular perfusion rates was significantly increased (24.8%). The studies provide evidence that coronary artery disease is associated with increased heterogeneity of local myocardial perfusion rates. They indicate that radiographically significant vascular pathology of the right or left coronary artery may be associated with significant reductions of myocardial capillary perfusion in the region supplied by the diseased vessel.

Adult↗
PubMed1975

The relationship between regional myocardial perfusion at rest and arteriographic lesions in patients with coronary atherosclerosis.

Measurements of mean left ventricular (LV) and regional myocardial blood flow rates were made at rest in 161 patients with 133Xe and a multiplecrystal scintillation camera. Myocardial perfusion rates were correlated with assessments of the degree of coronary artery disease made from the arteriograms obtained during the same studies. In patients with normal coronary arteries without heart failure, the presence of hypertension, aortic stenosis, or aortic insufficiency was not associated with changes in mean LV perfusion from the control value of 61+/-7 ml/100 g-min. However, mean LV perfusion was significantly reduced in patients with normal coronary arteries who had cariomyopathy and impaired ventricular performance. Mean LV perfusion was not significantly different from control values in patients with "mild" coronary artery disease (less than 50% obstruction) or in patients with significant isolated disease (greater than 50% obstruction) of the left anterior descending (lad) artery. Significant reductions in mean LV perfusion were found in patients with greater than 50% obstruction of two coronary arteries (LAD + right or LAD + circumflex) and in patients with triple-vessel disease. The average perfusion rate for regions distal to LAD obstructions in patients with isolated LAD disease was not lower than the LAD perfusion in control patients, but was significantly reduced in patients with LAD + right coronary artery disease (43+/-14 ml/100 g-min). In the latter group average perfusion distal to the LAD lesion was significantly lower than the average regional perfusion rate for the remainder of the LV. However, the mean blood flow rate for the remainder of the LV was also significantly lower than control values despite the lack of significant circumflex disease. The data demonstrate that the presence of radiographically "mild" or significant isolated LAD coronary disease is not associated with reductions in mean LV perfusion at rest, but that mean LV perfusion is reduced in the presence of significant disease of two or three coronary artieries. None of the patients experienced angina during the resting studies and most had clinical evidence of ventricular failure. The observation of depressed LV perfusion in this group, as in the patients with cardiomyopathy, raises the possibility that a lowered resting blood supply may be adequate for a reduced level of performance of a diseased ventricle. The lack of selective reductions of regional perfusion at rest in the majority of the patients with LAD lesions suggests that regional myocardial blood flow must be measured during an intervention which increases myocardial oxygen consumption in order to assess the physiological significance of lesions which are observed at coronary arteriography.

Adult↗
PubMed1999

Mathematical modelling of extracorporeal circulation: simulation of different perfusion regimens.

Computer- and sensor-aided control of the heart-lung machine is considered a major goal for perfusion sciences for the next few years. At present, control of perfusion is achieved by surgeons, anaesthesiologists and perfusionists making short-term decisions, which leads to variations of the perfusion regimens between different centres and even between different teams in the operating theatre. As the basis for an integrated control of extracorporeal circulation (ECC), we proposed a mathematical model for simulating haemodynamics during pulsatile perfusion. This model was then modified to allow it to simulate the effects of different perfusion regimens on arterial haemodynamics and whole body oxygen consumption. The model was constructed on a PC using MATLAB/SIMULINK. The human arterial tree was divided into a multibranch structure consisting of 128 segments characterized by their particular physical properties. Peripheral branches were terminated by a resistance term representing smaller vessels like arterioles and capillaries. Flow and pressure were expressed by the intensity of current and voltage in an electrotechnical analogon; inductivity, resistance and capacitance were implemented according to the physical properties of the arterial tree and the rheology of blood. The effects of different perfusion regimens (pulsatility, flow amount, acid-base regulation) were studied. After introducing an input signal to the model, flow and pressure waves established themselves throughout the simulated arterial tree. During the simulation experiments, marked differences among different perfusion regimens were displayed by the model. Variations in acid-base management mainly influenced the distribution of perfusion: during simulation of low-flow perfusion (1.2 l/min/m2), cerebral blood flow was 6.2 ml/s using an alpha-stat regimen, while it was increased to 9.4 ml/s during pH-stat, caused by an implementation of reduced cerebral resistance. Whole body oxygen consumption was predominantly regulated by the perfusion rate. While central venous oxygen saturation was calculated to be 84.7% during simulation of high-flow perfusion (2.4 l/min/m2), it dropped to 70% during simulation of low-flow perfusion regimens. The model proved to be useful for a realistic simulation of different perfusion regimens. Therefore it can be considered a continuing step for the derivation of a 'state' observer leading to the realization of an automatically controlled heart-lung machine.

Blood Transfusion↗
PubMedDate not supplied

The effect of hydralazine dose on blood perfusion changes during hyperthermia.

Experiments were performed to determine the dose-related effects of the intravenous administration of a vasodilator (hydralazine) on normal muscle blood perfusion during localized hyperthermia. Fourteen anaesthetized outbred canines were investigated, seven receiving the recommended dose level of 0.5 mg/kg and seven receiving one-quarter of that level. The changes in blood perfusion were estimated using two methods: calculation of an effective blood perfusion magnitude and the use of state and parameter estimation techniques. Both methods showed that the changes in blood perfusion induced by the hydralazine were significant, and that the differences between the results for the two drug doses were not significantly different. This suggests that low doses may be useful in humans, giving the same resultant blood perfusion increase but with a decreased patient risk relative to standard therapeutic doses of hydralazine. While the trends in the blood perfusion changes were the same for both calculation methods the effective perfusion method frequently yielded blood perfusion magnitudes significantly different from those obtained using the state and parameter estimation technique. The differences are postulated to be due to the fact that the effective perfusion values include conduction effects, thus overpredicting the amount of perfusion present. Thus, while the effective blood perfusion can be used as a qualitative indication of blood perfusion changes under certain conditions, we do not recommend its use as a quantitative measure of perfusion.

Animals↗
PubMed1999

Prediction of improvement of regional left ventricular function after revascularization using different perfusion-metabolism criteria.

UNLABELLED: Increased myocardial uptake of 18F-fluorodeoxyglucose (FDG) in regions with perfusion defects (perfusion-FDG mismatch) has been shown to predict functional recovery after revascularization; conversely, a concordant decrease in perfusion and FDG uptake (perfusion-FDG match) represents scar tissue (varying from subendocardial to transmural scar) that will not improve in contractile function after revascularization. Several recent studies have used a mild reduction in perfusion or FDG uptake (or both) as an indicator of viable tissue. To our knowledge, this criterion has not been validated against functional outcome after revascularization. This study aimed to compare the predictive value for functional recovery of these different perfusion-metabolism criteria. METHODS: Forty-two patients referred for revascularization were studied with early resting 201Tl SPECT (to evaluate perfusion) and FDG SPECT. Contractile function was evaluated before and 3-4 mo after revascularization using two-dimensional echocardiography. Angiography was not repeated. RESULTS: Two hundred six dysfunctional segments were identified; functional recovery occurred in 71 segments. The 206 dysfunctional segments were divided into five groups: group I, segments (n = 37) with normal perfusion; group II, segments (n = 69) with a mild reduction in perfusion (> or =60% of normal 201Tl uptake) without increased FDG uptake (mild match); group III, segments (n = 29) with a mild reduction in perfusion and increased FDG uptake (mild mismatch); group IV, segments (n = 46) with a more severe reduction in perfusion (<60% of normal 201Tl uptake) without increased FDG uptake (severe match); and group V, segments (n = 25) with a 201Tl activity < 60% and increased FDG uptake (severe mismatch). The mean wall motion score improved significantly in groups I, III and V but not in groups II and IV. Improvement of function was observed in 76% of group I segments, in 69% of group III segments and in 68% of group V segments. In contrast, only 13% of group II segments and 7% of group IV segments improved after revascularization. CONCLUSION: The results indicate that normal perfusion and mismatch patterns (either mild or severe) are predictive of functional recovery, whereas match patterns (either mild or severe) are predictive of absence of recovery. Match patterns are likely to represent different degrees of scar tissue, ranging from subendocardial to transmural scars. To identify segments with a high likelihood of improvement of function after revascularization, integration of information on perfusion and FDG uptake appears mandatory.

Angioplasty, Balloon, Coronary↗
PubMed2000

Non-invasive quantification of liver perfusion with dynamic computed tomography and a dual-input one-compartmental model.

Various liver diseases lead to significant alterations of the hepatic microcirculation. Therefore, quantification of hepatic perfusion has the potential to improve the assessment and management of liver diseases. Most methods used to quantify liver perfusion are invasive or controversial. This paper describes and validates a non-invasive method for the quantification of liver perfusion using computed tomography (CT). Dynamic single-section CT of the liver was performed after intravenous bolus administration of a low-molecular-mass iodinated contrast agent. Hepatic, aortic and portal-venous time-density curves were fitted with a dual-input one-compartmental model to calculate liver perfusion. Validation studies consisted of simultaneous measurements of hepatic perfusion with CT and with radiolabelled microspheres in rabbits at rest and after adenosine infusion. The feasibility and reproducibility of the CT method in humans was assessed by three observers in 10 patients without liver disease. In rabbits, significant correlations were observed between perfusion measurements obtained with CT and with microspheres (r=0.92 for total liver perfusion, r=0.81 for arterial perfusion and r=0.85 for portal perfusion). In patients, total liver plasma perfusion measured with CT was 112+/-28 ml.min(-1).100 ml(-1), arterial plasma perfusion was 18+/-12 ml.min(-1).100 ml(-1) and portal plasma perfusion was 93+/-31 ml.min(-1).100 ml(-1). The measurements obtained by the three observers were not significantly different from each other (P>0.1). Our results indicate that dynamic CT combined with a dual-input one-compartmental model provides a valid and reliable method for the non-invasive quantification of perfusion in the normal liver.

Adult↗
PubMed2001

Perfusion and functional abnormalities outside the septal region in patients with left bundle branch block assessed with gated SPECT.

BACKGROUND: The presence of a left bundle branch block (LBBB) pattern on the electrocardiogram may frequently lead to perfusion defects in the septum not necessarily due to ischemic heart disease, but probably due to abnormal septal wall motion. The introduction of gated single photon emission computed tomography (SPECT) allows the evaluation of myocardial perfusion and function in one study. Accordingly, we analysed perfusion and function and the relation between perfusion and regional function in the septal region in patients with a LBBB without evidence of a previously sustained myocardial infarction. METHODS: We selected 37 patients with a LBBB without a history of a previous myocardial infarction, which was confirmed by echocardiography and/or coronary angiography. All patients underwent technetium-99m tetrofosmin gated SPECT myocardial imaging. Twelve control patients with a low likelihood of coronary artery disease and a normal technetium-99m tetrofosmin gated SPECT myocardial perfusion scintigram were selected as a reference population. The left ventricle (LV) was divided into 18 segments, which were scored for perfusion and function (wall motion and wall thickening) on a 4-point scale. RESULTS: The average LV end-diastolic volume was higher and the average LV ejection fraction was lower in patients with LBBB as compared to controls (142+/-90 vs. 81+/-18 ml, and 48+/-19 vs 62+/-7%, p=0.03 and p=0.02, respectively). Not only in the septum, but also in the other segments, reduced myocardial perfusion and abnormal wall motion/wall thickening was observed in the patients with LBBB (p<0.0001 vs controls). Patients with LBBB showed no correlation between perfusion and function in the septum, and between perfusion in septum and global LV function (r=0.21, p=0.2; r=0.10, p=0.6, respectively). Conversely, a good correlation was found between perfusion and function, either regional or global, in the remote segments (both r=0.79, p<0.0001). CONCLUSIONS: We conclude that patients with LBBB without a previous myocardial infarction show cardiomyopathic changes with perfusion and wall motion abnormalities, involving the entire left ventricle. The severity of diminished septal perfusion is not directly associated with the severity of septal wall motion abnormalities or global LV function. However, in the myocardial segments remote from the septum, reduced perfusion is closely associated with functional abnormalities.

Bundle-Branch Block↗
PubMed2005

Establishment and evaluation of the system of extracorporeal liver perfusion in pigs.

BACKGROUND: In recent years, extracorporeal liver perfusion (ECLP) has been regarded as a treatment of acute liver failure (ALF); but the system of ECLP has many problems. The purpose of this experiment was to detect the factors affecting the system of ECLP and to establish a stable and effective system of ECLP. METHODS: Livers were harvested from health pigs, according to the different styles of perfusion and oxygenation, which were randomly divided into 3 groups. The livers in group A (n=4) were subjected to single portal vein perfusion, oxygenating perfusion blood; the livers in group B (n=4) to dual (portal vein and hepatic artery) vessel perfusion, oxygenating blood, together; and the livers in group C (n=4) to dual (portal vein and hepatic artery) vessel perfusion, but oxygenating blood, separately. The perfusion time, the data of bile production, and hemodynamic parameters of extracorporeal livers in each group were tested. The histological examination of liver tissues from each group was performed at the end of perfusion. RESULTS: The perfusion time of the liver in group A is significantly shorter than in groups B and C (P<0.05). At 1, 3, 6 hours after perfusion, the data of bile production and hemodynamic parameters of livers in group A were statistically different from those of livers in groups B and C (P<0.05). At 1, 3, 6 hours after perfusion, the data of group B were not statistically different from those of livers in group C (P>0.05). But at 12 hours after perfusion, the data of group B were statistically different from those of livers in group C (P<0.01). CONCLUSION: The system of ECLP, which is performed by dual (portal vein and hepatic artery) vessel perfusion and oxygenating blood separately, is more stable and effective to keep the function of extracorporeal liver.

Animals↗
PubMed1981

Tumoricidal responses in spontaneous canine neoplasms after extracorporeal perfusion over immobilized protein A.

I describe morphologic, histologic, immunohistochemical, and serologic changes in dogs with spontaneous breast adenocarcinoma, squamous cell carcinoma, hemangiopericytoma, and fibrosarcoma after extracorporeal perfusion of plasma over heat-killed and formalin-stabilized Staphylococcus aureus Cowans I (SAC), which was embedded in a membrane filtration system. In 12 dogs with breast adenocarcinoma, tumor necrosis was observed within 12 hours after perfusion; 24 hours after perfusion, multiple visible lesions in 6 of 6 dogs exhibited necrosis, but there was no reaction in uninvolved normal mammary tissue. In 8 dogs, healing of large ulcerated areas of cutaneous tumor was observed within 8 to 18 days after perfusion. Similar tumoricidal responses were observed in dogs with other neoplasms after SAC perfusion. Tumor cell necrosis oserved within 4 hours after extracorporeal perfusion was associated with immunohistochemical deposits of IgG and C'3 and ultrastructural evidence of lytic lesions on tumor cell membranes. No tumoricidal effects were observed after perfusion over Staphylococcus aureus Woods (SAW) (non-protein A bearing) in 3 dogs that previously or subsequently responded to SAC perfusion. No tumoricidal reactions were noted after phlebotomy of up to 50% of plasma volume in 6 tumor-bearing dogs that subsequently responded to SAC perfusion. SAC but not SAW perfusion was followed by increases in circulating tumor associated antibodies (TAA) for up to 48 hours after perfusion. Immune complexes increased after perfusion and remained elevated fo 72 hours. Findings suggest that the acute tumoricial responses are not due to mere removal of circulating immune reactants and may be initiated by TAA that are rendered operational after extracorporeal perfusion over SAC. The rapidity, specificity, and magnitude of the observed tumoricidal effects in various canine neoplastic diseases suggests that this may have potentially broad-based therapeutic and biologic implications for canine neoplasia.

Adenocarcinoma↗
PubMed1989

Results of regional isolation perfusion with cytostatics in patients with soft tissue tumors of the extremities.

From 1975 to 1986, 26 patients with soft tissue tumors of the extremities underwent a total of 29 perfusions. The cytostatics used were doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) (19 perfusions), melphalan (two perfusions), and a combination of these agents (eight perfusions). Before perfusion most patients had been treated by surgical excision(s), radiotherapy, or systemic chemotherapy. Of 17 patients perfused because of local inoperable tumor, four showed prolonged complete remission of the tumor mass, stable disease was seen in three, and ten showed progression. The complete remissions observed in three patients with aggressive fibromatosis and in one with lymphangiosarcoma occurred after perfusion with doxorubicin combined with melphalan. Doxorubicin added to the perfusate as the sole cytostatic was not effective. Local recurrence was observed in five of nine patients treated by adjuvant perfusion, always after dubiously radical tumor excision. Toxicity was high, especially in the first few years. Tissue necrosis necessitated amputation in three cases (in two after perfusion with doxorubicin and melphalan and in one after repeated perfusion with doxorubicin only). This complication was no longer seen after adjustment of the dosage and dose distribution of doxorubicin, but the morbidity after perfusion with doxorubicin remained considerable.

Adolescent↗
PubMed1989

Effects of hyperthermia on xanthine oxidase activity and glutathione levels in the perfused rat liver.

The hepatotoxic effects of hyperthermic liver perfusion were investigated in male Fischer 344 rat livers. Perfusions were carried out at 37, 41, 42, 42.5, and 43 degrees C for 2 hr. During the 2 hr, the perfusate was analyzed for activity of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), N-acetyl-beta-glucosaminidase (NAG), and glutathione (GSH), oxidized glutathione (GSSG), allantoin, and potassium. After perfusion, each liver was homogenized and analyzed for total xanthine oxidase (XO) activity, percentage type-D and type-O XO, and total GSH content. Perfusate AST, LDH, NAG, and potassium levels were increased significantly with time and were significantly different in all hyperthermic perfusions from the 37 degrees C perfusion values by the end of the perfusion. Perfusate GSH + GSSG levels were increased significantly in all hyperthermic perfusions after 60 min. Liver GSH levels were significantly lowered following perfusion at hyperthermic temperatures. There was a temperature-dependent increase in the percentage of XO in the type-O form following perfusion at hyperthermic temperatures, which was strongly and positively correlated with the loss of hepatic GSH. These data support the hypothesis that hyperthermic toxicity to the liver is the result of oxidative stress brought about by conversion of XO to the type-O form.

Acetylglucosamine↗
PubMed1995

Further investigations into the mechanism of antifibrillatory action of the specific IK1 blocker, RP58866, assessed using the rat dual coronary perfusion model.

RP58866 (1-[-2-(3,4-dihydro-2H-1-benzopyran-4-yl)ethyl]-4- (3,4-dimethoxyphenyl)-piperidine), a specific blocker of the inwardly rectifying K+ current (IK1), is an extremely effective antiarrhythmic agent in rat, rabbit and primate (marmoset) isolated hearts in the settings of acute ischaemia and reperfusion (Rees and Curtis, 1993a). In the present study we further examined the mechanism of action of RP58866. We used the new dual coronary perfusion cannula that allows left and right sides of the heart to be perfused independently. The model has not previously been used for pharmacological investigations. Isolated rat hearts (n = 112) were randomized to one of four groups: perfusion of the left and right coronary beds with drug-free solution (n = 28), perfusion of the left coronary bed with 3 mumol/l RP58866 (n = 28), perfusion of the right coronary bed with 3 mumol/l RP58866 (n = 28) or perfusion of left and right coronary beds with 3 mumol/l RP58866 (n = 28). After 5 min perfusion, left regional ischaemia was induced and maintained for 30 min. Regional coronary flow was measured by in-line flowmeters. Epicardial monophasic action potentials (MAP) were recorded from the left (n = 15/group) and right (n = 13/group) perfusion regions using a suction electrode. Delivery of RP58866 to the uninvolved zone (right perfusion bed) suppressed ischaemia-induced ventricular fibrillation (VF): incidences (%) of VF were 80, 60, 33 (P < 0.05) and 27% (P < 0.05) in groups with no drug, with RP58866 delivered to the left bed, with RP58866 to the right bed and with RP58866 to the left plus right beds, respectively. Protection correlated with widening of MAP duration in the uninvolved zone which at 100% repolarization was 130.6 +/- 8.0, 129.1 +/- 7.0, 155.8 +/- 6.5 (P < 0.05 versus control) and 155.3 +/- 8.7 (P < 0.05) in the four groups, respectively after 5 min of ischaemia (just prior to the onset of ventricular arrhythmias). Corresponding values recorded from the involved zone (left perfusion bed) were 102.6 +/- 7.8, 131.2 +/- 11.1 (P < 0.05), 138.2 +/- 11.6 (P < 0.05) and 147.1 +/- 8.9 ms (P < 0.05), suggesting that RP58866 may gain access to ischaemic tissue via collatoral flow from the right perfusion bed. In order to suppress ischaemia-induced VF, it appears that the IK1 blocker RP58866 must widen APD in uninvolved tissue. APD widening activity restricted to the involved tissue alone is insufficient to prevent VF. However, caution should be exercised when using the dual coronary perfusion model to assess pharmacological activity since, even in rat, a species with extremely low collateral flow, there is evidence of cross-flow between the left and right ventricles.

Animals↗
PubMed1984

A comparison of the effects of different perfusion regimes on the structure of the isolated human placental lobule.

Isolated lobules of normal term human placentas were perfused using two different procedures. In the first more conventional system, open-circuit perfusion of both the maternal and the fetal circulations with Earle's solution containing dextran was established and maintained for either 30 min or 1 h. In the second series of experiments both circulations were perfused in separate closed circuits with a mixture of fresh autologous fetal blood and Earle's solution for 0, 1, 2 or 3 h. In both series the lobule was then fixed by perfusion through the fetal circulation. Light- and electron-microscopic examination of a set of tissue samples from each perfused lobule showed substantial differences between the effects of these two types of perfusion procedure. Tissue from lobules perfused by the open-circuit blood-free procedure showed patchy but severe cell swelling and vacuolation of the trophoblast after only one hour's perfusion. Particularly striking was swelling and disruption of a large proportion of the mitochondria in all placental cell types. By contrast, placental tissue from the closed-circuit perfusion with blood-containing medium showed little change over a period of two hours, while after three hours it showed oedema and microvillous damage, but no sign of cell swelling and little mitochondrial damage. It is concluded that the viability of the perfused human placental lobule depends on the type of perfusate used, and that the use of a fetal blood-enriched perfusate is of considerable value in maintenance of the preparation as assessed by structural criteria.

Culture Media↗
PubMedDate not supplied

Leukocyte activation by isolated hyperthermic liver and limb perfusion due to malignancy.

Fourteen patients with liver tumor malignancy and sixteen patients with malignant melanoma localized to one limb were studied regarding leukocyte activation with the release of polymorphonuclear neutrophilic (PMN) elastase and of neopterin and formation of cytokines (TNF-alpha and IL-6) during the surgical treatment. Patients undergoing liver resection (n = 10), abdominal hysterectomy (n = 10), or hip replacement surgery (n = 10) served as control groups. Isolated hyperthermic liver perfusion was performed with cytostatic-containing perfusate (melphalan and cisplatinum). Patients with recurrent malignant melanoma confined to one limb underwent isolated hyperthermic limb perfusion with cytostatic-containing perfusate (melphalan). Blood samples for determination of PMN elastase, neopterin, TNF-alpha, and IL-6 were drawn from the patients preoperatively, 1 minute before the start of the perfusion, 60 and 120 minutes after the start of the perfusion, and 24 hours postoperatively. Samples from the perfusate were drawn 60 minutes after the start of the perfusion. High concentration of plasma PMN elastase were found in both patients undergoing liver and limb perfusion and in patients undergoing liver resection surgery. Elevated concentrations of IL-6 were found in the patients undergoing liver perfusion and in patients undergoing liver resection. In none of the patients were there increased concentrations of neopterin or TNF-alpha. The perfusate contained high concentrations of PMN elastase, neopterin, and IL-6. This study also demonstrated that major surgery leads to elevated concentrations of PMN elastase and IL-6. An increase of PMN elastase and IL-6 was seen in response to perfusion and to surgical trauma.

Adult↗
PubMed1997

Electrolyte equilibration of human kidneys during perfusion with HTK-solution according to Bretschneider.

Twelve surgically removed human kidneys (mainly tumor kidneys) were investigated. The investigations comprised perfusion criteria (perfusion flow, perfusion pressure, perfusion resistance, electrolyte equilibration). During perfusion of the kidneys with HTK solution, the perfusion resistance was nearly three times as high in human kidneys as in canine kidneys perfused under the same conditions in previous studies. Beside possible species differences the raised perfusion resistance may be explained by the greater trauma to the human kidneys due to the surgery, the primary ischemic stress which cannot be avoided clinically and the often nonoptimal initial diuresis. Nevertheless definitive perfusion is possible under clinical conditions although pronounced increases of perfusion resistance may occur. As indicated by the raised perfusion resistance of human kidneys under clinical conditions as compared with canine kidneys in an experimental model, electrolyte equilibration of human kidneys was protracted. For this reason, a duration of perfusion of at least 10 min is necessary in clinical application of HTK solution, i.e., longer than in animal experiments.

Glucose↗