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Stimulation of bile and pancreatic secretion by duodenal perfusion with Na-taurocholate in the cat compared with jejunal and ileal perfusion.

In the anesthetized cat duodenal perfusion with Na-taurocholate (TC, 0.2 M, pH 6.1, 290 mosmol, 45 ml x h-1) stimulated pancreatic volume (0 to 326 +/- 236 mg x 10 min-1) and bicarbonate secretion (0 to 34.2 +/- 4.1 mumol x 10 min-1), whereas pancreatic enzyme output was sparse. Simultaneously with the pancreatic response, bile flow increased from 139 +/- 74 mg to 484 +/- 146 mg x 15 min-1 (p < 0.05). During perfusion of the upper jejunum both pancreatic and biliary responses were significantly lower than the responses to duodenal TC perfusion (p < 0.05). During TC perfusion of the terminal ileum there was no response from the pancreas, whereas the increase in bile flow accounted only for an increase in the bile-acid-dependent fraction. The concomitant stimulation of both the hydrokinetic function of the pancreas and the bile-acid-independent bile flow might be mediated by a release of secretin.

Animals↗

Comparison of 2 techniques for regional antibiotic delivery to the equine forelimb: intraosseous perfusion vs. intravenous perfusion.

The purpose of this study was to compare the synovial fluid concentrations and pharmacokinetics of amikacin in the equine limb distal to the carpus following intraosseous and intravenous regional perfusion. The front limbs of 6 horses were randomly assigned to either intraosseous or intravenous perfusion. A tourniquet was placed distal to each carpus and the limb perfused with 500 mg of amikacin. Systemic blood samples and synovial fluid samples were collected over 70 min from the distal interphalangeal (DIP) joint, metacarpophalangeal joint, and digital flexor sheath. The tourniquet was removed following the 30 min sample collection. The mean peak amikacin concentration for the DIP joint was significantly higher with intravenous perfusion. There were no significant differences in time to peak concentration or elimination half-life between methods at each synovial structure. Each technique produced mean peak concentrations ranging from 5 to 50 times that of recommended peak serum concentrations for therapeutic efficacy.

Amikacin↗

Geometric resistance to blood flow in solid tumors perfused ex vivo: effects of tumor size and perfusion pressure.

In a vascular network blood flow rate is proportional to the arteriovenous pressure difference and inversely proportional to the viscous and geometric resistances. The geometric resistance to tumor blood flow was determined by perfusing tissue-isolated mammary adenocarcinoma (R3230AC; N = 40; tumor weight, 1.8 +/- 1.2 (SD) g; range, 0.5-6.6 g) ex vivo with an acellular Krebs-Henseleit medium (viscosity, 0.9 g/m/s) at rates of 0.1 to 60 ml/h and arteriovenous pressure differences of 0 to 120 mm Hg. Below perfusion pressures of 40 mm Hg, pressure-flow behavior was always nonlinear, indicating elevated geometric resistance and a reduction in vascular cross-sectional area with decreasing microvessel pressure. However, above 40 mm Hg, pressure-flow behavior was linear demonstrating a constant geometric resistance, z0 and a constant vascular cross-sectional area for flow. z0 increased linearly from 1.6 to 17.3 X 10(8) g/cm3 as tumor weight increased from 0.5 to 6.6 g. This dependence of z0 upon tumor size is in agreement with the decrease in tumor perfusion rates with tumor growth observed in vivo. Comparison with previous studies of normal organs and tissues shows that z0 in tumors can be as much as 1-2 orders of magnitude higher, depending upon tumor weight. This dependence of geometric resistance on perfusion pressure and tumor size offers novel insights into the dynamics of tumor microcirculation and has significant clinical implications.

Animals↗

Furosemide choleresis in isolated perfused rat liver: partial dependency on perfusate sodium and chloride.

The effect of furosemide on hepatic bile formation was studied in isolated perfused rat liver to determine if 1) the observed cholestatic effect at lower dose of furosemide in vivo is a primary effect or a secondary effect due to decreased hepatic blood flow caused by the furosemide-induced volume contraction and if 2) the observed choleretic effect at higher doses can be explained by the osmotic effect of furosemide and its metabolites in bile. A single dose of furosemide (initial perfusate concentration 0.01, 0.1 or 1 mM) produced choleresis, whereas 0.001 mM furosemide did not affect bile flow significantly. Because furosemide failed to produce cholestasis at tested doses, the observed cholestasis in vivo at similar blood concentrations must be a secondary effect. Furosemide choleresis was associated with biliary secretion of furosemide and its metabolites. However, the choleretic effect expressed as microliters per micromole of drug secreted declined with increasing dose and biliary secretion. Furosemide choleresis was also associated with an increase in the net biliary secretion of Na+ and Cl-. The effect of Na+ and Cl- replacement on furosemide choleresis was studied to determine if the choleresis was a result of direct effect of furosemide on hepatic electrolyte transport. Replacement of perfusate Na+ completely by Li+ or partially by choline+ resulted in a 30 to 50% reduction in choleretic effect and furosemide-induced biliary Cl- secretion. A similar decline in choleretic effect and net furosemide-induced biliary Na+ secretion was also observed when perfusate Cl- was replaced by nitrate, acetate or isethionate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Myocardial protection by intermittent perfusion with cardioplegic solution versus intermittent coronary perfusion with cold blood.

The myocardial protection provided by cardioplegic solution using buffered, isosmotic potassium (30 mEq. per liter) was compared with intermittent cold coronary perfusion for 2 hours of aortic cross-clamping in dogs. The cardioplegic solution (Group CS) or cold blood (Group CB) was infused every 15 minutes through a cooling coil to reduce the perfusate temperature to 5 degrees C. Myocardial function after 30 minutes of reperfusion and rewarming was reduced in Group CB with a significant reduction in peak systolic pressure at a left ventricular (LV) balloon volume of 20 ml. and a significant reduction of dp/dt. In contrast, in Group CS, LV function was unchanged from the base-line period. LV compliance also was significantly reduced in Group CB while being unchanged in Group CS. Myocardial extravascular water content, obtained by dessication, was significantly higher in Group CB than in Group CS, which may explain the reduction in compliance. Electron microscopy showed normal ultrastructure in Group CS but extracellular edema in Group CB. Total coronary blood flow showed a sustained increase during reperfusion in both groups. Oxygen consumption rose with rewarming to base-line levels in both groups, whereas lactate and pyruvate consumption was reduced in both groups, particularly Group CB. Cardioplegic solution thus appears to be superior to the intermittent perfusion of cold blood for myocardial protection. The addition of potassium arrest, by markedly reducing myocardial metabolism, improves the protection afforded by cold blood perfusion alone.

Animals↗

[Effect of potassium concentration of the perfusion solution on organ resistance of the perfused dog pancreas].

The influence of different potassium concentrations in the perfusate on the perfusion pressure of isolated dog pancreas is reported. A potassium concentration above 30 mmol/l leads both under hypothermic and normothermic conditions to an increase of the vascular resistance, That's why organs with a small blood flow should be perfused with solutions poor in potassium also in the initial perfusion.

Animals↗

Twenty-four hour intermittent perfusion storage of the isolated rat heart: the effect of perfusion intervals on functional preservation.

We investigated the effect of intermittent perfusion intervals on heart preservation. The isolated rat heart was flushed with a cardioplegic solution, CP-11EB, and stored at 0 degrees C for 24 hours. During storage, the heart was perfused periodically at 60 mm Hg for 3 minutes with 25 degrees C oxygenated CP-11EB. The perfusion schedules were as follows: group I, every 4 hours; group II, every 6 hours; group III, every 8 hours; group IV, every 10 hours; group V, 10 and 17 hours of storage; group VI, every 11 hours. Poststorage function was assessed after 30 minutes of working reperfusion. Function of the unstored hearts including aortic flow (51.5 +/- 2.5 ml/min), coronary flow (24.5 +/- 1.3 ml/min), cardiac output (75.6 +/- 3.0 ml/min) and work (85.0 +/- 5.4 g-ml/min) served as controls. Group V hearts were best preserved with aortic flow recovered to 65%; coronary flow 44%; cardiac output 58%; and work 53% of the control. Recovery in group IV was comparable with group V. Groups I, II, III, and VI recovered significantly less than group V. Myocardial adenosine triphosphate content (micromoles per gram dry) in group V was 23.8 +/- 1.7, 20.8 +/- 0.9, 13.5 +/- 2.4, and 15.0 +/- 4.0, at 0, 10, 17, and 24 hours of storage, respectively. Intermittent perfusion at 10 and 17 hours elevated adenosine triphosphate to 99% and 88% of prestorage level. Poststorage reperfusion did not improve improve adenosine triphosphate content (16.2 +/- 2.4) over the end-storage level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

[Experimental study of optimal perfusion pressure during retrograde cerebral perfusion].

The effects of retrograde perfusion pressure on the brain was experimentally investigated during profound hypothermic circulatory arrest. Fifteen adult mongrel dogs were placed cardiopulmonary bypass and induced profound hypothermia of 20 degrees C at nasopharyngeal temperature. Retrograde cerebral perfusion (RCP) with perfusion pressure of 10 mmHg (RCP10; n = 5), 20 mmHg (RCP20; n = 5), 30 mmHg (RCP30; n = 5) underwent for 60 minutes. The oxygenated blood was infused via the bilateral maxillary veins, and the flow rate was kept to maintain a desired pressure in the external jugular vein for each group. Regional cerebral blood flow (rCBF), excess lactate, cerebrospinal fluid pressure (CSFP), adenosine triphosphate (ATP) concentration of cerebral tissue, and water content of cerebral tissue were measured. In the RCP10 group, cerebral excess lactate was positive and ATP concentration was low. In the RCP30 group, the water content of cerebral tissue was significantly higher than those in the other groups. In the RCP20 group, the excess lactate was maintained in a negative range, and ATP concentration was significantly higher than in the RCP10 group. In conclusion, RCP may provide metabolically adequate support for the brain and a perfusion pressure of 20 mmHg was appropriate for RCP in dogs.

Animals↗

[Effect of ritodrine hydrochloride on fetal perfusion pressure in dually perfused human placenta].

Ritodrine hydrochloride is widely used in clinical obstetrics for the prevention of premature labor, but the knowledge of its effect on fetal circulation is limited. The purpose of this study was to elucidate changes in vascular resistance in the fetal placental circulation by using the dually perfused human placenta in vitro. The viability of the perfused placenta was maintained during the experiments because the production rate of hCG was constant. The transfer of ritodrine hydrochloride was observed and its concentration on the fetal side was about one third of maternal side at 120 min subsequent to the injection. The fetal perfusion pressure during the control period was 38.6 +/- 7.0 mmHg (mean +/- S.D., n=3). After the addition of ritodrine hydrochloride to the maternal circulation, the fetal perfusion pressure was decreased dose-dependently. The pressure was 95.4 +/- 1.8% at 80 ng/ml of ritodrine hydrochloride which was within the clinical concentration limits. It is concluded that ritodrine hydrochloride acts as a vasodilator on the fetal vasculature in the human placenta.

Adrenergic beta-Agonists↗

Determination of antiviral nucleoside analogues AM365 and AM188 in perfusate and bile of the isolated perfused rat liver using HPLC.

Development, validation and application of an HPLC assay for new antiviral nucleoside analogues AM365 and AM188 in isolated perfused rat liver perfusate and bile were performed. An analytical column (Phenosphere-NEXT, 250 x 4.6 mm, C(18), 4 microm, Phenomenex) was used in tandem with a guard column (4 x 3 mm, C(18), Phenomenex) and operated at 25 degrees C. The mobile phase [methanol:10 mmol/L sodium orthophosphate buffer (pH 7.0), 15:85, v/v] was pumped at 1 mL/min. The signal from a diode array detector was collected from 190 to 300 nm. The chromatogram was processed at 220 and 252 nm for AM365 and AM188, respectively. The HPLC method was validated by six intraday and seven interday runs. Standard curves were linear in the range 0.125-8.00 microg/mL for AM365 and AM188, and the lower limit of quantification for AM365 and AM188 was 0.125 microg/mL. Mean interday precision and accuracy of IPL perfusate quality control samples were within 8.8%, and mean intraday precision and accuracy were within 13.1%. The assay has been successfully used in the study of metabolism and disposition of AM365 in the isolated perfused rat liver.

Animals↗

Sensitivity of mechanical and metabolic functions to changes in coronary perfusion: A metabolic basis of perfusion-contraction coupling.

Experimental evidence indicates a metabolic basis of contraction-perfusion coupling during an increase in cardiac work load. This study aims to characterize adjustment of myocardial energy metabolism in response to acute low flow ischemia (LFI), and to determine its involvement in perfusion-contraction coupling. Intracellular parameters were measured in isolated rat hearts by NMR spectroscopy and biochemical methods during 30 min of graded LFI and reperfusion as compared to continuous perfusion (control). Oxygen pressure was set to reach maximal oxygen extraction at 70% coronary flow rate (CFR), therefore oxygen limitation was proportional to coronary underperfusion. At 69, 38 and 10% CFR left ventricular pressures decreased to 71, 43 and 25% of pre-ischemic values respectively (P<0.005 v 97% in control) without an increase in diastolic tone, and recovered to 92+/-3% after 30 min of reperfusion. Despite hydrolysis of high energy phosphates and cellular acidification, ADP concentrations were stable in underperfused hearts. At 69, 38 and 10% CFR, cytosolic phosphorylation potentials (PP) decreased from 74+/-10 m M(-1)during pre-ischemia to 40+/-6, 25+/-4 and 14+/-4 m M(-1)respectively (P<0.05 v 63+/-9 m M(-1)in control), and lactate efflux increased to 256+/-18, 386+/-22 and 490+/-43 micromol /gdw respectively (P<0.005 v 186+/-22 micromol/gdw in control). Glycogen contents decreased (P<0.005 v control) and accounted for 27-30% of lactate efflux. These results indicate: (a) proportionate depression of contraction force and glycogen contents, and increased glucose uptake and anaerobic energy production in the underperfused myocardium. Coordinated modulation of these parameters attributes cytosolic PP a regulatory function; (b) resetting of cytosolic PP to lower levels mediates perfusion-contraction coupling during graded LFI. The data are consistent with the concept that glycolytic energy production improves myocardial tolerance to ischemia.

Aerobiosis↗

Comparison of technetium-99m sestamibi left ventricular wall motion and perfusion studies with thallium-201 perfusion imaging: in search of the combination of variables with the highest accuracy in predicting coronary artery disease.

Measurements of myocardial perfusion and ventricular function are expected to provide additional information in the detection of coronary artery disease (CAD). The purpose of this study was threefold: (1) to determine to what extent technetium-99m sestamibi wall motion yields different information compared with 99mTc-sestamibi and thallium-201 perfusion; (2) to test which information unique to either study is of value in diagnosing CAD; and (3) to assess the combination of variables with the highest diagnostic accuracy. Perfusion and wall motion scores (at rest and during exercise) obtained from visual and quantitative planar 201Tl and 99mTc-sestamibi scintigraphy of 60 patients with suspected CAD were compared with the angiographic results by means of a polytomous logistic regression model and the diagnostic values were compared with one another. All univariate variables were significantly related to the probability of CAD and its extent. Comparative studies revealed a large degree of correlation between 201Tl stress and redistribution variables. The rest 99mTc-sestamibi and wall motion studies contained partially different information. Stepwise logistic regression analysis showed the strongest diagnostic power for the combination of 201Tl visual analysis of the stress images with quantitative redistribution images (sensitivity 93%, specificity 71%). The diagnostic power was similar for all combinations of visual and quantitative analyses of the exercise and redistribution images. The strongest diagnostic power of the 99mTc-sestamibi variables was the score of the diastolic stress image (sensitivity 91%, specificity 79%). Comparable sensitivity and specificity estimates were found when both optimal models were compared. Wall motion studies did not have additional diagnostic power. Although 99mTc-sestamibi wall motion studies, both at rest and during exercise, provide information in addition to the 99mTc-sestamibi or 201Tl myocardial perfusion variables, the information does not enhance the diagnostic power with regard to the prediction of CAD.

Coronary Angiography↗

Evolution of pulmonary perfusion defects demonstrated with contrast-enhanced dynamic MR perfusion imaging.

Pulmonary perfusion defects can be demonstrated with contrast-enhanced dynamic MR perfusion imaging. We present the case of a patient with a pulmonary artery sarcoma who presented with a post-operative pulmonary embolus and was followed in the post-operative period with dynamic contrast-enhanced MR perfusion imaging. This technique allows rapid imaging of the first passage of contrast material through the lung after bolus injection in a peripheral vein. To our knowledge, this case report is the first to describe the use of this MR technique in showing the evolution of peripheral pulmonary perfusion defects associated with pulmonary emboli.

Contrast Media↗

The role of neuropeptides in the regulation of adrenal vascular tone: effects of vasoactive intestinal polypeptide, substance P, neuropeptide Y, neurotensin, Met-enkephalin, and Leu-enkephalin on perfusion medium flow rate in the intact perfused rat adrenal.

There is evidence that adrenal blood flow may be regulated in part by neuropeptides released from the capsular region of the adrenal gland in response to splanchnic nerve stimulation. The present study investigated the effects of various neuropeptides on the rate of perfusion medium flow through an intact in situ perfused rat adrenal preparation. Vasoactive intestinal polypeptide (VIP) had the greatest effect, causing a 136% increase in flow at the highest dose used (10 nmol in a 200 microliters bolus). Of the other peptides tested Met-enkephalin caused a 50% increase in flow, and the others (Leu-enkephalin, neurotensin and substance P) had only a minor effect, increasing perfusion medium flow rate by no more than around 35%. Neuropeptide Y, in contrast, caused a significant decrease in perfusion medium flow rate: the maximum effect was a 30% decrease with a dose of 1 nmol in a 200 microliters bolus. The significance of this observation awaits elucidation. It is clear from the actions of the neuropeptides tested that they may have a significant role in the regulation of adrenal blood flow. In view of the findings of other authors: that VIP is released in response to splanchnic nerve stimulation, and that it is specifically localised in the capsular region of the adrenal, it seems most likely that VIP is the major peptide involved in mediating the increased adrenal blood flow following splanchnic nerve stimulation.

Adrenal Glands↗

Prevalence and prognostic value of perfusion defects detected by stress technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography in asymptomatic patients with diabetes mellitus and no known coronary artery disease.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in diabetics. Early diagnosis of CAD and identification of high-risk subgroups, followed by appropriate therapy, may therefore enhance survival. This study sought to determine the value of stress myocardial perfusion single-photon emission computed tomography (SPECT) with technetium-99m sestamibi to detect perfusion defects and predict cardiac events in asymptomatic diabetics. One hundred eighty asymptomatic diabetics without known CAD who underwent 2-day stress technetium-99m sestamibi SPECT were followed up for 36 +/- 18 months. End points were defined as hard (myocardial infarction or cardiac death) or total events (myocardial infarction, cardiac death, or late revascularization). Logistic regression analysis evaluated clinical variables, type of stress, exercise treadmill test (ETT), and SPECT as predictors of end points. Perfusion defects were found in 26% of patients (15% reversible, 6% mixed, and 5% fixed). Clinical or ETT variables were not associated with perfusion defect type or with hard events. However, male gender predicted total events (chi-square 3.3; p = 0.01). An abnormal SPECT significantly increased the risk of hard events (chi-square 5.4; p = 0.001) and total events (chi-square 7.4; p = 0.0001). Extensive defects determined the highest risk of total events (chi-square 18.8; p = 0.0001). Event rates increased according to SPECT: 2% of hard events per year and 5% of total events per year in patients with normal SPECT versus 9% per year and 38% per year, respectively, in those with abnormal SPECT. Importantly, a normal SPECT identified a relatively low-risk subgroup of patients. Thus, stress technetium-99m sestamibi SPECT was useful in evaluating asymptomatic diabetics for the presence of CAD, and effectively risk-stratified this population.

Aged↗

Prospective randomized neurocognitive and S-100 study of hypothermic circulatory arrest, retrograde brain perfusion, and antegrade brain perfusion for aortic arch operations.

BACKGROUND: To determine the optimal method of brain protection during deep hypothermic circulatory arrest (DHCA) for arch repair. METHODS: Of 139 potential aortic arch repairs (denominator), we randomized 30 patients to either DHCA alone (n = 10), DHCA plus retrograde brain perfusion (RBP) (n = 10), or antegrade perfusion (ANTE) (n = 10); a further 5 coronary bypass (CAB) patients were controls. Fifty-one neurocognitive subscores were obtained for each patient at each of four intervals: preoperatively, 3 to 6 days postoperatively, 2 to 3 weeks postoperatively, and 6 months postoperatively. Intraoperative and postoperative S-100 blood levels and electroencephalograms were also obtained. RESULTS: For the denominator, the 30-day and hospital survival rate was 97.8% (136 of 139) and the stroke rate 2.8% (4 of 139). For the randomized patients, the survival rate was 100% and no patient suffered a stroke or seizure. Circulatory arrest (CA) times were not different (DHCA: RBP:ANTE) for 11 total arch repairs (including 6 elephant trunk; mean, 41.4 minutes; standard deviation, 15). Hemiarch repairs (n = 17) were quickest with DHCA (mean 10.0 minutes; standard deviation, 3.6; p = 0.011) and longest with ANTE (mean 23.8 minutes; standard deviation, 10.28; p = 0.004). Of the patients, 96% had clinical neurocognitive impairment at 3 to 6 days, but by 2 to 3 weeks only 9% had a residual new deficit (1 DHCA, 1 RBP, 1 ANTE), and by 6 months these 3 patients had recovered. Comparison of postoperative mean scores showed the DHCA group did better than RBP patients in 5 of 7 significantly different (p < 0.05) scores and versus 9 of 9 ANTE patients. There were no S-100 level differences between CA groups, but levels were significantly higher versus the CAB controls, particularly at the end of bypass (p < 0.0001); however, these may have been influenced by other variables such as greater pump time, cardiotomy use, and postoperative autotransfusion. Circulatory arrest (p = 0.01) and pump time (p = 0.057) correlated with peak S-100 levels. CONCLUSIONS: The results of hypothermic arrest have improved; however, there is no neurocognitive advantage with RBP or ANTE. Nevertheless, retrograde brain perfusion may, in a larger study, potentially reduce the risk of strokes related to embolic material. S-100 levels may be artificial. In patients with severe atheroma or high risk for embolic strokes, we use a combination of retrograde and antegrade perfusion on a selective basis.

Aged↗

The effect of short-term coronary perfusion using a perfusion apparatus on canine heart transplantation from non-heart-beating donors.

BACKGROUND: We investigated the effects of briefly perfusing hearts from non-heart-beating donors (NHBDs) with a Celsior solution before cardiac transplantation. METHODS: Donor hearts were left in situ for 20 minutes after cardiac arrest was induced by rapid exsanguination. Twelve donor-recipient pairs of mongrel dogs were divided into 2 groups, the simple immersion (SI, n = 6) group and the coronary perfusion (CP, n = 6) group. Both groups underwent coronary flushing with Celsior, after which hearts from the SI group were stored using simple immersion for 4 hours and hearts from the CP group underwent 1 hour of further perfusion followed by storage for 3 hours. Orthotopic transplantation was then performed. We measured cardiac output, end-systolic maximal elastance (E(max)), left ventricular pressure, and rate pressure product 1 and 2 hours after weaning from cardiopulmonary bypass (CPB). Two hours after weaning from CPB, the hearts were harvested for histopathologic study and to determine the percentage of water content. RESULTS: The cardiac output (CO) recovery rate was significantly higher in the CP group than in the SI Group 1 hour after weaning from CPB (p < 0.05). The CO recovery rate, E(max), and rate pressure product were significantly higher and the percentage of water content was significantly lower in the CP group than in the SI Group 2 hours after weaning from CPB (p < 0.05). Histopathologic damage was more severe in the SI group. CONCLUSIONS: The results of this study suggest that short-term coronary perfusion with a Celsior solution may be useful for heart transplantation from NHBDs.

Animals↗