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At least 19 recordsLinked to original sources
PubMed1992

Kinin metabolism in the perfused ventilated rat lung. II: Influence of ventilation, perfusion, and perfusate composition variation on bradykinin metabolism in uninjured lung.

Bradykinin metabolism by peptidases of the pulmonary endothelium has been investigated in the previously uninjured, ventilated, and asanguinously perfused rat lung. The influence of short-duration (up to 20 min) abnormal ventilation and perfusion conditions on bradykinin metabolism was assessed. Neither variation of the oxygen concentration (0 to 45%) nor omission of carbon dioxide in the ventilatory gas altered bradykinin metabolism significantly. Tidal volume variation did not alter bradykinin metabolism, and exclusion of one lung from the perfusion circuit reduced the capacity to degrade bradykinin proportionately. Acidification of the perfusion medium to pH 5 did not alter bradykinin metabolism. Acetylsalicylic acid in the perfusate protected the lung from an otherwise irreversible pressure increase associated with high-dose bradykinin perfusion. Endotoxin and hydrogen peroxide in the perfusate did not alter bradykinin metabolism. However, ammonia in the ventilatory gas caused immediate pulmonary edema, diminished lung capacity to metabolize bradykinin and altered the pattern of bradykinin metabolic products. The pulmonary endothelium itself, in the absence of blood, maintains its capacity to metabolize bradykinin under an extraordinary range of conditions.

Amino Acid Sequence↗
PubMed1992

The response to ischemia in blood perfused vs. crystalloid perfused isolated rat heart preparations.

With a research hypothesis that the behavior of blood perfused hearts was different from that of crystalloid perfused hearts, we tested the null hypothesis that the functional and metabolic status of blood-perfused (paracorporeal oxygenation) and Krebs-Henseleit (bubble oxygenation) perfused Langendorff isolated rat hearts is the same before, during and after global myocardial ischemia. Thirty isolated rat hearts were studied under identical conditions except that in equal numbers they were randomly assigned to either blood or crystalloid perfusion. In the blood perfused and crystalloid perfused hearts subjected to 22 min of normothermic ischemia and 30 min of reperfusion, mean systolic recovery was 72 +/- 3.9% (S.E.) and 20 +/- 10% (P = 0.001), respectively; coronary resistance increased 21 +/- 16% and 158 +/- 27% (P = 0.0003) (unadjusted for viscosity); mean water content after reperfusion was 82.0 +/- 0.43% and 86.7 +/- 0.42% (P < 0.0001), ATP content was 8.4 +/- 1.9 and 4.3 +/- 0.5 mumol/g dry wt (P = 0.08), and energy charge was 0.74 +/- 0.114 and 0.59 +/- 0.048 (P = 0.3). A major qualitative difference during reperfusion was spontaneous relaxation of contracture and rapid resumption of sinus rhythm in blood perfused hearts, in contrast to continued contracture and rise in intraventricular pressure in 9 of 10 crystalloid perfused hearts. One crystalloid perfused heart did not develop contracture, and its phenomena during reperfusion were similar to those of blood perfused hearts. The data support the research hypothesis, and suggest caution in extrapolating to blood perfused systems inferences from crystalloid perfused models. Better preservation of reactive hyperemia early in reperfusion may explain the better performance of blood perfused hearts.

Adenosine Triphosphate↗
PubMedDate not supplied

Low-pressure perfusion results in effective microvascular perfusion of isolated rabbit hearts during hypothermic preservation for twenty-four hours.

Hypothermic, low-pressure coronary artery perfusion with oxygenated electrolyte solutions containing oncotic agents has resulted in successful orthotopic transplantation of hearts after extended preservation periods. Coronary flow may not, however, be consistently maintained during preservation. Previous research has demonstrated that coronary flow during preservation is related to contractile function after preservation. Specific mechanisms leading to reduced coronary flow during preservation remain undefined. This study was designed to determine whether low-pressure perfusion is a mechanism for decreased coronary flow and decreased microvascular perfusion during preservation. With India ink used as a marker of flow, microvascular perfusion was measured in rabbit hearts immediately after isolation (controls) or after 24 hours of hypothermic perfusion at 13 mm Hg (preserved hearts). There were no differences in the percentage of perfused microvessels in the control hearts perfused at either 13 or 80 mm Hg (94% +/- 2% and 99% +/- 1%, respectively). Nor was there a difference in the percentage of perfused microvessels in hearts perfused at either 13 or 80 mm Hg after 24 hours of hypothermic, low-pressure perfused preservation (67% +/- 9% and 74% +/- 6%, respectively). There was a significant difference, however, between the percentage of perfused microvessels in control hearts and in hearts preserved for 24 hours. These differences were independent of the pressure at which the India ink solution was administered. A perfusion pressure of 13 mm Hg is as effective as is 80 mm Hg in providing perfusion of the coronary microvascular beds during long-term hypothermic perfused preservation.

Analysis of Variance↗
PubMed1992

Comparison of ischemic vulnerability and responsiveness to cardioplegic protection in crystalloid-perfused versus blood-perfused hearts.

The possibility of differences between crystalloid-perfused and blood-perfused hearts in their vulnerability to ischemia and responsiveness to protective interventions has been investigated in isolated rabbit hearts perfused with bicarbonate buffer or arterial blood. In preliminary studies with 165 minutes of aerobic perfusion at constant perfusion pressure (55 +/- 3 mm Hg), the stability of left ventricular developed pressure was significantly better in blood-perfused hearts. In subsequent studies, hearts were subjected to 20 minutes of aerobic perfusion (coronary flow, 2.0 +/- 0.3 ml/min/gm wet weight in blood-perfused hearts versus 11.3 +/- 3.0 ml/min/gm wet weight in crystalloid-perfused hearts; left ventricular developed pressure, 90 +/- 4 and 91 +/- 2 mm Hg, respectively) followed by 30, 45, 60, 75, 90, or 105 minutes of normothermic global ischemia and 40 minutes of reperfusion (n = 4 per group). In the buffer-perfused groups the postischemic recoveries of left ventricular developed pressure were 74% +/- 6%, 45% +/- 7%, 39% +/- 6% 32%, +/- 5%, 27% +/- 4%, and 12% +/- 3% of preischemic control, respectively. In blood-perfused groups they were consistently greater (91% +/- 3%, 55% +/- 5%, 46% +/- 5%, 45% +/- 1%, 33% +/- 2%, and 19% +/- 3%, respectively). In further studies, hearts (n = 5 per group) were perfused with buffer (groups 1 and 2) or blood (groups 3 and 4), and each was subjected to 60 minutes of normothermic global ischemia, with (groups 2 and 4) or without (groups 1 and 3) a 3-minute preischemic infusion of St. Thomas' Hospital cardioplegic solution. After 60 minutes of reperfusion, the postischemic recoveries of left ventricular developed pressure in groups 1, 2, 3, and 4 were 32% +/- 3%, 44% +/- 4%, 43% +/- 7%, and 72% +/- 6%, respectively, with coronary flow recovering to 64% +/- 7%, 82% +/- 4%, 82% +/- 4%, and 110% +/- 5%, respectively. Left ventricular end-diastolic pressures were 20 +/- 5, 24 +/- 7, 15 +/- 4, and 4 +/- 3 mm Hg, and tissue water contents were 4.76 +/- 0.11, 4.87 +/- 0.55, 3.93 +/- 0.05, and 3.68 +/- 0.02 ml/gm dry weight, respectively. In conclusion, compared with crystalloid perfusion, the blood-perfused rabbit heart has a greater resistance to ischemia, a superior response to cardioplegic protection, and a lower tissue water content.

Animals↗
PubMed1992

The role of regional isolated perfusion in the eradication of melanoma micrometastases in the inguinal nodes: a comparison between an iliac and femoral perfusion procedure.

Regional perfusion therapy of melanoma is followed by an apparent decrease in lymph node metastases. When regional isolated perfusion is performed by cannulating the blood vessels at the iliac level, at least the middle and distal parts of the inguinal nodal zone are included. This is not the case with femoral perfusion. These two types of perfusion were therefore compared to determine whether iliac perfusion eradicates micrometastases present in the inguinal nodes. The regional node recurrence rate and time to regional node relapse of 97 patients treated with iliac perfusion were compared with those of 20 patients who received femoral perfusion. Prognostic factors such as sex, MD Anderson stage of disease, Breslow thickness and Clark level of the primary melanoma, and number of nodules of those with recurrent melanoma were equivalent in both groups. All patients were perfused with melphalan under normothermic conditions during the period 1978-1990. Five of 20 patients (25%) receiving femoral perfusion and 31 of 97 patients (32%) receiving iliac perfusion (P = 0.7, chi 2 test) developed inguinal node metastases after a median period of 25 (8-40) and 19 (2-71) months, respectively (Mann-Whitney U test, P = 0.9). There was no statistically significant difference in the 5-year survival rate (55% versus 62%, respectively; log rank test P = 0.5). Since no advantage could be seen in terms of reduction of inguinal node relapse for iliac perfusion, it is concluded that perfusion of the distal nodes is not the major cause of reduction of regional node metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1975

Viscous and inertial fractions of total perfusion energy dissipation in the coronary circulation of the in situ perfused dog heart.

The effects of changes in viscosity on pressure flow relations in the in situ perfused left circumflex coronary artery were studied in open chest dogs. Vascular reactivity was abolished by maximal pharmacological coronary dilatation. Blood and suspensions of red cells (hematocrit 8-14%) in dextran solutions were used as perfusates. Total perfusion energy dissipation, represented by perfusion pressure drop across the perfused vascular bed, can be separated into a viscous and an inertial fraction: P = Pvisc + Pinert. Perfusing the heart with approximately Newtonian fluids of different viscosities enabled us to compute the amount of the inertial fraction of total perfusion pressure dissipation. At constant viscosity, the inertial fraction increased with flow rate. However, the rise of the inertial fraction due to reduced viscosity at a constant perfusion pressure was much more pronounced. Variations of perfusion pressure and viscosity of the perfusates between 70 to 130 mm Hg and 1.2-3.2 cP, respectively, resulted in inertial perfusion pressure dissipation between 16 and 54%. This inertial pressure drop may become a noteworthy factor under conditions of low whole blood viscosity (e.g. anemia or therapeutical hemodilution.

Animals↗
PubMed1975

Analysis of the optimal perfusion pressure and flow rate of the renal vascular resistance and oxygen consumption in the hypothermic perfused kidney.

Thirty-six dog kidneys were perfused with different perfusion pressures (between 15 and 60 mm. Hg) for 72 hours and then transplanted. Hypothermic human albumin was the perfusion fluid. Enzyme release, kidney weight, and renal oxygen consumption were measured during perfusion. Kidneys perfused with a flow rate of 0.8 ml. per gram per minute (21 mm. Hg mean perfusion pressure) showed the smallest increase in kidney weight and the best function after transplantation. Renal vascular resistance was independent of the level of the perfusion pressure and renal oxygen consumption was independent of the applied flow rate. It is concluded that the perfusion pressure applied with hypothermic perfusion should be as low as possible because in this way kidney damage caused by perfusion can be avoided most easily.

Animals↗
PubMed1978

Stretch receptor control of renin release in perfused rat kidney: effect of high perfusate potassium.

1. These studies were conducted in the isolated perfused rat kidney to determine the effect of high perfusate K on the renin release induced by low perfusion pressure, renal vasoconstriction and isoprenaline, and to determine whether the magnitude of the K-induced inhibition equalled that observed with renal vasodilation and high perfusion pressure. 2. Raising perfusate K concentration from 4.2 to 56 mM suppressed basal renin release, and the 56 mM-K inhibited the renin release induced by low perfusion pressure (50 mmHg) or phenylephrine (0.83 micrometers). 3. Isoprenaline (0.79 micrometers) induced a marked increase in renin release; but high perfusate K, propranolol (0.28 mM), papaverine (0.39 mM), or high perfusion pressure (150 mmHg) inhibited this effect. 4. It is concluded that high perfusate K has a powerful inhibitory effect on the renin release induced by renal hypotension, vasoconstriction, and isoprenaline infusion, and that this effect may be mimicked by high perfusion pressure or renal vasodilation. A mechanism is proposed whereby these signals may inhibit renin release by depolarizing the juxtaglomerular granular cells.

Animals↗
PubMed1992

Ventilation-perfusion relationships in isolated blood-free perfused rabbit lungs.

The multiple inert gas elimination technique (MIGET) was applied to blood-free perfused isolated rabbit lungs. Commonly accepted criteria for reliability of the method were found to be fulfilled in this model. Ventilation-perfusion (VA/Q) distributions in isolated control lungs corresponded to those repeatedly detected under physiological conditions. In particular, a narrow unimodal dispersion of perfusate flow was observed: perfusion of low-VA/Q areas ranged below 1% and shunt flow approximately 2-3%; perfusion of high-VA/Q regions was not detected. Gas flow was characterized by narrow dispersion in the midrange-VA/Q areas. Application of a low level of PEEP (1 cmH2O) reduced shunt flow to less than 1%, and low-VA/Q areas were no longer noted. By using this PEEP-level, stable gas exchange conditions were maintained for greater than 5 h of extracorporeal perfusion. Graded embolization with small air bubbles caused a typical rightward shift (to higher VA/Q ratios) of mean ventilation, associated with the appearance of high-VA/Q regions and an increase in dead space ventilation. Mean perfusion was shifted leftward, and shunt flow was approximately doubled. Whole lung lavage with saline for washout of surfactant evoked a progressive manifold increase in shunt flow, accompanied by a moderate rise of perfusate flow to low-VA/Q areas. We conclude that the MIGET can be applied to isolated blood-free perfused rabbit lungs for assessment of gas exchange and that typical patterns of VA/Q mismatch are reproduced in this model.

Animals↗
PubMed1992

Effect of angiotensin II-induced changes in perfusion flow rate on chlorothiazide transport in the isolated perfused rat kidney.

Angiotensin II was used as a probe to study the effect of changes in perfusate flow rate on the renal clearance parameters of chlorothiazide in the isolated perfused rat kidney. Perfusion studies were performed in five rats with no angiotensin II present in the perfusate and in five rats with a 1-4 ng/min infusion of angiotensin II into the perfusate. Angiotensin II had a dramatic effect on the renal hemodynamics, resulting in a 43% decrease in perfusate flow, a 16% decrease in glomerular filtration rate (GFR), and a 45% increase in filtration fraction. Values for the fractional excretion of glucose were low and consistent, with or without angiotensin II. Although the unbound fraction (fu) of chlorothiazide was unchanged between treatments, the renal (CLr) and the secretion clearances were reduced by about 50% in the presence of angiotensin II; the excretion ratio [ER = CLr/(fu.GFR)] was reduced by 38% with angiotensin II present in the perfusate. Analysis of the data was complicated by the presence of a capacity-limited transport for renal tubular secretion. Transport parameters (+/- SD) were obtained and the corrected intrinsic secretory clearance [(Vmax/GFR)/Km] of chlorothiazide was 123 +/- 18 without angiotensin II vs. 72.8 +/- 30.0 with angiotensin II. These results demonstrate that alterations in organ perfusion can significantly reduce the clearance parameters of chlorothiazide in the rat IPK. These flow-induced changes in intrinsic secretory transport may reflect perturbations other than that of perfusion flow rate alone.

Angiotensin II↗
PubMed1992

An improved technique for isolated perfusion of rat livers and an evaluation of perfusates.

We have modified the apparatus for isolated rat liver perfusion (IPRL) in order to be able to perform two perfusions simultaneously. In addition, we studied the quality and stability of livers by comparison of five different perfusates: Blood (Group A), Original Krebs Henseleit buffer (Group B), Krebs buffer with glucose (Group C) or bovine serum albumin (BSA) added, (Group D). In a last group (E) albumin, glucose, and taurocholic acid were added to Krebs. After 180 min of perfusion, livers perfused with solutions including 2% albumin (Group D, E) had a significantly higher release of hepatocellular and endothelial cell (purine nucleoside phosphorylase) enzymes and lower bile production as compared to Groups A, B, and C (P less than 0.0001). Increasing levels of purine nucleoside phosphorylase (PNP), a reflection of damage to the microvascular endothelium preceded the increases in hepatocellular enzymes. Histologically, damages of sinusoidal endothelial cells and hepatocytes are appreciated moderate to severe in Groups D and E, slight to mild in Groups A and B, and not significant in Group C. These results suggest that BSA may have toxic effects to the perfused rat liver. These data also confirm that the IPRL modified for simultaneous perfusion of two livers is efficient, and that with this technique the rat liver can be optimally perfused for up to 3 hr with oxygenated Krebs Henseleit buffer without additives (Group B) and without blood. These two improvements should allow those performing studies with perfused rat livers to obtain data in a more efficient, accurate, and inexpensive fashion.

Animals↗
PubMed1978

Perfusate effects upon resistance to aqueous humor outflow in the rhesus monkey eye. A comparison of glutathione-bicarbonate Ringer's solution to pooled aqueous humor as perfusate.

In vivo perfusion of the anterior chamber of normal rhesus monkeys with pooled rhesus aqueous humor gives an initial total facility of 0.48 +/- 0.08 (+/-S.E.) microliter/min/mm Hg. With continued intermittent perfusion for 2 hr this value increased only slightly to 0.57 +/- 0.10 microliter/min/mm Hg. Perfusion of the paired eyes of the same monkeys with glutathionebicarbonate Ringer's solution gives an initial total facility of 0.55 +/- 0.08 microliter/min/mm Hg. This value increased to 1.21 +/- 0.15 microliter/min/mm Hg with continued intermittent perfusion. Thus aqueous is a satisfactory perfusate for experiments requiring prolonged stability of the eye, but glutathione-bicarbonate Ringer's solution is not a satisfactory substitute perfusate. Neither addition of physiologic amounts of ascorbic acid to the buffered salt solution nor careful modification of the pH of the solution to the physiologic level prevented the increase of total facility it produces when used as a perfusate. A reversible, fast-phased small-magnitude increase in total facility was noted in eyes perfused with either perfusate. It is speculated this is caused by neural mechanisms for intraocular pressure control.

Animals↗
PubMed1976

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

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

Child↗
PubMed1992

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

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

Adult↗
PubMed1976

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

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

Animals↗
PubMed1978

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

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

Animals↗
PubMed1979

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

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

Adenosine Triphosphatases↗