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PubMed2003

Suppressed complement activation in human decay accelerating factor transgenic porcine liver cross-circulated with nonhuman primates.

BACKGROUND: We developed an extracorporeal liver perfusion (ECLP) system as a liver-assist device. In this study, we evaluated the safety of the ECLP using human decay accelerating factor (hDAF) transgenic porcine livers in healthy baboons. METHODS: Livers were isolated from five hDAF transgenic pigs and five nontransgenic pigs for the ECLP. Ten cross-circulations between the ECLP and healthy baboons were performed without immunosuppressive agents. Cross-circulation was discontinued in any of the following circumstances: elevated hepatic arterial (>200 mm Hg) or portal (>60 mm Hg) perfusion pressure, massive exudate from the graft liver, mild macroscopic hemolysis, thrombocytopenia, or 24-hr well-conditioned cross-circulation. RESULTS: The cross-circulations with nontransgenic porcine livers were discontinued at 4.4+/-1.2 hr (mean+/-standard deviation) because of high perfusion pressure (n=2) or hemolysis (n=3). Three cross-circulations with hDAF transgenic porcine livers were performed for 24 hr; the other two cross-circulations were discontinued at 13 and 17 hr because of massive exudate and thrombocytopenia, respectively. The duration was 20.4+/-5.1 hr. Deposition of membrane attack complex in the hDAF transgenic porcine liver was less than that in the nontransgenic liver, although immunoglobulin-M deposition was comparable. The porcine livers showed no apparent interlobular bleeding or lobular necrosis. All porcine livers maintained bile production during the cross-circulation. No baboons showed any serious complications after the cross-circulation. CONCLUSION: The hDAF transgenic porcine liver reduced complement activation in xenoperfusion with healthy nonhuman primate blood and led to extended duration of cross-circulation.

Animals↗
PubMed1984

Effects of homologous plasma cross-circulation on liver function in galactosamine-induced hepatic necrosis in rats.

Plasma cross-circulation that resembles clinical plasma exchange was carried out in rats with galactosamine (GalN)-treated hepatic failure to investigate its effect on the damaged liver function. Twenty-four hours after the injection of GalN, plasma cross-circulation was performed at a plasma flow rate of 0.1 ml/min for 6 h. At 48 h after the injection of GalN, survival was obtained in 6 of 8 GalN-injected rats treated with plasma cross-circulation as compared with 4 of 10 GalN-injected rats treated with sham circulation. State 3 oxygen consumption and ATP synthesis (mitochondrial respiratory function) and ATP, ADP, and total adenine nucleotide contents in the liver were significantly higher in the former group than in the latter group at that period, as determined by sacrificing the surviving animals. Although the survival rate was not significantly improved, evidence suggests that plasma cross-circulation enhanced mitochondrial phosphorylative activity and produced an augmented high-energy state of the liver, which had been markedly reduced by GalN administration. An efficient removal of toxic metabolites as well as an influx of a large amount of fresh plasma by plasma cross-circulation would be beneficial for the regenerative process of the necrosing liver tissues.

Adenine Nucleotides↗
PubMed1976

Evaluation in dogs of cross-circulation in the treatment of acute hepatic necrosis induced by yellow phosphorus.

The efficacy of cross-circulation in the treatment of acute liver failure has been evaluated in dogs. Four of 5 dogs administered a dose of yellow phosphorus that is lethal 90% of the time survived after treatment by cross-circulation of whole blood for between 1 and 8 hr with a normal dog. In 2 normal unmatched dogs plasma cross-circulations were performed over a period of 31 days without any clinical or laboratory manifestation of hypersensitivity except for lymphocytotoxic antibody titer rise. The results suggest that whole blood cross-circulation is effective and imply that a single donor could be utilized for prolonged periods of plasma cross-circulation with avoidance of immunological consequences of whole blood exchange.

Acute Disease↗
PubMed1986

Cross-circulation in experimental hepatic failure in the pig.

In experimental liver failure (pigs with totally devascularized liver) the effect of different types of extracorporeal hepatic assistance was evaluated. Group I (N = 6) were untreated controls, Group II (N = 6), simple cross-circulation, Group III (N = 6), cross-circulation with inflow in the donor directly into the portal vein and Group IV (N = 4), cross-perfusion with isolated perfused liver. The cross-circulation was started 20 h after devascularization. There was no change in survival time. Bilirubin was decreased by a factor of 2 and the prothrombin index increased by a factor of 2 after initiation of the cross-circulation due to the dilution. In contrast to this, ammonia was unchanged. During the perfusion no significant changes were found. In Group V (N = 4), extended cross-perfusion with isolated perfused liver for 20 h, starting just after exclusion of liver function in the recipient and with a new liver in the perfusion system every 6th hour, the survival time was significantly increased. Furthermore, changes in the biochemical variables were prevented. It is concluded that with a supply of quantitatively sufficient hepatic assistance it is possible to extend the survival time in experimental liver failure.

Ammonia↗
PubMed1993

[Evaluation of cross circulation in conjoined twins].

This report describes the evaluation of cross circulation in conjoined twins. Female thoracoomphalopagus conjoined twins were delivered by cesarean section after 37 week's gestation. CT, MRI and echography were performed. A partial communication of pericardium and sternum, and a union of the liver were found. For the preoperative evaluation of cross circulation, a bolus of indigo carmine was injected, and the pigment appeared in the urine of the other twin. RI angiography showed that radionuclides in one twin were similar to those in the other after 5-10 minutes. During the operation, an injected bolus of SCC to one twin was not effective for the other twin. Inhaled isoflurane in one twin did not appear in the expired gas of the other twin. After the intentional hemorrhage for 3 minutes from one twin, the hemoglobin concentration of one of the twin was the same as that of the other. This demonstrates that acute hemorrhage from one twin seems to result in a significant and rapid decrease of hemoglobin in both babies equally. However, intravenous infusion of drugs to one of the twins requires a relatively long time to take effect in the other baby. We must be careful in anesthetic management of the surgical separation of conjoined twins.

Anesthesia, Inhalation↗
PubMed1986

Effects on blood pressure of cross circulation between spontaneously hypertensive and normotensive rats.

In order to examine the role of humoral factors for the development of hypertension in the spontaneously hypertensive rat of the Münster strain (SHR) cross circulation experiments with normotensive Wistar Kyoto rats were performed. Cross circulation between SHR and normotensive rats for 30 min increased mean arterial pressure in the latter by 29.1 +/- 7.6 mm Hg (p less than 0.01). Transmission of hypertension by cross circulation was abolished by nephrectomy, adrenalectomy, volume depletion or chronic salt restriction in the SHR. It is concluded that hypertension in SHR is caused by a circulating hypertensive agent produced in kidneys and adrenals, the secretion of which can be suppressed by volume or salt depletion.

Adrenalectomy↗
PubMed1976

Cross-circulation study of natriuretic factors in postobstructive diuresis.

To study the role of circulating natriuretic factors in the postobstructive diuresis that occurs after relief of bilateral, but not unilateral ureteral ligation, cross-circulation was carried out between normal recipient rats and donor rats have either 24-h bilateral (BUL) or unilateral (UUL) ureteral ligation. With BUL donors, there was a rapid marked increase in sodium and water excretion in the recipient rats, sustained for 80-140 min, with a peak approximately 10 times control values. With UUL donors, no significant natriuretic response occurred. Changes in glomerular filtration rate, renal plasma flow, blood pressure, hematocrit, or circulating levels of aldosterone or Pitressin did not explain the diuresis-natriuresis produced by cross-circulation with BUL donors. Differences in the intrinsic renal damage produced by bilateral as compared to unilateral ureteral obstruction did not appear to account for this response, since UUL donors given an acute urea load and urine reinfusion caused a similar diuresis-natriuresis. Moreover, normal donor rats given a urea load also caused a diuresis-natriuresis nearly equal to that produced by BUL rats, and the relationship between increased urea excretion and sodium excretion or urine flow in the recipients was not different in the two groups. Total urine reinfusion for 3 h in donor rats produced a significant, although less marked, diuresis-natriuresis in recipient animals, with only a slight elevation of the blood urea nitrogen level, much less increase in urea excretion rate, and no significant relationship between urea excretion and sodium excretion or urine flow. The results indicate that potent natriuretic factors, which act by decreasing the tubular reabsorption of sodium and water, are present in the blood of rats with bilateral, but not unilateral, ureteral ligation. High blood and urine urea levels appear to be the factors responsible for the marked natriuresis-diuresis occurring in normal rats during cross-circulation with BUL donors, although suggestive evidence of other natriuretic factors in urine reinfused intravenously was also obtained. The data suggest that urea osmotic diuresis is an important mechanism for determining the striking difference between the postobstructive diuresis observed after relief of bilateral as compared to unilateral ureteral ligation.

Adenosine Triphosphatases↗
PubMedDate not supplied

Controlled cross circulation in dogs: effects on donor hemodynamics.

Controlled cross circulation (CCC) was performed in six pairs of dogs for 45 minutes with aortic cross clamping and cardioplegia. Data were collected in donor dogs at 10 minute intervals three times before, three times during, and three times after CCC and included arterial blood pressure, pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac index (CI), heart rate (HR), blood gas analysis, temperature, maximum rate of rise of left ventricular pressure dP/dt max/End diastolic volume (EDV), blood volume (BV), complete blood count (CBC) and activated clotting times (ACT). Pulse pressure (PP), systemic vascular resistance (SVR), oxygen delivery (DO2), and left ventricular cardiac work (LVCW) were calculated. Arterial blood pressure, CVP, blood gas analysis, temperature, BV, CBC, and ACT were measured in recipient dogs. During CCC, donor hemodynamic changes resembled those observed in models of acute onset arteriovenous fistulas. Insidious BV shifts can occur despite the use of occlusive roller pumps. After CCC, donor hemodynamics resembled acute blood loss, characterized by decreases in mean arterial pressure (MAP), CVP, PCWP, and CI, and increases in SVR and dP/dt max/EDV. These changes were probably caused by pump imbalance and BV shift to the recipient dog.

Animals↗
PubMed1993

The shivering response during cross-circulation in the common eider duck (Somateria mollissima).

The possible role of humoral factors in the control of shivering in the common eider duck (Somateria mollissima) was investigated using a cross-circulation technique. Pairs of animals were coupled so that the arterial system of one animal was connected to the venous system of the other. The rate of blood transferral was 12.8 ml min-1. By adequate heparinization of the extracorporeal blood supply, cross-circulation could be maintained for periods of up to 12 h. The temperature of blood entering each animal Tinlet) was controlled by heat exchangers. During control experiments Tinlet was maintained at a temperature close to normal body temperature. During cooling experiments Tinlet was maintained at c. 20 degrees C. Changes in metabolic heat production and oesophageal temperature in response to blood cooling were measured in cross-circulated pairs of animals cooled simultaneously or individually. Based on analysis of the metabolic responses under the different experimental situations, no evidence was found to indicate that blood-borne substances are involved in the shivering response in these animals.

Animals↗
PubMed1990

Comparison of cardiovascular effects of pirmenol with those of disopyramide in isolated canine heart preparations cross-circulated with a donor dog.

To assess the cardiovascular profiles of pirmenol, a new antiarrhythmic drug, and to compare them with those of disopyramide, isolated canine sinoatrial node, papillary muscle and atrioventricular node preparations cross-circulated with a donor dog were used. Pirmenol injected intraarterially into the isolated preparations showed negative chronotropic and inotropic effects, which were comparable to those of disopyramide; and it also showed coronary vasodilator and negative dromotropic effects on atrio-His as well as His-ventricular conduction, which were significantly more potent than those of disopyramide. Similarly, pirmenol administered intravenously into the donor dog showed more potent negative dromotropic effects on the PQ interval and QRS width than disopyramide, while in the isolated preparations cross-circulated by the donor dog, pirmenol and disopyramide showed equipotent cardiodepressant effects. In the same preparation, pirmenol decreased coronary blood flow following a transient increase, while disopyramide only decreased coronary blood flow. Since the antiarrhythmic action of class I drugs is considered to result from inhibition of the fast inward current, which generates and propagates action potentials and also induces ventricular automaticity, our results suggest that pirmenol possesses an electrophysiologic effect typical to an efficacious class I agent such as disopyramide.

Action Potentials↗
PubMed1991

Comparison of cardiovascular effects of a novel class Ic antiarrhythmic agent, NIK-244, with those of flecainide in isolated canine heart preparations cross-circulated with a donor dog.

To assess the cardiovascular effects of a new class I antiarrhythmic agent, NIK-244, and to compare them with those of flecainide, canine isolated, sinoatrial node, papillary muscle and atrioventricular node preparations cross-circulated with a donor dog were used. NIK-244 injected intraarterially into the isolated preparations showed dose-related negative chronotropic, negative inotropic, and coronary vasodilator effects, which are comparable to those of flecainide, and it also showed a dose-related negative dromotropic effect on both atrio-His (AH) and His-ventricular (HV) conduction. The prolongation of AH interval by NIK-244 was significantly more potent than that by flecainide, while that of the HV interval by NIK-244 was slightly more potent, but not significantly, compared with that by flecainide. NIK-244 administered intravenously into the donor dog showed bradycardic and depressor effects in both the donor dog and the cross-circulated sinus node and papillary muscle preparations, which are comparable to the effects of flecainide. Although the negative dromotropic effects of NIK-244 on both the donor dog heart and the cross-circulated atrioventricular node preparation started more slowly, they were more potent and longer-lasting than those of flecainide. Our results suggest that NIK-244 may be a more powerful and longer-lasting antiarrhythmic agent than flecainide, since the antiarrhythmic action of class I drugs is considered to result from inhibition of the fast inward current, which is the most important depolarizing current responsible for the intraatrial and His-Purkinje-ventricular conduction.

Animals↗
PubMed1980

The effects of homologous cross-circulation and in situ liver perfusion on fulminant hepatic failure rats.

A galactosamine-induced fulminant hepatic failure (FHF) rat model was used to study the effects of homologous cross-circulation and in situ liver perfusion. Cross-circulation with homologous donors did not significantly improve the survival time or recovery rate of grade II hepatic coma rats. Homologous in situ liver perfusion significantly improved the survival time and recovery in FHF only when started in grade II coma; it has no effect in the later stage of coma.

Animals↗
PubMed1988

Pressure-volume relation around zero transmural pressure in excised cross-circulated dog left ventricle.

Left ventricular (LV) pressure-volume (PV) relations of quasi-isobaric contractions around zero transmural pressure were studied with a new volumetric method. Left ventricles of isolated cross-circulated dog hearts were connected to a large air tank through the mitral annulus. The volume of the air space was changed with a volume servo pump to oscillate the transmural pressure (P) around zero. Instantaneous LV volume (V) was computed from P by Boyle's law (P.V = constant) to draw the PV trajectories of the isobaric contractions. The end-systolic PV relation (ESPVR) and end-diastolic PV relation (EDPVR) curves intercepted the volume axis at two different volumes (Vo and Vu, respectively). The slopes of both ESPVR and EDPVR curves as well as Vo and Vu were variably influenced by positive and negative inotropic states, heart rate changes, arrhythmias, ischemia, and rigor. In control before any interventions, LV stroke and suction volume (delta V = Vu - Vo) at zero P was 7.5 +/- 2.5 (SD) ml/100 g left ventricle, which changed with the changes in Vo and Vu. delta V decreased with decreases in P from zero and virtually vanished at a pressure (Pn) of -9.5 +/- 2.0 mm Hg. Directly measured LV dead volume (Vd) at Pn was 4.1 +/- 1.3 ml/100 g. The results seem essential for evaluation of LV filling and suction during diastole.

Animals↗
PubMed1989

Renal and circulatory effects of medullipin I, as studied in the in-vivo cross-circulated isolated kidney and intact Wistar-Kyoto (WKY) rat.

The renal medulla harbours powerful humoral antihypertensive mechanisms, as earlier explored in unclipping experiments on renal hypertensive rats or in normotensive isolated kidneys cross-circulated at increased perfusion pressures from 'donor rats', in which renal function also seemed to be affected. Injection of the renomedullary factor medullipin I (Med I; formerly ANRL) mimics these haemodynamic responses, and Med I seems to be one of the most important mediators of the depressor effects. The present study was performed to analyse further the haemodynamic and, particularly, the renal effects of Med I, using anaesthetized intact WKY rats and constant-pressure perfused (90 mmHg) isolated WKY kidneys, cross-circulated by these intact 'donor' rats. Mean arterial pressure (MAP), heart rate (HR) and renal function were followed for one 30-min period before and two 30-min periods after injection of 1 mg Med I (M; n = 7) or an equal volume of saline as control (C; n = 13). In the intact 'donor' WKY, MAP and HR remained largely constant in C during the three periods, being 126 +/- 5, 125 +/- 5, and 120 +/- 5 mmHg, while MAP fell in the M group after Med I, from 121 +/- 5 to 107 +/- 7 and 107 +/- 5 mmHg (P less than 0.05), and also HR tended to decrease in M. Renal resistance (RR) fell while renal plasma flow (RPF) and glomerular filtration rate (GFR) increased significantly (P less than 0.05) after Med I in the M donor rats despite their MAP reduction. However, in the constant-pressure perfused, cross-circulated kidneys the RR, RPF and GFR changes were clearly more pronounced (P less than 0.01) and also diuresis, natriuresis, osmolar excretion and osmolar clearance increased significantly after Med I (P less than 0.01). In conclusion, the present results support the view that Med I not only has important and long-lasting depressor effects but also affects renal function in important ways, inducing vasodilatation and increasing GFR, RPF, diuresis and sodium-osmolar excretion.

Animals↗
PubMed1978

Cross-circulation study of natriuretic factors in rats with reduced nephron mass.

The importance of humoral factors, including urea, in the adaptations in electrolyte excretion which occur with acute or chronic reduction in nephron mass was studied using isovolemic cross-circulation in 38 pairs of anesthetized rats. After initial clearance studies, donor rats with acute (48 h) three-quarter nephrectomy or sham operation, acute urea loading, or chronic (2-3 wk) three-quarter nephrectomy or sham operation, underwent cross-circulation with normal recipient animals. Donor rats with acute three-quarter nephrectomy caused a marked natriuresis-kaliuresis in normal recipients. Natriuresis resulted from inhibition of tubular reabsorption independent of changes in GFR or renal plasma flow. Urea was a major but not the only factor involved in the cross-circulation natriuresis-kaliuresis. The severity of reduction in nephron mass, as indicated by the GFR of the donor rat, correlated with the increase in electrolyte excretion in the recipient. Donor rats with chronic three-quarter nephrectomy produced a slight but significant natriuresis in recipients which was much less than that seen with acute three-quarter nephrectomy. Since the GFR and blood urea nitrogen level of donors with acute and chronic renal insufficiency were similar, it was evident that the chronicity of reduced nephron mass, through mechanisms that are not clear, had a significant effect on the level of circulating natriuretic and kaliuretic factors in renal insufficiency.

Animals↗
PubMed1981

[Supero-inferior ventricles and hearts with crossed circulation. Apropos of 2 cases. Review of the literature].

Two cases of supero-inferior heart are reported. Segmental analysis of the first case showed: situs solitus, atrioventricular (left sided loop) and ventriculoarterial discordance, resulting in a corrected transposition with the aorta in L malposition. The second malformation arose on a situs inversus, atrioventricular concordance (left sided loop) and double outlet right ventricle. The right ventricle was on the right and above the left ventricle giving an appearance of paradoxal discordance. The atrioventricular connections determined a plane of cleavage between right and left circulations in the supero-inferior ventricles and an appearance of crossed circulations in the second case. Hypoplasia of the inflow tract, of the right ventricular sinus is almost constant in this type of spatial orientation of the ventricles. The embryological hypoplasias are suggestive of an abnormality in the rotation of the cardiac tube in a frontal plane for the superimposed ventricles and abnormal rotation secondary to ventricular septation in the hearts with crossed circulations. The different classifications proposed in the literature are discussed with respect to these cases.

Child↗
PubMed1979

Increased hepatic cholesterol synthesis in normal rats by cross-circulation with ileal bypassed partners.

Aortic cross-circulation between Holtzman rat littermates was employed to investigate the possible role of a blood-borne factor from the small intestine in the regulation of hepatic cholesterol synthesis. Experimental pairs, consisting of a normal rat and a distal 50% small bowel excluded partner, demonstrated significantly increased combined hepatic cholesterol synthesis when compared to control pairs, consisting of two normal rats, both at 3 and 5 days following parabiosis. This difference was accounted for by increased hepatic cholesterol synthesis in the normal rat in each experimental pair. Neither weight loss nor differences in dietary intake contributed to this effect. Whole blood cholesterol in the common circulation of both experimental and control pairs was lowered; while hepatic cholesterol content was transiently increased, at 3 but not 5 days following parabiosis. Thus, the intestinal bypassed rat stimulates, or releases inhibition of, hepatic cholesterol synthesis in a non-bypassed parabiotic partner. The mechanism for this phenomenon has yet to be defined.

Acetates↗
PubMed1997

Effects of intracoronary fentanyl on left ventricular mechanoenergetics in the excised cross-circulated canine heart.

BACKGROUND: It is still unclear whether fentanyl directly alters left ventricular (LV) contractility and oxygen consumption. This is because of the difficulty in defining and evaluating contractility and energy use independently of ventricular loading conditions and heart rate in beating whole hearts. METHODS: This study was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl in six excised cross-circulated canine hearts. The authors used the framework of the E(max) (a contractility index)-PVA (systolic pressure-volume area, a measure of total mechanical energy)-VO2 (myocardial oxygen consumption per beat) relationship practically independent of ventricular loading conditions. The authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen content difference to calculate E(max), PVA, and VO2. They first obtained the VO2-PVA relationship for varied LV volumes at control E(max). The authors then obtained the VO2-PVA relationship at a constant LV volume, whereas coronary blood fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they obtained the VO2-PVA relationship for varied LV volumes at the final dose of fentanyl. RESULTS: Fentanyl at any concentrations did not significantly change E(max), PVA, and VO2 from the control. The linear end-systolic pressure-volume relations and their slopes were virtually the same between the control and fentanyl volume loading in each heart. Further, either the slope (oxygen cost of PVA) or the VO2 intercept (unloaded VO2) of the linear VO2-PVA relationship remained unchanged by fentanyl. CONCLUSIONS: These results indicate that intracoronary fentanyl produces virtually no effects on LV mechanoenergetics for a wide range of its blood concentration.

Anesthetics, Intravenous↗