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At least 19 recordsLinked to original sources

Transmission of hypertension in rats by cross circulation.

Cross circulation was performed in 54 couples of spontaneously hypertensive and normotensive rats. Blood was pumped through two anastomoses between the carotid arteries and external jugular veins in both directions with equal flow rate. In normotensive rats cross-circulated with untreated spontaneously hypertensive rats mean arterial pressure increased by 20.9 +/- 12.2 mm Hg (p less than 0.01). Administration of digoxin antibody in a dose binding 0.25 mg digoxin to the spontaneously hypertensive rats before cross circulation prevented the transmission of hypertension to the normotensive rat, whereas chemical sympathectomy with 6-hydroxydopamine and intravenous injection of inactive Fab fragments had no inhibitory effect. It is concluded that, in this strain of spontaneously hypertensive rats, a circulating hypertensive factor exists. The factor binds to digoxin antibody and is not produced in sympathetic nervous tissue.

Animals

The first open-heart repairs of ventricular septal defect, atrioventricular communis, and tetralogy of Fallot using extracorporeal circulation by cross-circulation: a 30-year follow-up.

From March 26, 1954, to July 19, 1955, 45 patients with major cardiac malformations not previously correctable underwent open repair utilizing cross-circulation between patient and donor without donor deaths. All operations were carried out at normothermia with lowered flow rates based on azygos flow studies. Twenty-seven patients, more than half of them infants, had ventricular septal defects closed. There were 8 hospital deaths, and there have been only 2 late deaths in 30 years. Fourteen (87.5%) of 16 who underwent recatheterization have closed defects. The 17 30-year-survivors are all in New York Heart Association Functional Class I. Five patients 4 months to 10 years old were operated on for atrioventricular canal (complete form). All had intractable failure, and 4 had pulmonary hypertension. Two of the 3 hospital deaths were due to heart block. The long-term survivor, a 15-month-old infant at the time of operation (severe pulmonary hypertension, 90/50 mm Hg), underwent repair 31 years ago and is now married with 3 children. Recatheterization disclosed normal pulmonary pressure (20/4 mm Hg), no shunts, and mild mitral regurgitation. Ten cyanotic tetrads 13 months to 14 years old were operated on with 5 hospital deaths. Of the 3 late deaths, 1 was accidental at 17 years, 1 occurred suddenly at home 13 years after operation in infancy for atresia, and the third occurred at reoperation 10 years later. The 2 remaining patients (1 the first patient operated on) are in excellent health. The surgical methods used and the physiological advantages of cross-circulation (temporary placenta) that made these results possible at a time when surgical knowledge was primitive are described.

Cardiac Catheterization

Cerebral metabolism during cross-circulation in experimental hepatic failure in the pig.

The effect of hepatic assistance on cerebral metabolism was evaluated in a series using cross-circulation, anticipating increased efficiency of hepatic support. The experimental model for liver failure was pigs with totally devascularized liver. Cross-circulation with a normal sibling pig, cross-circulation with inflow in the donor directly into the portal vein and cross-perfusion with isolated perfused liver starting 20 h after elimination of liver function in the recipient and lasting for 3 h did not increase survival. Before cross-circulation in these three groups, the cerebral flow and oxygen uptake were decreased; during the cross-circulation a significant but temporary increase was found. In experiments with early and prolonged perfusion with isolated perfused liver no changes in cerebral flow, oxygen or glucose uptake were found, and these variables were still normal 6 h after termination of the perfusion. The survival time was significantly increased. In the control group a significant rise in blood and CSF ammonia was found with a mean CSF/blood ratio of 0.92. After cross-circulation, the CSF/blood ratio was 0.52 and 0.62, respectively, indicating a proportionally greater elimination of ammonia from the cerebrospinal fluid than from the blood. Cross-circulation did not significantly change the alpha-ketoglutarate, glutamate or glutamine CSF concentrations. After prolonged cross-perfusion, the ammonia blood/CSF ratio was 0.24. It is concluded that by extended extracorporeal hepatic assistance it is possible to increase survival and to prevent changes in cerebral metabolism and ammonia accumulating in the cerebrospinal fluid.

Ammonia

[Significance of cross-circulation on obstructive jaundice in rats with special reference to the mitochondrial function of the liver and kidney].

Cross-circulation was performed to investigate the mitochondrial respiratory function of the liver and kidney in rats after 1, 2 and 3 weeks of biliary obstruction. Serum bilirubin and total bile acids concentration in blood in rats with biliary obstruction markedly decreased with 3 hours cross-circulation. There demonstrated, however, no significant change in mitochondrial function in the liver after cross-circulation. In contrast, mitochondrial function in the kidney showed significant improvement after 3 hours cross-circulation. Mitochondrial respiratory function in normal partner rats cross-circulation with jaundiced rats demonstrated temporal deterioration in the kidney and prolonged deterioration in the liver. It can be concluded that cross-circulation or plasma exchange might be useful for the prevention of renal failure in obstructive jaundice, since cross-circulation induced persistent improvement of the mitochondrial respiratory function in the kidney deteriorated by biliary obstruction.

Animals

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

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

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

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

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

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

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

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

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

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

Cross-circulation studies on the influence of hypoxia and hypoxaemia on neuro-epithelial bodies in young rabbits.

The reactions of the previously described neuro-epithelial bodies (NEB)(Lauweryns et al., 1969, 1970, 1972a, b, 1973a, b, c 1974, 1975) in young rabbits to: (1) hypoxia with normoxaemia in the arteria pulmonalis on the one hand, and (2) hypoxaemia in the arteria pulmonalis with normoxic aeration on the other hand, has been investigated by means of cross-circulation experiments and light microscopical, electron microscopical and morphometrical techniques. Hypoxically aerated young rabbits, which received normoxaemic blood in their arteria pulmonalis from a donor rabbit by means of an arterio-arterial cross-circulation with mutal exchange transfusion, revealed an increased exocytosis of the dense-core vesicles of their NEB. Normoxically aerated young rabbits which received hypoxaemic blood in an identical manner, did not exhibit an increased exocytosis. It is concluded that the NEB apparently react directly to the hypoxia of the inhaled air and not to the hypoxaemia of the pulmonary blood. By the release of serotonin and a polypeptide substance, they may produce a local vasoconstriction in hypoxically aerated lung areas, enabling an intrapulmonary regulation of the V/Q ratio. This is regarded as additional proof that the NEB--while being modulated by the CNS--probably are intrapulmonary chemoreceptors with local secretory activities, reacting to the composition of the inhaled air.

Animals

An X-ray diffraction study of the cross-circulated canine heart.

1. The equatorial X-ray diffraction pattern was recorded from a papillary muscle of a cross-circulated canine heart at different phases of the cardiac cycle. The intensity ratio of the 1, 0 and the 1, 1 reflexions (I1, o/I1,1) was 0-79 in the systolic phase and 1-19 in the diastolic phase. 2. Using the intensity ratio obtained, the approximate proportion of the myosin projections present in the vicinity of the thin filaments was calculated. This was 70-71% in the systolic phase and 51-52% in the diastolic phase of the total myosin projections. 3. The peak systolic tension was roughly proportional to the proportion of the projections present in the vicinity of the thin filaments during systole. 4. The projections which stayed in the vicinity of the thin filaments during diastole did not produce significant contractile force.

Animals