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PubMed1987

Humoral vasopressor agents in primary hypertension.

In essential hypertension and in the spontaneously hypertensive rat, there are indications for a yet unidentified vasopressor agent which may play an important role in pathogenesis. It has been demonstrated in the spontaneously hypertensive rat by parabiosis, cross-circulation, cross-transplantation of kidneys and by injection of hypertensive plasma fractions. In plasma from essential hypertensives, an agent sensitizing the vasculature to pressor hormones and a substance with direct vasopressor actions have been found. The relationship of the hypertensive factor to the natriuretic hormone is not clear.

Animals↗
PubMed1985

A fast-acting humoral factor mediates pressor hyperresponsiveness in deoxycorticosterone-salt rabbits.

Six rabbits were sham operated and were given water to drink (sham-water group); six additional rabbits were sham operated and were given saline to drink (sham-salt group); another six rabbits received an implant of deoxycorticosterone (DOCA) and were given water to drink (DOCA-water group); a final group of six rabbits received implants of DOCA and were given saline to drink (DOCA-salt group). Two weeks later, all four groups of rabbits had approximately the same mean arterial pressures, and the sham-salt, DOCA-water, and DOCA-salt groups all had plasma renin activity values less than the sham-water group. The DOCA-salt group had greater pressor responses to norepinephrine (NE) at several doses than did the other three groups of rabbits. In another group of six sham-water and six DOCA-salt rabbits, measurements of cardiac output before and during infusions of NE at 800 ng/min/kg body wt revealed no changes in cardiac output before or during NE infusion, but the DOCA-salt group had significantly greater increases in mean arterial pressure and total peripheral resistance during NE than did the sham-water group. In another group of six DOCA-salt rabbits, the pressor response to several doses of NE were determined during infusion of the angiotensin II (AII) antagonist, [Sar1, Ile8] AII; this AII antagonist failed to alter the enhanced pressor responses to NE. A final experiment examined pressor responses to NE in six normal rabbits before and after cross circulation of blood with six DOCA-salt rabbits. After blood cross circulation the normal rabbits had exaggerated pressor responses to NE at 5, 15, and 30 min, but not at 60 min. Similar cross-circulation experiments between six pairs of normal rabbits did not show any transfer of pressor hyperresponsiveness. These studies indicated that pressor and vascular hyperresponsiveness in DOCA-salt rabbits is conveyed by a fast-acting hormonal factor and that AII probably is not involved in mediating this hyperresponsiveness.

Animals↗
PubMedDate not supplied

New assist method for orthotopic heart transplantation in the dog.

We used cross circulation as an assist method for orthotopic heart transplantation in eight dogs. Seven of the eight dogs could be extubated on the first to third postoperative day and were able to eat and walk several hours after extubation. The survival times and the causes of death in these eight dogs were as follows: 436 days (alive), 5 days (sudden death), 17 days (rejection), 17 days (pyothorax), 3 days (accidental death), 59 days (rejection), 19 days (pneumothorax), and 188 days (alive). None of the dogs died of any problems related to the use of cross circulation. Hematologic and biochemical studies revealed that the CK, CK-MB, LDH, GOT, GPT, and lactate levels increased shortly after the operation and returned to the preoperative values within 14 days. The blood urea nitrogen, creatinine, amylase, hematocrit, and total protein levels remained almost unchanged. No free hemoglobin was detected. These findings indicated that no severe damage occurred to the recipient's organs. The key factors for performing successful cross circulation are as follows: (1) The body weight of the support dog should be at least three times that of the recipient. (2) The systolic pressure of the support dog and the pressure gradient between the support and the recipient should be kept above 150 mm Hg and 50 mm Hg, respectively. (3) The flow rate in the arterial tube should be maintained at between 30% and 50% of the basal cardiac output of the recipient. In conclusion, cross circulation is a suitable assist method for orthotopic heart transplantation in the dog.

Animals↗
PubMed1978

Evidence that a humoral factor possessing relaxin-like activity is responsible for uterine quiescence in the late pregnant rat.

When post-partum ovariectomized rats were linked to 21-day-pregnant rats by a cross-circulation system their myometrial activity was almost completely inhibited. No reduction in activity was induced by cross-circulation with other post-partum rats, or with rats in which myometrial activity had been suppressed with oestrogen. Changes in uterine activity could not be correlated with alterations in arterial blood pressure occurring during the experiments. Uteri rendered inactive by cross-circulation were found to be responsive to oxytocin. It is concluded that a humoral myometrial inhibitor is present in late pregnancy in rat blood and the possibility that it is relaxin is discussed.

Animals↗
PubMed1977

Compensatory renal hypertrophy in hypophysectomized rats.

1. After hypophysectomy, both body and kidney weights fall, but at different rates. The rate at which the kidney decreases in weight is faster than that of the whole body.2. Seven days after unilateral nephrectomy, the dry weight of the remaining kidney of hypophysectomized rats, with the exception of rats which had been hypophysectomized for 2 days only, was always heavier than the kidney of control hypophysectomized rats of similar body weight.3. The difference between the dry weight of kidneys of unilaterally nephrectomized hypophysectomized and control hypophysectomized rats increased from 15% in early hypophysectomized (9 days) to about 35% in late hypophysectomized animals (23 days).4. The implantation of renal cortical cells from 2 day hypophysectomized rats into unilaterally nephrectomized control litter-mates inhibited compensatory renal hypertrophy in the latter. When a similar operation was made using kidney cells from animals which had been hypophysectomized for 23 days, there was no significant inhibition of compensatory renal hypertrophy.5. The renal contents of adenosine-3',5'-monophosphate (cyclic AMP) and of guanosine-3',5'-monophosphate (cyclic GMP) in rats hypophysectomized for 2 days were of the same order as those in normal rats, but were markedly lower in rats hypophysectomized for 23 days.6. In contrast to what had been observed in normal rats, in hypophysectomized (2 or 23 days) rats, unilateral nephrectomy did not affect significantly the levels of cyclic nucleotides in the remaining kidney.7. Cross-circulating anephric normal rats with 2 day hypophysectomized animals resulted in an increase of cyclic GMP content in their kidneys. The cross-circulation between anephric normal rats and 23 days hypophysectomized rats had no effect on the level of renal cyclic GMP of the latter.8. When rats hypophysectomized for either 2 or 23 days and which had been nephrectomized were cross-circulated with normal rats, there were no changes in the content of cyclic GMP in the kidneys of the latter.

Animals↗
PubMed1988

Effect of blood purification on the kidney function of the jaundiced rat.

This paper is aimed at evaluating the effect of blood purification on the mitochondrial functions of the kidney in jaundiced rats. At 1, 2, or 3 weeks after bile duct ligation and dissection, obstructive jaundiced rats were utilized for experiment. Cross circulation in 1 ml/min between jaundiced rats and normal rats was performed for 1 or 3 h. Immediately and 24 h after cross circulation, the rats were killed and mitochondrial respiratory functions of the kidney were assessed by measuring oxygen consumption. Mitochondrial function, especially ATP synthesis, showed significant improvement in jaundiced rat with 2 or 3 weeks of biliary obstruction. Cross circulation for 3 h was more effective than that for 1 h. These data suggest that the renal energy production can be increased significantly in obstructive jaundice by blood purification treatment.

Animals↗
PubMed1987

Regulated systemic activation of rat plasma prorenin.

Nephrectomized rats have above-normal plasma prorenin levels, presumably of extra-renal origin, but essentially no renin, suggesting a lack of "convertase" for prorenin activation. Adrenalectomized rats have low plasma prorenin levels accompanied by high renin activity, suggesting enhanced prorenin activation by the action of a stimulated "convertase" mechanism. Cross-circulation between adrenalectomized and nephrectomized rats for 15 or 30 minutes, dramatically lowered prorenin and raised renin levels in both types of rats, suggesting extensive activation of prorenin to renin. Similarly, in vitro mixing of these bloods (without cross-circulation) raised renin activity over five times the expected calculated level, while prorenin essentially disappeared. In both cases, prorenin from nephrectomized rat plasma apparently was activated to renin by the enhanced action of "convertase" in the adrenalectomized rat plasma. This newly generated renin activity was, like normal plasma renin, almost completely inhibited by a monoclonal antibody against hog renin and generated an immunoreactive angiotensin I. In contrast, cross-circulation or in vitro mixing of blood from normal control and nephrectomized rats produced little detectable activation of prorenin and only modest increments of renin, suggesting relative inactivity of the "convertase" mechanism in normal plasma. Our data suggest that activation of plasma prorenin is a significant regulated pathway for renin production, as it is greatly stimulated after adrenalectomy and deficient after nephrectomy, thereby implicating the kidney as an important contributor to the "convertase" mechanism operating within the circulation.

Adrenalectomy↗
PubMed1991

[Orthotopic heart transplantation with sinus venosus incision of right atrium in dogs--preservation of sinus node and original right atrium].

Orthotopic heart transplantation with sinus venosus incision of right atrium was aimed to preserve the sinus node, terminal crista, sinus node artery and whole right atrial muscle of the transplanted heart. This transplant procedure was performed in eight mongrel dogs and electrocardiogram was followed up to five postoperative months. Direct cross circulation technique was employed as an alternative of cardiopulmonary bypass. Donors and recipients were 6 to 8 kg mongrel puppies, and 19 to 25 kg adult dogs supported the cross circulation. Myocardial protection of the donor heart was carried out by low-flow continuous potassium cardioplegia and topical cooling. Right atrial incision of the donor heart was made longitudinally in the posterior wall of sinus venosus. After a median sternotomy, ascending aorta and superior and inferior venae cavae of the recipient were cannulated and connected respectively with carotid artery and jugular vein of the cardiopulmonary support dog. Electrocardiogram, arterial pressure and central venous pressure of the recipient were monitored, and an electro-magnetic flow meter was employed for measuring the blood flow of direct cross circulation. The native heart was resected after aortic cross-clamping, and left atrium and atrial septum were sutured continuously. Sinus venosus incision of the donor heart was anastomosed to the recipient's right atrium. Ascending aorta and pulmonary trunk were reconstructed in the standard fashion. Aortic cross-clamp time was less than one hour and sinus rhythm of the transplanted heart was continued in all cases. Five of the eight dogs were alive postoperatively for one week to five months.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

The evolution of the helical reservoir pump-oxygenator system at the University of Minnesota.

Open heart surgery was not possible before the early 1950s. The development of controlled cross-circulation at the University of Minnesota in 1953 was a major contributing factor toward operating safely on the interior of the heart. Cross-circulation required connecting a donor's arterial and venous blood vessels to those of a smaller recipient whose heart could then be opened for corrective surgery. At that time no mechanical system was available to serve the role of the donor. The need to replace the donor was recognized. The author describes his experience with the development of the helical reservoir bubble oxygenator, which replaced the donor in cross-circulation supported open heart surgery. Other sidelights of the author's experience during the early days of open heart surgery at the University of Minnesota Department of Surgery are also recounted.

History, 20th Century↗
PubMed2003

Origin of the helical reservoir bubble oxygenator heart-lung machine.

Open-heart surgery was not possible before the early 1950s. Such surgery awaited the development of cardiopulmonary bypass. The development of controlled cross-circulation at the University of Minnesota in 1953 was a major contributing factor towards operating safely on the interior of the heart. Cross-circulation required connecting a donor's arterial and venous blood vessels to those of a smaller recipient whose heart could then be opened for corrective surgery. At that time, no mechanical system was available to serve the role of the donor. The need to replace the donor as soon as possible was recognized. The author has recounted his experience with the development of a bubble oxygenator system, which replaced the donor as was used in cross-circulation open-heart surgery.

Animals↗
PubMed1988

Similar normalized Emax and O2 consumption-pressure-volume area relation in rabbit and dog.

The end-systolic pressure-volume relation (ESPVR), a measure of ventricular contractile state, and systolic pressure-volume area (PVA), a primary determinant of cardiac oxygen consumption per beat (VO2), have been derived from the pressure-volume diagram of the cross-circulated dog left ventricle. The slope of the PVA-VO2 relation represents the efficiency of chemomechanical energy transduction of the contractile machinery. To see whether these relationships were similar in other animals, we studied the isovolumic ESPVR and the VO2-PVA relation in nine excised, cross-circulated rabbit left ventricles. The base-line ESPVR was linear (r = 0.94-0.99) with the slope (Emax) and volume-axis intercept (V0) equal to 83.4 +/- 18.3 mmHg/ml and 0.43 +/- 0.17 ml, respectively. When normalized for left ventricular weight, Emax (4.1 +/- 1.1 mmHg.ml-1.100 g) and V0 (8.9 +/- 3.7 ml/100 g) were similar to values reported for the dog left ventricle. The correlation between PVA and VO2 was linear (r = 0.93-1.00), and the slope (1.90 X 10(-5) +/- 0.44 X 10(-5) ml O2.mmHg-1.ml-1) and VO2-axis intercept (0.040 +/- 0.009 ml O2.beat-1.100 g-1) were similar to values found in the dog left ventricle. Hence, despite the greatly different heart size, the base-line contractile state and chemomechanical energy conversion efficiency of the excised, cross-circulated rabbit left ventricle are similar to those of the dog left ventricle.

Animals↗
PubMed1994

The Society Lecture. European Society for Cardiovascular Surgery Meeting, Montpellier, France, September 1992. The birth of open-heart surgery: then the golden years.

The development of open-heart surgery has been reviewed beginning with general body hypothermia and inflow stasis, then continuing with extracorporeal circulation by controlled cross-circulation. The successes with the latter technique stimulated rapid development of the simple disposable highly effective bubble oxygenator for extracorporeal circulation to permit correction of virtually all forms of congenital and acquired heart disease. For the few conditions not amenable to corrective procedures, heart replacement became a practical reality. The creation of chronic heart block in the early operations had a very deleterious effect upon survival until highly effective electrical pacing was developed.

Cardiac Surgical Procedures↗
PubMed1972

A humoral component of the natriuretic mechanism in sustained blood volume expansion.

A natriuretic and diuretic response to whole blood infusion in the rat, exaggerated and sustained by intravenous reinfusion of excreted urine, was shown to be associated with increased glomerular filtration and reduced tubular reabsorption. Cross-circulation of animals so responding (donor rats) with isovolemic recipients led to a modest natriuretic and diuretic response in the latter, not accounted for by altered physical composition of the blood nor by observed changes in filtration rate or arterial blood pressure. The recipient natriuresis was unchanged when nephrectomized donors were used and it occurred in experiments in which donor urine was simultaneously replaced by intravenously infused Ringer-Locke solution; the natriuretic property of the cross-circulating blood could therefore not have been due to reinfusion of urinary constituents, nor to accumulation of metabolites, nor to a factor of renal origin. A recipient natriuresis was also observed when the expanded and urine reinfused donor had been acutely adrenalectomized, ruling out an altered secretion of adrenal cortical or medullary hormones as a principal cause of this natriuresis; the data, however, do not exclude participation of reduced aldosterone secretion in the normal effector mechanism. In control experiments in which whole blood was exchanged for donor blood, a small delayed natriuresis did occur in the recipient; this could be completely prevented by administration of aldosterone. In similar exchange experiments with adrenalectomized donors, a small natriuresis developed in the recipient before blood administration but declined afterwards. These minor natriuretic effects probably resulted from altered mineralocorticoid content of the cross-circulating blood due to factors other than blood volume change. The larger natriuretic response seen in all recipients when the donor was volume expanded must have been due largely to a humoral natriuretic factor of other than renal or adrenal origin.

Adrenal Glands↗
PubMed1987

Investigation of the central and peripheral actions of clonidine and methoxamine using a new in vivo rat preparation.

A cross-circulation technique was developed in rats to distinguish central from peripheral cardiovascular actions of drugs. The right common carotid arteries were ligated, and the left common carotid arteries and left and right external jugular veins of two pentobarbital-anesthetized rats were connected with PE tubing so that peripheral blood from one rat, A, supplied the head of another rat, B, and then returned to the body of A, and vice versa, for peripheral blood from rat B. Each rat was artificially ventilated with O2, the chest was opened, and both subclavian arteries were ligated. The distribution of blood flow was verified by the microsphere technique. Prior to ligation of the subclavian arteries, blood flow from rat A supplied its own brain and both brain hemispheres but not the brain stem of rat B. Following subclavian artery ligation, blood flow from rat A did not supply A's brain, but supplied both hemispheres and the brain stem of rat B. The head of each rat was, therefore, rendered dependent on the carotid arterial blood supply from another rat. The i.v. injection of clonidine (25 micrograms/kg) into rat A significantly increased mean arterial pressure and slightly, but not significantly, decreased heart rate in rat A, whereas it significantly decreased mean arterial pressure and slightly, but not significantly, decreased heart rate in rat B. Conversely, i.v. injection of methoxamine (25 micrograms/kg) in rat A significantly increased mean arterial pressure and decreased heart rate in rat A, and significantly increased mean arterial pressure and slightly, but not significantly, increased heart rate in rat B. Therefore, this rat cross-circulation preparation can be used to separate the central and peripheral cardiovascular actions of drugs.

Animals↗
PubMed1987

A circulating hypertensive factor in primary hypertension: effect of antihypertensive therapy.

In this study the role of a humoral hypertensive factor in spontaneously hypertensive rats (SHR) of the Münster strain was examined by cross-circulation. It was demonstrated that hypertension of the SHR could be transmitted to cross-circulation normotensive Wistar-Kyoto rats. The results led to the following conclusion: primary hypertension is caused by a circulating factor which is produced by kidneys and adrenals and suppressed by acute volume depletion and chronic dietary salt restriction. The antihypertensive effect of nifedipine probably leads to a compensatory stimulation of the hypertensive factor in SHR.

Adrenalectomy↗
PubMed1979

Experimental evaluation of hypothermic intermittent coronary perfusion.

The recovery of the myocardial contractility of blood-perfused papillary muscle from the rabbit hearts was used to determine if hypothermia would minimize the myocardial injury associated with intermittent aortic cross-clamping (IACC). Continuous normothermic coronary perfusion for 2 hours with either cross circulation or a membrane oxygenator had only minimal adverse effects on contractility. None of the hearts tolerated normothermic IACC (45 minutes of anoxia and 10 minutes of reperfusion, repeated twice), When the myocardial temperature was reduced to 32 degrees C., the recovery following IACC was 41.25 +/- 11.21 percent (n=8). With hypothermia of 28 degrees C., it was 70.43 +/- 13.03 percent (cross circulation group, n=7) or 68.36 +/- 13.11 percent (membrane oxygenator group, n=7). If the hearts were cooled to 24 degrees C., the recovery of the myocardial contractility following IACC was 90.95 +/- 5.42 percent (n=11). The improvement of the degree of recovery by hypothermia was statistically highly significant (p less than 0.005). Creatine phosphokinase (CPK) and isoenzymes (CPK-MB) were also measured in some groups, but the results warrrant further studies before they can be correlated with the myocardial function.

Animals↗
PubMed1975

Is there any transtubular reabsorption of filtered proteins in rat kidney?

The bovine protease inhibitor aprotinin (Trasylol) has a high affinity to the kidney and is preferentially pinocytized in the proximal tubule. After i.v. injection of 1mug 124 I aprotinin the blood content decreases to 2.8% of the primary injected amount within 3 hrs, while simultaneously each kidney contains 29%. This substance was used to test whether or not a peptide which is pinocytized, is released in the intact form into the peritubular blood. By a cross circulation technique with two unilaterally nephrectomized rats we were unable to detect any transport of pinocytized, intact peptide through the proximal tubule cell over the observed cross circulation period of 1-8 hrs even when using 5000 times the above dosage. Since the total amount of aprotinin in the kidney is immunologically reactive (ca. 97%), and 65% of the radioactivity in the blood is not reactive after 6 hrs, we believe that the last step in the absorption process consists in digestion inside the lysosomes and instantaneous release of the split products into the blood.

Animals↗