[Certain results of the use of regional intra-arterial chemotherapy in inoperable cancer of the stomach].
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Adult↗
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Results for “Infusions, Intra-Arterial”
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Systemic arterial blood pH servocontrol of mechanical ventilation.
Servocontrol of mechanical ventilation using systemic arterial blood pH, measured by a dual-function pH/PCO2 intra-arterial sensor, as the controlled variable uas carried out in 30 dogs anesthetized with pentobarbital, 30 mg/kg. The control loop consisted of the animal, an intra-arterial dual-function pH/PCO2 sensor and sensor amplifier, a controller, and a Siemans-Elema 900 servoventilator. The system responded appropriately to changes in set-point pH from 7.30 to 7.50, as well as to infusions of lactic acid, which, with the control loop open, decreased systemic arterial blood pH 0.1 TO 0.2 PH units. Long-term (16 hr) ventilation of one dog with the systemic arterial blood pH servocontrol ventilator was shown to be feasible.
Acid-Base Equilibrium↗
Cardiovascular studies with impromidine (SK&F 92676), a new very potent and specific histamine H2-receptor agonist.
Impromidine (SK & F 92676) has recently been identified as a potent and specific histamine H2-receptor agonist. The present paper describes some cardiovascular studies with the drug. Impromidine lowers blood pressure in cats and rats by interaction with H2-receptors. During continuous intravenous infusions of impromidine, the fall in blood pressure is due to a reduction in total peripheral resistance; cardiac output increases during hypotension. The responses to impromidine are similar to responses to histamine in mepyramine-treated cats. Impromidine administered intra-arterially also causes vasodilatation in the femoral and mesenteric vasculature by interaction with H2-receptors. Impromidine stimulates all measured parameters including coronary flow in the isolated working heart of the guinea-pig. Dose-response curves to impromidine were displaced to the right in the presence of cimetidine.
Animals↗
Improvement in arterial oxygenation by saralasin infusion in man.
Simultaneous hemodynamic and blood gas measurements were performed in 26 hypertensive adults, who were cigarette smokers, before and after a 30-minute infusion of saralasin (5 microgram/kg/min) which is a highly specific competitive antagonist of angiotensin II (AII). The arterial pressure fell in nine, rose in seven and was unchanged in ten patients. The mean cardiac index for the entire group remained unchanged. Pulmonary arterial or wedge pressure, pulmonary vascular resistance, arterial PCO2 and pH did not change. Unrelated to the hemodynamic changes, the mean arterial oxygen pressure (PaO2) increased from 68.6 +/- 2.2 mm Hg to 73.9 +/- 2.1 mm Hg (P less than 0.001). In the absence of a significant increase in alveolar ventilation as indicated by an unchanged mean PCO2 and lacking a hemodynamic explanation, the mechanism for the rise in PaO2 is speculative at this stage. The possibility of an improvement in the distribution of ventilataion by saralasin infusion is under investigation.
Adult↗
Nonperipheral chemoreceptor stimulation of ventilation by cyanide.
To assess the ventilatory responses elicited by changes of tissue hypoxia, sodium cyanide (0.12 mg/kg-min for 10 min) was infused into the upper abdominal aorta of anesthetized dogs. These infusions produced decreases in oxygen consumption, increases in arterial lactate concentration, and increases in arterial lactate/pyruvate ratio. Coincident with these metabolic changes of hypoxia, minute ventilation (VE) increased 228 +/- SE 36% and arterial PCO2 decreased 21 +/- SE 2 mmHg; therefore, pH increased both in arterial blood in and cisternal cerebrospinal fluid. Following infusion of cyanide into the abdominal aorta, small quantities of cyanide (48 +/- SE 14 mumol/liter) appeared in carotid arterial blood. To evaluate the possibility that the observed increases in VE were due to stimulation of peripheral arterial chemoreceptors by the recirculating cyanide, the carotid and aortic chemoreceptors were denervated in four dogs. Nonetheless, after intra-aortic infusion of sodium cyanide (1.2 mg/kg), ventilation in these chemodenervated animals again increased considerably (154 +/- SE 36%). In order to explore the possibility that cyanide infusion can stimulate ventilation by an extracranial mechanism, heads of vagotomized dogs (including the carotid bodies) were perfused entirely by donor dogs. The intra-aortic infusion of sodium cyanide (0.9 mg/kg) into these head-perfused animals still caused large increases in VE (163 +/- SE 19%). It is concluded that intra-aortic cyanide infusions stimulate VE by an extracranial mechanism other than the carotid and aortic chemoreceptors.
Animals↗
Pyloroduodenal bleeding and intraarterial vasopressin: clinical results.
Intraarterial vasopressin infusions were given to 46 patients with pyloroduodenal hemorrhage. Hemorrhage was angiographically and clinically controlled in 15 patients, with recurrent bleeding in five. Bleeding was not controlled in 31 patients; seven of these underwent Gelfoam embolization, with bleeding controlled in three. It is concluded that intraarterial vasopressin infusions are not as effective in controlling pyloroduodenal hemorrhage as in other areas of the gastrointestinal tract.
Adolescent↗
In vivo pulmonary metabolism of bradykinin, angiotensin I and 5-hydroxtryptamine in the rat.
Involvement of the pulmonary vasculature of the rat in the in vivo metabolism of bradykinin, angiotensin I and 5-hydroxytryptamine was studied by monitoring the systemic blood pressure response of the test animal during intravenous or intraarterial administration of these substances. Observation of essentially the same blood pressure response regardless of the route of injection indicated that neither agiotensins I or II nor 5-hydroxytryptamine was metabolized by the pulmonary vasculature, while bradykinin was inactivated to the extent of 95+% on one passage through the lung. In the rat the major portion of bradykinin inactivation and angiotensin conversion apparently occur at different places in the vascular tree and therefore could not be carried out by the same enzyme. Differential inhibition by 2-mercaptoethanol and the bradykinin potentiating peptide, Pyr-Lys-Trp-Ala-Pro, support this postulate. One rat was found which had no pulmonary kininase but could convert angiotensin I to angiotensin II. In addition, infusion of large doses of known inhibitors of lung converting enzyme had no effect on either angiotensin I conversion or bradykinin inactivation in this system. These results support the idea that the pulmonary vasculature is not a major site for conversion of angiotensin I in the rat.
Angiotensin II↗
Central antihypertensive effects of inhibitors of the renin-angiotensin system in rats.
The possibility that mean arterial pressure (MA) might be maintained by an effect of angiotensin II or its precursors on the central nervous system in rats made hypertensive by occluding the aorta between the renal arteries was investigated. Aortic coarctation produced severe hypertension (MAP greater than 150 mmHg) and plasma renin activity values (radioimmunoassay) at least 10 times normal within 2-6 days after surgery. [Sar1, IIe8]angiotensin II, an angiotensin II antagonist administered centrally via an intracerebroventricular (icv) injection (10-100 mug), lowered the MAP in a dose-dependent manner. Peripheral administration of [Sar1, IIe8]angiotensin II (bolus injection) at 100 mug intra-arterially was ineffective, but the antagonist did lower arterial pressure when infused intravenously for 1 h at 4 times this dose. Less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, a converting enzyme inhibitor, and pepstatin, a renin inhibitor, were ineffective via an icv injection. These results suggest that angiotensin II is in part responsible for the elevation in blood pressure following aortic coarctation in rats. Both central and peripheral administration of [Sar1, Ile8]-angiotensin II lowered mean arterial pressure but the antagonist lowered arterial pressure at lower doses and produced a more rapid decline in arterial pressure when administered into the central nervous system then when administered intra-arterially or intravenously.
Angiotensin II↗
Failure of prostaglandins E1 and E2 to alter canine gastric mucosal cyclic nucleotides.
The action of prostaglandins and indomethacin on gastric mucosal cyclic nucleotide concentrations was evaluated in 18 anesthetized mongrel dogs. Prostaglandins E1 (PGE1) and E2 (PGE2) (25 microgram/kg bolus, then 2 micrograms/kg/min) were administered both intravenously (4 experiments; femoral vein) and directly into the gastric mucosal circulation (10 experiments; superior mesenteric artery). The possible synergistic effect of pre-treatment and continuous arterial infusion of indomethacin (5 mg/kg bolus for 5 min, then 5 mg/min), a prostaglandin synthetase inhibitor, with PGE2 was studied in 4 experiments. Antral and fundic mucosa were biopsied and measured by radioimmunoassay for cyclic nucleotides. Doses of PGE1 and PGE2 which inhibited histamine-stimulated canine gastric acid secretion did not significantly alter antral or fundic mucosal cyclic nucleotide concentrations. Concomitant infusion of PGE2 with indomethacin did not potentiate the mucosal nucleotide response compared to PGE2 alone. These studies fail to implicate cyclic nucleotides as mediators of the inhibitory acid response response induced by PGE1 or PGE2 in intact dog stomach.
Animals↗
Effect of local or parenteral application of ACTH or hydrocortisone on bovine corpus luteum function.
Studies were conducted to determine the effect on corpus luteum (CL) function of ACTH or hydrocortisone administered by ovarian perfusion on day 11 of the oestrous cycle or by carotid infusion on days 2-9 of the oestrous cycle. No significant local effects on CL function were observed during the ovarian perfusion study. Continuous carotid infusion of ACTH or hydrocortisone on days 2-9 resulted in a decreased slope of the progesterone increase during the infusion period. However, no difference in plasma progesterone level on days 9-11 between control and treated cycles was detected and there was no difference between treated and control CL at day 11 with regard to CL weight or progesterone content. The data suggest a possible direct effect of hydrocortisone on either the hypothalamus or pituitary which results in decreased progesterone secretion but not CL development. No residual effect was observed.
Adrenal Cortex Hormones↗
Acute myocardial infarction: intracoronary application of nitroglycerin and streptokinase.
In five patients with acute myocardial infarction, the effects of both intracoronary nitroglycerin (NTG) and subsequent intracoronary streptokinase application were evaluated. In addition, transluminal recanalization was performed in one of these patients. Injection of NTG into the infarct-related coronary artery resulted in improved distal filling of the subtotally occluded left circumflex artery in one patient, and in transient patency of the completely occluded right coronary artery in a second patient. In a third patient patency of the totally occluded left anterior descending artery (LAD) was achieved by transluminal recanalization with a guide wire. In a forth patient with occulsion of the LAD, there was no response to intracoronary NTG and mechanical recanalization was not attempted. Subsequent intracoronary infusion of streptokinase (1,000--2,000 U/min for 15--60 min) resulted in a further and long-term reduction of narrowing at the site of acute occlusion in patients I-III and in opening of the completely occluded LAD in patient IV. Improvement of lumen was paralleled by alleviation of symptoms. In a fifth patient, in whom the LAD was subtotally occluded, the degree of coronary obstruction could not be changed by intracoronary application of NTG or by lysis. In this patient, symptoms and ECG changes improved with reduction of pathologically elevated blood pressure values. The findings suggest that myocardial infarction had been caused by thrombotic occulsion in four patients, and that spasm of the infarct vessel could have been an additional factor in two of these patients. In the fifth patient, an increase of afterload in the presence of a subtotal lesion might have caused the critical imbalance between oxgen supply and demand, resulting in cell death.
Cardiac Catheterization↗
Systemic and arterial infusion chemotherapy for metastatic liver cancer.
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Ambulatory Care↗
Combined intra-arterial actinomycin D and radiation therapy for surgically unresectable hypernephroma.
One primary goal of preoperative radiotherapy for hypernephroma is to reduce the volume of tumor and, therefore, improve the possibility of resection. It is important that this goal be accomplished promptly so that 4 to 6 weeks after radiation therapy nephrectomy can be attempted. A longer waiting period may allow fibrosis of the normal surrounding tissues and make surgery more difficult. In addition, longer waiting periods could theoretically increase the probability of metastasis. Therefore, we plan to continue clinical investigation on the use of combined intra-arterial actinomycin D and radiotherapy as a possible useful means of improving the possibility of prompt surgical resection, since theoretically this regimen may be a method of increasing the effective radiation dose to the hypernephroma without increasing the effective radiation dose to surrounding normal tissue, such as bowel. The method may also have merit as an improved means of palliating selected patients with metastases who are symptomatic from a bulky primary hypernephroma.
Adenocarcinoma↗
Renal function in sheep during infusion of alkali metal ions into the renal artery.
1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron.
Aminohippuric Acids↗
Transcatheter occlusion of the gastroduodenal artery.
The gastroduodenal arteries of 7 patients were occluded for treatment of duodenal bleeding in 4, hepatic devascularization in 2, and redistribution of blood flow for intra-arterial chemotherapy in one patient. In 6 patients, occlusion was performed with Gianturco coils, and with Gelfoam in one. No major complication was encountered. This approach was successful in the control of bleeding from peptic ulcers, arteriovenous malformation and invasion of duodenum by retroperitoneal metastatic lymph nodes from carcinoma of the testicle. Occlusion of the gastroduodenal artery was utilized for further dearterialization of hepatic neoplasms. Redistribution of hepatic blood flow was accomplished by the occlusion of the gastroduodenal and replaced right hepatic arteries allowing infusion of chemotherapeutic agents into the entire liver through the left hepatic artery.
Adenoma, Bile Duct↗
Blood-brain barrier opening by isotonic saline infusion in normotensive and hypertensive animals.
The blood-brain barrier to intravascular Evans blue-albumin was opened in monkeys and rabbits by infusing isotonic saline for 15 s into the common carotid artery, when the external carotid was clamped temporarily and the lingual was catheterized for measuring pressure. Barrier opening correlated better with infusion pressure than with infusion rate, and occurred at carotid artery pressures above 170 mmHg. Systemic hypertension induced by Aramine increased barrier vulnerability by causing a higher net carotid artery pressure to be attained at a given infusion rate.
Animals↗
Studies of phenolic steroids in human subjects. XIX. Renal conjugation of 15alpha-hydroxyestradiol-3-sulfate.
In order to elucidate further the role of the kidney in the conjugation and excretion of 15alpha-hydroxy-estrogens, we synthesized doubly and singly labeled 15alpha-hydroxyestradiol-3-sulfate (15alpha-OHE-S) and determined its urinary excretory pattern after administering differently labeled 15alpha-OHE2-S into the renal artery and concomitantly into a peripheral vein and by the infusion of doubly labeled 3H-15alpha-OHE2-S-35S into the renal artery. The excretion of radioactivity in the early urinary samples and the conjugate pattern in these urines were determined. About twice as much radioactivity was excreted in the early urine samples originating from the renal artery injection than from samples obtained following peripheral administration, indicating renal conjugation and excretion of the 15alpha-OHE2-S. The latter was preponderantly excreted as the S-NAG with only a small part (about 10%) of the administered sulfate being hydrolyzed to the aglycone. The latter was then either conjugated with N-acetylglucosamine (NAG) or glucuronide, probably also in the kidney. Most of the 15-alpha-OHE2-S could not be accounted for, possibly because of biliary excretion and enterohepatic circulation. The results obtained and those already published indicate that the human kidney is capable of conjugating 15alpha-OHE2, its NAG, and its sulfate conjugates.
Adult↗
Hepatic artery infusion of 5-FUDR after prior systemic 5-fluorouracil.
Twenty-one patients with disseminated colon carcinoma and clinically significant liver metastases were treated with 5-FUDR via hepatic artery infusion (HAI). All patients had previously received systemic chemotherapy consisting of either 5-fluorouracil aone or in combination with other agents. At the time of the initiation of the HAI, clinical disease in all patients was progressing. A PR of hepatic metastases was noted in eight patients (35%) with a median and mean duration of response of 4.5 and 5.0 months respectively. The median and mean survival from the start of HAI for responders was 8.0 and 9.0 months and for nonresponders was 1.0 and 1.6 months respectively. It appears that a significant response rate can be achieved with HAI of 5-FUDR in spite of previous exposure to fluorinated pyrimidines.
Adult↗