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Biomedical subjects

P Kilzer

Publications and source records attributed to P Kilzer.

4 recordsLinked to original sources

Tissue differences in vascular permeability changes induced by histamine.

A new method is described for assessing changes in vascular permeation by albumin in multiple tissues of the same animal in response to intravascular injection of vasoactive agents. Following intravenous injection of 51Cr-RBC, 125I-BSA, and 57Co-EDTA, a test substance (i.e., histamine) is injected intravascularly or subcutaneously. Eight minutes later approximately 2.0 ml of blood is withdrawn and the heart is severed from the great vessels. Samples of tissue are then taken for determination of water content and for the ratio of counts in 125I and 51Cr in each tissue. That ratio is then divided by the corresponding ratio of the same isotopes in the blood. If the resulting quotient is greater than 1, it indicates that the volume of distribution of 125I in the tissues is greater than the ratio of plasma to red cells in large blood vessels and is indicative of permeation of the vasculature by albumin into the extravascular space. With this technique we have demonstrated that following intravenous injection of histamine, albumin permeation of vessels in the cecum is increased much more than for vessels in any other tissue in the body including skin and muscle. Following intravenous injection of 1.5 mg/kg histamine, albumin permeation in the cecum is increased 4-fold while that in skin is unchanged, except at sites where histamine also has been injected subcutaneously where it is increased 1.7-fold by 3 microgram and 10-fold by 15 micrograms of histamine. The magnitude of increases in albumin permeation of the vasculature after intravenous injection of 7.5 mg/kg of histamine was: cecum--5.1 X greater than pancreas--2.8 X greater than small intestine--2.7 X greater than cremaster and stomach--2.0 X greater than eye and aorta--1.9 X greater than fat--1.7 X greater than skin--1.6 X greater than diaphragm and forelimb--1.5 X. Even at this high dose of histamine, tissue to blood isotope ratio (tbir)-I/Cr values were not increased for heart, brain, kidney, lung, or testis. These findings attest to marked tissue differences in sensitivity to histamine-induced changes in vascular permeation by albumin. The additional that histamine-induced tbir-I/Cr increases in most tissues far exceed tbir-Co/Cr increases indicates that the increase in albumin permeation of vessels is mediated in large part by an increased rate of diffusion (rather than filtration) via an increase in the number and/or size of vascular pores large enough to accommodate albumin.

Animals↗

Albumin permeation of new vessels is increased in diabetic rats.

125I-bovine serum albumin (BSA) permeation of the vasculature of 3-wk-old granulation tissue (induced by subcutaneous implantation of polyester fabric) formed in the diabetic milieu was assessed in female BB/W, spontaneously diabetic rats and in male, Sprague-Dawley rats with streptozocin-induced diabetes as well as in corresponding nondiabetic controls. Albumin permeation of new granulation tissue vessels was markedly increased in both groups of diabetic animals relative to that of nondiabetic controls, while albumin permeation of vessels in most other tissues did not differ for controls and diabetics. These observations indicate that the functional integrity of new vessels formed in the diabetic milieu is impaired: (1) to a greater extent than that of older vessels formed before induction of diabetes and (2) relative to new vessels in nondiabetics. The implication of these observations is that molecular constituents of vessels synthesized in the diabetic milieu are quantitatively and/or qualitatively abnormal and/or their incorporation into vessels is defective.

Animals↗

Clinically significant allo-anti-I in an I-negative patient with massive hemorrhage.

A 37-year-old white man who had never been transfused was admitted as an emergency patient with a ruptured spleen and a falling hematocrit (19% on admission). All crossmatches were incompatible. His serum contained anti-I, and his red cells (RBCs) were I-negative and strongly i-positive. Only 4 units of crossmatch-compatible I-negative frozen RBCs were available immediately. Because of the likelihood that more than 4 units would be required, chromium survival studies were performed using I-positive cells. Samples obtained at 15 and 30 minutes after injection revealed less than 1 percent survival of the donor RBCs. He received the 4 units of I-negative RBCs during the operation in addition to reinfusion of RBCs harvested from 1800 ml of blood aspirated from the abdominal cavity. The postoperative hematocrit remained greater than 30 percent and the bilirubin less than 1.5 mg per dl. Before recommending frozen storage of autologous RBCs, 51Cr labeled I-positive RBCs from the patient's daughter (obligate li heterozygote) were infused. Survival was 100 percent at 15 and 30 minutes, 90 percent at 3 hours, 85 percent at 26 hours; the remaining RBCs disappeared at a normal rate (T 1/2 27 days) over the succeeding 2 weeks. A repeat 51Cr-labeled RBC study with the original I-positive donor confirmed greater than 92 percent destruction in 90 minutes. The clinical significance of this allo-anti-l (apparently primarily against RBCs from homozygous I-positive donors) is in marked contrast to reported findings with auto-anti-l antibodies.

Adult↗