Philip N. Sawyer

THE EFFECT OF VARIOUS METAL INTERFACES ON BLOOD AND OTHER LIVING CELLS

Understanding of the interreaction of blood and the surrounding vessel wall is critical to both the design and the construction of artificial interfaces used in the replacement of sections of the cardiovascular system. It has now been 15 years since the initial report by members of this group 1-4 of the rediscovery that a positively charged blood vessel interface would produce intravascular thrombosis. At that time, it was discovered that the inner surface of blood vessel walls in vivo, with blood flowing through the lumen, has a negative potential when looked at by an electrode pair placed across the blood vessel walls2 (FIGURE 1 ) . Either spontaneous or induced reversal of this normal polarity, so that the inner electrode developed a positive potential with reference to the adventitial electrode, was found to herald intravascular t h r o m b o ~ i s ~ J , ~ (FIGURE 2). Subsequent application of a positive-negative electrode pair to the normal blood vessel wall in an attempt to induce thrombosis revealed thrombus formation beneath the positive electrode only.335 The original findings were further confirmed by two attempts to detexmine the size of current, or potential difference, necessary to produce thrombosis in capillaries and small veins and arterioles ( 10-30 microns in diameter). We discovered that small currents of the order of 5-20 aamps would produce occI~s ion .~ However, it was not possible to determine accurately the potential drop across the blood intimal interface in the capillaries observed in this experiment. Additional information had to await later experiments. Excised muscle placed beneath overlying rat mesentery was then shown to produce occlusion in the mesenteric vessels (FIGURE 3 ) . The rate of thrombosis was directly related to the measured surface “injury potential” on the surface of the m ~ s c l e . ~

THE RELATIONSHIP BETWEEN SURFACE CHARGE (POTENTIAL CHARACTERISTICS) OF THE VASCULAR INTERFACE AND THROMBOSIS

Thus, it can be shown that highly theoretical experiments carried out to evaluate the electrochemistry of thrombosis can also be shown to have significance in the generation of new products, which relates the scientific findings to successful modern prosthesis and medically useful devices.

Electroosmotic Characteristics of Canine Aorta and Vena Cava Wall

Experiments in which canine aorta and vena cava walls are subjected to electroosmosis in an open system at constant pressure are described. Electroosmosis reveals that the blood vessel walls studied have a negative zeta potential. The calculated zeta potentials are different for aorta and vena cava, -9.0 +/- 5.0 mv compared with -4.7 +/- 1.2 mv, respectively, and again of different magnitude with different bathing solutions. The calculated membrane pore charge per centimeter of effective pore surface in statcoulombs is approximately 6.2 x 10(3) for aorta compared with 3.5 x 10(3) for vena cava. The implications of the negative electroosmotic zeta potential in terms of the surrounding electric double layer, ion transport, and thrombosis are briefly discussed.

Ten year experience with the negatively charged glutaraldehyde-tanned vascular graft in peripheral vascular surgery: Initial multicenter trail☆☆☆

Abstract The negatively charged glutaraldehyde-tanned vascular graft was developed to determine the utility of grafts of biologic origin to provide satisfactory revascularization for ischemic limbs with advanced arteriosclerotic peripheral vascular disease. The bovine carotid artery was modified under a number of conditions using a large number of variables and evaluated in the carotid artery and aorta of dogs. Eventually ficin-digested carboxylated glutaraldehyde-tanned grafts were selected as being most antithrombotic and most resistant to aneurysm formation. Under an Investigational Device Exemption with the Food and Drug Administration, 146 grafts were evaluated in 108 patients with patency approaching 67 percent for all grafts at 5 years and 59 percent at 9 years plus. Total aneurysm formation has been 4 percent (six grafts) occurring only in hypertensive patients. The graft is now undergoing clinical use and evaluation worldwide.

Wound Healing Effects of Debrisan on Varicose, Postoperative, Decubitus, and Sickle-Cell Ulcers in Man

From the Vascular Research Laboratories and the Vascular Surgical Services, the Departments of Surgery and Surgical Research, Downstate Medical Center, Brooklyn, New York. Supported in part by grants-in-aid from Pharmacia Inc. and the Sawyer Foundation. Our experience in treating 66 patients with Debrisan (dextranomer) to produce wound healing has provided us with extremely useful data on the effects of this material on nonhealing and slow-healing wounds and cutaneous ulcers. An additional area of information now must be developed to explain why Debrisan induces the rapid healing of cutaneous ulcers. As paradoxical as it may seem, it has been observed in at least 5 patients with large wound abscesses following surgery that dextranomer will generate fibroplastic proliferation, sometimes through and around abscesses and around the inflammatory processes. The material appears to stimulate the rapid trellis or structural growth of fibroblasts. While forming this meshlike structure, the fibroblasts loculated the pus in defined areas in three cases. The fibroplasia occurred in spite of overt necrosis in the wounds.

New approaches in the therapy of the peripheral vascular ulcer.

It can readily be seen that Debrisan represents a more effective mode of therapy for several groups of patients which tend to have chronic disabling ulcers of limbs of various etiologies, including venous stasis ulcers, chronic sickle-cell ulcers, decubiti, etc. The more effective treatment of this patient populations, which is provided by Debrisan, would provide a very significant decrease in the total cost of health care in the United States, approximating half a billion dollars per year.

Long-Term Function of NCGT Vascular Conduits in a Multicenter Trial: Evaluation of Physical Chemical Parameters

Our experience with the NCGT graft has now encompassed 12 years in experimental animals and 4.5 years clinical experience with 134 grafts in man. It has previously been suggested that vessel wall structure, interface-charge, electric potential, and polarity of the blood intimal interface appear critical in the prevention of intravascular thrombosis in all vascular prosthetic bypass grafts. This concept has now been confirmed using ferritin, colloidal iron and fluorescamine intimal labelling. These provide a quantitative special characterization of the surface charges of several grafts, including the NCGT graft. Study indicates that each step in the production of the NCGT graft results in a cumulative increase in the structured negative charge of the vascular interface. The more dense the structured negative charge of the prosthesis, the more resistant is the graft to short and long-term thrombosis in experimental animals and man. The experience has been confirmed with a comparative analysis of implantation results in 105 patients up to 4.5 years with 65 to 70% patency rate over that time interval. Statistical analysis of parameters confirm again that the polarity and structure of the vascular interface is important in the effective function and patency rate of the grafts.

Nonthrombogenic ac Polarized Copper Prosthesis

In previous studies from our laboratories, it was shown that metals and alloys which register negative potentials in blood vs the normal hydrogen electrode tend to be antithrombogenic while those with positive potentials are invariably thrombogenic. The present paper deals with a novel approach of maintaining an implanted metallic prosthesis at a negative potential. A copper vascular prosthesis in a dog was maintained at cathodic potentials by a small amplitude (+/- 10 mV) high-frequency ac (100 kHz) on the prosthesis. The prostheses were removed after 2 hours, 6 hours, 1 day, and 42 days, with subsequent visual and scanning electron microscopic examination of the prostheses completed. All tubes were free of thrombus deposits. Minimal junctional thrombi were found, probably due to differences in physicochemical characteristics of the vascular prostheses and recipient vessels. The results are compared with those in the control group (copper tubes with no current) and dc polarized copper tubes. While the control tubes occluded in 2 to 6 hours, the dc and ac polarized tubes remained patent. Of the ac and dc polarized tubes, the former tubes lasted up to 6 weeks with less thrombus deposit. The mechanism of operation of the ac polarized copper prosthesis is not fully understood.

Electrical potential difference across blood vessels.

A technique for measuring the potential difference across blood vessel wall in vitro is described. It was found that the potential difference across canine blood vessel wall in vitro is roughly 0 ± 50 μv. under the conditions of this experiment.

The computer as an unbiased medical investigator: Experience on an active surgical service

An adaptable on-line computer system for entry, retrieval, and analysis of medical discharge summaries has been developed and applied in the Trauma Service of a busy city hospital. Each summary occupied 5 to 10 minutes of the physicians time and compared favorably in cost to the standard dictated summary. While the average dictated summary contained 15 +/- 7 relevant facts, the machine-generated summaries were found to have 53 +/- 20 relevant facts. The summaries are well organized, easily comprehensible, and a duplicate copy can be obtained at any time by using the patients name or number for identification. To date, 495 discharge summaries have been entered and reside in the memory of the computer. Statistical analysis from the data base is done by the computer, thus eliminating human prejudice. It provides facility for rapid and accurate retrospective studies as well as pattern-of-care and individual case review.