Richard M. Ikeda

Acute and chronic complications of laser angioplasty: Vascular wall damage and formation of aneurysms in the atherosclerotic rabbit

Acute and chronic vascular responses to laser exposure in atherosclerotic rabbits were studied. In 7 rabbits fed an atherogenic diet for 3 to 5 months before the study to induce aortic atherosclerosis, a flexible quartz fiber, 400 micron core diameter, attached to an argon ion laser was passed anterogradely or retrogradely to the atherosclerotic ascending aorta. The laser was turned on using power intensities of 1 to 2 W for 3 seconds. After laser treatment, the aortas were studied acutely in 3 rabbits and chronically in 4 rabbits after recovery for 1 to 14 days. In 2 rabbits studied acutely, the argon laser produced a vaporized crater within the atherosclerotic plaque at the endothelial surface; however, in 1 there was also vascular damage extending deep into the medial layer. In addition, aortic aneurysm with muscular wall damage occurred in 2 of the 4 animals studied chronically. Thus, vascular complications may arise when catheter laser angioplasty is randomly applied without visualizing specific plaque targets or without using safe dose increments of power intensities and durations of exposure. This study suggests caution in the clinical use of intensive phototherapy to cardiovascular lesions and stresses the need for further understanding of laser vascular consequences before application of laser angioplasty in patients.

The qualitative effects of laser irradiation on human arteriosclerotic disease

To determine the effects of laser irradiation upon human coronary atherosclerotic disease, coronary plaques were extracted from fresh human cadaver hearts. Seventy-four diseased artery samples were sectioned either transversely or longitudinally and subjected to laser treatment from argon-ion and carbon dioxide sources. The laser beam affected vaporization and patency in fibrous, lipoid, and calcified plaques as observed histologically. Calcified blockage showed greater extent of charred remnants following controlled thermal injury than did fibrous or lipoid obstructions. The area and depth of penetration varied directly with intensity and duration of photoirradiation and inversely with the density of the atherosclerotic tissue. This study supports further research work on the use of lasers to effect relief of atherosclerotic obstructions.

Laser irradiation of human atherosclerotic obstructive disease: Simultaneous visualization and vaporization achieved by a dual fiberoptic catheter

Received for publication Apr. 2, 1982; accepted May 4, 1982. Reprint requests: Garrett Lee, M.D., Cardiovascular Medicine, Suite 202. UCD Professional Bldg., 4301 X St., Sacramento, CA 95817. The use of laser energy to produce controlled thermal injury to coronary atherosclerotic obstructive plaques, thereby widening vascular luminal diameter, has been demonstrated histologically.‘,’ The application of fiberoptic bundles to view internally the blood vessels of living dogs has been described.‘,” To illustrate the practicality and potential of using the laser to enhance vessel patency, a flexible catheter equipped with both fiberoptic viewing capabilities and a quartz fiber for laser delivery (Trimedyne, Inc., Arlington Heights, Ill.) was inserted into normal aorto-iliac arteries in living dogs (Fig. 1, left) and into human cadavers with diseased arteries (Fig. 1, right, and Fig. 2). A fatty hyalinized diseased area adjacent to the lumen was viewed and targeted for laser irradiation (Fig. 2, left). Following a 3-second 7 W burst from an argon ion laser source, a vaporized patent area was produced which can be visualized through the fiberoptic

Feasibility of intravascular laser irradiation for in vivo visualization and therapy of cardiocirculatory diseases.

Reprint requests: Garrett 1,~. M.D., Cardiovascular Medicine, Suite 202. LICD Professional Bldg.. 4301 S St., Sacramento, CA 95817. therapy” of heart and circulatory disorders is virtually unexplored. To determine the in vivo feasibility of transmitting laser energy intravascularly for the purposes of visualizing and treating peripheral artery pathoanatomy, a flexible fiberopticscope (Trimedyne, Inc., Arlington Heights, Ill.), equipped with a quartz fiber, was inserted via the left subclavian artery to the aortoiliac bifurcation in open-chest dogs (Fig. 1, A). For improved viewing, blood was diverted by normal saline infusion through the flushing channel of t,he fiberopticscope (Fig. 2, A). In addition, an area within the origin of the right iliac artery was then photoirradiated by a neodymium-YAG laser (five 2 to 3 second bursts of 60 W) (Fig. 2, B). Following these studies, the intervened vessels were removed, thereby verifying that the photoirradiation had indeed produced a lesion of coagulation necrosis (Fig. 1, A and B). Thus this investigation provides the initial demonstration of the practicality of conducting laser energy into living blood vessels and related structures as a new modality in the management of cardiovascular diseases.

Effects of laser irradiation on human thrombus: Demonstration of a linear dissolution-dose relation between clot length and energy density

Because vascular thrombosis often accompanies arteriosclerotic disease in occluding blood vessels, the dissolution properties of laser irradiation were investigated and the energies needed to penetrate different lengths of thrombus were quantitated. Spectrophotometric studies show that the blood clot due to the presence of hemoglobin is well absorbed by argon laser energies, which emit blue-green wavelengths between 454 and 514 nm. Thus, laser energies transmitted directly from an argon-ion source produced vaporization and penetration of human thrombus in a linear dose-response fashion; the longer the thrombus, the greater the power intensity or time exposure necessary to penetrate the clot.

Shared antigenic determinants between rabbit antihuman brain and rabbit antihuman thymocyte sera: Relationship to the lymphocytotoxic antibodies of systemic lupus erythematosus☆

Abstract Antibodies to human brain, liver, and choroid plexus were produced by immunization of rabbits with fresh autopsy material in Freunds complete adjuvant, and then were absorbed with human AB cells. Rabbit anti-human brain serum was cytotoxic for peripheral blood T cells using the two-stage microcytotoxicity assay. In the presence of complement, it prevented formation of E rosettes and reduced responsiveness to Con A, PHA-P, and allogeneic cells. In the absence of complement, it was strongly mitogenic, much like rabbit anti-human thymocyte sera. Similarly, rabbit anti-human-brain sera could be absorbed with human peripheral blood T cells, but not with B cells or liver. Rabbit anti-human-liver and choroid plexus sera did not exhibit such T-cell specificity. Lymphocytotoxic antibodies were also studied in the cerebrospinal fluid of 11 patients with systemic lupus erythematosus, and of 31 neurologic disease controls. There was no correlation in SLE with presence of CNS disease and either titer or target cell specificity of lymphocytotoxic antibodies. In contrast, patients with multiple sclerosis or meningitis, possessing CSF lymphocytotoxic antibodies, had specificities directed only against T cells, suggesting their origin as autoimmunization with inflamed brain.

The immunopathology of spontaneously acquired dysgammaglobulinemia in chickens

Abstract The acquired immunopathology of lymphoid and parenchymal organs of University of California, Davis (UCD), line 140 White Leghorn chickens, previously demonstrated to have an inherited dysgammaglobulinemia with associated autoimmune phenomena, is described and compared to normal UCD chicken lines 159, 011, and 440. Although, at autopsy, morbid birds had signs of anemia, congestive heart failure, and splenomegaly, the most prominent features were immunologic in origin. Specifically, there was evidence for immune complex disease, including deposition of immunoglobulin in renal glomeruli, vasculitis, and synovitis. However, of particular importance were age-dependent abnormalities of thymus and bursa of 140 but not those of control chickens. Thymi of 1-year-old birds were dramatically enlarged with microscopic appearance of both hyperplasia and thymoma; the thymi of birds less than 6 months of age were normal. In contrast, bursa from neonatal birds of line 140 but not those of control chickens were markedly underdeveloped and revealed cystic degeneration of bursal epithelium. Furthermore, the size of the bursa and the mitotic index of bursacytes of line 140 were significantly reduced compared to controls. Similarly, although the primary response to SRBC and Brucella antigen was of comparable magnitude in young line 140 and control birds, the percentage of mercaptoethanol-resistant secondary response was lower in line 140 animals. This anomaly of line 140 bursa is unique and suggests that this syndrome of inherited acquired dysgammaglobulinemia of birds, and perhaps acquired agammaglobulinemia of humans, is due to a primary maturational defect of bursa.

Immunological, electrophoretic and kinetic properties of cardiac myosins from various species.

1. In a homologous radioimmunoassay for canine ventricular myosin light chains, the following percentages of cross-reactivities were obtained using the dog as a reference: human, 28%; sheep, 21%; cat, 8%; guinea-pig, 7%; rabbit, 5%; and rat, 4%. 2. In a homologous double diffusion immunoassay using specific gamma G to canine cardiac myosin heavy chains, dog cardiac myosin showed immunological identity with human and sheep cardiac myosin but partial identity with myosins of other species. 3. On a 5-20% polyacrylamide gradient, light chain C1 was electrophoretically distinct in some species; light chain C2 was electrophoretically identical in all species. 4. The K+-activated myosin ATPase of small animals was higher than that of larger animals at an alkaline pH; the same was true for Ca2+-activated myosin when assayed at pH 6.3.

Experimental reversal of acute coronary thrombotic occlusion and myocardial injury in animals utilizing streptokinase

Fresh autologous thrombus, 1.0 to 1.5 ml, was injected into the left anterior descending and/or left diagonal coronary arteries of 19 open-chest dogs to produce evolving acute myocardial infarction (AMI). Thrombotic obstruction was documented by coronary angiography. Multilead epicardial ECGs showed ST segment elevations of affected left ventricular (LV) areas within 2 minutes after thrombus injection, and LV segmental wall cyanosis with hypocontraction was observed within 10 minutes in the myocardial areas supplied by the thrombosed artery. Ten animals then received an initial dose of streptokinase (STK), 250,000 U (intravenous), followed by STK, 1000 to 3000 U/min (intracoronary), while nine control dogs untreated with STK received normal saline infusion. All but one STK-treated animal (all nine animals receiving intracoronary STK) had reestablishment of blood flow in the previously occluded vessels within 1 1/2 hours, disappearance of ventricular cyanosis, return of normal LV contractile function, and normalization of elevated ST segments within 1 hour after intracoronary STK therapy. In contrast, in the non-STK-treated control group, all animals had continued coronary obstruction, progressive ST elevations, and worsening LV cyanosis and hypocontraction until death or for more than 3 hours post thrombus; three control animals died of ventricular fibrillation (VF) within 1 hour of thrombus occlusion, three more died of VF within 2 hours post thrombus, and only three survived beyond 2 hours post thrombus. Postmortem examination of non-STK-treated animals revealed extensive residual coronary thrombus. All intracoronary STK-treated animals evidenced absence of residual coronary thrombus at postmortem examination. These data provide clinically relevant evidence that early intracoronary STK effects thrombolysis in AMI by reopening coronary vessels occluded by fresh thrombus, thereby protecting myocardium from further ischemia and necrosis, preserving LV function, and also reversing cardiac muscle injury.

DMBA induced papillomas in congenitally athymic (nude) and hereditarily asplenic (Dh/+) mice: Contrasts and comparisons with immunologically intact littermates

Congenitally athymic (nude) and hereditarily asplenic (Dh/+) mice were painted with dimethylbenzanthracene (DMBA) to compare skin tumor development in these immunodeficient animals with their immunologically normal littermate controls. Papillomas were induced in all groups of mice. However, nude and Dh/+ mice were significantly more resistant than their normal littermates to tumor induction. Furthermore, the number of papillomas/mouse and the total tumor incidence were significantly greater in control mice and the latency period for tumor appearance was shorter and the tumor growth rate greater in normal mice compared to their immunodeficient littermates. Finally, nu/+ skin transplanted to nude mice and then painted with DMBA behaved in similar fashion as nude skin. These findings, when discussed in terms of target organs for DMBA, suggest a major role for the immune system in stimulating papilloma induction.