Effect of argon laser irradiation on rabbit aortic smooth muscle: evidence for endothelium independent contraction and relaxation.

To study the effect of argon laser irradiation on vascular smooth muscle reactivity, ring segments of rabbit thoracic aorta were mounted isometrically in Krebs bicarbonate buffer. Laser irradiation was performed via a 200-micron core optical fibre interfaced with an argon ion gas laser. Laser irradiation at powers greater than 1.0 watt (W) (n = 34) produced contraction in each case, regardless of the duration of exposure. Conversely, irradiation at powers less than 0.1 W (n = 41) consistently produced relaxation. When the power employed ranged from 0.1 to 1.0 W (n = 100), the typical response consisted of a combination of low amplitude contraction and relaxation. At each power level, the responses observed were independent of the presence or absence of intact endothelium, assessed functionally by the response to acetylcholine and anatomically by scanning electron microscopy. Recordings of tissue temperature profiles performed during continuous-wave laser irradiation suggest that the findings observed in this study may be explained by a combination of heat induced contraction and light induced relaxation. At powers greater than 1.0 W, heat generated by laser irradiation is predominant, causing contraction. At powers less than 0.1 W, light predominates over heat, causing relaxation. When the power range is intermediate between these values, the heterogeneous response recorded reflects the combination of light and heat. In all cases, contraction and relaxation are endothelium independent.

Interleukin-10 prevents death in lethal necrotizing pancreatitis in mice.

BACKGROUND: Cytokines derived from macrophages may play an integral role in the evolution of acute pancreatitis. Interleukin-10 (IL-10), a potent antiinflammatory cytokine, prevents the activation of macrophages and their release of inflammatory cytokines. The aim of this study was to determine whether treatment with IL-10 decreased the severity of experimental acute pancreatitis. METHODS: Thirty female Swiss Webster mice were divided into three groups. Acute pancreatitis was induced by using a choline-deficient, 0.5% ethionine supplemented (CDE) diet. Group A (controls) received CDE diet alone. Group B was pretreated with 10,000 units of intraperitoneal IL-10 at the onset of feeding and every 8 hours thereafter. Group C received IL-10 33 hours after beginning the CDE diet and every 8 hours thereafter. One half of the animals in each group was killed at 54 hours; the remaining living animals were killed at 80 hours. Serum amylase levels (units per liter) were determined at 54 and 80 hours. Pancreata were harvested and fixed in formalin. Histologic characteristics were graded on a scale from 0 to 4 (normal to most abnormal) in a blinded fashion by two investigators. RESULTS: Serum amylase level and histologic score (edema, inflammation, hemorrhage, and necrosis) were significantly reduced when IL-10 was administered either prophylactically or therapeutically (p < 0.01). At 54 hours all animals were alive. Mortality was reduced at 80 hours in both groups treated with IL-10 compared with those fed the CDE diet alone (p < 0.001). CONCLUSIONS: These results suggested that macrophages play an integral role in determining the severity of acute pancreatitis in this animal model. The finding that IL-10 decreased inflammation and prevented death, even when given after acute pancreatitis was established, suggests that it may have potential for clinical use.

Interleukin-10 reduces circulating levels of serum cytokines in experimental pancreatitis.

Over the past few years, evidence has accumulated that implicates proinflammatory cytokines as the mediators responsible for the escalation of acute pancreatitis into a multisystem disease. It has been shown that the degree of serum cytokine elevation, particularly the macrophage-derived cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha, correlates with the severity and outcome of acute pancreatitis. Interleukin-10 is an anti-inflammatory cytokine that inhibits cytokine production from the macrophage. The aim of this study was to determine whether interleukin-10 would decrease both the severity of acute pancreatitis and the level of circulating proinflammatory cytokines. Ninety female mice were divided into three equal groups. Group 1 (controls) received intraperitoneal saline solution. Groups 2 and 3 received intraperitoneal cerulein (50 mg/kg/hr) for 7 hours. In addition, group 3 was given 1500 units of intraperitoneal interleukin-10, beginning 1 hour after the induction of acute pancreatitis and every 3 hours thereafter. Animals were killed at 3-hour intervals. Blood samples were obtained for serum amylase and cytokine determinations (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha). Pancreata were dissected free and fixed in formalin for blinded histologic scoring. Interleukin-10 reduced the serum levels of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and amylase in comparison to untreated animals with pancreatitis (P < 0.05). Pancreatic edema, necrosis, and inflammatory cell infiltrate were also reduced in those animals given interleukin-10 (P <0.05). Histologic score, serum cytokines, and amylase levels are elevated during acute pancreatitis. Interleukin-10 given therapeutically, that is, after the onset of acute pancreatitis, lessened the severity of disease, probably through inhibition of the macrophage. This was associated with a decrease in circulating cytokine levels.

Interleukin-10 protects against lethality of intra-abdominal infection and sepsis.

The aim of this study was to determine whether interleukin-10 would alter locally derived and systemic proinflammatory cytokine expression and protect from the lethality of cecal ligation and puncture. Three groups of Sprague-Dawley rats were used. Group 1 underwent cecal manipulation. Groups 2 and 3 underwent cecal ligation and puncture. Group 2 received intraperitoneal saline injections beginning 1 hour after cecal ligation and puncture and every 3 hours thereafter for 24 hours. Group 3 received intraperitoneal interleukin-10 one hour after cecal ligation and puncture and every 3 hours thereafter. Animals were killed at 6 and 24 hours after cecal ligation and puncture or sham operation. Serum tumor necrosis factor-alpha (TNF-alpha) levels were determined by enzyme-linked immunosorbent assay. TNF-alpha messenger RNA expression was determined by reverse transcriptase-polymerase chain reaction using Beta-actin as the internal standard. There was a twofold increase (P <0.001) in TNF-alpha mRNA in the liver at 6 and 24 hours after cecal ligation and puncture when compared to rats treated with interleukin-10. There was a twofold increase (P <0.05) in TNF-alpha mRNA in the lung observed only at 24 hours after cecal ligation and puncture when compared to rats treated with interleukin-10. Serum levels of TNF-alpha were elevated at 6 hours in control animals, and this effect was abolished by the administration of interleukin-10. There was no difference in mortality rates at 6 hours (0% for all groups); however, at 24 hours 57% (4/7) mortality was observed in group 2 vs. 0% (0/20) in groups 1 and 3. Interleukin-10 given after the onset of cecal ligation and puncture protects against the lethality of intra-abdominal sepsis.

Adjuvant hormonal treatment with peptide YY or its analog decreases human pancreatic carcinoma growth.

BACKGROUND: Recent studies have revealed decreased pancreatic cancer cell growth upon administration of peptide YY (PYY). We examined whether adjuvant treatment with PYY or its synthetic analog, BIM-43004, would decrease human pancreatic adenocarcinoma growth. MATERIALS AND METHODS: Human pancreatic ductal adenocarcinomas, MiaPaCa-2 and BxPC-3, were cultured and assessed for growth by MTT assay. Pancreatic cancer cells received 500 pmol of PYY or BIM-43004 for 24 hours prior to 5-fluorouracil (5-FU; 10 micrograms/mL) and leucovorin (40 micrograms/mL) administration. Cell membrane epidermal growth factor (EGF) receptors were analyzed by Western blotting after exposure to peptides and chemotherapy. RESULTS: Cancer cell growth was reduced in all groups receiving hormonal pretreatment (23% PYY/5-FU/leucovorin versus control; 27% BIM-43004/5-FU/leucovorin versus control) as compared with groups receiving 5-FU and leucovorin only (16% versus control). The EGF receptor expression was reduced by 30% in cells treated with PYY/5-FU/leucovorin and by 45% in cells treated with BIM/5-FU/leucovorin as compared with control cells without treatment. CONCLUSION: Human pancreatic cancer cell growth is further decreased when pretreated with PYY or its synthetic analog prior to chemotherapy.

The Delorme procedure: a useful operation for complicated rectal prolapse in the elderly.

Full thickness rectal prolapse is a distressing and debilitating condition that often affects elderly patients. Fecal incontinence is usually present. Frequently, comorbid conditions or previous pelvic procedures complicate surgical care. A perineal approach may be used in these patients to avoid the complications of pelvic surgery and general anesthesia. The Delorme operation involves mucosal stripping and muscle plication of the rectal prolapse and is performed externally under regional or general anesthesia. We report our experience with this procedure in six elderly candidates who have undergone the Delorme procedure at the UCLA Center for Health Sciences in the past year. Two men and four women with a mean age of 78 +/- 12 years were followed over a mean of 11 +/- 4 months. Complicating factors included a mean of 1.7 failed prolapse operations per patient (0-6), pelvic radiation in two patients, and severe cardiac and pulmonary disease in two patients. Outpatient bowel preparations and same day admissions were used. Operative time averaged 80 minutes. No blood transfusions were required and postoperative stay averaged 2.7 days. A total of 67 per cent report improvement in continence. There was no major morbidity or mortality and only one recurrence. We conclude that the Delorme procedure is a safe and useful procedure for the treatment of complete rectal prolapse. Elderly patients, patients with failed prolapse operations, and those with prior pelvic surgery or radiation should be considered for this procedure.

Ductography is a useful technique in evaluation of abnormal nipple discharge.

The purpose of this study was to evaluate the utility of ductography, or galactography, in identifying ductal abnormalities in patients presenting with abnormal nipple discharge and to correlate these findings with pathologic results. Abnormal nipple discharge was defined as either bloody or testing positive for occult blood. Milky discharge (galactorrhea) was not evaluated. From July 1992 to June 1994, a total of 43 women presented to the UCLA Breast Center with complaints of abnormal nipple discharge. Mean age of the patients was 54.9 years. All patients underwent technically adequate ductography. A total of 25 patients then underwent 26 excisional biopsies for abnormal ductographic findings. Surgery was usually simplified by the appropriate ductal injection of methylene blue immediately preoperatively. No complications from the procedure were identified. Pathologic entities were correlated with ductographic findings. Ductography identified ductal abnormalities in 33/45 (73%) of ductograms. Filling defects were noted in 19/45 (42%) of ductograms, ductal dilatation in 3/45 (7%), both filling defects and dilatation were noted in 11/45 (24%) of ductograms, and 12/45 (27%) were normal ductograms. Pathologically, ductographic anomalies correlated well with histologic findings. We conclude that ductography is an effective and safe means of identifying ductal abnormalities in patients with abnormal breast discharge. A high incidence of benign intraductal papilloma and a moderate risk of cancer and precancerous lesions were identified. We believe that patients with abnormal nipple discharge should undergo routine ductography and dye localization before surgery.

[Effects of continuous laser on arterial vasomotoricity in vitro]. / Effets du laser continu sur la vasomotricité artérielle in vitro.

The effects of a continuous-wave argon laser irradiation on arterial vasomotricity were studied isometrically on 19 aortic segments obtained from rabbits. The segments had a resting tension of 1 g and were suspended in a perfusion chamber filled with a Krebs-bicarbonate buffer solution at 37 degrees C gassed with 95 p. 100 O2 and 5 p. 100 CO2. Irradiation was performed with an argon laser emitting principally at 488-514 nm, via a flexible optical fibre 200 microns in diameter. The tension of each specimen, measured with a strain gauge, was recorded at the same time as the arterial wall temperature, measured by a thermistor probe. The integrity of the endothelium was checked by scanning electron microscopy and acetylcholine test. The endothelium of 5 specimens was deliberately abrased, and this was checked by the same methods. Laser irradiations of more than 1 watt regularly (n = 34) induced a contraction the kinetics of which were parallel to those of the arterial wall heating and usually reversible after the end of irradiation. With irradiations of less than 0.1 watt, the parietal temperature never rose by more than 5 degrees C, and the vasomotor response always (n = 41) was a relaxation which was reversible after irradiation. At intermediate levels of power, the vasomotor response was biphasic and of low amplitude (n = 100). At all levels, similar responses were given by specimens whose endothelium had been removed. Thus, at the powers used for angioplasty, irradiation of the arterial wall by continuous-wave argon laser induces and intense vasoconstriction which is independent of the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of pulsed excimer laser on arterial smooth muscle]. / Effet du laser pulsé à excimères sur le muscle lisse artériel.

The effect of pulsed lasers on vasomotricity was measured on 22 segments of isolated rabbit thoracic aorta. The segments were isometrically suspended in a bath of Krebs-bicarbonate buffer and irradiated with two excimer lasers (XeCl and XeF) emitting at 308 and 351 nm respectively and coupled with a 400 mu optical fibre. The 10 to 120 seconds irradiations were performed at frequencies ranging from 10 to 100 Hz and pulse energies comprised between 1 and 7 mJ. These parameters were on both sides of the tissue ablation threshold. On the 22 segments studied the irradiation induced in every case (n = 118) relaxation of the vascular smooth muscle. The presence or absence of an anatomically and functionally intact endothelium was checked by scanning electron microscopy and by induction of relaxation with acetylcholine. Identical results were observed on specimens that had been subjected to deliberate endothelial abrasion. Relaxation was increased by drug-induced precontraction. The rise in arterial wall temperature, as measured by thermistor microprobe, never exceeded 5 degrees C, and histological examination of the specimens never showed thermal damage. It is concluded that on the isolated rabbit aorta pulsed excimer laser irradiation induces an endothelium-independent smooth muscle relaxation most probably due to photorelaxation combined with a lack of significant heating of the arterial wall. These experimental data support the use of pulsed sources for laser angioplasty.

Peptide YY inhibits growth of human breast cancer in vitro and in vivo.

BACKGROUND: Hormonal manipulation is important in the treatment of breast cancer. Gastrointestinal hormones may have antiproliferative effects on malignancies arising outside the gastrointestinal tract. Peptide YY (PYY) suppresses growth of, and levels of, intracellular cyclic adenosine monophosphate (cAMP) in pancreatic adenocarcinoma. We hypothesized that PYY would inhibit growth of breast cancer. MATERIALS AND METHODS: MCF-7 human breast infiltrative ductal carcinoma cells in 96-well plates were treated with PYY at 1.25 pmol/mcl. Control wells received an equal volume of bovine serum albumin to mimic experimental conditions. In vitro survival was determined by MTT assays, which reflect cell viability by measuring mitochondrial NADH-dependent dehydrogenase activity. MCF-7 cells in six-well plates were treated with PYY or albumin as described above. Intracellular cAMP levels in cell lysates were determined with a tritiated cAMP assay. One million MCF-7 cells were injected into mammary fat pads of 20 female athymic nude mice. Pellets releasing PYY at 400 pmol/kg/h were placed subcutaneously in 10 mice 24 h prior to cell inoculation. Tumors were harvested after 21 days, weighed, and measured with vernier calipers. RESULTS: PYY reduced in vitro growth by 40% (P < 0.001). Intracellular cAMP levels in PYY-treated cells were 62.4% less than those of controls (P < 0.001). Tumors from control mice weighed twice as much as those from PYY-treated mice (P < 0.006); volume of PYY-exposed tumors was one-third that of controls (P < 0.005). CONCLUSIONS: PYY inhibits growth of breast cancer in vitro and in vivo and may be of benefit in the treatment of this malignancy. The reduction in intracellular cAMP levels may contribute to the observed suppression of cell proliferation.

Interleukin-10 prevents early cytokine release in severe intraabdominal infection and sepsis.

Early release of macrophage-derived proinflammatory cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, are important in the pathogenesis of septic shock and multisystem organ failure in various models of sepsis. IL-10 is a mediator that inhibits cytokine release from activated macrophages. The aim of this study was to determine if IL-10 would decrease serum cytokine elevation in a murine model of cecal ligation and puncture (CLP). CLP in animals is a model that closely mimics the physiologic changes seen in human sepsis. Four groups of 14 female Swiss-Webster mice were used. Group 1 underwent laparotomy alone, groups 2, 3, and 4 underwent laparotomy and CLP. Groups 1 and 2 received intraperitoneal (IP) saline injections to serve as control vehicle. Group 3 (prophylactic) received 10,000 U IP IL-10 1 hr prior to CLP and every 3 hr thereafter. Group 4 (therapeutic) received 10,000 U IP IL-10 1 hr following CLP and every 3 hr thereafter. Animals were sacrificed at 3 and 9 hr following CLP. Serum TNF-alpha, IL-1 beta, and IL-6 were determined by enzyme-linked immunosorbent assay (ELISA), CLP produced a significant rise in serum TNF,IL-6, and IL-1 in untreated controls. Prophylactic or therapeutic administration of IL-10 significantly attenuated this early rise in serum cytokines. These results support the hypothesis that (1) CLP produces an early systemic rise in macrophage-derived cytokines and (2) IL-10 given either before or after the onset of CLP-induced intraabdominal infection and sepsis is able to inhibit this early release of macrophage-derived systemic mediators. IL-10 has potential clinical benefits in the therapeutic management of intraabdominal infection and sepsis.

EGF and TGF stimulate proabsorption of glucose and electrolytes by Na+/glucose cotransporter in awake canine model.

Growth factor-stimulated intestinal absorption has recently been described, but the cellular transport mechanisms mediating this response are unknown. The purposes of this study were to examine the effect that intraluminal and systemic EGF and TGF have in intestinal absorption, elucidate a possible mechanism through which they exert their activity, and compare this response to that of a mixed meal only. Jejunal and ileal Thiry-Vella intestinal segments were constructed in six dogs. Absorption was measured by infusing the loops with a physiological electrolyte solution containing either 10 mmol or 50 mmol glucose and [14C]PEG as the impermeant marker. In vivo studies show that the addition of either EGF or TGF resulted in increased absorption of Na+, Cl-, H2O, and glucose in the intestine. This response was significantly greater than that seen when giving a mixed meal alone. Luminal phloridzin, an inhibitor of the SGLT-1 transporter, inhibited intestinal absorption observed in response to EGF and TGF. In conclusion, these results suggest that growth factors are capable of up-regulating intestinal absorption of electrolytes and nutrients and, these effects are mediated, at least in part, by SGLT-1 pathways.

Interleukin 10 reduces the severity of acute pancreatitis in rats.

BACKGROUND & AIMS: Previous studies have documented the effectiveness of interleukin (IL)-10 if given before the onset of experimental acute pancreatitis. This study examined whether IL-10, a cytokine that inhibits macrophage release of inflammatory mediators, would alter the severity of acute pancreatitis if given before or after the induction of disease. METHODS: Eighty-four Sprague-Dawley rats were divided into four groups. Group 1 received intravenous saline, and groups 2, 3, and 4 received intravenous cerulein (8.5 microg x kg(-1) x h(-1)). Group 3 was also given 150,000 U of intraperitoneal IL-10 1 hour before cerulein infusion and every 3 hours thereafter. Group 4 received 150,000 U intraperitoneal IL-10 2 hours after cerulein infusion and every 3 hours thereafter. Serum amylase and tumor necrosis factor (TNF)-alpha levels were measured before and 3, 9, or 15 hours after induction of pancreatitis. Animals were killed at these time points. Pancreata were analyzed for edema and TNF-alpha mRNA and TNF-alpha protein concentrations and were graded histologically. RESULTS: Serum amylase, TNF-alpha mRNA, and TNF-alpha protein levels, pancreatic edema, and histological score were significantly reduced when IL-10 was administered either before or after induction of pancreatitis. Serum TNF-alpha levels were undetectable. CONCLUSIONS: IL-10 attenuated the severity of experimental acute pancreatitis if given either before or after the induction of the disease. These results are consistent with the hypothesis that the macrophage is important in determining the severity of acute pancreatitis in this model.

Epidermal growth factor improves intestinal adaptation during somatostatin administration in vivo.

Somatostatin (SMS) is administered to patients with short bowel syndrome and enterocutaneous fistulae. Previous studies have shown detrimental effects of SMS on intestinal adaptation after bowel resection. We examined whether administration of epidermal growth factor (EGF) could reverse the deleterious effects of SMS seen after enterectomy. Sixty-four Sprague-Dawley rats underwent an 80% small bowel resection or transection as control. Rats received either SMS at 50 ng x kg(-1) x h(-1), EGF/Urogastrone at 1.5 microg x kg(1-) x h(-1), or both via subcutaneous miniosmotic pumps. Samples were obtained at 1 day and 1 week after surgery for histologic examination, analysis of apical Na+/glucose cotransporter protein and mRNA expression, and analysis of basolateral Na+/K+ ATPase protein and mRNA expression. Protein expression was analyzed by Western blotting whereas mRNA expression was compared by ribonuclease protection assay. Histologically, villus to crypt length after intestinal resection showed increased adaptation in EGF/SMS vs SMS treated animals in both jejunum and ileum. Analysis of mRNA and protein of epithelial transporters show early increases when EGF is administered with SMS vs SMS only. We conclude that combination therapy using EGF and SMS may be beneficial to intestinal adaptation after small bowel resection. Both histologic and molecular data suggest an enhanced absorptive potential and adaptation of the remaining intestine when EGF is administered.

Mechanism of laser ablation in an absorbing fluid field.

Selection of a laser source for intravascular applications has frequently been predicated upon assumptions involving transmissibility in blood of the wavelength of light emitted by a given laser. Standard absorption curves for ultraviolet radiation in blood and infrared radiation in water would suggest that transmission of ultraviolet radiation through a blood field and infrared radiation through any aqueous fluid field would be insufficient for tissue ablation. The present series of experiments was undertaken to determine whether these theoretical predictions would in fact obviate the use of these wavelengths in a blood field. Specimens of normal human myocardium and/or polyvinylchloride were submerged under blood and water and irradiated with ultraviolet radiation (351 nm) delivered as a focused beam and via an optical fiber and infrared radiation (10,600 nm) delivered as a focused beam. Ablation of myocardium was successfully accomplished with a focused beam of both ultraviolet and infrared radiation under as much as 5 mm of blood and with ultraviolet radiation via an optical fiber with the fiber tip up to 3 mm distant from the tissue specimen. High-speed cine recordings of ablation carried out using a focused beam of laser radiation demonstrated that formation of a dynamic optical cavity is the basis for successful pulsed ultraviolet and infrared laser transanguineous tissue ablation. These results thus demonstrate that prediction of wavelength transmission through fluid media based on optical properties of a static fluid does not predict ability to accomplish ablation under dynamic circumstances of laser irradiation.

Vascular spasm complicates continuous wave but not pulsed laser irradiation.

Preliminary clinical experience with laser angioplasty has suggested that arterial spasm may complicate attempts to employ laser light to accomplish vascular recanalization. The present study was designed to investigate the role of energy profile on the development of arterial spasm during laser angioplasty. Laser irradiation was delivered percutaneously in vivo to New Zealand white rabbits and to Yucatan microswine with or without atherosclerotic lesions induced by a combination of balloon endothelial denudation and atherogenic diet. Continuous wave (CW) laser irradiation from an argon ion gas laser (wavelength 488 to 514 nm) was applied to 23 arteries, while 16 arteries were irradiated using a pulsed xenon chloride (308 nm) or xenon fluoride (351 nm) excimer laser. Arterial spasm, defined as greater than 50% reduction in luminal diameter narrowing, complicated delivery of laser light to 17 (74%) of the 23 arteries irradiated with the CW argon laser. Spasm was consistently observed at powers greater than 2 W, at cumulative exposures greater than 200 seconds, and at total energy greater than 200 joules. Spasm was typically diffuse (including the length of the vessel) and protracted (lasting up to 120 minutes). Intra-arterial nitroglycerin (up to 300 micrograms) produced only temporary and incomplete resolution of laser-induced spasm. In contrast, spasm was never observed in any of the 16 arteries in which laser angioplasty was performed using a pulsed laser (0.95 to 6.37 joules/cm2, 10 to 50 Hz, 48 to 370 seconds). Thus CW but not pulsed laser angioplasty may be complicated by arterial spasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsed ultraviolet laser irradiation produces endothelium-independent relaxation of vascular smooth muscle.

Recent studies have shown that continuous wave laser irradiation induces contraction of vascular smooth muscle, except at powers far below the threshold for tissue ablation. To determine the corresponding effects of pulsed laser irradiation on vascular smooth muscle tone, vascular rings of rabbit thoracic aorta were mounted isometrically with 1 g tension in Krebs-bicarbonate buffer and irradiated with 308 or 351 nm from an excimer laser through a 400-microns optical fiber. A total of 250 exposures were performed with 1-6.5 mJ/pulse (fluence = 0.8-5.5 J/cm2), 10-50 Hz, and cumulative exposures of 10-120 seconds. Excimer laser irradiation in combinations of pulse energy (PE), repetition rate (RR), and cumulative exposure below, at, or above threshold for tissue ablation consistently produced relaxation unassociated with contraction in each of the 250 exposures. For the total 250 exposures, the magnitude of relaxation (reduction in recorded tension, Rmax) was 55 +/- 4% (mean +/- SEM) of maximum vasomotor reactivity recorded in the specimen in response to administration of serotonin. Rmax varied directly with both PE and RR. When PE was increased from 1 to 5 mJ/pulse (n = 13), Rmax increased from 57 +/- 19% to 80 +/- 19% (p less than 0.0001); when RR was increased from 10 to 50 Hz (n = 10), Rmax increased from 27 +/- 8 to 46 +/- 8 (p less than 0.0001). Rmax varied independently of endothelial integrity (assessed anatomically and pharmacologically) and wavelength (308 vs. 351 nm). Simultaneously recorded tissue-temperature profiles disclosed that during pulsed laser irradiation, tissue temperature rise did not exceed 5 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous, in vivo excimer laser angioplasty: results in two experimental animal models.

Pulsed ultraviolet light from an excimer laser was successfully transmitted via conventional fused silica optical fibers and used to accomplish recanalization of stenotic or totally occluded arteries in an intact, flowing blood field of two atherosclerotic animal models. The fibers, 300-600 micron in diameter, were delivered percutaneously in wire-guided multilumen catheters and then used to transmit wavelengths of 308 or 351 nm from excimer lasers with pulse durations of 12 nsec or less. Lesions from 70-100% diameter narrowing, and 0.6 to 5.5 cm in length were successfully recanalized (less than 50% residual diameter narrowing) in eight animals, using 3-4 J/cm2/pulse, 10-50 Hz, and 48-370-sec cumulative exposure. Necropsy examination in six of the eight animals disclosed no signs of thermal injury. Perforations were observed in four of eight animals. Thus, while use of an excimer laser power source did not obviate vascular perforation as a complication of laser angioplasty, these preliminary results indicate that energies of pulsed ultraviolet light sufficient to ablate atherosclerotic plaque can be both transmitted via conventional fused silica optical fibers and used successfully within an intact, flowing blood field. It may therefore be possible to use pulsed ultraviolet light from an excimer laser to accomplish percutaneous ablation of atherosclerotic arterial obstructions in humans.

Atherosclerotic Yucatan microswine: an animal model with high-grade, fibrocalcific, nonfatty lesions suitable for testing catheter-based interventions.

A new breed of swine, the Yucatan microswine, that was derived from repetitive inbreeding of selected, small Yucatan swine, was investigated as an animal model of advanced vascular atherosclerosis. Nineteen animals were fed an atherogenic diet for 9.9 +/- 1.5 (mean +/- SEM) weeks before and 19.9 +/- 1.8 weeks after balloon endothelial denudation of all four iliac arteries. In 18 (94.7%) of the 19 microswine, angiography performed at 33 to 87 weeks of age disclosed some degree of luminal diameter narrowing: six animals (33.3%) had one-vessel, six (33.3%) had two-vessel, four (22.2%) had three-vessel, and two (11.1%) had four-vessel disease. In 38 (50%) of 76 denuded arteries, angiographically apparent luminal diameter narrowing was observed as follows: three arteries (7.9%) were narrowed less than 50%; 10 arteries (26.3%) were narrowed 50% to 75%; seven arteries (18.4%) were narrowed 76% to 99%; and 18 arteries (47.3%) were occluded. Sixty-four arteries were harvested from 16 of the 18 microswine with angiographically apparent luminal narrowing, which yielded 748 histologic sections. Maximum cross-sectional area narrowing from atherosclerotic plaque exceeded 90% in 135 (18%) of the sections examined, while 65 sections (9%) were narrowed 76% to 90%, and 127 sections (17%) were narrowed 51% to 75%. Atherosclerotic plaque in these animals appeared histologically similar to the so-called "complex" lesion that is typical of human atherosclerosis, which consists predominantly of collagen with focal calcific deposits and a minor lipid component. The smaller size and lower weight of these animals, in comparison with full-size farm pigs and "minipigs," facilitated transportation, handling, and instrumentation. These findings establish the Yucatan microswine as a useful, representative, and economical atherosclerotic animal model for the evaluation of novel interventional techniques.