Search

Vasoreactivity of laser-treated vessels was investigated in two different experimental conditions. The canine left circumflex coronary artery (LCx) was lased under perfusion with Krebs-bicarbonate buffer by means of a thermal laser (hot-tip probe, HT) at 7 W for 6 seconds and an argon laser beam through a 300 microns optical fiber at 3 W (tip power) for 1 second at 12 spots. A nontreated segment of the LCx served as a control. Two 3-mm long segments were obtained from the treated segment: one to measure the results of potassium (K) induced contraction, and another 3, 4 diaminopyridine (DAP; K channel inhibitor) induced contraction. In 11 instances, coronary angiography of the perfused artery showed less than 50% stenosis after laser treatment. The segments were then mounted isometrically with 1 g tension in Krebs-bicarbonate buffer. Contraction was induced either with 30 mM KCI or 10(-2) M DAP and expressed as developed tension (gram; g). KCI induced vasocontraction of 4.15 +/- 0.93 g in the control, 0.33 +/- 0.71 g in laser irradiated segments (P < 0.0001 vs control), and 0.02 +/- 0.06 g in thermally-treated segments (P < 0.0001 vs control). DAP induced vasocontraction of 5.21 +/- 1.32 g in the control, 0.39 +/- 0.83 g in laser irradiated segments (P < 0.0001 vs control), and 0.07 +/- 0.13 g in thermally treated segments (P < 0.001 vs control). In 4 instances, more than 50% stenosis remained and additional balloon dilatation reduced the stenosis to less than 50%. The lesions also showed reduced vasoreactivity. In vivo thermal angioplasty resulted in reduced vasoreactivity compared to control in 4 anesthetized dogs. Thus, laser and thermal angioplasty reduced vasoreactivity induced by either KCI or 3, 4 DAP. Neither acetylcholine at 10(-6) M nor papaverine at 10(-4) M was able to induce relaxation of treated segments. In conclusion, 1) the lased coronary artery loses its vasoreactivity to either a constrictive or relaxing agent, 2) although stenosis may be produced by laser energy, additional balloon dilatation can reduce residual stenosis, and 3) laser thermal or argon laser angioplasty may prevent severe coronary spasm.

Vasoconstriction is a clinical problem associated with invasive vascular procedures, microvascular reconstruction and subarachnoid hemorrhage. We sought to characterize the ability of pulsed-dye laser irradiation to reverse and prevent vasoconstriction in an anesthetized rabbit model of surgically and pharmacologically induced vasoconstriction. Five groups of experiments were performed to study the effect of pulsed-dye laser irradiation delivered through a 320 microns core ball-tip fiber into the femoral artery. The studies demonstrated that pulsed-dye irradiation can reproducibly cause vascular dilatation. The zone of vasodilatation propagated equally proximal and distal to the site of irradiation within the vessel. When saline was infused into the vessel to replace flowing blood during delivery of laser irradiation, no significant vasodilatation occurred. After laser irradiation reversed surgical and pharmacologic vasoconstriction, the vessel was resistant to further pharmacologic vasoconstriction. This resistance to pharmacologic vasoconstriction did not occur if the vessel was pharmacologically predilated before delivery of laser irradiation. Pathologic analysis of the vessels revealed endothelial damage and mild to moderate medial necrosis, most significant at the site of energy delivery. These studies provide characterization of pulsed-dye laser-mediated vasodilatation in an in vivo model. Delivery of pulsed-dye laser energy has potential clinical application and warrants further investigation.

Segments of endothelium-denuded aorta, pulmonary arterial rings and strips of corpus cavernosum from rabbits were superfused with Krebs medium. Photorelaxation elicited by ultraviolet light (366 nm) was significantly enhanced by either BAY K 8644 (20 nM) or N-nitro-L-arginine (100 and 500 microM) and was associated with increased cyclic GMP. This action of both drugs was greater in pulmonary artery than aorta and corpus cavernosum and persisted in vascular rings for 90 min after drug removal. The effect was significantly attenuated by hemoglobin (10 microM) but was unaltered by superoxide dismutase (30 u/ml). The mechanism of such photosensitization is presently unclear.

1. The relaxant actions of acetylcholine, substance P and calcitonin gene-related peptide, and the levels of neuropeptide Y and calcitonin gene-related peptide were assessed in the rabbit central ear artery 1, 4 and 6 weeks after a single dose of 45 Gy X-irradiation, a dose similar to that used clinically in intraoperative radiotherapy. 2. Relaxant responses induced by acetylcholine and substance P (both endothelium-dependent) and calcitonin gene-related peptide (endothelium-independent) were reduced, and endogenous neuropeptide Y and calcitonin gene-related peptide levels were unaffected after X-irradiation. 3. The mechanism(s) by which a single dose of 45 Gy X-irradiation may selectively damage relaxant, but not direct, contractile responses of the smooth muscle (as we have shown previously) of the rabbit central ear artery are discussed.

The characteristics of carbon monoxide (CO)-induced, endothelium-independent relaxation of rabbit aorta were compared with those of nitric oxide (NO)-induced and light-induced relaxation and endothelium-dependent relaxation mediated by endothelium-dependent relaxing factor (EDRF). CO was less than one thousandth as potent as NO as a relaxant. Various findings, including an increase in cyclic GMP associated with CO-induced relaxation, led to the conclusion that CO - like NO, EDRF and light - produces relaxation as a result of its stimulation of guanylate cyclase. LY 83583, which generates superoxide, was a potent, fast-acting inhibitor of acetylcholine-induced endothelium-dependent relaxation and NO-induced relaxation, and a fairly potent, moderately fast-acting inhibitor of photorelaxation, but only a very weak inhibitor of CO-induced relaxation. The ability of LY 83583 as well as hemoglobin to inhibit photorelaxation is consistent with the hypothesis that on radiation a photo-induced relaxing factor is formed which can stimulate guanylate cyclase and which can be inactivated by superoxide and by hemoglobin.

Mouse tails bearing DMH-II tumours were irradiated to a total of 80 Gy in 8 Gy fractions, twice a day for 5 consecutive days. The normal tail vasculature was minimally affected for up to 60 days post-irradiation. In contrast tumour capillaries which showed minor changes on day 6 post-irradiation were severely affected by day 14. DMH-II proved to be a radioresistant tumour. The radiation dose used in this experiment was the maximum total dose which could be tolerated by the mouse tail. The tumour began to regenerate at approximately 40 days post-irradiation. Tumour infiltrating into the surrounding normal tissue was observed by 60 days following irradiation. As the tumour regenerated, there was no accompanying regeneration of tumour capillaries. This study suggests that: a) tumour capillaries were more acutely radioresponsive than the normal microvasculature in the murine tail, and b) regenerating tumour did not elicit a neovascular response from the irradiated tumour bed.

Tissue reactions and vascular damage in rat tumours (rhabdomyosarcoma R1H) were studied with morphological methods during fractionated treatments with 60Co-gamma-irradiation of 75 Gy alone and in combination with ten fractions of microwave hyperthermia at 43 degrees C, 60 min for five weeks. The nature and time course of tissue and vascular damage change individually with the treatment applied. During radiation-heat treatment congestion, dilation and rupture of tumour blood vessels were observed. The cellular and vascular damage, especially in the central parts of the tumours, occurred earlier and were generally more intense during the combined treatment than found after irradiation alone. The enhanced tissue damage can be related to the local temperatures in the R1H tumours during the microwave heat treatments.

We evaluated the response of cerebral arterioles to angiotensin II (ANG II) in anesthetized rats equipped with a closed cranial window. Topical application of 10(-10)-10(-5) M ANG II induced dose-dependent arteriolar vasodilation. Maximum vasodilation of 24 +/- 2.2% (+/- SE) was attained at a concentration of 10(-6) M ANG II. The dilation in response to ANG II was blocked by 3 micrograms/ml indomethacin, a cyclooxygenase inhibitor, and was reversed to minimal vasoconstriction by 10(-5) M methylene blue, a substance that has been reported to eliminate endothelium-dependent vasodilation. Coapplication of indomethacin with methylene blue reduced the arteriolar response to ANG II to a similar extent as the application of indomethacin alone. Indomethacin or methylene blue did not inhibit the vasodilation induced by 10(-5) M adenosine, which is not endothelium and cyclooxygenase dependent. Mercury light illumination of the pial vessels after intravenous injection of fluorescein dye, a technique that has been used by others to functionally damage endothelial cells, reversed ANG II (10(-6) M)-induced vasodilation into a -14.2 +/- 2.3% constriction while not affecting the response to adenosine. Our data suggest that ANG II produces vasodilator responses of rat cerebral arterioles by the release of a factor that is derived from the endothelium and may be generated through a cyclooxygenase-dependent mechanism.

The response of blood vessels to laser irradiation in vivo was studied in the dorsal skin flap glass window chamber model of hamsters. The vasodilatory response of venules was critically dependent on the wavelength of irradiating laser. Relaxation was not produced in arterioles, although it was tried repeatedly. Vessels were irradiated with the 514.5 nm single line argon laser with irradiances from 1 to 10 W/cm2 on a 1.2 mm-diameter spot. Irradiation of venules with 2.2 W/cm2 and 4.25 W/cm2 produced reversible relaxation. Venules relaxed initially and after the interruption of irradiation returned to their original diameter. At higher irradiances (8.5 W/cm2) an irreversible relaxation was observed. At irradiances of 10 W/cm2 and above initial relaxation was accompanied with constriction, focal coaguli, and hemostasis. Irradiation with the argon-pumped dye laser at 595 nm did not produce any significant relaxation.

Chicago sky blue, also known as Niagara sky blue, is a vital dye that can successfully be used as an intravascular energy absorbing target for the light from a helium-neon (HeNe) laser. The result of this light/dye interaction is endothelium damage which can be controlled by adjusting the duration of the laser exposure and the amount of dye injected intravenously. The endothelial damage probably is the result of the heat generated by the dyes absorption of energy at the interface between plasma and endothelium. The most minimal damage resulted in selective loss of the dilation normally produced by acetylcholine and bradykinin, two endothelium dependent dilators. The dilation produced by sodium nitroprusside, a dilator acting directly on vascular smooth muscle, was preserved. More severe injury (i.e. more prolonged exposure to light and/or more dye, resulted in local platelet aggregation at the site of laser impact.

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)

The purpose of this study was to establish a standardized experimental system to investigate the local effects of ionizing irradiation in the absence of systemic responses due to radiation. Twenty fully healed rabbit ear chambers in 13 rabbits were irradiated with single exposures of 7500 rads of beta-rays from a strontium-90 source. The irradiation resulted in an acute response, with cellular infiltration of the ear chambers, loss of vasomotion in arterioles, and vasodilatation. Over the weeks following irradiation, a gradual reduction in the number of blood and lymphatic vessels was noticed. A gradual reduction in the number of cells in the interstitium was also observed. Finally, only a few thin-walled blood vessels remained. Their endothelium contained no recognizable organelles and in places had disappeared completely, to expose the vascular basement membrane to the blood. These vessels were observed to be still flowing. No evidence either of capillary blockage due to swelling of endothelial cells or of platelet aggregation leading to thrombosis was obtained.

Vasomotor activity in cutaneous tail veins was indexed by changes in local skin temperature during exposure of the whole body to 12.3-centimeter continuous microwaves. At an ambient temperature (26 degrees C) just below that at which tail vessels normally vasodilate, criterion dilation was initiated by 5-minute exposures to a microwave power density of 8 milliwatts per square centimeter. This intensity deposits energy equivalent to approximately 20 percent of the monkey's resting metabolic rate but produces no observable change in deep body temperature. Intensity increments of 3 to 4 milliwatts per square centimeter for 1 degree C reductions in ambient temperature below 26 degrees C produced identical responses. That no vasodilation occurred during infrared exposures of equivalent power density suggests that noncutaneous thermosensitive structures may mediate microwave activation of thermoregulatory responses in the peripheral vasomotor system.

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.

This study demonstrates endothelium-dependent relaxation in the surface arterioles of the brain. A helium-neon laser was used to injure endothelium in situ following i.v. injection of Evans blue dye, which sensitizes the bed to the laser. Areas 18 or 36 micron in diameter were injured and no longer relaxed to either 1 ml of acetylcholine chloride or bradykinin triacetate, 80 micrograms/ml delivered for 60 seconds. Dilations to sodium nitroprusside (30 micrograms/ml) were unaffected. Normal responses to nitroprusside, plus electron microscopy, established that vascular smooth muscle was uninjured. Endothelium-dependent relaxation was impaired when only minor ultrastructural damage was present. Dilation was inhibited downstream and upstream as far as 80 micron from the center of the laser beam. This suggests a spread of endothelium injury around the site of laser impact. However, inhibition was somewhat more marked downstream than upstream, implying that a portion of the downstream response was dependent on a substance released from an upstream site. To date, very few studies have reported endothelium-dependent relaxation in vivo, especially in the microcirculation. The present study accomplishes this. Moreover, in contrast to in vitro observations of endothelium-dependent relaxation in large vessels, the in vivo elimination of endothelium-dependent relaxation in the microcirculation required neither removal of endothelium nor injury to large numbers of endothelium cells. Since endothelium-dependent relaxation in the microcirculation has now been demonstrated using three different techniques to injure endothelium, it is reasonable to conclude that the phenomenon is real.

Changes in serum albumin, A1-globulin, A1-macroglobulin, haptoglobin, hemopexin, and ceruloplasmin concentration in rats irradiated continuously with a daily dose of 2.055 Gy up to a total dose of 14.385 Gy of gamma rays after peroral indomethacin administration were followed by two-dimensional immunoelectrophoresis. The use of indomethacin evoked a beneficial response particularly in the serum concentration of albumin, A1-globulin, and A1-macroglobulin on the 21st day after irradiation. In contrast with the concentrations in the irradiated control group, protein values in rats treated with indomethacin were less reduced. We did not observed significant differences between the serum concentration of haptoglobin, hemopexin, and ceruloplasmin of irradiated, indomethacin-treated and irradiated control, up to the 58th day after irradiation.

In rings of rabbit aorta mounted in muscle chambers, endothelial-independent reversible relaxation produced by irradiation with long wavelength was potentiated in the presence of 1 mM NaNO2. Photorelaxation in the presence of NaNO2, but not in its absence, was further potentiated by superoxide dismutase. The interaction of light and NaNO2 in producing relaxations was studied in a perfusion-superfusion system in which Krebs' solution (37 degrees C, 95% O2-5% CO2) with or without added NaNO2 was perfused (2 ml/min) through a glass tube (1.25 mm, inside diameter) on its way to superfusing an endothelium-free aortic ring a few seconds downstream. UV irradiation either of the solution flowing through the tube or of the aortic ring could be made separately. The ring, mounted for tension recording, was precontracted to a similar level of tone in the absence or presence of NaNO2 by l-phenylephrine HCl. Photorelaxation on direct irradiation of the ring was potentiated markedly by 1 mM NaNO2, was not significantly potentiated further by 10 U/ml of superoxide dismutase, and was inhibited markedly by Hb (1-10 microM) but not by MetHb (10 microM). Irradiation of the perfusing solution produced no relaxation of the aortic ring downstream in the absence of NaNO2, and only small relaxation at 1 mM NaNO2. When superoxide dismutase was present along with NaNO2, irradiation of the perfusing solution (15-120 sec) produced marked relaxation, with magnitude increasing with concentration of NaNO2 (1 microM-1 mM). This relaxation was inhibited by Hb (complete at 0.3-1 microM) but only partly by MetHb (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of the laser energy to the cerebral vascular reactivity and the blood brain barrier. A Nd:YAG laser with 20 watt impacts of 0.5, 1.0, 2.5 and 5.0 seconds duration time were irradiated through the cranial window made at the parietal regions of anesthetized adult cats. The disruption of the blood brain barrier was examined by checking the degree of the extravasation of Evans blue dye administrated in the vein. The cortical vessel reactivity was observed through the cranial window and evaluated using an intravital microscope and a videoangiometer. The extravasation of Evans blue dye was seen uniformly extending from the histologically changed area into the surrounding tissue in all experiments. The extent of the extravasation of dye was 1 to 1.5 mm larger than the extent of the histologically changed area produced by laser irradiation. Pial arteries in the area with histological changes dilated markedly and some of them lost their blood stream. Pial arteries in the area of Evans blue extravasation, but outside it histological changes also dilated markedly. Furthermore, pial arteries within a distance of 200 to 400 microns from the edge of the Evans blue extravasation area also dilated moderately. A statistical estimation showed that the degree of dilatation of arteries in the area outside the histological change improved significantly in the time course of five minutes.

Brief pulses of 577-nm radiation have recently been shown to selectively damage superficial cutaneous blood vessels, resulting clinically in purpura. There was a sharp threshold of exposure dose necessary for causing purpura in any given subject, which correlated with histologic evidence of extravasation and specific vascular injury. As a means of studying mechanisms for such damage, heat, cold, pressure, suction, UV radiation, and intradermal epinephrine were used to alter human cutaneous microvasculature prior to and during 577-nm pulsed dye laser exposures. When compared with control sites, only cooling of the skin significantly affected the exposure dose needed to cause purpura. The magnitude of this effect is quantitatively most consistent with intravascular microvaporization as the cause of vessel rupture and hence purpura.