John Eugene

PHOTOSENSITIZATION OF EXPERIMENTAL ATHEROMAS BY PORPHYRINS

Arteriosclerotic arteries have been shown to fluoresce when treated with hematoporphyrin derivative. This study investigates the incorporation and distribution of a partially purified form of hematoporphyrin derivative (Photofrin II) in normal and arteriosclerotic rabbit aortas. A thoracoabdominal exploration was performed in 15 rabbits. Group I comprised normal rabbits, Group II normal rabbits given 5 mg/kg Photofrin II 48 hours before surgery, Group III arteriosclerotic rabbits and Group IV arteriosclerotic rabbits given 5 mg/kg Photofrin II 48 hours before surgery. Multiple aortic biopsy specimens for frozen section were taken from all rabbits. In addition, open laser endarterectomy (with an argon ion laser) was performed on Group III and Group IV rabbits. Frozen sections were studied by digital video fluorescence microscopy to determine the distribution of Photofrin II within the layers of the aortic wall. The fluorescence of the intima of Group IV rabbits was found to be significantly greater than that of the intima, internal elastic lamina, media or adventitia of the other groups (p less than 0.01) and significantly greater than that of the internal elastic lamina, media or adventitia of Group IV rabbits (p less than 0.01). When open laser endarterectomy was performed, Group III rabbits required 103 +/- 14 J/cm2 and Group IV required 33 +/- 3 J/cm2 (p less than 0.01). It is concluded that porphyrins are selectively localized within the intima of arteriosclerotic arteries. This localization sensitizes atheromas to argon ion laser light and facilitates laser endarterectomy.

Clinical choices for circulatory assist devices.

Approximately 1.0% of open heart surgery patients become unweanable from cardiac bypass during the surgical procedure. In addition, nearly 20% of patients accepted for cardiac transplantation die while waiting for a donor heart. Pulsatile pneumatic ventricular assist devices (VADs) provide a realistic solution to these dilemmas. Currently, there are five manufacturers who are competing for the major market share in the clinical use of these devices. Novacor, Thermetics, Thoratec, Symbion, and Abiomed all have competitive VAD systems. Because no one system is optimal for all patients, the limitations, similarities, and strengths of each system should be known to enhance the patients outcome when using these devices. Successful use of VAD systems, either as a bridge to transplantation or to ventricular recovery, is best approached by adherence to strict patient selection. Once instituted, VAD management centers on detailed attention to anticoagulation and prompt diagnosis and treatment of various complications.

Reduction Pneumonoplasty for Patients With a Forced Expiratory Volume in 1 Second of 500 Milliliters or Less

BACKGROUND: Patients with severely impaired pulmonary function are considered at high risk for emphysema operations. We prospectively evaluated 44 patients with a forced expiratory volume in 1 second of 0.5 L or less undergoing reduction pneumonoplasty for dyspnea uncontrolled by medical management (confirmed by Borg and modified Medical Research Council dyspnea scales). METHODS: There were 28 men and 16 women (mean age, 66 years) with a mean preoperative forced expiratory volume in 1 second of 0.41 L (range, 0.23 L to 0.50 L). Preoperative therapy consisted of bronchodilators (100% of patients), oxygen (80%), and steroids (72%). Hypercarbia was seen in 80% of patients, and 66% had pulmonary hypertension. Unilateral reduction pneumonoplasty by a video-assisted thoracic surgical approach was performed in 34 patients, 6 patients underwent bilateral reduction pneumonoplasty by a video-assisted thoracic surgical approach, and 4 patients underwent bilateral reduction pneumonoplasty by a video-assisted thoracic surgical approach, and 4 patients underwent bilateral reduction pneumonoplasty by median sternotomy. Discrete emphysematous regions were resected using staplers with buttressing, and regions of homogeneous emphysema were plicated with KTP or neodymium:yttrium-aluminum garnet laser radiation. RESULTS: There was one death within 30 days, two additional deaths within 60 days, and five additional deaths within 1 year. Hospital stay averaged 12 days. Intensive care unit stay averaged 4 days. Subjective improvement was noted by 89%. Borg and modified dyspnea scores improved from 7.6 to 4.5 (p < 0.01) and from 3.9 to 2.35 (p < 0.01), respectively. Forced expiratory volume in 1 second was 0.62 L at 1 year, a 51% improvement (p < 0.001). Forced vital capacity was 1.32 L preoperatively and 2.05 L at 1 year (a 56% improvement) (p < 0.001). CONCLUSIONS: This experience documents that patients with severely impaired lung function can successfully undergo operation for emphysema. To obtain these results one must tailor the operative approach to the patients disease.

Experimental arteriosclerosis treated by conventional and laser endarterectomy

Open laser endarterectomy was compared to standard surgical endarterectomy in the rabbit arteriosclerosis model. The aorta was exposed by a thoracoabdominal exploration in 16 rabbits. In Group I (8 rabbits), a conventional endarterectomy (CE) was performed with standard vascular instruments. In Group II (8 rabbits), laser endarterectomy (LE) was performed with an argon ion laser (488 nm and 514.5 nm) at a power of 1.0 W. Aortas were fixed, serially sectioned (6 micron) and stained (H +/- E) following each procedure. Gross and light microscopic examination revealed identical results for the endarterectomy surfaces of CE and LE. The proper cleavage plane within the media was developed with both techniques and the remaining arterial wall was not damaged with either procedure. The end points of LE were consistently superior to those of CE because of phototherapy fusion. The LE end points were tapered and the intima was fused. Intimal flaps were seen in 2/8 CE experiments and the remaining end points exhibited an uneven transition. LE required an average energy density of 124 +/- 9 J/cm2. We conclude that LE provides a satisfactory method for the in vivo evaluation of laser radiation upon arteriosclerotic arteries. LE may be the way to begin clinical laser trials.

Initial clinical evaluation of carotid artery laser endarterectomy

Clinical study of carotid artery laser endarterectomy began April 15, 1988. This report describes the first 10 cases that were performed in nine patients (five men and four women, mean age 70 years). Indications were asymptomatic stenosis (5), transient ischemic attacks (4), and stroke in evolution (1). There were two emergency cases and eight elective cases (including one reoperative case). Surgical exposure, systemic heparinization, vascular control, and a longitudinal arteriotomy were used. The cleavage plane between atheromas and media was developed with argon ion laser radiation (488 and 514.5 nm) directed through a 300 microns quartz fiber at power 1.0 W. Laser radiation was used to cut the atheromas out of the arteries and weld the end points. Residual atheromatous debris were vaporized with individual laser exposures. Arteriotomies were closed with sutures, and blood flow was restored. The endarterectomies were 3.9 +/- 1.1 cm long and required 330 +/- 97 joules. Mean clamp time was 22.5 +/- 7.9 minutes. Shunts were used in two cases. There were no arterial perforations or injuries as a result of laser light. Complications were hematoma (1), respiratory arrest (1), and transient neurologic deficit (1). Carotid endarterectomy is technically feasible with argon ion laser radiation. In the present series, postoperative observations, averaging 12 months and ranging from 5 to 19 months, have shown satisfactory results. No angiographic follow-up examinations were carried out.

The thrombogenic potential of argon ion laser endarterectomy

The surface thrombogenicity of atheromas, conventional endarterectomy (CE), laser endarterectomy (LE), and laser angioplasty (LA) were compared in the rabbit arteriosclerosis model. Normal (N = 6) and arteriosclerotic (N = 15) rabbits underwent thoracoabdominal exploration. Multiple CEs and LEs were performed in 12 arteriosclerotic rabbits leaving a segment of intact atheroma between each endarterectomy. Multiple LAs were performed in three arteriosclerotic rabbits. Argon ion laser radiation was used for all laser procedures. Blood (0.05 ml) from normal rabbits was placed on the CE surface, LE surface, LA surface, atheroma, and normal intima and clotting times were determined. Surface thrombogenicity was calculated as the ratio of the clotting time of the CE, LE, LA, or atheroma to normal intima. Surface thrombogenicity was 1.0 +/- 0.03 for normal intima (control), 0.58 +/- 0.06 for atheromas (P less than 0.001), 0.46 +/- 0.08 for CE (P less than 0.001 from atheromas), 0.46 +/- 0.08 for LE (P = NS from CE), and 0.27 +/- 0.09 for LA (P less than 0.001 from CE and LE). The thrombogenicity of LE is the same as the thrombogenicity of CE. Both forms of endarterectomy are less thrombogenic than LA in the rabbit model.

Concepts in the application of pneumatic ventricular assist devices for ischemic myocardial injury

&NA; The clinical results of “bridge‐to‐recovery” from ischemic myocardial injury using pneumatic ventricular assist devices (VADs) have been disappointing, because no significant improvement in the hospital discharge rate (25%) has been observed during the past 10 years. Interestingly, similar results have been reported using the less sophisticated and more widely available centrifugal pumps. It is well recognized that appropriate patient selection and early device implantation are important determinants of patient survival; however, it is less clear why there is a lack of difference in the results between pneumatic VADs and the centrifugal pumps. The reasons for the lack of difference in the results between pneumatic VADs and centrifugal pumps are multifactorial, and to some extent may be due to a conservative approach in the application of the more capable pneumatic VADs. In an effort to provide a more effective approach to the clinical application of pneumatic VADs for bridge‐to‐recovery, two pneumatic devices (the Jarvik 7‐70 total artificial heart and the Symbion acute VAD) were functionally characterized using an in vitro mock circulatory system. The performance under pneumatic VAD asynchronous pumping compared to electrocardiogram synchronous counterpulsation was also evaluated. Based upon the results obtained, a two phase approach was developed. In the initial phase (i.e., the first 12‐48 hrs), device output is maximized through asynchronous pumping to rapidly reverse the effects of cardiogenic shock. During the second phase (i.e., after hemodynamic stabilization and early evidence of end‐organ recovery), electrocardiogram synchronous counterpulsation is used to focus more specifically on recovery of the heart. Unlike previous approaches, this two phase approach provides a more physiologic setting to enhance recovery by effectively reducing myocardial oxygen consumption through asynchronous pumping (Phase 1) and maximally increasing myocardial oxygen delivery through electrocardiogram synchronous counterpulsation (Phase 2). This approach, coupled with appropriate patient selection and early device institution, may improve recovery in the clinical setting of reversible myocardial injury. ASAIO Journal 1995; 41:162‐168.

Comparison of contact and free beam laser endarterectomy

Free beam laser endarterectomy (LE) and contact laser endarterectomy (CLE) were compared in 15 arteriosclerotic New Zealand white rabbits. The rabbits underwent balloon catheter trauma to the thoracoabdominal aorta and were fed a 2% cholesterol diet for 18 weeks. Thoracoabdominal exploration was performed under general anesthesia and multiple endarterectomies were performed in each rabbit. Atheromas were dissected from arteries with laser radiation and end points were welded in place with laser radiation. LEs (N = 8) were performed with argon ion radiation delivered through a 400 microns fiberoptic. Power was kept constant at 1 W and the average fluence was 97.5 +/- 6.6 J/cm2. CLEs were performed with conical sapphire probes powered by either argon ion radiation (N = 12) or Nd-YAG radiation (N = 10). Power used was 1 W to 4 W for each laser. Average argon ion fluence was 117.8 +/- 3.1 J/cm2 and average Nd-YAG fluence was 611.1 +/- 34.4 J/cm2. Following the operations, aortas were removed, fixed, serially sectioned, and stained. Microscopic study revealed welded end points with LE but not with CLE. There were no perforations with LE. There were 11/12 perforations with argon ion CLE and 8/10 perforations with Nd-YAG CLE. Free beam laser endarterectomy is superior to contact laser endarterectomy for experimental atheromas.

Regional myocardial perfusion measured by the avalanche radiation probe during cardiopulmonary bypass: Pharmacologic and physiologic alterations

Ronald P. Karlsberg, John Eugene, Kenneth P. Lyons, William E. Shell, and Vincent L. Gelezunas. Los Angeles and Long Beach, Calif. The health and function of myocardium is critically dependent on myocardial perfusion. However, cur- rent techniques for measurement of tissue perfusion are limited. More attention has focused on large- vessel blood flow or coronary anatomy, which pro- vides only indirect indications of perfusion to the myocardium. Investigation of the microcirculation in vivo has been hampered, in part, by the inability to obtain convenient, reliable measures of regional perfusion. In order to obtain repetitive in vivo measurement of regional microcirculation, we used the avalanche radiation probe to measure the clearance of intracor- onary xenon-133, a function of capillary flow. We have previously demonstrated the use of the ava- lanche radiation probe for determination of myocar- dial perfusion by detection of xenon-133 washout in a limited setting.’ Measurements of regional blood flow in detection volumes of 0.5 cm3 correlate closely to measurements of regional flow obtained by radio- active microspheres.’ Nevertheless, some variation from animal to animal and within animals was observed. Some of this variation was possibly because of the instability of the animal model and the inability to precisely stabilize and regulate regional perfusion. These factors include coronary blood flow and myocardial oxygen consumption. In order to perform further reliability and validity studies in a model in which the factors which control regional perfusion are more closely controlled, we validated measurements of regional perfusion

Experimental cholelitholysis with the pulsed tunable dye laser.

This study evaluates the pulsed tunable dye laser with wavelength 504 nm, frequency 10 Hz, and pulse width 1.2 microseconds for cholelitholysis. Power of 10-40 kW was directed through a 250-microns quartz fiber optic to ablate 55 gallstones (removed from 14 patients). The fiber was positioned in direct contact with the stones under saline. Power delivery was begun at 10 kW and increased in 10-kW increments until litholysis began. The range of power and energy necessary to fragment the gallstones was evaluated on four common bile ducts (fresh autopsy specimens). Following fragmentation, all stones were analyzed. There were 35 cholesterol stones (3 calcified) and 20 bilirubin stones (4 calcified). Size ranged from 0.012 to 7.56 cm3 (mean 0.96 +/- 1.41 cm3). Energy necessary for fragmentation ranged from 0.4 to 11.2 J (exposure time 1.0-28 s). Power necessary for fragmentation was 20 kW for 2/55 stones and 40 kW for 53/55 stones. At 40 kW (40 mJ/pulse), common bile duct perforation occurred within 1.1 +/- 0.1 s (0.44 +/- 0.04 J). The pulsed tunable dye laser can fragment gallstones of all compositions. The threshold for fragmentation is 40 kW, but common bile duct perforation occurs at this power. We conclude that laser radiation sufficient to fragment gallstones can injure the common bile duct.