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Biomedical subjects

K A Kadipasaoglu

Publications and source records attributed to K A Kadipasaoglu.

At least 19 recordsLinked to original sources

Sustained angina relief 5 years after transmyocardial laser revascularization with a CO(2) laser.

BACKGROUND: Although transmyocardial laser revascularization (TMR) has provided symptomatic relief of angina over the short term, the long-term efficacy of the procedure is unknown. Angina symptoms as assessed independently by angina class and the Seattle Angina Questionnaire (SAQ) were prospectively collected up to 7 years after TMR. METHODS: Seventy-eight patients with severe angina not amenable to conventional revascularization were treated with a CO(2) laser. Their mean age was 61+/-10 years at the time of treatment. Preoperatively, 66% had unstable angina, 73% had had >/=1 myocardial infarction, 93% had undergone >/=1 CABG, 42% had >/=1 PTCA, 76% were in angina class IV, and 24% were in angina class III. Their average pre-TMR angina class was 3.7+/-0.4. RESULTS: After an average of 5 years (and up to 7 years) of follow-up, the average angina class was significantly improved to 1.6+/-1 (P=0.0001). This was unchanged from the 1.5+/-1 average angina class at 1 year postoperatively (P=NS). There was a marked redistribution according to angina class, with 81% of the patients in class II or better, and 17% of the patients had no angina 5 years after TMR. A decrease of >/=2 angina classes was considered significant, and by this criterion, 68% of the patients had successful long-term angina relief. The angina class results were further confirmed with the SAQ; 5-year SAQ scores revealed an average improvement of 170% over the baseline results. CONCLUSIONS: The long-term efficacy of TMR persists for >/=5 years. TMR with CO(2) laser as sole therapy for severe disabling angina provides significant long-term angina relief.

Adult↗

Transmyocardial laser revascularization: effect of laser parameters on tissue ablation and cardiac perfusion.

Dr. Mahmood Mirhoseini from Milwaukee, WI, transformed transmyocardial revascularization (TMR) into transmyocardial laser revascularization (TMLR) more than 2 decades ago. The controversial nature of this laser procedure and the prospect of its successful application to refractory cases of chronic debilitating angina have created spirited interest in TMLR. As a natural component of this interest, various laser modalities have been proposed and employed during the performance of the TMLR procedure both in the experimental and the clinical setting. However, it is the nature of laser-tissue interactions that is primarily responsible for the long-term fate of the channels, the angiogenesis that occurs in the vicinity of these laser channels, and the resulting increase (if any) in myocardial perfusion. These interactions with tissue are, in turn, determined by laser variables such as photonic absorption and scattering by the target tissue, pulse energy and duration, and the peak power generated. The CO2 laser has the advantages of producing high-energy pulses that create a transmural channel with a single pulse, low-peak power that minimizes structural tissue trauma, and high photonic absorption to minimize thermal damage. The holmium:YAG and excimer lasers, in turn, have the advantage of being coupled to a fiber optic catheter for transluminal endocardial delivery. Importantly, long-term clinical and perfusional data showing a cause and effect relationship between the use of TMLR and these end-points are available for the CO2 laser only. Prospective randomized trials are, therefore, warranted to delineate the use of each laser modality in relation to that of the CO2 laser in the TMLR setting.

Coronary Circulation↗

Transmyocardial laser revascularization in allograft coronary artery disease.

We used transmyocardial laser revascularization to treat accelerated cardiac allograft atherosclerosis in 2 patients. One patient received transmyocardial laser revascularization as sole therapy, the other as an adjunct to coronary artery bypass grafting. The systolic function improved in both patients, although the patient who had adjunctive transmyocardial laser revascularization died of systemic infection and renal failure on postoperative day 55. The second patient is alive and well 1 1/2 years after the laser procedure. We discuss 4 other patients who received transmyocardial laser revascularization treatment elsewhere in the United States. Transmyocardial laser revascularization has the potential to become important in the treatment of transplant atherosclerosis. Randomized clinical trials are warranted to assess the efficacy of transmyocardial laser revascularization in this setting.

Coronary Artery Bypass↗

Transmyocardial laser revascularization. Does it have a role in the treatment of ischemic heart disease?

Transmyocardial laser revascularization, with or without coronary artery bypass grafting, is an alternative modality for complete revascularization in selected patients with coronary artery disease. Arguably, this modality works by shunting left ventricular blood directly into the ischemic myocardium via laser-mediated transmural channels. In clinical trials, drilling of laser channels has been strongly correlated with long-term improvement of angina, but a causal relationship has not yet been documented. For now, the usefulness of transmyocardial laser revascularization and the nature of its mechanism remain controversial. Some researchers question the existence of myocardial sinusoids altogether. Others question the physiologic possibility of moving blood from the left ventricular cavity into the myocardium against a pressure gradient. Further questions concern the possible routes through which the additional blood gains access to the myocardium; the difficulty of objectively documenting improved myocardial perfusion after transmyocardial laser revascularization; and the nature of the mechanism responsible for the observed clinical benefit. This article examines the different aspects of this controversy and discusses the current status of transmyocardial laser revascularization, as well as possible future directions.

Cardiac Output↗

Long- and short-term effects of transmyocardial laser revascularization in acute myocardial ischemia.

BACKGROUND AND OBJECTIVE: This study examined the effect of transmyocardial laser revascularization (TMLR) on infarct size and global and regional left ventricular (LV) function. STUDY DESIGN/MATERIALS AND METHODS: Acute ischemia was induced in 24 dogs by ligating the left anterior descending artery. TMLR was done through a left thoracotomy in 12 dogs. The 12 control dogs had ligation only. Global and regional LV function were measured before ligation, then at 6 hours or 3 months after ligation. We calculated the volumetric ratio of damaged myocardium to myocardium at risk (Vd/Vr). RESULTS: At 6 hours, global compensation despite regional dyskinesia was universal; Vd/Vr was the same in control and TMLR dogs. At 3 months, global function during stress was significantly higher in TMLR dogs than in control dogs (P < .05); regional contractions were synergic only in TMLR dogs; mean Vd/Vr was significantly lower in TMLR dogs. CONCLUSION: TMLR limits infarct expansion and improves long-term global and regional function after acute ischemia.

Animals↗

Refractory angina pectoris in end-stage coronary artery disease: evolving therapeutic concepts.

Refractory angina pectoris in coronary artery disease is defined as the persistence of severe anginal symptoms despite maximal conventional antianginal combination therapy. Further, the option to use an invasive revascularization procedure such as percutaneous coronary balloon angioplasty or aortocoronary bypass grafting must be excluded on the basis of a recent coronary angiogram. This coronary syndrome, which represents end-stage coronary artery disease, is characterized by severe coronary insufficiency but only moderately impaired left ventricular function. Almost all patients demonstrated severe coronary triple-vessel disease with diffuse coronary atherosclerosis, had had one or more myocardial infarctions, and had undergone aortocoronary bypass grafting (70% of cases). We present three new approaches with antiischemic properties: long-term intermittent urokinase therapy, transcutaneous and spinal cord electrical nerve stimulation, and transmyocardial laser revascularization.

Aged↗

Laser-tissue interaction during transmyocardial laser revascularization.

BACKGROUND: The clinical procedure known as transmyocardial revascularization has recently seen its renaissance. Despite the promising preliminary clinical results, the associated mechanisms are subject to much discussion. This study is an attempt to unravel the basics of the interaction between 800-W CO2 laser radiation and biological tissue. METHODS: Time-resolved flash photography was used to visualize the laser-induced channel formation in water and in vitro porcine myocardium. In addition, laser-induced pressures were measured. Light microscopy and birefringence microscopy were used to assess the histologic characteristics of laser-induced thermal damage. RESULTS: The channel depth increased logarithmically with time (ie, with pulse duration) in water and porcine myocardium. Pressure measurements showed the occurrence of numerous small transients during the laser pulse, which corresponded with channel formation, as well as local and partial channel collapse during the laser pulse. Twenty millimeters of myocardium was perforated in 25 ms. Increasing the pulse duration had a small effect on the maximum transversable thickness, but histologic analysis showed that thermal damage around the crater increased with increasing pulse duration. CONCLUSIONS: Several basic aspects of the interaction of high-power CO2 laser radiation with myocardial tissue and tissue phantoms were studied in vitro. Although the goal of this study was not to unravel the mechanisms responsible for the beneficial effects of transmyocardial revascularization, it provided important information on the process of channel formation and collapse and tissue damage.

Animals↗

PTCA in angulated segments: effects of balloon material, balloon length, and inflation sequence on straightening forces in an in vitro model.

We sought to determine the effect of balloon material, balloon length, and inflation sequence on the straightening forces generated during percutaneous transluminal coronary angioplasty (PTCA) in angulated segments. Using an in vitro model consisting of a curved channel (3/4" radius) with a displaceable pressure sensor, we examined four different balloon materials: compliant (POC), semicompliant (PE600 and Duralyn), and noncompliant (PET), two balloon lengths (20 mm and 40 mm), and two inflation sequences (rapid and slow) with continuous recording of straightening force during each balloon inflation. Three balloons were tested for each combination of materials, length, and inflation sequence. Long balloons exerted significantly lower straightening forces. There were significantly higher straightening forces with noncompliant, particularly short, balloons. Varying the inflation sequence had no significant effect. For PTCA in angulated segments: (1) long balloons produce lower straightening force, (2) noncompliant balloons produce higher straightening force, particularly with short balloons, and (3) varying the inflation sequence has no significant effect on straightening force.

Angioplasty, Balloon, Coronary↗

Transmyocardial laser revascularization: clinical experience with twelve-month follow-up.

We are investigating a new technique for myocardial revascularization in which an 800 W carbon dioxide laser is used to drill 1 mm diameter channels into a beating heart after left thoracotomy. Clotting occludes the channels on the subepicardium, and in the long-term setting, blood from the left ventricular cavity flows through these channels to perfuse the ischemic subendocardium. To test the efficacy of this technique in a preliminary clinical trial, we used it as sole therapy for 21 consecutive patients. All patients had hibernating myocardium, reduced coronary flow reserve, or both, had distal diffuse coronary artery disease, and had angina refractory to normal therapy. Eight patients were excluded from follow-up because of death (n=5), rerevascularization (n=2), or diaphragmatic paralysis resulting in postoperative respiratory incapacity (n=1). In the remaining 13 patients available for follow-up, the mean angina class (Canadian Cardiovascular Society) was 3.7 +/- 0.4 before operation and 1.8 +/- 0.6 12 months after operation (p < 0.01). Mean resting left ventricular ejection fraction was 48% +/- 10% before operation and 50% +/- 8% at 12-month follow-up. At 12 months, resting mean subendocardial/subepicardial perfusion ratio had increased by 20% +/- 9% in septal regions treated by laser but decreased by 2% +/- 5% in untreated regions (n=11, p <.001). These results suggest that revascularization by this laser technique positively affects subregional myocardial perfusion and may result in clinical benefits for patients with reversible myocardial ischemia. Studies to date have not demonstrated significant changes in global and regional ventricular contractile function.

Aged↗

Myocardial revascularization with laser. Preliminary findings.

BACKGROUND: We assessed the transmyocardial laser revascularization (TMLR) as sole therapy in patients with symptomatic coronary artery disease refractory to interventional or medical treatment. METHODS AND RESULTS: Thirty-one patients were evaluated with positron emission tomography (PET), dobutamine echocardiography, 201Tl single-photon emission computed tomography (201Tl-SPECT), and multigated acquisition radionuclide ventriculography (MUGA). TMLR was performed in 21 patients who had demonstrable ischemia in viable myocardium. The mean Canadian Cardiovascular Society (CCS) angina class was 3.70 +/- 0.7 (4 patients with unstable angina). Untreated septal segments were used as controls. At 3 months, (n = 15 patients), the mean CCS angina class was to 2.43 +/- 0.9 (P < .05). On dobutamine echocardiography, the mean resting wall motion score index was improved by 16% in lased segments (P < .03 vs control), and mean LVEF at peak stress increased by 19% (P = NS vs baseline). On 201Tl-SPECT, perfusion of lased and nonlased segments did not change. On PET, the mean ratio of subendocardial to subepicardial perfusion (SEn/SEp) increased 14% over baseline (P < .001 vs control). At 6 months (n = 15 patients), the mean CCS angina class was 1.7 +/- 0.8 (P < .05). The mean resting wall motion score index was up by 13% in lased segments (P < .05 vs control). Resting LVEF was unchanged. Stress LVEF increased 21% (P = NS vs baseline). Myocardial perfusion remained unchanged by 201Tl-SPECT. On PET, 36% of the lased segments were better, and 25% were worse compared with baseline. The resting SEn/SEp by PET was up 21% (P < .001 vs control). All deaths (two perioperative and three late) occurred in patients with preoperative congestive heart failure. Two patients required repeat revascularization of new coronary lesions. CONCLUSIONS: These results suggest that TMLR improves anginal status, relative endocardial perfusion, and cardiac function in patients who do not have preoperative congestive heart failure.

Aged↗

Transmyocardial laser revascularization. Anatomic evidence of long-term channel patency.

Transmyocardial laser revascularization, a new surgical technique, is being tested in patients with chronic obstructive coronary artery disease that is refractory to conventional revascularization techniques and to maximal medical therapy. During the operation, which is performed on the beating heart through a left thoracotomy, a high-energy CO2 laser is used to bore transmural channels (1 mm in diameter) into the left ventricle. Each high-energy laser pulse is delivered during end diastole and transects the heart within 10 to 60 msec. The operation is based on the theory that blood will flow directly from the left ventricle into the channels and then into the myocardial vascular plexus. Restoring perfusion should alleviate ischemia in potentially viable myocardium and improve ventricular function. Recently, one of our patients died 3 months after transmyocardial laser revascularization of causes unrelated to the operation. Histologic analysis enabled us to obtain, for the 1st time, anatomic evidence of patent laser channels. Routine staining of cardiac tissue with hematoxylin and eosin revealed multiple patent channels, running perpendicular to and interconnecting with the native vasculature. Although reactive fibrous scar tissue had caused narrowing of the original laser tract, the channels had endothelialized and they contained red blood cells. These findings suggest that the laser channels were functional. We report this interesting case and briefly discuss the anatomic and physiologic phenomena involved in establishing camerosinusoidal blood flow by use of transmyocardial laser revascularization.

Coronary Disease↗

Determination of the role of cuticular carbohydrates in the hemocompatibility of Dirofilaria immitis (Nematoda).

We have partially characterized surface glycoproteins of the canine heartworm, Dirofilaria immitis. Histochemical studies indicated the presence of neutral and acidic mucopolysaccharides at the blood-cuticle interface. Fluorescein isothiocyanate-conjugated lectin binding patterns suggested the presence of alpha-D-glucosyl and/or alpha-D-mannosyl, beta-galactosyl, N-acetylneuraminyl and N-acetylated-D-hexosaminyl (sialic and glucuronic acids, respectively) terminal residues among the constituent sugars of the glycocalyx. An additional goal of this study was to assess the significance of each carbohydrate in parasite hemocompatibility by using scanning electron microscopy, internal reflection infrared spectroscopy, and comprehensive contact angle measurements. Each carbohydrate identified in the glycocalyx was selectively cleaved with the appropriate exoglycosidase. Heart-worms bearing native and enzyme-altered surfaces were exposed to platelet-rich canine plasma. Activation and aggregation of platelets were significantly increased on enzyme-treated surfaces as compared with native surfaces. Enzyme-induced cleavage of carbohydrate residues was associated with an increase in critical surface tension or a loss in cuticular structural integrity or both. Hemocompatibility of the heartworm cuticle depends on the retention of a stable saccharide-rich layer that minimizes interaction with plasma proteins and platelets; thus, carbohydrate residues on the glycocalyx may contribute to parasite hemocompatibility. The presence of similar low-critical-surface-tension coatings with high mechanical integrity may impart thromboresistance to other polyphenolic or chitinous substances.

Alcian Blue↗

An ex vivo model for the reperfusion of explanted human hearts.

A model of an ex vivo-reperfused human heart was developed by using a modified Langendorff coronary perfusion circuit. The technical and physiologic aspects of reestablishing myocardial contractility are described. Preliminary studies were conducted in animals. In the present study, we obtained 12 human hearts that had been arrested with cardioplegic solution and excised from cardiac transplant recipients. The perfusate contained type-specific human donor red blood cells in a lactated Ringer's solution containing 5% dextrose. Myocardial contractility was successfully reestablished in 11 hearts and sustained for an average of 98 minutes (range, 79 to 180 minutes) at a coronary perfusion pressure of 80 mmHg. Left ventricular contraction pressures reached 40 mmHg (against intraventricular balloons at an internal pressure of 50 to 75 mmHg). Partial oxygen pressure (PO2) dropped significantly across the empty beating myocardium (from 498 +/- 40 mmHg to 219 +/- 53 mmHg [mean +/- SD]), but no significant change in hemoglobin saturation was observed. Myocardial failure generally stemmed from edematous changes leading to progressive impairment of myocardial relaxation. The intracoronary insertion of over-the-wire catheters did not adversely affect myocardial function. In conclusion, an ex vivo-supported human heart model has been developed that may have a number of applications, including the preclinical evaluation of new interventional diagnostic and therapeutic techniques aimed at the coronary circulation, and the investigation of myocardial mechanics, preservation, and metabolism.

Adult↗

Preliminary results of intraoperative excimer laser angioplasty: phase 1: an adjunct to coronary artery bypass surgery.

The excimer laser underwent phase I clinical trials at three centers to determine its safety for intraoperative coronary laser angioplasty as an adjunct to coronary artery bypass grafting. A 308-nm Xenon-Chloride, pulsed-wave excimer laser was used to perform angioplasty in 30 patients undergoing coronary artery bypass surgery. Forty vessels (30 patients) were treated, in which the extent of occlusion ranged from 30% to 100%, with complete occlusion in 40% of all vessels. Improvement in vessel luminal caliber was achieved in 33 (79%) vessels, with perforations occurring in 4 (12%) vessels, 2 of which required surgical repair. The lumens of the remaining 8 (19%) vessels were not enlarged, and 2 (5%) of these vessels were perforated. Luminal enlargement was most often achieved in totalled occluded vessels in which 16/17 (94%) were recanalized. No patients died within 30 days postoperatively. Five patients demonstrated biochemical and electrocardiographic evidence of myocardial injury 48 hr postoperatively, and one patient died of cardiac arrest 139 days postoperatively. On the basis of these results, we believe that excimer laser angioplasty can be performed safely to improve coronary luminal patency, even in totally occluded vessels, in an operative setting. The long-term value of this procedure remains to be elucidated.

Aged↗

Surface characterization of the cuticle of Dirofilaria immitis.

The surface reactivity of the dog heartworm (D. immitis) was evaluated by comprehensive contact angle measurements and a platelet retention test. Contact angle data yielded calculated surface energy terms very similar to those previously reported for intact vascular endothelium. The platelet test revealed the native worm surface to be nonreactive, retaining fewer platelets than glass or worms whose surfaces had been modified by extraction with acid and high salt solutions. The cuticular morphology of the heartworm was studied with both light and electron microscopy, the latter coupled with ferritin-conjugated double-layer immunolabeling to reveal adsorbed host protein on the cuticle surfaces. Multiple attenuated internal reflection (MAIR) IR spectroscopy confirmed the general composition of this surface layer to be glycoproteinaceous. Morphological and histochemical studies confirmed and extended previous descriptions of nematode cuticle, adding ultrastructural detail on cortical, medial, and basal layers. A trilaminar membrane, apparently corresponding to a mammalian cell membrane (plasmalemma), constituted the external cortical layer as observed in high magnifications. The existence of a glycocalyx of varying thickness was demonstrated in ruthenium red-stained sections. MAIR IR spectra showed this glycoproteinaceous film to appear, in fully hydrated samples, as a loose biological gel. Ferritin-antibody conjugate labeling confirmed the presence of adsorbed dog albumin, dog immunoglobulin class G (IgG) and dog complement fraction 3 (C3) in the cuticular surface layer. It is likely, therefore, that D. immitis heartworms demonstrate long-term thromboresistance at least in part due to their passive low-surface-energy overcoating with host proteins.

Animals↗

Human intraperitoneal response to a left ventricular assist device with a Ti-6AI-4V alloy surface.

The soft tissue reaction to long-term implantation of an intraperitoneal left ventricular assist device (LVAD) was investigated. The HeartMate 1000 (Thermo Cardiosystems, Inc., Woburn, MA) is a pneumatically driven blood pump with smooth titanium alloy (Ti-6AI-4V) outer surfaces that is placed intraperitoneally in the left upper quadrant and sutured to the anterior abdominal wall. It is being used currently as a bridge to cardiac transplant, which sometimes requires extended support times. We examined the tissue capsule that formed around the rigid circular pump housing of four LVADs (duration of implant: 61, 86, 128, and 153 days) for gross, histologic, immunohistochemical, and ultrastructural analysis. Immunostaining was performed using monoclonal and polyclonal antibodies against cytoskeletal tissue markers (vimentin, desmin, alpha-smooth muscle actin), T and B lymphocytes, carcinoembryonic antigen, factor VIII, and cytokeratins (CAM 5.2 AE1/AE3, 34 beta E12, and 35 beta H11). Direct fluorescent immunolabeling for fibrinogen was also performed to characterize cell and tissue type. Histologic analysis of the 3 to 4 mm thick capsule with white, glistening inner surfaces showed fibrovascular tissue with multipotential subserosal cells (MSCs), capillary endothelium, collagen, and a few mononuclear infiltrates. The immunohistochemical profile of the MSCs differed from myofibroblasts despite a morphologic similarity. Transmission electron microscopy revealed abundant rough endoplasmic reticulum and peripherally arranged myofilaments within the spindle shaped cells. It was hypothesized that capsule formation was initiated by fibrin deposition, followed by proliferation of MSCs and subsequent formation of fibrovascular tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Simultaneous evaluation of cardiac wall motion and myocardial ischemic injury by measurement of electrical impedance.

The authors devised a new method to simultaneously evaluate cardiac wall motion and myocardial ischemic injury by measurement of myocardial electrical impedance. This method is based on the principle that electrical properties of the myocardium are affected by intra- or extracellular structure. Impedance was assessed by measuring voltage while a constant alternating current (0.4 mA, 50 kHz) was being applied to the myocardium by way of an electrode that had two parallel 6 mm long needles. In five dogs, an electrode was placed in the left ventricular wall, adjacent to a pair of ultrasonic crystals that were used to estimate regional wall thickness. To change regional contractility and to induce ischemic injury, the left anterior descending coronary artery was ligated. The impedance waveforms were observed to be synchronized with cardiac contraction, and changes in impedence correlated well with changes in wall thickness. Dyskinetic movements in the ischemic myocardium could also be detected through assessment of the impedance waveform. During the first 2 hr, the average value of impedance increased significantly, from 254 +/- 38 omega-cm to 329 +/- 13 omega-cm (P < 0.005), and then decreased, indicating a correlation with the progression and irreversibility of ischemic injury. This simple technique may eventually allow us to simultaneously assess cardiac wall motion and myocardial ischemia in humans.

Animals↗