Biomedical subjects

P W Cho

Publications and source records attributed to P W Cho.

11 recordsLinked to original sources

PubMed1998

Less invasive techniques for mitral valve surgery.

OBJECTIVE: Minimally invasive surgical techniques aim at reducing the consequences of currently used large incisions, such as bleeding, pain, and risk of infection. Although this new approach developed rapidly in coronary surgery, it remains questionable in mitral valve surgery. This article reports the longest experience with minimally invasive mitral valve surgery, with particular attention to approach and techniques. METHODS: From February 1996, the date of the first case of minimally invasive mitral valve reconstruction, to April 1997, 22 patients with a mean age of 54 +/- 2.7 years were subjected to mitral valve surgery performed with less invasive techniques. Exposure of the mitral valve was achieved through a minithoracotomy (n = 12) or a ministernotomy (n = 10). Video assistance was used in all cases. Peripheral arterial cannulation (n = 21) and venous drainage (n = 22) were used in most cases. RESULTS: In this series, valve surgery consisted in 19 repairs, two replacements, and one closure of a periprosthetic leak. In two cases it was necessary to convert to a larger incision. The average duration of cardiopulmonary bypass was 157 +/- 8.2 minutes, ventilatory assistance 16 +/- 4.6 hours, and intensive care unit stay 2.1 +/- 0.4 days. Two patients required reoperation for bleeding and another for early recurrence of mitral valve regurgitation. There were no deaths and all patients were discharged with normal valve function. At most recent follow-up, all patients were in functional class I, with resumption of normal activity. CONCLUSION: Mitral valve surgery can be performed safely by means of less invasive techniques, but with increased technical difficulty. A low asymmetric median sternotomy seems preferable to an anterior thoracotomy.

Cardiopulmonary Bypass↗

PubMed1995

Reverse remodeling from cardiomyoplasty in human heart failure. External constraint versus active assist.

BACKGROUND: Cardiomyoplasty (CM) is a novel surgical therapy for dilated cardiomyopathy. In this procedure, the latissimus dorsi muscle is wrapped around the heart and chronically paced synchronously with ventricular systole. While studies have found symptomatic improvement from this therapy, the mechanisms by which CM confers benefit remain uncertain. This study sought to better define these mechanisms by means of serial pressure-volume relation analysis. METHODS AND RESULTS: Serial pressure-volume studies were performed by the conductance catheter method in three patients (total to date) with dilated cardiomyopathy (New York Heart Association class III) who underwent CM. Data were measured at baseline (before surgery) and at 6 and 12 months after CM. Chronic left ventricular (LV) systolic and diastolic changes induced by CM were evaluated with the stimulator in its stable pacing mode (every other beat) and after temporarily suspending pacing. CM-stimulated beats were compared with pacing-off beats to evaluate active systolic assist effects of CM. In each patient, CM resulted in a chronic lowering of cardiac end-diastolic volume and an increased ejection fraction. Most notably, the end-systolic pressure-volume relation shifted leftward, consistent with reversal of chronic chamber remodeling. In contrast, the diastolic pressure-volume relation was minimally altered, and the loops shifted down along the same baseline relation. These marked chronic changes in LV function measurable with CM stimulation off contrasted to only minor acute effects observed when the muscle wrap was activated. This suggests that the benefit of CM derived less from active systolic assist than from remodeling, perhaps because of an external elastic constraint. CONCLUSIONS: These data, while limited to a small number of patients, suggest that CM can reverse remodeling of the dilated failing heart. While systolic squeezing assist effects of CM may play a role in some patients, our study found that this was not required to achieve substantial benefits from the procedure. We speculate that CM may act more passively, like an elastic girdle around the heart, to help reverse chamber remodeling.

Adult↗

PubMed1995

Platelet activating factor inhibition reduces lung injury after cardiopulmonary bypass.

Because cardiopulmonary bypass (CPB) produces a diffuse inflammatory reaction that may injure multiple organs and complicate cardiac surgical procedures, we examined the use of a competitive inhibitor of platelet activating factor (SDZ HUL-412) in a porcine model of CPB as a means to ameliorate pulmonary injury after CPB. Thirteen pigs (35 to 40 kg) underwent CPB at 28 degrees C for 2 hours, followed by 2 hours of observation. Group I (n = 6) received SDZ HUL-412 (a quinolinium compound) intravenously (3 mg/kg loading dose and 2 mg.kg-1.h-1 continuous infusion) starting before sternotomy. Group II (n = 7) received a saline vehicle. Peak airway pressure, pulmonary arterial pressure, left atrial pressure, and arterial blood gases were measured and flow cytometry evaluated surface expression of adhesion molecule subunit CD18 on circulating neutrophils. Pulmonary function was significantly improved in group I. Fifteen minutes after CPB, dynamic lung compliance in group I was 91% +/- 12% of baseline versus 49% +/- 5.2% in group II (p = 0.06 by analysis of variance). After CPB, the arterial oxygen pressure was also significantly better in group I than in group II (425 +/- 61 versus 234 +/- 76 mm Hg) (p < 0.05). The rise in pulmonary vascular resistance after CPB was less in group I (p < 0.05) (323 +/- 55 to 553 +/- 106 dynes.s.cm-5) than in group II (531 +/- 177 to 884 +/- 419 dynes.s.cm-5) at the end of the observation period. CD18 up-regulation increased similarly in the two groups during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

PubMed1995

Thalidomide as replacement for steroids in immunosuppression after lung transplantation.

Steroids have been implicated in postoperative complications after lung transplantation: infections, delayed wound healing, and poor bronchial anastomotic healing. Thalidomide (alpha-phthalimidoglutarimide), a sedative drug with known immunomodulatory properties, was used to replace corticosteroids after canine lung transplantation. Fifteen mongrel dogs underwent single-lung transplantation: group I (n = 5) received cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Group II (n = 5) received standard immunosuppression of cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and prednisone (2 mg/kg once a day), and group III (n = 5) received cyclosporin A (10 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Open lung biopsy and bronchoscopy were performed weekly until sacrifice on day 28. Serum thalidomide and cyclosporin A levels were followed up weekly. Group I showed essentially no rejection until week 2 and minimal rejection (grade 1) until day 28. Group II had moderate rejection (grade 2) of the graft at all time points. Group III animals had moderate to severe rejection (grades 3 to 4) after 21 days (p < 0.05 for group I versus groups II and III). The number of clinically evident episodes of pneumonia was also significantly lower in group I than in groups II and III (p < 0.05). We conclude that thalidomide appears to replace corticosteroids effectively in early postoperative immunosuppression after lung transplantation and is associated with a decreased incidence of pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

New method for mechanistic studies of cardiomyoplasty: three-dimensional MRI reconstructions.

The imaging modalities used to study the mechanism of cardiomyoplasty, such as echocardiography and radionuclide scintigraphy, are seriously limited by their two-dimensional format. Radiofrequency-pulse-tagged magnetic resonance imaging was used to generate three-dimensional reconstructions of the left ventricle throughout the cardiac cycle after cardiomyoplasty. In 2 dogs that had undergone conditioned, right anterior cardiomyoplasty, wrap stimulation with alternating heartbeats was found to produce marked translation of the left ventricle in the short-axis plane, rotation around the long axis, and displacement along the long axis with net long-axis compression; there was no augmentation of radial squeeze. The findings from this study suggest that any systolic augmentation produced by the right anterior wrap is due primarily to long-axis compression. Our study demonstrates a new, more accurate technique of assessing the mechanical effects of cardiomyoplasty in three dimensions, thus permitting a more rational optimization of wrap configurations, and emphasizes the perils of using standard two-dimensional imaging modalities in this setting of exaggerated three-dimensional motion.

Animals↗

PubMed1994

Mitral valve operation in patients with the Marfan syndrome.

Optimal surgical treatment of mitral regurgitation in the Marfan syndrome (valve repair versus replacement) is controversial because the underlying connective tissue defect theoretically might compromise repair durability. To examine the results of mitral valve repair in these patients, we did a retrospective review of 160 patients with the Marfan syndrome who had cardiac surgical procedures between January 1983 and January 1993. Thirty-six patients had mitral procedures, 29 of which were repairs. Mitral valve replacement was necessary in seven patients because of extensive annular calcification and/or severe anterior leaflet abnormalities. The 18 men and 11 women undergoing mitral valve repair had a mean age of 26.5 +/- 2.6 years (range 9 months to 54 years); seven patients were less than 18 years of age. Twenty-four of the 29 patients had concomitant aortic root replacement because of aortic dilation or valvular insufficiency. All 29 repairs included annuloplasty, and 11 patients also required leaflet resection. There were no operative deaths. At mean follow-up of 26.6 +/- 4.8 months, there have been three late deaths, two caused by arrhythmia and one by complications of type III aortic dissection. All survivors are in New York Heart Association class I or II. In three patients recurrent mitral regurgitation developed (grade III or IV); 5-year actuarial freedom from significant mitral regurgitation was 88.3%. One patient required repeat mitral annuloplasty after endocarditis of the composite aortic graft spread to the mitral valve. No patient required late mitral valve replacement. These results demonstrate that (1) 22% of patients with the Marfan syndrome who undergo cardiac operation require a mitral valve procedure, (2) most can be treated by mitral repair rather than replacement, and (3) at early follow-up, results of mitral repair in this population are satisfactory.

Actuarial Analysis↗

PubMed1993

Neutrophil activation mediates protamine-induced pulmonary hypertension.

Protamine reversal of heparin anticoagulation can cause catastrophic pulmonary hypertension, systemic hypotension, and hypoxemia. This reaction is thought to be associated with pulmonary sequestration of activated neutrophils. To examine whether this reaction could be prevented by blocking neutrophil activation with NPC 15669 (N-(9H-(2,7-dimethylfluorenyl-9-methoxy)carbonyl)-L-leucine), an inhibitor of Mac-1 adhesion molecule up-regulation, we gave 12 piglets a heparin bolus (300 IU/kg i.v.) followed by protamine (3 mg/kg i.v. over 90 sec) 15 min later. Six of the piglets received NPC 15669 (10 mg/kg i.v. bolus, then 6 mg/kg/hr i.v. infusion) 15 min before the heparin bolus. Two minutes after protamine administration, CD18 (beta-subunit of Mac-1) expression measured by immunofluorescence flow cytometry increased 128 +/- 9% (mean +/- SEM) over preprotamine levels in control piglets but remained unchanged in NPC piglets (99 +/- 2%, P < 0.05). Fifteen minutes after protamine, lung myeloperoxidase activity, an index of neutrophil degranulation, was significantly lower in the NPC group (87.83 +/- 10.04 versus 57.23 +/- 2.59 mumol/10 mg; P < 0.005). NPC 15669 also prevented postreversal pulmonary artery hypertension (158 +/- 30, 150 +/- 20, and 140 +/- 13 versus 91 +/- 7, 91 +/- 18, and 85 +/- 9% preprotamine at Minutes 2, 5, and 10; P < 0.05). Systemic arterial pressure, cardiac output, and circulating neutrophil counts were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Pressure-volume analysis of changes in cardiac function in chronic cardiomyoplasty.

Reports of clinical improvement in human studies of dynamic cardiomyoplasty lack support by consistent objective hemodynamic evidence. Animal studies have also yielded conflicting results, likely due to nonuniform models, particularly the use of unconditioned wraps, and to limitations in commonly used study modalities caused by exaggerated heart motion during wrap stimulation. Our purpose was to assess the primary functional properties of the heart wrapped by conditioned muscle using pressure-volume relation analysis based on conductance catheter volume data. Compared with the unstimulated state, 1:1 stimulation caused an increase in contractility and decreases in end-diastolic volume and stroke work. Assisted beats during 1:2 stimulation showed an increase in contractility and a decrease in end-diastolic volume. Unassisted beats (1:2) showed decreases in end-diastolic volume and stroke work. There was no augmentation of cardiac output or ejection fraction with stimulation (1:1 or 1:2). We conclude that in the nonfailing heart, increased contractility does not augment cardiac output, ejection fraction, and stroke work because of a simultaneous decrease in end-diastolic volume. These changes in contractility and end-diastolic volume may prove therapeutic for dilated cardiomyopathy.

Animals↗

PubMed1990

Calcium-free reperfusion prevents mitochondrial calcium accumulation but exacerbates injury.

Excessive accumulation of intracellular calcium has been proposed as a mediator of cell injury during ischemia and reperfusion. To test whether restriction of extracellular calcium might ameliorate hepatic injury following hypothermic ischemic preservation, isolated perfused rat livers were reperfused with a medium with normal extracellular calcium (mM-Ca) or no added calcium (microM-Ca) following 26 hr preservation at 4 degrees C. During reperfusion mitochondria from mM-Ca livers accumulated calcium and respiratory activity declined. Although mitochondrial calcium accumulation was prevented by microM-Ca reperfusion, damage to respiratory activity was exacerbated. Edema formation and loss of gluconeogenesis were similarly exacerbated in microM-Ca. This accelerated damage was not reversed by subsequent restoration of calcium. These results demonstrate that rather than ameliorating cell injury, calcium deprivation during reperfusion exacerbates damage to mitochondrial and cellular functions. Thus, cellular or mitochondrial calcium accumulation does not appear to be a sine qua non for hepatocyte injury during reperfusion following hypothermic ischemia.

Animals↗

PubMed1984

Powder suspension method for critically re-examining the two-site model for hydroxyapatite dissolution kinetics.

A powder dissolution method has been developed, and experiments with the hydroxyapatite suspensions confirm earlier conclusions based on dissolution from hydroxyapatite disks. Although a quantitative assessment of the properties of site 1 was not possible from the data obtained in the present study, a rather accurate and independent evaluation of the properties and the behavior of site 2 of the two-site model for hydroxyapatite dissolution was possible, and the results clearly validate the original two-site model. The present work together with the earlier disk studies show that dissolution from site 2 is well described by a first-order expression, rate = kc2 (Cs2-C), where kc2 is a first-order rate constant, Cs2 is the apparent solubility for site 2 (defined by an ion activity product, KHAP, of the form a10Ca2+PO43-a2OH-, and the solution conditions), and C is the microenvironmental solution concentration of hydroxyapatite. For four different precipitated hydroxyapatite preparations, a single KHAP value of 1 X 10(-128) +/- 1 was found to be consistent with experiments using solutions covering wide ranges of partial saturation and calcium-phosphate ratios. The hydroxyapatite powder and pellet methods (including the data evaluation procedures) now offer a powerful combination for investigating the complex kinetics associated with dental enamel dissolution in particular and enamel chemistry in general.

Calcium↗

PubMedDate not supplied

Arterial delivery of genetically labelled skeletal myoblasts to the murine heart: long-term survival and phenotypic modification of implanted myoblasts.

The ability to replace damaged myocardial tissue with new striated muscle would constitute a major advance in the treatment of diseases that irreversibly injure cardiac muscle cells. The creation of focal grafts of skeletal muscle has been reported following the intramural injection of skeletal myoblasts into both normal and injured myocardium. The goals of this study were to determine whether skeletal myoblast-derived cells can be engrafted into the murine heart following arterial delivery. The murine heart was seeded with genetically labeled C2C12 myoblasts introduced into the arterial circulation of the heart via a transventricular injection. A transventricular injection provided access to the coronary and systemic circulations. Implanted cells were characterized using histochemical staining for beta-galactosidase, immunofluorescent staining for muscle-specific antigens, and electron microscopy. Initially the injected cells were observed entrapped in myocardial capillaries. One week after injection myoblasts were present in the myocardial interstitium and were largely absent from the myocardial capillary bed. Implanted cells underwent myogenic development, characterized by the expression of a fast-twitch skeletal muscle sarcoendoplasmic reticulum calcium ATPase (SERCA1) and formation of myofilaments. Four months following injection myoblast-derived cells began to express a slow-twitch/cardiac protein, phospholamban, that is normally not expressed by C2C12 cells in vitro. Most surprisingly, regions of close apposition between LacZ labeled cells and native cardiomyocytes contained structures that resembled desmosomes, fascia adherens junctions, and gap junctions. The cardiac gap junction protein, connexin43, was localized to some of the interfaces between implanted cells and cardiomyocytes. Collectively, these findings suggest that arterially delivered myoblasts can be engrafted into the heart, and that prolonged residence in the myocardium may alter the phenotype of these skeletal muscle-derived cells. Further studies are necessary to determine whether arterial delivery of skeletal myoblasts can be developed as treatment for myocardial dysfunction.

Animals↗