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Biomedical subjects

M C Oz

Publications and source records attributed to M C Oz.

At least 163 records · Page 9Linked to original sources
PubMed1995

Use of explanted human hearts as a model for the study of cardiac pathophysiologic conditions.

The purpose of this paper is to describe an isolated heart model that uses human hearts to study cardiomyopathy. Techniques of organ preparation and perfusion are described that result in successful restoration of explanted human hearts to a beating condition. Native hearts of transplant recipients were placed on an isolated perfusion circuit immediately after explant. After appropriate organ and circuit preparation these hearts were restored to a functional state. Studies were done to assess the stability over time and response to inotropic stimulation. Six of seven hearts were returned to a functional condition. Left ventricular pressure generation ranged from 56 to 118 mm Hg (mean 84.8 +/- 34.11) at physiologic loading conditions. Hearts remained functional from 67 to 271 minutes (mean 152 +/- 71.7) and retained up to 70% of functional capacity after 120 minutes. Hearts performed in isovolumic and ejecting modes. Hearts had a marked response to inotrope administration not previously described. We conclude that human hearts can be reproducibly restored to a functional condition after explant from transplant recipients and can be maintained in a beating state with reasonably stable pressure generation for an extended period of time, which makes this a useful model with which to study cardiac pathophysiologic conditions. These hearts demonstrate an appropriate response to inotropes not previously observed, most likely because of improved myocardial preservation and stringent control of perfusate chemical make-up.

Adult↗
PubMed1995

Safety and efficacy of aprotinin under conditions of deep hypothermia and circulatory arrest.

Aprotinin has been successfully used to reduce blood loss and blood product requirements in patients undergoing primary and reoperative cardiac operations. Its safety and efficacy during profound hypothermia and circulatory arrest have been questioned, however. A retrospective review compared 24 patients who received aprotinin during complex aortic procedures under profound hypothermia and circulatory arrest with 24 age-matched patients undergoing similar procedures without aprotinin. Activated clotting time was maintained at longer than 500 seconds (kaolin activating agent) or longer than 750 seconds (celite). We observed no statistically significant difference in the incidence of neurologic events (p not significant) or myocardial infarctions (p not significant), and there was a trend toward reduced in-hospital mortality rate in aprotinin-treated patients. A higher incidence of postoperative renal dysfunction was encountered in aprotinin-treated patients. Aprotinin recipients had a significant reduction in requirements for postoperative homologous erythrocytes (p = 0.01). We conclude that aprotinin may be safely and effectively used in patients undergoing deep hypothermia and circulatory arrest.

Aortic Dissection↗
PubMed1995

Inhaled nitric oxide fails to confer the pulmonary protection provided by distal stimulation of the nitric oxide pathway at the level of cyclic guanosine monophosphate.

It has been suggested that inhaled nitric oxide gas may be beneficial after lung transplantation, because endogenous levels of pulmonary nitric oxide decline rapidly after reperfusion. However theoretical concerns remain about the formation of highly toxic oxidants during the quenching of nitric oxide by superoxide. To determine whether distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate might confer the beneficial vascular effects of nitric oxide without its potential toxicities, we studied an orthotopic rat left lung transplant model. In this model, hemodynamic and survival measurements can be obtained independent of the native right lung. Lungs were preserved for 6 hours at 4 degrees C in Euro-Collins solution alone (control, n = 6) or supplemented with the cyclic guanosine monophosphate analog, 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic guanosine monophosphate (cGMP, n = 4). In additional experiments in which lungs were preserved with Euro-Collins solution alone, inhaled nitric oxide was administered during reperfusion (NO, n = 12). Thirty minutes after transplantation and ligation of the native right pulmonary artery, pulmonary vascular resistance, arterial oxygenation, graft neutrophil infiltration (myeloperoxidase activity), and recipient survival were evaluated. Cyclic guanosine monophosphate decreased pulmonary vascular resistance (1.1 +/- 0.2 vs 12.1 +/- 6.3 mm Hg/ml/min, p < 0.05), improved oxygen tension (369 +/- 56 vs 82.8 +/- 48 mm Hg, p < 0.05), reduced myeloperoxidase activity (1.7 +/- 0.3 vs 3.1 +/- 0.9 delta Abs 460 nm/min, p < 0.05), and improved recipient survival (100% vs 0%, p < 0.005) compared with Euro-Collins solution alone (control group). Animals receiving inhaled nitric oxide during reperfusion did not differ from control animals with respect to any of these parameters. These data suggest that distal stimulation of the nitric oxide-cyclic guanosine monophosphate pathway at the level of cyclic guanosine monophosphate has a protective effect that is not seen with inhaled nitric oxide in the immediate pulmonary reperfusion period.

Administration, Inhalation↗
PubMed1995

Nitroglycerin maintains graft vascular homeostasis and enhances preservation in an orthotopic rat lung transplant model.

Transplanted lungs often fail during the peritransplantation period for poorly understood reasons. Because the nitric oxide pathway regulates pulmonary vascular tone, helps to maintain the integrity of the endothelial barrier, and modulates neutrophil adhesivity and activation, we hypothesized that perturbation of this pathway during the preservation and reperfusion of transplanted lungs might play a critical role in mediating early graft failure. To evaluate whether supplementing the preservation solution with the nitric oxide donor nitroglycerin enhances lung preservation for transplantation, we obtained hemodynamic measurements in a model of orthotopic left lung transplantation in the rat after ligation of the native right pulmonary artery. In these experiments, recipient survival and hemodynamics depended solely on the transplanted lung. The left lung was harvested from 22 rats, flushed with either lactated Ringer's solution alone (control, n = 11) or Ringer's solution supplemented with nitroglycerin (0.1 mg/ml, n = 11), preserved for 4 hours at 4 degrees C, and then transplanted using a rapid cuff technique for bronchial and vascular anastomoses. Nitroglycerin significantly improved arterial blood oxygenation (339 +/- 66 versus 130 +/- 12 mm Hg, p < 0.05), increased pulmonary arterial flow (7.6 +/- 1.9 versus 0.9 +/- 0.2 ml/min, p < 0.005), decreased pulmonary vascular resistance (1.7 +/- 0.4 versus 6.6 +/- 1.9 x 10(3) Wood units, p < 0.05), and enhanced recipient survival (64% versus 0%, p < 0.05). Control grafts had significantly greater neutrophil accumulation (50% greater as quantified by myeloperoxidase activity, p < 0.05) than grafts preserved in the presence of nitroglycerin. These studies show that supplementation of the preservation solution with the nitric oxide donor nitroglycerin maintains graft vascular homeostasis and significantly improves pulmonary function and recipient survival after transplantation.

Animals↗
PubMed1995

The effects of self-hypnosis on quality of life following coronary artery bypass surgery: preliminary results of a prospective, randomized trial.

The effects of complementary techniques and alternative medicine on allopathic therapies is generating much interest and research. To properly evaluate these techniques, well controlled studies are needed to corroborate the findings espoused by individuals practicing complementary medicine therapies. To this end, we evaluated the role of one of these therapies, self-hypnosis relaxation techniques, in a prospective, randomized trial to study its effects on quality of life after coronary artery bypass surgery. Subjects were randomized to a control group or a study group. Study group patients were taught self-hypnosis relaxation techniques the night prior to surgery. The control group received no such treatment. Patients then underwent routine cardiac management and care. The main endpoint of our study was quality of life, assessed by the Profile of Moods Scale. Results demonstrated that patients undergoing self-hypnosis the night prior to coronary artery bypass surgery were significantly more relaxed than the control group (p = 0.0317). Trends toward improvement were also noted in depression, anger, and fatigue. This study demonstrates the beneficial effects of self-hypnosis relaxation techniques on coronary surgery. This study also identifies endpoints and a study design that can be used to assess complementary medicine therapies. Results of this preliminary investigation are encouraging and demonstrate a need for further well-controlled studies.

Affect↗
PubMed1995

Surgical management of cardiac pheochromocytoma. Resection versus transplantation.

OBJECTIVE: The authors review their experience and that of others who have reported cases in the literature on the surgical management of cardiac pheochromocytomas. SUMMARY BACKGROUND DATA: Cardiac pheochromocytomas are rare cathecolamine-producing tumors that can be densely adherent to myocardium. Because resection can be associated with significant morbidity, we sought to determine the best mode of treatment for these difficult tumors. METHOD: The authors reviewed the experience for management of cardiac pheochromocytomas in their two institutions and those reported in the literature. Follow-up was available for 21 of 26 patients up to 9 years after resection. RESULTS: Twenty-five patients had reconstruction of the native heart; five (20%) died intraoperatively from hemorrhage, one (4%) died postoperatively from sepsis, three (12%) sustained myocardial infarction, one (4%) required a mitral valve replacement, and three (12%) had incomplete resections, two of whom subsequently developed metastatic disease and died. One patient, thought to be a high risk for resection, received an orthotopic heart transplantation. CONCLUSIONS: Surgical resection of cardiac pheochromocytomas can be performed successfully. However, resection of lesions that aggressively invade adjacent myocardium is associated with significant mortality and inadequate control of the neoplasm. Cardiac transplantation should be available as an option before embarking on resection, and it should be performed if mandated by intraoperative findings.

Adult↗
PubMed1995

Preperitoneal placement of ventricular assist devices: an illustrated stepwise approach.

Improvement in left ventricular assist device (LVAD) implantation techniques may favorably impact on the significant perioperative morbidity and mortality that follows placement of these devices. Based on the difficulties faced and complications encountered during our 45 case experience, we developed a quick-reference illustrated guide which outlines in detail the steps and considerations critical for successful LVAD implantation.

Anastomosis, Surgical↗
PubMed1995

Enhanced preservation of orthotopically transplanted rat lungs by nitroglycerin but not hydralazine. Requirement for graft vascular homeostasis beyond harvest vasodilation.

Nitric oxide (NO) produced within the lungs maintains pulmonary vascular homeostatic properties, modulating leukocyte traffic, platelet aggregation, and vasomotor tone. Because reactive oxygen intermediates generated during reperfusion react rapidly with available NO, we hypothesized that the NO donor nitroglycerin (NTG) would enhance lung preservation for transplantation by improving graft blood flow and reducing graft neutrophil and platelet sequestration. By use of an orthotopic rat left lung transplant model, with ligation of the native right pulmonary artery to ensure that recipient survival and physiological measurements depend entirely on the transplanted lung, transplants were performed in 70 male Lewis rats after 6-hour 4 degrees C preservation in Euro-Collins solution (EC) alone or EC with supplemental NTG. Compared with EC alone, supplemental NTG significantly increased pulmonary arterial flow (2.2 +/- 1.4 to 21.4 +/- 2.9 mL/min, P < .01), decreased pulmonary vascular resistance (7.4 +/- 2.0 to 1.4 +/- 0.1 x 10(3) Woods units, P < .05), improved arterial oxygenation (163 +/- 57 to 501 +/- 31 mm Hg, P < .01), and enhanced recipient survival (17% to 100%, P < .001). These beneficial effects of NTG were dose dependent over a range of 0.001 to 0.1 mg/mL. Although NTG caused significant pulmonary vasodilation during the harvest/flushing period, the direct-acting vasodilator hydralazine caused greater vasodilation than did NTG but was associated with poor graft function, elevated pulmonary vascular resistance, and poor recipient survival. To explore nonvasodilator protective mechanisms of NTG, graft neutrophil and platelet sequestration were studied; supplemental NTG significantly reduced both neutrophil and platelet accumulation compared with either hydralazine or EC alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Forskolin stimulates swelling-induced chloride current, not cardiac cystic fibrosis transmembrane-conductance regulator current, in human cardiac myocytes.

Whole-cell patch clamp was used to look for cystic fibrosis transmembrane-conductance regulator (CFTR)-like chloride currents in calcium-tolerant human cardiac myocytes. Potassium-containing solutions were used initially. Steady state currents were measured with hyperpolarizing ramps (-16.25 mV/s). Peak net inward currents during voltage steps from -50 to +5 mV were used as an index of L-type calcium current. Isoproterenol (1 mumol/L) or forskolin (10 mumol/L) were used in attempts to evoke CFTR-like chloride current. No forskolin- or isoproterenol-induced steady state current was found in any of 17 atrial cells from seven patients in the absence of cell swelling. Every cell exhibited a large increase in net inward current in response to forskolin, suggesting that cAMP-dependent stimulation of L-type calcium current was present. Swelling with osmotic stress induced an outwardly rectifying steady state current with a reversal potential close to the chloride equilibrium potential. Once this current was activated, exposure to forskolin caused a further increase that subsided on washout (four of four cells, two patients). The atrial swelling-induced current was studied in more detail by using cesium-containing solutions. The current was determined to be a chloride current because the reversal potential was sensitive to changes in intracellular chloride and outward currents were blocked by 150 mumol/L DIDS. Ventricular cells were isolated from five failing human hearts. No CFTR-like current was found in any of 17 cells. In eight of eight ventricular cells, a swelling-induced current was found. The amplitude of the swelling-induced current was enhanced by forskolin.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1995

Perfusion technique for treatment of right heart failure.

A simple heparin-bonded circuit to facilitate a femoral vein to femoral artery shunt for the treatment of right-sided circulatory failure is proposed. Desaturated venous blood is shunted to the left-sided circulation to increase systemic blood pressure at the expense of saturation. The circuit comprised 1/4 inch x 3/32 inch tubing with a paediatric Bio-Medicus centrifugal pump head allowing adequate regulation of flow. Paediatric Bio-Medicus cannulae provide flows between 500 and 2000 ml/min. Measurements of pulmonary artery pressure, central venous pressure, arterial pressure, arterial saturation and cardiac output were recorded. In the four case studies presented, the treatment included unloading of the right ventricle with venous to arterial shunting. Likewise, eight Holstein calves underwent shunt utilization after placement of a left ventricular assist device and induction of right ventricular failure. The future use of this device may be instrumental in aiding the cardiothoracic surgical team in the treatment of right-sided circulatory failure.

Adult↗
PubMed1995

Laser-assisted fibrin clot soldering of human menisci.

Fibrin mixtures have been used as a solder in conjunction with argon ion lasers to create strong tissue welds in several organ systems. An analogous method of meniscus repair could obviate the need for partial meniscectomy and its subsequent degenerative effects in a subset of meniscal tears. This study measured the in vitro tensile strength in 4 groups of human menisci (1-mm x 2-mm x 5-mm sections): (1) bisected menisci repaired with fibrin clot mixture, (2) bisected menisci bonded by fibrin clot mixture and exposure to argon laser energy (energy density, 60 W/cm2), (3) bisected menisci repaired with 2 interrupted sutures, and (4) untreated meniscal controls. After irradiation with argon ion laser energy, the tensile strength of the laser-assisted fibrin clot-bonded menisci increased 40-fold over that of nonirradiated fibrin clot-bonded menisci. Suture controls (0.515 +/- 0.221 MPa) had a higher tensile strength than the fibrin clot mixture and irradiated groups; however, the suture controls had only 8.5% the strength of native menisci (6.081 +/- 0.221 MPa). Laser-assisted fibrin clot soldering may allow the opposing edges of a meniscal tear to be held together with a biologic scaffold, possibly inducing reparative cell migration and proliferation.

Combined Modality Therapy↗
PubMed1994

The nitric oxide/cyclic GMP pathway in organ transplantation: critical role in successful lung preservation.

Reestablishment of vascular homeostasis following ex vivo preservation is a critical determinant of successful organ transplantation. Because the nitric oxide (NO) pathway modulates pulmonary vascular tone and leukocyte/endothelial interactions, we hypothesized that reactive oxygen intermediates would lead to decreased NO (and hence cGMP) levels following pulmonary reperfusion, leading to increased pulmonary vascular resistance and leukostasis. Using an orthotopic rat model of lung transplantation, a porphyrinic microsensor was used to make direct in vivo measurements of pulmonary NO. NO levels measured at the surface of the transplanted lung plummeted immediately upon reperfusion, with levels moderately increased by topical application of superoxide dismutase. Because cGMP levels declined in preserved lungs after reperfusion, this led us to buttress the NO pathway by adding a membrane-permeant cGMP analog to the preservation solution. Compared with grafts stored in its absence, grafts stored with supplemental 8-Br-cGMP and evaluated 30 min after reperfusion demonstrated lower pulmonary vascular resistances with increased graft blood flow, improved arterial oxygenation, decreased neutrophil infiltration, and improved recipient survival. These beneficial effects were dose dependent, mimicked by the type V phosphodiesterase inhibitor 2-o-propoxyphenyl-8-azapurin-6-one, and inhibited by a cGMP-dependent protein kinase antagonist, the R isomer of 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate. Augmenting the NO pathway at the level of cGMP improves graft function and recipient survival following lung transplantation.

Amino Acid Oxidoreductases↗
PubMed1994

Exposure of the intramyocardial left anterior descending artery.

A systematic approach incorporating several discrete technical maneuvers is described that facilitates localization of the intramyocardial left anterior descending coronary artery. These simple maneuvers reliably afford localization of the initially hidden intramyocardial vessel and are easily incorporated into one's technical armamentarium.

Coronary Artery Bypass↗
PubMed1994

Preservation of anterior leaflet chordae tendineae during mitral valve replacement.

Preservation of anterior mitral leaflet papillary muscle attachments during mitral valve replacement was achieved in 20 patients by excising the central portion of the anterior leaflet and suturing the rim of leaflet tissue containing marginal chordae to the remaining edge of leaflet attached to the left atrium. This closure tacks the chordae to the fibrous trigones, opens the subvalvular area, and avoids a potentially thrombogenic or obstructive redundant leaflet ridge along the rim of an inserted valve. The technique is simple, safe, reproducible, and teachable.

Cardiac Surgical Procedures↗
PubMed1994

Potential of left ventricular assist devices as outpatient therapy while awaiting transplantation.

Left ventricular assist devices (LVADs) increasingly are being used as a bridge to transplantation. We studied changes in New York Heart Association class, mean arterial pressure, resting cardiac output, end-organ function, exercise oxygen consumption, and exercise cardiac output in 12 LVAD recipients. In addition, resting levels of neurohormonal factors were evaluated 4 to 16 weeks after implantation. Two of the 12 patients died of right heart failure and 1 of aspiration; all deaths occurred in the first 2 weeks after LVAD implantation. Of the other 9 patients, 8 improved to New York Heart Association class I and 1 to class II, all of whom were in class IV preoperatively. The 4 patients who underwent exercise testing achieved an exercise oxygen consumption of 15.0 +/- 2.7 mL.kg-1.min-1, which was paralleled by an increase in resting cardiac output from 3.07 +/- 0.9 L.min-1 preoperatively to 5.66 +/- 1.1 L.min-1 at 2 months, and mean arterial pressure from 60 +/- 8 to 91 +/- 10 mm Hg at 2 months, a benefit that was maintained for up to 10 months. End-organ function revealed comparable improvement at 2 months for both creatinine (1.68 +/- 0.7 to 1.0 +/- 0.19 mg.dL-1) and total bilirubin (1.37 +/- 1.17 to 0.54 +/- 0.26 mg.dL-1) levels. Levels of neurohormones were within normal limits. Adverse clinical events after the perioperative period were minimal, and no thromboembolic complications occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

1987: Adjustable annuloplasty for tricuspid insufficiency. Updated in 1994.

De Vega described a technique for tricuspid annuloplasty using synthetic suture to reduce the size of the dilated annulus. We present our experience with an adjustable modification of de Vega's suture annuloplasty technique. The records of 12 patients followed for 15 to 30 months were reviewed. All 10 survivors had a significant drop in right-sided filling pressure (average, 39% decrease) and an associated improvement in clinical status. The 2 deaths in the series were not related to persistent tricuspid insufficiency. This technique represents a reliable, rapid, and readily teachable method for the surgical management of tricuspid insufficiency.

Hemodynamics↗