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Biomedical subjects

N M Katz

Publications and source records attributed to N M Katz.

At least 19 recordsLinked to original sources

Platelet activating factor antagonist enhances lung preservation.

Platelet activating factor (PAF) is a potent phospholipid mediator of the immune and inflammatory responses, which causes physiologic effects similar to post-transplant pulmonary dysfunction. This study investigates the hypothesis that the use of a specific PAF antagonist (PAFA), BN 52021, in canine lung transplantation improves lung preservation. Twelve pairs of canines underwent left lung allotransplantation after pulmonary artery flushing with modified Euro-Collins (EC) solution (40 ml/kg). The experimental group (N = 6) received EC with BN 52021 (10 mg/kg). BN 52021 was administered to donors prior to harvest and to recipients prior to reperfusion. The preservation interval was 20 hr and the study period was 12 hr post-transplant. Differential pulmonary function and hemodynamics were monitored, comparing the transplanted left lung and the native right lung. Recipients were ventilated on 100% O2. Administration of the platelet activating factor antagonist, BN 52021, was associated with improvement in transplant lung oxygenation, pulmonary vascular resistance, and compliance. At 12 hr, transplant lung pulmonary venous oxygen tension in the treatment group (EC + BN 52021) was 154 +/- 21 mm Hg versus 87 +/- 10 mm Hg in the control group (EC) (P less than 0.05). Pulmonary vascular resistance of the transplant lung at 12 hr was 146 +/- 24 Dynes.sec.cm-5 in the EC + BN 52021 group as compared to 320 +/- 51 Dynes.sec.cm-5 in the EC group (P less than 0.05). Dynamic pulmonary compliance of the transplant lung at 12 hr was 32 +/- 2.9 ml/cm H2O in the EC + BN 52021 group versus 13 +/- 2.0 ml/cm H2O in the EC group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Double aortic arch.

In conclusion, the diagnosis of DAA should be suspected in an infant with either biphasic stridor or feeding-related respiratory distress. Radiographic studies combined with appropriate thorough endoscopic evaluation should confirm clinical suspicion. Thoracotomy with surgical division of the DAA has given excellent long-term results.

Aorta, Thoracic

Platelet activating factor antagonist enhances lung preservation in a canine model of single lung allotransplantation.

Optimal techniques for lung preservation are yet to be defined. Platelet activating factor is a phospholipid released by a variety of cells and produces pulmonary abnormalities similar to posttransplantation pulmonary dysfunction. We investigated the strength of the effect of the platelet activating factor antagonist BN 52021 as compared with that of deferoxamine, an iron chelator previously shown to improve lung preservation. Differential lung function and pulmonary hemodynamics were used to assess preservation after a 6-hour period of cold ischemic storage in a modified canine model of left lung allotransplantation. Thirty size- and weight-matched mongrel male dogs were used for 15 transplant procedures randomized to one of three preservation techniques. The University of Wisconsin solution was used as the basic flush solution for all experimental animals. BN 52021 was added to the flush solution in one group (10 mg/kg, n = 5) and deferoxime in another group (10 mg/kg, n = 5). No additives were used for the control animals (n = 5). BN 52021 and deferoxime were administered to respective donor animals 30 minutes before organ harvesting (10 mg/kg) and to recipient animals 30 minutes before reperfusion (10 mg/kg). The pulmonary artery flush solution was administered (40 ml/kg) over 4 minutes. Recipient animals received double-lumen endotracheal tubes and were monitored with balloon-tipped, flow-directed catheters in both pulmonary arteries and dual-angle ultrasonic flow probes around each pulmonary artery. Solid-state high-fidelity micromanometers were used to measure pressures in the pulmonary artery, the left atrium, and the left ventricle. Systemic arterial, right and left pulmonary venous, and mixed venous blood samples were analyzed at 1, 2, 4, and 6 hours after transplantation. Pulmonary venous oxygen tension of the transplanted lung for the control group was 202 +/- 81 mm Hg versus 282 +/- 53 mm Hg for the BN 52021 group 6 hours after transplantation (p less than 0.05). Pulmonary vascular resistance of the transplanted lung for the control group was 319 +/- 54 dynes.sec.cm-5 versus 149 +/- 71 dynes.sec.cm-5 for the BN 52021 group (p less than 0.05). Proton magnetic resonance spectroscopy was performed on segments of upper and lower lobes of the native and transplanted lung from recipient animals to determine total lung water content. The BN 52021 group had a total lung water content of 57.3% as compared with 51.9% for the deferoxime group (p = not significant) and 88.6% for the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine

Long-term lung preservation with the PAF antagonist BN 52021.

Platelet activating factor (PAF, 1-alkyl-2(R)-acetyl-glycero-3- phosphorylcholine) is a phospholipid that is released by a variety of cells. The similarity between the pathophysiological effects of PAF and posttransplant pulmonary dysfunction led to an evaluation of a PAF antagonist as an adjunct to lung preservation. The ginkgolide B, BN 52021, was selected as the PAF antagonist to be studied because of the large data base available on this compound. BN 52021 was given to the donor and recipient (10 mg/kg i.v.) prior to harvest and transplantation and was included in 1 L of preservation solution (10 mg/kg) used for flushing the pulmonary artery and for storage. Left single-lung transplantation was performed following a 22-hr preservation period at 10 degrees C. Arterial oxygen tension (pO2), pulmonary vascular resistance (PVR), alveolar arterial oxygen difference (A-aDO2), and dynamic lung compliance (DLC) were recorded for 6 hours following ligation of the native pulmonary artery. At the end of 6 hr pO2 was 243.5 +/- 61.5 vs. 71.7 +/- 10.2 mmHg (P less than 0.02) for the controls. A-aDO2 was less in the BN 52021 groups: 431.8 +/- 58.3 vs. 606.0 +/- 9.8 mmHg in the control groups (P less than 0.001), and PVR was significantly less in the BN 52021 group: 346 +/- 70.8 vs. 663 +/- 64.3 dynes/sec/cm-5 (P less than 0.035). We conclude that PAF antagonists like BN 52021 may be useful adjuncts for lung preservation. The effects of BN 52021 are easily explained by PAF antagonist activity in ischemic and reperfusion-induced pulmonary dysfunction. However this study does not exclude that BN 52021 may have direct effects.

Animals

Iron chelation therapy and lung transplantation. Effects of deferoxamine on lung preservation in canine single lung transplantation.

Reperfusion injury is a limiting factor in lung transplantation. Deferoxamine is an iron chelator that inhibits the formation of oxygen-derived free radicals. We investigated the effects of deferoxamine on posttransplantation lung function in a canine model of single lung transplantation. Twelve dogs underwent left lung transplantation after 20- to 24-hour hypothermic storage in a modified Euro-Collins solution. In six experiments donor and recipient received a 10 mg/kg dose of deferoxamine before harvest and transplantation, and 10 mg/kg was added to the preservation solution. Arterial oxygen tension, alveolar-arterial oxygen difference, pulmonary vascular resistance, and dynamic lung compliance were measured. Data were recorded for 6 hours after ligation of the native pulmonary artery. At the end of the study the mean arterial oxygen tension was 175.1 mm Hg for the deferoxamine treated group versus 71.1 mm Hg for the control group (p less than 0.001), and the alveolar-arterial oxygen difference was less in the deferoxamine-treated group: 502.3 versus 606.0 mm Hg (p less than 0.001). The mean pulmonary vascular resistance was lower throughout the study, and after 6 hours it was 455.1 dynes/sec/cm(-5) in the deferoxamine-treated group versus 663.7 dynes/sec/cm(-5) in the control group (p less than 0.035). Compliance was similar in both groups. We conclude that deferoxamine improves lung preservation and early posttransplantation function in canine single lung transplantation.

Animals

Reduction of myocardial infarction after emergency coronary artery bypass grafting for failed coronary angioplasty with use of a normothermic reperfusion cardioplegia protocol.

Emergency coronary artery bypass grafting is necessary in 2.7% to 13.5% of patients undergoing elective percutaneous transluminal coronary angioplasty. Myocardial infarction develops in 11% to 49% of these patients, with 18% to 46% of infarcts resulting in new Q waves. Since February 1987 a revised protocol for myocardial preservation has been used in 19 patients undergoing emergency bypass grafting for failed angioplasty. Cardioplegia is induced with a normothermic blood cardioplegic solution. Multiple maintenance doses of cold (4 degrees C) blood cardioplegic solution are then delivered through the aortic root and vein grafts. Before the aortic crossclamp is removed, normothermic reperfusion cardioplegic solution is delivered through the aortic root and vein grafts. This group was compared with all patients undergoing emergency bypass grafting for failed angioplasty before February 1987. These 45 patients received cold induction of cardioplegic solution, multiple maintenance doses of cold cardioplegic solution, and no reperfusion cardioplegic solution. The prevalence of myocardial infarction in the group receiving cold cardioplegic solution was 65% versus 26% in the group receiving normothermic cardioplegic solution (p less than 0.007). Multivariate analysis identified the use of the normothermic cardioplegia protocol (p less than 0.005), nontotal occlusion of the angioplasty vessel (p less than 0.03), and presence of collateral flow to the angioplasty vessel (p less than 0.04) as being independently associated with absence of myocardial infarction.

Angioplasty, Balloon, Coronary

An approach to reoperative median sternotomy.

Cardiac reoperations using a previous median sternotomy incision are becoming more common as the population of patients who have had cardiac surgery increases. Repeat median sternotomy can be complicated by major hemorrhage and secondary myocardial ischemia. A standard approach to reoperative median sternotomy has been developed over the past several years at Georgetown University. Details of the method are presented. From January 1, 1980 through April 30, 1988, 179 patients underwent repeat median sternotomy. The technical approach to the operation became standard as of July 1,1983. Two of 66 patients operated before this date sustained major hemorrhage requiring emergent institution of cardiopulmonary bypass. One mortality in the group was directly related to hemorrhage at the sternotomy. No episode of major hemorrhage and no mortality related to the sternotomy occurred in 113 patients who underwent repeat sternotomy after July 1, 1983. Reoperation for bleeding occurred in 8.4% of the patients. We believe the technical considerations presented increase the safety of reoperative cardiac surgery.

Blood Loss, Surgical

Extracorporeal membrane oxygenation for neonatal respiratory failure. A report of 50 cases.

From February 1985 through June 1987, 50 newborn infants in whom maximal ventilator therapy failed (80% predicted mortality) were treated with extracorporeal membrane oxygenation (ECMO) according to the following inclusion criteria: arterial oxygen tension less than 50 torr (alveolar-arterial oxygen gradient greater than 630 torr) for 2 hours or arterial oxygen tension less than 60 torr (alveolar-arterial oxygen gradient greater than 620 torr) for 8 hours. Criteria for exclusion from ECMO therapy included birth weight less than 2000 gm, gestational age less than 35 weeks, presence of intracranial hemorrhage, presence of other major congenital anomalies including cyanotic heart disease, and high levels of ventilatory support for more than 7 days. Mean birth weight was 3.28 +/- 0.56 kg, mean gestational age was 39.6 +/- 1.7 weeks, and mean age at the start of ECMO was 48.6 +/- 36.9 hours. Meconium aspiration, usually associated with persistent pulmonary hypertension, was the most common cause of pulmonary failure (62%). Mean pre-ECMO arterial oxygen tension during maximal ventilatory and pharmacologic support was 34.5 +/- 14.5 torr. Mean ventilatory support immediately before the institution of ECMO was as follows: peak inspiratory pressure 46.8 +/- 9.9 cm H2O, positive end-expiratory pressure 4.6 +/- 1.6 cm H2O, and intermittent mandatory ventilation rate 101.0 +/- 22.7 breaths/min with all patients receiving an inspired oxygen fraction of 1.0. Lung management to prevent pulmonary atelectasis during ECMO consisted of moderate levels of positive end-expiratory pressure (mean 10.3 +/- 2.6 cm H2O, range 8 to 14 in 94% of patients. Other mean ventilator parameters during ECMO were as follows: peak inspiratory pressure 22.8 +/- 1.6 cm H2O, intermittent mandatory ventilation rate 11.8 +/- 2.9, and inspired oxygen fraction 0.21. The overall long-term patient survival rate was 90%. Mean values for arterial blood gases and ventilator settings immediately after the discontinuation of ECMO were as follows: oxygen tension 78.4 +/- 22.1 torr, pH 7.39 +/- 0.10, carbon dioxide tension 37.4 +/- 10.7 torr, peak inspiratory pressure 25.2 +/- 3.9 cm H2O, positive end-expiratory pressure 5.6 +/- 1.2 cm H2O, and intermittent mandatory ventilation rate 41.3 +/- 12.6 with an inspired oxygen fraction of 0.42 +/- 0.17. Despite slightly higher levels of ventilator support (peak inspiratory pressure 46.8 versus 45.0 cm H2O, not significant) mean pre-ECMO oxygen tension was significantly lower than that reported from the National ECMO Registry (34.5 versus 42.0 torr, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Extracorporeal Membrane Oxygenation

Effects of hypothermia and hemodilution on oxygen metabolism and hemodynamics in patients recovering from coronary artery bypass operations.

The coexistence of hypothermia and hemodilution in patients in the intensive care unit immediately postoperatively after coronary artery bypass graft operations presents concerns regarding the adequacy of hemodynamics and oxygen metabolism. We evaluated the hemodynamic status and oxygen metabolism during the postoperative recovery period in six patients with moderate hemodilution (hematocrit value 34% +/- 3%) and in eight patients with marked hemodilution (hematocrit value 23% +/- 2%). All patients were well sedated and paralyzed with pancuronium bromide during the study period, during which their body temperature was slowly returning toward normal. In both groups, cardiac index at 34 degrees C was about 40% lower than at 37 degrees C. This was associated with 50% higher systemic vascular resistance and 30% lower oxygen availability to tissue. Oxygen consumption, however, was proportionally lower (45%) and coronary perfusion pressure was higher (28%) at 34 degrees C than at 37 degrees C; thus neither mixed venous nor coronary sinus blood oxygen saturation was compromised under hypothermic conditions. Although the trends in hemodynamic changes were similar in both groups, cardiac indices in patients with marked hemodilution were higher than cardiac indices in those with moderate hemodilution at all temperatures. This observation indicates that the hemodilution-induced rise in cardiac index remains intact even under hypothermic conditions. Under the conditions we studied, hypothermia with or without hemodilution had no significant adverse effects on hemodynamics and oxygen metabolisms of the whole body or of the heart.

Aged

Venovenous extracorporeal membrane oxygenation for noncardiogenic pulmonary edema after coronary bypass surgery.

A 71-year-old woman with noncardiogenic acute pulmonary edema early after having a coronary operation was treated with venovenous extracorporeal membrane oxygenation for uncontrollable hypoxia. Adequate oxygenation was achieved, the rapid deterioration of her condition was reversed, and ventilatory settings could be moderated. Two and a half days later, the patient was weaned from the system. At the time of this writing, the patient was in her sixth postoperative month and doing well. Details of this fairly simple but powerful technique are described.

Aged

Predictors of length of hospitalization after cardiac surgery.

The cardiac surgical data base at Georgetown University Hospital was reviewed for patients operated on between January 1, 1980, and September 30, 1986, to determine predictors of length of postoperative hospitalization. Mortality among the 1,919 operations was 115 (6%). In the study group of 1,804 operations resulting in survival for at least 30 days, the following factors were analyzed: type of operation, age, sex, New York Heart Association (NYHA) Functional Class, urgency of operation, preoperative myocardial infarction (MI), weight, body surface area, hypertension, diabetes mellitus, previous cardiac operation, smoking history, and family history of cardiac disease. The overall mean length of hospitalization was 10.7 +/- 5.6 days. The analyses indicated that valve operation, age less than 30 and greater than 60 years, female sex, NYHA Class IV, urgent operation, preoperative MI 1 to 4 weeks before operation, and diabetes mellitus requiring medical treatment prolonged hospitalization, but generally by only 2 days. Major prolongation of hospitalization was associated with age in the 20- to 30-year and 80- to 90-year brackets. Unexpectedly, heavy body weight and smoking were not predictive.

Age Factors

Effects of CGS-13080, a thromboxane inhibitor, on pulmonary vascular resistance in patients after mitral valve replacement surgery.

Pulmonary hypertension with an elevated pulmonary vascular resistance was observed during the immediate recovery period in patients who underwent mitral valve surgery. In eight such patients, intravenous infusion of CGS-13080, imidazo(1,5-a)pyridine-5-hexanoic acid (a thromboxane synthetase inhibitor), at a dose range of 0.08-0.1 mg/kg/hr, effectively reduced pulmonary hypertension (from a mean pulmonary arterial pressure of 36 +/- 2 to 31 +/- 2 torr) and pulmonary vascular resistance (from 339 +/- 38 to 238 +/- 37 dynes.sec.cm-5) within 30 minutes and remained reduced for the entire infusion period (48 hours in five patients and 18 hours in three patients). Mean arterial pressure or systemic vascular resistance were not significantly affected by the drug infusion. Serum thromboxane B2 levels (a stable metabolic product of thromboxane A2) were significantly reduced after administration of the compound, with the maximum effect of greater than 90% reduction. All patients tolerated the drug infusion without significant side effects.

6-Ketoprostaglandin F1 alpha