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Biomedical subjects

M J Krowka

Publications and source records attributed to M J Krowka.

At least 55 records · Page 3Linked to original sources
PubMed1992

Endothelium-derived relaxing factor in pulmonary and renal circulations during hypoxia.

The pulmonary and renal vasculatures, in contrast to the systemic vasculature, constrict during hypoxia. The endothelium has been implicated in mediating these vascular responses to acute hypoxia via the production of endothelium-derived vasoactive factors. The present study, performed in anesthetized dogs, was designed to investigate the role of endothelium-derived relaxing factor (EDRF) to attenuate the vasoconstrictor response of the pulmonary and renal circulations during acute hypoxia. In response to hypoxia, pulmonary (2.2 +/- 0.3 to 4.5 +/- 0.6 mmHg.l-1.min) and renal (0.60 +/- 0.07 to 0.90 +/- 0.14 mmHg.ml-1.min) vascular resistances increased. Inhibition of endogenous EDRF with NG-monomethyl-L-arginine resulted in similar increases in pulmonary (3.0 +/- 0.1 to 4.8 +/- 0.4 mmHg.l-1.min) and renal (0.67 +/- 0.07 to 0.90 +/- 0.09 mmHg.ml-1.min) vascular resistances as in hypoxia. However, in the presence of both hypoxia and EDRF inhibition, an exaggerated pulmonary vascular response was observed (2.2 +/- 0.2 to 7.4 +/- 0.9 mmHg.l-1.min), in contrast to the renal vascular response to EDRF inhibition during hypoxia (0.61 +/- 0.05 to 0.95 +/- 0.10 mmHg.ml-1.min), which was not different from hypoxia or EDRF inhibition individually. The endothelium-derived contracting factor endothelin, which modestly increased during hypoxia (11.7 +/- 1.9 to 15.6 +/- 2.4 pg/ml), may also contribute to this vasoconstrictive response to hypoxia. This study suggests in the intact animal that EDRF serves to oppose the pulmonary vasoconstrictor response to hypoxia and further characterizes the role of endothelium-derived factors in the regulation of vascular function during hypoxia.

Animals↗
PubMed1992

A prospective study of pulmonary function and gas exchange following liver transplantation.

Pulmonary function and gas exchange were prospectively studied in 95 patients before and 9 to 15 months following liver transplantation. Pretransplant, the most common PF abnormality was impaired efficiency of gas exchange as measured by Dss. As a group, the mean Dss was 78.0 +/- 16.6 percent predicted and was found to be less than 80 percent predicted in 50 patients. As a group, patients with the most severe liver diseases clinically (Child's C classification) had the lowest mean Dss pretransplant. Posttransplant, three findings were of clinical importance: PaCO2 significantly improved posttransplantation, suggesting a resolution of pretransplant respiratory alkalosis. Expiratory airflow obstruction, measured by a change in the FEV1/FVC, was extremely uncommon posttransplant. Mean Dss improved significantly in patients with Child's C severity of liver disease. The most frequent deteriorations in Dss statistically were associated with posttransplant thoracotomy, ARDS, nonspecific pneumonitis, significant pleural effusions and hepatic retransplantation.

Female↗
PubMed1991

Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked.

We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjögren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1990

A prospective study of airway reactivity before bone marrow transplantation.

The purposes of this study were to assess baseline airway function and to determine the frequency of airway reactivity in patients before bone marrow transplantation (BMT). The ratio of the forced expiratory volume at 1 second to the forced vital capacity (FEV1/FVC) was the measure of baseline airflow. Using methacholine challenge, we tested 53 patients before conditioning chemotherapy, total-body irradiation, and BMT. All patients had a baseline FEV1/FVC of 70% or more. The mean baseline FEV1/FVC was 84(+)/- 6%. The response to methacholine challenge was defined by the change in FEV1 from baseline (delta FEV1). A positive response (delta FEV1 of 20% or more) occurred in 11 of 53 patients (21%), a borderline response of (delta FV1 of less than 20% but greater than or equal to 10%) was was found in 10 (19%), and no response (Delta FEV1 of less than 10%) was elicited in 32 (60%). In our group of patients with a positive or borderline response to methacholine, we found no significant relationship to baseline FEV1/FVC, smoking history, hematologic diagnosis or study, or major post-BMT pulmonary complications including bronchiolitis obliterans. We concluded that pretransplantation airway reactivity, as measured by methacholine challenge and in the setting of normal baseline FEV1/FVC, was common before BMT. The presence of a borderline or positive response to methacholine challenge before transplantation was not associated with the development of either clinical or pathologically proven posttransplantation bronchiolitis obliterans.

Adolescent↗
PubMed1990

Intrapulmonary vascular dilatations (IPVD) in liver transplant candidates. Screening by two-dimensional contrast-enhanced echocardiography.

Intrapulmonary vascular dilatations (IPVD) are extrahepatic complications of acute and chronic liver disorders that can result in severe hypoxemia. Contrast-enhanced (CE) echocardiography provides a noninvasive method to detect right-to-left shunting associated with IPVD. We prospectively studied 40 consecutive liver transplant candidates to determine the relationship between CE echocardiography, arterial blood gases, and standard pulmonary function tests. Two patients had technically unacceptable results of echocardiographic studies. Thirty-eight patients had acceptable results of studies; seven (18.4 percent) of 38 were hypoxemic (PaO2 less than 70 mm Hg). Thirty-one patients (81.6 percent) had PaO2 greater than or equal to 70 mm Hg. Positive CE echocardiograms suggesting IPVD were found in five (13.2 percent) of 38. Three (9.7 percent) of the 31 patients with PaO2 greater than or equal to 70 mm Hg had positive CE echocardiograms. Two (28.6 percent) of the seven hypoxemic patients had positive CE echocardiography. Mean PaO2 and pulmonary function parameters were not significantly different between those with positive CE echocardiogram compared with those with normal CE echocardiograms. We conclude that for our group of liver transplant candidates, (1) IPVD as suggested by CE echocardiography were not uncommon (13.2 percent), and (2) positive CE echocardiography could be documented in patients who were not hypoxemic (9.7 percent).

Adult↗
PubMed1989

Severe hypoxemia and liver disease.

Severe hypoxemia and orthodeoxia in patients with chronic liver disease is uncommon, but, when present, it is incapacitating. The purpose of this study was to determine the distribution of alveolar ventilation-perfusion (VA/Q) in six patients with mild liver disease and severe hypoxemia (PaO2 at rest in sitting or standing position ranged from 35 to 67 mm Hg). Orthodeoxia was documented with improvement in PaO2 in the supine position in each patient (PaO2 at rest in supine position ranged from 46 to 75 mm Hg). VA/Q distribution was measured by the multiple inert gas elimination technique. The dispersion of VA/Q was increased with small portions of the cardiac output (0.5 to 14.8%) perfusing low VA/Q areas (O less than VA/Q less than 0.1). Another major finding was a large right-to-left shunt (VA/Q less than 0.005) that ranged from 4 to 28%. The VA/Q mismatching and the right-to-left shunt both contributed to the hypoxemia. The predicted PaO2 was 5.5 mm Hg (p less than 0.01) larger than the measured PaO2. In each patient, the mean pulmonary artery pressure was low and the cardiac output was elevated. These results show that the low PaO2 in these patients was due to both increased right-to-left shunt and VA/Q mismatching, but impaired diffusion could not be ruled out.

Adult↗
PubMed1989

Pulmonary aspects of liver disease and liver transplantation.

This article has summarized the liver-lung relationships from a clinical perspective. The physiology, biochemistry, and molecular biology that link the two organs are of great importance in that many disorders described affect young patients. Indeed, pulmonary abnormalities in patients with hepatic disorders are frequent, and both the pulmonary and hepatic problems may be reversible in the current era of organ transplantation.

Humans↗
PubMed1987

Severe hypoxemia associated with liver disease: Mayo Clinic experience and the experimental use of almitrine bismesylate.

Severe hypoxemia associated with chronic liver disease is an uncommon disorder most likely due to an intrapulmonary vascular abnormality that has characteristics of both ventilation-perfusion mismatching and diffusion limitation. Anatomically, the intrapulmonary vascular abnormalities can occasionally be detected by angiography. Physiologically, the gas exchange abnormalities can be substantiated by contrast-enhanced two-dimensional echocardiography. Although orthodeoxia and platypnea have frequently been found in these patients, echocardiographic data suggest that vascular abnormalities can exist in the absence of orthodeoxia. We describe 11 patients who had severe hypoxemia and chronic liver disease and review their pulmonary angiographic, contrast echocardiographic, and arterial blood gas findings. Among five of these patients who were given almitrine bismesylate, an experimental medication thought to alter ventilation-perfusion relationships in patients with chronic obstructive pulmonary disease, one had improved oxygenation. We recommend that patients with hypoxemia associated with chronic liver disease have detailed studies to rule out reversible forms of hypoxemia and that those with severe hypoxemia undergo testing to determine the existence of intrapulmonary vascular abnormalities, especially if liver transplantation is considered.

Adult↗
PubMed1987

Effect of effort on measurement of forced expiratory volume in one second.

The American Thoracic Society recommends that the largest FEV1 be reported from a set of forced expiratory vital capacity maneuvers performed with maximal expiratory effort. However, increased expiratory effort can decrease the FEV1. When we evaluated the peak expiratory flow rate (PEFR) in 5 normal subjects, measured from flow-volume curves, as a noninvasive index of expiratory effort, it was positively correlated with indices of effort obtained by using an esophageal balloon. We then measured the difference (dFEV1)between the largest FEV1 and FEV1 from the maneuver with the highest PEFR during 10 test sessions in 10 normal subjects. Thus, dFEV1 was always greater than or equal to 0. The mean dFEV1 was 110 ml for all sessions but decreased to 80 ml when maneuvers with poorly reproducible PEFR or forced expiratory vital capacity values were discarded. We also reviewed 9.471 spirometry sessions from outpatients and found dFEV1 to be greater than 50 ml in 26% of this population and greater than 151 ml in 7%. We concluded that during standard spirometry, FEV1 is inversely dependent on effort. Maximal effort decreases FEV1 because of the effect of thoracic gas compression on lung volume. We recommend that values from spirometry maneuvers that demonstrate submaximal effort, indicated by a decreased PEFR, be discarded. The flow-volume curve display of superimposed efforts facilitates the recognition of submaximal efforts.

Biophysical Phenomena↗
PubMed1987

Cardiac dysrhythmia following pneumonectomy. Clinical correlates and prognostic significance.

Cardiac tachydysrhythmias occurred in 53 (22 percent) of 236 consecutive patients undergoing pneumonectomy. All patients had preoperative electrocardiograms which showed normal sinus rhythm. Patients did not receive digitalis before surgery. Atrial fibrillation was the most common dysrhythmia (64 percent; 34/53), followed by supraventricular tachycardia (23 percent; 12/53) and atrial flutter (13 percent; 7/53). No episodes of ventricular tachycardia were documented. Elevated concentrations of cardiac enzymes were associated with 12 (28 percent) of 43 tachydysrhythmias. Recurrent or persistent dysrhythmias were documented in 29 (55 percent) of 53 patients despite medical management or electrocardioversion (or both). Thirty-one percent (9/29) of these patients subsequently died during their hospitalization. There was no correlation between standard preoperative pulmonary function tests and the incidence of postoperative dysrhythmia. In addition, there was no correlation of dysrhythmia with postoperative diagnoses, surgical staging for lung cancer, postoperative arterial blood gas levels, or the fact that a completion pneumonectomy or chest wall resection was undertaken. An increased incidence of tachydysrhythmia was noted in patients undergoing intrapericardial dissections and those who developed postoperative interstitial or perihilar pulmonary edema. Twenty-five percent (13) of the patients experiencing tachydysrhythmias died within 30 days following their pneumonectomy. We conclude that tachydysrhythmias after pneumonectomy are associated with significant mortality, have poor correlation to preoperative pulmonary function, and occur more frequently following intrapericardial dissection and in patients who develop postoperative interstitial pulmonary edema or perihilar pulmonary edema.

Arrhythmias, Cardiac↗
PubMed1985

Pulmonary aspects of chronic liver disease and liver transplantation.

A vast spectrum of pulmonary pathologic conditions occurs in association with chronic liver diseases, and clinically important manifestations, such as arterial hypoxemia, can result. Both pulmonary vascular and parenchymal abnormalities can contribute to the dysfunction, as evidenced by results of pulmonary function tests and gas exchange studies. The clinical implications of identifying such pulmonary problems range from alleviation of symptoms, especially dyspnea, to comprehensive assessment of patients before and after liver transplantation. Physicians should be aware of these potential pulmonary disorders that can complicate liver disease and liver transplantation so that management of affected patients can be improved.

Chronic Disease↗
PubMed1985

Pulmonary complications of bone marrow transplantation.

Bone marrow transplantation (BMT) for hematologic disorders is potentially curative in selected persons. These patients may be immunocompromised for months after engraftment as a consequence of chemotherapy, irradiation, acute and chronic graft-vs-host disease (GVHD), and maturing recipient marrow. Pulmonary complications commonly occur during the early and late periods after BMT and are associated with significant morbidity and mortality. The leading early-onset complication is interstitial pneumonitis, most commonly associated with cytomegalovirus infection but also related to possible toxicities from chemotherapy and irradiation. Major late-onset problems include bacterial sinopulmonary infections and obstructive airway disease thought to be associated with chronic GVHD. The exact mechanisms of lung injury are probably quite complex, and unfortunately, often cause irreversible pulmonary disease, even in the patient who has had successful transplantation. Antimicrobial prophylaxis, modified chemotherapy and irradiation dosages, and antiviral immunization have been shown to reduce the incidence of early-onset pulmonary problems. Early recognition and treatment of late-onset problems will, it is hoped, minimize respiratory limitations.

Anti-Bacterial Agents↗
PubMed1983

Azathioprine-associated pulmonary dysfunction.

We present a case of azathioprine-associated alveolitis diagnosed by gallium-67 scanning and transbronchial biopsy. The patient denied respiratory symptoms, exhibited spiking fevers, and had normal chest roentgenograms. Allopurinol inhibition of azathioprine metabolism may have been a contributing factor.

Adult↗