Pulmonary cholesterol crystal embolization.

BACKGROUND: Cholesterol crystal embolization (CCE) has been documented to affect nearly every organ system. However, CCE involving the lung is distinctly uncommon and has been documented only in the setting of an aortocaval fistula. DESIGN: A case at the Massachusetts General Hospital and a MEDLINE search of English-language medical articles published between 1966 and 1997 provide the basis for this report. RESULTS: The precipitants of CCE include invasive vascular procedures, anticoagulant therapy, and thrombolysis. The most common symptoms include claudication of the calf, gastrointestinal bleeding, and weight loss. The most common signs include livedo reticularis, gangrene, and ulcers. Azotemia, proteinuria, normocytic anemia, and eosinophilia often are found. Herein is described the first pathologically confirmed case of CCE to the lung in the absence of an arteriovenous fistula. CONCLUSION: Pulmonary hemorrhage should now be included in the diverse list of presenting signs of CCE. Moreover, CCE should be considered in the differential diagnosis of pulmonary-renal syndromes.

Maximum cardiac output during incremental exercise by first-pass radionuclide ventriculography.

STUDY OBJECTIVE: To validate a noninvasive first-pass radionuclide ventriculographic (FPRV) measurement of maximum cardiac output (Qv) during exercise. DESIGN: Comparison of Qv to that measured by the Fick principle (Qf) at peak exercise. SETTING: Academic cardiopulmonary exercise laboratory. PATIENTS: Seventy-eight consecutive patients without a history of septal defect undergoing clinically indicated maximum incremental cardiopulmonary exercise testing with pulmonary arterial catheterization and FPRV. MEASUREMENTS AND RESULTS: Ventilation and gas exchange were measured breath-by-breath or by a mixing chamber/mass spectrometer system. Arterial and mixed venous O2 content were measured each minute during exercise. When patients without left-to-right ventricular stroke count ratio evidence for left-sided regurgitation were isolated, peak Qv was linearly related to Qf (r=0.75, p=0.0001). To account for a small systematic overestimation (bias) of Qf by Qv, the linear equation for the Qv/Qf relation was derived for patients studied between 1990 and 1993 and applied to those studied subsequently. The resulting corrected peak Qv was tightly related to peak Qf (r=0.90, p<0.001) with confidence intervals for slope and intercept overlapping identity. CONCLUSION: FPRV can reasonably estimate maximum cardiac output during incremental exercise in patients for whom the technique has ruled out left-sided cardiac regurgitant lesions.

Breathing reserve at the lactate threshold to differentiate a pulmonary mechanical from cardiovascular limit to exercise.

STUDY OBJECTIVES: Criteria used to define the respective roles of pulmonary mechanics and cardiovascular disease in limiting exercise performance are usually obtained at peak exercise, but are dependent on maximal patient effort. To differentiate heart from lung disease during a less effort-dependent domain of exercise, the predictive value of the breathing reserve index (BRI=minute ventilation [VE]/maximal voluntary ventilation [MVV]) at the lactate threshold (LT) was evaluated. DESIGN: Thirty-two patients with COPD and a pulmonary mechanical limit (PML) to exercise defined by classic criteria at maximum oxygen uptake (VO2max) were compared with 29 patients with a cardiovascular limit (CVL) and 12 normal control subjects. Expired gases and VE were measured breath by breath using a commercially available metabolic cart (Model 2001; MedGraphics Corp; St. Paul, Minn). Arterial blood gases, pH, and lactate were sampled each minute during exercise, and cardiac output (Q) was measured by first-pass radionuclide ventriculography (System 77; Baird Corp; Bedford, Mass) at rest and peak exercise. RESULTS: For all patients, the BRI at lactate threshold (BRILT) correlated with the BRI at VO2max (BRIMAX) (r=0.85, p<0.0001). The BRILT was higher for PML (0.73+/-0.03, mean+/-SEM) vs CVL (0.27+/-0.02, p<0.0001), and vs control subjects (0.24+/-0.03, p<0.0001). A BRILT > or = 0.42 predicted a PML at maximum exercise, with a sensitivity of 96.9%, a specificity of 95.1%, a positive predictive value of 93.9%, and a negative predictive value of 97.5%. CONCLUSIONS: The BRILT, a variable measured during the submaximal realm of exercise, can distinguish a PML from CVL.

Evaluation of right ventricular systolic pressure during incremental exercise by Doppler echocardiography in adults with atrial septal defect.

STUDY OBJECTIVES: Pulmonary hypertension is the most important complication in patients with atrial septal defect (ASD), but its role in limiting exercise has not been examined. This study sought to evaluate exercise performance in adults with ASD and determine the contribution of elevated pulmonary artery pressure in limiting exercise capacity. DESIGN: We used Doppler echocardiography during exercise in 10 adults (aged 34 to 70 years) with isolated ASD (New York Heart Association class I, II) and an equal number of matched control subjects. Incremental exercise was performed on an electrically braked upright cycle ergometer. Expired gases and VE were measured breath-by-breath. Two-dimensional and Doppler echocardiographic images were obtained at rest prior to exercise to determine ASD size, stroke volume (SV), shunt ratio (Qp:Qs), right ventricular outflow tract (RVOT) size, and right ventricular systolic pressure at rest (RVSPr). Doppler echocardiography was repeated at peak exercise to measure right ventricular systolic pressure during exercise (RVSPex). RESULTS: Resting echocardiography revealed that RVOT was larger (21+/-4 vs 35+/-8 mm, mean+/-SD; p=0.0009) and RVSPr tended to be higher (17+/-8 vs 31+/-8 mm Hg; p=0.08) in ASD; however, left ventricular SV was not different (64+/-23 vs 58+/-23 mL; p>0.05), compared with control subjects. Despite normal resting left ventricular function, ASD patients had a significant reduction in maximum oxygen uptake (VO2max) (22.9+/-5.4 vs 17.3+/-4.2 mL/kg/min; p=0.005). RVSPex was higher (19+/-8 vs 51+/-10 mm Hg; p=0.001) and the mean RVSP-VO2 slope (1+/-2 vs 18+/-3 mm Hg/L/min; p=0.003) and intercept (17+/-4 vs 27+/-4 mm Hg; p=0.05) were higher in the ASD group. VO2max correlated inversely with both RVSPr (r=-0.69; p=0.007) and RVSPex (r=-0.67; p=0.01). CONCLUSION: These findings suggest that adults with ASD have reduced exercise performance, which may be associated with an abnormal increase in pulmonary artery pressure during exercise.

Preoperative predictors of operative morbidity and mortality in COPD patients undergoing bilateral lung volume reduction surgery.

Bilateral volume reduction surgery (VRS) improves lung function for selected patients with emphysema. However, predictors of outcome are not well defined. We reviewed the preoperative characteristics of the first 47 consecutive patients who underwent bilateral VRS at the Massachusetts General Hospital in order to define potential predictors of unacceptable outcome. Preoperative data included spirometry, plethysmography, diffusion of carbon monoxide (Dco), maximum inspiratory pressure (MIP), maximum expiratory pressure, resting arterial blood gases (ABG), cardiopulmonary exercise testing with ABG and lactate sampling, and radionuclide ventriculography. Prepulmonary and postpulmonary rehabilitation 6-min walk tets (6MWT), and preoperative chest CT scans were also obtained. Twenty-two subjects were male and 17 of the subjects were on the lung transplant list. Patient characteristics included age of 60.5 +/- 7.5 years, FEV1 of 0.67 +/- 0.20 L, total lung capacity of 7.56 +/- 1.7 L, Dco of 7.40 +/- 4.1 mL/min/mm Hg, and PaCO2 of 41.6 +/- 6.4 mm Hg (mean +/- SD). The FEV1, vital capacity, MIP, resting room air PaCO2, prepulmonary and postpulmonary rehabilitation 6MWT, and PaCO2 at maximum oxygen consumption correlated with length of hospitalization (p < 0.05). Based on analysis of 41 of 47 patients for whom there were complete data, the inability to walk more than 200 m on the 6MWT before or after preoperative pulmonary rehabilitation, and resting PaCO2 > or = 45 mm Hg were the best predictors of an unacceptable outcome. If either of these characteristics was present, six of 16 vs zero of 25 died (Fisher's Exact Test, p = 0.0025, one-tailed) and 11 of 16 vs four of 25 had hospital courses > 21 days (p < 0.002). Both the 6MWT < 200 m and resting PaCO2 > or = 45 mm Hg alone correlated with death (p = 0.004 and p = 0.012, respectively) and the resting PaCO2 > or = 45 mm Hg correlated with hospital days > 21 (p = 0.0002). In conclusion, the data suggest that the inability to walk at least 200 m in 6 min before or after pulmonary rehabilitation and a resting room air PaCO2 > or = 45 mm Hg are excellent preoperative predictors of unacceptable postoperative outcomes.

Exercise performance in cystic fibrosis before and after bilateral lung transplantation.

BACKGROUND: Lung transplantation improves pulmonary function and quality of life for patients with end-stage cystic fibrosis; however, a systematic evaluation of exercise performance in lung transplant recipients with cystic fibrosis has not been reported. METHODS: Ten patients with end-stage cystic fibrosis performed incremental exercise testing before and after bilateral lung transplantation; their results were compared with those of 10 age-similar healthy volunteers. Breath-by-breath measurements of gas exchange and ventilation were obtained, arterial blood was sampled each minute, and cardiac output determined at rest and peak exercise by radionuclide ventriculography. The arterial-venous O2 content difference was derived by the Fick principle. RESULTS: After transplantation, peak O2 uptake improved (31% +/- 3% vs 45% +/- 4% predicted, P = .03) but was still reduced versus normal (100% +/- 8% predicted, p < .0001). Exercise was limited by pulmonary mechanics in all patients before transplantation but in only 2 after transplantation. Compared with control subjects, the lactate threshold occurred early, both before and after transplantation. Peak exercise cardiac output and arterial O2 content were not different from normal, either before or after transplantation. In contrast, the peak exercise arterial-venous O2 content difference was markedly reduced before and after transplantation versus normal (7.1 +/- 1.2 and 9.3 +/- 0.9 vs 17.1 +/- 1.2 mL/dL, p < or = .0001 for each) and without significant improvement. CONCLUSIONS: Exercise performance in patients with end-stage cystic fibrosis improves after lung transplantation but remains well below normal. Reduced systemic O2 extraction is an important factor limiting exercise in patients with cystic fibrosis after transplantation and may also contribute to the exercise limit before transplantation.

Skeletal muscle ECF pH error signal for exercise ventilatory control.

An autonomic reflex linking exercising skeletal muscle metabolism to central ventilatory control is thought to be mediated by neural afferents having free endings that terminate in the interstitial fluid of muscle. To determine whether changes in muscle extracellular fluid pH (pHe) can provide an error signal for exercise ventilatory control, pHe was measured during electrically induced contraction by 31P-magnetic resonance spectroscopy and the chemical shift of a phosphorylated, pH-sensitive marker that distributes to the extracellular fluid (phenylphosphonic acid). Seven lightly anesthetized rats underwent unilateral continuous 5-Hz sciatic nerve stimulation in an 8.45-T nuclear magnetic resonance magnet, which resulted in a mixed lactic acidosis and respiratory alkalosis, with no net change in arterial pH. Skeletal muscle intracellular pH fell from 7.30 +/- 0.03 units at rest to 6.72 +/- 0.05 units at 2.4 min of stimulation and then rose to 7.05 +/- 0.01 units (P < 0.05), despite ongoing stimulation and muscle contraction. Despite arterial hypocapnia, pHe showed an immediate drop from its resting baseline of 7.40 +/- 0.01 to 7.16 +/- 0.04 units (P < 0.05) and remained acidic throughout the stimulation protocol. During the on- and off-transients for 5-Hz stimulation, changes in the pH gradient between intracellular and extracellular compartments suggested time-dependent recruitment of sarcolemmal ion-transport mechanisms. pHe of exercising skeletal muscle meets temporal and qualitative criteria necessary for a ventilatory metaboreflex mediator in a setting where arterial pH does not.

Skeletal muscle chemoreflex and pHi in exercise ventilatory control.

To determine whether skeletal muscle hydrogen ion mediates ventilatory drive in humans during exercise, 12 healthy subjects performed three bouts of isotonic submaximal quadriceps exercise on each of 2 days in a 1.5-T magnet for 31P-magnetic resonance spectroscopy (31P-MRS). Bilateral lower extremity positive pressure cuffs were inflated to 45 Torr during exercise (BLPPex) or recovery (BLPPrec) in a randomized order to accentuate a muscle chemoreflex. Simultaneous measurements were made of breath-by-breath expired gases and minute ventilation, arterialized venous blood, and by 31P-MRS of the vastus medialis, acquired from the average of 12 radio-frequency pulses at a repetition time of 2.5 s. With BLPPex, end-exercise minute ventilation was higher (53.3 +/- 3.8 vs. 37.3 +/- 2.2 l/min; P < 0.0001), arterialized PCO2 lower (33 +/- 1 vs. 36 +/- 1 Torr; P = 0.0009), and quadriceps intracellular pH (pHi) more acid (6.44 +/- 0.07 vs. 6.62 +/- 0.07; P = 0.004), compared with BLPPrec. Blood lactate was modestly increased with BLPPex but without a change in arterialized pH. For each subject, pHi was linearly related to minute ventilation during exercise but not to arterialized pH. These data suggest that skeletal muscle hydrogen ion contributes to the exercise ventilatory response.

Disseminated Mycobacterium chelonae infection presenting as progressive multifocal osteomyelitis: Report of two cases and a review of the literature.

Two long term hospitalized patients developed disseminated infections caused by Mycobacterium chelonae, subspecies chelonae, over an eight-month period. In both cases, the disease was characterized by cutaneous and osseous involvement. The infections were indolent and marked by progressive bony destruction. These cases and a review of the literature are presented.

Ventilatory and cardiovascular responses to inspired He-O2 during exercise in chronic obstructive pulmonary disease.

Blunted maximum cardiac output and systemic O2 extraction could constitute primary limits to exercise in severe chronic obstructive pulmonary disease (COPD) or they could simply reflect cessation of exercise because of abnormal pulmonary mechanics. To determine which is the case, eight consecutive patients with severe COPD (FEV1 = 0. 56 +/- 0.04 L, mean +/- SEM), five of whom had alpha1-antiprotease deficiency, performed two incremental cycling tests while breathing N2-O2 or He-O2. Expired gases and V E were measured, and radial and pulmonary arterial blood was simultaneously sampled each minute. Peak exercise V E was higher with He-O2 than with N2-O2 (25.5 +/- 2. 2 versus 19.3 +/- 1.5 L/min, p = 0.002) and PaCO2 was lower (42 +/- 2 versus 46 +/- 2 mm Hg, p = 0.0003). V O2max improved only modestly (594 +/- 75 versus 514 +/- 54 ml/min, p = 0.04), and was accompanied by an increase in peak exercise CaO2 (18.7 +/- 0.9 versus 17.6 +/- 0. 9 ml/dl, p = 0.02). Peak Fick cardiac output was decreased (39 +/- 3% pred) and CvO2 was elevated (130 +/- 10% pred), and neither improved with He-O2 (p > 0.05 for each). Abnormal peak exercise cardiac output and systemic O2 extraction in severe COPD cannot be fully accounted for by limiting pulmonary mechanics and may contribute to exercise intolerance.

Systemic oxygen extraction during incremental exercise in patients with severe chronic obstructive pulmonary disease.

To determine if decreased systemic oxygen (O2) extraction contributes to the exercise limit in severe chronic obstructive pulmonary disease (COPD), 40 consecutive incremental cycle ergometer exercise tests performed by such patients, from which a "log-log" lactate threshold (LT) was identified, were compared to those of 8 patients with left ventricular failure (LVF) and 10 normal controls. Pulmonary gas exchange and minute ventilation were measured continuously and arterial blood gas tensions, pH, and lactate concentrations were sampled each minute. Cardiac output (Qc) was measured by first-pass radionuclide ventriculography. The systemic O2 extraction ratio (O2ER) was calculated as arterial - mixed venous O2 content difference (CaO2 - CvO2)/CaO2. Peak exercise O2 uptake (VO2peak) was markedly reduced in both COPD and LVF [41 (3) and 42 (3)% predicted, respectively], compared to controls [89 (2)% predicted, P < 0.0001 for each]. Similarly, the LT occurred at a low percentage of predicted maximal oxygen consumption in both COPD and LVF [25 (2) and 27 (3)%] compared to normals [46 (3)%, P < 0.0001 for each]. The systemic O2ER at peak exercise was severely reduced in COPD [0.36 (0.02)] compared to the other groups [P < 0.0001 for each], for whom it was nearly identical [0.58 (0.03) vs 0.63 (0.04), LVF vs control, P > 0.05]. In the COPD group, an early LT correlated with reduced systemic O2ER at peak exercise (r = 0.64, P < 0.0001), but not with any index of systemic O2 delivery. These data suggest that lactic acidemia during exercise in patients with severe COPD is better related to abnormal systemic O2 extraction than to its delivery and contributes to the exercise limit.