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Biomedical subjects

D R Dantzker

Publications and source records attributed to D R Dantzker.

At least 37 records · Page 2Linked to original sources
PubMed1991

Oxygen delivery and utilization.

Under normal circumstances, O 2 transport (TO 2 = cardiac output x arterial O 2 content) is regulated to provide sufficient O 2 to meet the demands of oxidative phosphorylation, quantified as the O 2 consumption (VO 2). When metabolic demands increase, TO 2 is augmented and in addition, the fractional extraction of the delivered O 2 by the tissues, the O 2ER, also increases, to levels as high as 0.80 at maximum VO 2. If TO 2 is decreased, at least in the experimental animal, VO 2 can be maintained initially by an increase in O 2ER, but eventually this mechanism is exhausted, VO 2 begins to fall, and the body invokes anaerobic means of energy generation to maintain cell integrity. In normal man, this critical level of TO 2 (TO 2crit) has not been determined, but in experimental animals it has been found once the O 2ER exceeds 0.50. Patients with sepsis and the adult respiratory distress syndrome have a very high mortality and usually die as a result of multiple organ failure. They have in addition, an apparent abnormality in their ability to extract and utilize the delivered O 2. Despite a TO 2 which is often higher than normal, patients with sepsis commonly have a lactic acidosis and when TO 2 is reduced, both groups of patients are usually unable to increase their O 2ER above the normal resting value of 0.33.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Clinical role of bronchoalveolar lavage in adults with pulmonary disease.

BAL remains a powerful investigative tool. In a short span of 20 yr, it has helped tremendously in understanding some of the aspects of the pathogenesis of diseases involving the lower respiratory tract. To realize its full potential in the diagnosis and management of diseases involving the lower respiratory tract, there is a great need for standardization of the technical aspects of BAL as well as processing and analysis of the BAL cellular- and fluid-phase components. Despite these hurdles, BAL has been found to be diagnostic in several infectious and noninfectious diseases involving the lower respiratory tract, and it provides valuable information that may be helpful in characterizing the prognosis and response to therapy in certain interstitial diseases of the lung. It is expected that with future research, in particular long-term prospective epidemiologic and clinical studies in pneumoconioses and in other interstitial lung disease, BAL will prove more valuable in the diagnosis and management of such disease.

Bronchoalveolar Lavage Fluid↗
PubMed1990

Oxygen transport and utilization in ARDS.

The process of tissue O2 transport and utilization is complex and incompletely understood. It depends on the successful interaction of the respiratory and cardiovascular system in order to deliver O2 in sufficient amounts and at a high enough capillary partial pressure to allow for adequate diffusion into the cell. Normally, adequate amounts of O2 are available and the system can easily augment transport to meet increased metabolic demands. Under these circumstances O2 utilization is the independent variable. In adult respiratory distress syndrome (ARDS) it appears that O2 transport is not sufficient to provide for the aerobic production of all the required energy and O2 utilization becomes limited by O2 transport. The mechanism of this supply dependency is unknown, but has been shown to be associated with a poor clinical outcome.

Adenosine Triphosphate↗
PubMed1989

Vasodilators and primary pulmonary hypertension. Variability of long-term response.

Long-term response to vasodilator therapy was assessed in six patients with PPH. Following an acute trial, each patient was restudied after (1) two months of drug administration, (2) one month of abstinence from therapy, and (3) an additional two months of therapy. Three of six patients had no long-term reduction of PVR after treatment; one showed a progressive increase. Of the three patients whose PVR was still reduced at the end of the second therapy period none showed a return of PVR to baseline during the abstinence phase, which may suggest that long-term reduction of pulmonary vascular tone may modify the vasoconstrictive component of this disease. The heterogeneous response of this small number of patients to sequential drug administration and withdrawal demonstrates the difficulty of interpreting previously reported clinical trials and underscores the need for a well-designed controlled study of vasodilator administration in these patients.

Adult↗
PubMed1987

Does rib cage-abdominal paradox signify respiratory muscle fatigue?

Studies suggesting that abnormal motion of the rib cage (RC) and abdomen (Ab) may indicate respiratory muscle fatigue have not separated the influence of respiratory load from that of fatigue in its pathogenesis. We hypothesized that abnormalities on RC-Ab motion are primarily related to increased load rather than fatigue. We tested this hypothesis in subjects breathing against resistive loads while maintaining 30 and 60% of maximum mouth pressure (Pmmax). RC-Ab asynchrony and paradox and the degree of variation in compartmental contribution to tidal volume were measured by inductive plethysmography and quantitated by the Konno-Mead method of analysis. Comparing measurements of base line and 30 and 60% of Pmmax indicated that the degree of asynchrony, paradox, and variation in compartmental contribution were significantly related to the level of the load; significant abnormalities were observed at even 30% of Pmmax, a target pressure that can be sustained indefinitely. In another group of subjects, fatigue was induced by sustaining 60% of Pmmax to the limits of tolerance. Indexes of abnormal RC-Ab motion increased from base line during the 1st min of loaded breathing but displayed no progression from the beginning to the end of the fatigue run. Immediately on discontinuation of the load, the indexes returned to levels similar to base line despite persistence of the fatigue state. These results in healthy subjects breathing against severe resistances indicate that RC-Ab asynchrony and paradox and variation in compartmental contribution to tidal volume are predominantly due to increases in respiratory load rather than muscle fatigue.

Abdomen↗
PubMed1987

Konno-Mead analysis of ribcage-abdominal motion during successful and unsuccessful trials of weaning from mechanical ventilation.

Respiratory muscle fatigue is considered a common cause of weaning failure but its detection is hampered by the lack of a satisfactory diagnostic test. Abdominal paradox has been proposed as a valuable clinical index of fatigue and thus its presence may lead to curtailment of weaning trials. However, sensitivity and specificity of this sign as a predictor of weaning outcome is unknown. We hypothesize that abnormal ribcage-abdominal (RC-Ab) motion is a common finding in the early stages of weaning and its presence does not inevitably imply an unsuccessful weaning outcome. We tested this hypothesis in patients undergoing a weaning trial: one group had a successful weaning outcome and were extubated (n = 10) and the other group failed the trial (n = 7). Normal RC-Ab motion was separately characterized in 17 healthy subjects. Employing a calibrated respiratory inductive plethysmograph, quantitative assessment of asynchrony and paradox was obtained by computing several indices from series of breaths at fixed time periods using the Konno-Mead method of analysis. During the weaning trial, both groups of patients displayed significant increases in asynchrony and Ab paradox compared to normal values. As a group, patients who failed the trial displayed significantly greater asynchrony and paradox of the RC and Ab than patients with a successful outcome. However, there was considerable overlap between the individual patients in the 2 study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1987

Comparison of progressive exercise performance of normal subjects and patients with primary pulmonary hypertension.

The extent of exercise limitation and the mechanisms for that limitation in 11 patients with primary pulmonary hypertension (PPH) were studied by progressive, upright cycle ergometry. All patients had a mean pulmonary artery pressure of 30 mm Hg or higher (mean, 56 +/- 15), normal pulmonary function testing, normal pulmonary capillary wedge pressure, and pulmonary angiography consistent with the diagnosis. Rest and exercise data obtained from the patients with PPh were compared with data obtained from 11 matched, sedentary control subjects. Mean maximal oxygen consumption (VO2) was 13 +/- 4 ml/kg/min in the PPH group compared with 28 +/- 7 ml/kg/min in the controls. At maximal VO2 the minute ventilation (VE) was similar; however, the VE at any level of carbon dioxide production (VCO2) during rest and exercise was significantly higher in the PPH group. Maximal heart rate and oxygen pulse (VO2/heart rate) was significantly higher in the control group (148 +/- 18 vs 180 +/- 24, and 6.3 +/- 2.2 vs 9.9 +/- 3.9, respectively). Anaerobic threshold occurred earlier during progressive exercise in the PPH group and correlated positively with the maximal oxygen pulse achieved in patients with PPH. In conclusion, patients with PPH have severe exertional limitation due to cardiovascular factors with an inability to maintain appropriate oxygen delivery to the body during exercise. No respiratory impairment was recognized; however, an exaggerated ventilatory response to exercise at any level of VCO2 was found.

Adult↗
PubMed1987

Primary pulmonary hypertension. A national prospective study.

A national registry was begun in 1981 to collect data from 32 centers on patients diagnosed by uniform criteria as having primary pulmonary hypertension. Entered into the registry were 187 patients with a mean age (+/- SD) of 36 +/- 15 years (range, 1 to 81), and a female-to-male ratio of 1.7:1 overall. The mean interval from onset of symptoms to diagnosis was 2 years. The most frequent presenting symptoms included dyspnea (60%), fatigue (19%), and syncope (or near syncope) (13%). Raynaud phenomenon was present in 10% (95% of whom were female) and a positive antinuclear antibody test, in 29% (69% female). Pulmonary function studies showed mild restriction (forced vital capacity [FVC], 82% of predicted) with a reduced diffusing capacity for carbon monoxide (DLCO), and hypoxemia with hypocapnia. The mean (+/- SD) right atrial pressure was 9.7 +/- 6 mm Hg; mean pulmonary artery pressure, 60 +/- 18 mm Hg; cardiac index, 2.3 +/- 0.9 L/min X m2; and pulmonary vascular resistance index, 26 +/- 14 mm Hg/L/min X m2 for the group. Although no deaths or sustained morbid events occurred during the diagnostic evaluation of the patients, the typically long interval from initial symptoms to diagnosis emphasizes the need to develop strategies to make the diagnosis earlier.

Adolescent↗
PubMed1986

Oxygen delivery and utilization in hypothermic dogs.

Hypothermia produces a decrease in metabolic rate that may be beneficial under conditions of reduced O2 delivery (Do2). Another effect of hypothermia is to increase the affinity of hemoglobin for O2, which can adversely affect the release of O2 to the tissues. To determine the overall effect of hypothermia on the ability of the peripheral tissues to extract O2 from blood, we compared the response to hypoxemia of hypothermic dogs (n = 8) and of normothermic controls (n = 8). The animals were anesthetized, mechanically ventilated, and paralyzed to prevent shivering. The inspired concentration of O2 was progressively reduced until the dogs died. The core temperatures of the control and hypothermic dogs were 37.7 +/- 0.3 and 30.5 +/- 0.1 degree C, respectively (P less than 0.01). The O2 consumption (VO2) of the control dogs was significantly greater than that of the hypothermic dogs (P less than 0.05), being 4.7 +/- 0.4 and 3.2 +/- 0.3 ml X min-1 X kg-1, respectively. Hypothermia produced a left shift of the oxyhemoglobin dissociation curve (ODC) to a PO2 at which hemoglobin is half-saturated with O2 of 19.8 +/- 0.7 Torr (control = 32.4 +/- 0.7 Torr, P less than 0.01). The O2 delivery at which the VO2 becomes supply dependent (DO2crit) was 8.5 ml X min-1 X kg-1 for control and 6.2 ml X min-1 X kg-1 for hypothermia. The hypothermic dogs maintained their base-line VO2's at lower arterial PO2's than control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Breathing pattern and metabolic behavior during anticipation of exercise.

The mechanisms responsible for the marked increase in ventilation at the onset of exercise are incompletely defined. A conditioned response to exercise anticipation has been suggested as an influencing factor, but systematic measurements have not been made during the transition from rest to the time when exercise is anticipated but has not yet commenced. We tested the hypothesis that cortical activity associated with the anticipation of exercise causes hyperpnea, which is at least partly responsible for the increased ventilation at the onset of exercise. To assess the influence of continuous cortical activity in the absence of exercise anticipation the subjects performed mental arithmetic tasks. Fifteen subjects performed the two experiments in a random order. Ventilation was measured noninvasively using a calibrated respiratory inductive plethysmograph and end-tidal CO2 concentration (FETCO2) was monitored at the nasal vestibule. Both exercise anticipation and mental arithmetic caused an increase in minute ventilation (VI) (P less than 0.01) and mean inspiratory flow (VT/TI, P less than 0.01), which reflects respiratory center drive, although the derivation differed in that the former was volume based, whereas the latter was due to alteration in timing. Despite the increase in VI, FETCO2 remained constant in both instances. In a complementary study the constant FETCO2 in the face of increased VI was shown to be due to increased CO2 output. The results show that the mere anticipation of exercise causes an increase in ventilation. The mechanism responsible for this hyperpnea cannot be due solely to respiratory center activation because of the constancy of FETCO2 and the associated alterations in cardiac and metabolic behavior.

Adult↗
PubMed1986

Noninvasive assessment of hemodynamic improvement during chronic vasodilator therapy in obliterative pulmonary hypertension.

The ability to treat selected patients with obliterative pulmonary hypertension (OPH) with vasodilator therapy has been clearly demonstrated. However, the dangers involved in their use in patients who fail to have a beneficial response have also been well documented. A major problem in the management of these patients has been the lack of an easily measurable, noninvasive index of alterations in cardiopulmonary status that could be used at relatively frequent intervals to monitor the response to therapy. We have studied the utility of changes in noninvasively assessed exercise performance to predict changes in pulmonary vascular tone. In 10 patients with OPH, we compared symptom-limited oxygen consumption (Vo2ex) and oxygen pulse (Vo2/heart rate) at Vo2ex (O2 Pex) determined during progressive treadmill exercise with invasive measurements of cardiovascular function during steady-state supine bicycle submaximal exercise prior to and 8 wk after initiation of vasodilator therapy with nifedipine or diltiazem. After vasodilator therapy, total pulmonary vascular resistance decreased at rest and during exercise in 6 patients. At the same time, changes in Vo2ex ranged from -33 to 47% and in O2Pex from -26 to 57%. There was an excellent relationship between the magnitude of the change in exercise and resting total pulmonary vascular resistance and the change in both Vo2ex and O2Pex. We suggest that changes in Vo2ex and O2Pex may be a useful means of following the ability of vasodilators to improve cardiovascular function in patients with OPH.

Adult↗
PubMed1986

The pattern of breathing during successful and unsuccessful trials of weaning from mechanical ventilation.

We prospectively examined the pattern of breathing in patients being weaned from mechanical ventilation: one group (n = 10) underwent a successful weaning trial and were extubated, whereas another group (n = 7) developed respiratory failure and required the reinstitution of mechanical ventilation. During the period of ventilator support, minute ventilation (VI), tidal volume (VT), and respiratory frequency (f) were similar in the 2 groups. After discontinuation of the ventilator, VI remained similar in the 2 groups, but VT was lower and f was higher in the patients who failed the trial compared with those who were successful, 194 +/- 23 and 398 +/- 56 ml (p less than 0.001), respectively, and 32.3 +/- 2.3 and 20.9 +/- 2.8 breaths/min (p less than 0.001), respectively. The failure group displayed a significant increase in PaCO2 (p less than 0.005) during spontaneous breathing, without a concomitant increase in the alveolar-arterial PO2 difference. Eighty-one percent of the variance in PaCO2 was accounted for by the pattern of rapid, shallow breathing. During weaning, resting respiratory drive (reflected by mean inspiratory flow, VT/TI) and fractional inspiratory time (TI/Ttot) were similar in the 2 groups. The patients in the failure group showed significant increases in VT/TI, 265 +/- 27 to 328 +/- 32 ml/s (p less than 0.01), and VI, 5.82 +/- 0.53 to 7.32 +/- 0.52 L/min (p less than 0.01), from the beginning to the end of the weaning trial; VT and f showed no further change.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Respiratory↗
PubMed1986

The effect of exercise on pulmonary gas exchange in patients with severe chronic obstructive pulmonary disease.

The effect of low level, steady-state exercise on pulmonary gas exchange was studied in 7 patients with severe chronic obstructive pulmonary disease and pulmonary hypertension. Exercise led to a significant fall in the arterial PO2 from 76 +/- 10 to 63 +/- 8 mm Hg, a rise in the arterial PCO2 from 56 +/- 6 to 62 +/- 8 mm Hg, and a fall in the mixed venous PO2 from 38 +/- 2 to 32 +/- 2 mm Hg. There was, however, no significant change in the degree of ventilation-perfusion inequality as quantified by the multiple inert gas technique and no evidence that impaired O2 diffusion was playing a role in the increased hypoxemia. We conclude that the worsening hypoxemia with exercise in patients with severe COPD is due to an inadequate ventilatory response (leading to a rise in arterial PCO2) and the impact of a decreased mixed venous PO2 on the end-capillary PO2 of low VA/Q lung units and shunt.

Carbon Dioxide↗
PubMed1986

Gas exchange in acute lung injury.

The predominant mechanism of abnormal gas exchange in patients with the adult respiratory distress syndrome is intrapulmonary shunting. However, other abnormalities of cardiopulmonary function may modify the degree of hypoxemia that is seen, and must be considered when interpreting the effect of therapy.

Airway Resistance↗