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Biomedical subjects

J L Robotham

Publications and source records attributed to J L Robotham.

At least 73 records · Page 4Linked to original sources

Mitral and aortic blood flows during spontaneous respiration in dogs.

Left sided hemodynamic events during respiration remain a controversial subject. Left ventricular (LV) hemodynamic events were evaluated during obstructed and partially obstructed inspiration in anesthetized dogs acutely instrumented with mitral (Qm) and ascending aortic (Qa) flow probes. This allows classification of the inspiratory decrease in LV stroke volume as either a diastolic event (e.g., ventricular interdependence) in which case the LV inflow volume (integral of Qm) should decrease before the LV outflow volume (integral of Qa), or a systolic event (e.g., afterload or contractility) in which case outflow (integral of QA) should decrease before inflow (integral of Qm). During either unobstructed (n =8) or partially obstructed (n = 5 spontaneous ventilation, Qm reached both its inspiratory minimum and expiratory maximum prior to the associated minimum and maximum values for integral of in 80% or more of the respiratory cycles. Thus, a diastolic event dominates both in reducing the subsequent LV outflow during the expiratory increase in intrathoracic pressure. However, because a diastolic event did not occur first at all times, a systolic event must occur first at all times, a systolic event must also be present. If a rapid change in intrathoracic pressure occurred during diastole, integral of Qm invariably immediately increased. If a rapid in intrathoracic pressure occurred during systole, integral of Qa could change independently of the preceding integral of Qm. Both systolic and diastolic mechanisms contribute to the inspiratory fall in LV output. These mechanisms will not be clearly delineated without evaluating the effects of intrathoracic pressure within a single cardiac cycle.

Airway Obstruction↗

Transient analysis of cardiopulmonary interactions. I. Diastolic events.

The etiology of the fall in left ventricular stroke volume (LVSV) with negative intrathoracic pressure (NITP) during inspiration has been ascribed to a reduction in LV preload. This study evaluated the effects of NITP with and without airway obstruction confined to early (ED), mid- (MD), or late diastole (LD) on the subsequent LVSV, anteroposterior (AP), and right-to-left (RL) aortic diameters (DAO) (series I, n = 6) as well as on phasic arterial blood flow out of the thorax (series II, n = 6) in anesthetized dogs. Transient NITP was obtained by electrocardiogram-triggered phrenic nerve stimulation. In series I, NITP applied for 60% of diastole with the airway obstructed caused decreases of LVSV during ED [-7.7 +/- 3.2% (SE) NS], MD (-11.7 +/- 3.9%, P less than 0.05), and LD (-14.6 +/- 1.5%, P less than 0.01) associated with significant increases of left ventricular end-diastolic pressures relative to both atmospheric and esophageal pressures during MD and LD. NITP increased DAO(AP) and DAO(RL), resulting in increases in diastolic aortic cross-sectional area by an average of 6.1-8.3% (P less than 0.01). Similar changes were seen with the airway unobstructed during NITP. In series II, NITP caused diminished diastolic antegrade carotid artery and/or descending aortic flow run off in all dogs. Transient retrograde arterial flows with NITP were observed in more than half of the animals consistent with increases in aortic diameters. We conclude that a decrease of intrathoracic pressure confined to diastole can 1) diminish the ensuing LVSV, presumptively reducing preload by ventricular interdependence; 2) distend the intrathoracic aorta; 3) diminish antegrade flow out of the thorax independent of effects on cardiac performance; and 4) cause transient retrograde carotid and aortic blood flow. The intrathoracic aorta and, presumably, the arterial intrathoracic vascular compartment can be viewed as an elastic container driven by changes in intrathoracic pressure.

Animals↗

Transient analysis of cardiopulmonary interactions. II. Systolic events.

The etiology of the fall in left ventricular stroke volume (LVSV) and arterial pressure with a negative intrathoracic pressure (NITP) during inspiration is controversial. An increase in LV afterload produced by NITP has been proposed as one explanation but is difficult to evaluate if preload is also altered. To test the hypothesis that a systolic event alone, i.e., a change in LV afterload or contractility, can reduce LVSV during inspiration independent of changes in LV preload, a rapid transient NITP confined to systole was produced by electrocardiogram-triggered phrenic nerve stimulation in eight anesthetized dogs. Intrathoracic descending aortic diameters were measured by sonomicrometry to transduce qualitative changes in aortic transmural pressure. With the airway completely obstructed systolic NITP resulted in a decrease in LVSV (-8.1%, P less than 0.001) but an increase in the systolic anteroposterior (0.54 mm, P less than 0.01) and right-to-left (0.45 mm, P less than 0.01) aortic diameters compared with preceding beat. Similar significant changes were observed with the airway unobstructed. These observations are consistent with an increased afterload imposed on the LV reducing LVSV and egress of blood out of the thorax. Prolonging NITP to include both systole and diastole, a profound fall in LVSV is observed, consistent with the independent influences of systolic and diastolic events combining to diminish LVSV.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗

Correlation of left phrenic arterial flow with regional diaphragmatic blood flow.

Previous work has assumed that left phrenic arterial blood flow (Qpa) reflects diaphragmatic blood flow. We have tested this assumption in four anesthetized mechanically ventilated dogs by measuring Qpa with a Doppler flow probe and regional diaphragmatic blood flow with radiolabeled microspheres. Flows were examined during control 1 (diaphragm at rest), pacing (phrenic pacing: rate 20/min, duty cycle 0.33), control 2, hypotension (rest with mean arterial pressure reduced by 45% of the control 1 value), and hypotension and pacing. As a percent of the control 1 value, Qpa was 511 +/- 107% during pacing, 139 +/- 12% during control 2, 40 +/- 13% during hypotension, and finally 347 +/- 31% during hypotension and pacing. Similarly, percent left hemidiaphragmatic blood flow (Qlh) was 362 +/- 91% during pacing, 91 +/- 10% during control 2, 14 +/- 2% during hypotension, and finally 213 +/- 50% during hypotension and pacing. The changes in flow to the left costal and crural diaphragm were similar to those recorded for Qlh. We conclude that Qpa correlates with total and regional diaphragmatic blood flow (r = 0.77-0.81, P less than 0.001) under conditions of supramaximal phrenic nerve stimulation in which the metabolic demands of the region perfused by the phrenic artery are presumed to be similar to the metabolic demands of the rest of the diaphragm.

Animals↗

Effects of changes in left ventricular loading and pleural pressure on mitral flow.

The cause of the fall in left ventricular (LV) stroke volume (SV) during a fall in pleural pressure (Pp1) has been in dispute for over a century. We have defined the changes in the temporal relationship between LV inflow (Qm) and outflow (Qa) in a canine preparation to test the mutually exclusive hypotheses that the fall in LVSV is caused only by changes during diastole (e.g., ventricular interdependence) or only by changes during systole (e.g., afterload). The ability of the experimental preparation to measure the results of acute changes in right heart volume or output and acute changes in LV afterload was validated in open-chest studies with and without pericardial constraint. In closed-chest studies, with a fall in Pp1 during a Mueller maneuver Qm reached both its inspiratory minimum and expiratory maximum before Qa in 80% of the Mueller maneuvers, invalidating both hypotheses, which each required that one flow lead the other in 100% of the Mueller maneuvers. Review of individual records suggested that if the rapid changes in Pp1 occurred during systole, Qa could vary in a manner independent of the preceding Qm. These studies suggest that both diastolic and systolic events may contribute to the fall in SV, while causing opposite changes in LV volumes.

Animals↗

Interaction between high frequency jet ventilation and cardiovascular function.

We have studied the interaction of high frequency jet ventilation with cardiovascular pressures and flows. Results in dogs show that the amplitude of all intrathoracic pressures and flows fluctuate with a frequency equal to the difference between the heart rate and ventilator rate. The magnitude of this amplitude variation may be sufficient to obliterate periodically the pulsations in pulmonary artery and right atrial pressures. It is also shown that these cardiovascular beats can occur when the ventilator rate is close to integral multiples of the heart rate. Direct measurement of pleural pressure and the observation that the beats are markedly reduced when the chest is open support the hypothesis that the primary mechanism responsible for these beats is the interaction of the respiratory fluctuations in pleural pressure with the cardiac-generated pressure pulsations.

Animals↗

Ventilatory management of infant baboons with hyaline membrane disease: the use of high frequency ventilation.

We tested the hypothesis that high frequency oscillatory ventilation (HFOV) would result in decreased pulmonary barotrauma in infants with hyaline membrane disease by comparing HFOV at 10 Hz to conventional positive pressure ventilation with continual distending airway pressure (PPV/PEEP) in premature baboons with hyaline membrane disease. Nineteen baboon fetuses were randomized to one of two treatment groups, delivered at 140 +/- 2 days, and, after stabilization and instrumentation of PPV/PEEP, placed in their respective ventilator group. Animals on conventional ventilation were managed by adjustment of tidal volume and frequency (to 1 Hz) to keep PaCO2 below 55 and by adjustment of the mean airway pressure. One of the "HFOV" group died of cardiovascular complications before going on HFOV and was eliminated from data analysis. The remaining HFOV baboons survived the 11-day experimental period without evidence of airleak. Six of the 11 prematures treated with PPV/PEEP developed pulmonary interstitial emphysema and/or pneumothorax and five of the animals died within 48 h. The intergroup differences in airleak were significant (p less than 0.05). Mean airway pressure (measured at the proximal airway) was higher initially with HFOV but then was lowered more rapidly than in the PPV/PEEP animals. The arterial to alveolar oxygen ratio rose and the FIO2 could be lowered more rapidly with HFOV than with conventional ventilation. These differences reached significance by 20 h. After 60 h there were no significant differences between HFOV and the PPV/PEEP survivors. HFOV resulted in more uniform saccular expansion, higher arterial to alveolar oxygen ratio, less oxygen exposure, and decreased acute barotrauma when compared to PPV/PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Left ventricular geometry during positive end-expiratory pressure in dogs.

We evaluated changes in left ventricular (LV) geometry in ten dogs during intermittent positive-pressure ventilation (IPPV) with and without 10 cm H2O of positive end-expiratory pressure (PEEP). The dimensions during expiration and inspiration decreased in all three orthogonal axes during PEEP, consistent with decreased LV end-diastolic (ED) and end-systolic (ES) volumes. Within a respiratory cycle, the anterior-posterior (AP) ED dimension during inspiration increased with IPPV alone but decreased when PEEP was added, consistent with presumed differences in pulmonary venous return. This caused opposite changes in AP percent regional shortening. Septal-lateral free wall (SL) percent regional shortening decreased during inspiration with both IPPV and PEEP, but the respiratory variation was significantly less during PEEP. Thus, PEEP did not simply produce a smaller version of the same events seen during IPPV alone. The larger decreases with PEEP observed in ED compared to ES dimensions in the AP and SL axes suggest a dominant regional preload effect, whereas the larger fall in the long axis ES compared to ED dimension suggests a primary regional decrease in afterload. Measurements of the right ventricular SL axis in three dogs showed an overall reduction with PEEP, with the inspiratory dimensions being minimal during both IPPV alone and with PEEP. Thus, ventricular interdependence cannot account for the diminished LV SL dimension with PEEP during any part of the respiratory cycle. These findings suggest that the motion of the LV free wall influenced by changes in lung volume may be at least as important as septal motion in determining LV geometry with PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of changes in abdominal pressure on left ventricular performance and regional blood flow.

Many clinical conditions are associated with an increase in abdominal pressure. While the effects on venous return have been studied in the past, little attention has been given to the effect of abdominal pressure on left-sided hemodynamic events. The effects of acute changes in abdominal pressure (Pab) on left ventricular (LV) hemodynamics and outflow distribution were evaluated in ten open-chest dogs, which had undergone right heart bypass to eliminate the influence of changes in Pab on systemic venous return. Pressures were measured in the left atrium (Pla), aorta (Pao), and stomach (Pab). Electromagnetic flow probes were positioned around the ascending aorta (Qaa), descending aorta (Qda) and the innominate or subclavian artery (Qin) to reflect total cardiac output and the respective regional caudad and cephalad blood flows. Compressing the abdomen to increase acutely Pab (9.2 +/- 0.6 torr) also significantly increased Pao (7.8 +/- 1.2 torr), Pla (1.7 +/- 0.4 torr), and Qin (15.2 +/- 4.5%), while Qaa (-9.5 +/- 2.0%) and Qda (-26.3 +/- 7.0%) significantly decreased. Opposite findings were obtained immediately after release of abdominal compression. Thus, an acute increase in Pab with a constant pulmonary artery inflow increased the afterload imposed on the left ventricle and redistributed LV output, with a reduction in flow to the abdomen. Part of the fall in Qaa and increase in Pla could be attributed to passive elevation of the diaphragm by the increase in Pab, i.e., heart-lung-diaphragm interdependence.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Pulmonary interstitial emphysema in the premature baboon with hyaline membrane disease.

During experiments designed to develop an appropriate ventilatory strategy for high-frequency ventilation (HFV) in the premature baboon with hyaline membrane disease (HMD), we observed the development of pulmonary interstitial emphysema (PIE). Four study groups of 5 animals each received positive-pressure ventilation and positive end-expiratory pressure (PPV/PEEP) or HFV and 1 of 3 sighing techniques. Pathologically, all animals ventilated with PPV/PEEP or HFV with a carefully controlled intermittent sigh developed dilatation of the distal conducting airway and alveolar duct, with poorly expanded pulmonary saccules. The imposition of a sigh with inappropriate timing or excessive volume ruptured the dilated airway walls and caused interstitial air to accumulate. This was evident from the location of striking dilation of the distal airways and pseudocysts in areas of atelectasis. Thus, early in the course of HMD when saccular aeration is minimal, the pathogenesis of PIE is related to airway rather than alveolar rupture.

Animals↗

Temporal changes after death in primate diaphragm muscle oxidative enzyme activity.

We have previously reported that muscle fibers in fresh samples of the diaphragm muscle of prenatal baboons have moderate to high oxidative capacity and are resistant to fatigue in vitro. These conclusions are in conflict with those of others on diaphragmatic muscle fibers studied in autopsy specimens from human infants. Reasons for these divergent interpretations could include species difference and the use of autopsy specimens rather than fresh tissue samples. We have, therefore, tested whether characteristics of human infant diaphragm muscle fibers differ from those of premature baboons, and whether the use of autopsy specimens alters interpretations of histochemical results. Samples obtained from premature, newborn, or adult baboons were quick-frozen immediately after death or after storage for as long as 24 h. Samples were obtained at autopsy from human infants at 4 to 24 h after death. Histochemical assay for NADH-TR activity was performed on cross sections. Samples from baboons at any age showed deterioration with storage, but the muscles from premature and newborn animals were considerably more susceptible to damage than those of adults. Fibers in human infant diaphragm obtained within 10 h of death looked remarkably similar to those of the infant baboons. However, samples obtained at later times after death showed deterioration and loss of oxidative enzyme activity. We conclude that diaphragmatic muscle fibers of humans and nonhuman primates are similar in enzymatic profile, but that elapsed time after death can reduce the intensity of mitochondrial enzyme assays. The decrement in tissue preservation with elapsed time after death is less pronounced in more mature muscles.

Animals↗

Cooling-induced contraction of guinea pig tracheal smooth muscle.

Cooling of isolated guinea pig tracheal smooth muscle from 38 to 28 degrees C over 2.25 min produced a transient contraction followed by sustained relaxation. The cooling-induced contraction was blocked either by pretreatment with ouabain at concentrations of 10(-5) M or greater or by substitution of normal physiological salt solution with K-free solution. In contrast, the contractile response to cooling was not inhibited by pretreatment with phentolamine (10(-5) M), atropine (10(-5) M), tetrodotoxin (3 X 10(-7) M), diphenhydramine (10(-5) M), cromolyn sodium (10(-3) M), indomethacin (3 X 10(-7) M), nifedipine (10(-7) M), or verapamil (3 X 10(-6) M). Addition of NaHCO3 to the bath during cooling, preventing a change in pH of the physiological salt solution, did not affect the cooling-induced contraction. It is concluded that cooling of isolated guinea pig trachea produces a transient ouabain-sensitive contraction, and that the data suggest the contraction is mediated by inhibition of Na-K-ATPase in the smooth muscle rather than through neuronal stimulation or chemical mediator release.

Animals↗

Systolic pressure amplification in pedal arteries in children.

Sphygmomanometric indirect blood pressure readings on the arm were compared to direct blood pressure readings from the radial and pedal arteries in pediatric patients. The direct systolic pressure in the pedal arteries was significantly (p less than 0.001) greater (25.1 +/- 12.3 mm Hg) than the indirect arm systolic pressure. The direct systolic pressure from the radial artery was identical to the indirect systolic arm pressure. Although there were no statistical differences between direct and indirect diastolic pressures, correlations for diastolic pressures were relatively poor. These data indicate that (1) there is a significant and unpredictable amplification of systolic pressure in the pedal arteries which may result in erroneous diagnosis of hypertension or jeopardize early detection of circulatory shock, (2) indirect blood pressure measurement with the recommended cuff width (125% of arm diameter or 40% of arm circumference) accurately reflects direct systolic pressure in the radial artery, and (3) indirect blood pressure measurement gives a relatively poor prediction of direct diastolic pressures.

Adolescent↗

A re-evaluation of the hemodynamic consequences of intermittent positive pressure ventilation.

The hemodynamic effects of intermittent positive pressure ventilation (IPPV) have generally been considered straightforward, being dominated by the inspiratory reduction in systemic venous return. Paradoxically, there is considerable debate regarding the effects of PEEP. We have studied both right ventricular (RV) and left ventricular (LV) performance during a single IPPV respiratory cycle in dogs with intact circulatory systems or the right heart bypassed in open and closed chest conditions. We have found that the "reverse pulsus paradoxus" during inspiration reflects both transmission of the increased intrathoracic pressure to the thoracic aorta and an increase in LV stroke volume (SV). This inspiratory increase in LVSV has been found to be influenced by, but not dependent on: (a) respiratory variations in RVSV; (b) variations in functional residual capacity or tidal volume altering pulmonary venous return and the degree of physical compression of the heart by the lungs; (c) an inspiratory decrease in RV volume, increasing LV diastolic compliance and, thus, probably improving pulmonary venous return; (d) a decreased transmural aortic diastole pressure reflecting an effective decrease in LV afterload produced by both the general increase in intrathoracic pressure and the direct compression of the heart; and (e) variations in the pulmonary vascular volume as indicated by changes in the transmural LV end-diastolic pressure. An understanding of IPPV during a single respiratory cycle facilitates an appreciation of the steady state hemodynamic effects of IPPV with or without PEEP. Our results imply that measurements made only at end-expiration, ignoring inspiratory events, may have serious limitations. Furthermore, they suggest that IPPV with PEEP should be evaluated as a form of LV assist in LV failure.

Animals↗

Development of histochemical and functional properties of baboon respiratory muscles.

We assessed morphological, histochemical, and physiological characteristics of respiratory muscles of a non-human primate, Papio cynocephalus, from midgestation through adult life. Samples were taken of diaphragm muscles for histochemical analysis, electron microscopy, and assessment of contractile properties and fatigability. Histochemical analyses were also performed on samples of intercostal muscles. Initially, developing fibers are type IIc but differentiate into types I and IIa fibers by term. We observed no IIb fibers in respiratory muscles of premature baboons. Beginning late in gestation, muscle fibers grew rapidly. After term, IIb fibers were found, and fiber size ranked by increasing mean fiber area became types I, IIa, and IIb. After term, we rarely observed type IIc fibers. In electron micrographs we observed large numbers of interfibrillar mitochondria in all muscle fibers of premature baboons but not in all IIb fibers of adults. Histochemical observations were supported by contractile properties. Muscles of premature baboons had significantly longer contraction and relaxation times than adult muscles. Muscles from premature baboons were more resistant to fatigue than those of adult baboons. We conclude that the fibers of respiratory muscles are high in oxidative capacity and are resistant to fatigue during gestation. Fatigue of the respiratory muscle fibers secondary to low oxidative capacity is not a likely cause of respiratory distress in premature baboons.

Animals↗

Mechanical heart-lung interaction with positive end-expiratory pressure.

Recent reports have suggested that positive end-expiratory pressure (PEEP) depresses left ventricular (LV) function or shifts LV pressure-volume (PV) relationships due to neural, humoral, or mechanical events. These studies have usually utilized pressures measured during expiration. To study the mechanical effects of PEEP in expiration and inspiration, the circulation was arrested in 12 open-chest dogs, and the coronaries were perfused with a cold cardioplegic agent. Balloons were placed in the ventricles to measure ventricular pressures. Shifts in cardiopulmonary blood volume were prevented by venting the atria to atmosphere. Having ablated neural reflexes and humoral changes, we varied ventricular volumes, chest wall compliance, tidal volume, and PEEP. We found that isovolumic ventricular pressures (relative to atmosphere) increase with PEEP (P less than 0.001), and heart-lung interaction with PEEP is significantly greater in inspiration (P less than 0.001). The effect of PEEP is modified by heart volume (P less than 0.01) and respiratory system compliance (P less than 0.01). We conclude that a mechanical compressive force can be applied to the heart by the lungs as they expand, and this may explain the previous reports of diminished LV function or LV diastolic compliance with PEEP and, in part, explain the decreased cardiac output associated with PEEP. The marked increase in mechanical compressive forces applied to the heart during inspiration with PEEP may have far greater hemodynamic consequences than events during expiration.

Animals↗