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Biomedical subjects

D A Grant

Publications and source records attributed to D A Grant.

At least 19 recordsLinked to original sources
PubMed2001

Left ventricular stroke volume in the fetal sheep is limited by extracardiac constraint and arterial pressure.

1. Extracardiac constraint and sensitivity to arterial pressure may be critical factors that limit the functional reserves of the developing fetal heart in utero. We hypothesise that extracardiac constraint is the predominant factor that limits fetal stroke volume (SV). To test this hypothesis we studied six chronically instrumented fetal sheep to determine the relative roles that extracardiac constraint and arterial pressure play in determining left ventricular (LV) function. 2. Pregnant ewes (128-131 days gestation, term = 147 days) were anaesthetised (5 mg kg(-1) Propofol I.V., then 1.5 % halothane, 50 % O(2), balance N(2)O by inhalation) and instrumented using sterile surgical techniques to record LV end-diastolic pressure (P(lved)), aortic pressure (P(ao)), pericardial pressure (P(per)), and LV SV. 3. After a minimum of 72 h recovery, LV function was assessed by altering fetal blood volume to vary P(lved). Ventricular function curves were generated using two measures of ventricular function, SV and stroke work index (SWI = SV x P(ao)), and two measures of ventricular filling, P(lved) and LV end-diastolic transmural pressure (P(lved,tm) = P(lved) - P(per)). 4. Although decreasing P(lved) from the resting level decreased SV, increasing P(lved) from the resting level did not increase SV because the ventricular function curve plateaued. This plateau was not explained solely by an increase in aortic pressure, as the plateau remained present in the SWI versus P(lved) curve. When extracardiac constraint was accounted for (SV against P(lved,tm)), the plateau was largely eliminated (approximately 80 %). The remaining portion of the plateau (approximately 20 %) was eliminated when both extracardiac constraint and arterial pressure were accounted for (SWI versus P(lved,tm)). 5. Thus, the major limitation upon LV function in the near-term fetus results from extracardiac constraint limiting ventricular filling while, at the same time, a much smaller limitation arises from increasing arterial pressure.

Animals↗
PubMed2001

Age-related differences in the distortion of the sheep lung in response to localised pleural stress.

In order for diastolic filling to occur, the heart must displace the lung. Given the changes in lung structure and compliance that follow birth, we sought to determine whether the neonatal lung resists neighbouring structures encroaching into its space more than the adult lung and whether the lung surface making up the cardiac fossa resists distortion more than the lateral surface does. Pleural distortions, induced by applied pressures (Pappl) of 20-120 g cm(-2) at airway pressures (Paw) of 2.5-15 cm H2O, were recorded in isolated lungs of adult, neonatal (4-week-old) and newborn (1-week-old) sheep. The depth of pleural distortion increased (P < 0.05, ANOVA) with increasing Pappl in all lungs. Adult lungs were significantly more distortable than newborn and neonatal lungs (P < 0.05). As Paw increased, the distortability of the adult lung decreased progressively (P < 0.05) while the distortability of the newborn and neonatal lung remained constant at Paw of 2.5 and 5 cm H2O. Adult lungs also differed from newborn and neonatal lungs in that the cardiac fossal surface was significantly less distortable than the lateral surface. As newborn and neonatal lungs are less easily distorted than adult lungs, the potential for the lungs to limit cardiac filling is greater in the newborn and neonate than in the adult.

Aging↗
PubMed2001

Nitric oxide inhibition abolishes sleep-wake differences in cerebral circulation.

Nitric oxide (NO), being produced by active neurones and also being a cerebral vasodilator, may couple brain activity and blood flow in sleep, particularly during active sleep (AS), which is characterized by widespread neural activation and markedly elevated cerebral blood flow (CBF) compared with quiet wakefulness (QW) and quiet sleep (QS). This study examined CBF and cerebral vascular resistance (CVR) in lambs (n = 6) during spontaneous sleep-wake cycles before and after infusion of N(omega)-nitro-L-arginine (L-NNA), an inhibitor of NO synthase. L-NNA infusion produced increases in CVR and decreases in CBF during all sleep-wake stages, with the greatest changes occurring in AS (DeltaCVR, 88 +/- 19%; DeltaCBF -24 +/- 8%). The characteristic CVR and CBF differences among AS, QS, and QW disappeared within 1-3 h of L-NNA infusion, but had reappeared by 24 h despite persisting cerebral vasoconstriction. These experiments show that NO promotes cerebral vasodilatation during sleep as well as wakefulness, particularly during AS. Additionally, NO is the major, although not sole, determinant of the CBF differences that exist between sleep-wake states.

Animals↗
PubMed2001

Right atrial pressure as measure of ventricular constraint in newborn lambs.

Although the lungs and pericardium constrain the heart and limit cardiac output, no method exists to assess this constraint in sick newborns. We hypothesize that a useful estimate of ventricular constraint may be obtained by measuring right atrial pressure (P(RA)) in the newborn. To test this hypothesis, we measured P(RA), thoracic inferior vena caval pressure (P(IVC); saline-filled catheters), and ventricular constraint (pericardial pressure, P(PER); liquid-containing balloon) in 4-wk-old (neonatal, n = 12) and 3-day-old (newborn, n = 6) anesthetized lambs. The measurements were made while LV filling pressure was altered (0-20 mmHg) and while positive end-expiratory pressure (PEEP) was maintained at 2.5 or 15 cmH2O. In all of the lambs, a strong linear relationship (r) existed between P(RA) and P(PER) (P(RA) = 1.19 P(PER) + 0.0, r = 0.99) and between P(IVC) and P(PER) (P(IVC) = 1.24 P(PER) + 0.1, r = 0.99; PEEP of 2.5 cmH2O). Similar relationships were also observed with increased PEEP (P(RA) = 1.29 P(PER)-1.2, r = 0.98 and P(IVC) = 1.32 P(PER)-1.2, r = 0.97). Because P(RA) provides an accurate measure of ventricular constraint in the normal lamb, it may be a useful measure of ventricular constraint in the sick newborn.

Animals↗
PubMed2001

Cost segregation of assets offers tax benefits.

A cost-segregation study is an asset-reclassification strategy that accelerates tax-depreciation deductions. By using this strategy, healthcare facility owners can lower their current income-tax liability and increase current cash flow. Simply put, certain real estate is reclassified from long-lived real property to shorter-lived personal property for depreciation purposes. Depreciation deductions for the personal property then can be greatly accelerated, thereby producing greater present-value tax savings. An analysis of costs can be conducted from either detailed construction records, when such records are available, or by using qualified appraisers, architects, or engineers to perform the allocation analysis.

Cost Allocation↗
PubMed2000

Effects of positive intrathoracic pressure on pulmonary and systemic hemodynamics.

The Frank-Starling Law accounts for many changes in cardiac performance previously attributed to changes in contractility in that changes in contractility might have been incorrectly inferred from changing ventricular function curves (i.e. systolic performance plotted against filling pressure) if diastolic compliance also changed. To apply the Frank-Starling Law in the presence of changing diastolic compliance, it is necessary to measure end-diastolic volume directly or to calculate end-diastolic transmural pressure, which requires that pericardial pressure be known. Under most normal circumstances, increased intrathoracic pressure (and other interventions, such as vasodilators or lower-body negative pressure, that decrease central blood volume) decreases the transmural end-diastolic pressures of both ventricles, their end-diastolic volumes and stroke work. However, when ventricular interaction is significant, the effects of these interventions might be quite different; this may be important in patients with heart-failure. Although these interventions decrease RV transmural pressure, they may increase LV transmural pressure, end-diastolic volume, and thus stroke work by the Frank-Starling mechanism.

Animals↗
PubMed1999

Repetitive hypoxia rapidly depresses cardio-respiratory responses during active sleep but not quiet sleep in the newborn lamb.

1. Arousal from sleep is an important protective response to hypoxia that becomes rapidly depressed in active sleep (AS) when hypoxia is repeated. This study questioned whether there might also be selective depression of cardio-respiratory responses to hypoxia during AS. 2. Nine newborn lambs (7-22 days of age) were studied over three successive nights. The first and third nights were baseline studies (inspired oxygen fraction, Fi,O2 = 0.21). During the second night, during every epoch of sleep, lambs were exposed to 60 s episodes of isocapnic hypoxia (Fi,O2 = 0.10). 3. During quiet sleep (QS), the probability of arousal in hypoxia exceeded the probability of spontaneous arousal (P < 0.001) throughout repeated exposures to hypoxia. Similarly, there were persisting increases in ventilation (135 +/- 25 %), blood pressure (3 +/- 1 %) and heart rate (3 +/- 1 %). 4. By contrast, rapid depression of all responses occurred during repetitive hypoxia in AS. Thus, the probability of arousal in hypoxia exceeded the probability of spontaneous arousal during the first 10 hypoxia exposures (P < 0.001) but not thereafter. Similarly, during the first 10 exposures to hypoxia, the changes in ventilation (88 +/- 15 %) and blood pressure (5 +/- 1 %) were greater than subsequent responses (P < 0.05). 5. We conclude that, when repeated, hypoxia rapidly becomes ineffective in stimulating protective arousal, ventilatory and blood pressure responses in AS, but not in QS. Selective depression of responses during AS may render the newborn particularly vulnerable to hypoxia in this state.

Animals↗
PubMed1999

Interactions between the right ventricle and pulmonary vasculature in the fetus.

A midsystolic plateau differentiates the pattern of fetal pulmonary trunk blood flow from aortic flow. To determine whether this plateau arises from interactions between the left (LV) and right ventricle (RV) via the ductus arteriosus or from interactions between the RV and the lung vasculature, we measured blood flows and pressures in the pulmonary trunk and aorta of eight anesthetized (ketamine and alpha-chloralose) fetal lambs. Wave-intensity analysis revealed waves of energy traveling forward, away from the LV and the RV early in systole. During midsystole, a wave of energy traveling back toward the RV decreased blood flow velocity from the RV and produced the plateau in blood flow. Calculations revealed that this backward-traveling wave originated as a forward-traveling wave generated by the RV that was reflected from the lung vasculature back toward the heart and not as a forward-traveling wave generated by the LV that crossed the ductus arteriosus. Elimination of this backward-traveling wave and its associated effect on RV flow may be an important component of the increase in RV output that accompanies birth.

Animals↗
PubMed1999

Ventricular constraint in the fetus and newborn.

Birth is accompanied by a series of rapid adaptations of the cardiovascular system, one of the most notable being a doubling of left ventricular (LV) stroke volume. What makes this increase in LV stroke volume remarkable is that before birth the heart functions at a maximal level that cannot easily be increased with acute interventions such as volume infusion. Although changes in heart rate, contractility and afterload contribute to the adaptations of birth they do not adequately explain the doubling of LV stroke volume. Early studies obscured the role that ventricular preload plays in controlling fetal and newborn cardiac function by focusing on these other mechanisms and by failing to appreciate fully the significance of ventricular constraint in limiting heart function. Recent evidence suggests that ventricular constraint, arising from the tissues that surround the heart (chest wall, lungs and pericardium), limits fetal ventricular preload and thus determines the limits of fetal cardiac function. Relief of this constraint at birth, with aeration of the lungs and clearance of the lung liquid associated with the fetal lungs, may be the key mechanism that increases LV preload and thus increases LV stroke volume in the newborn.

Female↗
PubMed1998

Repetitive hypoxia rapidly depresses arousal from active sleep in newborn lambs.

1. Arousal from sleep is an important protective mechanism that is depressed by repeated episodes of hypoxia. We aimed to determine how rapidly arousal depression occurs during repeated hypoxia and to determine if the depression is sleep state specific. 2. Three successive 12 h overnight sleep recordings were performed in six newborn lambs instrumented to record sleep state, blood pressure, heart rate and blood gases. The first (control) and third (recovery) nights were baseline studies (inspired oxygen fraction, FI,O2 = 0.21) to determine the spontaneous arousal probability. During the second (test) study night, lambs were exposed to a 60 s episode of isocapnic hypoxia (FI,O2 = 0.10; inspired carbon dioxide fraction, FI,CO2 = 0.03) during every epoch of sleep. 3. During quiet sleep (QS), the probability of arousing to hypoxia (56%) remained significantly higher than the probability of arousing spontaneously (18%) throughout the repeated hypoxic exposures (chi(2) = 81.5, P < 0.001). By contrast, during active sleep (AS) arousal rapidly became depressed with repetition of the hypoxic stimulus; the probability of arousal in hypoxia (52%) was significantly higher than the probability of spontaneous arousal (12%) during the first ten hypoxic exposures (chi(2) = 18.2, P < 0.001), but there was no difference thereafter. 4. We conclude that, when repeated, moderate hypoxia very rapidly becomes ineffective as an arousing stimulus in AS, but not in QS. These results suggest that the arousal mechanism is particularly vulnerable to failure during AS.

Animals↗
PubMed1998

Cerebral circulation in sleep: vasodilatory response to cerebral hypotension.

Little is known of the factors that regulate CBF in sleep. We therefore studied 10 lambs to assess the vasodilatory processes that underlie cerebral autoregulation during sleep. Lambs, instrumented to measure CBF (flow probe on the superior sagittal sinus), sleep state, and cerebral perfusion pressure (CPP), were rapidly made hypotensive by inflating a cuff around the brachiocephalic artery to reduce CPP to 30 mm Hg in each state. During control periods, cerebral vascular resistance (CVR in mm Hg/mL/min) was lower in active sleep (2.8 +/- 0.3, mean +/- SD, P < or = 0.001) than in wakefulness (3.9 +/- 0.6) and quiet sleep (4.3 +/- 0.6). The CVR decreased promptly in each state as CPP was lowered. The time (seconds) required for maximal cerebral vasodilation to occur was longer in active sleep (35 +/- 11) than in quiet sleep (20 +/- 6, P < or = 0.001) and wakefulness (27 +/- 11, P < or = 0.05). The CVR decreased less in active sleep (0.6 +/- 0.3, P < or = 0.001) than in quiet sleep (1.5 +/- 0.3), although the changes in CPP induced with brachiocephalic occlusion were equal in each state. In conclusion, our studies provide the first evidence that the vasoactive mechanisms that underlie autoregulation of the cerebral circulation function during sleep. Moreover, our data reveal that the speed and the magnitude of the vasodilatory reserves available for autoregulation are significantly less in active sleep than in quiet sleep.

Animals↗
PubMed1997

Oxygen transport and utilization during feeding in the young lamb.

1. Five lambs (19-27 days old) were studied to determine the effects of feeding on cardiorespiratory function. 2. Each lamb was instrumented to record cardiac output, aortic and pulmonary artery pressure and arterial and mixed venous oxyhaemoglobin saturations (Sa,O2 and Sv,O2). 3. During feeding, arterial haemoglobin desaturated and resaturated sequentially during the periods of sucking and non-sucking. The nadir of these Sa,O2 desaturations (83 +/- 2%, mean +/- S.E.M.) was significantly lower than the baseline value (92 +/- 2%, P < or = 0.05, ANOVA). Sa,O2 returned to the baseline level between periods of sucking. Sv,O2 also decreased (55 +/- 3% baseline, 46 +/- 3% sucking, P < or = 0.05) but, in contrast to Sa,O2, it remained significantly lower than baseline levels in the pauses between periods of sucking. 4. Arterial pressure increased during feeding (94 +/- 4 mmHg baseline, 113 +/- 6 mmHg feeding, P < or = 0.05), while heart rate and cardiac index did not change. 5. Total body oxygen consumption rose during the pauses between sucking periods (10.9 +/- 1.1 ml O2 min-1 kg-1 baseline, 13.9 +/- 1.2 ml O2 min-1 kg-1 non-sucking, P < or = 0.05) and was provided for by a significant increase in total body oxygen extraction as systemic oxygen transport was unchanged. 6. Our results reveal that during feeding in young lambs oxygen consumption increases and body stores of oxygen (e.g. Sv,O2) become depleted; this combination may promote rapid arterial desaturation and cyanosis during feeding.

Analysis of Variance↗
PubMed1997

Monensin toxicity in a flock of ostriches.

A total of 42 birds from a flock of 104 farmed ostriches showed signs of toxicity after the accidental inclusion of monensin in their concentrate ration. The initial clinical signs were muscle weakness and ataxia which progressed to recumbency, dyspnoea and death, despite intensive supportive therapy. The serum activity of the enzymes creatine kinase, aspartate aminotransferase and lactate dehydrogenase was high in the affected birds, indicating significant muscle pathology. Few gross lesions were identifiable postmortem, but widespread lesions of degenerative myopathy were present at the histopathological level. However, these degenerative changes were restricted to the skeletal muscle and there was no evidence of cardiomyopathy in any of the birds examined. The birds were fed a ration which contained 215 to 224 ppm monensin for 13 days. New clinical cases ceased to occur shortly after the withdrawal of the source of monensin, but all the individuals which showed clinical signs of toxicity died or were euthanased on humane grounds.

Animal Feed↗
PubMed1996

Pleural and pericardial pressures limit fetal right ventricular output.

BACKGROUND: The chest wall, lungs, and pericardium limit diastolic filling of the left ventricle in the fetus, neonate, and adult. To determine the effect that these tissues have on the fetal right ventricle (RV), we studied six fetal lambs (142 days of gestation) METHODS AND RESULTS: Pregnant ewes were anesthetized (ketamine and alpha-chloralose), and the fetuses were partially delivered by cesarean section. Fetuses were instrumented to record RV stroke volume, RV end-diastolic pressure (Prved), intrapericardial pressure (Pip), and pleural pressure. Prved was varied between 2 and 20 mm Hg under three conditions: initially with a closed chest and a closed pericardium (CCCP); subsequently with an open chest (chest wall and lungs retracted) and a closed pericardium (OCCP); and finally after the chest wall, lungs, and pericardium were retracted (OCOP). At equal Prved, stroke volume increased substantially when the chest wall and lungs were retracted from the heart and increased further on subsequent retraction of the pericardium (eg, at Prved of 9 mm Hg, stroke volume increased from 1.2 +/- 0.2 mL [mean +/- SEM] in the CCCP condition to 2.9 +/- 0.4 and 4.2 +/- 0.3 mL in the OCCP and OCOP conditions, respectively, P < or = .05). The limitation of stroke volume in the CCCP and OCCP conditions occurred because Pip increased in an almost one-to-one fashion as Prved increased; as a consequence, RV preload (RV end-diastolic transmural pressure, Prved minus Pip) was relatively unchanged. CONCLUSIONS: The chest wall-lung combination and the pericardium each significantly constrain the fetal RV and together limit RV stroke volume.

Animals↗
PubMed1995

Automated scoring of sleep in the neonatal lamb.

The study of sleep is an important and rapidly expanding area of research that generates large bodies of data. Manual scoring of sleep states from polygraph recordings is a laborious and often subjective task. Even when care is taken, the opportunity for disagreement between investigators and between laboratories remains great. To avoid this difficulty and to reduce the subjectivity of sleep state scoring we have designed a computer-based algorithm for scoring sleep state in the lamb. The algorithm underlying the system relies upon spectral analysis of the electrocorticogram and upon amplitude analysis of the electrooculogram and nuchal electromyogram. Partitioning the spectral power observed within the electrocorticogram (1-4 Hz frequency range) reliably identifies deep quiet sleep. Wakefulness and active sleep are then identified based upon threshold crossings of the electrooculogram and of the electromyogram of the nuchal muscles. We compared the sleep states returned by the algorithm to those scored visually by trained personnel for 1 hour of data collected from each of five 19-day-old lambs. There was good agreement between the two methods of scoring sleep. The percents agreement between the algorithm-derived scores and visual scores were as follows: active wakefulness 97%, quiet wakefulness 87%, quite sleep 85% and phasic active sleep 82%. As such, our algorithm provides a fast, reliable and objective method for scoring sleep state in the young lamb.

Algorithms↗
PubMed1995

Continuous measurement of blood flow in the superior sagittal sinus of the lamb.

We assessed the validity of recording blood flow in the superior sagittal sinus (Qss) as a measure of cerebral blood flow (CBF). While anesthetized, 10 lambs were instrumented with a transit-time ultrasonic flow probe around the superior sagittal sinus to measure Qss, electrodes to assess sleep state, catheters to measure cerebral perfusion pressure (Pcp), and an occlusive cuff around the common brachiocephalic artery to vary blood pressure. After 72 h recovery, lambs were studied during spontaneous sleep-wake cycles to establish 1) the normal range of Qss and 2) the response rate of Qss to rapid alterations of Pcp. Subsequently, the lambs were reanesthetized, and the measurement of Qss was calibrated and validated. Qss was linearly related to the arterial inflow of 35% of the brain mass (y = 0.5 x + 1.6, r = 0.93, n = 4). Qss was greater in active sleep (154.1 +/- 45.7 ml.min-1 x 100 g-1, mean +/- SD, n = 5) than in quiet sleep (97.1 +/- 40.8 ml.min-1 x 100 g-1) and quiet wakefulness (107 +/- 44.3 ml.min-1 x 100 g-1, P < 0.05). Qss responded rapidly (within one beat) to spontaneous and to induced transient changes in Pcp. We conclude that recording blood flow in the superior sagittal sinus provides a simple, continuous, and quantitative measure of CBF from a defined area of the brain and is appropriate for studying transient changes in the cerebral circulation.

Animals↗
PubMed1995

Periodontal microbiota of mobile and non-mobile teeth.

The mechanism of accelerated periodontal destruction around teeth with occlusal trauma and increased mobility remains unclear. One possibility is that tooth mobility creates a subgingival environment conducive to overgrowth by periodontal pathogens. This study compared the subgingival microflora in mobile and non-mobile teeth of 35 adults on supportive maintenance therapy and 15 with untreated adult periodontitis. In each subject, subgingival paper-point samples were obtained from a mobile tooth with a probing depth of 4 mm or greater and from a non-mobile tooth with similar probing depth and gingival index. Samples were transported in VMGA III medium. Pockets around mobile teeth harbored significantly higher proportions of Campylobacter rectus (P = 0.001) and Peptostreptococcus micros (P = 0.05) than pockets with non-mobile teeth. Mobile teeth also tended to show elevated levels of Porphyromonas gingivalis, but this did not reach statistical significance. This study suggests that tooth mobility may constitute a risk for periodontal breakdown due to an increased subgingival occurrence of specific periodontopathogens. This hypothesis needs to be verified in longitudinal clinical and microbiological studies.

Adult↗