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Biomedical subjects

M J Sullivan

Publications and source records attributed to M J Sullivan.

At least 109 records · Page 6Linked to original sources

The anaerobic threshold in chronic heart failure. Relation to blood lactate, ventilatory basis, reproducibility, and response to exercise training.

In patients with chronic heart failure (CHF), the anaerobic threshold by gas exchange (ATge) represents a potentially useful parameter for assessing functional disability and the response to therapeutic interventions designed to improve exercise tolerance. We measured the ventilatory, hemodynamic, and metabolic responses to maximal bicycle exercise in 64 patients with CHF and 38 age-matched normal subjects. The ratio of ventilation to carbon dioxide production (VE/VCO2) was increased during exercise in patients as compared with normal subjects although VE was closely related to VCO2 in both individual normal subjects and patients (all, r greater than 0.92, p less than 0.01). Increased VE/VCO2 in patients was unrelated to increased pulmonary vascular pressures but was closely linked to increases in the pulmonary dead space to tidal volume ratio (Vd/Vt). Despite hemodynamic abnormalities in patients, PaCO2 was regulated at normal levels during exercise. In a second study, we determined the ATge in 18 patients with CHF and 18 normal subjects by the ventilatory equivalents method. The ATge could be identified from unaveraged breath-by-breath data as the initial increase in VE/VO2 without an increase in the VE/VCO2 in 15 of 18 patients and in 16 of 18 normal subjects. The ATge demonstrated good day-to-day reproducibility (r = 0.91, p less than 0.001, SEE = 1.74 ml/kg/min) and low interobserver variability and was associated with comparable increases in arterial lactate in the two groups above the resting value, 0.9 +/- 0.4 mM/l in patients and 0.8 +/- 0.5 mM/l in normal subjects. To examine the effects of a chronic intervention on the ATge, 12 patients with CHF underwent exercise training for 4-6 months. Training resulted in a 23% improvement in peak VO2 and a decrease in blood lactate accumulation during submaximal exercise. This was associated with decreased VE and VCO2 during submaximal exercise, an increased VO2 at which the ATge occurred from 10.1 +/- 1.2 ml/kg/min to 12.1 +/- 2.6 ml/kg/min (p less than 0.01) and an increase in exercise duration during a symptom-limited, constant work-rate protocol (938 +/- 110 seconds vs. 1,421 +/- 691 seconds, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Anaerobic Threshold↗

Free scapular osteocutaneous flap for mandibular reconstruction.

Seventeen patients, 4 of whom had osteoradionecrosis, underwent mandibular reconstruction with a revascularized scapular osteocutaneous flap. The mean length of revascularized scapular bone used was 10.4 cm. Nine of the 17 flaps healed uneventfully; however, previously irradiated patients had a higher incidence of postoperative complications. There was only 1 flap failure. We found the free revascularized scapular osteocutaneous flap to be reliable and ideal for the reconstruction of large composite defects of the oral cavity.

Adult↗

"Challenges in pain management". Part 4. Teaching coping strategies to adolescents with migraine.

A treatment program was developed involving cognitive and behavioral strategies for the treatment of migraine headaches with adolescents at the Children's Hospital of Eastern Ontario. These techniques include: a headache diary, progressive relaxation techniques, cognitive restructuring, distraction or attention focusing, mental activities, thought stopping, imagery, behavior rehearsal, assertiveness and problem solving. The article details the therapeutic use of these techniques. An analysis of each strategy is presented in three sections: a rationale to the adolescent, recommendations to the therapist and a troubleshooting section.

Adaptation, Psychological↗

Exercise training in patients with chronic heart failure delays ventilatory anaerobic threshold and improves submaximal exercise performance.

We have recently demonstrated that exercise training can induce important hemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examines the accompanying changes in submaximal exercise performance and the ventilatory response to exercise in these patients. Before and after 16-24 weeks of exercise training, subjects underwent two symptom-limited bicycle exercise tests, one with an incremental graded workload, and one with a constant workload that represented 79 +/- 11% of the pretraining peak oxygen consumption. Breath-by-breath expired gas analysis was performed continuously during each test, and central hemodynamic, leg blood flow, and blood lactate measurements were obtained during the incremental protocol. The ventilatory anaerobic threshold was determined during the incremental exercise study from coplotted breath-by-breath ventilatory data with standard criteria by observers who were unaware of patient identity or training status. As previously reported, exercise training increased peak oxygen consumption by 23% from 16.8 +/- 3.8 to 20.6 +/- 4.7 ml/kg/min and reduced blood lactate levels during submaximal exercise. The training-induced decrease in lactate accumulation was accompanied by a decrease in carbon dioxide production, respiratory exchange ratio, and ventilation during submaximal exercise. The ventilatory anaerobic threshold was delayed from 284 +/- 43 to 352 +/- 91 seconds of exercise (p = 0.02), and it occurred at an increased oxygen consumption (10.1 +/- 1.2 vs. 12.1 +/- 2.6 ml/kg/min, p = 0.01). Exercise duration during the constant workload protocol increased from 938 +/- 410 to 1,429 +/- 691 seconds (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure.

We studied the central hemodynamic, leg blood flow, and metabolic responses to maximal upright bicycle exercise in 30 patients with chronic heart failure attributable to severe left ventricular dysfunction (ejection fraction, 24 +/- 8%) and in 12 normal subjects. At peak exercise, patients demonstrated reduced oxygen consumption (15.1 +/- 4.8 vs. 32.1 +/- 9.9 ml/kg/min, p less than 0.001), cardiac output (8.7 +/- 3.2 vs. 18.6 +/- 4.4 l/min, p less than 0.001), and mean systemic arterial blood pressure (116 +/- 15 vs. 135 +/- 13 mm Hg, p less than 0.01) compared with normal subjects. Leg blood flow was decreased in patients versus normal subjects at rest and matched submaximal work rates and maximal exercise (2.1 +/- 1.9 vs. 6.4 +/- 1.4 l/min, all p less than 0.01). Mean systemic arterial blood pressure was no different in the two groups at rest or at matched submaximal work rates, whereas leg vascular resistance was higher in patients compared with normal subjects at rest, submaximal, and maximal exercise (all p less than 0.01). Although nonleg blood flow was decreased at rest in patients, it did not decrease significantly during exercise in either group. Peak exercise leg blood flow was related to peak exercise cardiac output in patients (r = 0.66, p less than 0.01) and normal subjects (r = 0.67, p less than 0.01). In patients, leg vascular resistance was not related to mean arterial blood pressure, pulmonary capillary wedge pressure, arterial catecholamines, arterial lactate, or femoral venous pH at rest or during exercise. Compared with normal subjects during submaximal exercise, patients demonstrated increased leg oxygen extraction and lactate production accompanied by decreased leg oxygen consumption. Thus, in patients with chronic heart failure compared with normal subjects, skeletal muscle perfusion is decreased at rest and during submaximal and maximal exercise, and local vascular resistance is increased. Our data indicate that nonleg blood flow and arterial blood pressure were preferentially maintained during exercise at the expense of leg hypoperfusion in our patients. This was associated with decreased leg oxygen utilization and increased leg oxygen extraction when compared to normal subjects, providing further evidence that reduced perfusion of skeletal muscle is important in causing early anaerobic skeletal muscle metabolism during exercise in subjects with this disorder.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Differential effects of aminopeptidase inhibitors on angiotensin-induced pressor responses.

Recent iontophoretic data suggest that conversion of angiotensin II (AII) to angiotensin III (AIII) may be necessary before the peptide can activate central angiotensin-sensitive neurons. Furthermore, this conversion may be inhibited by the aminopeptidase A inhibitor, amastatin. In the present study we investigated the importance of aminopeptidase activity on central angiotensin-induced pressor responses. Intracerebroventricular (i.c.v.) pretreatment with amastatin, suppressed i.c.v. AII-induced pressor responses. Pretreatment with the aminopeptidase B inhibitor, bestatin, increased pressor responses to AIII. Pressor responses induced by the aminopeptidase-resistant analogue, [Sar1]angiotensin II, were not affected by pretreatment with angiotensin inhibitors. These results support the hypothesis that AII must be converted to AIII to be active in the brain.

Aminopeptidases↗

A controlled trial of digoxin in congestive heart failure.

Because of conflicting results from studies examining the usefulness of digoxin in congestive heart failure (CHF) patients in sinus rhythm, a cross-over trial was conducted in which 20 patients received 7 weeks of digoxin titrated to a level of 1.54 to 2.56 nmol/liter and 7 weeks of matched placebo. The order of treatments was determined by random allocation and patients, clinicians and research staff were blind to allocation. In patients with deteriorating condition, the treatment period was terminated and outcome measures were obtained. If deterioration occurred during the first period, the patient was crossed over without the code being broken. Seven patients required premature termination of study periods because of increasing symptoms of CHF. All 7 were taking placebo at the time (p = 0.016). Small differences in dyspnea (p = 0.044), walking test score (p = 0.055), clinical assessment of CHF (p = 0.036) and ejection fraction (p = 0.004) favored the digoxin treatment group. Patients with more severe CHF were more likely to benefit from digoxin administration. It was concluded that oral digoxin, in doses titrated to produce a serum level of 1.54 to 2.56 nmol/liter, improved quality of life and functional exercise capacity in some patients with CHF in sinus rhythm.

Aged↗

Osteocutaneous free scapular flap for one-stage mandibular reconstruction.

Developments in microvascular surgery have overcome much of the problem of inadequate vascularity encountered by more conventional methods of mandibular reconstruction. The advantage of the osteocutaneous scapular flap compared with earlier described revascularized bone grafts or composite flaps is its greater versatility in reconstruction of soft-tissue defects of the oral cavity concomitant with mandibular reconstruction. This is primarily related to the independent vascular pedicles of the cutaneous and osseous portions of the flap. This flap is our preferred method of reconstructing mandibular defects.

Adult↗

Dose-response hearing loss for white noise in the Sprague-Dawley rat.

The effect of noise exposure on the inner ear is well documented. However, the sensitivity to noise-induced damage varies with animal species. The purpose of this investigation was to generate a hearing loss dose-response curve for a 20-day white noise exposure in the Sprague-Dawley rat. Eight male rats were exposed to 110, 100, 95 or 85 dB sound pressure level (SPL) for 6 hr/day, 5 days/week for 4 weeks in a sound-attenuated chamber fitted with a bank of overhead speakers. Controls were placed in an identical chamber without speakers. Four weeks after the exposure period ended, brainstem auditory evoked response (BAER) thresholds were recorded in all rats at 32, 16, 8, 4, 2, 1, and 0.5 kHz. Rats were then killed and cochlear tissues were processed for surface preparation. Hair cells were counted. Outer hair cell loss in the organ of Corti was observed in rats exposed to 95, 100, and 110 dB. Summary cytocochleograms were prepared for each rat by graphing the percentage of all hair cells remaining vs the percentage of distance along the basilar membrane as measured from the apex. The summary cytocochleograms were averaged and the area above this curve, corresponding to hair cell loss, was calculated. BAER threshold elevations (dB) were converted into percentage loss overall hearing function. Noise exposure level (dB) and (1) percentage area above the group average summary cytocochleogram and (2) percentage hearing loss were plotted as dose-response curves. Log-probit analysis was used to calculate ED50 noise exposure levels of 117 and 104 dB (SPL), (1), and (2), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of blood toluene levels after inhalation and oral administration.

The purpose of this investigation was to compare blood toluene levels in Sprague-Dawley rats after oral and inhalation administration. Groups of 30 rats were dosed by gavage with 86.7, 217, 433, or 867 mg toluene/kg body wt or exposed for up to 6 hr, 5 rats per exposure, to an atmosphere of either 200 or 1000 ppm toluene. Blood was sampled by cardiac puncture from 5 rats in each of the six dose groups at 0.5, 1.0, 2.0, 4.0, 6.0, and 24.0 hr after gavage dosing or the beginning of the inhalation exposure. Blood toluene levels were analyzed. A four-parameter model was fitted to the blood toluene levels of the orally dosed rats. The area under the curve generated by this model, representing total blood toluene concentration over 6 hr, was calculated and compared to the area under the blood toluene curve for the 6-hr inhalation exposure. Integrated areas from the two routes of exposure were used for direct comparison of oral and inhalation exposures. The data demonstrate that gavage dosing can be used to approximate inhalation exposure to toluene.

Administration, Inhalation↗

Inability of [125I]Sar1, Ile8-angiotensin II to move between the blood and cerebrospinal fluid compartments.

The angiotensin II competitive antagonist [125I]-Sar1, Ile8-angiotensin II was not transported from the vascular space to the cerebroventricular space in either intact or nephrectomized rats. In addition [125I]Sar1, Ile8-angiotensin II lacked the capacity to move in the opposite direction over a 20-min collection period following cerebroventricular infusion. These data suggest that angiotensins lack the capacity to move freely between the blood and cerebrospinal fluid compartments and are consistent with the notion that blood-borne and cerebroventricular angiotensins access different receptor populations.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities.

This study was designed to determine the pathophysiologic basis of increased exercise ventilation in the presence of chronic heart failure. Sixty-four ambulatory patients with chronic heart failure and 38 age-matched normal control subjects performed exercise according to identical staged, symptom-limited bicycle exercise protocols with measurement of hemodynamic, ventilatory, and metabolic responses. Compared with normal subjects, ventilation and the ratio of ventilation to CO2 production (Ve/VCO2), and pulmonary capillary wedge pressure were elevated in patients at rest and during exercise. The ratio of pulmonary dead space to tidal volume (Vd/Vt) also was elevated in the heart failure group at rest and during exercise and was closely related to Ve/VCO2 (all r greater than .72, p less than .001). Rest and exercise arterial PCO2 regulation was normal in patients. Peak exercise Ve/VCO2 did not correlate with pulmonary vascular pressures, but was inversely related to cardiac output (r = -.49, p less than .001). Thus, neurohumoral ventilatory control mechanisms are intact in patients with chronic heart failure and act to maintain normal PaCO2 levels in the face of increased pulmonary dead space. Activation of abnormal reflexes due to hemodynamic derangements during exercise are not important in determining ventilation in the presence of chronic heart failure. The demonstration of a correlation between decreased cardiac output and increased ventilation in the patient group suggests that attenuated pulmonary perfusion may play a role in causing exercise hyperpnea in the presence of chronic heart failure by producing ventilation perfusion abnormalities and thereby increasing physiologic pulmonary dead space.

Exercise Test↗

Exercise training in patients with severe left ventricular dysfunction. Hemodynamic and metabolic effects.

We studied the effects of exercise training in patients with chronic heart failure attributed to left ventricular dysfunction (ejection fraction, 24 +/- 10%). Twelve ambulatory patients with stable symptoms underwent 4-6 months of conditioning by exercising 4.1 +/- 0.6 hr/wk at a heart rate corresponding to 75% of peak oxygen consumption. Before and after training, patients underwent maximal bicycle exercise testing with direct measurement of central hemodynamic, leg blood flow, and metabolic responses. Exercise training resulted in a decrease in heart rate at rest and submaximal exercise and a 23% increase in peak oxygen consumption from 16.8 +/- 3.8 to 20.6 +/- 4.7 ml/kg/min (p less than 0.01). Heart rate, arterial lactate, and respiratory exchange ratio were unchanged at peak exercise after training. Maximal cardiac output tended to increase from 8.9 +/- 2.7 to 9.9 +/- 3.2 1/min and contributed to improved peak oxygen consumption in some patients, although this change did not reach statistical significance (p = 0.13). Rest and exercise measurements of left ventricular ejection fraction, left ventricular end-diastolic volume, and left ventricular end-systolic volume were unchanged. Right atrial, pulmonary arterial, pulmonary capillary wedge, and systemic arterial pressures were not different after training. Training induced several important peripheral adaptations that contributed to improved exercise performance. At peak exercise, systemic arteriovenous oxygen difference increased from 13.1 +/- 1.4 to 14.6 +/- 2.3 ml/dl (p less than 0.05). This increase was associated with an increase in peak-exercise leg blood flow from 2.5 +/- 0.7 to 3.0 +/- 0.8 l/min (p less than 0.01) and an increase in leg arteriovenous oxygen difference from 14.5 +/- 1.3 to 16.1 +/- 1.9 ml/dl (p = 0.07). Arterial and femoral venous lactate levels were markedly reduced during submaximal exercise after training, even though cardiac output and leg blood flow were unchanged at these workloads. Thus, ambulatory patients with chronic heart failure can achieve a significant training effect from long-term exercise. Peripheral adaptations, including an increase in peak blood flow to the exercising leg, played an important role in improving exercise tolerance.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗