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Effects of theophylline-ethylendiamine on chronic pulmonary arterial hypertension secondary to chronic obstructive pulmonary disease.

The use of theophylline in the treatment of chronic lung disease is wide spread thanks to the positive effects on the bronchial tree, on ventilation and on diaphragmatic contractile activity, which are well documented. On the other hand, the cardiovascular effects of this drug have not been studied much, particularly the effects on the hemodynamics of the pulmonary circulation. The latest studies were carried out by Parker (1966 and 1967) and by Jezek (1970) with heart catheterization and by Matthay (1978) with isotopic angiocardiography, but the problem has not been fully explored from the standpoint of pulmonary arterial hypertension. Therefore we are studying the effects of intravenous infusions of aminophylline in patients with chronic obstructive lung disease, trying to examine the effects of this drug on three different groups of patients: the 1st without pulmonary arterial hypertension; the 2nd with latent pulmonary arterial hypertension; the 3rd with evident pulmonary arterial hypertension. We consider pulmonary arterial hypertension as pulmonary arterial pressure greater than 20 mmHg at rest and pulmonary arterial pressure greater than 35 mmHg at the end of 8 min of exercise in the supine position, with 40 W load cycle ergometer. The experimental protocol includes the clinical and functional identification of subjects with chronic obstructive long disease, the performance of right heart catheterization and the cannulation of a peripheral artery, measuring all pressure levels, cardiac output, hemogasanalytic data and theophylline levels in steady state (20-30 min. after the end of invasive manoeuvres) at the 10th, 20th and 30th min after the end of an infusion of 10 mg/kg of aminophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Ventilatory failure during loaded breathing: the role of central neural drive.

Minute ventilation (VE), arterial blood gases, diaphragmatic electromyogram (EMG) activity, centroid frequency (Fc) and peak inspiratory airway pressures (Paw) were measured in five unanesthetized tracheostomized infant monkeys during various intensities of inspiratory resistive loaded breathing (IRL) until either 1) ventilatory failure occurred (failed trial) or 2) normocapnia was sustained for 1 h (successful trial). During successful trials VE and arterial PCO2 (PaCO2) were sustained at base-line levels, and an increase in peak integrated diaphragmatic EMG activity and peak inspiratory Paw occurred. In contrast, during ventilatory failure runs, VE decreased and PaCO2 rose compared with their respective base-line values. The fall in VE occurred secondary to a significant decline in breathing frequency. Tidal volume was sustained at base-line levels during all trials (both successful and failed groups). Inspiratory Paw's and peak moving time average EMG were sustained at elevated levels during ventilatory failure runs, suggesting that the respiratory muscles did not fail as pressure generators. Furthermore, the EMG Fc did not change from base line during either successful or failed trials. These data suggest that peripheral muscle fatigue did not occur, although in the absence of a more direct test of muscle performance, i.e., a force-frequency curve, we cannot rule out the possibility that a component of peripheral failure contributed to our results. Ventilatory failure during severe IRL in the infant monkey was most clearly associated with an alteration in the respiratory center timing mechanism, i.e., such failure was a function of a decline in respiratory frequency.

Animals↗

Hyperinflation and respiratory muscle interaction.

Hyperinflation clearly affects respiratory muscle interaction. It commonly increases the rib cage contribution to chest wall motion, whilst it reduces the abdominal contribution. This change is thought to result from the fact that hyperinflation severely reduces the mechanical advantage of the diaphragm, whilst it affects the mechanical advantage of the neck and rib cage muscles to a lesser extent. The mechanical disadvantage in the diaphragm induced by hyperinflation is presumably primarily the result of the length changes undergone by the diaphragm in acute hyperinflation. Changes in diaphragmatic geometry are generally considered to be less important in the reduction of the diaphragm's force-generating capacity. Further factors contributing to the mechanical disadvantage in the diaphragm include a reduction in the appositional component of diaphragmatic action (through reduction in the zone of apposition), and a reduction in the insertional component (through a shift in the alignment of the diaphragmatic fibres from axial to radial). In chronic hyperinflation, the diaphragm adapts to the chronically hyperinflated state. This adaptation to chronic foreshortening is similar to the adaptation occurring in the skeletal muscle. It is caused by a dropout of sarcomeres in series along the muscle fibres. It restores the force-generating capacity of the muscle, in part, but it reduces the capacity of the muscle to undergo length changes. The mechanical advantage of the parasternal intercostals and the scalenes is possibly less affected, because the length changes undergone by these muscles during hyperinflation are smaller. The factors determining the mechanical advantage of the parasternal intercostals are complex. Variables related to the mechanical advantage of the parasternal intercostals include: length changes; changes in angle between the parasternal intercostals and the sternum and between rib and sternum; and changes in mechanical arrangement among different parasternals. At present, it is difficult to develop an integrated view of these factors and of their change with hyperinflation. Finally, hyperinflation commonly results in recruitment of expiratory muscles. The functional significance of this expiratory muscle recruitment in patients is still debated.

Diaphragm↗

Hepatic toxocariasis: US, CT and MRI findings.

Visceral larva migrans (VLM) most commonly occurs as a febrile disease of childhood particularly affecting children between 1 and 7 years of age. Pulmonary, dermatological, hepatic, lymphatic, cardiac, rheumatological and neurological manifestations may occur. VLM seems to be a rare disease in adults. We report the imaging findings of a woman with hepatic toxocariasis. Ultrasonography showed a solitary hepatic lesion measuring 4 x 3 cm, displaying a hypoechoic-heterogeneous pattern with ill-defined borders and distal acoustic enhancement, located in the right sub-diaphragmatic area. Two enlarged periportal lymph nodes and moderately dilated intrahepatic biliary ducts were also noted. The probability of toxocariasis was discussed, based on sonographic and biopsy findings, and the final diagnosis was confirmed by a specific ELISA test. In summary, a clinical picture of cholestasis initially resembling hepatitis or malignancy should be further evaluated by imaging techniques, and the ultrasound examiner should be familiar with the possible findings of hepatic toxocariasis, which consist of focal ill-defined hepatic lesions, hepato-splenomegaly, biliary dilatation, sludge and periportal lymph node enlargement.

Adult↗

The relation of ventilatory failure to pulmonary, respiratory muscle and central nervous system disturbances in calves with an experimentally produced pneumonia.

To explore the pathophysiology of respiratory failure in an experimental pneumonia, a Pasteurella haemolytica broth culture was injected intratracheally into 12 calves, which were then studied over a period of 10 h. Measurements were made of inspired minute ventilation (VE), ventilatory pattern [inspiratory time (TI), expiratory time (TE), respiratory rate (RR) and tidal volume (VT)], transdiaphragmatic pressure (Pdi), occlusion pressure at the airway opening 100 milliseconds after onset of inspiration (Pawo100ms), arterial blood gas tensions and pH and recorded diaphragmatic electromyogram (EMGdi) and rectal temperature (Tr). On and after the third hour after inoculation, the animals varied in respect of clinical signs, Tr, RR, VE, Pawo100ms/EMGdi, and arterial gases and pH. In benign cases, diminished alertness, laboured respiration and fall of arterial oxygen pressure (PaO2) worsened up to 7 h after inoculation, but then progressively improved, VE being maintained at approximately 150% baseline throughout the study (10 h). Neither arterial carbon dioxide pressure (PaCO2) nor pH was altered. Moderate cases resembled benign cases in respect of laboured respiration, VE, PaO2 and PaCO2; however, pH was at first maintained at preinoculation levels, but declined thereafter. In severe cases, the animals were drowsy between hours 3 and 7, and became comatose between hours 8 and 10; in contrast to both benign and moderate cases: (1) RR was reduced by hour 5, (2) there was no trend towards recovery of PaO2 and pH, (3) VE, Pdi, Pawo100ms and Pawo100ms/EMGdi were severely decreased, and (4) PaCO2 increased. These results suggest that pneumonia does not alter ventilatory neuromuscular pump function in calves, unless concomitant cardiovascular collapse occurs. It is not clear whether fatal ventilatory failure is caused mainly by deterioration in ventilatory muscle fibre processes or structures, altered central nervous system adjustment of ventilatory timing, or cardiovascular dysfunction. However, inspiratory pressures fall when excitation to the diaphragm is still growing, which suggests peripheral respiratory muscle fatigue.

Acidosis, Respiratory↗

Lung interdependence and lung-chest wall interaction of sublobar and lobar units in pigs.

In anesthetized and paralyzed pigs in the left decubitus position we obstructed, at functional residual capacity (FRC), either the right middle and lower lobes, or a small posterior basal lung unit, and then passively inflated the unobstructed remaining lung. Measurements were made of alveolar pressure in the obstructed and unobstructed lung regions as well as of esophageal pressure. The tendency of the obstructed lung region to inflate as the remainder of the lung was inflated was assessed by an index (A), which was the end-inspiratory pressure difference between unobstructed and obstructed alveolar pressures, normalized by the change in elastic recoil of unobstructed lung. With the chest wall intact, inflation of unobstructed lung resulted in a tendency to inflate the obstructed regions. This tendency was abolished with the chest wall removed. In a second group of pigs with the basilar lung unit obstructed, the height of the unit was changed by turning a pig from right to left decubitus positions. In each position A was assessed with both spontaneous and positive pressure ventilation. The magnitude of A was found to vary directly with the magnitude of caudal diaphragmatic motion and was greatest with the lung unit dependent and with spontaneous ventilation. These results suggest that lung-chest wall interaction was a more important factor tending to preserve homogenous inflation than lung tissue interdependence.

Animals↗

Effects of emphysema on diaphragm microvascular oxygen pressure.

Pulmonary emphysema impairs lung and respiratory muscle function leading to restricted physical capacity and accelerated morbidity and mortality consequent to respiratory muscle failure. In the absence of direct evidence, an O2 supply-demand imbalance within the diaphragm and other respiratory muscles in emphysema has been considered the most likely explanation for this failure. To test this hypothesis, we utilized phosphorescence quenching techniques to measure mean microvascular PO2 (PO2m) within the medial costal diaphragm of control (C, n = 10) and emphysematous (E, elastase instilled, n = 7) hamsters. PO2m and mean arterial pressure (MAP) were measured in the spontaneously breathing anesthetized hamster at inspired O2 percentages of 10, 21, and 100, and across a range of mean MAPs from 40 to 115 mm Hg. At each inspired O2, diaphragm PO2m was significantly (p < 0.05) lower in E animals (10%: C, 19 +/- 3; E, 9 +/- 2; 21%: C, 32 +/- 2; E, 21 +/- 2; 100%: C, 60 +/- 8; E, 36 +/- 9 mm Hg). At 21% inspired O2, the PO2m decrease was correlated with reduced MAP in both C (r = 0.968) and E (r = 0.976) animals. We conclude that diaphragmatic PO2m (and therefore microvascular O2 content) is decreased in emphysematous hamsters reflecting a greater diaphragmatic O2 utilization at rest and a lower O2 extraction reserve. According to Fick's law, this lower PO2m will mandate an exaggerated fall in intramyocyte PO2, which is expected to accelerate muscle glycogen depletion and consequently fatigue. This provides empirical evidence in support of one possible mechanism for respiratory muscle failure in emphysema.

Analysis of Variance↗

Physiological determinants of inspiratory effort sensation during CO2 rebreathing in normal subjects.

1. The physiological basis of inspiratory effort sensation remains uncertain. Previous studies have suggested that pleural pressure, rather than inspiratory muscle fatigue, is the principal determinant of inspiratory effort sensation. However, only a limited range of inspiratory flows and breathing patterns have been examined. We suspected that inspiratory effort sensation was related to the inspiratory muscle tension-time index developed whatever the breathing pattern or load, and that this might explain the additional rise in sensation seen with hypercapnia. 2. To investigate this we measured hypercapnic rebreathing responses in seven normal subjects (six males, age range 21-38 years) with and without an inspiratory resistive load of 10 cm H2O. Pleural and transdiaphragmatic pressures, mouth occlusion pressure and breathing pattern were measured. Diaphragmatic and ribcage tension-time indices were calculated from these data. Inspiratory effort sensation was recorded using a Borg scale at 30s intervals during each rebreathing run. 3. Breathing pattern and inspiratory pressure partitioning were unrelated to changes in inspiratory effort sensation during hypercapnia. Tension-time indices reached pre-fatiguing levels during both free breathing and inspiratory resistive loading. 4. Stepwise multiple regression analysis using pooled mechanical, chemical and breathing pattern variables showed that pleural pressure was more closely related to inspiratory effort sensation than was transdiaphragmatic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparative formaldehyde-induced and glyoxylic acid-induced fluorescence histochemical studies on the intrinsic adrenergic innervation of the intestine and the liver of normal and vagotomized cats.

The inbuilt intrinsic adrenergic nervous apparatus of the intestine and liver of the cat was studied using 1. the formaldehyde-induced fluorescence histochemical method and 2. the glyoxylic acid-induced fluorescence histochemical method for serial microtome sections and whole mount tissue layers or smear preparations. In addition, the effect of I) total abdominal infra-diaphragmatic vagotomy with or without associated Finney-type gastro-duodenostomy and II) unilateral (left or right) and bilateral cervical vagotomy with or without tracheostomy on the intrinsic adrenergic innervation was tested. Fluorescing varicose axons, both "free" (i.e. unrelated to the blood vessels) and gathered to typical perivascular nerve plexuses were observed in all segments and all layers of the wall of the intestine. The density of the adrenergic innervation varied remarkably from an area to another, even in the same segment and tissue layer, which makes comparative estimations of the density of the innervation very difficult. However, the intrinsic adrenergic innervation of the circular muscle layer of the colon and the rectum seems to be consistently quite rich, and in the rectum, also the longitudinal muscle layer is relatively heavily innervated. It thus seems obvious that (in the cat) also the direct adrenergic innervation of the external smooth muscle layers is of considerable importance, specially in the rectum. In contrast, the results of the present study clearly indicate that the liver parenchyma (of the cat) is devoid of functional intrinsic adrenergic innervation. Vagotomies did not cause any changes in the intrinsic adrenergic innervation of the intestine and liver: even after complete vagotomy no reduction was observed in the number of fluorescing axons or in the intensity of the fluorescence. Consequently, the vagal contribution of adrenergic axons to the liver and the intestine must be negligible, at least in the cat. The use of the glyoxylic acid-induced fluorescence histochemical method and whole-mount tissue layers was found most suitable for mapping and comparative estimation of the density of the intrinsic adrenergic nerve net, and is therefore recommended for other similar or related studies.

Adrenergic Fibers↗

Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease.

RATIONALE: Oxidative stress is involved in the skeletal muscle dysfunction observed in patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that the diaphragms of such patients might generate greater levels of oxidants than those neutralized by antioxidants. OBJECTIVES: To assess the levels of both oxidative and nitrosative stress and different antioxidants in the diaphragms of those patients, and to analyze potential relationships with lung and respiratory muscle dysfunctions. METHODS AND MEASUREMENTS: We conducted a case-control study in which reactive carbonyl groups, hydroxynonenal-protein adducts, antioxidant enzyme levels, nitric oxide synthases, and 3-nitrotyrosine formation were detected using immunoblotting and immunhistochemistry in diaphragm specimens (thoracotomy) obtained from six patients with severe COPD, six patients with moderate COPD, and seven control subjects. MAIN RESULTS: Diaphragms of patients with severe COPD showed both higher protein carbonyl groups and hydroxynonenal-protein adducts than control subjects. When only considering patients with COPD, negative correlations were found between carbonyl groups and airway obstruction, and between hydroxynonenal-protein adducts and respiratory muscle strength. Although diaphragmatic neuronal nitric oxide synthase did not differ among the three groups and no inducible nitric oxide synthase was detected in any muscle, muscle endothelial nitric oxide synthase was lower in patients with severe COPD than in control subjects. Muscle nitrotyrosine levels were similar in both patients with severe COPD and control subjects. CONCLUSIONS: This study shows that oxidative stress rather than nitric oxide is likely to be involved in the respiratory muscle dysfunction in severe COPD.

Aged↗

Configuration of the chest wall and occlusion pressures in awake humans.

During CO2 rebreathing in sitting position seven of nine conscious men showed a progressive fall in expiratory reserve volume, most of it due to a decrease in abdominal volume. Diaphragm length at end expiration was thus increased, and some elastic recoil pressure became available to drive inspiration. In four out of six subjects, when CO2 tension was greater than 55 Torr, there was a dip in abdominal pressure at the beginning of inspiration, and the change in transdiaphragmatic pressure during the first 100 ms of an occluded inspiration was smaller than the simultaneous change in mouth pressure (P0.1). In the subjects who showed the smallest diaphragmatic pressure in this 100 ms, electromyogram recordings showed that abdominal activity ceased before the onset of inspiration, and diaphragm activity did not appear until later than 100 ms into inspiration. We conclude that, in four our of our six subjects in the sitting posture, P0.1 can be generated in whole or in part by release of chest wall elastic recoil or in intercostal muscle contraction. In the supine posture, there was no change by end-expiratory chest wall configuration, and onset of diaphragm contraction coincided with beginning of inspiration in the two subjects in whom diaphragm electromyogram was recorded.

Abdomen↗

Central and peripheral cardio-respiratory effects of saxitoxin (STX) in urethane-anesthetized guinea-pigs.

Effects of saxitoxin (STX; 10 micrograms/kg; i.p.) on cardio-respiratory activities were evaluated in urethane-anesthetized guinea-pigs. Concurrent recordings were made of electrocorticogram (ECoG), bulbar respiratory-related unit activities, diaphragmatic electromyogram (DEMG), electrocardiogram (Lead II ECG), blood pressure, heart rate, end-tidal CO2, arterial O2/CO2 tensions, and arterial pH. The average time to STX-induced respiratory failure was about 10 min. The most striking effect prior to apnea was a state of progressive bradypnea which emerged 5-7 min after the toxin administration. Other noteworthy responses included (i) a time-dependent decrease in ECoG amplitudes which typically began before the development of a bradypneic profile; (ii) an increasing degree of diaphragm neuromuscular blockade; (iii) a state of combined hypercapnia and uncompensated acidemia; (iv) a declining blood pressure; (v) an incrementally dysfunctional myocardial performance; and (vi) an increasingly degenerative central respiratory activity profile which ultimately culminated in a complete loss of central respiratory drive. The therapeutic effect of intratracheally administered oxygen was equivocal in that the cardio-respiratory activities, be they of central of peripheral nature, remained conspicuously dysfunctional and precarious despite 100% oxygen ventilation. What can be inferred from this study is two-fold. First, STX-induced ventilatory insufficiency can be attributed to a loss of functional integrity of both central and peripheral respiratory system components. That is, although diaphragm blockade contributes significantly to STX-induced respiratory failure, analyses of single respiratory unit activity data revealed that the central respiratory rhythmogenic mechanism also appeared to play a pivotal role in the development of a bradypneic profile which promotes, and directly causes, a complete loss of respiratory drive. Second, a state of unabating depression of central respiratory activities, which seemed to be refractory to the effect of O2, suggests STX has a direct and persistent action on medullary rhythmogenic mechanisms. In conclusion, these findings indicate that both central and peripheral cardio-respiratory components are critically involved in STX-induced apnea, dysfunctional cardiovascular performance, and lethality.

Anesthesia↗

Complications and failings of the combined Collis-Belsey operation.

Eighty-three patients with risk factors predisposing to recurrent reflux after standard hiatal hernia repairs have undergone the Collis-Belsey operation. There were two postoperative deaths. Complications related to multiple operations on the lower esophagus included injury to the spleen (three patients); gastrocutaneous fistula (two patients), and localized ischemic necrosis of esophagus two patients). There were two esophageal perforations. In four of 15 patients, the combination of esophagomyotomy and the Collis-Belsey operation produced functional esophageal obstruction. Three patients have experienced late major lower esophageal bleeding from ulceration of mucosa adjacent to the gastroplasty tube; two the these patients have no demonstrable gastroesophageal reflux. In addition to postoperative interviews and barium swallows, 77 patients have been evaluated with esophageal manometry and acid reflux testing. After an average follow-up of 12 montsh, 19 percent have symptomatic reflux, but 30 percent have moderate-to-severe reflux with pH reflux testing. The recent enthusiasm for the combined Collis-Belsey operation should be tempered by continued, cautious, objective assessment of its long-term results.

Adolescent↗

[The relationship between mouth pressure or tracheal pressure and esophagus pressure and diaphragmatic pressure].

OBJECTIVE: To investigate the relationship between mouth pressure (Pmo) or tracheal pressure (Ptr) and esophagus pressure (Pes) or transdiaphragmatic pressure. METHODS: Seventeen patients were involved in the study. Maximal inspiratory pressure (MIP), maximal transdiaphragmatic pressure (Pdi(max)), maximal esophagus pressure (Pes(max)), twitch mouth pressure (TwPmo), twitch transdiaphragmatic pressure (TwPdi) and twitch esophagus pressure (TwPes) were measured before narcotization as a normal procedure for the abdominal operation and twitch tracheal pressure (TwPtr(nar)), twitch esophagus pressure (TwPes(nar)) and twitch transdiaphragmatic pressure (TwPdi(nar)) were dynamically monitored during narcotization. RESULTS: (1) The correlation coefficient (r) values between Pdi(max) and MIP, TwPdi and TwPmo, TwPdi(nar) and TwPtr(nar), Pes(max) and MIP, TwPes and TwPmo, TwPes(nar) and TwPtr(nar) were 0.976 +/- 0.030, 0.816 +/- 0.155, 0.923 +/- 0.446, 0.981 +/- 0.185, 0.829 +/- 0.168 and 0.955 +/- 0.292, respectively. (2) The coefficient variation (CV) of MIP, Pes(max), Pdi(max), TwPmo, TwPes and TwPdi were (14.2 +/- 4.7)%, (15.2 +/- 4.3)%, (15.5 +/- 4.1)%, (30.4 +/- 15.9)%, (10.8 +/- 5.1)% and (9.9 +/- 4.0)%, respectively. The CV of TwPmo was the highest (compare with others, all P < 0.05) and that of TwPes and TwPdi was the lowest (compare with others, all P < 0.05). There was no significant difference among MIP, Pes(max) and Pdi(max) (P > 0.05). (3) The r value between the changing values of TwPtr(nar) and TwPdi(nar) or TwPes(nar) during narcotization were 0.839 or 0.894 (P = 0.000, respectively). CONCLUSION: The measurement of MIP and TwPmo should be repeated and the highest value should be chosen in order to reduce the possibility of underestimating the function of diaphragm, which could be dynamically monitored by TwPtr(nar).

Abdomen↗

The current status of single lead dual chamber sensing and pacing.

The use of single lead, atrial synchronous ventricular (VDD) pacing in patients with high grade atrioventricular (AV) block and normal sinus node function is an acceptable alternative to dual chamber (DDD) pacing. Implantation and follow up procedures are simplified, and cost is usually reduced by more than the cost of an additional atrial lead. With the use of either diagonally arranged dipole or closely spaced ring electrodes, reliable atrial sensing can be achieved using differential atrial amplifier and high atrial sensitivity. Also oversensing is infrequently observed using provocation tests and dynamic recordings, clinical undersensing is unusual and minimized by programming to the highest atrial sensitivity. However, as atrial pacing is not possible, loss of AV synchrony and rate response may occur for unrecognized or progressive sinus node disease and lower rate limit. The development of single lead dual chamber pacing system may overcome this limitation. Recent studies have demonstrated that atrial pacing can be effective either with the use of a special pacing lead configuration or via floating atrial electrode with a novel stimulation method. Overlapping Biphasic Impulse (OLBI) can reduce atrial pacing threshold. Early clinical experience suggested that this new pacing method can provide effective and reliable atrial pacing with a relatively low incidence of diaphragmatic pacing. Thus the problem of atrial sensing is solved with a single pass lead but further long term evaluation is required to assess the efficacy and feasibility of new instrumentation for single lead dual chamber pacing.

Cardiac Pacing, Artificial↗

Atrial sensing and pacing with a single pass ventricular lead.

The use of single lead for atrial synchronous ventricular (VDD) pacing in patients with high grade atrioventricular (AV) block and normal sinus node function is an acceptable alternative to dual chamber (DDD) pacing. Implantation and follow up procedures are simplified, and cost is usually reduced by more than the cost of an additional atrial lead. With the use of either diagonally arranged dipole or closely spaced ring electrodes, reliable atrial sensing can be achieved using differential atrial amplifier and high atrial sensitivity. Also oversensing is infrequently observed using provocation tests and dynamic recordings, clinical undersensing is unusual and minimized by programming to the highest atrial sensitivity. However, as atrial pacing is not possible, loss of AV synchrony and rate response may occur for unrecognized or progressive sinus node disease and lower rate limit. The development of single lead dual chamber pacing system may overcome this limitation. Recent studies have demonstrated that atrial pacing can be effective either with the use of a special pacing lead configuration or via floating atrial electrode with a novel stimulation method. Overlapping biphasic impulse (OLBI) can reduce atrial pacing threshold. Early clinical experience suggested that this new pacing method can provide effective and reliable atrial pacing with a relatively low incidence of diaphragmatic pacing. Thus the problem of atrial sensing is solved with a single pass lead but further long term evaluation is required to assess the efficacy and feasibility of new instrumentation for single lead dual chamber pacing.

Cardiac Pacing, Artificial↗

Effect of alterations in muscle fiber length on diaphragm blood flow.

A variety of studies have examined the response of diaphragmatic blood flow (Qdi) to rhythmic pleiometric (i.e., shortening) and isometric contractions. The effect of changes in diaphragm fiber length on Qdi are, however, unknown. The present study examined the effect of changes in diaphragm fiber length on Qdi and the effect of alterations in length on the response of Qdi to increases in diaphragm contractile activity. Studies were performed on 21 anesthetized mechanically ventilated dogs in which a strip of costal diaphragm was developed in situ. The strip was immobilized in a rigid metal frame that permitted precise adjustment of muscle length. Strip blood flow was assessed with a drop counter attached to a catheter in the branch of the phrenic vein draining the strip. Strips were electrically stimulated via intramuscular electrodes, and the isometric tension developed was measured with a force transducer. Fiber length was expressed as a percentage of the length at which active isometric tension was maximum (Lo). With the diaphragm at rest, steady-state blood flow fell by 59 +/- 6% (SE) (P less than 0.001) as fiber length was increased from 92 to 107% Lo. Blood flow also varied as a function of length when muscles contracted rhythmically (15 contractions/min, duty cycle 50%) to generate isometric tensions equal to 20 and 80% of maximum. As fiber length increased from 92 to 106% Lo, Qdi fell by 36 +/- 6% (SE) when tension was 80% of maximum (P less than 0.01) and by 38 +/- 6% (SE) when tension was 20% of maximum (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synchronously stimulated skeletal muscle graft for myocardial repair. An experimental study.

We studied the feasibility of augmentation of impaired myocardium with synchronously paced skeletal muscle grafts. The short contractile period of skeletal muscle required development of a new stimulator to ensure that the pedicle graft contraction would simulate that of the myocardium. In four dogs each, rectus and diaphragmatic muscles were wrapped around a balloon and electrically stimulated in synchrony with the electrocardiogram, varying stimulation currents and frequency of discharge during systole. For this purpose, a prototype hybrid stimulator was developed which senses the cardiac R wave and modulates the electrical output to the skeletal muscle by delivering a train of impulses of varying frequencies within the systolic intervals. The contraction characteristics in response to such stimulation were similar in rectus and diaphragmatic muscles, but the former developed higher maximum tensions because of the greater muscle bulk. Square-wave output was found to be more effective than sine-wave stimulation, and a single stimulating electrical pulse of 40 msec duration produced a maximum tension of 60 mm Hg lasting for 120 msec, whereas a train of 4 pulses within a 320 msec period was able to achieve a maximum tension of 100 mm Hg lasting nearly 400 msec, the latter approximating that of the myocardium. In six other dogs, the rectus muscle pedicle graft was used to replace a segment of the left ventricle (25.5% +/- 2.1% of left ventricular mass) excised under cardiopulmonary bypass. Left ventricular isometric contraction was studied using a left ventricular balloon with stimulators turned on and off. Significant augmentations of left ventricular maximum tension (+19.3% +/- 2.5%, p less than 0.001, paired t test) and left ventricular contractility (+38.3% +/- 9.4%, p less than 0.001) were achieved when the skeletal muscle grafts were stimulated. Thus, in this preliminary study, skeletal muscle graft properly oriented and stimulated is able to augment the left ventricular isometric contractile function after significant loss of left ventricular myocardial mass.

Abdomen↗