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PubMed2001

Morphological and functional recovery from diaphragm injury: an in vivo rat diaphragm injury model.

Our objective was to develop an in vivo model to study the timing and mechanisms underlying diaphragm injury and repair. Diaphragm injury was induced in anesthetized rats by the application of a 100 mM caffeine solution for a 10-min period to the right abdominal diaphragm surface. Diaphragms were removed 1, 4, 6, 12, 24, 48, 72, and 96 h and 10 days after the injury, with contractile function being assessed in strips in vitro by force-frequency curves. The extent of caffeine-induced membrane injury was indicated by the percentage of fibers with a fluorescent cytoplasm revealed by inward leakage of the procion orange dye. One hour after caffeine exposure, 32.9 +/- 3.1 (SE) % of fibers showed membrane injury that resulted in 70% loss of muscle force. Within 72-96 h, the percentage of fluorescent cells decreased to control values. Muscle force, however, was still reduced by 30%. Complete muscle strength recovery was observed 10 days after the injury. Whereas diaphragmatic fiber repair occurred within 4 days after injury induction, force recovery took up to 10 days. We suggest that the caffeine-damaged rat diaphragm is a useful model to study the timing and mechanisms of muscle injury and repair.

Animals↗

PubMed1992

[Dyspnea and ventilatory muscle function during exercise on air and oxygen breathing in patients with chronic obstructive pulmonary disease (COPD)].

Exercise performance and dyspnea in COPD patients have been shown to be improved with supplemental oxygen, although the exact mechanisms resulting in the improvement are still unclear. The purpose of the present study was to investigate a possible relationship between ventilatory muscle function and sensation of dyspnea (modified Borg Scale) during exercise on 20% O2 and 30% O2. Eight patients with COPD (FEV1 1.06 L +/- 0.30 L) exercised on a treadmill two times breathing compressed air or 30% oxygen with a one hour rest in between. The electrical activity of the diaphragm (EMGdi) was recorded with esophageal electrodes, and that of the sternomastoid muscle (EMGsm) was recorded from the fine wire electrodes. The ratio of high frequency (150 to 350 Hz) to low frequency (20 to 47 Hz) power (H/L) of EMGdi was analyzed to assess diaphragmatic fatigue, which was defined as a 20% fall of H/L ratio from the control value. Flow, volume, O2 Saturation (SaO2), esophageal pressure (Pes) and transdiaphragmatic pressure (Pdi) were measured. Tension time index (TTdi) was calculated from Pdi and the ratio of inspiratory time to total time for one cycle (Ti/Ttot). At rest, we measured maximal esophageal pressure (Pesmax), maximal transdiaphragmatic pressure (Pdimax), maximal integrated EMGdi (EMGdimax) and EMGsm (EMGsmmax). Incremental exercise was discontinued by dyspnea. The walking distance achieved was increased in all patients on 30% O2. Dyspnea and desaturation were significantly improved on 30% O2 breathing, and the onset of diaphragmatic fatigue was delayed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Functional importance of a highly elastic ligament on the mammalian diaphragm.

The diaphragm of mammals is a musculotendinous dome separating the thoracic and abdominal cavities. With no skeletal elements to stretch it, the diaphragm has the problem of positioning its muscle fibres at a length appropriate for the onset of an inspiratory contraction. This is achieved through a negative intrapleural pressure, resulting from the opposing elastic recoil of the ribcage and lungs, which sucks the diaphragm into the thorax and extends the muscle fibres. A consequence of this negative pressure is that the diaphragm muscle is under tension when inactive during expiration. This is an unusual condition for skeletal muscles, which can suffer irreversible changes when stretched to long length, or they may respond by growing longer. We now describe a highly elastic and resilient diaphragmatic ligament which sets a sarcomere length enabling the muscle to use its full operating range, reduces stress on the diaphragm muscle fibres, and assists shortening of the diaphragm muscle at the onset of inspiration by means of elastic recoil.

Animals↗

PubMed1989

Congenital myotonic dystrophy: respiratory function at birth determines survival.

The clinical features of 14 neonates with congenital myotonic dystrophy were retrospectively reviewed. These babies represent all the new cases of congenital myotonic dystrophy seen in this department since 1982. Twelve babies were referred because of either difficulties in diagnosis or difficulties in the management of their respiratory problems. Of the 14 babies, 13 had birth asphyxia, 11 were premature, and four had intrauterine growth retardation. Ten babies required artificial ventilation from birth. Abnormalities on chest radiography included thin ribs (n =9) and raised right hemidiaphragms (n = 5). Recurrent episodes of collapse and consolidation of the lungs secondary to poor swallowing occurred in all ventilated babies. All babies ventilated for longer than four weeks died of respiratory complications before the age of 15 months. One baby was successfully extubated after diaphragmatic plication, but he died a few months later. Duration of ventilation was the best guide to prognosis.

Female↗

PubMed2001

Investigation of the intra-abdominal oesophagus and hiatus in fetal rats with oesophageal atresia and tracheo-oesophageal fistula.

After surgical management of their oesophageal atresia (OA) and tracheo-oesophageal fistula (TOF), most patients exhibit evidence of gastro-oesophageal reflux (GOR) and many have oesophagitis. However, the aetiology of the GOR is still controversial. This study was undertaken to document whether there are congenital abnormalities in the intra-abdominal oesophagus and the hiatus in the fetal rat with OA and TOF following exposure to adriamycin (ADR). Time-pregnant rats were injected daily with either saline or 2 mg/kg ADR intraperitoneally on gestational days (GD) 6-9. The fetuses (n = 56) from 8 litters were harvested on GD 21 for examination. The length of the oesophagus between the diaphragmatic crura and the gastro-oesophageal junction (GOJ) and the sizes of the stomach and the oesophageal hiatus were measured under a dissecting microscope. The length of the oesophagus between the diaphragmatic crura and the GOJ in the ADR-treated fetuses (0.85 +/- 0.37 mm) was significantly shorter than in control fetuses (2.41 +/- 0.32 mm) (P < 0.0001). The size of the stomach in ADR-treated fetuses (5.30 +/- 1.01 mm) was significantly smaller than in the controls (8.07 +/- 0.49 mm) (P < 0.001). Moreover, the size of the oesophageal hiatus in ADR-treated fetuses (1.16 +/- 0.43 mm) was markedly larger than in the controls (0.32 +/- 0.1 mm) (P < 0.0001). These results showed that the congenital abnormalities in ADR-treated rat fetuses may account for the oesophageal functional disorders seen after surgical correction in patients who have OA and TOF.

Abnormalities, Drug-Induced↗

PubMed1997

Chronic congestive heart failure elicits adaptations of endurance exercise in diaphragmatic muscle.

BACKGROUND: During rest and exercise, patients with heart failure hyperventilate; therefore, the diaphragm can be viewed as undergoing constant moderate-intensity exercise. Accordingly, we hypothesized that heart failure elicits adaptations in the diaphragm similar to those elicited by endurance exercise in the limb muscles of normal subjects. METHODS AND RESULTS: Costal diaphragmatic biopsy samples were obtained from 7 normal subjects (age, 36 +/- 20 years) and 10 patients (age, 50 +/- 6 years; left ventricular ejection fraction, 18 +/- 8%) at the time of transplant or left ventricular assist-device placement. We measured the distribution of myosin heavy chain isoforms I, IIa, and IIb by SDS gel electrophoresis. We also measured the activities of the following enzymes: citrate synthase, a marker of oxidative metabolism; beta-hydroxyacyl-CoA dehydrogenase, a marker of lipolytic metabolism; and lactate dehydrogenase, a marker of glycolytic metabolism. In normal subjects, the distribution of myosin heavy chain isoforms I, IIa, and IIb was 43 +/- 2%, 40 +/- 2%, and 17 +/- 1%, respectively. In contrast, in heart failure subjects, the fiber distribution was 55 +/- 2%, 38 +/- 2%, and 7 +/- 2% for types I, IIa, and IIb, respectively. Therefore, in heart failure, myosin heavy chain I is increased (P < .0001) and myosin heavy chain IIb decreased from normal levels (P < .001). Additionally, citrate synthase activity (normal, 0.33 +/- 0.14; heart failure, 0.54 +/- 0.21 mumol.min-1.mg protein-1; P < .05) and beta-hydroxyacyl-CoA dehydrogenase activity (normal, 0.27 +/- 0.04; heart failure, 0.38 +/- 0.02 mumol.min-1.mg protein-1; P < .05) were greater in heart failure patients than in normal subjects, whereas lactate dehydrogenase activity was significantly less in heart failure patients than in normal subjects (normal, 11.6 +/- 4.6; heart failure,: 4.3 +/- 2.2 mumol.min-1.mg protein-1; P < .01). CONCLUSIONS: In the diaphragm in heart failure, there is a shift from fast to slow myosin heavy chain isoforms with an increase in oxidative capacity and a decrease in glycolytic capacity. These diaphragmatic muscle changes are consistent with those elicited by endurance training of the limb muscles in normal subjects.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2003

Prognostic features of residual pleural thickening in parapneumonic pleural effusions.

The objective of the study was the identification of predictive factors for the development of residual pleural thickening (RPT) in patients with parapneumonic effusion. The design of the prospective study involved investigating patients with parapneumonic pleural effusions diagnosed between March 1991 and December 2000 in the respiratory department of Hospital Ramón y Cajal (Madrid, Spain) which is a 1,500 tertiary-care hospital. The clinical and radiological characteristics and measurements of microbiological and biochemical variables in the pleural fluid taken from the patients were studied. RPT was defined in a posteroanterior chest radiograph as pleural thickening of > or = 10 mm measured at the lateral chest wall at the level of an imaginary line, tangent to the diaphragmatic dome. A total of 48 of the 348 patients studied (13.79%) were found to have RPT. Among the factors studied, only presence of pus in the pleural space, Fine classes IV and V, temperature > or = 38 degrees C and delayed resolution of pleural effusions after diagnosis (> 15 days) were independently associated with the risk of RPT. This study showed that significant residual pleural thickening was not a common complication of parapneumonic pleural effusions. There are certain risk factors for the development of residual pleural thickening. However, this complication was not associated with long-term functional repercussions in the series of patients involved in this study.

Adult↗

PubMed1988

Coarctation of the aorta in prenatal life: an echocardiographic, anatomical, and functional study.

In a prospective echocardiographic study of over 2000 pregnancies, 24 fetuses were found to have dilatation of the right ventricle and pulmonary artery when these structures were compared with those of the left heart. In 18 of these cases the diagnosis of coarctation or interruption of the aorta was correctly inferred from these findings. On direct echocardiographic examination of the aortic arch, arch hypoplasia or interruption of the aortic arch was recognisable prenatally in 10 of these 18 cases, most readily between 20-30 weeks' gestation. In 11 of 12 cases of aortic arch anomaly studied by Doppler echocardiography, a reduction in blood flow in the ascending aorta was demonstrated. The intracardiac appearances were suggestive of coarctation but the Doppler findings were within normal limits in two further cases which later proved to be normal. A diaphragmatic hernia was found in four fetuses and the intracardiac echocardiography and Doppler findings were the same as those found in fetuses with aortic coarctation. Five cases of coarctation were overlooked on the prenatal echocardiogram but these were found at follow up of the infants. Thus coarctation of the aorta can be diagnosed prenatally, although the condition may be missed or incorrectly predicted by the criteria examined in the present study. Reduced aortic blood flow is a demonstrable feature of aortic arch abnormalities but it is found in other conditions that are not associated with coarctation.

Aorta↗

PubMed1991

Modulation by mu opioid antagonism of sleep and respiration in neonatal swine.

Young (3-13 days) and older (26-34 days) piglets were instrumented aseptically for chronic recording of sleep/wake states (biparietal electrocorticogram, horizontal and vertical electrooculogram, submental muscle electromyogram (EMG)), heart rate, arterial pressure, pH and gas tensions, posterior cricoarytenoid and diaphragmatic EMG (EMGpca, EMGdi). After recovery from surgery, piglets underwent 1 h daily recordings for 5 consecutive days. Experimental sessions comprised control periods followed by study periods with CTOP (10-40 micrograms/kg i.v.), a somatostatin analogue with mu opioid antagonistic activity. In the young group, CTOP decreased percent time spent in active sleep (AS), increased heart rate during wakefulness, increased breathing frequency during transitional and quiet sleep (TS, QS) and decreased the duration of EMGdi activity during TS, QS and AS. In the older group, CTOP decreased the duration of EMGdi activity during QS. Changes in cardiorespiratory functions with age simulated those reported previously (Scott et al. (1990) Respir. Physiol. 80: 83-102). We conclude that, in early neonatal life, the mu opioid system influences both sleep pattern and respiratory timing, and that this influence diminishes with postnatal age.

Aging↗

PubMed1997

A wheezy infant unresponsive to bronchodilators.

When infants with recurrent wheezing have a clinical course inconsistent with asthma, an extensive list of alternative diagnoses needs to be considered. Anatomic malformations, such as congenital heart disease, laryngotracheomalacia, and diaphragmatic hernia, should be considered for immediate medical stabilization and early surgical correction. Life-threatening infections such as bacterial epiglottitis, retropharyngeal cellulitis, and viral myocarditis require prompt intervention. A careful history and physical examination reveal important diagnostic clues that, in this case, prompted a directed evaluation to rule out common masqueraders of asthma such as foreign body aspiration, cystic fibrosis, gastroesophageal reflux, viral pneumonitis, or pulmonary tuberculosis. On occasion, such a search is unrevealing and a diagnostic challenge remains. In those situations, judicious use of modern technology to scrutinize anatomic (high-resolution computed tomography) and functional (infant pulmonary function tests) pathology, and justifiable invasive procedures such as bronchoscopy and lung biopsy, uncover the true diagnosis, allowing for optimal management.

Asthma↗

PubMed2005

Structure and function of the esophagus of the American alligator (Alligator mississippiensis).

Esophageal structure and function were studied in juvenile American alligators (Alligator mississippiensis). The anatomy of alligators differs from humans in several important aspects: the crocodilian esophagus is more muscular and is composed entirely of smooth muscle. Functionally, the crocodilian esophagus is similar to that of mammals, but alligators have peak esophageal peristaltic pressures that are 2-3-fold greater than pressures in the human esophagus. As is found in humans, the incidence of esophageal reflux increased in postprandial animals compared with the fasting state. We observed a large increase in pressure in the lower esophageal sphincter (LES) during ventilation that ranged from 200% to 3000% of the pressures measured during apnea. These pressure changes appear to be intrinsic to the LES. Alligators lack a mammalian-type diaphragm; thus, there is no crural diaphragmatic contribution to LES pressure. These features recommend the alligator as a useful model for the study of regulation of the LES.

Alligators and Crocodiles↗

PubMed1993

Assessment of diaphragm function using mouth pressure twitches in chronic obstructive pulmonary disease patients.

The relative invasiveness of the balloon catheter technique in measuring twitch transdiaphragmatic pressure (Pdit) limits its clinical use. By phrenic stimulation we obtained swings in mouth pressure (Pmt) in six COPD patients (age 50 to 72, FEV1 18 to 48% of predicted) at relaxed FRC (rFRC) and during graded inspiratory efforts (IE; twitch occlusion, TO). At rFRC, Pmt was damped and time lagged relative to the esophageal pressure twitch (Pes(t)), as if pressure had equilibrated through an RC system. Pmt was not correlated with Pdit. Conversely, Pmt and Pes(t) were always well matched during IE [Pmt = 0.971 (SEM +/- 0.028) Pes(t), r > 0.89], possibly in relation to a decrease in upper airway compliance or more uniform pleural pressure swings. Pmt decreased with the level of voluntary diaphragmatic contraction (Pdivol) in proportion to Pdit, reflecting a progressive increase in the level of diaphragm activation. During IE, Pmt was closely related to the voluntary mouth pressure in five subjects but not in the remaining subject, indicating intersubject variability in the level of diaphragmatic recruitment relative to other inspiratory muscles. We submit that measuring Pm during inspiratory efforts upon which bilateral phrenic stimulation is superimposed offers a relatively simple method for the assessment of diaphragm activation, potentially applicable in the clinical field.

Aged↗

PubMed2000

Long-term outcome of critical illness polyneuropathy.

The aim of this study was to describe the outcome of patients with critical illness polyneuropathy (CIP). Twenty-six patients with CIP were studied to determine the clinical and electrophysiological profile 13-24 months after the onset of CIP. Seven patients refused to participate in the study; 6 patients died within the 1st year. Eleven of the 13 survivors showed clinical evidence of polyneuropathy. Five of these patients also had mononeuropathies, including peroneal and ulnar nerves. The quality of life was markedly impaired in all patients. Nerve conduction studies, including limb motor and sensory nerve conductions, bilateral phrenic nerve onset latencies, and bilateral diaphragmatic compound muscle action potentials, were abnormal in all patients. Incomplete recovery within 1-2 years after the onset of disease occurs frequently in patients with CIP.

Action Potentials↗

PubMed1995

Cardiorespiratory and sleep-wake behavior in developing swine: kappa-opioid influence.

Effects of specific kappa-opioid antagonism with norbinaltorphimine (NorBNI) on sleep-wake state, blood pressure and heart rate, and on diaphragmatic and posterior cricoarytenoid electromyographic activities were assessed in 3 to 13 and 23 to 33 day-old, chronically instrumented, unanesthetized piglets. Preliminary experiments established the pharmacodynamics and dose-response for NorBNI. In the main study, each piglet was studied twice daily, once before and once after 3.7 mg kg-1 NorBNI iv, for up to five consecutive days. During each study session, piglets underwent 10 min trials with 21% O2 in 79% N2 followed by 10% O2 in 90% N2 while lying in a sling within a plexiglass box. Sleep-wake distribution and cardiorespiratory functions matured with age. NorBNI produced a modest increase of arterial pressure and heart rate in the older group only, and altered neither state nor respiration at either age. These results suggest that, in the developing piglet model, the kappa-opioid system influences neither breathing nor state, but modulates cardiovascular regulation to a modest degree and later in ontogeny.

Aging↗

PubMed1999

Delayed diaphragm recovery in 12 patients after high cervical spinal cord injury. A retrospective review of the diaphragm status of 107 patients ventilated after acute spinal cord injury.

STUDY DESIGN: The functional outcome of the diaphragm after acute spinal cord injury was reviewed over a 16 year period for 107 patients who had required assisted ventilation in the acute phase. OBJECTIVES: To quantify the incidence of recovery of diaphragm function which occurred beyond the period of acute oedema; to produce a time-related profile of this as a guide to clinicians considering phrenic nerve pacing; and to assess the value of phrenic nerve testing in predicting recovery. SETTING: The Southport Regional Spinal Injuries Centre, Southport, England. METHODS: Bilateral phrenic nerve and diaphragm integrity was assessed clinically, by spirometry, and by fluoroscopy without and with phrenic nerve stimulation. RESULTS: Thirty-one per cent of all the ventilated patients (33 cases), with a level of injury between C1 and C4 (Scale A in ASIA Impairment Scale), had diaphragmatic paralysis at the time of respiratory failure. The subsequent diaphragm recovery which appeared in seven of these patients, between 40 and 393 days (mean 143), permitted weaning from ventilatory support at 93 to 430 days (mean 246) after the acute injury, with a vital capacity of over 15 ml kg(-1) at that stage. The diaphragm recovery in a further five patients, whose vital capacity remained below 10 ml kg(-1) and who could not be fully weaned, occurred significantly later, between 84 and 569 days (mean 290), P=0.053. Negative phrenic nerve tests were followed by weaning at a later interval in several cases. By contrast, one patient with an early positive phrenic stimulation test and subsequent diaphragm activity could not be weaned from the ventilator. CONCLUSION: Twenty-one per cent of the patients with initial diaphragm paralysis were ultimately able to breathe independently after 4 and 14 months, whilst a further 15% had some diaphragm recovery. Phrenic nerve testing should be repeated at 3 monthly intervals for the first year after high tetraplegia.

Acute Disease↗

PubMedDate not supplied

Male reproductive potential after MOPP therapy for Hodgkin's disease: a long-term survey.

The testicular function of 47 men who had been treated by MOPP chemotherapy for a Hodgkin's disease was studied in a long-term survey. Azoospermia was constant during at least 14 months after completion of the treatment. After a follow-up period of 89.4 +/- 54.7 months, 26 men were still azoospermic. No correlation could be found between the therapeutic regimen and the results of semen analysis. For the same treatment, some men recovered spermatogenesis within 5 years, others after more than 10 years while some were still azoospermic after 20 years. However, the association of infra-diaphragmatic irradiation to high dose MOPP therapy had a profound detrimental effect on spermatogenesis: only 3/13 men recovered. Sperm recovery was often incomplete: 17/21 men had a sperm count below 20 million ml-1. Yet, spontaneous pregnancies were obtained with severe oligozoospermia: only 1/11 sperm counts performed close to fertilization exceeded 20 million ml-1, and 8 were below 5 millions ml-1. FSH failed to be either a sensitive or a specific marker of sperm recovery, a discrepancy between FSH level and spermiogram being noticed in 18.2% of cases.

Adult↗

PubMed1996

Assessment of the voluntary activation of the diaphragm using cervical and cortical magnetic stimulation.

The twitch occlusion technique is a promising tool for use in accessing central drive to the diaphragm and determining maximal transdiaphragmatic pressure (Pdi) from submaximal efforts. It clinical use is limited by difficulties inherent to bilateral electrical stimulation (BES) of the phrenic nerves. This study was designed to revisit the technique using cervical magnetic stimulation (CMS). In addition, the effects of a voluntary contraction on diaphragm response to magnetic stimulation of the cortex (CxMS) were studied. Seven volunteers aged 23-33 yrs were studied. Pdi was determined at relaxed functional residual capacity (FRC) in response to BES (Pdi,P-ES) and CMS (Pdi,p-CMS), and the effects of an increasing voluntary contraction (Pdi, vol) were assessed, The same procedure was applied to CxMS. Pdi,p-CMS at relaxed FRC was 27.5 +/- 2.2 cmH2O (mean+/-SEM), about 20% higher than Pdi,p-ES, and reported previously. Pd,p-CMS linearly decreased with Pdi, vol, and six out of seven subjects were capable of producing voluntary contractions sufficient to extinguish the twitch. More complex patterns were observed with CxMS. Cervical magnetic stimulation provides diaphragmatic twitch occlusion data very similar to bilateral electrical phrenic stimulation. Magnetic stimulation, be it cervical or cortical, could probably be helpful for the assessment of central and peripheral mechanisms of diaphragmatic dysfunction in the clinical setting.

Adult↗

PubMed2000

[Experimental study on effect of Shenmai injection in improving contractility of fatigue diaphragm in rats].

OBJECTIVE: To study and compare the effects of Shenmai Injection (SMI) and aminophylline on pathogenesis and developing process of diaphragmatic fatigue. METHODS: SMI group, aminophylline group, SMI plus aminophylline group and control group of isolated rat's diaphragmatic muscular strip of equal length were set up, and electric stimulation was applied. Changes of related parameters in the fatigue inducing and recovery process were estimated. RESULTS: During fatigue inducing process, the lowering on maximal rates of relaxation (dR/dtmax) was earlier than that on maximal contraction peak (Pt) and contraction rate (dT/dtmax), and restoring of these parameters were restored later and incompletely. SMI could prolong the time Pt needed for reducing 50%, speed up the restoration of Pt. Although aminophylline could increase Pt, it shortened the fatigue inducing time and postponed the recovery. CONCLUSION: Disturbance in the function of relaxation plays important role in diaphragm fatigue induction. Through strengthening the capability to relax, SMI could improve the function of fatigue diaphragm. Aminophylline would damage the relaxation function together with the increasing contraction of diaphragm simultaneously, and this side-effect could be antagonised partly by SMI.

Aminophylline↗