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Biomedical subjects

L Bernardi

Publications and source records attributed to L Bernardi.

At least 73 records · Page 4Linked to original sources

Dynamic right and left ventricular interactions in the rabbit: simultaneous measurement of ventricular pressure-volume loops.

PURPOSE: This study was performed to characterize the dynamic factors determining ventricular interdependence in an open-pericardium intact animal model. MATERIALS AND METHODS: Simultaneous measures of right ventricular (RV) and left ventricular (LV) pressures and volumes in 6 urethane-anesthetized open-chested, open-pericardium rabbits. RV and LV V were calculated every 2 milliseconds. Measurements were made at initial baseline blood volume, and again after two infusions of 20 mL/kg isoconductive colloid solution. At each blood volume level, partial aortic (AO), pulmonary artery (PAO), and inferior vena caval (IVC) occlusions were performed. Biventricular diastolic compliance and end-systolic elastance were calculated from these data. RESULTS: Baseline end-diastolic (ED) and end-systolic (ES) V were 3.29 +/- 0.55 and 2.43 +/- 0.33 mL (mean +/- SD) for the LV, and 3.38 +/- 1.56 and 2.84 +/- 1.36 mL for the RV, respectively. AO increased all LV pressure and volume (P < .05) but did not alter RV ED volume (2.85 +/- 1.20 mL) or ED pressure (3.3 +/- 2.0 to 3.6 +/- 2.1 mm Hg). PAO increased RV ES pressure (P < .05) but did not alter RV ED volume, ED pressure, or ES volume, although it decreased LV ED volume (2.82 +/- 0.59, P < .05). AO also immediately increased end-systolic RV elastance to a value greater than that defined by IVC (7.9 +/- 4.4 to 10.9 +/- 6.6 mm Hg/mL, P < .05). Intravascular volume expansion though increasing baseline pressure and volume, did not alter qualitatively biventricular responses to AO, PA, or IVC. CONCLUSION: Ventricular interdependence has both systolic and diastolic components that have differing directional effects. In the pericardectomized rabbit, increases in RV ED volume decrease LV ED volume by decreasing LV diastolic compliance, but do not alter LV systolic function. Whereas, increases in LV ED volume decrease RV ES volume resulting in an increase in RV maximal elastance, but minimally alter RV diastolic function.

Animals↗

Autonomic control of skin microvessels: assessment by power spectrum of photoplethysmographic waves.

1. Although it is well known that the microvessels of the skin constantly undergo spontaneous variations in volume, the significance of these rhythmic changes remains uncertain. 2. In 10 healthy males and in 15 patients in intensive care, we assessed the origin of the autonomic influences on spontaneous fluctuations in the microcirculation of the skin, obtained by an infra-red photoplethysmographic device; we used spectral analysis techniques to compare these fluctuations (which were recorded simultaneously in two sites) with those of blood pressure, in order to test the presence of autonomic control of any synchronous fluctuations in these different measurements from the cardiovascular system. In order to minimize mechanical fluctuations caused by occasional slow breaths, rather than nervously mediated fluctuations in skin blood flow, respiration was controlled at 15 breaths/min (0.25 Hz). 3. Spontaneous infra-red photoplethysmographic fluctuations were observed in different body areas (left index finger and left ear lobe, right and left index finger), and all were evident at 0.1 Hz, as well as respiration-related components at 0.25 Hz. Active standing increased the power of the 0.1 Hz fluctuations (sympathetic activity) in both blood pressure (from 62.7 +/- 7.1 to 79.2 +/- 3.7 normalized units, P < 0.05) and IRP (finger: from 68.5 +/- 6.4 to 86.9 +/- 3.4 normalized units, P < 0.05; ear: from 59.0 +/- 5.9 to 88.1 +/- 2.0, P < 0.01). There was a high (> 0.5) coherence between the fluctuations obtained in blood pressure, in IRP signals obtained simultaneously at the finger and at the ear, and in R-R interval. This synchronization between the oscillations in all these signals, which were unrelated to the respiratory frequency or to the pulse rate, suggests a common neural, non-local origin. The phase between IRP and blood pressure was positive in the 0.1 Hz region (+1.65 +/- 0.41 radians, i.e. IRP was leading blood pressure, showing that 0.1 Hz fluctuations were not passively transmitted to the skin microvessels from large arteries) and negative in the 0.25 Hz region (-0.74 +/- 0.19 radians, P < 0.01 compared with phase in the 0.1 Hz region, i.e. IRP was lagging behind blood pressure, suggesting possible passive transmission to the skin microvessels of blood pressure fluctuations caused by respiration). Fluctuations at lower frequency were observed in all IRP recordings, suggesting a local origin for these. Intra-arterial and IRP fluctuations were compared in the 15 intensive care patients and gave similar results. 4. The skin microcirculation is thus not only under local control, but also reflects changes in sympathetic activity; the effect of these changes on the skin microcirculation can be easily evaluated by the spectral analysis of the IRP signal obtained simultaneously in multiple areas, in conjunction with the spectra of R-R interval and blood pressure.

Adult↗

Effect of different interventions on heart rate variability after heart transplantation: non-autonomic vs autonomic factors.

1. The human transplanted heart is initially denervated, hence any fluctuation present in the RR interval variability can be either due to reacquired innervation, or to the effect of some non autonomic activity, such as a direct effect of respiration on atrial (sinus node) stretch. 2. In order to distinguish between sympathetic, vagal and non autonomic factors we examined the effects of various physical and pharmacologic manoeuvres on the respiratory and non-respiratory components of heart rate variability. 3. We found that sinusoidal neck suction appears a useful, noninvasive tool to characterise the relative importance of the different factors, which can influence heart rate variability in the transplanted heart.

Autonomic Nervous System↗

Cardiovascular reflex changes preceding episodes of vasovagal syncope in paediatric subjects.

1. The cardiovascular reflex changes preceding episodes of vasovagal syncope (VVS) in paediatric age were investigated in 12 subjects and in 20 controls, supine and upright, by spectral analysis of RR interval, respiration, systolic and diastolic blood pressure. 2. The sympatho-vagal control on the heart and blood pressure was assessed by the power of the low- (LF: index of sympathetic activity) and high-frequency oscillations (index of vagal activity to the heart). 3. In VVS group the supine blood pressure was lower than in controls and fell after tilt, while remained unchanged in controls. The blood pressure LF increased in control group during early and prolonged orthostasis, whereas in the VVS group the LF tended to decrease after early orthostasis and were not significantly greater than supine before VVS. 4. In the VVS group the sympathetic control of blood pressure appears reduced or ineffective, and progressively worsens before the VVS episode.

Adolescent↗

Impact of changes in respiratory frequency and posture on power spectral analysis of heart rate and systolic blood pressure variability in normal subjects and patients with heart failure.

1. Autonomic dysfunction is a major feature of congestive cardiac failure and may have an important role in determining progression and prognosis. The low-frequency/high-frequency ratio derived from power spectral analysis of heart rate variability has been proposed as a non-invasive method to assess sympatho-vagal balance. However, the effects of different respiratory rates or posture are rarely accounted for, but may be relevant in patients with heart failure in whom clinical improvement is accompanied by a fall in respiratory rate and an increased proportion of the day in the upright position. 2. We have assessed the effect of controlled respiration at different rates (10, 15, 20 breaths/min or 0.17, 0.25 and 0.33 Hz), while supine and standing, on power spectral analysis of heart rate and blood pressure variability in 11 patients with heart failure and 10 normal subjects. 3. Heart rate variance and low-frequency power (normalized units) were reduced in patients with heart failure (absent in six). During controlled breathing while supine, the power of the high-frequency component was significantly greater at 10 breaths/min than at 20 breaths/min in patients with heart failure, whether expressed in absolute units (P = 0.005) or percentage of total power (P = 0.03). 4. On standing, controlled breathing in patients with heart failure produced less change in high-frequency power (P = 0.054), but the low-frequency/high-frequency ratio at lower respiratory rates was reduced (P = 0.05). In normal subjects, as expected, respiratory rate had a highly significant effect on high-frequency power. Also, in normal subjects there was the expected increase in heart rate low-frequency power (P = 0.04) moving from supine to standing with an increase in the low-frequency/high-frequency ratio (P = 0.003), while in the patients with heart failure this was absent, reflecting blunted cardiovascular reflexes. 5. Systolic blood pressure low- and high-frequency components and their ratio were significantly affected by respiration (P < 0.03) and change in posture (P < 0.03) in both patients with heart failure and normal subjects, with a significant increase in the low-frequency/high-frequency ratio (P = 0.03) on standing in patients with heart failure, indicating that autonomic modulation of blood pressure is still operating in heart failure. 6. Thus, respiratory rate and changes in posture have a significant effect on measurements derived from spectral analysis of heart rate and blood pressure variability. Studies that use power spectral analysis as a measure of sympatho-vagal balance should control for these variables.

Adult↗

Progressive withdrawal of muscle nerve sympathetic activity preceding vaso-vagal syncope during lower-body negative pressure.

We report the observation of a vaso-vagal syncope (VVS) occurring during lower body negative pressure in a young male volunteer. Recording of the peripheral blood flow, blood pressure and muscular sympathetic nerve activity revealed first a progressive withdrawal of muscle nerve sympathetic activity with redistribution of blood flow before the onset of the VVS.

Adult↗

Alterations of breathing in chronic heart failure: clinical relevance of arterial oxygen saturation instability.

1. In patients with chronic heart failure (CHF) alterations of breathing such as Cheyne-Stokes respiration (CSR) or periodic breathing, (PB) have been frequently described during both day- and night-time. These respiratory rhythm disorders are associated with marked oscillations of arterial oxygen saturation (SaO2) which may expose the patients to prolonged hypoxia. 2. In 40 stable CHF patients and 8 controls during awake day-time, we studied the relationship between alterations of breathing and SaO2, to verify the effect of voluntary control of respiration or oxygen therapy on the instability of SaO2 (analyzed as standard deviation (SD) of the mean value). Simultaneous recordings of ECG, lung volumes and SaO2 were made during 10 min. resting and 4 min. controlled breathing In a subgroup of 5 CHF the effect of oxygen therapy was compared to that of controlled breathing. 3. It was found that 62% of CHF had CSR or PB. Mean SaO2 and SD of SaO2 were significantly different in CHF as compared to controls (respectively 92.4 +/- 2.5 vs 95.4 +/- 0.5%, p < 0.002 and (1.27 +/- 0.9 vs 0.28 +/- 0.13%, p < 0.01), but among CHF pts those with CSR and PB had a lower SaO2 and a more pronounced instability of SaO2. Controlled breathing eliminated apneas and reduced or abolished the variation of tidal volume. In both control and CHF it resulted in an increase of mean SaO2 while a significant reduction of SaO2 instability was observed only in CHF, particularly if CSR or PB were present. Voluntary control of respiration was similar to oxygen therapy in increasing SaO2, but more effective on SaO2 SD. 4. It is concluded that in stable CHF, resting SaO2 is reduced and showed a marked instability particularly when periodic alterations of breathing were present. Continuous beat-to-beat recording of SaO2 may detect patients who have PB or CSR. Training to produce more regular breathing, regardless of the amount of ventilation, may represent a useful intervention.

Adult↗

Autonomic regulation of heart rate and peripheral circulation: comparison of high altitude and sea level residents.

1. To evaluate the activity of the autonomic nervous system on the heart and peripheral circulation in native high-altitude residents, during a Himalayan expedition we studied 12 men (age: 48 +/- 4, mean +/- SEM), life-long resident in a village at 4800 m (Sumdo village, Zanskar, India) and 7 healthy sea-level residents (age: 37 +/- 4) after 7 days of acclimatization (acclimatized lowlanders) at the same altitude. Furthermore 25 sea level residents (age: 46 +/- 2) underwent the same protocol at sea level. 2. R-R interval (RR), respiratory signal, non-invasive blood pressure, and skin arteriolar blood flow were evaluated in three different conditions: during free breathing in supine position and during controlled breathing (at 0.15 Hz), in supine and upright position, and analysed by autoregressive spectral analysis [low- (around 0.1 Hz) and high-frequency (respiratory) fluctuations, LF and HF, markers of sympathetic and vagal activity, respectively]. 3. High-altitude residents showed in supine position a higher RR than acclimatized lowlanders, similar to sea-level residents. RR variability was reduced in acclimatized lowlanders compared to both high-altitude residents and sea level residents. Systolic blood pressure (SBP) did not show significant differences between the three groups. High altitude residents showed in supine lower LF in RR signal compared to sea-level residents, and, compared to acclimatized lowlanders, higher HF and lower LF/HF ratio; high-altitude residents showed a reduction in skin microcirculation variability compared to sea-level residents, but this was eight fold greater than in acclimatized lowlander, thus indicating a much greater vasoconstriction in acclimatized lowlanders than in high-altitude residents. 4. In upright position, high-altitude residents showed the same behaviour as sea-level residents, with increase in LF-RR, and decrease in HF and LF-SBP. Acclimatized lowlanders showed similar directional trends though not significant changes for RR-LF. 5. After one week of acclimatization, lowlanders still manifested sympathetic activation and skin vasoconstriction; high-altitude residents did not show reduced vagal tone compared to sea-level residents, but a mild vasoconstriction appeared to be present. In conclusion, normal or enhanced vagal tone and preserved vasomotion are probably evidence of adaptation at high altitude hypoxia.

Adaptation, Physiological↗

Physical training enhances sympathetic and parasympathetic control of heart rate and peripheral vessels in chronic heart failure.

1. Physical training has been proposed to increase vagal control of heart rate in chronic heart failure. We studied the effects of physical training on cardiovascular control in 6 moderate to severe heart failure (NYHA II-III) patients and 6 age matched normal controls in a randomized controlled cross over trial (Training vs Detraining). 2. Five weeks training (20 min/day, 5 days/week bicycle exercise) increased peak VO2 in both C (from 31.2 +/- 1.4 to 37.7 +/- 2.4 ml/kg/min p < 0.01) and CHF patients (from 12.16 +/- 2.2 to 14.13 +/- 2 ml/kg/min p < 0.05). The sympathovagal control of heart rate and sympathetic control of the resistance vessels was assessed by the power of the oscillations (LF:0.03-0.15 Hz index of sympathetic activity, HF: 0.18-0.35 Hz index of vagal activity) in RR interval, blood pressure (systolic and diastolic by Finapres) and respiration by autoregressive spectral analysis, during free and controlled breathing (15b/min), in order to increase vagal activity. 3. T increased heart rate vagal control both in C (LF/HF ratio fb to cb: (D) 1.73 +/- 0.35 to 1.19 +/- 0.43 p = NS: (T) 2.9 +/- 1.2 to 1.13 +/- 0.3 p < 0.05) and in CHF patients (LF/HF ratio fb to cb: (D) 2.05 +/- 0.56 to 1.24 +/- 0.21 p = NS; (T) 2.6 +/- 0.89 to 0.87 +/- 0.15 p < 0.05; and in cb HF%: 36.2 +/- 2.7 (D) to 46.2 +/- 4.8 (T) p < 0.05). Before T, the sympathetic modulation of peripheral vessels (% LF compared to total variability) was depressed in CHF vs C (SBP: 9 +/- 2 vs 42 +/- 12% p < 0.05; DBP: 29 +/- 7 vs 55 +/- 31%, p < 0.05), and increased significantly after T in CHF (SBP from 9 +/- 2 (D) to 19 +/- 5% (T) p < 0.05; DBP from 29 +/- 7 to 41 +/- 11% (T) p < 0.05). This suggests an overall increase of autonomic control, both vagal on the heart and sympathetic on the peripheral vessels, in CHF by physical training.

Autonomic Nervous System↗

Twenty-four-hour pattern of blood pressure and spectral analysis of heart rate variability in diabetic patients with various degrees of autonomic neuropathy. Comparison to standard cardiovascular tests.

We performed four cardiovascular tests of autonomic function (deep breathing, lying to standing, Valsalva manoeuvre, postural hypotension) and simultaneous 24h recordings of blood pressure (BP) and ECG in 35 normotensive diabetic subjects. Autoregressive power spectrum analysis of RR interval variability was applied to 24h ECG recordings to obtain for day and night periods power of low- (0.03-0.15 Hz, LF) and high-frequency (0.18- 0.40 Hz, HF) components, relative markers of sympathetic and vagal activity respectively, and their ratio (LF/HF), assumed as index of sympathovagal balance. Eighteen patients showed normal cardiovascular tests, 6 patients one abnormal heart rate test, 5 patients two abnormal heart rate tests, and 6 patients also abnormal postural hypotension test. In diabetic patients with increasing degree of autonomic neuropathy, there was a progressive reduction of day-night change in systolic BP (p < 0.01), of LF during the day (p < 0.01), of HF during the night (p < 0.04), of day-night change in HF (p < 0.02), and of day-night change in HF/LF (p < 0.03). Day-night change in systolic BP was related to postural hypotension (p < 0.001) and to deep breathing (p < 0.01). Day LF was related to lying to standing (p < 0.001), to postural hypotension (p < 0.005) and to deep breathing (p < 0.007). Night HF was related to deep breathing (p < 0.0002) and to lying to standing (p < 0.02). Day-night change in HF/LF was slightly related to deep breathing, lying to standing, and to postural hypotension (p < 0.04). In a multiple regression analysis including age, diabetes duration, and cardiovascular tests as independent variables, day-night change in BP and day LF were only related to postural hypotension, whereas night HF was related to deep breathing. In conclusion, in diabetic patients with increasing autonomic damage, there is a progressive impairment of nocturnal fall of BP and of sympathetic activity during the day, blunted nocturnal increase of vagal activity and lower circadian variation in sympathovagal balance. The significant but not very close correlation of day-night pattern of BP and sympathovagal activity to standard cardiovascular reflex tests, supports the independent usefulness of 24h BP monitoring and spectral analysis of heart rate variability in diabetic neuropathy.

Adult↗

Impaired cardiovascular autonomic response to passive tilting in cirrhosis with ascites.

The autonomic regulation of cardiovascular function was evaluated in 15 cirrhotic patients with ascites and in 13 healthy subjects by the autoregressive power spectral analysis (PSA) of the intervals between adjacent R waves of the electrocardiogram (RR) interval and arterial pressure variability. Total power, low frequency (LF; index of the sympathetic activity of the heart and circulation), and high frequency (HF; index of vagal tone to the heart) components of the RR interval, systolic, and diastolic arterial pressure were evaluated in the supine position and during passive tilting, together with plasma norepinephrine levels. In the supine position, no significant differences in the PSA data were observed between the control subjects and cirrhotic patients, who had higher plasma norepinephrine levels. In healthy subjects, tilting was associated with an increase in the LF of the RR interval and arterial pressure and a decrease in the HF of the RR interval. In contrast, patients with cirrhosis showed a decrease of both LF and HF. Consequently, the LF/HF ratio significantly increased in healthy subjects, whereas it was unchanged in cirrhotic patients. The LF component of the diastolic pressure also decreased during tilting in cirrhotic patients. Plasma norepinephrine increased after tilting in both groups. These results indicate that the autonomic response to passive tilting is impaired in cirrhotic patients with ascites at both the cardiac and vascular levels, as a result of an altered sympatho-vagal balance, with reduced sympathetic predominance. These alterations occurred despite an appropriate response to the tilting of plasma norepinephrine, pointing to a receptorial or postreceptorial site of the autonomic impairment.

Adult↗

Determinants of heart rate variability in heart transplanted subjects during physical exercise.

Respiratory sinus arrhythmia has been described in heart transplanted subjects. In order to investigate the mechanisms involved in the generation of this condition in the transplanted heart and its evolution after surgery, graded exercise was performed (0-75 W in 25 W steps) on a cycle ergometer by 41 subjects (mean age 44 years) who had undergone heart transplantation 28 months (range 3-60) earlier and by six age matched-control subjects. R-R interval, respiratory signal, O2 consumption (VO2) and CO2 production (VCO2) were measured. Respiratory sinus arrhythmia was assessed by the autoregressive power spectrum of the R-R interval and respiration. All subjects reached the anaerobic threshold (heart transplants: 60% at 50 W, 40% at 75 W Controls: 150 W). In control subjects, the respiratory sinus arrhythmia was higher than in heart transplanted subjects (5.80 +/- 0.30 vs 1.45 +/- 0.16 1n ms2) and it decreased significantly (4.66 +/- 0.30 1n ms2, P < 0.05) during exercise, despite the increase in breathing rate and depth. When, the group of heart transplanted subjects was considered as a whole, respiratory sinus arrhythmia was found to be present in all conditions. It significantly increased at 25 W (from 1.45 +/- 0.16 to 2.00 +/- 0.17 1n ms2, P < 0.01), then significantly fell below baseline during recovery (to 0.97 +/- 0.23 1n ms2, P < 0.01). Multiple regression analysis showed that a linear combination of heart rate (inverse correlation) and VO2 (direct correlation) together with months having passed since transplantation surgery, could explain the observed changes in heart rate during exercise (multiple regression: r = 0.658, P < 0.0001). In five long-term transplanted subjects, non respiratory-related low frequency (0.1 Hz) waves were present on the R-R spectrum, but respiratory sinus arrhythmia is also present in the recently transplanted heart and depends on the opposing effects of ventilation and heart rate. In a few cases, sympathetic modulation (re-innervation) could not be excluded.

Adult↗

Demonstrable cardiac reinnervation after human heart transplantation by carotid baroreflex modulation of RR interval.

BACKGROUND: After heart transplantation, respiration-synchronous fluctuations (0.18 to 0.35 Hz, high frequency [HF]) in RR interval may result from atrial stretch caused by changes in venous return, but slower fluctuations (0.03 to 0.15 Hz, low frequency [LF]) not due to respiration suggest reinnervation. In normal subjects, sinusoidal neck suction selectively stimulates carotid baroreceptors and causes reflex oscillations of RR interval. METHODS AND RESULTS: To evaluate the presence of reinnervation, we measured the power of RR-LF and RR-HF in 26 heart transplant recipients and 16 control subjects before and during sinusoidal neck suction at 0.1 Hz and 0.20 Hz (similar to but distinct from that of controlled respiration, 0.25 Hz) and before and during administration of atropine or beta-blocker (esmolol hydrochloride) by spectral analysis. All transplant recipients showed small respiratory HF fluctuations. Nonrespiratory LF fluctuations were present in 13 of 26 transplant recipients and increased with months since transplantation (r = .53, P < .01). HF neck suction induced a 0.20-Hz component in all 16 control subjects and none of the 26 transplant subjects. LF neck suction increased RR-LF (from 0.73 +/- 0.20 to 1.30 +/- 0.26 ln ms2, P < .001), similar to but less than in control subjects (from 6.12 +/- 0.21 to 8.27 +/- 0.21 ln ms2, P < .001). Atropine reduced all fluctuations in control subjects and blocked the HF increase caused by 0.20-Hz neck suction but not the LF increase during 0.10-Hz stimulation. Neck suction-induced changes in LF fluctuations persisted after administration of atropine in transplant recipients but were attenuated by esmolol hydrochloride, suggesting sympathetic rather than vagal reinnervation. CONCLUSIONS: The presence of baroreceptor-induced RR oscillations is evidence of functional, although incomplete, autonomic reinnervation.

Adrenergic beta-Antagonists↗

Effects of pulsed beta-stimulant therapy on beta-adrenoceptors and chronotropic responsiveness in chronic heart failure.

In animals, intermittent sympathomimetic stimulation with dobutamine produces benefits analogous to those of physical conditioning. Longer intermittent or continuous beta-stimulant therapies have not, however, been successful in managing patients with chronic heart failure. We have investigated the role of beta-receptor stimulants in patients with severe chronic heart failure by changing the method of administration to intermittent, very short-duration pulsed intrope therapy (PIT). We studied 10 patients (mean age 64 [SE 2] years) with stable moderate to severe chronic heart failure (ejection fraction 23 [3]%) who received PIT, and 10 control patients matched for age and severity. We infused sufficient dobutamine to raise heart rate to 70-80% maximum for 30 min per day, 4 days per week for 3 weeks. PIT increased exercise tolerance (from 10.4 [1.2] min at baseline to 13.0 [1.5] min at 3 weeks; p < 0.001, 95% CI for difference 1.6 to 3.9) and lowered peripheral vascular resistance (19.8 [3.1] to 17.7 [2.4] mm Hg.min.L-1; p < 0.05, -4.1 to -0.1). PIT produced significant increases in lymphocyte beta-receptor density (502 [110] to 1200 [219] per cell, p < 0.02, 258 to 1138) and chronotropic responsiveness to exercise (change in heart rest to peak exercise 51.0 [3.2] to 57.5 [3.9] beats per min; p < 0.01, 2.9-10.1). Plasma noradrenaline concentrations (2.39 [0.28] to 1.65 [0.19] nmol/L, p < 0.05) were reduced. The patients' symptoms were also improved. By contrast, no change in autonomic function or exercise capacity was seen in the control group. Short-duration PIT induces pharmacological conditioning with improved symptoms, autonomic balance, exercise tolerance, beta-receptor up-regulation, and enhanced chronotropic responsiveness in chronic heart failure.

Aged↗

HLA-DRB1 compatibility in cadaver kidney transplantation: correlation with graft survival and function.

The introduction of genomic HLA-DR typing has stimulated a re-evaluation of the role of HLA-DR compatibility on cadaver kidney transplantation. We retrospectively studied the influence of HLA-DRB1 matching on the survival of 416 patients using univariate and Cox regression analysis as well as its influence on the occurrence of rejection episodes and on creatinine level at the 3rd month in the 198 recipients for whom these data were available. The following parameters were also considered: HLA-A,B compatibility, donor and recipient age, graft number, pre-transplant blood transfusions and panel reactive antibodies (PRA). Twenty-four month graft survival was 100% for transplants with zero mismatches (n = 47), 87.9% for those with one mismatch (n = 191) and 81.3% for those with two mismatches (n = 178). In the Cox model, HLA-DRB1 matching was the most significant variable influencing graft survival (47% of chi 2 P = 0.001), followed by HLA-A,B matching (23%, P = 0.02) and donor age (19%, P = 0.04). Ninety-two percent of the patients with zero mismatches experienced no rejection episodes in the first 3 posttransplant months compared with 62% and 41% of patients with one and two mismatches, respectively. Mean creatinine level (mg/dl) was 1.2, 1.4, and 1.5 in patients with zero, one, and two mismatches, respectively. Should these results be confirmed by prospective studies, HLA-DRB1 compatibility will have to be considered as an organ allocation criterion.

Adolescent↗

Neuromuscular disorders associated with failure to wean from the ventilator.

OBJECTIVE: To determine, by retrospective chart analysis, the frequency, type and significance of neuromuscular disorders in patients whose clinical features suggested a neuromuscular cause of failure to wean. BACKGROUND: Failure to wean is a common and difficult problem in critical care units. While a neuromuscular cause may be suspected in some patients, the frequency and type has not been determined utilizing comprehensive electrophysiological studies of limbs and the respiratory system. Such knowledge may aid in patient management and prognosis. METHODS: The clinical setting was a critical care/trauma centre that admits 1500 patients per year, approximately 500 being on ventilators for longer than five days. We analyzed the hospital charts of 40 patients admitted to the unit during three years, whose respiratory assessment suggested a neuromuscular cause for failure to wean from the ventilator. To investigate this possibility, we performed electrophysiological studies of the limbs and also of the respiratory system by phrenic nerve conduction and needle electromyography of the chest wall and diaphragm. The results were compared to 25 healthy controls. RESULTS: 38 of 40 patients (95%) had a neuromuscular disorder: 25--critical illness polyneuropathy, 2--Guillain-Barré syndrome, 4--diabetic and critical illness polyneuropathy, 2--uremic and critical illness polyneuropathy, 10--an abnormality of central drive, 5--unilateral phrenic nerve palsy, 3--a neuromuscular transmission defect, and 5--a primary myopathy. Fifteen (38%) had a combination of disorders. Patients with more severe polyneuropathy took longer to wean, a mean of 136 versus 52 days (p = 0.007). The severity of the polyneuropathy had no effect on mortality. CONCLUSIONS: Electrophysiological studies of limbs and the respiratory system are together valuable in confirming the presence, and identifying the specific type of neuromuscular cause for difficulty in weaning from the ventilator. This information is important in patient management and prognosis.

Adolescent↗