Open retromuscular versus laparoscopic ventral hernia repair for medium-sized defects: where is the value?

PURPOSE: There is increasing emphasis on value in health care, defined as quality over cost required to deliver care. We analyzed outcomes and costs of repairing medium-sized ventral hernias to identify whether an open retromuscular or laparoscopic intraperitoneal onlay approach would provide superior value to the patient and healthcare system. METHODS: A retrospective analysis of prospectively collected data from the Americas Hernia Society Quality Collaborative was performed for patients undergoing clean, elective repair of ventral hernias between 4 and 8 cm in width at our institution between 4/2013 and 12/2016 for whom at least 1-year follow-up was available. Recurrence rates, wound complications, length of stay, patient-reported outcomes, and perioperative costs were compared. RESULTS: One hundred and eighty-six patients met criteria (105 open, 81 laparoscopic) with 93.5% having ≥ 2-year follow-up. Patients undergoing laparoscopic repair had higher BMI, lower ASA classification, slightly lower prevalence of recurrent hernias and less prior mesh utilization, and slightly smaller hernias. Length of stay was shorter in the laparoscopic group (median 1 vs. 3 days, p < 0.001), without increased readmissions. Recurrence rates, wound complications, and patient-reported outcomes were similar. Laparoscopic repair had higher up-front surgical costs, yet equivalent total perioperative costs. CONCLUSION: Both laparoscopic and open approaches for elective repair of medium-sized ventral hernias offer similar clinical outcomes, patient-reported outcomes, and total perioperative costs. Laparoscopic repair appears to offer superior value based on a significantly reduced postoperative length of stay.

Potential of saprophage Diptera to acquire culturable livestock-associated antibiotic-resistant bacteria.

The increasing prevalence of antibiotic resistance among bacteria is one of the most intractable challenges in 21st-century public health. Dipterans that associate with livestock, livestock waste products and cadavers have the potential to acquire livestock-associated antibiotic-resistant bacteria (LA-ARB) and transmit them to humans. In this study, piglet cadavers were used to attract saprophage dipterans from the environment and those dipterans were sampled for the presence of LA-ARB. In the first trial, culturable microbes resistant to both aminoglycoside and ß-lactam antibiotics were found in all cadavers and masses of dipteran larvae, and in three-quarters of adult dipterans. In the second trial, over 130 culturable bacterial colonies resistant to ß-lactams were isolated from the cadavers, larval and adult dipterans. Over 100 of those colonies were coliform or metabolically similar bacteria. Adult dipterans carried ß-lactam resistant staphylococci, whereas those bacterial types were absent from larval dipterans and cadavers, suggesting they were picked up from elsewhere in the environment. This research indicates that LA-ARB are ubiquitous in pig farms, and dipterans have the potential to carry medically important microbes. Further research is encouraged to determine the extent to which dipterans acquire microbes from animal agriculture relative to other environments.

Color vision impairment in multiple sclerosis points to retinal ganglion cell damage.

Multiple Sclerosis (MS) results in color vision impairment regardless of optic neuritis (ON). The exact location of injury remains undefined. The objective of this study is to identify the region leading to dyschromatopsia in MS patients' NON-eyes. We evaluated Spearman correlations between color vision and measures of different regions in the afferent visual pathway in 106 MS patients. Regions with significant correlations were included in logistic regression models to assess their independent role in dyschromatopsia. We evaluated color vision with Hardy-Rand-Rittler plates and retinal damage using Optical Coherence Tomography. We ran SIENAX to measure Normalized Brain Parenchymal Volume (NBPV), FIRST for thalamus volume and Freesurfer for visual cortex areas. We found moderate, significant correlations between color vision and macular retinal nerve fiber layer (rho = 0.289, p = 0.003), ganglion cell complex (GCC = GCIP) (rho = 0.353, p < 0.001), thalamus (rho = 0.361, p < 0.001), and lesion volume within the optic radiations (rho = -0.230, p = 0.030). Only GCC thickness remained significant (p = 0.023) in the logistic regression model. In the final model including lesion load and NBPV as markers of diffuse neuroaxonal damage, GCC remained associated with dyschromatopsia [OR = 0.88 95 % CI (0.80-0.97) p = 0.016]. This association remained significant when we also added sex, age, and disease duration as covariates in the regression model. Dyschromatopsia in NON-eyes is due to damage of retinal ganglion cells (RGC) in MS. Color vision can serve as a marker of RGC damage in MS.

Mitochondrial tissue specificity of substrates utilization in rat cardiac and skeletal muscles.

As energetic metabolism is crucial for muscles, they develop different adaptations to respond to fluctuating demand among muscle types. Whereas quantitative characteristics are known, no study described simultaneously quantitative and qualitative differences among muscle types in terms of substrates utilization patterns. This study thus defined the pattern of substrates preferential utilization by mitochondria from glycolytic gastrocnemius (GAS) and oxidative soleus (SOL) skeletal muscles and from heart left ventrical (LV) in rats. We measured in situ, ADP (2 mM)-stimulated, mitochondrial respiration rates from skinned fibers in presence of increasing concentrations of pyruvate (Pyr) + malate (Mal), palmitoyl-carnitine (Palm-C) + Mal, glutamate (Glut) + Mal, glycerol-3-phosphate (G3-P), lactate (Lact) + Mal. Because the fibers oxygen uptake (Vs) followed Michaelis-Menten kinetics in function of substrates level we determined the Vs and Km, representing maximal oxidative capacity and the mitochondrial sensibility for each substrate, respectively. Vs were in the order GAS < SOL < LV for Pyr, Glu, and Palm-C substrates, whereas in the order SOL = LV < GAS with G3-P. Moreover, the relative capacity to oxidize Palm-C is extremely higher in LV than in SOL. Vs was not stimulated by the Lact substrate. The Km was equal for Pyr among muscles, but much lower for G3-P in GAS and lower for Palm-C in LV. These results demonstrate qualitative mitochondrial tissue specificity for metabolic pathways. Mitochondria of glycolytic muscle fibers are well adapted to play a central role for maintaining a satisfactory cytosolic redox state in these fibers, whereas mitochondria of LV developed important capacities to use fatty acids.

L-arginine reduces exercise-induced increase in plasma lactate and ammonia.

To investigate the effect of L-arginine supplementation (L-ARG) on physiological and metabolic changes during exercise, we determined in a double-blind study the cardiorespiratory (heart rate, oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) and the metabolic (lactate and ammonia) responses to maximal exercise after either an intravenous L-ARG hydrochloride salt or placebo load in 8 healthy subjects. Exercise-induced increases in heart rate, VO(2) and VCO(2) were not significantly different after L-ARG or placebo. By contrast, peak plasma ammonia and lactate were significantly decreased after L-ARG load (60.6 +/- 8.2 vs. 73.1 +/- 9.1 micro mol x l(-1), p < 0.01 and 7.1 +/- 0.7 vs. 8.2 +/- 1.1 mmol x l(-1), p < 0.01, for ammonia and lactate, respectively). Plasma L-citrulline increased significantly during exercise only after L-ARG load, despite a concomitant decrease in plasma L-ARG. Furthermore, a significant inverse relationship was observed between changes in lactate and L-citrulline concentrations after L-ARG load (r = -0.84, p = 0.009). These results demonstrate that intravenous L-ARG reduces significantly exercise-induced increase in plasma lactate and ammonia. Taken together, the specific L-citrulline increase and the inverse relationship observed between L-citrulline and plasma lactate after L-ARG might support that L-ARG supplementation enhances the L-arginine-nitric oxide (NO) pathway during exercise.

Physical activity changes the regulation of mitochondrial respiration in human skeletal muscle.

This study explores the importance of creatine kinase (CK) in the regulation of muscle mitochondrial respiration in human subjects depending on their level of physical activity. Volunteers were classified as sedentary, active or athletic according to the total activity index as determined by the Baecke questionnaire in combination with maximal oxygen uptake values (peak V(O2), expressed in ml min(-1) kg(-1)). All volunteers underwent a cyclo-ergometric incremental exercise test to estimate their peak V(O2) and V(O2) at the ventilatory threshold (VT). Muscle biopsy samples were taken from the vastus lateralis and mitochondrial respiration was evaluated in an oxygraph cell on saponin permeabilised muscle fibres in the absence (V(0)) or in the presence (V(max)) of saturating [ADP]. While V(0) was similar, V(max) differed among groups (sedentary, 3.7 +/- 0.3, active, 5.9 +/- 0.9 and athletic, 7.9 +/- 0.5 micromol O2 min(-1) (g dry weight)(-1)). V(max) was correlated with peak V(O2) (P < 0.01, r = 0.63) and with V(T) (P < 0.01, r = 0.57). There was a significantly greater degree of coupling between oxidation and phosphorylation (V(max)/V(0)) in the athletic individuals. The mitochondrial K(m) for ADP was significantly higher in athletic subjects (P < 0.01). Mitochondrial CK (mi-CK) activation by addition of creatine induced a marked decrease in K(m) in athletic individuals only, indicative of an efficient coupling of mi-CK to ADP rephosphorylation in the athletic subjects only. It is suggested that increasing aerobic performance requires an enhancement of both muscle oxidative capacity and mechanisms of respiratory control, attesting to the importance of temporal co-ordination of energy fluxes by CK for higher efficacy.

Oxidative capacity of skeletal muscle in heart failure patients versus sedentary or active control subjects.

OBJECTIVES: We investigated the in situ properties of muscle mitochondria using the skinned fiber technique in patients with chronic heart failure (CHF) and sedentary (SED) and more active (ACT) controls to determine: 1) whether respiration of muscle tissue in the SED and ACT groups correlates with peak oxygen consumption (pVO(2)), 2) whether it is altered in CHF, and 3) whether this results from deconditioning or CHF-specific myopathy. BACKGROUND: Skeletal muscle oxidative capacity is thought to partly determine the exercise capacity in humans and its decrease to participate in exercise limitation in CHF. METHODS: M. Vastus lateralis biopsies were obtained from 11 SED group members, 10 ACT group members and 15 patients with CHF at the time of transplantation, saponine-skinned and placed in an oxygraphic chamber to measure basal and maximal adenosine diphosphate (ADP)-stimulated (V(max)) respiration rates and to assess mitochondrial regulation by ADP. All patients received angiotensin-converting enzyme (ACE) inhibitors. RESULTS: The pVO(2) differed in the order CHF < SED < ACT. Compared with SED, muscle alterations in CHF appeared as decreased citrate synthase, creatine kinase and lactate dehydrogenase, whereas the myosin heavy chain profile remained unchanged. However, muscle oxidative capacity (V(max), CHF: 3.53 +/- 0.38; SED: 3.17 +/- 0.48; ACT: 7.47 +/- 0.73, micromol O(2).min(-1).g(-1)dw, p < 0.001 vs. CHF and SED) and regulation were identical in patients in the CHF and SED groups, differing in the ACT group only. In patients with CHF, the correlation between pVO(2) and muscle oxidative capacity observed in controls was displaced toward lower pVO(2) values. CONCLUSIONS: In these patients, the disease-specific muscle metabolic impairments derive mostly from extramitochondrial mechanisms that disrupt the normal symmorphosis relations. The possible roles of ACE inhibitors and level of activity are discussed.

Selective changes in mitochondria respiratory properties in oxidative or glycolytic muscle fibers isolated from G93AhumanSOD1 transgenic mice.

Cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in cytosolic copper, zinc superoxide dismutase (SOD1). Total SOD activity and functional mitochondrial properties were studied in muscles and nervous tissues of control and transgenic mice mimicking the disease. It was found that total SOD activity was lower in nervous tissues than in muscles in both transgenic and control mice. In addition SOD activity increased during progression of disease in muscle but not in nervous tissue of transgenic mice. Maximal oxygen consumption and apparent Km for ADP were decreased in mitochondria from transgenic soleus (an oxidative muscle). However there was no difference between control and transgenic mice in respiratory parameters of mitochondria in the EDL muscle (a glycolytic muscle). These findings indicate that oxidative stress due to SOD1 mutations could alter energy metabolism in FALS mice, thereby affecting primarily oxidative muscle of the limbs, independently of motoneuron loss.

Non-invasive cardiac output evaluation during a maximal progressive exercise test, using a new impedance cardiograph device.

One of the greatest challenges in exercise physiology is to develop a valid, reliable, non-invasive and affordable measurement of cardiac output (CO). The purpose of this study was to evaluate the reproducibility and accuracy of a new impedance cardiograph device, the Physio Flow, during a 1-min step incremental exercise test from rest to maximal peak effort. A group of 12 subjects was evaluated to determine the reproducibility of the method as follows: (1) each subject performed two comparable tests while their CO was measured by impedance cardiography using the new device (COImp1, COImp2), and (2) in a subgroup of 7 subjects CO was also determined by the direct Fick method (COFick) during the second test. The mean difference between the values obtained by impedance (i.e. COImp1-COImp2) was -0.009 l.min-1 (95% confidence interval: -4.2 l.min-1, 4.2 l.min-1), and CO ranged from 3.55 l.min-1 to 26.75 l.min-1 (n = 146). When expressed as a percentage, the difference (COImp1-COImp2) did not vary with increasing CO. The correlation coefficient between the values of COImp and COFick obtained during the second exercise test was r = 0.94 (P < 0.01, n = 50). The mean difference expressed as percentage was -2.78% (95% confidence interval: -27.44%, 21.78%). We conclude that COImp provides a clinically acceptable evaluation of CO in healthy subjects during an incremental exercise.

Effect of cyclosporin A and its vehicle on cardiac and skeletal muscle mitochondria: relationship to efficacy of the respiratory chain.

Although cyclosporin (CsA) is considered to be the best immunosuppressive molecule in transplantation, it has been suspected to alter mitochondrial respiration of various tissues. We evaluated the acute effect of CsA and its vehicle on maximal oxidative capacity (V(max)) of cardiac, soleus and gastrocnemius muscles of rats by an oxygraphic method in saponin skinned muscle fibres. The effects of Sandimmun (a formulation of CsA), vehicle of Sandimmun (cremophor and ethanol (EtOH)), CsA in EtOH and EtOH alone were tested. Increasing concentrations (5 - 20 - 50 - 100 microM) of CsA (or vehicles) were used. Sandimmun profoundly altered the V(max) of all muscles. For example, at 20 microM, inhibition reached 18+/-3, 23+/-5, 45+/-5%, for heart, soleus and gastrocnemius respectively. There were only minor effects of CsA diluted in EtOH and EtOH alone on V(max) of cardiac muscle. Because the effects of vehicle on V(max) were similar or higher than those of Sandimmun, the inhibition of oxidative capacity could be entirely attributed to the vehicle for all muscles. Next, we investigated the potential sites of action of the vehicle on the different complexes of the mitochondrial respiratory chain by using specific substrates and inhibitors. The vehicle affected mitochondrial respiration mainly at the level of complex I ( approximately -85% in skeletal muscles, and -32% in heart), but also at complex IV ( approximately -26% for all muscles). The mechanism of action of the vehicle on the mitochondrial membrane and the implications for the clinical use of immunosuppressive drugs are discussed.

Exercise training with a heart device: a hemodynamic, metabolic, and hormonal study.

PURPOSE: The mechanisms of the training-induced improvements in left ventricular assist (LVAD) patients are unknown. METHODS: We measured the hemodynamic, gas exchange, and metabolic and hormonal effects of 6-wk exercise training in a cardiogenic shock patient who was assisted by an LVAD. RESULTS: After training, the peak power and VO2 increased by 166% and 56%, respectively (80 W and 16.1 mL x min(-1) x kg(-1)), whereas the ventilatory drive decreased. Although the LVAD output increased little with exercise, the systemic cardiac output rose (adequately for the VO2) from 5.91 and 4.90 L x min(-1) at rest to 9.75 and 9.47 L x min(-1) at peak work rate, before and after training, respectively. Thus, the left ventricle ejected again through the aortic valve. Unloading and/or retraining resulted in a left ventricular filling pressure decrease. Although the right ventricular ejection fraction increased with exercise, it decreased again at the maximal load after training. For a given work rate the arterial lactate, the norepinephrine (NE) and epinephrine (E) concentrations fell after training, but the enhanced maximal work rate elicited higher NE and E concentrations (4396 and 1848 pg x mL(-1), respectively). The lack of right ventricular unloading might have kept the atrial natriuretic peptide higher after training, but the blood cyclic GMP and endothelin were lower after training. CONCLUSION: In an LVAD patient, retraining returns the exercise capacity to the class III level by peripheral and left ventricular hemodynamic improvements, but the safety of maximal exercise remains to be proven in terms of right ventricular function and orthosympathetic drive.

A new impedance cardiograph device for the non-invasive evaluation of cardiac output at rest and during exercise: comparison with the "direct" Fick method.

The objectives of this study were to evaluate the reliability and accuracy of a new impedance cardiograph device, the Physio Flow, at rest and during a steady-state dynamic leg exercise (work intensity ranging from 10 to 50 W) performed in the supine position. We compared cardiac output determined simultaneously by two methods, the Physio Flow (QcPF) and the direct Fick (QcFick) methods. Forty patients referred for right cardiac catheterisation, 14 with sleep apnoea syndrome and 26 with chronic obstructive pulmonary disease, took part in this study. The subjects' oxygen consumption values ranged from 0.14 to 1.19 l x min(-1). The mean difference between the two methods (QcFick - QcPF) was 0.04 l x min(-1) at rest and 0.29 l x min(-1) during exercise. The limits of agreement, defined as mean difference +/- 2SD, were -1.34, +1.41 l x min(-1)] at rest and -2.34, +2.92 l x min(-1) during exercise. The difference between the two methods exceeded 20% in only 2.5% of the cases at rest, and 9.3% of the cases during exercise. Thoracic hyperinflation did not alter QcPF. We conclude that the Physio Flow provides a clinically acceptable and non-invasive evaluation of cardiac output under these conditions. This new impedance cardiograph device deserves further study using other populations and situations.

Lack of acute cyclosporine nephrotoxicity in late heart-transplant recipients.

BACKGROUND: Cyclosporine induces daily renal hypoperfusion in subjects with normal atrial natriuretic peptide (ANP) levels, but its acute effects in heart transplant patients with increased ANP remain to be determined. METHODS: Cyclosporinemia and creatinine clearance were monitored during 7 hours following cyclosporine administration in 6 heart transplant patients. CONCLUSIONS: No acute cyclosporine-induced decrease in creatinine clearance was observed after heart transplantation. These data suggest that maintenance cyclosporine dose may be less nephrotoxic than suspected and that increased ANP might protect the renal function late after heart transplantation.

VO(2) kinetics reveal a central limitation at the onset of subthreshold exercise in heart transplant recipients.

Because the cardiocirculatory response of heart transplant recipients (HTR) to exercise is delayed, we hypothesized that their O(2) uptake (VO(2)) kinetics at the onset of subthreshold exercise are slowed because of an impaired early "cardiodynamic" phase 1, rather than an abnormal subsequent "metabolic" phase 2. Thus we compared the VO(2) kinetics in 10 HTR submitted to six identical 10-min square-wave exercises set at 75% (36 +/- 5 W) of the load at their ventilatory threshold (VT) to those of 10 controls (C) similarly exercising at the same absolute (40 W; C40W group) and relative load (67 +/- 14 W; C67W group). Time-averaged heart rate, breath-by-breath VO(2), and O(2) pulse (O(2)p) data yielded monoexponential time constants of the VO(2) (s) and O(2)p increase. Separating phase 1 and 2 data permitted assessment of the phase 1 duration and phase 2 VO(2) time constant (). The VO(2) time constant was higher in HTR (38.4 +/- 7.5) than in C40W (22.9 +/- 9.6; P < or = 0. 002) or C67W (30.8 +/- 8.2; P < or = 0.05), as was the O(2)p time constant, resulting from a lower phase 1 VO(2) increase (287 +/- 59 vs. 349 +/- 66 ml/min; P < or = 0.05), O(2)p increase (2.8 +/- 0.6 vs. 3.6 +/- 1.0 ml/beat; P < or = 0.0001), and a longer phase 1 duration (36.7 +/- 12.3 vs. 26.8 +/- 6.0 s; P < or = 0.05), whereas the was similar in HTR and C (31.4 +/- 9.6 vs. 29.9 +/- 5.6 s; P = 0.85). Thus the HTR have slower subthreshold VO(2) kinetics due to an abnormal phase 1, suggesting that the heart is unable to increase its output abruptly when exercise begins. We expected a faster in HTR because of their prolonged phase 1 duration. Because this was not the case, their muscular metabolism may also be impaired at the onset of subthreshold exercise.

Immunosuppressive treatment affects cardiac and skeletal muscle mitochondria by the toxic effect of vehicle.

In order to examine whether immunosuppressive treatment could be responsible for the reduced exercise capacity of heart transplant recipients (HTR), we studied the effects of long-term immunosuppressive treatment with cyclosporin A (CsA) and its vehicle (2/3 cremophor and 1/3 alcohol diluted in olive oil) on in situ mitochondrial respiration of different muscles. Rats were fed for 3 weeks with 10 or 25 mg/kg/day CsA in its vehicle (CsA10 and CsA25 groups), or vehicle or H(2)O. Oxygen consumption rate was measured in saponin skinned fibers without (V(0)) and with ADP until maximal respiration (V(max)) was reached and K(M)for ADP as well as V(max)were calculated using non-linear fit of the Michaelis-Menten equation. In the cardiac muscle of the CsA25 group, V(0)and V(max)were decreased by immunosuppressive treatment respectively from 6.33+/-0.51 to 3.18+/-0.3micromol O(2)/min/g dw (P<0.001) and from 29.0+/-1.5 to 18.1+/-1.6micromol O(2)/min/g dw (P<0.001), an effect which could be entirely attributed to the vehicle itself, with no difference between CsA10 and CsA25. Regulation of cardiac mitochondrial respiration by ADP was altered by vehicle with the K(M)for ADP decreasing from 371+/-37 to 180+/-21microm(P<0.001). A similar trend was observed in the diaphragm or soleus, although to a lesser extent. In contrast, V(0)and V(max)decreased in glycolytic gastrocnemius muscle respectively from 1.7+/-0.2 to 0.94+/-0.14 (P<0. 01) and from 6.8+/-0.3 to 5.1+/-0.4micromol O(2)/min/g dw (P<0.001) in the CsA25 group, but the main effects could be attributed to CsA itself. It was concluded that immunosuppressive treatment induces a deleterious effect on cardiac and skeletal muscle oxidative capacities, mainly due to cremophor, the main component of vehicle.

Interrupter technique versus plethysmography for measurement of respiratory resistance in children with asthma or cystic fibrosis.

The purpose of the present study was to compare measurements of respiratory system resistance by the interrupter method (Rrsint) with those of airway resistance by plethysmography (Raw) in nonobstructed children with asthma or cystic fibrosis (ratio of forced expiratory volume in 1 sec to vital capacity, FEV(1)/VC >/=80% with a forced expiratory flow rate between 25-75% of forced vital capacity, FEF(25-75) >/=75% of normal values) and in obstructed children with the same diseases (FEV(1)/VC <80% and/or FEF(25-75) <75% of normal values). Eighty-one children (47 asthmatics and 34 suffering from cystic fibrosis) aged 5-18 years (mean 11.2 +/- SD 3.4 years) were included in the study. For the overall group, we observed generally lower values for Raw (4.7 +/- 2. 8 cmH(2)O.L(-).s) than for Rrsint20 (extrapolation of the mouth pressure during occlusion to 40 ms after interruption) (5.6 +/- 1.7 cmH(2)O.L(-1).s) (P < 0.02), or for Rrsint40 (extrapolation of the mouth pressure during occlusion to 60 ms after interruption) (6.6 +/- 2.2 cmH(2)O.L(-1).s) (P < 0.001), but there was no difference between Rrsint20 and Raw in the obstructed subgroup. Moreover, we observed a correlation between the difference (Rrsint20 - Raw) expressed in percentage of predicted values and the degree of obstruction estimated by FEV(1)/VC (r = 0.56, P < 0.001). The differences between the specific resistances (sRrsint20 - sRaw, sRrsint40 - sRaw) were also correlated with the severity of the obstruction (r = 0.65, P < 0.001 and r = 0.57, P < 0.001, respectively). We observed also that the tendency to underestimate resistance by Rrsint in obstructed children was not the same in children with asthma and cystic fibrosis. We conclude that the tendency of Rrsint, as measured with our method, to underestimate airway obstruction appears to increase in proportion to the severity of the airway obstruction.

Lung membrane diffusing capacity, heart failure, and heart transplantation.

The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure and remains decreased after heart transplantation. This decrease in DLCO may depend on a permanent alteration after transplantation of one or the other of its components: diffusion of the alveolar capillary membrane or the pulmonary capillary blood volume (Vc). Therefore, we measured DLCO, the membrane conductance, and Vc before and after heart transplantation. At the time of hemodynamic measurements, the Roughton and Forster method of measuring DLCO at varying alveolar oxygen concentrations was used to determine the membrane conductance, Vc, DLCO/alveolar volume (VA), the membrane conductance/VA and thetaVc/VA (theta = carbon monoxide conductance of blood, VA = alveolar volume) in 21 patients with class III to IV heart failure before and after transplantation, and in 21 healthy controls. Transplantation normalized pulmonary capillary pressure and increased cardiac index. DLCO was decreased before transplantation (7.11 vs 10.0 mmol/min/kPa in controls), but DLCO/VA was normal (1.67+/-0.44 vs 1.71+/-0.26 mmol/min/kPa/L in controls). DLCO/VA remained unchanged after transplantation, because the decrease in Vc (82+/-30 vs 65+/-18 ml before and after transplantation) and thetaVc/VA was not compensated by the changes in membrane conductance (11+/-4 vs 12+/-5 mmol/min/kPa before and after transplantation, respectively) and membrane conductance/VA. We conclude that the decrease in DLCO in patients with chronic heart failure is due to a restrictive ventilatory pattern because their DLCO/VA remains normal; the decrease in the membrane conductance is compensated by the increase in Vc. After transplantation, the decrease in Vc due to normalization of pulmonary hemodynamics is not completely compensated for by an increase in membrane conductance. Because the membrane conductances, measured before and after transplantation, are negatively correlated with duration of heart failure, its abnormal pulmonary hemodynamics may have irreversibly altered the alveolar capillary membrane.

Enhanced brain natriuretic peptide response to peak exercise in heart transplant recipients.

We investigated the atrial (ANP) and brain natriuretic peptides (BNP), catecholamines, heart rate, and blood pressure responses to graded upright maximal cycling exercise of eight matched healthy subjects and cardiac-denervated heart transplant recipients (HTR). Baseline heart rate and diastolic blood pressure, together with ANP (15.2 +/- 3.7 vs. 4.4 +/- 0.8 pmol/l; P < 0.01) and BNP (14.3 +/- 2. 6 vs. 7.4 +/- 0.6 pmol/l; P < 0.01), were elevated in HTR, but catecholamine levels were similar in both groups. Peak exercise O2 uptake and heart rate were lower in HTR. Exercise-induced maximal ANP increase was similar in both groups (167 +/- 34 vs. 216 +/- 47%). Enhanced BNP increase was significant only in HTR (37 +/- 8 vs. 16 +/- 8%; P < 0.05). Similar norepinephrine but lower peak epinephrine levels were observed in HTR. ANP and heart rate changes from rest to 75% peak exercise were negatively correlated (r = -0.76, P < 0.05), and BNP increase was correlated with left ventricular mass index (r = 0.83, P < 0.01) after heart transplantation. Although ANP increase was not exaggerated, these data support the idea that the chronotropic limitation secondary to sinus node denervation might stimulate ANP release during early exercise in HTR. Furthermore, the BNP response to maximal exercise, which is related to the left ventricular mass index of HTR, is enhanced after heart transplantation.