Key points Despite growing interest in right ventricular form and function in diseased states, there is a paucity of data regarding characteristics of right ventricular function – namely contractile and lusitropic reserve, as well as ventricular‐arterial coupling, in the healthy heart during rest, as well as submaximal and peak exercise. Pressure‐volume analysis of the right ventricle, during invasive cardiopulmonary exercise testing, demonstrates that that the right heart has enormous contractile reserve, with a three‐ or fourfold increase in all metrics of contractility, as well as myocardial energy production and utilization. The healthy right ventricle also demonstrates marked augmentation in lusitropy, indicating that diastolic filling of the right heart is not passive. Rather, the right ventricle actively contributes to venous return during exercise, along with the muscle pump. Ventricular‐arterial coupling is preserved during submaximal and peak exercise in the healthy heart.AbstractKnowledge of right ventricular (RV) function has lagged behind that of the left ventricle and historically, the RV has even been referred to as a ‘passive conduit’ of lesser importance than its left‐sided counterpart. Pressure‐volume (PV) analysis is the gold standard metric of assessing ventricular performance. We recruited nine healthy sedentary individuals free of any cardiopulmonary disease (42 ± 12 years, 78 ± 11 kg), who completed invasive cardiopulmonary exercise testing during upright ergometry, while using conductance catheters inserted into the RV to generate real‐time PV loops. Data were obtained at rest, two submaximal levels of exercise below ventilatory threshold, to simulate real‐world scenarios/activities of daily living, and maximal effort. Breath‐by‐breath oxygen uptake was determined by indirect calorimetry. During submaximal and peak exercise, there were significant increases in all metrics of systolic function by three‐ to fourfold, including cardiac output, preload recruitable stroke work, and maximum rate of pressure change in the ventricle (dP/dtmax), as well as energy utilization as determined by stroke work and pressure‐volume area. Similarly, the RV demonstrated a significant, threefold increase in lusitropic reserve throughout exercise. Ventricular‐arterial coupling, defined by the quotient of end‐systolic elastance and effective arterial elastance, was preserved throughout all stages of exercise. Maximal pressures increased significantly during exercise, while end‐diastolic volumes were essentially unchanged. Overall, these findings demonstrate that the healthy RV is not merely a passive conduit, but actively participates in cardiopulmonary performance during exercise by accessing an enormous amount of contractile and lusitropic reserve, ensuring that VA coupling is preserved throughout all stages of exercise.
Lymphadenopathy is the commonest presentation in lIIV positive individuals. Fine needle aspiration cytology of 196 HIV positive patients was studied during six monthly review. 75% paients in this stud)' who were asymptomatic were detected to have lymphadenopathy during the surveillance. 82% had lymph nodes smaller than Icm size, Lymphadenopathy at more than one site was observed In 46.8% cases. Commonest opportunistic infection noticed was tuberculosis (TB) in~.2%. Cyto-morphologically reactive pattern with Add fast bacilli (AFB) poshivfty was observed in 16.4% of TB cases. In 2.9% cases AFB were detected even in the tissue fluid. Negative Images of AFB were observed in the macrophages in 3 cases. TB was detected with equal frequency In both asymptomatic and symptomatic groups. Axillary nodes pose problem due to deeper location. False positives were a case of dermatopathic lymphadenopathy and a case of Kimura's disease. False negatives include two cases of TB lymphadenitis. Pathogens should be looked for Irrespective of cyto-morphology. Biopsy should be done to confirm cases of lymphomas. Fine needle aspiration cytology should be included In the protocol of six monthly review of HIV infected cases.
Lung dysfunction is an important part of the pathology of the neurodegenerative disorder, Niemann-Pick C1 (NPC1). We have studied the pulmonary disease in the Npc1NIH/NIH mouse model. On histology, we find large numbers of alveolar foamy macrophages but no alveolar proteinosis. Lung weight as percent of body weight was markedly increased; using the flexiVent small animal ventilator (SCIREQ, Inc.), we find inspiratory capacity, elastance and hysterisivity to be increased while resistance was not changed. Cholesterol measurements show a doubling of lung cholesterol levels. Collagen is also increased. Treatment of Npc1−/− mice with hydroxypropyl-β-cyclodextrin (HPBCD), despite efficacious effects in brain and liver, results in little difference from age-matched controls (using a CNS-expressed transgene to extend the life expectancy of the Npc1−/− mice) for these variables.
We have studied the pathophysiology of lung disease which occurs in two mouse models of Niemann-Pick C1 disease. We utilized Npc1−/− mice transgenic for normal gene expression in glia or neurons and glia at ages several fold the usual and a mouse model of the juvenile form of NPC1, a point mutation, at one age to confirm some findings. Lung weights, as per cent of body weight, increase much more than liver and spleen weights. Although pulmonary function parameters only vary for hysteresis between young and older Npc1−/− mice, they are markedly different than those found in normal control mice. Cholesterol accumulation continued in the older mice but sphingosine-1-phosphate was not increased. Bronchoalveolar lavage (BAL) showed a massive increase (26X) in the number of macrophages. Histologic examination from the older, transgenic Npc1−/− mice showed small foci of alveolar proteinosis and evidence of hemorrhage, as well as dense macrophage accumulation. A large subset of macrophages was immunopositive for Fizz1 or arginase-1, markers of the alternative activation pathway, while no Fizz1 or arginase-1 positive macrophages were found in wild-type mice. The percentage of marker positive macrophages was relatively stable at 5–10% at various ages and within the 2 transgenic models. Phosphohistone H3 and Ki67 showed low levels of proliferation of these macrophages. Apoptosis was prominent within lung capillary endothelial cells, but limited within macrophages. Thus, activation of the alternative pathway is involved in Niemann-Pick C1 associated pulmonary macrophage accumulation, with low proliferation of these cells balanced by low levels of apoptosis.
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