Citations

To perform a range of ventilatory and nonventilatory behaviors, the diaphragm muscle (DIAm) must be able to generate sufficient forces throughout the lifespan. We hypothesized that sarcopenia impacts DIAm force generation and thus limits performance of expulsive, higher force, nonventilatory behaviors. Male and female mice ( n = 79) at 6 and 24 mo of age (100 vs. 70–75% survival, respectively) were used to examine transdiaphragmatic pressure (Pdi) generation across motor behaviors in vivo and in vitro DIAm specific force. We found a significant effect of age on maximum Pdi (20–41% decline during tracheal occlusion and bilateral phrenic nerve stimulation), maximum DIAm specific force (30% decline), and DIAm fatigue resistance (15% increase). There were no differences between sexes in these age effects on DIAm performance. These results support our hypothesis that sarcopenia primarily impacts higher force, nonventilatory motor behaviors of the DIAm. Such functional limitations may have negative implications in the ability of the DIAm to generate forces needed for airway clearance in old age and thereby contribute to age-related respiratory complications.

Infusion of ANG II at a rate not sufficient to evoke an immediate vasoconstrictor response, produces a slow increase in blood pressure. Circulating levels of ANG II may be within ranges found in normotensive individuals, although inappropriately high with respect to sodium intake. When ANG II levels are dissociated from sodium levels, oxidative stress (OXST) occurs, which can increase blood pressure by several mechanisms. These include inadequate production or reduction of bioavailability of nitric oxide, alterations in metabolism of arachidonic acid, resulting in an increase in vasoconstrictors and decrease in vasodilators, and upregulation of endothelin. This cascade of events appears to be linked, because ANG II hypertension can be blocked by inhibition of any factor located distally, blockade of ANG II, OXST, or endothelin. Such characteristics are shared by other models of hypertension, such as essential hypertension, hypertension induced by reduction in renal mass, and renovascular hypertension. Thus these findings are clinically important because they reveal 1) uncoupling between ANG II and sodium, which can trigger pathological conditions; 2) the various OXST mechanisms that may be involved in hypertension; and 3) therapeutic interventions for hypertension developed with the knowledge of the cascade involving OXST.

Hypercholesterolemia (HC) is characterized by increased circulating 8- epi-prostaglandin-F2α(isoprostane), a vasoconstrictor, marker, and mediator of increased oxidative stress, whose vascular effects might be augmented in HC. Anesthetized pigs were studied in vivo with electron beam computed tomography after a 12-wk normal ( n = 8) or HC ( n = 8) diet. Mean arterial pressure (MAP), single-kidney perfusion, and glomerular filtration rate (GFR) were quantified before and during unilateral intrarenal infusions of U46619 (10 ng · kg−1· min−1) or isoprostane (1 μg · kg−1· min−1). Basal renal perfusion and function were similar, and isoprostane infusion elevated its systemic levels similarly in normal and HC (333 ± 89 vs. 366 ± 48 pg/ml, respectively, P < 0.01 vs. baseline). Both drugs markedly and comparably decreased cortical perfusion and GFR in both groups, whereas medullary perfusion decreased significantly only in HC. Moreover, MAP increased significantly only in HC (+9 ± 3 and +11 ± 3 mmHg, respectively, P≤ 0.05). Hence, in HC, renal functional responses to high-dose isoprostane are largely similar to normal, but the systemic circulation exhibits augmented sensitivity to pathophysiological levels of isoprostane and U46619 , which may potentially play a role in development of hypertension and vascular injury associated with increased oxidative stress.

Appropriate nephron function is dependent on the intrarenal arrangement of blood vessels. The preferred and primary means to study the architecture of intrarenal circulation has been by filling it with opaque substances such as india ink, radio-opaque contrast material, or various polymers for study by light or scanning electron microscopy. With such methodologies, superficial vessels may obscure deep vessels and little quantitative information may be obtained. Serial-section microtomy has not been practical because of problems relating to alignment and registration of adjacent sections, lost sections, and preparation time and effort. Microcomputed tomography (micro-CT) overcomes such limitations and provides a means to study the three-dimensional architecture of filled vessels within an intact rodent kidney and to obtain more quantitative information. As an example of micro-CT's capabilities, we review the use of micro-CT to study the alterations in renal microvasculature caused by the development of liver cirrhosis after chronic bile duct ligation. In this example, micro-CT evidence shows a selective decrease in cortical vascular filling in the kidney, with a maintenance of medullary vascular filling. These changes may contribute to the salt and water retention that accompanies cirrhosis. These results indicate that micro-CT is a promising method to evaluate renal vascular architecture in the intact rodent kidney relative to physiological and pathological function.

Our experiments were designed to determine the acute effects of 17β-estradiol on femoral veins from intact and ovariectomized female pigs. Rings of femoral veins with or without endothelium were suspended in organ chambers for measurement of isometric force. Concentration-response curves to 17β-estradiol (10−9to 10−5M) were obtained in veins contracted with prostaglandin F2αin the absence and presence of inhibitors of either estrogen receptors (ICI-182780; 10−5M), nitric oxide synthase [ NG-monomethyl-l-arginine (l-NMMA); 10−4M], soluble guanylate cyclase (1- H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 10−5M), or potassium channels (tetraethylammonium; 10−2M). Estrogen receptors were identified with the use of Western blotting and immunostaining in veins of both groups. 17β-Estradiol caused acute endothelium-dependent relaxations in both groups. Relaxations to 17β-estradiol were inhibited byl-NMMA and 1- H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one but not ICI-182780. Tetraethylammonium inhibited relaxations only in veins with endothelium from intact females. Results indicate that 17β-estradiol causes acute endothelium-dependent relaxations in femoral veins. The relative contribution of nitric oxide and K+channels as mechanisms involved in relaxations to 17β-estradiol in femoral veins is modulated by ovarian status.

Experiments were designed to determine how ovariectomy modulates mitogenic factors in platelets and how these factors affect proliferation of coronary arterial smooth muscle. Platelet-derived growth factors (PDGFABand PDGFBB), transforming growth factors (TGF-β1and TGF-β2), and vascular endothelial growth factor (VEGF165) were quantified in platelet lysates and platelet-poor plasma from adult gonadally intact and ovariectomized female pigs by ELISA. Proliferation of cultured coronary arterial smooth muscle cells (SMCs) from both groups of pigs was determined in response to autologous or heterologous platelet lysates. Platelet concentrations of PDGFBB, but not PDGFAB, TGF-β1, and TGF-β2, increased with ovariectomy. VEGF165was not detected in platelets from either group. Proliferation of SMCs from ovariectomized females was significantly greater on exposure to autologous or heterologous platelet lysates than proliferation of SMCs from intact females. These results indicate that ovariectomy increases concentrations of PDGFBBin platelets. Higher levels of PDGFBBin platelets in synergy with other platelet-derived products could contribute to increased proliferative arterial response to injury after ovariectomy.

Purpose. To explore perceptions and experiences of Peruvian medical students about observed, preferred, and feasible decision-making approaches. Methods. We surveyed senior medical students from 19 teaching hospitals in 4 major cities in Peru. The self-administered questionnaire collected demographic information, current approach, exposure to role models for and training in shared decision making, and perceptions of the pertinence and feasibility of the different decision-making approaches in general as well as in challenging scenarios. Results. A total of 327 senior medical students (51% female) were included. The mean age was 25 years. Among all respondents, 2% reported receiving both theoretical and practical training in shared decision making. While 46% of students identified their current decision-making approach as clinician-as-perfect-agent, 50% of students identified their teachers with the paternalistic approach. Remarkably, 53% of students thought shared decision making should be the preferred approach and 50% considered it feasible in Peru. Among the 10 challenging scenarios, shared decision making reached a plurality (40%) in only one scenario (terminally ill patients). Conclusion. Despite limited exposure and training, Peruvian medical students aspire to practice shared decision making but their current attitude reflects the less participatory approaches they see role modeled by their teachers.