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PubMed2002

Gender governs the relationship between exercise intensity and growth hormone release in young adults.

We previously reported that in young adult males growth hormone (GH) release is related to exercise intensity in a linear dose-response manner (Pritzlaff et al. J Appl Physiol 87: 498-504, 1999). To investigate the effects of gender and exercise intensity on GH release, eight women (24.3 +/- 1.3 yr, 171 +/- 3.2 cm height, 63.6 +/- 8.7 kg weight) were each tested on six randomly ordered occasions [1 control condition (C), 5 exercise conditions (Ex)]. Serum GH concentrations were measured in samples obtained at 10-min intervals between 0700 and 0900 (baseline) and 0900 and 1300 (Ex + recovery or C). Integrated GH concentrations (IGHC) were calculated by trapezoidal reconstruction. During Ex, subjects exercised for 30 min (0900-0930) at one of the following intensities [normalized to the lactate threshold (LT)]: 25 and 75% of the difference between LT and rest, at LT, and at 25 and 75% of the difference between LT and peak O2 uptake. No differences were observed among conditions for baseline IGHC. To determine whether total (Ex + recovery) IGHC changed with increasing exercise intensity, slopes associated with individual linear regression models were subjected to a Wilcoxon signed-rank test. To test for gender differences, data in women were compared with the previously published data in men. A Wilcoxon ranked-sums two-tailed test was used to analyze the slopes and intercepts from the regression models. Total IGHC increased linearly with increasing exercise intensity. The slope and intercept values for the relationship between total IGHC and exercise intensity were greater in women than in men. Deconvolution analysis (0700-1300 h) revealed that, regardless of gender, increasing exercise intensity resulted in a linear increase in the mass of GH secreted per pulse and summed GH production rate, with no changes in GH secretory pulse frequency or apparent half-life of elimination. Exercise reduced the half-duration of GH secretory burst in men but not in women. Gender comparisons revealed that women had greater basal (nonpulsatile) GH secretion across all conditions, more frequent GH secretory pulses, a greater GH secretory pulse amplitude, a greater production rate, and a trend for a greater mass of GH secreted per pulse than men. We conclude that, in young adults, the GH secretory response to exercise is related to exercise intensity in a linear dose-response pattern. For each incremental increase in exercise intensity, the fractional stimulation of GH secretion is greater in women than in men.

Adolescent↗
PubMed2004

Diaphragm electromyogram root mean square response to hypercapnia and its intersubject and day-to-day variation.

Diaphragm activation can be quantified by measuring the root mean square of crural EMG (RMSdi) (Beck J, Sinderby C, Lindstrom L, and Grassino A, J Appl Physiol 85: 1123-1134, 1998). To examine intersubject and day-to-day variation in the RMSdi-Pco(2) relationship, end-tidal Pco(2), minute ventilation (Ve), respiratory frequency (f(B)), and RMSdi were measured in seven healthy subjects on two occasions during steady-state ventilation at seven levels of inspired O(2) fraction (Fi(CO(2))) from 0 to 0.08 in random order. RMSdi was measured with a multielectrode esophageal catheter and controlled for signal contamination and diaphragm position. RMSdi was normalized for values obtained during quiet breathing at functional residual capacity, at Fi(CO(2)) of 0.04, and during an inspiratory capacity maneuver (RMSdi%max) as well as ECG R-wave amplitude at functional residual capacity (RMSdi/ECG(R)), f(B), and thickness of the costal diaphragm measured by ultrasound. RMSdi increased linearly with Pco(2) (mean r(2) = 0.83 +/- 0.10); at the highest Fi(CO(2)), RMSdi%max was 40.2 +/- 11.6%. Relative to the intersubject variation in the Ve-Pco(2) relationship, intersubject variations in the slopes and intercepts of the RMSdi-Pco(2) relationships were 1.7 and 1.8 times, respectively, and RMSdi%max-Pco(2) relationships 0.9 and 1.3 times, respectively, and were unrelated to f(B) and diaphragm thickness. Relative to the day-to-day variation in the Ve-Pco(2) relationship, day-to-day variation in the slopes and intercepts of the RMSdi-Pco(2) relationships were 2.8 and 4.4 times, respectively, and RMSdi/ECG(R)-Pco(2) relationships 1.3 and 2.2 times, respectively. It was concluded that the RMSdi-Pco(2) relationship measures chemosensitivity and is best compared between subjects via RMSdi%max and on separate occasions in the same subject via RMSdi/ECG(R).

Adult↗
PubMed1983

Swimming pattern in intact and decerebrated stingrays.

Stingrays swim with a rostral-to-caudal wave of elevation and depression of the enlarged pectoral fins. The present study compares the timing relations of swimming before and after decerebration in the same animals using electromyograms (EMGs). EMGs were recorded from several freely swimming, intact animals. Most recordings, however, were from stingrays suspended by vertebral clamps. Activity recorded from restrained animals exhibited the same timing relations as freely swimming animals. Therefore, the restrained preparation was used to compare locomotor rhythm in intact and decerebrate stingrays. The delay from the onset of activity recorded at a rostral segment to the onset of activity at successively caudal recording sites (intersegmental delay) was linearly related to the extent of the segmental separation. This relation was not changed by decerebration. Both the intersegmental delay and the EMG burst duration were linearly related to the period of the swim cycle. The intercepts for both relations fell around the origin. Therefore, stingray swimming demonstrates constant phase coupling. Neither the slopes nor the intercepts of the coupling relations were altered by decerebration. Histological examination of the fins indicates that at least two types of muscles exist. Superficial muscle is activated during slow swimming, while the deeper muscle is recruited during faster swimming.

Animals↗
PubMed1983

Swimming rhythm in decerebrated, paralyzed stingrays: normal and abnormal coupling.

Rhythmic motoneuronal activity was recorded from decerebrated, paralyzed stingrays and compared with electromyograms recorded from the same animals. Before and after paralysis, a rostral-to-caudal sequence of alternation occurred between dorsal (elevator) and ventral (depressor) efferents. The swimming pattern was thus observed in the absence of phasic afferent input, and this constitutes fictive locomotion. After paralysis, both the intersegmental delay (time between activation at progressively caudal recording sites) and the burst duration remained linearly related to the swim cycle period. In many instances, neither the slope nor the intercept was significantly altered by immobilization. The intercepts all fell near the origin, indicating that the fictive rhythm remains constant phase coupled. Although the swimming rhythm was obtained after paralysis, some differences occurred. These included fewer and shorter spontaneous sequences, a greater range of cycle periods, and longer burst durations. During fictive swimming, the burst duration:cycle period ratio usually increased to 0.53 from 0.39 observed before paralysis. Therefore, the silent periods seen between burst discharges in antagonist efferents during movement were often absent after paralysis. Mechanical stimulation of the tail reduced both cycle periods and burst durations; however, the burst:cycle ratio remained greater than or equal to 0.50. The linear relation between burst duration and cycle period found for spontaneous sequences was not changed by stimulation of the tail. During fictive swimming the inter- and intrasegmental coupling that characterizes stingray swimming becomes labile. Abnormal coupling appears more often during sequences with long swim cycles. Intrasegmental coupling is tighter than intersegmental coupling at any cycle period. Rhythmic activity at one segmental level can be independent of activity at other levels. This suggests that multiple oscillator circuits exist that are not dependent on propriospinal circuits interconnecting different segments. Rhythmicity in elevator and depressor motoneurons is not dependent on reciprocal connections between the circuitry driving the motor nuclei. Therefore, separate oscillators for elevators and depressors appear to be present within one spinal segment.

Animals↗
PubMed1994

Interactions between the eye and hand motor systems: disruptions due to cerebellar dysfunction.

1. We tested the hypothesis that interactions occur between eye and hand movements produced in conjunction. This was accomplished by having human subjects with cerebellar dysfunction and age-matched controls perform two tasks: 1) tracking a moving target with the hand and 2) performing a pointing movement to intercept the target. Our prediction was that the inaccuracies that are characteristic of eye and hand movements generated in isolation by cerebellar subjects would be accentuated in each system during combined eye-hand tasks. 2. The cerebellar subjects took longer to respond to the onset of target motion in both tasks. This was true for both the eyes and hand, regardless of whether the eye and hand movements were generated in isolation or in conjunction with each other. 3. The cerebellar subjects also displayed a larger degree of error and/or variability in their hand movements than the control subjects. A significant amount of this increased variability was due to systematic changes in the trajectory of the hand during the critical periods leading up to and after each ocular saccade. These systematic changes were consistent with an overestimation of target velocity in the perifoveal visual field. 4. The increased variability of the cerebellar subjects' hand movements was markedly reduced by restricting eye movements. A similar reduction in variability occurred when vision of the hand was restricted in the tracking task. This effect was accompanied by improved eye movements. 5. For both sets of subjects the eye movements were affected by the hand movements produced in the tracking task. In particular, eye movement accuracy was improved in the controls and degraded in the cerebellar subjects when compared with the eye movements generated in isolation. In contrast, no changes were observed in the interception task. 6. Taken together, these results imply that a reciprocal interaction occurs between the eye and hand motor systems and/or that common "upstream" sites influence each of these systems in a similar manner. The functional anatomy and neurophysiological characteristics of several sites where such interactions may take place are discussed.

Adult↗
PubMed1998

Orienting gaze shifts during muscimol inactivation of caudal fastigial nucleus in the cat. I. Gaze dysmetria.

The cerebellar control of orienting behavior toward visual targets was studied in the head-unrestrained cat by analyzing the deficits of saccadic gaze shifts after unilateral injection of muscimol in the caudal part of the fastigial nucleus (cFN). Gaze shifts are rendered strongly inaccurate by muscimol cFN inactivation. The characteristics of gaze dysmetria are specific to the direction of the movement with respect to the inactivated cFN. Gaze shifts directed toward the injected side are hypermetric. Irrespective of their starting position, all these ipsiversive gaze shifts overshoot the target by a constant horizontal error (or bias) to terminate at a "shifted goal" location. In particular, when gaze is directed initially at the future target's location, a response with an amplitude corresponding to the bias moves gaze away from the actual target. Additionally, when gaze is initially in between the target and this shifted goal location, the response again is directed toward the latter. This deficit of ipsiversive gaze shifts is characterized by a consistent increase in the y intercept of the relationship between horizontal gaze amplitude and horizontal retinal error. Slight increases in the slope sometimes are observed as well. Contraversive gaze shifts are markedly hypometric and, in contrast to ipsiversive responses, they do not converge onto a shifted goal but rather underestimate target eccentricity in a proportional way. This is reflected by a decrease in the slope of the relationship between horizontal gaze amplitude and horizontal retinal error, with, for some experiments, a moderate change in the y-intercept value. The same deficits are observed in a different setup, which permits the control of initial gaze position. Correction saccades rarely are observed when visual feedback is eliminated on initiation of the primary orienting response; instead, they occur frequently when the target remains visible. Like the primary contraversive saccades, they are hypometric and the ever-decreasing series of three to five correction saccades reduces the gaze fixation error but often does not completely eliminate it. We measured the position of gaze after the final correction saccade and found that fixation of a visible target is still shifted toward the inactivated cFN by 4.9 +/- 2.4 degrees. This fixation offset is correlated to, but on average 54% smaller than, the hypermetric bias of ipsiversive responses measured in the same experiments. In conclusion, the cFN contributes to the control of saccadic shifts of the visual axis toward a visual target. The hypometria of contraversive gaze shifts suggests a cFN role in adjusting a gain in the translation of retinal signals into gaze motor commands. On the basis of the convergence of ipsiversive gaze shifts onto a shifted goal, the straightness of gaze trajectory during these responses and the production of misdirected or inappropriately initiated responses toward this shifted goal, we propose that the cFN influences the processes that specify the goal of ipsiversive gaze shifts.

Animals↗
PubMed2000

Manual tracking in two dimensions.

Manual tracking was studied by asking subjects to follow, with their finger, a target moving on a touch-sensitive video monitor. The target initially moved in a straight line at a constant speed and then, at a random point in time, made one abrupt change in direction. The results were approximated with a simple model according to which, after a reaction time, the hand moved in a straight line to intercept the target. Both the direction of hand motion and its peak speed could be predicted by assuming a constant time to intercept. This simple model was able to account for results obtained over a broad range of target speeds as well as the results of experiments in which both the speed and the direction of the target changed simultaneously. The results of an experiment in which the target acceleration was nonzero suggested that the error signals used during tracking are related to both speed and direction but poorly (if at all) to target acceleration. Finally, in an experiment in which target velocity remained constant along one axis but the perpendicular component underwent a step change, tracking along both axes was perturbed. This last finding demonstrates that tracking in two dimensions cannot be decomposed into its Cartesian components. However, an analytical model in a hand-centered frame of reference in which speed and direction are the controlled variables could account for much of the data.

Acceleration↗
PubMed1999

Effect of deferoxamine on post-hypoxic-ischemic reperfusion injury of the newborn lamb heart.

UNLABELLED: Post-hypoxic-ischemic (HI) reperfusion induces excess production of non-protein-bound iron (NPBI), leading to formation of the highly reactive hydroxyl radical. We investigated whether the iron-chelator deferoxamine (DFO) could reduce reperfusion injury and improve left ventricular (LV) function. We produced severe HI in 14 newborn lambs and measured pre-HI, upon reperfusion, 60 and 120 min after HI the following parameters: mean aortic blood pressure, total peripheral resistance, stroke volume (SV), ejection fraction (EF) and LV contractility (pre-HI, 60 and 120 min post-HI). These parameters were assessed by measuring LV pressure (tip manometer) and volume (conductance catheter), using inflow occlusion to obtain slope (Ees) and volume intercept of the end-systolic P-V relationship (V10). We determined the antioxidative capacity, i.e. the ratio of ascorbic acid and dehydroascorbic acid (AA/DHAA) and malondialdehyde from coronary sinus blood at pre-HI and at 15, 60 and 120 min post-HI. Seven lambs received DFO (10 mg/kg i.v.) immediately after HI, 6 control lambs received a placebo. While neither Ees nor EF changed significantly in either group, the volume intercept V10 in the DFO-treated group was significantly smaller (0.25 +/- 0.03 vs. 0.70 +/- 0.09, p < 0.05), whereas SV was larger (3.6 +/- 0.6 vs. 2.2 +/- 0.2 ml, p < 0.05) and the AA/DHAA ratio was significantly lower at 15 min post-HI (p < 0.05) providing evidence for HI damage and for the protective effect of DFO. IN CONCLUSION: post-HI treatment of the newborn lamb with DFO has a modifying effect on free radical-induced damage to the myocardium and protects myocardial performance.

Animals↗
PubMed1998

Difference in hepatic tissue oxygenation between total vascular exclusion and inflow occlusion of the liver and the possible role of hepatic venous blood under liver ischemia.

The difference between total vascular exclusion (TVE) and inflow occlusion (IO) of the liver was assessed by the extent of DNA injury in rats and by hepatic tissue oxygen saturation (SahtO2) in pigs. Moreover, the role of hepatic venous blood under liver ischemia was discussed. Seventy percent of the rat livers were exposed to complete IO (hepatic artery + portal vein) or to TVE (IO + hepatic vein) for 30 or 60 min. DNA strand breaks following blood flow interception were measured using the in situ nick translation technique as an indicator of liver damage. IO/TVE were performed on pigs as well under portosystemic bypass, and the oxygen saturation of the hepatic venous blood (SahvO2) was altered by changing the fraction of inspiratory oxygen or by oxygenating the inferior caval blood using an extracorporeal membrane oxygenator. The changes in SahtO2 were measured sequentially using near-infrared spectroscopy. The results were as follows: (1) DNA injury occurred more severely under TVE than under IO of the rat liver at the end of ischemia, as well as 30 min after revascularization. (2) SahtO2 during TVE was significantly lower than that during IO. (3) The increase in SahvO2 by oxygenation of the inferior caval blood resulted in the elevation of SahtO2 under IO. In conclusion, TVE could cause greater damage to the liver than IO due to the lack of the hepatic venous blood. Hepatic venous blood might play an important role in hepatic tissue oxygenation in the case of hepatic blood flow interception.

Animals↗
PubMed2002

Preclinical development of a vaccine 'against smoking'.

BACKGROUND: Nicotine is the main culprit for dependence on tobacco-containing products, which in turn are a major etiologic factor for cardiovascular diseases and cancer. This publication describes a vaccine, which elicits antibodies against nicotine. The antibodies in the blood stream intercept the nicotine molecule on its way to its receptors and greatly diminish the nicotine influx to the brain shortly after smoking. METHODS: The nicotine molecule is chemically linked to cholera toxin B as a carrier protein in order to induce antibodies. The potential to elicit antibodies after subcutaneous as well as intranasal immunization is evaluated. In order to simulate realistic conditions, nicotine pumps delivering the nicotine equivalent of 5 packages of cigarettes for 4 weeks are implanted into the mice 1 week prior to vaccination. The protective effect of the vaccine is measured 5 weeks after vaccination by comparing the influx of radiolabeled nicotine in the brains of vaccinated and non-vaccinated animals 5 min after challenge with the nicotine equivalent of 2 cigarettes. RESULTS: The polyclonal antibodies induced by the vaccine show a mean avidity of 1.8 x 10(7) l/Mol. Subcutaneous immunization elicits high antibody levels of the IgG class, and significant IgA antibody levels in the saliva of vaccinated mice can be found after intranasal vaccination. The protective effect also in the animals with implanted nicotine pumps is significant: less than 10% of radiolabeled nicotine found in the brains of non-vaccinated animals can be found in the brains of vaccinated animals. CONCLUSIONS: These data provide credible evidence that a vaccine can break the vicious circle between smoking and instant gratification by intercepting the nicotine molecule. Astonishingly, there is no sign of exhaustion of specific antibodies even under extreme conditions, which makes it highly unlikely that a smoker can overcome the protective effect of the vaccine by smoking more. Finally, the high titers of specific antibodies after 1 year let us hope that booster vaccinations are probably only necessary in intervals of years.

Administration, Intranasal↗
PubMed2003

Glomerular filtration rate estimation in patients with advanced chronic renal insufficiency based on serum cystatin C levels.

BACKGROUND: Cystatin C has an obvious advantage in the recognition of the initial stages of renal impairment. It is questionable whether cystatin C possesses the same benefit in follow-up of pre-dialysis patients. If cystatin C were also a sensitive marker of GFR in pre-dialysis patients, then it could be expected that, for the same degree of a decrease in GFR, the increase in S(cyst) would be higher than in S(cr) because of the significant increase in tubular secretion of creatinine in residual nephrons. The aim of this study was to evaluate whether S(cyst) in patients with GFR <or=40 ml/min/1.73 m(2) provides a more accurate estimate of GFR than S(cr) does. METHODS: The study was performed in 67 patients (mean age 41.5 +/- 7.6 years) with chronic renal insufficiency (GFR = 19.8 +/- 9.9 ml/min/1.73 m(2)) caused by various chronic renal diseases (predominantly by chronic glomerulonephritis and chronic interstitial nephritis). GFR was measured by inulin clearance under conditions of stabilized plasma concentrations and water loading. Creatinine clearance and serum cystatin C concentration (using immunonephelometry) were measured at the same time. For statistical evaluation, linear regression analysis, receiver-operating characteristic (ROC) curves analysis and the method of Bland and Altman were used. RESULTS: A significant correlation (r = 0.813, p < 0.001) was demonstrated between 1/S(cyst) and C(in) as well as between 1/S(cr) and C(in) (r = 0.815, p < 0.001). There were no significant differences between the regression coefficients and the intercepts of regression straight lines characterizing these relationships. ROC curves analysis using the cut-off values for C(in) = 20 ml/min/1.73 m(2) and C(in) = 10 ml/min/ 1.73 m(2) did not show significant differences of corresponding AUC values for S(cyst) and S(cr) although there was a trend for superiority of S(cyst) in comparison with S(cr). The multiples of upper reference values of S(cyst) and S(cr) in examined patients did not differ significantly. There was a highly significant linear correlation between C(in) and C(cr) in pre-dialysis patients (r = 0.921, p < 0.001). The regression coefficient of this relation (1.279) was significantly higher than 1.0 (p < 0.001) and the value of intercept (6.50 ml/min/1.73 m(2)) was significantly higher than zero (p < 0.001). The average of C(cr)/C(in) in patients with C(in) <10 ml/min/1.73 m(2) was 2.11 (+/- 0.29) and 1.72 (+/- 0.35) for those with C(in) 10-20 ml/min/1.73 m(2). CONCLUSIONS: The findings suggest that in patients with advanced chronic renal insufficiency (CRI) for the same decrease in GFR the increase of S(cyst) is not significantly higher than that of S(cr), although the tubular secretion of creatinine is significantly increased. Further studies (especially those focused on nonrenal elimination of cystatin C) are needed to elucidate the lack of difference between changes in S(cyst) and S(cr) in patients with CRI.

Adolescent↗
PubMed2006

Macrophage colony-stimulating factor aggravates rather than regenerates emphysematous lungs in mice.

BACKGROUND: Lung regeneration is an innovative strategy that may cure pulmonary emphysema. The bone marrow (BM) harbors pulmonary stem cells. Hematopoietic cytokine-driven mobilization of BM cells may thus support lung regeneration. OBJECTIVES: The aim of this study was to determine whether systemic administration of macrophage colony-stimulating factor (M-CSF) leads to the regeneration of lungs in a murine model of elastase-induced emphysema. METHODS: C57BL/6J mice were administered elastase intratracheally. Four weeks later, in the absence or presence of elastase treatment, mice were intraperitoneally given either M-CSF or saline on days 1-5 each week for 3 weeks. Lung tissue was harvested 24 h after the last injection. RESULTS: M-CSF administration without prior elastase did not affect the mean linear intercept, surface area, or surface area/lung volume. In contrast, M-CSF administration following elastase injury caused a greater increase in the mean linear intercept and greater decreases in surface area and surface area/lung volume than saline administration following elastase, indicating that M-CSF aggravated emphysema. This aggravation of emphysema was accompanied by accumulation of pulmonary alveolar macrophages (AMs) expressing metalloproteinase (MMP)-9 and MMP-12. M-CSF stimulated AMs to express MMPs in vitro. CONCLUSIONS: These results suggest that M-CSF administration does not support lung regeneration but rather aggravates the lung destruction associated with elastase injury.

Animals↗
PubMed1981

Continuous registration of blood velocity and cardiac output with a hot-film anemometer probe, mounted on a Swan-Ganz thermodilution catheter.

In order to construct a catheter, capable of monitoring cardiac output, a specially designed double-conical hot-film anemometer probe was fastened at the tip of a Swan-Ganz thermodilution catheter. Common sources of error for most catheter velocity probes include difficult calibration, unknown velocity profile at the point of measurement and unknown position of the probe in this profile. By using mongrel dogs and in order to exclude these sources of error, the intermittent thermodilution method was used to in vitro calibrate the hot-film anemometer, which registered velocity continuously. A mean correlation coefficient between these two methods was found to be 0.886. A mean line of regression between thermodilution (abscissa) and anemometer (ordinate) had a slope of 0.796 +/- 0.223 (+/- SD) and a y-intercept of 24 +/- 14 ml/min/kg. The slope was significantly lower than one (t test, p less than 0.05) and the y-intercept significantly larger than zero (t test, p less than 0.02). As a control of the thermodilution method, electromagnetic flow in the ascending aorta was registered and a mean correlation coefficient of 0.967 found. The hot-film sensor itself can be used as thermodilution method with the hot-film anemometer's continuous registration of velocity.

Animals↗
PubMed1984

Adrenergic blockade does not change ventilatory response to CO2 in awake resting goats.

Although adrenergic agonists increase resting ventilation and responsiveness to CO2, there are conflicting data about the effect of adrenergic blockade on ventilatory responses. In this study, we investigated the effect of alpha- or beta-adrenergic blockade on the response to hyperoxic CO2 rebreathing in awake goats. In 5 goats, studied before and after intravenous administration of phentolamine or propranolol, there was no difference (compared to control studies) in the mean slope, x-intercept, or ventilation at end-tidal PCO2 (PETCO2) = 70 torr for the CO2 response curves after either drug. When mean inspiratory flow rate (VT/Ti) was plotted against PETCO2, there was also no change in these measurements after propranolol. After phentolamine, there was a slight decrease in the slope and x-intercept, but no change in VT/Ti at PETCO2 = 70 torr. We conclude that acute administration of alpha- or beta-adrenergic blockers does not affect ventilatory response to CO2 inhalation in goats, and suggest that adrenergic activity is not an important modulating influence for CO2 responsiveness in this species.

Animals↗
PubMedDate not supplied

Effects of PGE1 in experimental vasoconstrictive pulmonary hypertension.

The pulmonary vascular and systemic effects of PGE1 were studied in a canine model of pulmonary hypertension. Systemic arterial, central venous and pulmonary arterial pressures were monitored and an electromagnetic flow probe was placed around the ascending aorta for continuous cardiac index (CI) measurements. Through a laparotomy, an arteriovenous fistula was created between the abdominal aorta and inferior vena cava. Gradual opening of this fistula significantly affected CI and these values were used to generate pressure-flow curves (pulmonary arterial pressure (PAP)/CI). Following PGF2 alpha infusion (5-10 micrograms/kg/min) significant pulmonary hypertension was observed (2- to 3-fold increase in PAP). PGF2 alpha infusion also resulted in a significant rise in heart rate and systemic vascular resistance (SVR) while CI was reduced. PGF2 alpha significantly increased both the line slope (vascular resistance) and intercept (outflow pressure) of the pressure-flow curves. Intravenous PGE1 infusion in doses ranging from 40 to 320 ng/ml/min elicited a dose-dependent reduction of both pulmonary and systemic vascular resistances, the former being slightly more affected. With PGE1 infusions only the intercept of the pressure-flow curve was affected suggesting that specific components of the pulmonary vascular bed modulating the outflow pressure were involved. High doses of PGE1 significantly decreased arterial PO2, indicating that this prostaglandin derivative deteriorates pulmonary gas exchanges.

Alprostadil↗
PubMed1985

Ventilatory responses of aged male and female rats to hypercapnia and to hypoxia.

Ventilatory parameters such as tidal volume, minute ventilation (VE), and inspiratory flow rate decrease in 24- vs. 12-month-old male and female rats. Differences between male and female values are maintained with age. Ventilatory response male and female rats exhibit to hypercapnia is altered by a decrease of the intercept, but not the slope value. The pattern of breathing exhibited by young females and males in response to hypercapnia (i.e. an increase of VT and f) is different than that noted in old males and females (i.e. an increase in VT only). In contrast, the ventilatory response both of slope and intercept male rats show by 24 months is decreased compared to the 12-month value; but the slope value is actually increased in the older vs. younger female rats in response to hypoxia.

Age Factors↗
PubMed2001

Endothelin-1 has a unique oxygen-saving effect by increasing contractile efficiency in the isolated rat heart.

BACKGROUND: The effect of endothelin (ET)-1 on cardiac energetics is not fully understood. METHODS AND RESULTS: In isolated, coronary-perfused rat hearts, we measured left ventricular contractility index (E(max)), pressure-volume area (PVA), and myocardial oxygen consumption (MVO(2)) before and after administration of ET-1 (1x10(-)(9) mol/L). ET-1 increased E(max) by 48+/-16% (P<0.01) and the total MVO(2) by 24+/-11% (P<0.01). The MVO(2)-PVA relations were linear both before and after ET-1 (r>0.99). ET-1 shifted MVO(2)-PVA upward, increasing the MVO(2) intercept by 24+/-13%. At the same time, ET-1 decreased the slope (S), with 1/S (contractile efficiency) being 46+/-5% before and 56+/-5% after ET-1 (P<0.01). ET-1-induced increases in E(max) and in contractile efficiency were abolished by an ET(A) receptor blocker (S-0139) but not by an ET(B) blocker (BQ-788). Although high [Ca(2+)] perfusion increased E(max) and the intercept to the same extent as ET-1, it did not change S. N(G)-Nitro-L-arginine (an inhibitor of nitric oxide synthase) increased the coronary perfusion pressure as much as ET-1, but S again remained unchanged. Dimethylamyloride (Na(+)/H(+) exchanger inhibitor) partially blocked the positive inotropic effect of ET-1 but not the ET-1-induced increase in the contractile efficiency. CONCLUSIONS: Agonistic effects of ET-1 on the ET(A) receptor economized the chemomechanical conversion efficiency of the left ventricular unit myocardium by a mechanism independent of the Na(+)/H(+) exchanger. This unique oxygen-saving effect of ET-1 may play an adaptive role in the failing myocardium, in which local accumulation of ET-1 is present.

Amiloride↗
PubMed1986

Assessment of the end-systolic pressure-volume relationship in human beings with the use of a time-varying elastance model.

The analysis of left ventricular end-systolic pressure-volume relationships in human beings has been hindered by the lack of a practical method of serial volume assessment and by an imprecise definition of end-systole. Modifications of the end-systolic relationship that have been used to circumvent these problems have included the use of single-point end-systolic pressure-volume ratios, the use of peak systolic pressure/minimum ventricular volume points for end-systolic points, and the use of end-ejection as a marker for end-systole. To assess the correlation between the parameters generated by these modifications with the slope (Emax) and volume intercept (VO) of the end-systolic line as defined by Sagawa's model of time-varying elastance, simultaneous measurement of left ventricular pressure and gated radionuclide volume was made in 26 patients under various loading conditions and pressure-volume diagrams were constructed for each loading condition from 32 simultaneous pressure-volume coordinates. Two pressure-volume diagrams were recorded in 14 patients and three pressure-volume diagrams were recorded in 12 patients. Emax and VO were determined in all patients from the slope and volume intercept of the isochronic pressure-volume line with the maximum time-varying elastance as described by Sagawa's model and were designated true Emax and true VO, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗