Age-related effects of digoxin on myocardial contractility and Na-K pump in sheep

1982 ◽  
Vol 243 (4) ◽  
pp. H517-H522
Author(s):  
T. J. Hougen ◽  
W. F. Friedman
Keyword(s):  
Active Transport ◽  
Monovalent Cation ◽  
Left Ventricular ◽  
Rate Of Change ◽  
Control Group ◽  
Base Line ◽  
Experimental Conditions ◽  
Adult Sheep ◽  
Age Related ◽  
Age Dependent

The age-dependent effects of an acute nontoxic, positively inotropic dose of digoxin on myocardial monovalent cation active transport were determined in fetal, newborn, and adult sheep. Thirty-five lightly sedated, closed-chest animals were instrumented to record electrocardiogram, left ventricular (LV) pressure, and rate of change of LV pressure (LV dP/dt). Ouabain-inhibitable uptake of Rb+ (86Rb+) was measured in both right ventricular (RV) and LV slices from control animals and in animals infused with [3H]digoxin (0.04 mg/kg) sufficient to cause an increase in LV dP/dt without toxicity. Sixty minutes after digoxin, LV dP/dt increased 123% over base-line values in fetuses, 131% in newborns, and 165% in adult animals. RV and LV myocardial digoxin concentrations were similar in all groups. Rb+ active transport was significantly reduced in both RV and LV tissue from all animals 60 min after digoxin. Control animals showed no significant changes in contractility or Rb+ active transport among the control group of fetal, newborn, or adult sheep. Acute infusions of digoxin increased LV contractility in each age group and was accompanied by digoxin-induced inhibition of myocardial Rb+ active transport. No age-related differences in the extent of Rb+ active transport among control or among digoxin-treated animals were observed under these experimental conditions. These studies suggest that the differential response to the therapeutic and toxic effects of digoxin in sheep of various ages does not reside in an age-dependent response of the myocardial sodium pump to digoxin.

scholarly journals Merit of Anisodamine Combined with Opioidδ-Receptor Activation in the Protection against Myocardial Injury during Cardiopulmonary Bypass

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Xuan Hong ◽  
Huimin Fan ◽  
Rong Lu ◽  
Paul Chan ◽  
Zhongmin Liu
Keyword(s):  
Cardiopulmonary Bypass ◽  
Troponin T ◽  
Ischemia Reperfusion ◽  
Combined Treatment ◽  
Left Ventricular Pressure ◽  
Receptor Activation ◽  
Left Ventricular ◽  
Rate Of Change ◽  
Control Group ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia/reperfusion (MIR) injury easily occurrs during cardiopulmonary bypass surgery in elderly patients. In an attempt to develop an effective strategy, we employed a pig model of MIR injury to investigate the maximum rate of change of left ventricular pressure, left ventricular enddiastolic pressure, and left intraventricular pressure. Coronary sinus cardiac troponin T (TnT) and adenosine-triphosphate (ATP) content in myocardium were measured. The ultrastructures for MIR injury were visualized by transmission electron microscopy (TEM). The role ofδ-opioid receptor activation using D-Ala2, D-Leu5-enkephalin (DADLE) in both early (D1) and late (D2) phases of cardioprotection was identified. Also, the merit of cardioprotection by DADLE in combination with anisodamine, the muscarinic receptor antagonist (D+M), was evaluated. Glibenclamide was employed at the dose sufficient to block ATP-sensitive potassium channels. Significant higher cardiac indicators, reduced TnT and increased ATP contents, were observed in D1, D2, and D+M groups compared with the control group. DADLE induced protection was better in later phase of ischemia that was attenuated by glibenclamide. DADLE after the ischemia showed no benefit, but combined treatment with anisodamine showed a marked postischemic cardioprotection. Thus, anisodamine is helpful in combination with DADLE for postischemic cardioprotection.

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

2006 ◽  
Vol 105 (4) ◽  
pp. 746-752 ◽  
Author(s):  
James D. Ross ◽  
Richard Ripper ◽  
William R. Law ◽  
Malek Massad ◽  
Patricia Murphy ◽  
...  
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Left Ventricular ◽  
Rate Of Change ◽  
Control Group ◽  
Prolonged Storage ◽  
Mean Values ◽  
Isolated Hearts ◽  
Lactate Dehydrogenase Release ◽  
Positive Rate

Background Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone. Methods After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured. Results All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. Conclusions Adding bupivacaine to a depolarizing cardioplegia solution reduces cell damage and improves cardiac function after prolonged storage. Metabolic inhibition may contribute to this phenomenon, which is not entirely explained by sodium channel blockade.

Adenosine A3-receptor stimulation attenuates postischemic dysfunction through KATP channels

1999 ◽  
Vol 277 (1) ◽  
pp. H228-H235 ◽  
Author(s):  
Vinod H. Thourani ◽  
Masanori Nakamura ◽  
Russell S. Ronson ◽  
James E. Jordan ◽  
Zhi-Qing Zhao ◽  
...  
Keyword(s):  
Katp Channels ◽  
Left Ventricular ◽  
Rate Of Change ◽  
Control Group ◽  
Receptor Stimulation ◽  
Rat Hearts ◽  
Positive Rate ◽  
Perfused Rat Hearts ◽  
Adenosine Agonists ◽  
Developed Pressure

We tested the hypothesis that selective adenosine A3-receptor stimulation reduces postischemic contractile dysfunction through activation of ATP-sensitive potassium (KATP) channels. Isolated, buffer-perfused rat hearts ( n = 8/group) were not drug pretreated (control) or were pretreated with adenosine (20 μM), 2-chloro- N 6-(3-iodobenzyl)-adenosine-5′- N-methyluronamide (Cl-IB-MECA; A3 agonist, 100 nM), Cl-IB-MECA + 8-(3-noradamantyl)-1,3-dipropylxanthine (KW-3902; A1 antagonist, 5 μM), Cl-IB-MECA + glibenclamide (Glib; KATP-channel blocker, 0.3 μM), or Glib alone for 12 min before 30 min of global normothermic ischemia followed by 2 h of reperfusion. After 2 h of reperfusion, left ventricular developed pressure (LVDP, %baseline) in control hearts was depressed to 34 ± 2%. In hearts pretreated with Cl-IB-MECA, there was a statistically significant increase in LVDP (50 ± 6%), which was reversed with coadministration of Glib (37 ± 1%). Control hearts also showed similar decreases in left ventricular peak positive rate of change in pressure (dP/d t). Therefore, the A3 agonist significantly attenuated postischemic cardiodynamic injury compared with the control, which was reversed by Glib. Cumulative creatine kinase (CK in U/min) activity was most pronounced in the control group (10.4 ± 0.6) and was significantly decreased by Cl-IB-MECA (7.5 ± 0.4), which was reversed by coadministration of Glib (9.4 ± 0.2). Coronary flow was increased during adenosine infusion (160% of baseline) but not during Cl-IB-MECA infusion. Effects of Cl-IB-MECA were not reversed by the specific A1 antagonist KW-3902. We conclude that cardioprotection afforded by A3-receptor stimulation may be mediated in part by KATP channels. Cl-IB-MECA may be an effective pretreatment agent that attenuates postischemic cardiodynamic dysfunction and CK release without the vasodilator liability of other adenosine agonists.

scholarly journals Circulating miRNA expression in asthmatics is age-related and associated with clinical asthma parameters, respiratory function and systemic inflammation

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aleksandra Wardzyńska ◽  
Małgorzata Pawełczyk ◽  
Joanna Rywaniak ◽  
Joanna Makowska ◽  
Joanna Jamroz-Brzeska ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Mirna Expression ◽  
Serum Levels ◽  
Control Group ◽  
Serum Mirna ◽  
Age Related ◽  
Age Dependent ◽  
Elderly Asthmatics ◽  
Clinical Asthma ◽  
Lower Expression

Abstract Background The course of asthma may differ between elderly asthmatics (EA) and non-elderly asthmatics (nEA), which may be partially associated with an age-dependent aberrant immune response. The aim of the study was to determine the influence of serum miRNA expression on asthma characteristics and systemic inflammation markers in EA and nEA. Methods Control and severity of asthma, pulmonary function and FeNO were assessed in 28 EA and 31 nEA patients. The control group included 59 elderly and non-elderly healthy individuals. The expression of selected miRNAs in serum was measured with rt-PCR, and proinflammatory cytokine activity was assayed by ELISA or flow cytometry. Results No difference in serum miRNA expression was observed between the asthmatics and healthy controls. EA demonstrated lower expression of miRNA-106a and miRNA-126a than nEA (p = 0.003 and p = 0.02) and EC had lower expression of miRNA-146a, -126a, -106a and 19b than nEC (p = 0.001, p = 0.003, p = 0.005 and p < 0.001 respectively). Only nEA demonstrated a relationship between the expression of selected miRNAs and the level of asthma control (assessed with ACT) and with airway inflammation, measured by FeNO level. All patients with asthma demonstrated elevated TNFα, IL-6 and sTNF RI levels compared to controls (p = 0.026, p = 0.03 and p < 0.001 respectively). EA demonstrated a higher TNFα level than EC (p < 0.001), and EA had a higher level of sTNF RI than nEA (p < 0.001). A significant correlation was observed between serum levels of proinflammatory cytokines and selected miRNAs. Conclusion Serum miRNA expression was found to correlate with clinical characteristics of asthma and systemic inflammation in an age-dependent fashion, suggesting that miRNA may differentially contribute to asthma pathogenesis in elderly and non-elderly patients.

Multilevel model estimation of age-dependent individual-specific trajectories for left ventricular echocardiographic indexes in an asymptomatic elderly cohort

2012 ◽  
Vol 112 (7) ◽  
pp. 1128-1134 ◽  
Author(s):  
Yu-hong Wang ◽  
Yu-ping Jiang ◽  
Shan-shun Luo ◽  
Fang-fang Qiao ◽  
Hui Han
Keyword(s):  
Multilevel Models ◽  
The Elderly ◽  
Left Ventricular ◽  
Individual Variability ◽  
Ratio Test ◽  
Age Related ◽  
Age Dependent ◽  
Aging Study ◽  
Elderly Cohort ◽  
The Individual

Few studies have been performed on the individual-specific trajectory of left ventricular aging as assessed by echocardiography in an asymptomatic elderly cohort. In the present study, a representative cohort of elderly men, who were long-term asymptomatic for cardiovascular issues, were selected from an ongoing observational aging study. Annual echocardiographic data were used to establish an age-dependent hierarchical model. Based on two-level linear regression results, four echocardiographic indexes [left ventricular mass (LVmass; −1.872 g/yr), posterior ventricular wall thickness (−0.048 mm/yr), fraction shortening (0.097/yr), and transmitral peak A velocity (−0.006 m·s−1·yr−1)] changed significantly with increasing age and were age- and subject-dependent. The most characterized results of the study were the significant, age-related, within-individual variances in echocardiographic results, which were observed using the likelihood ratio test at an occasion-dependent level. Of these, fluctuated amplitudes of two systolic variables [i.e., LVmass (con/age = −0.012 ± 0.004; P = 0.0007) and fraction shortening (con/age = −0.001 ± 0.004; P = 0.05)] were significantly attenuated with increasing age within individuals. On the other hand, the age-related variability of four diastolic Doppler variables [i.e., peak A velocity (con/age = 0.003 ± 0.002; P = 0.0009), peak E velocity (con/age = 0.004 ± 0.003; P = 0.01), E/A ratio (con/age = 0.007 ± 0.003; P = 0.0002), and deceleration time of E wave (con/age = 0.025 ± 0.007; P < 0.0001)] significantly increased with increasing age within individuals. The age-related individual variability of left ventricular indexes observed in this continuous asymptomatic cohort may reflect the mechanism of preclinical, individualized heart aging. In conclusion, successfully fitted multilevel models were applied as a valuable tool to determine the mechanism of individual cardiac aging in the elderly.

Cardiac changes during behavioral stress in dogs

1979 ◽  
Vol 236 (5) ◽  
pp. H750-H758 ◽  
Author(s):  
R. A. Galosy ◽  
L. K. Clarke ◽  
J. H. Mitchell
Keyword(s):  
Heart Rate ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Avoidance Task ◽  
Base Line ◽  
Sidman Avoidance ◽  
Ventricular Systolic Pressure ◽  
Behavioral Stress ◽  
Left Ventricular Systolic Pressure

Alterations in heart rate (HR), left ventricular systolic pressure (LVP), and maximum rate of left ventricular pressure development (LV dP/dtmax) during a Sidman avoidance task were studied in eight chronically prepared dogs. Four of these animals comprised a nonstressed control group. In the experimental group, in addition to phasic increases in HR, LVP, and LV dP/dtmax during the avoidance period of each day, tonic increases in these measures were also observed over the 13 days of the experiment. Left ventricular systolic pressure was found to be least sensitive to the stress procedure inasmuch as the phasic changes were no longer present after the 10th day and tonic levels were within base-line values by the 13th day. When alterations in cardiac activity were observed in the nonstressed animals, there were decreases in function. It was concluded that controlled behavioral stress produces increased cardiac performance without increased bodily activity. It was also hypothesized that preavoidance increases in heart rate in experimental animals were the result of vagal influences on the heart, whereas avoidance increases in HR, LV dP/dtmax, and LVP were functions of increased beta-sympathetic activity on the heart and adaptive peripheral vascular changes.

Coronary arterial inflow impediment during systole is little affected by capacitive effects

1993 ◽  
Vol 264 (3) ◽  
pp. H715-H721 ◽  
Author(s):  
P. Bouma ◽  
P. Sipkema ◽  
N. Westerhof
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Rate Of Change ◽  
Cardiac Contraction ◽  
Ventricular Pressure ◽  
Experimental Conditions ◽  
Dynamic Contractions ◽  
Arterial Inflow ◽  
Static Contractions

During cardiac contraction coronary arterial inflow is impeded, whereas venous flow is augmented. These effects are assumed to be caused by diameter reductions of intramyocardial blood vessels. The reduction in vascular diameter (and thus vascular volume) during contraction increases coronary resistance and/or decreases back pressure so that flow decreases and the rate of change of volume results in a capacitive flow. The aim of this study was to estimate the contribution of capacitive flow to total coronary inflow impediment. Isolated blood-perfused (100 mmHg and constant), maximally vasodilated, ryanodine-pretreated rat hearts (n = 8) with intraventricular balloons were used. The coronary inflow impediment during isovolumic beats at a heart rate of 2–3 Hz (dynamic contractions) and during prolonged systoles obtained by fast pacing (static contractions, no capacitive flow impediment) were compared. Changing left ventricular balloon volume enabled us to vary left ventricular pressure and to relate systolic flow to systolic left ventricular pressure. We found that for the same contractility (expressed in terms of systolic pressure-volume relationship and maximal elastance) and same left ventricular pressure, the ratio of coronary inflow impediment in dynamic and static contractions is not significantly different from unity (P < 0.005). This implies that under our experimental conditions coronary inflow impediment in dynamic contractions is little affected by capacitive effects.

scholarly journals Coenzyme Q10 Supplementation and Oocyte Aneuploidy in Women Undergoing IVF-ICSI Treatment

2014 ◽  
Vol 8 ◽  
pp. CMRH.S14681 ◽  
Author(s):  
Yaakov Bentov ◽  
Thomas Hannam ◽  
Andrea Jurisicova ◽  
Navid Esfandiari ◽  
Robert F. Casper
Keyword(s):  
Coenzyme Q10 ◽  
Polar Body ◽  
Comparative Genomic ◽  
Control Group ◽  
Human Menopausal Gonadotropin ◽  
Power Calculation ◽  
Base Line ◽  
Aneuploidy Rate ◽  
Age Related ◽  
Polar Body Biopsy

Background The age-related reduction in live-birth rate is attributed to a high rate of aneuploidy and follicle depletion. We showed in an animal model that treatment with Coenzyme Q10 (CoQ10) markedly improved reproductive outcome. The aim of this study was to compare the post-meiotic oocyte aneuploidy rate in in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) patients treated with CoQ10 or placebo. Methods We conducted a double blind placebo controlled randomized trial that included IVF-ICSI patients 35-43 years of age. The patients were treated with either 600 mg of CoQ10 or an equivalent number of placebo caps. We compared the post-meiotic aneuploidy rate using polar body biopsy (PBBX) and comparative genomic hybridization (CGH). According to the power calculation, 27 patients were needed for each arm. Results Owing to safety concerns regarding the effects of polar body biopsy on embryo quality and implantation, the study was terminated before reaching the target number of participants. A total of 39 patients were evaluated and randomized (17 CoQ10, 22 placebo), 27 were given the study medication (12 CoQ10, 15 placebo), and 24 completed an IVF-ICSI cycle including PBBX and embryo transfer (10 CoQ10, 14 placebo). Average age, base line follicle stimulating hormone (FSH), peak estradiol and progesterone serum level, as well as the total number of human menopausal gonadotropin (hMG) units–-did not differ between the groups. The rate of aneuploidy was 46.5% in the CoQ10 group compared to 62.8% in the control. Clinical pregnancy rate was 33% for the CoQ10 group and 26.7% for the control group. Conclusion No significant differences in outcome were detected between the CoQ10 and placebo groups. However, the final study was underpowered to detect a difference in the rate of aneuploidy.

Left ventricular function in malnutrition

1987 ◽  
Vol 253 (2) ◽  
pp. H380-H387 ◽  
Author(s):  
P. B. Alden ◽  
R. D. Madoff ◽  
T. J. Stahl ◽  
D. J. Lakatua ◽  
W. S. Ring ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Cardiac Function ◽  
Circumferential Stress ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Cardiac Mass ◽  
Control Group ◽  
Base Line ◽  
Total Body Mass ◽  
Protein Calorie Malnutrition

Twenty-one dogs were chronically instrumented with ultrasonic left ventricular dimension transducers and micromanometers to elucidate the effects of acute protein-calorie malnutrition on cardiac function. Ten dogs received a regular diet for 3 wk, whereas 11 dogs received a protein-calorie-deficient diet designed to achieve a mean weight loss of 20-25% over a 3-wk period. Studies of cardiac function were performed in awake intact animals at base line (1 wk postoperatively) and after 3 wk. In the malnourished dogs, cardiac mass was lost in proportion to total body mass loss. Mean cardiac mass fell from 115 to 91 g. This was largely due to wall thinning in this group. Heart rate dropped from 125 to 79 beats/min with malnutrition and ejection fraction increased from 29.8 to 34.6%. Cardiac output fell from 2.98 to 2.38 l/min, but cardiac index normalized to body surface area was unchanged. No significant changes in hemodynamics were observed in the control group. In the malnutrition group, global ventricular contractility, as measured by the load-independent index of systolic function or the slope of linear relationship between end-systolic pressure and end-systolic volume (EmaxPV), decreased slightly from 3.56 to 2.81 mmHg/ml (P = 0.07). However, Emax calculated from circumferential stress and strain data was unchanged. This indicates that depressed contractility was due to loss of cardiac muscle mass rather than any change in the myocardium per se. Response to beta-adrenergic stimulation was unchanged with starvation. Acute protein-calorie malnutrition causes significant cardiac atrophy that is reflected in decreased cardiac output and slightly reduced contractility but not in intrinsic properties of the myocardium.

Oral and Oropharyngeal Sensory Function in Adults With Chronic Obstructive Pulmonary Disease

2020 ◽  
Vol 29 (2) ◽  
pp. 864-872
Author(s):  
Fernanda Borowsky da Rosa ◽  
Adriane Schmidt Pasqualoto ◽  
Catriona M. Steele ◽  
Renata Mancopes
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Oral Cavity ◽  
Pulmonary Disease ◽  
Thermal Sensation ◽  
Sensory Function ◽  
Control Group ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Age Related ◽  
Copd Patients

Introduction The oral cavity and pharynx have a rich sensory system composed of specialized receptors. The integrity of oropharyngeal sensation is thought to be fundamental for safe and efficient swallowing. Chronic obstructive pulmonary disease (COPD) patients are at risk for oropharyngeal sensory impairment due to frequent use of inhaled medications and comorbidities including gastroesophageal reflux disease. Objective This study aimed to describe and compare oral and oropharyngeal sensory function measured using noninstrumental clinical methods in adults with COPD and healthy controls. Method Participants included 27 adults (18 men, nine women) with a diagnosis of COPD and a mean age of 66.56 years ( SD = 8.68). The control group comprised 11 healthy adults (five men, six women) with a mean age of 60.09 years ( SD = 11.57). Spirometry measures confirmed reduced functional expiratory volumes (% predicted) in the COPD patients compared to the control participants. All participants completed a case history interview and underwent clinical evaluation of oral and oropharyngeal sensation by a speech-language pathologist. The sensory evaluation explored the detection of tactile and temperature stimuli delivered by cotton swab to six locations in the oral cavity and two in the oropharynx as well as identification of the taste of stimuli administered in 5-ml boluses to the mouth. Analyses explored the frequencies of accurate responses regarding stimulus location, temperature and taste between groups, and between age groups (“≤ 65 years” and “> 65 years”) within the COPD cohort. Results We found significantly higher frequencies of reported use of inhaled medications ( p < .001) and xerostomia ( p = .003) in the COPD cohort. Oral cavity thermal sensation ( p = .009) was reduced in the COPD participants, and a significant age-related decline in gustatory sensation was found in the COPD group ( p = .018). Conclusion This study found that most of the measures of oral and oropharyngeal sensation remained intact in the COPD group. Oral thermal sensation was impaired in individuals with COPD, and reduced gustatory sensation was observed in the older COPD participants. Possible links between these results and the use of inhaled medication by individuals with COPD are discussed.

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