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71.
Sarcolemmal alterations during the development of genetically determined cardiomyopathy 总被引:2,自引:0,他引:2
V Panagia J N Singh M B Anand-Srivastava G N Pierce G Jasmin N S Dhalla 《Cardiovascular research》1984,18(9):567-572
The purpose of this study was to identify alterations in specific enzyme and Ca2+ binding activities in cardiac sarcolemmal fractions from UM-X7.1 myopathic Syrian hamsters during the development of cardiomyopathy. Experimental and healthy control animals were examined from 25 to 200 days of age. Sarcolemmal Na+, K+-ATPase activity was depressed in the myopathic hamsters throughout the time course of this study. Sarcolemmal ATP-independent Ca2+ binding was found to be depressed in experimental animals as early as 55 days of age. Ca2+ -stimulated, Mg2+ -dependent ATPase activity was depressed in the experimental animals by 90 days of age and this decrease in enzyme activity was accompanied by a decrease in ATP-dependent Ca2+ binding capacity of the sarcolemmal membranes. Mg2+ -ATPase and Ca2+ -ATPase activities were only affected in the latter stages of the disease (155 to 200 days old). NaF, epinephrine and Gpp(NH)p stimulation of the sarcolemmal adenylate cyclase activity was also observed to be attenuated during the latter stages of the disease. These defects in adenylate cyclase system of the sarcolemmal fraction appeared specific since basal adenylate cyclase activity was not altered at any age studied. The results demonstrate that the earliest lesions in sarcolemmal activity in myopathic hamster heart occur in Na+, K+-ATPase and ATP-independent Ca2+ binding capacity. These defects correspond temporally to the initial stages of cardiac necrotic development in this strain of myopathic hamster. 相似文献
72.
73.
Robert H. Eckel Robert R. Henry Patrick Yue Arvinder Dhalla Pamela Wong Philip Jochelson Luiz Belardinelli Jay S. Skyler 《Diabetes care》2015,38(7):1189-1196
OBJECTIVE
Ranolazine is an antianginal drug that mediates its effects by inhibition of cardiac late sodium current. Although ranolazine is not approved for the treatment of type 2 diabetes, in post hoc analyses of pivotal angina trials, ranolazine was associated with reductions in percent glycosylated hemoglobin (HbA1c) in subjects with type 2 diabetes. The study prospectively assessed the safety and efficacy of ranolazine in subjects with type 2 diabetes with inadequate glycemic control managed by lifestyle alone.RESEARCH DESIGN AND METHODS
The study was conducted worldwide in 465 subjects, with baseline HbA1c of 7–10% (53–86 mmol/mol) and fasting serum glucose of 130–240 mg/dL, randomized to placebo versus ranolazine.RESULTS
Compared with placebo, there was a greater decline in HbA1c at week 24 from baseline (primary end point) in subjects taking ranolazine (mean difference −0.56% [−6.1 mmol/mol]; P < 0.0001). Moreover, the proportion of subjects achieving an HbA1c <7.0% was greater with ranolazine (25.6% vs. 41.2%; P = 0.0004). Ranolazine was associated with reductions in fasting (mean difference −8 mg/dL; P = 0.0266) and 2-h postprandial glucose (mean difference −19 mg/dL; P = 0.0008 vs. placebo). Subjects taking ranolazine trended toward a greater decrease from baseline in fasting insulin (P = 0.0507), a greater decrease in fasting glucagon (P = 0.0003), and a lower postprandial 3-h glucagon area under the curve (P = 0.0031 vs. placebo). Ranolazine was safe and well tolerated.CONCLUSIONS
Compared with placebo, use of ranolazine monotherapy over 24 weeks, in subjects with type 2 diabetes and inadequate glycemic control on diet and exercise alone, significantly reduced HbA1c and other measures of glycemic control. 相似文献74.
Barta J Sanganalmath SK Kumamoto H Takeda N Edes I Dhalla NS 《Cardiovascular toxicology》2008,8(3):127-135
Antiplatelet agents, sarpogrelate (SAR), a 5-hydroxy tryptamine 2A receptor antagonist and cilostazol (CIL), a phosphodiesterase-III inhibitor, were observed to be beneficial in attenuating cardiac remodeling and improving cardiac function in congestive heart failure due to myocardial infarction in rats; however, CIL increased ventricular tachycardia and mortality. In order to study the effects of these antiplatelet agents on arrhythmias, Sprague-Dawley rats were pretreated with either SAR or CIL (5 mg/kg/day) for 2 weeks and were then either injected cumulative doses of epinephrine (Epi) or subjected to coronary occlusion. Saline-treated animals served as controls. Electrocardiographic analysis revealed that SAR pretreatment decreased the incidence and severity of ventricular arrhythmias (time of onset of arrhythmias as well as the occurrence of premature ventricular contractions, salvos, tachycardia, and fibrillations), whereas CIL treatment augmented the incidence of cardiac arrhythmias due to both Epi and coronary occlusion. None of the drugs affected the corrected QT interval significantly. Furthermore, the levels of cyclic adenosine monophosphate (cAMP) in left ventricle were markedly higher in CIL-pretreated rats when compared to SAR-pretreated or control rats. It is suggested that an excessive level of cAMP may contribute to increase incidence of ventricular arrhythmias and mortality in animals pretreated with CIL, unlike the SAR-pretreated rats. 相似文献
75.
Increased sensitivity of the denervated transplanted human heart to isoprenaline both before and after beta-adrenergic blockade 总被引:6,自引:0,他引:6
S Yusuf S Theodoropoulos C J Mathias N Dhalla J Wittes A Mitchell M Yacoub 《Circulation》1987,75(4):696-704
It is not known whether surgical denervation leads to increased beta-receptor sensitivity after human cardiac transplantation. We assessed cardiac beta-receptor sensitivity by studying the heart rate response to isoprenaline of the denervated donor heart as compared with the innervated recipient heart in eight patients who underwent heterotopic cardiac transplantation and in six patients with orthotopic transplantation. Changes in the donor and recipient hearts seen in these 14 patients were further compared with those seen in 10 normal volunteers. Incremental intravenous infusion of isoprenaline (5, 10, and 15 ng/kg/min) raised heart rate to a greater extent in the donor compared with the recipient hearts in the eight patients who had heterotopic grafts (slopes [beats/min/ng/kg]: donor = +2.26, recipient = +1.59; p less than .01). In addition, the donor hearts of the transplant patients were more sensitive than hearts of the normal volunteers (slopes: donor = +2.26, normal = +0.94; p less than .01). The changes in the two groups of donor hearts were similar (slopes: orthotopic = +2.24, heterotopic = +2.27; NS). The recipient hearts in the patients with heterotopic transplants were more sensitive than the hearts of the normal volunteers (p less than .05), suggesting that the observed differences in isoprenaline sensitivity in the patients with heterotopic grafts were not caused by a decreased sensitivity of the recipient heart. After beta-blockade, the heart rate responses to isoprenaline were attenuated to the same extent in denervated and innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
76.
Victor Chedid Elizabeth Rosenblatt Kunjal Gandhi Sameer Dhalla Monica C. Nandwani Ellen M. Stein John O. Clarke 《The American journal of the medical sciences》2018,355(2):126-131
Background
The advent of the Chicago Classification for esophageal motility disorders allowed for clinically reproducible subgrouping of patients with achalasia based on manometric phenotype. However, there are limited data with regards to racial variation using high-resolution esophageal manometry (HREM). The aim of our study was to evaluate the racial differences in patients with achalasia diagnosed with HREM using the Chicago Classification. We evaluated the clinical presentation, treatment decisions and outcomes between blacks and non-blacks with achalasia to identify potential racial disparities.Materials and Methods
We performed a retrospective review of consecutive patients referred for HREM at a single tertiary referral center from June 2008 through October 2012. All patients diagnosed with achalasia on HREM according to the Chicago Classification were included. Demographic, clinical and manometric data were abstracted. All studies interpreted before the Chicago Classification was in widespread use were reanalyzed. Race was defined as black or non-black. Patients who had missing data were excluded. Proportions were compared using chi-squared analysis and means were compared using the Student’s t-test.Results
A total of 1,268 patients underwent HREM during the study period, and 105 (8.3%) were manometrically diagnosed with achalasia (53% female, mean age: 53.8 ± 17.0 years) and also met the aforementioned inclusion and exclusion criteria. A higher percentage of women presented with achalasia in blacks as compared to whites or other races (P < 0.001). Non-blacks were more likely to present with reflux than blacks (P = 0.01), while blacks were more likely to be treated on the inpatient service than non-blacks (P < 0.001). There were no other significant differences noted in clinical presentation, treatment decisions and treatment outcomes among blacks and non-blacks.Conclusions
Our study highlights possible racial differences between blacks and non-blacks, including a higher proportion of black women diagnosed with achalasia and most blacks presenting with dysphagia. There is possibly a meaningful interaction of race and sex in the development of achalasia that might represent genetic differences in its pathophysiology. Further prospective studies are required to identify such differences. 相似文献77.
Cardiac function is compromised by oxidative stress which occurs upon exposing the heart to ischemia reperfusion (I/R) for a prolonged period. The reactive oxygen species (ROS) that are generated during I/R incur extensive damage to the myocardium and result in subcellular organelle remodeling. The cardiac nucleus, glycocalyx, myofilaments, sarcoplasmic reticulum, sarcolemma, and mitochondria are affected by ROS during I/R injury. On the other hand, brief periods of ischemia followed by reperfusion, or ischemic preconditioning (IPC), have been shown to be cardioprotective against oxidative stress by attenuating the cellular damage and alterations of subcellular organelles caused by subsequent I/R injury. Endogenous defense mechanisms, such as antioxidant enzymes and heat shock proteins, are activated by IPC and thus prevent damage caused by oxidative stress. Although these cardioprotective effects of IPC against I/R injury are considered to be a consequence of changes in the redox state of cardiomyocytes, IPC is considered to promote the production of NO which may protect subcellular organelles from the deleterious actions of oxidative stress. The article is intended to focus on the I/R-induced oxidative damage to subcellular organelles and to highlight the cardioprotective effects of IPC. In addition, the actions of various endogenous cardioprotective interventions are discussed to illustrate that changes in the redox state due to IPC are cardioprotective against I/R injury to the heart. 相似文献
78.
It is now becoming clear that two major systems namely the sympathetic nervous system and the renin-angiotensin system are
activated in response to ischemic injury; these result in the elevation of plasma catecholamines and angiotensin II during
the development of myocardial infarction as well as congestive heart failure. Although plasma levels of several other hormones
including aldosterone, endothelin, vasopressin, natriuretic peptides, growth factors and inflammatory cytokines are also increased
in heart failure, their relationship with changes in catecholamine and/or angiotensin levels as well as their significance
for the induction of congestive heart failure are poorly understood. In this article we have examined the evidence regarding
the role of endothelin and vasopressin in the pathogenesis of cardiac hypertrophy and congestive heart failure in addition
to evaluating the significance of their antagonism by using their receptor blockade for treatment of congestive heart failure.
Endothelin appears to maintain blood pressure by its vasoconstricting action whereas vasopressin primarily produces similar
effect by retention of body fluid. Myocardium is also known to express both ET-A and ET-B receptors in addition to V1 and V2 receptors for vasopressin, which have been shown to induce cardiac remodeling. Out of various ET-1 receptor antagonists,
which are available, a non-selective endothelin receptor antagonist, bosentan, as well as an ET-A receptor antagonist, BQ-123,
seem most promising for the treatment of congestive heart failure. Likewise, vasopressin antagonists such as a non-selective
antagonist, conivaptan, as well as V2 selective antagonist, tolvaptan, may prove highly valuable for the therapy of this condition. Since most of the existing
interventions are helpful in treating patients with congestive heart failure only partially, there appears to be a real challenge
for developing some combination therapy for the treatment of congestive heart failure. 相似文献
79.
Yuval A. Patel Sameer Dhalla Matthew T. Olson Anne Marie Lennon Mouen A. Khashab Vikesh K. Singh 《Pancreatology》2013,13(6):631-633
Solitary fibrous tumors are unusual spindle cell neoplasms that uncommonly originate from the kidney. We report a case of a 43-year old male who presented with acute recurrent pancreatitis secondary to a mass in the head of the pancreas. Endoscopic ultrasound with fine needle aspiration (EUS-FNA) was performed. Cytology revealed solitary fibrous tumor of the kidney. This is the first reported case of solitary fibrous tumor metastasizing to the pancreas and presenting as acute recurrent pancreatitis. 相似文献
80.
Li H Wetten S Li L St Jean PL Upmanyu R Surh L Hosford D Barnes MR Briley JD Borrie M Coletta N Delisle R Dhalla D Ehm MG Feldman HH Fornazzari L Gauthier S Goodgame N Guzman D Hammond S Hollingworth P Hsiung GY Johnson J Kelly DD Keren R Kertesz A King KS Lovestone S Loy-English I Matthews PM Owen MJ Plumpton M Pryse-Phillips W Prinjha RK Richardson JC Saunders A Slater AJ St George-Hyslop PH Stinnett SW Swartz JE Taylor RL Wherrett J Williams J Yarnall DP Gibson RA Irizarry MC Middleton LT 《Archives of neurology》2008,65(1):45-53