Physiological Impact of Afterload Reduction on Cardiac Mechanics and Coronary Hemodynamics Following Isosorbide Dinitrate Administration in Ischemic Heart Disease.
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SUBMITTER: Patterson T
PROVIDER: S-EPMC8575737 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To quantify the effect of sublingual isosorbide dinitrate (ISDN) administration on coronary magnetic resonance (MR) imaging.Written informed consent was obtained from all participants, and the HIPAA-compliant protocol was approved by the Institutional Review Board. Coronary MR imaging was performed at 1.5 T before and after administration of ISDN (2.5 or 5 mg) in 25 healthy adult volunteers (mean age, 23 years +/- 4; nine men, 16 women) with three-dimensional targeted (n = 20, randomized into four groups) or whole-heart (n = 5) acquisitions with gradient-recalled echo (GRE) or balanced steady-state free precession (SSFP) sequences. Image quality was assessed by two cardiologists on a four-point scale. Signal-to-noise ratio (SNR), vessel diameter, and vessel sharpness were characterized. A linear mixed-effects model was used for data analysis. A P value of less than .05 was considered to indicate a significant difference.The maximum SNR enhancement with 5 mg of ISDN (GRE: 22.0% +/- 10.7%; SSFP: 20.1% +/- 6.0%) was similar (P > .05) to that with 2.5 mg (GRE: 21.9% +/- 5.4%; SSFP: 19.1% +/- 3.0%). However, the time to maximum SNR enhancement for the 5-mg dose (15.5 minutes +/- 6.0) was earlier (P < .01) than that for 2.5 mg (23.5 minutes +/- 6.7). The increase in vessel diameter with 5 mg of ISDN was greater than that with 2.5 mg (P < .05 for both GRE and SSFP sequences). The coronary images were sharper after ISDN administration (P < .03). Subjective image quality score significantly improved after ISDN administration for GRE images (P < .05 for both doses) but was similar for SSFP images (P = .24 for 2.5 mg; P = .27 for 5 mg). Whole-heart coronary SNR was improved about 10% after ISDN administration (P < .05).Sublingual ISDN improves coronary MR imaging SNR. Practitioners need to consider the dose and temporal effects of ISDN when performing coronary MR imaging.
| S-EPMC2809925 | biostudies-other
Project description:Backgrounds/Aims:Acute pancreatitis is the most widespread complication of endoscopic retrograde cholangiopancreatography. Here, we investigated the efficacy of rectal suppository naproxen, sublingual isosorbide dinitrate and their co-administration in the prevention of post-ERCP pancreatitis. Methods:This double-blind randomized clinical trial carried out from June 2015 to February 2016 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 585 patients were selected from candidates for diagnostic or therapeutic ERCP by using the simple sampling method. Patients divided into three groups. Group A received 500 mg naproxen, group B took 5 mg isosorbide dinitrate, and group C was co-administrated both agents before ERCP. The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and increase of serum amylase activity more than 3 times over the upper normal limit (60-100 IU/L) within first the 24 h post-ERCP. Results:Totally, 80 patients developed PEP included 29 (4.9%), 24 (4.1%), and 27 (4.6%) patients in groups A, B, and C, respectively (p=0.845). Longer ERCP time (p=0.041), using diazepam (p=0.033), a higher number of pancreatic ducts cannulation (p?0.001), pancreatic duct injection (p=0.013), and using pancreatic stent (p=0.004) were the predisposing factors for PEP. Conclusions:Our findings indicated that prophylactic naproxen suppository or isosorbide dinitrate sublingually or co-administration had no significant difference in the prevention and severity of PEP, however, enhancing the endoscopist's skills can be effective. Departments and educational hospitals should develop their assessment and quality assurance measures for the training of fellows' not only technical training but also an understanding of the diagnostic and therapeutic roles of the procedure.
| S-EPMC7452799 | biostudies-literature
Project description:Mechanical stresses on aortic valve leaflets are well-known mediators for initiating processes leading to calcific aortic valve disease. Given that non-coronary leaflets calcify first, it may be hypothesized that coronary flow originating from the ostia significantly influences aortic leaflet mechanics and sinus hemodynamics. High resolution time-resolved particle image velocimetry (PIV) measurements were conducted to map the spatiotemporal characteristics of aortic sinus blood flow and leaflet motion with and without physiological coronary flow in a well-controlled in vitro setup. The in vitro setup consists of a porcine aortic valve mounted in a physiological aorta sinus chamber with dynamically controlled coronary resistance to emulate physiological coronary flow. Results were analyzed using qualitative streak plots illustrating the spatiotemporal complexity of blood flow patterns, and quantitative velocity vector and shear stress contour plots to show differences in the mechanical environments between the coronary and non-coronary sinuses. It is shown that the presence of coronary flow pulls the classical sinus vorticity deeper into the sinus and increases flow velocity near the leaflet base. This creates a beneficial increase in shear stress and washout near the leaflet that is not seen in the non-coronary sinus. Further, leaflet opens approximately 10% farther into the sinus with coronary flow case indicating superior valve opening area. The presence of coronary flow significantly improves leaflet mechanics and sinus hemodynamics in a manner that would reduce low wall shear stress conditions while improving washout at the base of the leaflet.
| S-EPMC4838673 | biostudies-literature
Project description:Pulmonary hypertension due to left heart disease is associated with poor outcomes. This study investigated the beneficial effects of isosorbide dinitrate (ISDN) inhalation on pulmonary pressure and ventricular remodeling in a rat model of heart failure (HF) following myocardial infarction (MI). To assess the effect of ISDN on pulmonary pressure, 20 male Sprague-Dawley (SD) rats were randomized to four groups: Normal saline (NS) 1 ml/kg, ISDN 1 mg/kg, NS 3 ml/kg or ISDN 3 mg/kg following coronary ligation. Assessments included pulmonary and systemic artery pressure alterations, lung weight/body weight and plasma nitric oxide (NO) concentration. To assess the effect of ISDN on ventricular remodeling, 30 SD rats were randomized to three groups: Sham surgery, MI-NS (intratracheal NS 3 ml/kg for 13 days following coronary ligation), and MI-ISDN (intratracheal ISDN 3 mg/kg for 13 days following coronary ligation). On day 15, all rats underwent echocardiogram and hemodynamic assessments. The area affected by MI was evaluated using microscopy and vascular endothelial growth factor (VEGF) expression was examined using immunohistochemistry. Plasma epinephrine, norepinephrine and brain natriuretic peptide (BNP) levels were assessed by ELISA. Intratracheal ISDN reduced pulmonary and systematic artery pressure without pulmonary edema when compared with NS. The reduction was associated with increased plasma NO levels. ISDN inhalation for 14 days reduced MI size and alleviated left and right ventricular remodeling following MI. These hemodynamic and morphological improvements were associated with decreased plasma epinephrine, norepinephrine and BNP levels, and an increased VEGF positive area at the border of MI region. In conclusion, intratracheal administration of ISDN was effective in improving ventricular remodeling and cardiac function in a rat model of HF following MI.
| S-EPMC5526058 | biostudies-other
Project description:BackgroundThe metabolic activity of endogenous nitric oxide (NO) and the medical use of nitrovasodilatory drugs like isosorbide dinitrate have been shown to be potential inducers inducers of cervical ripening prior to surgical evacuation of the uterus.ObjectiveTo assess the therapeutic efficacy and safety of combined isosorbide dinitrate-oxytocin in the management of intrauterine foetal death (IUFD).MethodsSixty women with IUFD after 20 weeks of gestation requesting uterine evacuation were randomly selected to receive isosorbide dinitrate gel solution (80 mg/1.5 mL; n = 30) or misoprostol gel solution (100 mcg/1.5 mL; n = 30) every 3 h with a maximum of four doses or until a Bishop score >7 was reached. Subsequently, patients received a high dose of intravenous oxytocin until complete uterus evacuation was achieved. Therapeutic efficacy was evaluated by mean the relative risk of the foetal expulsion based on comparison of event rates, and the proportion of women induced to labor at 7, 10 and 15 h after the administration of isosorbide dinitrate or misoprostol. Safety was assessed on the basis of woman´s vital signs and evaluation of adverse effects, including headache, abdominal pain, pelvic pain, lower back pain, nausea, dizziness and vomiting.ResultsThe foetal expulsion rate using the isosorbide dinitrate-oxytocin combination was approximately 4.4 times, and at least 2.1 times, the foetal expulsion rate with the misoprostol-oxytocin regimen at any given point in time. The proportion of women achieved vaginal delivery at 15 hours was 100% for the isosorbide dinitrate-oxytocin group and 86.7% for the misoprostol-oxytocin group. The average delivery induction interval was significantly lower when isosorbide dinitrate-oxytocin was used (8.7 ± 3.1 h) than when misoprostol-oxytocin (11.9 ± 3.1 h) was used. A total of 20% of patients in the isosorbide dinitrate-oxytocin group recorded headache, and no cases of uterine tachysystole, haemorrhage or coagulopathy were recorded.ConclusionThis study indicates that intravaginal isosorbide dinitrate followed by intravenous oxytocin was more effective than the conventional method used to induce labour in the medical management of foetal death in pregnancies after 20 weeks of gestation.Trial registrationClinicaltrials.gov NCT02488642.
| S-EPMC6872136 | biostudies-literature
Project description:Biomechanical cues dynamically control major cellular processes, but whether genetic variants actively participate in mechanosensing mechanisms remains unexplored. Vascular homeostasis is tightly regulated by hemodynamics. Exposure to disturbed blood flow at arterial sites of branching and bifurcation causes constitutive activation of vascular endothelium contributing to atherosclerosis, the major cause of coronary artery disease (CAD) and ischemic stroke (IS). Conversely, unidirectional flow promotes quiescent endothelium. Genome-wide association studies (GWAS) have identified chromosome 1p32.2 as strongly associated with CAD/IS; however, the causal mechanism related to this locus remains unknown. Using statistical analyses, assay of transposase accessible chromatin with whole-genome sequencing (ATAC-seq), H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs), our results demonstrate that rs17114036, a common noncoding polymorphism at 1p32.2, is located in an endothelial enhancer dynamically regulated by hemodynamics. CRISPR-Cas9-based genome editing shows that rs17114036-containing region promotes endothelial quiescence under unidirectional shear stress by regulating phospholipid phosphatase 3 (PLPP3). Chromatin accessibility quantitative trait locus (caQTL) mapping using HAECs from 56 donors, allelic imbalance assay from 7 donors, and luciferase assays demonstrate that CAD/IS-protective allele at rs17114036 in PLPP3 intron 5 confers increased endothelial enhancer activity. ChIP-PCR and luciferase assays show that CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. These results demonstrate that a human SNP contributes to critical endothelial mechanotransduction mechanisms and suggest that human haplotypes and related cis-regulatory elements provide a previously unappreciated layer of regulatory control in cellular mechanosensing mechanisms.
| S-EPMC6275533 | biostudies-literature
Project description:Background and purposeCerebral small vessel disease-a major cause of stroke and dementia-is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide mononitrate (ISMN) and cilostazol, alone or in combination, improved magnetic resonance imaging-measured cerebrovascular function in patients with lacunar ischemic stroke.MethodsParticipants were randomized to ISMN alone, cilostazol alone, both ISMN and cilostazol, or no medication. Participants underwent structural, cerebrovascular reactivity (to 6% carbon dioxide) and phase-contrast pulsatility magnetic resonance imaging at baseline and after 8 weeks of medication.ResultsOf 27 participants (mean age, 68±7.7; 44% female), 22 completed cerebrovascular reactivity and pulsatility imaging with complete datasets. White matter cerebrovascular reactivity increased in the ISMN (β=0.021%/mm Hg [95% CI, 0.003-0.040]) and cilostazol (β=0.035%/mm Hg [95% CI, 0.014-0.056]) monotherapy groups and in those taking any versus no medication (β=0.021%/mm Hg [95% CI, 0.005-0.037]).ConclusionsWhile limited by small sample size, we demonstrate that measuring cerebrovascular function with magnetic resonance imaging is feasible in clinical trials and that ISMN and cilostazol may improve cerebrovascular function. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02481323. URL: www.isrctn.com; Unique identifier: ISRCTN12580546. URL: www.clinicaltrialsregister.eu; Unique identifier: EudraCT 2015-001953-33.
| S-EPMC8700302 | biostudies-literature
Project description:We designed two Phase I studies that assessed healthy volunteers in order to evaluate the safety and to optimize the dosing of the combination of the drugs isosorbide dinitrate, a nitric oxide donor, and ibuprofen, a nonsteroidal antiinflammatory drug. We designed these studies with the aim of designing a Phase II trial to evaluate the drugs' efficacy in patients affected by Duchenne muscular dystrophy. For the first trial, ISOFEN1, a single-dose, randomized-sequence, open-label, active control, three-treatment cross-over study, was aimed at comparing the pharmacokinetics of ibuprofen 200 mg and isosorbide dinitrate 20 mg when given alone and concomitantly. The pharmacokinetics of ibuprofen given alone versus ibuprofen given concomitantly with isosorbide dinitrate were similar, as documented by the lack of statistically significant differences in the main drug's pharmacokinetic parameters (time to maximal concentration [Tmax], maximal concentration [Cmax], area under the curve [AUC]0-t, and AUC0-?). Similarly, we found that the coadministration of ibuprofen did not significantly affect the pharmacokinetics of isosorbide dinitrate. No issues of safety were detected. The second trial, ISOFEN2, was a single-site, dose titration study that was designed to select the maximum tolerated dose for isosorbide dinitrate when coadministered with ibuprofen. Eighteen out of the 19 enrolled subjects tolerated the treatment well, and they completed the study at the highest dose of isosorbide dinitrate applied (80 mg/day). One subject voluntarily decided to reduce the dose of isosorbide dinitrate from 80 mg to 60 mg. The treatment-related adverse events recorded during the study were, for the large majority, episodes of headache that remitted spontaneously in 0.5-1 hour - a known side effect of isosorbide dinitrate. These studies demonstrate that the combination of isosorbide dinitrate and ibuprofen does not lead to pharmacokinetic interactions between the two drugs; they also demonstrate that the combination of isosorbide dinitrate and ibuprofen has optimal tolerability and safety profiles that are similar to those previously reported for isosorbide dinitrate and ibuprofen given alone.
| S-EPMC4018313 | biostudies-literature
Project description:Heart failure is a global epidemic. Left ventricular assist devices provide added cardiac output for severe cases but cause infection and thromboembolism. Proposed direct cardiac compression devices eliminate blood contacting surfaces, but no group has optimized the balance between hemodynamic benefit and excessive ventricular wall strains and stresses. Here, we use left ventricular simulations to apply compressions and analyze hemodynamics as well as regional wall mechanics. This axisymmetric model corresponds with current symmetric bench prototypes. At nominal pressures of 3.1 kPa applied over the epicardial compression zone, hemodynamics improved substantially. Ejection fraction changed from 17.6% at baseline to 30.3% with compression and stroke work nearly doubled. Parametric studies were conducted by increasing and decreasing applied pressures; ejection fraction, peak pressure, and stroke work increased linearly with changes in applied compression. End-systolic volume decreased substantially. Regional mechanics analysis showed principal stress increases at the endocardium, in the middle of the compression region. Principal strains remained unchanged or increased moderately with nominal compression. However, at maximum applied compression, stresses and strains increased substantially providing potential constraints on allowable compressions. These results demonstrate a framework for analysis and optimization of cardiac compression as a prelude to biventricular simulations and subsequent animal experiments.
| S-EPMC6822737 | biostudies-literature
Project description:BackgroundAdequate hydration remains the mainstay of contrast-induced nephropathy prevention, and nitrates could reduce cardiac preload.HypothesisThis study aimed to explore the adequate hydration with nitrates for patients with chronic kidney disease (CKD) and congestive heart failure (CHF) to reduce the risk of contrast-induced nephropathy (CIN) and at the same time avoid the acute heart failure.MethodsThree hundred and ninty-four consecutive patients with CKD and CHF undergoing coronary procedures were randomized to either adequate hydration with nitrates (n = 196) or to routine hydration (control group; n = 198). The adequate hydration group received continuous intravenous infusion of isosorbide dinitrate combined with intravenous infusion of isotonic saline at a rate of 1.5 mL/kg/h during perioperative period. The definition of CIN was a 25% or 0.5 mg/dL rise in serum creatinine over baseline. This trial is registered with www.clinicaltrials.gov, number NCT02718521.ResultsBaseline characteristics were well-matched between the two groups. CIN occurred less frequently in adequate hydration group than the control group (12.8% vs 21.2%; P = 0.018). The incidence of acute heart failure did not differ between the two groups (8 [4.08%] vs 6[3.03%]; P = 0.599). Cumulative major adverse events (death, myocardial infarction, stoke, hospitalization for acute heart failure) during the 90-day follow-up were lower in the adequate hydration with nitrates group (P = 0.002).ConclusionsAdequate hydration with nitrates can safely and effectively reduce the risk of CIN in patients with CKD and CHF.
| S-EPMC6436482 | biostudies-literature