-
1.
Effects of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency, and myocardial contractile work in type 2 diabetes patients-a description of the DAPACARD study.
Åkerblom, A, Oldgren, J, Latva-Rasku, A, Johansson, L, Lisovskaja, V, Karlsson, C, Oscarsson, J, Nuutila, P
Upsala journal of medical sciences. 2019;(1):59-64
-
-
Free full text
-
Abstract
BACKGROUND Diabetes increases the risk for cardiovascular (CV) events. It has recently been shown that the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors leads to a reduction in CV outcomes in patients with type 2 diabetes mellitus (T2DM), including mortality and heart failure hospitalization. The exact mechanisms of how SGLT2 inhibitors lead to this CV risk reduction remain incompletely understood. The study of DAPAgliflozin on CARDiac substrate uptake, myocardial efficiency and myocardial contractile work in type 2 diabetes patients (DAPACARD) (NCT03387683) explores the possible effects of dapagliflozin, an SGLT2 inhibitor, on cardiac work, metabolism, and biomarker levels. METHODS DAPACARD is an international, randomized, double-blind trial that aims to examine the effects of dapagliflozin versus matching placebo in 52 patients with T2DM that are on stable metformin therapy prior to and during the 6 weeks of treatment. The primary efficacy endpoint is change in global longitudinal strain of the left ventricle (GLSLV) measured with magnetic resonance imaging (MRI) between baseline (pre-treatment) and end of study (on-treatment). The secondary endpoint is the corresponding change in myocardial efficiency measured as external left ventricular work divided by total left ventricular work, which is estimated using [11C]-acetate clearance using positron emission tomography (PET). CONCLUSION The DAPACARD study is an extensive investigation of cardiac function and metabolism, by advanced imaging with PET and MRI, as well as biomarkers, performed in order to further explore how the SGLT2 inhibitor dapagliflozin could influence cardiovascular outcomes in patients with T2DM.
-
2.
Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation.
Christ, T, Rozmaritsa, N, Engel, A, Berk, E, Knaut, M, Metzner, K, Canteras, M, Ravens, U, Kaumann, A
Proceedings of the National Academy of Sciences of the United States of America. 2014;(30):11193-8
-
-
Free full text
-
Abstract
Atrial fibrillation (AF) is the most common heart rhythm disorder. Transient postoperative AF can be elicited by high sympathetic nervous system activity. Catecholamines and serotonin cause arrhythmias in atrial trabeculae from patients with sinus rhythm (SR), but whether these arrhythmias occur in patients with chronic AF is unknown. We compared the incidence of arrhythmic contractions caused by norepinephrine, epinephrine, serotonin, and forskolin in atrial trabeculae from patients with SR and patients with AF. In the patients with AF, arrhythmias were markedly reduced for the agonists and abolished for forskolin, whereas maximum inotropic responses were markedly blunted only for serotonin. Serotonin and forskolin produced spontaneous diastolic Ca(2+) releases in atrial myocytes from the patients with SR that were abolished or reduced in myocytes from the patients with AF. For matching L-type Ca(2+)-current (ICa,L) responses, serotonin required and produced ∼ 100-fold less cAMP/PKA at the Ca(2+) channel domain compared with the catecholamines and forskolin. Norepinephrine-evoked ICa,L responses were decreased by inhibition of Ca(2+)/calmodulin-dependent kinase II (CaMKII) in myocytes from patients with SR, but not in those from patients with AF. Agonist-evoked phosphorylation by CaMKII at phospholamban (Thr-17), but not of ryanodine2 (Ser-2814), was reduced in trabeculae from patients with AF. The decreased CaMKII activity may contribute to the blunting of agonist-evoked arrhythmias in the atrial myocardium of patients with AF.
-
3.
Direct myocardial effects of levosimendan in humans with left ventricular dysfunction: alteration of force-frequency and relaxation-frequency relationships.
Givertz, MM, Andreou, C, Conrad, CH, Colucci, WS
Circulation. 2007;(10):1218-24
Abstract
BACKGROUND Enthusiasm for the development of Ca2+ sensitizers as inotropic agents for heart failure has been tempered by reports of impaired relaxation. Levosimendan, which increases myofilament Ca2+ sensitivity via Ca2+-dependent binding to troponin C, exerts positive inotropic and lusitropic effects in failing human myocardium in vitro. We sought to determine the direct effects of levosimendan on failing human myocardium in vivo, and in particular whether levosimendan exerts heart rate-dependent effects on systolic or diastolic function. METHODS AND RESULTS Ten patients with left ventricular dysfunction caused by nonischemic dilated cardiomyopathy (mean left ventricular ejection fraction, 27+/-2%) were instrumented with an infusion catheter in the left main coronary artery, a high-fidelity micromanometer-tipped catheter in the left ventricle, and a bipolar pacing wire in the right atrium. Inotropic (peak +dP/dt) and lusitropic (Tau) responses were assessed during continuous intracoronary drug infusion in sinus rhythm followed by atrial pacing at 20, 40, and 60 beats per minute above the sinus rate. Under control conditions (intracoronary 5% dextrose in water), atrial-pacing tachycardia decreased Tau by 13% (P<0.05), but did not increase +dP/dt. Intracoronary levosimendan (3.75 and 12.5 microg/min for 15 minutes each) increased +dP/dt dose-dependently and decreased Tau over a range of heart rates, but did not alter the slope of the force-frequency or relaxation-frequency relationship. CONCLUSIONS Myocardial calcium sensitization with levosimendan exerts mild inotropic and lusitropic effects in humans with left ventricular dysfunction, but does not alter the force-frequency or relaxation-frequency relationship.
-
4.
Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vitro contractility of myocardial tissue.
Rosenfeldt, F, Marasco, S, Lyon, W, Wowk, M, Sheeran, F, Bailey, M, Esmore, D, Davis, B, Pick, A, Rabinov, M, et al
The Journal of thoracic and cardiovascular surgery. 2005;(1):25-32
-
-
Free full text
-
Abstract
OBJECTIVES Previous clinical trials suggest that coenzyme Q(10) might afford myocardial protection during cardiac surgery. We sought to measure the effect of coenzyme Q(10) therapy on coenzyme Q(10) levels in serum, atrial trabeculae, and mitochondria; to assess the effect of coenzyme Q(10) on mitochondrial function; to test the effect of coenzyme Q(10) in protecting cardiac myocardium against a standard hypoxia-reoxygentation stress in vitro; and to determine whether coenzyme Q(10) therapy improves recovery of the heart after cardiac surgery. METHODS Patients undergoing elective cardiac surgery were randomized to receive oral coenzyme Q(10) (300 mg/d) or placebo for 2 weeks preoperatively. Pectinate trabeculae from right atrial appendages were excised, and mitochondria were isolated and studied. Trabeculae were subjected to 30 minutes of hypoxia, and contractile recovery was measured. Postoperative cardiac function and troponin I release were assessed. RESULTS Patients receiving coenzyme Q(10) (n = 62) had increased coenzyme Q(10) levels in serum (P = .001), atrial trabeculae (P = .0001), and isolated mitochondria (P = .0002) compared with levels seen in patients receiving placebo (n = 59). Mitochondrial respiration (adenosine diphosphate/oxygen ratio) was more efficient (P = .012), and mitochondrial malondialdehyde content was lower (P = .002) with coenzyme Q(10) than with placebo. After 30 minutes of hypoxia in vitro, pectinate trabeculae isolated from patients receiving coenzyme Q(10) exhibited a greater recovery of developed force compared with those in patients receiving placebo (46.3% +/- 4.3% vs 64.0% +/- 2.9%, P = .001). There was no between-treatment difference in preoperative or postoperative hemodynamics or in release of troponin I. CONCLUSIONS Preoperative oral coenzyme Q(10) therapy in patients undergoing cardiac surgery increases myocardial and cardiac mitochondrial coenzyme Q(10) levels, improves mitochondrial efficiency, and increases myocardial tolerance to in vitro hypoxia-reoxygenation stress.
-
5.
Myocardial function in early hours after coronary artery bypass grafting in patients with left ventricular dysfunction: comparison of blood and crystalloid cardioplegia.
Brat, R, Tosovsky, J, Januska, J
The Journal of cardiovascular surgery. 2004;(3):265-9
Abstract
AIM: This study was done to evaluate a myocardial function in the early hours after coronary artery bypass grafting (CABG) in patients with left ventricular dysfunction and to compare blood and crystalloid cardioplegia. METHODS One hundred consecutive patients with left ventricular ejection fraction <35% scheduled for CABG were randomly divided into 2 groups. In the 1st group we used cold blood cardioplegia, in the 2nd group cold crystalloid cardioplegia. We measured hemodynamic data in the early hours after operation, enzyme release and we collected relevant clinical data. RESULTS The mortality rate in the crystalloid and blood cardioplegia group was 2% and 0%, respectively. We didn't find any significant difference in the incidence of perioperative myocardial infarction, arrhythmia and use of intraaortic balloon pumping between groups. Differences between groups were found in the enzymatic response. Average creatine kinase and MB isoenzyme of creatine kinase (CK-MB), was lower in the blood cardioplegia group lower during the whole examined period. We also found some significant differences in hemodynamic data in the postoperative period. In the crystalloid cardioplegia group there was a decrease in left ventricular stroke work index immediately after operation. The preoperative value was reached in about 2 hours after operation. On the other hand, we didn't find this decrease in the blood cardioplegia group. This difference between groups was statistically significant. Other hemodynamic data didn't show any significant difference. CONCLUSION Blood cardioplegia shows earlier improvement of myocardial function after the operation. It could be beneficial in patients with severe left ventricular dysfunction.
-
6.
Effect of atorvastatin on myocardial contractile reserve assessed by tissue Doppler imaging in moderately hypercholesterolemic patients without heart disease.
Bountioukos, M, Rizzello, V, Krenning, BJ, Bax, JJ, Kertai, MD, Vourvouri, EC, Schinkel, AF, Biagini, E, Boersma, E, Roelandt, JR, et al
The American journal of cardiology. 2003;(5):613-6
Abstract
An improvement in myocardial longitudinal systolic velocities, assessed by pulsed-wave tissue Doppler imaging during low-dose dobutamine infusion, was observed at 6-month follow-up after 6 months of treatment with atorvastatin. Our findings indicate a favorable effect of atorvastatin on contractile reserve, possibly through an enhancement of flow-dependent coronary dilatation during stress.
-
7.
Low calcium dialysate increases cardiac relaxation in CAPD patients.
Tuncer, M, Ermiş, C, Süleymanlar, G, Yakupoglu, G, Ersoy, FF
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 2002;(6):714-8
Abstract
OBJECTIVE To establish whether changes in serum calcium affect left ventricular (LV) function in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS This study was conducted on 28 clinically stable CAPD patients (11 females, 17 males). Left ventricular relaxation and systolic function were echocardiographically examined in all patients during standard dialysate (containing 1.75 mmol/L calcium) treatment. All patients were then changed to low calcium dialysate (1.25 mmol/L calcium) for 1 month and all patients were re-examined echocardiographically. Decrement in isovolumic relaxation time (IVRT) and deceleration time (DT), and increment in the ratio of peak early to peak late diastolic velocities (E/Amax) were admitted as indexes showing improvement in LV relaxation. 17 age- and sex-matched controls were also echocardiographically examined. RESULTS Deceleration time, interventricular septal thickness at systole (IVSTS) and diastole (IVSTD), and posterior wall thickness at systole (PWS) and diastole (PWD) were higher in CAPD patients using standard dialysate than in normal controls. With the use of low calcium dialysate, DTs were similar but IVSTS, IVSTD, PWS, and PWD values remained higher. In normal controls, E/Amax values were higher than those in CAPD patients using standard dialysate (p < 0.001) and low calcium dialysate (p = 0.009). Serum intact parathyroid hormone level, weight, clinical volume status, and blood pressure were similar throughout the study period. Serum ionized calcium levels were decreased significantly during low calcium dialysate treatment. The changes in IVRT, DT, and E/Amax suggest improvement in LV relaxation during low calcium dialysate treatment. CONCLUSION Left ventricular relaxation is increased with the use of low calcium dialysate compared with standard dialysate treatment. The idea of possible beneficial effects of increment in LV relaxation on cardiovascular morbidity and mortality deserves further studies.
-
8.
Regional ischemic preconditioning enhances myocardial performance in off-pump coronary artery bypass grafting.
Laurikka, J, Wu, ZK, Iisalo, P, Kaukinen, L, Honkonen, EL, Kaukinen, S, Tarkka, MR
Chest. 2002;(4):1183-9
Abstract
OBJECTIVES We intended to investigate whether ischemic preconditioning (IP) enhances myocardial performance in patients who undergo off-pump coronary artery bypass grafting (CABG). DESIGN A controlled, randomized, prospective study. SETTING A university hospital. PATIENTS Thirty-two patients with left anterior descending coronary artery (LAD) or two-vessel heart disease (including LAD) who were to undergo off-pump CABG were randomized into an IP group and a control group. INTERVENTIONS IP was induced by occluding the LAD twice for a 2-min period followed by 3-min LAD reperfusion before bypass grafting of the first coronary vessel. MEASUREMENTS AND RESULTS Registration included hemodynamic data from the peripheral artery and the pulmonary artery, and the measurement of cardiac troponin I (CTnI) and creatine kinase isoenzyme MB (CK-MB) values. IP resulted in a complete recovery of the mean stroke volume index (SVI) after the operation. In the control subjects, the mean SVI showed a significant reduction postoperatively (p = 0.039). On the first postoperative day, the increase in the mean heart rate (HR) was also significantly lower in the IP patients. The CTnI level was statistically significantly lower in the IP group (p = 0.043), and IP patients tended to have a smaller CK-MB release after surgery (not significant). The duration of mechanical ventilation, the length of stay in the ICU, and the use of inotropic medication did not increase after the IP protocol. CONCLUSIONS Two cycles of regional 2-min IP in the LAD, followed by 3 min of reperfusion, proved to be applicable and safe in patients undergoing off-pump myocardial revascularization, it tended to decrease the immediate myocardial enzyme release, it prohibited the postoperative increase in HR, and it enhanced the recovery of SVI.