Nitric Oxide and Myocardial Contraction: Experimental Studies
Malcolm J. Lewis, Ajay M. Shah in Endothelial Modulation of Cardiac Function, 2020
NO may also have an important role in preventing the characteristic diastolic dysfunction observed after recovery from an ischaemic insult. In isolated cat papillary muscles, SNP inhibited the profound delay in myocardial relaxation during recovery from hypoxia, without influencing peak developed tension, consistent with a selective effect on relaxation (Brodie et al., 1976). Similarly, in isolated rat cardiac myocytes, pretreatment with a cyclic GMP analogue abolished the abnormal relaxation which follows brief hypoxia-reoxygenation (Shah et al., 1995). A possible role of impaired NO in cardiac autonomic dysfunction remains speculative. An interesting recent report in humans with heart failure suggested that whilst NO attenuated the ‘systolic’ response to β-agonists, the lusitropic effects were preserved (Hare et al., 1995c).
Heart failure with reduced ejection fraction in older adults
Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich in Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
As a geriatric syndrome, the development of HF in older adults involves multiple etiologies and pathogenetic pathways (Figure 21.1) (1). Aging is associated with multiple CV and non-CV structural and functional changes (41,42). These age-related changes, along with various other etiologies and pathogenetic pathways present in older adults interact with each other, thus increasing the risk of incident HF (Figure 21.1). For example, normal aging is associated with increased arterial stiffness, concentric remodeling of the LV myocardium, and reduced early diastolic relaxation and filling rates (43–46). Aging is also associated with reduced chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation (42,47). Reduced maximal stroke volume, reflecting reduced inotropic and lusitropic reserves, may contribute to HF in some older individuals though not in those screened to exclude occult coronary artery disease (48).
The cardiac myocyte: excitation and contraction
Neil Herring, David J. Paterson in Levick's Introduction to Cardiovascular Physiology, 2018
The SR Ca2+ pumps are regulated by an inhibitory pro-tein, phospholamban. The braking effect of phospholamban on the pump is reduced by adrenaline and noradrenaline. Consequently, adrenaline and noradrenaline increase the rate of myocardial relaxation (lusitropic action). The increased rate of SR Ca2+ pumping also increases SR Ca2+ content and hence the amount of Ca2+ released to activate contraction. This, as well as an increase in iCa, results in an increase of force (inotropic action), as described in the next section.
Clinical pharmacology of cardiac cyclic AMP in human heart failure: too much or too little?
Published in Expert Review of Clinical Pharmacology, 2023
An equally central role is played by cAMP in cardiac relaxation (positive lusitropy). The importance of this sometimes gets diluted by the focus given on cAMP's actions toward positive inotropy. Nevertheless, cAMP is essential for cardiac relaxation, a process necessary for proper ventricular filling during diastole, which, in turn, is a critical determinant of cardiac function, i.e. of the force of the next contraction (based on the Frank–Starling law of normal cardiac operation) [25,26] (Figure 1). Additionally, proper diastolic function is important for cardiac muscle oxygenation and nourishment, as the coronary arteries can only deliver blood to the cardiac cells during diastole (compressed during systole/contraction) [252626, . PKA is again the main mediator of cAMP's effects in cardiac relaxation. PKA lowers the free intracellular [Ca2+] (removes Ca2+ from the cytosol) via SERCA2a activation in the SR membrane (by phosphorylating phospholamban) and Na+/K+-ATPase (NKA) activation in the plasma membrane (by phosphorylating phospholemman), which induces the Na+/Ca2+-exchanger (NCX) to remove Ca2+ out of the cardiomyocyte [17,19] (Figure 1). At the same time, PKA reduces the Ca2+ sensitivity of actomyosin filaments and increases their distensibility via phosphorylation of cardiac troponin I (cTnI), titin, and cardiac myosin-binding protein-C3 (MyBPC3) [27,28,29] (Figure 1).
Cardioprotective effects of Galium verum L. extract against myocardial ischemia-reperfusion injury
Published in Archives of Physiology and Biochemistry, 2020
Jovana Bradic, Nevena Jeremic, Anica Petkovic, Jovana Jeremic, Vladimir Zivkovic, Ivan Srejovic, Jasmina Sretenovic, Stevan Matic, Vladimir Jakovljevic, Marina Tomovic
Our results clearly show that cardiodynamic parameters in control conditions were substantially reduced during reperfusion compared to values before ischemia. We obtained depression of cardiac function and impaired inotropic and lusitropic properties of the heart, as well as disturbed coronary circulation and HR, thus confirming that I/R injury is related to myocardial tissue dysfunction. On the other hand, 4 weeks treatment with G. verum extract did not only preserve contractile power of the heart, but even improved it, as evidenced by increase in dp/dt max values at the end of reperfusion compared to the values before ischemia. Additionaly, administration of G. verum significantly restored lusitropic property of myocardium and led to the recovery of systolic and diastolic function in comparison to hearts in control conditions. Restoration of flow was noticed in first minutes of reperfusion and it was followed by a slow continuous drop over 30 min reperfusion period, so at the end of recovery period it returned to the values observed before ischemia. The similar dynamic during reperfusion was noticed in terms of contractility force, thus suggesting that vasculature dilated in accordance with the demands of myocardial contraction. Insignificantly altered HR in rats who received G. verum provided sufficient time for myocardium to contract strongly.
Chronic testosterone administration improves cardiac contractility and has a beneficial effect on the haemostatic system by enhancing fibrinolytic activity and inducing hypocoagulation in healthy rats
Published in Archives of Physiology and Biochemistry, 2019
Naif M. Alhawiti, Sultan A. Alqahtani
Associated with the increased levels of circulatory testosterone in the serum of the treated rats, there was a significant increase in systolic blood pressure that was consistent with the significant increase in left ventricular (LV) inotropic functions as evident by the increments of the LVSP and of the positive dp/dtmax. Also, the testosterone-treated rats had increased cardiac lusitropic function as evident by the increment in negative dp/dt. Interestingly, LVEDP and heart rate (HR) and all measured intervals of ECG remained unchanged suggesting a maintained diastolic function. It has been confirmed that a change in heart rate is the most serious side effect of cardiac agents that lead to a side effect of arrhythmia (Angelakos et al.1969, Marquardt 1979). Taken together, these data suggest a positive inotropic and lusitropic effect of testosterone on control hearts.
Related Knowledge Centers
- Calcium
- Calcium Atpase
- Inotrope
- Phospholamban
- Sarcoplasmic Reticulum
- Catecholamine
- Troponin I
- Cardiac Muscle
- Cytosol
- Camp-Dependent Pathway