Opioid receptor independent effects of morphine on membrane currents in single cardiac myocytes

Hung, Chi‐Feng; Tsai, Chang‐Her; Su, Ming‐Jai

doi:10.1093/bja/81.6.925

Cited by 16 publications

(10 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…51 Morphine also hyperpolarizes the cardiac resting membrane potential by increasing the inwardly rectifying K + current (I KI ), an action apparently not mediated by opioid receptors. 52,53 Morphine and other opioids induce pharmacologic preconditioning of the myocardium. [54][55][56] The underlying mechanism involves K ATP channels, as with the inhalational anesthetics.…”

Section: Opioidsmentioning

confidence: 99%

Intravenous Anesthesia for the Patient with Left Ventricular Dysfunction

Bovill

2006

Semin Cardiothorac Vasc Anesth

101

View full text Add to dashboard Cite

Patients with heart failure have a diminished cardiac reserve capacity that may be further compromised by anesthesia. In addition to depression of sympathetic activity, most anaesthetics interfere with cardiovascular performance, either by a direct myocardial depression or by modifying cardiovascular control mechanisms. Etomidate causes the least cardiovascular depression. It is popular for induction of anesthesia in cardiac-compromised patients; however, it is not suitable for maintenance of anesthesia because it depresses adrenocortical function. Ketamine has a favorable cardiovascular profile related to central sympathetic stimulation and inhibition of neuronal catecholamine uptake. These counteract its direct negative inotropic effect. In patients with a failing myocardium, however, the negative inotropic effects may be unmasked, resulting in deterioration in cardiac performance and cardiovascular instability. Propofol is the most popular intravenous anesthetic for maintenance of anesthesia. It does have a negative inotropic effect, but the net effect on myocardial contractility is insignificant at clinical concentrations, probably because of a simultaneous increase in the sensitivity of the myofilaments to Ca2+. Propofol protects the myocardium against ischemia-reperfusion injury, an action derived from its antioxidant and free-radical-scavenging properties as well as the related inhibition of the mitochondrial permeability transition pore. For intravenous anesthesia, propofol is always combined with an opioid. Opioids have relatively few cardiovascular side effects and, in particular, do not cause myocardial depression. Indeed, they are cardioprotective, with antiarrhythmic activity, and induce pharmacologic preconditioning of the myocardium by a mechanism similar to the inhalational anesthetics.

show abstract

Section: Opioidsmentioning

confidence: 99%

Intravenous Anesthesia for the Patient with Left Ventricular Dysfunction

Bovill

2006

Semin Cardiothorac Vasc Anesth

101

View full text Add to dashboard Cite

show abstract

“…In rabbit ventricular myocytes, morphine significantly increased I K1 , independent of the opioid-receptor pathway [42]. In human atrial myocytes, morphine was unable to enlarge I K1 [63].…”

Section: Morphinementioning

confidence: 88%

Towards the Development of AgoKirs: New Pharmacological Activators to Study Kir2.x Channel and Target Cardiac Disease

Schoor

Hattum

Wilde

et al. 2020

IJMS

View full text Add to dashboard Cite

Inward rectifier potassium ion channels (IK1-channels) of the Kir2.x family are responsible for maintaining a stable negative resting membrane potential in excitable cells, but also play a role in processes of non-excitable tissues, such as bone development. IK1-channel loss-of-function, either congenital or acquired, has been associated with cardiac disease. Currently, basic research and specific treatment are hindered by the absence of specific and efficient Kir2.x channel activators. However, twelve different compounds, including approved drugs, show off-target IK1 activation. Therefore, these compounds contain valuable information towards the development of agonists of Kir channels, AgoKirs. We reviewed the mechanism of IK1 channel activation of these compounds, which can be classified as direct or indirect activators. Subsequently, we examined the most viable starting points for rationalized drug development and possible safety concerns with emphasis on cardiac and skeletal muscle adverse effects of AgoKirs. Finally, the potential value of AgoKirs is discussed in view of the current clinical applications of potentiators and activators in cystic fibrosis therapy.

show abstract

“…Moreover, it has been shown that the cardiac effects of opioids could be or not be dependent on opioid receptors. The effects of morphine on ionic currents in cardiac myocytes have shown not to depend on opioid receptor 24 or to be mediated via d-and k-receptors 25 . However, its cardioprotective effect is known to be due to the activation of d-receptors 26,27 .…”

Section: Discussionmentioning

confidence: 99%