Activation of ATP-Sensitive Potassium Channels Underlies Contractile Failure in Single Human Cardiac Myocytes During Complete Metabolic Inhibition

ATP-Sensitive Potassium Channels in Human Heart. Introduction: The purpose of this study was to examine the electrophysiologic derangements that underlie contractile failure in single human heart muscle cells exposed to metabolic inhibition. Methods and Results: Single myocytes were isolated from right atrial appendage specimens obtained intraoperatively from patients undergoing routine cardiac surgery. On exposure to lO-mM 2-deoxyglucose (to inhibit glycolysis) and 2-mM cyanide (to inhibit oxidative phosphorylation), twitch shortening decreased to undetectable levels over 5–6 minutes. The action potential duration declined in parallel with the contractile failure. Using voltage clamp depolarizations of a fixed duration the twitch was maintained in metabolic blockade until the development of maintained (rigor) contracture. At this time a large increase in K⁺ conductance, which can be attributed to the activation of ATP-sensitive K ⁺ channels (K _ATP channels), was measured. In isolated inside-out membrane patches, the ATP dependence of K_aTP channel activity was described by a sigmoid curve with K_i,_ATP (ATP concentration required for half-maximal inhibition of K _ATPchannel activity) = 8 μM and Hill coefficient (n_H) = 1.2. The single channel current-voltage relationship reversed close to the K ⁺ equilibrium potential and the conductance was approximately linear (g = 29 pS) over the voltage range included in the action potential (-60 m V to +20 mV). Conclusion: In human atrial cardiac myocytes subjected to complete metabolic inhibition, contractile failure is caused by action potential shortening resulting from an increase in K + conductance presumably through the activation of K_ATP channels. (J Cardiovasc Electrophysiol, Vol. 3, pp. 56–63, February 1992)     

Pain in elderly orthopaedic patients

Summary

• ? This paper focuses on one aspect of a study of elderly orthopaedic patients, namely pain control.
• ? One-hundred patients aged 70 years and over were interviewed on up to five occasions during admission to an acute orthopaedic unit.
• ? The majority of patients had significant post-operative and/or post-trauma pain, and backache and joint pain were reported frequently.
• ? None of the patients received more than half of the maximum prescribed number of doses of opioid analgesics over a period of 48 h following surgery.
• ? The well-recognized problem of inadequate pain relief among hospital in-patients is discussed, in particular its relevance to elderly orthopaedic patients.