Effect of repeated episodes of drug-induced ventricular dyskinesia on subsequent regional function in the dog: Comparison with myocardial stunning produced by repeated coronary occlusions

Abstract

Stunned myocardium can be produced by repeated short episodes of ischemia. Histochemical and ultrastructural abnormalities such as sarcomere lengthening and myofiber thinning have been noted in myocardium soon after the onset of ischemia and have been attributed to the mechanical stretching that occurs during ventricular systole. To test whether mechanical forces alone could produce the residual dysfunction seen in stunned myocardium, regional dyskinesia was produced in open chest dogs by six repeated intracoronary infusions of either potassium chloride, 0.2 mEq/min for 2.5 minutes, or lidocaine, a 10 mg bolus followed by 1 to 3 mg/min for 5 minutes. These dogs were matched with dogs that had six repeated coronary occlusions of 2.5 and 5 minutes' duration, respectively. Regional function was analyzed using fractional systolic shortening and the load-independent end-systolic pressure-length relation. Both potassium chloride and lidocaine produced regional dyskinesia that was similar to the dyskinesia produced by coronary occlusion. Although regional ventricular function after repeated coronary occlusions remained significantly reduced, function returned completely to normal within 5 minutes after the last drug-induced dyskinesia. In conclusion, regional dysfunction produced by potassium chloride and lidocaine does not produce residual dysfunction despite mechanical forces during systole similar to those seen during coronary occlusion.

The effect of coronary arterial pressure on myocardial distensibility. Absence of a “garden hose” effect during in-vivo conditions

“…Although KCI can produce primary vasoconstriction, ischemia is unlikely. In contrast to ischemia, discontinuation of the regional KCI infusion results in complete restoration of function (11,14).…”

“…In three dogs, potassium chloride (KCI) at a concentration of 1.0 mEq/ml was infused into the LAD perfusion line at a rate of 0.34 or 0.68 ml/min in order to abolish regional myocardial contraction (11,14). After 10 min of regional cardioplegia the segment length was recorded.…”

Nonischemic ST-Segment Elevation Induced by Negative Inotropic Agents

“…The time course of changes in the ∆ST and %SS appeared simultaneously with equal severity (Fig 4). Experimental models of drug-induced ventricular dyskinesia have been reported in other studies, 11,12 in which lidocaine and potassium chloride were used. In our study, 4 different agents that modify different ion channels showed similar results on ventricular dyskinesia and ST-segment elevation.…”

“…These mechanical changes could have altered the transmembrane potential and action potential duration due to mechanoelectrical feedback effects. 12 Mechanoelectrical feedback is defined as electrophysiological changes caused by mechanical effects or a hemodynamic loading condition, and is believed to be a cause of arrhythmogenesis in the presence of heart failure. 13 Lab demonstrated that stretching of the ventricular myocardium of frogs caused shortening of the action potential and depolarization of the resting potential.…”

Post-ischaemic myocardial dysfunction (stunning) results from myofibrillar oedema

“…We performed experiments in three groups of anaesthetised closed-chest pigs. In the first group we created myocardial stunning using repetitive ischaemia–reperfusion 6. We measured regional function in vivo using tagged magnetic resonance imaging (MRI) and measured myocardial water content (MWC) post mortem.…”