Effects of GIK (glucose–insulin–potassium) on stress-induced myocardial ischaemia

Abstract

Despite the evidence in experimental animal models that insulin, or GIK (glucose-insulin-potassium), improves left ventricular function and perfusion during both acute and chronic ischaemia, clinical studies have generated conflicting results. We tested the hypothesis that pretreatment with GIK attenuates the vascular and functional effects of stress-induced myocardial ischaemia in humans. Twenty-two patients with evidence of inducible myocardial ischaemia were enrolled; 11 patients with normal ventricular function underwent two dipyridamole echocardiography tests, and 11 with regional contractility defects from previous myocardial infarction were submitted to two ECG exercise tests combined with 201Tl myocardial perfusion scintigraphy; the tests were preceded by 60 min of either normal saline or an isoglycaemic GIK infusion. On a stress echocardiogram, a 30% reduction in the severity of ischaemia was observed. On ECG ergometry, GIK infusion slightly increased the time to ischaemia (+0.6 min, P=0.07); however, the higher workload (+8%, P=0.07) was achieved at a similar rate-pressure plateau. On scintigraphy, an increase in ischaemic segments (+48%, P<0.001) was imaged mainly at the expense of viable (but non-ischaemic) and non-viable segments, which were reduced by 60%. GIK affected stress-induced left ventricular underperfusion only marginally (GIK: 39.7+/-2.5 compared with saline: 35.4+/-2.2 units, P<0.05), but significantly improved its acute reversibility (-42+/-4 compared with -25+/-4%, P<0.001). We conclude that GIK pretreatment attenuates the effect of ischaemia on myocardial contractility, slightly improves exercise tolerance and causes a more rapid and diffuse recovery of post-ischaemic reperfusion.

Diabetes Blockade of Sevoflurane Postconditioning Is Not Restored by Insulin in the Rat Heart

“…On occasions when insulin is given as part of a metabolic cocktail, composed of glucose, insulin, and potassium, it reduced infarct size in animals 28 ; however, the timing of applying this intervention is controversial. In a recent human study, 41 pretreatment with glucose, insulin, and potassium reduced the severity of the stress-induced contractile dysfunction and improved postischemic reperfusion; however, another study 28 suggested that insulin effectively attenuates I/R-induced apoptosis when given after the ischemic interval (during reperfusion). According to our findings, we suggest that caution should be taken not to add insulin before the planned ischemic period.…”

Pretreatment with glucose–insulin–potassium improves ventricular performances after coronary artery bypass surgery: a randomized controlled trial

“…In brain death-induced heart failure, GIK infusion has been shown to increase LVEF as much as moderate doses of dobutamine while avoiding tachyarrhythmias and arterial hypotension [29]. Likewise in patients with severe coronary artery disease, GIK infusion at a similar dosage has been shown to increase the ischemic threshold and LVEF while improving exercise tolerance and correcting stressinduced LV dysfunction [30,31].…”

Glucose-Insulin-Potassium Alleviates Intestinal Mucosal Barrier Injuries Involving Decreased Expression of Uncoupling Protein 2 and NLR Family-Pyrin Domain-Containing 3 Inflammasome in Polymicrobial Sepsis

“…GIK, an effective prescription for coronary heart disease and other heart diseases clinically [9, 26, 27], has been shown to exert anti-inflammatory effects to attenuate the systemic inflammatory response in endotoxemia rats and humans by inactivating nuclear factor κ B or the phosphoinositide 3-kinase/Akt signaling pathway [28]. GIK is a “cocktail” recipe that consists of dextrose, insulin, and potassium: insulin has a bioactive role in the anti-inflammatory, antioxidation, and antiapoptotic effects in various conditions; dextrose resists hypoglycemia; insulin and dextrose together assist the transfer of potassium from extracellular to intracellular fluids; and all three components work together to exert bioactive effects without the side effects of hypoglycemia and hypokalemia [29].…”