Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1-13 C]pyruvate study.

Cardiac metabolism has received considerable attention in terms of both diagnostics and prognostics, as well as a novel target for treatment. As human trials involving hyperpolarized magnetic resonance in the heart are imminent, we sought to evaluate the general feasibility of detection of an imposed shift in metabolic substrate utilization during metabolic modulation with glucose-insulin-potassium (GIK) infusion, and thus the limitations associated with this strategy, in a large animal model resembling human physiology. Four [1-13 C]pyruvate injections did not alter the blood pressure or ejection fraction over 180 min. Hyperpolarized [1-13 C]pyruvate conversion showed a generally high reproducibility, with intraclass correlation coefficients between the baseline measurements at 0 and 30 min as follows: lactate to pyruvate, 0.85; alanine to pyruvate, 1.00; bicarbonate to pyruvate, 0.83. This study demonstrates that hyperpolarized [1-13 C]pyruvate imaging is a feasible technique for cardiac studies and shows a generally high reproducibility in fasted large animals. GIK infusion increases the metabolic conversion of pyruvate to its metabolic derivatives lactate, alanine and bicarbonate, but with increased variability.

Myocardial protection with Glucose-Insulin-Potassium infusion during adult cardiac surgery.

BACKGROUND & OBJECTIVE: Recent meta-analysis reports have called for more randomized trials to evaluate the effectiveness of GIK solution in patients of cardiac surgery. So this study was conducted to evaluate the effectiveness of Glucose-insulin-potassium (GIK) solutions in non-diabetic patients undergoing coronary artery bypass grafting. METHODS: A total number of one hundred and sixty (160) patients were randomized into two equal groups; GIK Group and non-GIK group. In GIK group, 5% dextrose containing 70 IU/L regular insulin and 70 meq/L of potassium was administered. The infusion was started at a rate of 30 ml/hour after induction of anesthesia and before the start of cardiopulmonary bypass. The infusion was started again after removal of aortic cross clamp and was continued for six hours after the operation. RESULTS: In early post-operative period, peak CKMB levels were high in non-GIK group 48.50±19.79 IU/L versus 33.40±14.69 IU/L in GIK group (p-value <0.001). There was no statistically significant difference in requirements of inotropic support between the groups. The mean duration of inotropic support in GIK group was only 5.50±6.88 hours in GIK group and 8.64±7.74 hours in non-GIK group (p-value 0.008). Mean ventilation time in GIK group was 5.06±2.39 hours versus 6.55±3.58 hours in non-GIK group (p-value 0.002). Similarly, ICU stay period was also shorter in GIK group (p-value 0.01). We did not found any detrimental effect of GIK infusion on non-cardiac complications e.g. renal, pulmonary and neurologic complications. CONCLUSION: Glucose-insulin-potassium (GIK) infusion has a beneficial role in myocardial protection and is associated with better post-operative outcomes without increasing the risk of non-cardiac complications.

Inhibitory Effect and Mechanism upon Glucose-Insulin-Potassium Administration on Postpartum Mice with Uterine Cramping Pain.

This study aimed to explore the effect of glucose-insulin-potassium (GIK) on postpartum uterine cramping pain(UCP) in mice and the possible underlying mechanisms. Thirty full-term pregnancy C57BL/6 mice, within 6 h after spontaneous labor, the mice were randomly assigned into the following three groups: the control group (group C), the oxytocin group (group O), and the GIK plus oxytocin group (group G). Group G and group O were administered GIK and normal saline, respectively, and 10 min later, oxytocin was injected intraperitoneally; group C received normal saline twice. The pain scores of the mice were assessed after establishment of the postpartum UCP model. The differential expressions of energy metabolism and oxidized lipid metabolites in the uterus were analyzed. The behavioral scores in group G were significantly lower than those in group O (P < 0.05).When compared to group O, group G showed a significant increase in ATP levels (P = 0.046), and group G exhibited elevated levels of amino acids, including L-glutamine, L-aspartic acid, and ornithine. Additionally, phosphate compounds (2-phosphoglyceric acid and 3-phosphoglyceric acid) showed elevated levels. When compared to group O, group G exhibited a decrease in 19R-hydroxy PGF2α, an increase in 9,10-EpOME and 12,13-EpOME, and a decrease in trans-EKODE-E-Ib. Additionally, group G showed an elevation in 16,17-EpDPE and 8-HDoHE. This study confirms the analgesic effect of GIK during postpartum oxytocin infusion. Metabolomics and glycolysis product analysis suggest that GIK's alleviation of UCP is associated with its enhancement of glycolysis and the influence of phenylalanine synthesis, aspartate metabolism, and arginine synthesis pathways. Additionally, the effects of GIK appears to be linked to its influence on the linoleic acid metabolic pathway.

Treatment of critical aluminum phosphide (rice tablet) poisoning with high-dose insulin: a case report.

BACKGROUND: Aluminum phosphide (rice tablet) is a highly efficient agent for preserving grains against rodents and insects. It accounts for a large number of poisoning cases. Aluminum phosphide poisoning has a high mortality rate of about 90%, and to date, no antidote is available. It releases phosphine gas after exposure to moisture, and this reaction is catalyzed by the acidity of the stomach. Phosphine is then absorbed throughout the respiratory or gastrointestinal tracts and causes toxicity through inhibition of cytochrome c oxidase and formation of highly reactive free radicals. Treatment of patients with aluminum phosphide poisoning is supportive, including mechanical ventilation and vasopressors. The usage of infusion of glucose-insulin-potassium in rice tablet poisoning has been suggested, after its positive beneficial cardiac inotropic effects in patients with beta-blocker and calcium channel blocker poisoning. CASE PRESENTATION: We report the case of a 30-year-old Iranian woman with critical aluminum phosphide poisoning, presented with hypotension and other signs of shock and severe metabolic acidosis, successfully treated with high-dose regular insulin and hypertonic dextrose and discharged from hospital in good condition. In contrast to our previous experiences, in which nearly all patients with critical aluminum phosphide poisoning died, this patient was saved with glucose-insulin-potassium. CONCLUSION: Aluminum phosphide poisoning has a high mortality rate, and to date, no antidote is available. Administration of high-dose intravenous regular insulin and dextrose is suggested as a potential life-saving treatment for patients with critical aluminum phosphide poisoning.

Effects of intermittent and long-term glucose-insulin-potassium infusion in patients with systolic heart failure.

BACKGROUND: Although single dose and short-term glucose-insulin-potassium (GIK) infusions are known to have positive cardiac effects, the effects of repeated and long-term GIK infusion on left ventricular (LV) systolic function and brain natriuretic peptide (BNP) levels are unknown. OBJECTIVE: To investigate the effects of repeated and long-term GIK infusion on LV systolic function and BNP levels. METHODS: Thirty-three patients diagnosed with ischemic cardiomyopathy were included in the study. Patients were divided into two groups: the GIK group (n=19) and the control group (n=14). GIK solutions (1000 mL 20% dextrose, 60 U insulin and 50 mmol/L KCl) were administered at 1 mL/kg/h for 24 h on the first, third and fifth days. The patients were examined by echocardiography at 24 h, one week and one month after the start of treatment. BNP levels were measured before and after GIK infusion. RESULTS: In the GIK group, baseline ejection fraction (EF) was 29.2+/-10.3%. After one week, EF elevated to 40.8+/-10.8% (P=0.001). The EF after one month (37.1+/-10.9%) was less than the EF in the first week, but it was significantly higher than baseline in the GIK group (P=0.01). However, no significant changes in EF were observed after one week and one month in the control group (P=0.1 and P=0.2, respectively). BNP levels after GIK infusion was significantly lower than baseline level in the GIK group (P=0.01). CONCLUSION: Intermittent and long-term GIK infusion has beneficial effects on LV systolic function in a short and intermediate amount of time. Decrease in BNP levels may indicate effective GIK treatment. Intermittent and long-term GIK infusion could be a promising treatment option in patients with systolic heart failure.

Experience using high-dose glucose-insulin-potassium (GIK) in critically ill patients.

PURPOSE: To audit the use of GIK in terms of safety, haemodynamic effects, and impact on catecholamine dosage. MATERIALS AND METHODS: A retrospective, descriptive, evaluative audit of GIK use within the adult ICU of a London teaching hospital was conducted. Rescue therapy of GIK (up to 1.0Unitsinsulin/kg/h) was administered to improve cardiac function. Outcomes were ICU survival, change in cardiac index (CI) and blood lactate levels, events of hypoglycaemia, hyperglycaemia, hypokalaemia and hyperkalaemia, and discontinuation time of catecholamine inotropes. RESULTS: Of 85 patients treated with GIK, 13 (15.3%) survived their ICU stay and 9 (10.5%) were discharged home. In patients surviving until 72h, a trend of improved CI and lactate levels was seen, often with reductions in catecholamine dosing. Inotropes were discontinued in 35 (54%) patients. Severe hypoglycaemia (<2mmol/l), hyperglycaemia (>20mmol/l), hypokalaemia (<2.5mmol/l) and hyperkalaemia (>7mmol/l) during GIK affected 1, 6, 8 and 1 patients, respectively. These abnormalities were quickly identified. No measurable harm was noted. CONCLUSIONS: High-dose GIK can be safely used in critically ill patients, though blood glucose and potassium levels must be monitored frequently. GIK was associated with improved CI and blood lactate levels. Impact on survival requires prospective evaluation.

A predictive model to identify patients with suspected acute coronary syndromes at high risk of cardiac arrest or in-hospital mortality: An IMMEDIATE Trial sub-study,,.

BACKGROUND: The IMMEDIATE Trial of emergency medical service use of intravenous glucose-insulin-potassium (GIK) very early in acute coronary syndromes (ACS) showed benefit for the composite outcome of cardiac arrest or in-hospital mortality. OBJECTIVES: This analysis of IMMEDIATE Trial data sought to develop a predictive model to help clinicians identify patients at highest risk for this outcome and most likely to benefit from GIK. METHODS: Multivariable logistic regression was used to develop a predictive model for the composite endpoint cardiac arrest or in-hospital mortality using the 460 participants in the placebo arm of the IMMEDIATE Trial. RESULTS: The final model had four variables: advanced age, low systolic blood pressure, ST elevation in the presenting electrocardiogram, and duration of time since ischemic symptom onset. Predictive performance was good, with a C statistic of 0.75, as was its calibration. Stratifying patients into three risk categories based on the model's predictions, there was an absolute risk reduction of 8.6% with GIK in the high-risk tertile, corresponding to 12 patients needed to treat to prevent one bad outcome. The corresponding values for the low-risk tertile were 0.8% and 125, respectively. CONCLUSIONS: The multivariable predictive model developed identified patients with very early ACS at high risk of cardiac arrest or death. Using this model could assist treating those with greatest potential benefit from GIK.

The heart is better protected against myocardial infarction in the fed state compared to the fasted state.

OBJECTIVE: A variety of calorie restriction diets and fasting regimens are popular among overweight people. However, starvation could result in unexpected cardiovascular effects. Therefore, it is necessary to evaluate the short-term effects of diets on cardiovascular function, energy metabolism and potential risk of heart damage in case of myocardial infarction. The objective of the present study was to investigate whether the increased level of glucose oxidation or reduction of fatty acid (FA) load in the fed state provides the basis for protection against myocardial infarction in an experimental rat model of ischemia-reperfusion. MATERIALS/METHODS: We tested the effects of the availability of energy substrates and their metabolites on the heart functionality and energy metabolism under normoxic and ischemia-reperfusion conditions. RESULTS: In a fasted state, the heart draws energy exclusively from FAs, whereas in a fed state, higher concentration of circulating insulin ensures a partial switch to glucose oxidation, while the load of FA on heart and mitochondria is reduced. Herein, we demonstrate that ischemic damage in hearts isolated from Wistar rats and diabetic Goto-Kakizaki rats is significantly lower in the fed state compared to the fasted state. CONCLUSIONS: Present findings indicate that postprandial or fed-state physiology, which is characterised by insulin-activated glucose and lactate utilisation, is protective against myocardial infarction. Energy metabolism pattern in the heart is determined by insulin signalling and the availability of FAs. Overall, our study suggests that even overnight fasting could provoke and aggravate cardiovascular events and high-risk cardiovascular patients should avoid prolonged fasting periods.

The value of creatine phosphate GIK in cardiac valve disease before operation / 中国基层医药

ObjectiveTo investigate the myocardial protection on cardiac valve replacement surgery with creatine phosphate of myocardial GIK (GIK) in order to reduce the surgical risk and improving the efficacy.Methods126 cases were unergone surgical treatment of heart valve disease,whose cardiac function on admission wereⅢor Ⅳ. 126 patients were randomly divided into two groups. Cardiopulmonary bypass time, aortic cross clamp time, postoperative myocardial injury markers ( CK-MB, cTNI) changes, arrhythmias, heart function recovery, length of stay and mortality rate and other indicators were compared between the two groups. ResultsThe age, gender, body mass,heart disease and surgery combined data were not statistically significant between the two groups( all P ＞0. 05). The cardiopulmonary bypass time, aortic cross clamp time and mortality had no significant differences between the two groups( all P ＞ 0.05 ). The CK-MB( 21.36± 9.21 ) U/L and cTNI(0.83 ± 0. 35 ) ng/ml of creatine phosphate group were significantly lower than those of the control group. The incidence of arrhythmia in phosphocreatine group (37. 1％ ) was significantly lower than ordinary group (57.8 ％ ) ( X2 ＝ 5. 418, P ＜ 0. 05 ). ConclusionThe application of creatine phosphate GIK before valve replacement surgery could effectively reduce reperfusion injury after myocardial ischemia,myocardial protection,and significantly reduce the incidence of arrhythmia and improve heart function in patients.

Glucose-Insulin-Potassium as an Adjunctive Therapy in Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: Glucose-insulin-potassium (GIK) fluid infusion may improve the myocardial energy metabolism in the ischemic condition. A prospective randomized clinical trial was designed to determine whether a GIK fluid infusion can reduce the ventricular remodeling in acute myocardial infarction. SUBJECTS AND METHODS: For the patients with acute myocardial infarction, during thrombolytic therapy with urokinase, GIK fluid (26% glucose 1000 mL, 50 IU insulin, and 80 mmol KCl) was administered for 24 hours. The ventricular volumes and function were evaluated by echocardiography during the admission period, at 6 months and at 12 months following discharge. RESULTS: This trial was done prospectively for 2 years in 73 patients; the GIK group included 41 patients and the control group included 32 patients. The median value of "the pain to door time" was 195 minutes in the GIK group and it was 120 minutes in the control group (p=NS). The wall motion score was 1.52+/-0.39 in the GIK group and it was 1.39+/-0.35 in the control group. The left ventricular volumes, ejection fractions, cardiac indices and the globular indices showed no significant difference between the two groups. The side effects of the GIK fluid were mild phlebitis in 6 patients (14.6%) and congestive heart failure in 5 patients (12.2%). CONCLUSION: This trial could not verify the beneficial effects of administering GIK fluid on the ventricular remodeling after acute myocardial infarction. The limitations of this trial were as follows: "the pain to door time" was too long and the severity of the myocardial infarction was mild. Low rates for the echocardiogrphy follow-up and the randomization failure in a few patients were also noted.

Effect of Intravenous Glucose-Insulin-Potassium on Cardiovascular Functions during Acute Hypoxia / 第三军医大学学报

The effect of intravenous infusion of glucose-insulin-potassium (G1K) on the cardiovascular functions during acute hypoxia was studied and was compared with that of normal saline(NS). 14 anesthetized dogs were forced to inhale a hypoxic gas mixture. After the first ten-minute inhalation, Pao2 and total peripheral vascular resistance decreased to 29~3l% and 66-67% of the pre-in-halation levels respectively while the pulmonary arterial pressure increased 43-49%. Then a bolus injection of GIK was given to 8 dogs, and an injection of NS to 6 dogs. Hypoxic gas inhalation was continued for 20 more minutes. 5 -10 minutes after GIK injection, the mean arterial pressure, cardiac output, stroke volume, stroke work , and left ventricular pressure all significantly increased, however, no apparent changes could be observed in any of the above mentioned parameters after NS injection. This result reveals that cardiovascular functions during acute hypoxia can be rapidly, markedly but temporarily improved when a small volume of GIK is administered intravenously.