Beneficial haemodynamic effects of insulin in chronic heart failure

Abstract

Objective-To characterise the central and regional haemodynamic eVects of insulin in patients with chronic heart failure. Design-Single blind, placebo controlled study. Setting-University teaching hospital. Patients-Ten patients with stable chronic heart failure. Interventions-Hyperinsulinaemic euglycaemic clamp and non-invasive haemodynamic measurements. Main outcome measures-Change in resting heart rate, blood pressure, cardiac output, and regional splanchnic and skeletal muscle blood flow. Results-Insulin infusion led to a dose dependent increase in skeletal muscle blood flow of 0.36 (0.13) and 0.73 (0.14) ml/dl/min during low and high dose insulin infusions (p < 0.05 and p < 0.005 v placebo, respectively). Low and high dose insulin infusions led to a fall in heart rate of 4.6 (1.4) and 5.1 (1.3) beats/min (p < 0.05 and p < 0.005 v placebo, respectively) and a modest increase in cardiac output. There was no significant change in superior mesenteric artery blood flow. Conclusion-In patients with chronic heart failure insulin is a selective skeletal muscle vasodilator that leads to increased muscle perfusion primarily through redistribution of regional blood flow rather than by increased cardiac output. These results provide a rational haemodynamic explanation for the apparent beneficial eVects of insulin infusion in the setting of heart failure. (Heart 2001;85:508-513)

Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium

“…We cannot exclude the possibility that higher insulin infusion rates could have additional beneficial effects. However, the rate chosen in the present study ensured an insulin infusion rate Ͼ6 U/h, which is comparable or even higher than that in most previous clinical studies documenting a beneficial effect in postoperative or acute ischemic states (7,26,29,30,33). We documented that circulating FFAs were totally suppressed and that we achieved plasma insulin levels in the supraphysiological range.…”

“…A plausible explanation is heterogeneity of the patient populations studied, i.e., inclusion of patients with relatively preserved EF (23,29), diabetes mellitus (23), and dilated cardiomyopathy (33). Furthermore, omission of viability testing (33), episodes of hypoglycemia (23), lack of a control study arm (23), and insensitive measures of contractile function (29,33) may contribute to the variable results. In the present study, we included nondiabetic patients with severe ischemic cardiomyopathy who were carefully characterized with respect to myocardial viability.…”

“…Although it has previously been demonstrated that wall motion may not improve with insulin infusion in patients with ischemic heart disease without heart failure (29), the effects of metabolic modulation on resting contractile function in patients with left ventricular dysfunction are not consistent (23,29,33). A plausible explanation is heterogeneity of the patient populations studied, i.e., inclusion of patients with relatively preserved EF (23,29), diabetes mellitus (23), and dilated cardiomyopathy (33). Furthermore, omission of viability testing (33), episodes of hypoglycemia (23), lack of a control study arm (23), and insensitive measures of contractile function (29,33) may contribute to the variable results.…”

“…At the same time, it has been reported that myocardial insulin sensitivity is preserved to a degree that allows an ample insulin-stimulated enhancement of glucose uptake in reversibly dysfunctional myocardium in patients with ischemic cardiomyopathy (29). Reversible myocardial dysfunction in ischemic cardiomyopathy is caused by stunning and hibernation (35,50), but it is unknown whether modulation of fuel substrate supply in patients affects cardiac performance (23,29,33) and whether increased glucose supply and decreased FFA supply improve cardiac function, such that therapeutic strategies designed to enhance myocardial glucose uptake could be rational goals. The main purpose of the present work was to study whether modulation of myocardial substrate metabolism affects contractile function of chronically stunned and hibernating myocardium at rest and after maximal exercise.…”

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

“…This result should be interpreted cautiously not only because of borderline statistical significance, but also because the differences were small and the ECG signs of ischaemia were observed at similar double-product rates. The effect on exercise tolerance could be due to improved systemic haemodynamics (secondary to peripheral vasodilatation, as seen in patients with chronic heart failure [21]) and/or to a slower rise in heart rate; this, in turn, could be the consequence of an improved skeletal muscle efficiency (i.e. ATP production per unit of oxygen consumption).…”