Ingemar Vanhanen

Glutamate and high-dose glucose-insulin-potassium (GIK) in the treatment of severe cardiac failure after cardiac operations

Postischemic derangement of myocardial metabolism that is further aggravated by the systemic neuroendocrine response to surgical trauma may explain reversible myocardial dysfunction after cardiac surgical procedures. Since 1991, all patients with signs of cardiac failure after operation for ischemic heart disease (45/515 patients) were treated according to our metabolic strategy. Sixteen patients in whom we previously would have considered use of an intraaortic balloon pump were treated by prolonged unloading of the heart with cardiopulmonary bypass, by glutamate infusion, and by high-dose glucose-insulin-potassium. Rapid improvement in hemodynamic performance was seen in the first hour and almost full recovery within 6 hours in the surviving patients (12/16). None of the 3 patients requiring mechanical assist survived. Our early clinical experience suggests that metabolic support with glutamate and high-dose glucose-insulin-potassium is a safe treatment with a high success rate in reversible cardiac failure.

Rationale for metabolic support with amino acids and glucose-insulin-potassium (GIK) in cardiac surgery

Myocardial metabolism and the current state of metabolic intervention under conditions relevant to cardiac surgery are reviewed. The rationale for metabolic support differs considerably in various settings of cardiac surgery. Although preventive measures are theoretically attractive, their use in the preoperative setting remains to be clarified. Amino acid enrichment of blood cardioplegia seems to be justified by an abundance of animal experimental data. In the postoperative setting of cardiac surgery, metabolic abnormalities may explain reversible myocardial dysfunction. Further, the combined effects of ischemia and the systemic neuroendocrine response to surgical trauma may adversely affect recovery. Amino acids, particularly glutamate, seem vital for metabolic recovery in this setting. Treating the relative shortage of glutamate occurring during this period by the administration of exogenous glutamate and counteracting the effects of the systemic neuroendocrine stress response by high-dose glucose-insulin-potassium are measures that have been shown to improve the metabolic state of the heart and subsequently myocardial performance.

METABOLIC AND HEMODYNAMIC EFFECTS OF INTRAVENOUS GLUTAMATE INFUSION EARLY AFTER CORONARY OPERATIONS

Amino acids, particularly glutamate, have been proposed to play an important role in the recovery of cardiac oxidative metabolism after ischemia. In this investigation, the metabolic and hemodynamic effects of glutamate infusion after coronary operations were studied. From 220 to 240 ml 0.1 mol/L l-glutamic acid solution was infused in 10 patients during 1 hour starting 2 hours after operation. A control group of 10 patients received an infusion of 240 ml saline solution. During glutamate infusion, there were significant increases in the uptake of glutamate (from 0.7 +/- 0.2 micromol/min in the basal state to a peak of 5.7 +/- 1.2 micromol/min at 20 minutes) and lactate (from 4.9 +/- 2.0 micromol/min in the basal state to 14.1 +/- 4.4 micromol/min at 60 minutes; p < 0.01), whereas the uptake and release of other substrates remained essentially unaffected. Arterial glutamate levels (in whole blood) increased from 103 +/- 10 micromol/L to 394 +/- 20 micromol/L at 60 minutes. Thirty minutes after discontinuation of the glutamate infusion, arterial levels had decreased to 129 +/- 17 micromol/L. The markedly improved utilization of lactate and the unchanged release of alanine together suggest that the oxidative metabolism of the heart was stimulated by glutamate. The metabolic changes were associated with improved myocardial performance. Left ventricular stroke work index increased from 26.8 +/- 2.1 gm x beat(-1) x m(-2) body surface area to 31.3 +/- 3.1 gm x beat(-1) x m(-2) body surface area during glutamate infusion. Metabolic support with amino acids may provide a means to improve recovery of metabolic and hemodynamic function of the heart early after cardiac operations.

Physiologic aspects in postoperative cardiac patients

After a cardiac operation, there is reversible myocardial dysfunction that also involves a metabolic disorder. In patients with cardiac failure, care must be taken to reduce the strain on the heart by minimizing systemic oxygen uptake, which is, in fact, the main determinant of cardiac output. Inotropic support may improve cardiac output and tissue oxygenation in cardiac failure, but it also increases myocardial stress directly by increasing myocardial demands and indirectly by increasing systemic energy demands. Mixed venous oxygen saturation reflects the balance between cardiac output and systemic oxygen consumption and indicates whether cardiac output can adequately provide the peripheral tissues with oxygen. This physiologic view toward the treatment of postoperative cardiac failure helps us avoid overtreatment, that is, stimulating cardiac output more than necessary for adequate tissue oxygenation. In this way, the strain on the heart can be reduced and myocardial recovery, enhanced.

Assessment of myocardial glutamate requirements early after coronary artery bypass surgery.

Glutamate is an important substrate for the intermediary metabolism of the heart, particularly in association with ischemia. Early after coronary artery bypass surgery (CABG) myocardial uptake of glutamate seems to be limited by substrate availability (arterial levels). However, glutamate is not an innocuous substrate. As arterial levels of glutamate are important both for myocardial uptake and adverse effects, an attempt was made to determine a minimum dose of glutamate sufficient to supply the needs of the heart after CABG. Ten patients received and infusion of 220-240 ml of 0.1 M L-glutamic acid solution at varying rates during two 30-min periods, starting 2 h after uncomplicated elective CABG. Intravenous glutamate infusion caused a dose-dependent linear increase in arterial glutamate and an increased myocardial uptake of glutamate. However, myocardial uptake of glutamate correlated with arterial levels only at lower infusion rates. Although maximal peak uptake in individual patients (6.6 +/- 1.1 mumol/min) occurred at an average increase of arterial whole blood glutamate of 172 +/- 34 mumol/L, the greatest impact on myocardial glutamate uptake was achieved by increasing arterial whole blood glutamate by less than 100 mumol/L. This implies that an infusion rate of 30-40 mg glutamate/kg BW/h could suffice to achieve a maximal or near maximal myocardial glutamate uptake in most patients after CABG. The adequacy of this dosage remains to be confirmed in high-risk patients.

A metabolic protective strategy could improve long-term survival in patients with LV-dysfunction undergoing CABG

Abstract Objective. Adverse outcome after CABG is closely related to postoperative heart failure precipitated by ischemia and myocardial infarction. Restrictive use of inotropes is therefore desirable. Patients with preoperative left ventricular dysfunction are a high-risk group in this respect. To reduce myocardial oxygen expenditure we evolved a metabolic strategy for perioperative care. Design. Observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. The metabolic strategy implied physiological measures to minimize myocardial oxygen expenditure including restrictive use of inotropes and specific measures such as extended CPB and metabolic support to facilitate myocardial recovery. Hemodynamic state was primarily assessed by mixed venous oxygen saturation (SvO2). Follow-up averaged 9.7±1.4 years. Results. LVEF was 0.30±0.05 (range 0.20–0.37) and 3.5±1.3 vessels were bypassed. Inotropes were used in 6.7% for weaning from CPB. Increase of s-creatinine by ≥50% compared to preoperative values was observed in 2.9%. Logistic EuroSCORE was 8.3% whereas observed 30-day mortality was 1.0%. Crude 5-year survival was 89.4%. Conclusions. The metabolic strategy allowed restrictive use of inotropes and was associated with encouraging long-term survival. Renal function was well preserved suggesting that SvO2 served as an adequate marker of circulation. Randomized trials with metabolic support are warranted.

Measurement of physical work capacity in patients with chronic aortic regurgitation: a potential improvement in patient management

Background:  Timing of surgery in aortic regurgitation (AR) is important. Exercise testing is recommended upon uncertainty about functional limitations but reports on cardiopulmonary exercise testing (CPET) in populations with pure chronic AR are scarce.

Myocardial Uptake and Release of Substrates in Patients Operated for Unstable Angina: Impact of Glutamate Infusion

Objective—To study cardiac uptake and release of substrates and the influence of intravenous glutamate in patients operated for unstable angina requiring intravenous nitrates. Design—Nineteen patients were randomized to blinded infusion of glutamate or saline. Arterial-coronary sinus differences of substrates were measured before cardiopulmonary bypass (CPB) and during early reperfusion. Results—Before CPB the only major substrates that Were extracted by the heart in the saline group were free fatty acids (FFAs). During reperfusion uptake of glucose and glutamate was found but FFAs remained the major substrate extracted by the heart. Initially transient low oxygen extraction and lactate release were found. Conversion to lactate uptake was not observed. Glutamate infusion was associated with an uptake of glutamate and in contrast to the control group there was also uptake of lactate before CPB and at the end of the study period. Conclusion—The metabolic situation before CPB with a reliance on myocardial FFA uptake is less than ideal with regard to ischemia. Early reperfusion was characterized by dynamic changes and a shift towards myocardial glucose uptake but FFAs remained the major substrate extracted. The qualitative findings associated with glutamate infusion agree with previous animal and human studies but have to be interpreted cautiously due to lack of flow measurements.

Resection of a plasma cell granuloma combining a conventional posterolateral left-sided thoracotomy with a minimally invasive valve approach

Plasma cell granuloma (PCG) is a rare benign tumor that is difficult to differentiate from malignancy. Depending on the location of the PCG, surgical management can be challenging. We describe a patient with a PCG involving the left lower lobe extending into the left atrium, that was resected en bloc using a conventional posterolateral thoracotomy combined with a surgical approach predominantly used for minimally invasive mitral valve surgery. This case illustrates how it is possible to utilize a technique used for cardiac surgery for tumors of pulmonary origin involving the heart.

Surgical management of outflow tract obstruction after transapical mitral valve implantation

Left ventricular outflow tract (LVOT) obstruction due to systolic anterior motion of the anterior mitral valve leaflet (AML) is a known complication after mitral valve repair or transfemoral/transapical mitral valve implantation (TMVI). We present a patient with a previous mitral valve repair who developed LVOT obstruction after TMVI in whom the AML was surgically resected using a transaortic approach.