A dose-response study of glutamate supplementation in isolated, perfused rat hearts undergoing ischaemia and cold cardioplegia.

OBJECTIVES: Several studies have reported superior post-cardioplegic recovery after glutamate supplementation. The optimum dose of glutamate supplementation is unknown. The purpose of this study was to find the optimal protective concentration of glutamate supplementation in a model of ischaemia/cardioplegia and reperfusion. METHODS: Isolated rat hearts (n = 77) were perfused with the Krebs-Henseleit buffer. After stabilization, the hearts were subjected to 25 min of normothermic ischaemia followed by a single 3-min infusion of cold (4-6 °C) St. Thomas' Hospital II cardioplegia and 87 min of cardioplegic ischaemic arrest and 60 min of reperfusion. Sodium-l-glutamate was added to the perfusate (control group had zero glutamate) in increasing concentrations (0.01, 0.1, 1, 10, 20, 30 and 100 mM) and given throughout perfusion. Corresponding concentrations were added to the cardioplegic solution. A balloon in the left ventricle inserted via the left atrium measured left ventricular pressures isometrically. Left ventricular developed pressure was calculated. Myocardial exchange of glucose and lactate was measured prior to ischaemia and during reperfusion. Myocardial content of glycogen and glutamate was measured at the end of reperfusion. RESULTS: During reperfusion left ventricular developed pressure increased (P < 0.0001) in groups supplemented with 0.1, 1.0, 10, 20 and 30 mM glutamate, whereas left ventricular end-diastolic pressure was attenuated (P = 0.008) when compared with the controls. No additional benefit on the continuous data left ventricular developed pressure and left ventricular end-diastolic pressure was observed with glutamate concentrations above 1 mM. Onset of LV pressure rise during the period of ischaemia was delayed by 100 mM of glutamate (P = 0.02). Myocardial content of glutamate was increased in a dose-related manner in Groups 10, 20, 30 and 100 compared with the control hearts (P < 0.0001). Glycogen was increased in the hearts supplemented with 100 mM of glutamate (P = 0.02). CONCLUSIONS: Even low concentrations of l-glutamate improved postischaemic and post-cardioplegic heart function and 1 mM seems to be optimal.

Adding Emulsified Isoflurane to Cardioplegia Solution Produces Cardiac Protection in a Dog Cardiopulmonary Bypass Model.

This study investigated whether caridoplegia solution with Emulsified Isoflurane (EI) could improve cardiaoprotection in a dog CPB model of great similarity to clinical settings. Adult dogs were randomly assigned to receive one of the following cardioplegia solutions: St. Thomas with EI (group ST+EI), St. Thomas with 30% Intralipid (group ST+EL) and St. Thomas alone (group ST). The aorta was cross-clamped for two hours followed by reperfusion for another two hours, during which cardiac output was measured and dosages of positive inotropic agent to maintain normal hemodynamics were recorded. Serum level of cardiac troponin I (cTnI) and CK-MB were measured. Deletion of cardiac mitochondrial DNA was examined at the end of reperfusion. Compared with ST, ST+EI decreased the requirement of dopamine support while animals receiving ST+EI had a significantly larger cardiac output. ST+EI reduced post-CPB release of cTnI and CK-MB. Mitochondrial DNA loss was observed in only one of the tested animals from group ST+EI while it was seen in all the tested animals from group ST+EL and ST. Addition of emulsified isoflurane into cardioplegia solution protects against myocardial ischemia reperfusion injury. This protective effect might be mediated by preserving mitochondrial ultrastructure and DNA integrity.

Propofol cardioplegia: A single-center, placebo-controlled, randomized controlled trial.

OBJECTIVES: Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is an effective treatment for coronary artery and aortic valve diseases. However, the myocardium sustains reperfusion injury after ischemic cardioplegic arrest. Our objective was to assess the benefits of supplementing cardioplegia solution with the general anesthetic propofol in patients undergoing either coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). METHODS: A single-center, double-blind randomized controlled trial was carried out to compare cardioplegia solution supplemented with propofol (concentration 6 µg/mL) versus intralipid (placebo). The primary outcome was cardiac troponin T release over the first 48 hours after surgery. RESULTS: We recruited 101 participants (51 in the propofol group, 50 in the intralipid group); 61 underwent CABG and 40 underwent AVR. All participants were followed to 3 months. Cardiac troponin T release was on average 15% lower with propofol supplementation (geometric mean ratio, 0.85; 95% confidence interval [CI], 0.73-1.01; P = .051). There were no differences for CABG participants but propofol-supplemented participants undergoing AVR had poorer postoperative renal function (geometric mean ratio, 1.071; 95% CI, 1.019-1.125; P = .007), with a trend toward longer intensive care stay (median, 89.5 vs 47.0 hours; hazard ratio, 0.58; 95% CI, 0.31-1.09; P = .09) and fewer with perfect health (based on the EQ-5D health utility index) at 3 months (odds ratio, 0.26; 95% CI, 0.06-1.05; P = .058) compared with the intralipid group. Safety profiles were similar. There were no deaths. CONCLUSIONS: Propofol supplementation in cardioplegia appears to be cardioprotective. Its influence on early clinical outcomes may differ between CABG and AVR surgery. A larger, multicenter study is needed to confirm or refute these suggestions.

Initial large-dose administration of modified St. Thomas' solution.

BACKGROUND: We introduced an initial large dose of modified St. Thomas' Hospital cardioplegic solution with the aim of providing both myocardial protection as well as a smooth intraoperative process. METHODS: In 90 cases of isolated aortic valve replacement, we used the modified technique of cardioplegia in 45 (group S) and conventional administration of glucose-insulin-potassium solution in 45 (group G). The patients were selected at random. In group S, we added 4 mEq of potassium to the original St. Thomas' Hospital solution and administered 30 mL·kg(-1) as an initial dose. The temperature was decreased to 2. RESULTS: The mean of reperfusion time after declamping in group S was significantly shorter (16.7 ± 6.4 vs. 21.5 ± 10.0 min; p = 0.007). The average of postoperative maximum creatine kinase-MB was significantly lower in group S (25.6 ± 9.5 vs. 40.6 ± 37.2 IU·L(-1); p = 0.014). On multivariate analysis, use of the modified cardioplegia and aortic crossclamp time were significantly associated with creatine kinase-MB level and reperfusion time after declamping. CONCLUSIONS: This modified technique was an acceptable option that provided a bloodless operative field and avoided multiple cardioplegic administrations.

Retrograde cardioplegia revisited: open technique for long aortic cross clamping.

BACKGROUND: The efficacy of retrograde cardioplegia for myocardial protection is still controversial. In our institution, we exclusively use intermittent administration of tepid, undiluted blood supplemented with potassium and magnesium for the cases with aortic insufficiency, requiring aortotomy, or undergoing mitral valve repair. In using this retrograde technique, we make a point of cannulating a retrograde perfusion catheter under direct vision following right atriotomy. The purpose of this retrospective study is to evaluate the clinical outcome of using this technique. METHODS: This study comprises 49 patients who underwent elective valve surgery using direct-vision retrograde cardioplegia exclusively, requiring more than 3h aortic cross-clamping. Their clinical outcome was reviewed retrospectively. RESULTS: There was no hospital mortality in this study. No patient was noted to have evidence of mediastinitis, myocardial infarction, or cerebral complications in the postoperative period. The case requiring the longest aortic cross-clamping time (380 min) survived the operation without the use of intra-aortic balloon pumping or percutaneous cardiopulmonary support, and the postoperative course was uneventful. CONCLUSIONS: Our result suggests that direct-vision retrograde cardioplegia is a safe and effective method of cardioplegia delivery, and provides a longer period of myocardial protection than previously thought.

L-arginine cardioplegia reduces oxidative stress and preserves diastolic function in patients with low ejection fraction undergoing coronary artery surgery.

PL-arginine cardioplegia decreases biochemical markers of myocardial damage and oxidative stress in patients with normal left ventricular function. We investigated the effects of L-arginine supplemented cardioplegic arrest in patients with reduced ejection fraction. Fifty-three adult patients with left ventricular ejection fraction <35% undergoing elective coronary artery bypass surgery were randomised to receive blood cardioplegia with or without L-arginine. Following cardiopulmonary bypass, measured endpoints were cardiac troponin-I concentration at 12 and 24 hours, coronary sinus concentrations of malondialdehyde and superoxide dismutase activity at five and 15 minutes, lactic acid flux at one, five and 15 minutes and left ventricular systolic and diastolic function after protamine administration. There were no differences in cardiac troponin-I between groups. Malondialdehyde was lower in the L-arginine group, 0.28 ± 0.12 vs 0.48 ± 0.32 (5 minutes) and 0.31 ± 0.14 vs 0.38 ± 0.15 nmol.ml(-1) (15 minutes) (P=0.0004). Superoxide dismutase activity was higher in L-arginine group, 229 ± 87 vs 191.3 ± 68 (5 minutes), 229 ± 54 vs 198 ± 15 nmol.minute(-1).m(l) (15 minutes) (P=0.005). Lactic acid flux was lower in L-arginine group, 0.15 ± 0.23 vs 0.48 ± 0.32 (1 minute), 0.08 ± 0.19 vs 0.38 ± 0.31 (5 minutes) and -0.15 ± 0.13 vs 0.26 ± 0.30 mmol.l(-1) (15 minutes), (P=0.0003). There was no difference in left ventricular systolic function. The mitral annular tissue Doppler inflow (e') velocity during early diastole improved in the L-arginine group following cardiopulmonary bypass (control 4.2 ± 1.9 cm.s(-1) to 3.6 ± 1.2 cm.s(-1) vs L-arginine 3.8 ±1.2 cm.s(-1) to 4.6 ± 1.4 cm.s(-1)) (P=0.018). In patients with reduced ejection fraction, L-arginine supplemented cardioplegic arrest did not affect postoperative cardiac troponin-I levels, but attenuated cardiac cellular peroxidation and improved early left ventricular diastolic function.

L-arginine supplemented nondiluted blood cardioplegia: a clinical trial.

AIM: L-arginine was shown to improve protection of the myocardium during coronary artery bypass graft (CABG) surgery. The objective of the present study was to determine the concentration of L-arginine to obtain the most effective protection of the myocardium during CABG surgery. METHODS: Seventy-five patients undergoing CABG surgery were randomized in 3 groups. The first group (N.=25) was administered a placebo injection in the blood cardioplegic solution, the second group (N.=25) received an injection of 4 mmol/L of L-arginine and a third group (N.=25) an injection of 6 mmol/L of L-arginine in the blood cardioplegic solution. Blood samples from the ascending aorta and the coronary sinus catheter were collected before, immediately after and at 20 minutes after aortic cross-clamping. Total plasmatic nitrite and nitrate ratio and lactate release from the myocardium in the collected blood samples were measured. RESULTS: Seventy-five patients averaging 62+/-7 years of age and undergoing 3.1+/-1 coronary bypass grafts during 41+/-17 minutes of aortic cross clamping time were recruited. Values of total plasmatic nitrite and nitrate ratio remains non-significant before and after aortic clamping and also between groups (P=0.9812 and 0.3573 respectively). Myocardial lactate release was statistically different before and after cross clamping (P=0.0002) and also between the 3 groups (P=0.0311). CONCLUSION: Nondiluted blood cardioplegic solution supplemented with 4 mmol/L of L-arginine was associated with a significant decrease of myocardial lactate release after aortic cross-clamping and reperfusion during CABG surgery.

[Effect of high dose glucose-insulin-potassium infusion in patients with acute ST-segment elevation myocardial infarction: analysis of 7510 patients in China as part of CREATE-ECLA study].

OBJECTIVE: To investigate the effect of high-dose glucose-insulin-potassium (GIK) infusion on the outcomes of ST-elevation myocardial infarction (STEMI) in China. METHODS: As part of the international multicentre CREATE-ECLA study, 7510 patients with STEMI, aged (62 +/- 12), presenting their symptoms within 12 hours of onset who were hospitalized in 274 centers throughout China from July 2001 through July 2004 were randomized to receive GIK intravenous infusion for 24 hours plus routine treatment (3739) or control group (n=3771) receiving routine treatment alone. The patients were flowed up in the out-patient department 30 days after the randomization to assess the rates of mortality, cardiac arrest, cardiogenic shock and re-infarction. RESULTS: The median time from symptom onset to randomization was 5.8 hours. The mortality of the control group was 10.4%, not significantly different from that of the GIK group (11.2%, hazard ratio = 1.05, 95% CI: 0.916-1.207, P = 0.476). There rates of cardiac arrest, cardiogenic shock, and re-infarction of the GIK group were 0.8%, 6.8%, and 2.0% respectively, all not significantly different from those of the control group (1.0%, 6.4%, and 1.9% respectively, all P > 0.05). At the Day 7 the heart failure rate of the GIK group was 19.7%, not significantly different from that of the control group (18.3%, P = 0.102). The symptomatic hypotension rate of the GIK group was 3.7%, significantly higher than that of the control group (1.2%, P < 0.01). The phlebitis rate of the GIK group was 2.2%, significantly higher than that f the control group (0.1%, P < 0.01). The net increased fluid volume of the control group wasl3 584 ml. more than that of the GIK group (1036 ml). CONCLUSIONS: High dose GIK infusion has neutral effect on mortality, cardiac arrest or cardiogenic shock in patients with acute STEMI in China.

[Myocardial protective effect of Shenfu injection in patients undergoing valve replacement].

OBJECTIVE: To investigate the myocardial protective effect of Shenfu injection in patients undergoing valve replacement. METHODS: Forty patients undergoing valve replacement surgery under cardio-pulmonary bypass (CPB) were randomly divided into two equal groups: group C (control group, given with 4:1 blood containing cardioplegic liquid during the CPB) and group SF (Shenfu injection, receiving the blood containing cardioplegic liquid with 20 ml/L of Shenfu injection additionally). Blood samples were withdrawn from the central vein before operation, 30 minutes after aorta declamping, and 4, 12, and 24 hours after CPB, to test the serum cardiac troponin I (cTnI), creatine phosphokinase (CK), and creatine phosphokinase isoenzyme (CK-MB). RESULTS: The CK, CK-MB, and cTnI level were normal before operation and there were no significant differences in these indexes between the two groups. 30 minutes after aorta declamping, the CK, CK-MB, and cTnI levels were higher than those before operation in both groups (P < 0.05, P < 0. 01), and the higher levels remained to 24 hours after CPB. 24 hours after CPB, the CK level of the group SF was significantly lower than that of the group C (P < 0.05), and 30 minutes after aorta declamping to 24 h after CPB, the CK-MB and cTnI levels were lower in the group SF compared with the group C (all P < 0. 05). CONCLUSION: Shenfu injection decreases the level of CK, CK-MB and cTnI, and reduces the myocardial injury.

Intravenous glucose-insulin-potassium during off-pump coronary artery bypass surgery does not reduce myocardial injury.

BACKGROUND: This randomized, double-blind, placebo-controlled study was designed to determine whether an intra-operative, intravenous infusion of glucose-insulin-potassium (GIK) could be helpful in the prevention of myocardial ischemia and in the maintenance of intra-operative cardiac performance in patients undergoing off-pump coronary artery bypass (OP-CAB) surgery. METHODS: Eighty two adults undergoing elective OP-CAB surgery were randomly divided into two groups that received intravenously either 5% dextrose in water or GIK (50% dextrose in 500 ml of water; regular insulin, 125 IU; potassium, 80 mmol) at 0.75 ml/kg/h immediately before the induction of anesthesia to the end of surgery. To evaluate myocardial damage, creatine kinase MB and troponin T were measured before surgery, immediately after arrival in the intensive care unit and on the first post-operative day. To assess cardiac performance, hemodynamic data were obtained before and after the induction of anesthesia, before and after the bypass graft and after sternal closure. Blood glucose was measured at the same time. RESULTS: There was no significant difference in cardiac enzymes, hemodynamic parameters and blood glucose between the two groups. The use of vasoactive, inotropic and/or anti-arrhythmic agents, insulin and supplemental glucose was not significantly different between the groups. CONCLUSION: The results suggest that the intravenous administration of GIK during OP-CAB surgery neither reduces myocardial damage nor improves intra-operative cardiac performance in patients without contractile dysfunction.

Anti-inflammatory effect of high-dose insulin treatment after urgent coronary revascularization surgery.

BACKGROUND: The administration of insulin has been shown to exert cardioprotective and immunomodulatory properties. Ischemia and inflammation are typical features of acute coronary syndrome, thus it was hypothesized that high-dose glucose-insulin-potassium (GIK) treatment could suppress the systemic inflammatory reaction and attenuate myocardial ischemia-reperfusion injury in patients with unstable angina pectoris after urgent coronary artery bypass surgery. METHODS: Forty patients with unstable angina pectoris scheduled for urgent coronary artery bypass surgery and cardiopulmonary bypass were randomly assigned to receive either high-dose insulin treatment (short-acting insulin 1 IU/kg/h with 30% glucose 1.5 ml/kg/h administered separately) or control treatment (saline). Blood glucose levels were targeted to 6.0-8.0 mmol/l in both groups by adjusting the rate of glucose infusion in the GIK group and by additional insulin in the control group as needed. RESULTS: High-dose insulin treatment was associated with significantly lower average C-reactive protein (23.8 vs. 40.1 mg/l, P= 0.008) and free fatty acid levels (0.22 vs. 0.41 mmol/l, P= < 0.001) post-operatively. Average blood glucose levels were comparable during the intensive care unit (ICU) stay (7.1 vs. 6.9 mmol/l, P= 0.5) and 95% of the control patients received supplemental insulin. The pro-inflammatory cytokine response [interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha)] did not differ between the groups and beneficial effects on myocardial injury were not detected. CONCLUSIONS: High-dose insulin treatment has potential anti-inflammatory properties independent of its ability to lower blood glucose levels. Even profound suppression of free fatty acid levels, the attenuation of myocardial ischemia-reperfusion injury was not detected.

"Initial, continuous and intermittent bolus" administration of minimally-diluted blood cardioplegia supplemented with potassium and magnesium for hypertrophied hearts.

BACKGROUND: Hypertrophied hearts are subject to the deleterious effects of intraoperative ischemia-reperfusion, and stable maintenance of myocardial cardioplegic arrest is essential. Continuous cardioplegia infusion appears an ideal modification to overcome this issue, except for a large amount of crystalloid solution infused into the myocardium. We previously introduced "initial, continuous and intermittent bolus" administration of minimally-diluted blood cardioplegia (mini-BCP) supplemented with potassium and magnesium, and this study was designed to elucidate its efficacy in patients with hypertrophied hearts. METHODS: Thirty patients (M:F=17:13, 69.2+/-7.8 years) with left ventricular mass index greater than 150 g/m(2) who underwent aortic valve replacement between 1996 and 2002 were enrolled, and were allocated to one of the two groups. The same infusion protocol was used for both groups as follows: initial and intermittent (every 20 min) BCP was antegradely infused for 2 min at the rate of 200 mL/min, and continuous retrograde BCP flow rate was set at 60-100mL/min. Group C (n=15) received 4:1-diluted BCP modified with Buckberg solution, and Group M (n=15) were given mini-BCP supplemented with potassium (initial/others: 15.4/9.8 mEq/L) and magnesium (initial/others: 6.5/4.0 mEq/L). RESULTS: Stable cardioplegic arrest was maintained in all study patients, and total amount of crystalloid solution as cardioplegia was lesser in Group M (79.4+/-27.5 mL) than in Group C (937.3+/-372. 1mL, p<0.01). Group M showed a higher incidence of spontaneous heartbeat recovery after aortic unclamping (13 versus 6, p<0.05) and a lower incidence of postoperative atrial fibrillation (0 versus 5, p<0.05). Postoperatively, maximum dopamine dose (3.35+/-2.27 microg/kg/min versus 5.49+/-2.30 microg/kg/min, p<0.05) and peak plasma creatine kinase-myocardial band (CK-MB) (21.7+/-7.2 IU/L versus 28.8+/-8.4 IU/L, p<0.05) were lower in Group M. Early postoperative echocardiography revealed a lower incidence of paradoxical ventricular septal motion (M versus C; 3 versus 10, p<0.05) and greater left ventricular ejection fraction (M versus C; 70.7+/-4.0% versus 67.0+/-5.3%, p<0.05) in Group M. CONCLUSIONS: These results suggest that "initial, continuous and intermittent bolus" administration of mini-BCP, supplemented with potassium and magnesium, is a novel modification for patients with hypertrophied hearts in terms of simplifying the maintenance of cardioplegic arrest with beneficial myocardial protective effects.

Age- and gender-related differences in ischemia/reperfusion injury and cardioprotection: effects of diazoxide.

BACKGROUND: Recent studies have demonstrated that aging is associated with reduced tolerance to ischemia and that the aged (not senescent) female heart has greater susceptibility to ischemia as compared with the aged male heart. Previously, we have shown that ischemia can be modulated with cardioplegia in the male heart; however, efficacy in the female heart was unknown. METHODS: In this study, male and female mature (15 to 20 weeks) aged (>32 months) rabbit hearts (n = 134) were subjected to Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia hearts received 30 minutes of equilibrium, 30 minutes of global ischemia, and 120 minutes of reperfusion. Cardioplegia +/- diazoxide was infused separately, 5 minutes before global ischemia. RESULTS: Global ischemia significantly decreased postischemic functional recovery and significantly increased infarct size in the mature and aged male and female heart (p < 0.05 versus control). The effects of global ischemia were significantly exacerbated (p < 0.05) in the aged heart as compared with the mature heart. Cardioplegia +/- diazoxide significantly increased postischemic functional recovery and significantly decreased infarct size in mature male and female hearts, but these effects were significantly decreased in the aged heart (p < 0.05) and in the aged female as compared with the aged male heart. CONCLUSIONS: Postischemic functional recovery and infarct size are affected by age but not by gender. The cardioprotection afforded by cardioplegia is affected by age and gender with a strong age-by-gender interaction for end-diastolic pressure and infarct size. Our results indicate that currently optimized cardioplegia protocols effective in the male heart are not as efficacious in the aged female heart.

Experimental study on myocardial protection by adjunct use of carperitide (hANP) in cardiac surgery.

BACKGROUND: In recent years, various beneficial roles of human atrial natriuretic peptide (hANP) have been demonstrated in the internal medicine and surgical fields. However, direct myocardial protection by hANP against myocardial ischemic reperfusion injury has been rarely investigated. Thus, we investigated it from aspects of cardiac surgery. METHODS: Twenty-four pigs underwent extracorporeal circulation and were divided into three groups: control group (treated with only cardioplegic solution after aorta clamping; cardioplegic arrest for 30 minutes followed by reperfusion for 60 minutes); low dose group (treated with cardioplegic solution and ANP (25 microg)); and high dose group (treated with cardioplegic solution and ANP (100 microg)). Blood and myocardial cGMP, myocardial Ca and ATP concentration were determined. Histological examinations were performed using an electron microscope. RESULTS: Blood and myocardial cGMP and myocardial ATP levels were significantly higher in the hANP treatment groups than the control group. Myocardial Ca concentrations were significantly lower in the hANP treatment groups than the control group. In electron microscopy, ischemic reperfusion injury was rarely observed in the hANP treatment groups. CONCLUSION: The study demonstrated that hANP improves ischemic reperfusion injury and suggested that hANP exerts direct myocardial protection against myocardial injury associated with cardiac surgery (cardioplegic arrest while cardiopulmonary bypass).

Initial, continuous and intermittent bolus cardioplegia administration: efficacy of potassium-chloride and magnesium-sulfate as minimal additives for minimally-diluted blood cardioplegia.

AIM: The most effective delivery of blood cardioplegia (BCP) remains controversial, and a combination of initial continuous and intermittent bolus BCP seems to compensate each demerit. However, a large amount of crystalloid solution is infused into the myocardium in this method, which may nullify the advantages of BCP. We examined the hypothesis that minimally-diluted BCP resolves this issue and provides superior myocardial protective effects. METHODS: Seventy patients undergoing elective coronary revascularization between 1997-2001 (M:F=55:15, mean age 67.6+/-7.5 years) were randomly allocated into one of 2 groups: Group C (n=35) was given the standard 4:1-diluted blood-crystalloid BCP, and Group M (n=35) was given minimally-diluted BCP supplemented with potassium-chloride and magnesium-sulfate. The BCP temperature was maintained at 30 degrees C. Cardioplegic arrest was induced with 2 minutes of initial antegrade BCP infusion, followed by continuous retrograde BCP infusion. Intermittent antegrade BCP was infused every 30 minutes for 2 minutes. RESULTS: The time required for achieving cardioplegic arrest was significantly shorter in Group M (47.5+/-16.3 vs 62.5+/-17.6 s, p<0.0001) and the number of patients showing spontaneous heart-beat recovery after aortic unclamping was significantly larger in Group M (28 vs 15, p=0.0029). The number of patients suffering from atrial fibrillation during the postoperative period was significantly smaller in Group M (3 vs 11, p=0.034). The total amount of crystalloid solution infused as cardioplegia was significantly smaller in Group M (62.8+/-22.3 vs 733.6+/-382.6 mL, p<0.0001). Postoperative maximum dopamine dose (3.57+/-2.46 vs 5.44+/-2.23 mg/kg/min, p=0.0014) and peak creatine kinase-MB (19.5+/-8.5 vs 25.8+/-11.9 IU/L, p=0.0128) were significantly lower in Group M. The number of patients showing paradoxical movement of the ventricular septum by early postoperative echocardiography was significantly smaller in Group M (9 vs 24, p<0.0007). CONCLUSIONS: These results demonstrate that initial continuous and intermittent bolus administration of minimally-diluted BCP supplemented with potassium and magnesium can be a simple, reliable and effective technique of intraoperative myocardial protection.

Severe electrolyte disorders following cardiac surgery: a prospective controlled observational study.

INTRODUCTION: Electrolyte disorders are an important cause of ventricular and supraventricular arrhythmias as well as various other complications in the intensive care unit. Patients undergoing cardiac surgery are at risk for development of tachyarrhythmias, especially in the period during and immediately after surgical intervention. Preventing electrolyte disorders is thus an important goal of therapy in such patients. However, although levels of potassium are usually measured regularly in these patients, other electrolytes such as magnesium, phosphate and calcium are measured far less frequently. We hypothesized that patients undergoing cardiac surgical procedures might be at risk for electrolyte depletion, and we therefore conducted the present study to assess electrolyte levels in such patients. METHODS: Levels of magnesium, phosphate, potassium, calcium and sodium were measured in 500 consecutive patients undergoing various cardiac surgical procedures who required extracorporeal circulation (group 1). A total of 250 patients admitted to the intensive care unit following other major surgical procedures served as control individuals (group 2). Urine electrolyte excretion was measured in a subgroup of 50 patients in both groups. RESULTS: All cardiac patients received 1 l cardioplegia solution containing 16 mmol potassium and 16 mmol magnesium. In addition, intravenous potassium supplementation was greater in cardiac surgery patients (mean +/- standard error: 10.2 +/- 4.8 mmol/hour in cardiac surgery patients versus 1.3 +/- 1.0 in control individuals; P < 0.01), and most (76% versus 2%; P < 0.01) received one or more doses of magnesium (on average 2.1 g) for clinical reasons, mostly intraoperative arrhythmia. Despite these differences in supplementation, electrolyte levels decreased significantly in cardiac surgery patients, most of whom (88% of cardiac surgery patients versus 20% of control individuals; P < 0.001) met criteria for clinical deficiency in one or more electrolytes. Electrolyte levels were as follows (mmol/l [mean +/- standard error]; cardiac patients versus control individuals): phosphate 0.43 +/- 0.22 versus 0.92 +/- 0.32 (P < 0.001); magnesium 0.62 +/- 0.24 versus 0.95 +/- 0.27 (P < 0.001); calcium 1.96 +/- 0.41 versus 2.12 +/- 0.33 (P < 0.001); and potassium 3.6 +/- 0.70 versus 3.9 +/- 0.63 (P < 0.01). Magnesium levels in patients who had not received supplementation were 0.47 +/- 0.16 mmol/l in group 1 and 0.95 +/- 0.26 mmol/l in group 2 (P < 0.001). Urinary excretion of potassium, magnesium and phosphate was high in group 1 (data not shown), but this alone could not completely account for the observed electrolyte depletion. CONCLUSION: Patients undergoing cardiac surgery with extracorporeal circulation are at high risk for electrolyte depletion, despite supplementation of some electrolytes, such as potassium. The probable mechanism is a combination of increased urinary excretion and intracellular shift induced by a combination of extracorporeal circulation and decreased body temperature during surgery (hypothermia induced diuresis). Our findings may partly explain the high risk of tachyarrhythmia in patients who have undergone cardiac surgery. Prophylactic supplementation of potassium, magnesium and phosphate should be seriously considered in all patients undergoing cardiac surgical procedures, both during surgery and in the immediate postoperative period. Levels of these electrolytes should be monitored frequently in such patients.

Minimally-diluted blood cardioplegia supplemented with potassium and magnesium for combination of 'initial, continuous and intermittent bolus' administration.

BACKGROUND: The present study was designed to examine the hypothesis that minimally-diluted blood cardioplegia (BCP) supplemented with potassium and magnesium provides superior myocardial protection in comparison with the standard-diluted BCP for a combination of 'initial, continuous, and intermittent bolus' BCP administration. METHODS AND RESULTS: Seventy patients undergoing elective coronary revascularization between 1997 and 2001 (M : F =55:15, mean age 67.6+/-7.5 years) were randomly divided into 2 groups: Group C (n=35) was given the standard 4:1-diluted blood-crystalloid BCP, and Group M (n=35) was given minimally-diluted BCP supplemented with potassium-chloride and magnesium-sulfate. The BCP temperature was maintained at 30 degrees C. Cardioplegic arrest was induced with 2 min of initial antegrade BCP infusion, followed by continuous retrograde BCP infusion. Intermittent antegrade BCP was infused every 30 min for 2 min. The time required for achieving cardioplegic arrest was significantly shorter in Group M (47.5+/-16.3 vs 62.5+/-17.6 s, p<0.0001). The number of patients showing spontaneous heart beat recovery after reperfusion was significantly larger in Group M (28 vs 15, p=0.0029), and the number of patients suffering from atrial fibrillation during the postoperative period was significantly smaller in Group M (n=3 vs 11, p=0.034). Both the postoperative maximum dopamine dose (3.57+/-2.46 vs 5.44+/-2.23 microg/kg per min, p=0.0014) and peak creatine kinase-MB (19.5+/-8.5 vs 25.8+/-11.9 IU/L, p=0.0128) were significantly less in Group M. The number of patients showing paradoxical movement of the ventricular septum in the early postoperative echocardiography was significantly smaller in Group M (9 vs 24, p=0.0007). CONCLUSIONS: These results suggest that 'initial, continuous and intermittent bolus' administration of minimally-diluted BCP supplemented with potassium and magnesium is a reliable and effective technique for intraoperative myocardial protection.

Effects of glucose-insulin-potassium solution on myocardial salvage and left ventricular function after primary angioplasty.

OBJECTIVE: To evaluate the effects of glucose-insulin-potassium (GIK) therapy on infarct size and left ventricular function when used as an adjuvant therapy to primary angioplasty. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Cardiac intensive care unit at a university hospital. PATIENTS: Thirty-seven patients with acute myocardial infarction for whom primary angioplasty was indicated. INTERVENTIONS: Eligible patients were randomized by a blinded pharmacist to GIK solution (30% glucose in water with insulin 50 U/L, and KCl 40 mM/L) vs. placebo at 1.5 mL/kg/hr for 24 hrs. MEASUREMENTS AND MAIN RESULTS: Tc 99m sestamibi myocardial scintigraphy was performed at admission and at 3 months. Primary end points were the changes in left ventricular ejection fraction (LVEF) and the size of salvaged myocardium. Baseline clinical characteristics were similar in both groups. At the 3-month follow-up, a significant overall decrease in infarct size (37 +/- 16% vs. 12 +/- 10%, p <.005) and an increase in LVEF (34 +/- 13% vs. 49 +/- 9%, p =.005) were observed. Patients randomized to GIK solution experienced a significant increase in their LVEF at 3 months (39 +/- 12 to 51 +/- 13, p =.002). Patients who received placebo had no significant differences between baseline and 3-month measurements (44 +/- 13 vs. 49 +/- 14, p = NS). There was a trend toward an increase in myocardial salvage in the GIK group, which did not reach statistical significance. When patients from both groups were compared directly, differences in LVEF improvement were no longer significant. CONCLUSIONS: GIK solution did not improve LVEF or decrease the infarct size among patients undergoing primary angioplasty.

Continuous addition of adenosine with a micropump system improves warm whole blood cardioplegia.

BACKGROUND: Micropump additive systems allow for continuous modification of cardioplegia composition during heart surgery. Although the use of such systems in warm heart surgery is theoretically desirable, the role of the systems has been clinically limited by coronary vasoreactivity with higher potassium concentration and unreliable mechanical arrest at lower potassium concentration. Adenosine, a potent coronary vasodilator and arresting agent, has the potential to reduce the potassium concentration required for arrest and to improve distribution of cardioplegia. However, clinical use of adenosine has been limited by a short half-life in blood and difficulty in titrating the dose. This study tested the hypothesis that continuous addition of adenosine with an in-line linear micropump system would facilitate whole blood hyperkalemic perfusion for cardiac surgery. METHODS: Canine hearts (n = 9) were randomized to 20 minutes of arrest with whole blood cardioplegia or cardioplegia with adenosine at either low (0.5 M) or high (8 M) concentration. Potassium was supplemented at an arresting dose (24 mEq/L) for 5 minutes and then at a maintenance dose (6 mEq/L) for an additional 15 minutes. Coronary flow was held constant (4 mL/kg per minute), and aortic root pressure was measured. Myocardial performance was assessed by measurement of the end-diastolic pressure to stroke volume relationship at constant afterload. Myocardial tissue perfusion was evaluated with colored microspheres. RESULTS: During the initial period of high-concentration potassium arrest, coronary resistance rose progressively regardless of adenosine addition. Coronary resistance remained elevated during the period of low potassium perfusion, except when high-concentration adenosine was added. With addition of 8 M adenosine, coronary resistance returned to baseline, and left ventricular endocardial perfusion was augmented. Electromechanical quiescence improved with adenosine perfusion and was complete with high-dose adenosine addition. Function was preserved in all hearts. CONCLUSION: Use of a modern micropump system allowed for continuous addition of adenosine and potassium to whole blood cardioplegia. Adenosine minimized potassium-induced coronary vasoconstriction and improved endocardial perfusion and mechanical quiescence. These findings supported addition of adenosine to the perfusate during warm whole blood cardioplegia.