Liisa Kaukinen

Beneficial Effects of Ischemic Preconditioning on Right Ventricular Function After Coronary Artery Bypass Grafting

BACKGROUND Preservation of right ventricular myocardium is unsatisfactory in patients with critical stenosis or occlusion of the right coronary artery. The aim of this study was to investigate whether ischemic preconditioning (IP) improved the recovery of right ventricular function after coronary artery bypass grafting. METHODS Forty patients with three-vessel disease who had coronary artery bypass grafting were randomly assigned to the IP group (n = 20) or control group (n = 20). In the IP group, two cycles of two minutes of ischemia after three minutes of reperfusion were given before cross-clamping. Hemodynamic data were collected. Right ventricular ejection fraction was measured by thermodilution. RESULTS Right ventricular ejection fraction and right ventricular systolic volume index were decreased post-operatively (lowest value at 6 hours postoperatively). The changes in right ventricular ejection fraction were significantly milder in the IP group postoperatively (p = 0.012). The decrease in right ventricular systolic volume index postoperatively was also less in IP patients (p = 0.002). Fewer inotropic drugs were used in the IP group compared with controls. CONCLUSIONS Ischemic preconditioning had a myocardial protective effect on recovery of right ventricular contractility in patients who had coronary artery bypass grafting.

Ischaemic preconditioning has a beneficial effect on left ventricular haemodynamic function after a coronary artery biopass grafting operation.

OBJECTIVE Ischaemic preconditioning (IP) is the most effective procedure for endogenous myocardial protection. However, studies on the effects of IP in cardiac surgery are rare and controversial. The present aim was to investigate whether IP improves the haemodynamic recovery of CABG patients. DESIGN The study included 40 stable CABG patients with 3-vessel disease, randomized into an IP group (n = 20) and a control group (n = 20). In the IP group two cycles of 2-min ischaemia following 3-min reperfusion before cross-clamping were induced. The haemodynamics of the patients were followed-up to the first postoperative morning. RESULTS The cardiac index decreased at 1 and 6 h after surgery in the control group but increased in the IP group (-0.33 vs 0.09 l/min/m2, p = 0.02 and -0.15 vs 0.57 l/min/m2, p = 0.001, respectively). Depressions in the left ventricular stroke work index and the right ventricular stroke work index at 6 h after surgery were more severe in controls and were statistically significant (p = 0.049 and 0.007, respectively). Less inotropic support was used in the IP group. There were no differences in serum CK-MB, cardiac troponin I, myoglobin or lactate values between the two groups. CONCLUSION IP has a beneficial effect on left ventricular haemodynamic recovery after a CABG operation.

Protective effect of unstable angina in coronary artery bypass surgery

OBJECTIVE To test the hypothesis that recent ischaemic episodes in unstable cases have a protective effect on coronary artery bypass graft (CABG) patients. MATERIALS AND METHODS Twenty unstable patients with ischaemic episodes within 3 days before operation were compared with 20 stable patients. Haemodynamic data were monitored up to the first postoperative day. Biochemical markers were measured up to the second postoperative day. RESULTS The cardiac index decreased at 1 and 6 h after declamping in the stable group (89% and 97% of baseline) but increased in unstable patients (104% and 122%, p =0.038 and 0.036, respectively). The depression in the right ventricular stroke work index was significantly attenuated in the unstable group (58%, 67% and 83% in stable and 90%, 97% and 117% in unstable patients, p = 0.027, 0.010 and 0.049 at 1 and 6 h after declamping and 1st POD). The release of cardiac troponin I (CTnI) and CK-MB was significantly lower in the unstable group at 6 h after declamping (5.6 +/- 2.9 and 19.0 +/- 6.3 microg/l in unstable vs 17.4 +/- 9.6 and 25.8 +/- 12.3 microg/l in stable patients, p = 0.000 and 0.039, respectively). CONCLUSION Recent unstable angina before CABG might act as an ischaemic preconditioning stimulus and could improve haemodynamic function and cellular viability. Delayed preconditioning most likely causes this protective effect.Objective—To test the hypothesis that recent ischaemic episodes in unstable cases have a protective effect on coronary artery bypass graft (CABG) patients. Materials and methods —Twenty unstable patients with ischaemic episodes within 3 days before operation were compared with 20 stable patients. Haemodynamic data were monitored up to the first postoperative day. Biochemical markers were measured up to the second postoperative day. Results—The cardiac index decreased at 1 and 6 h after declamping in the stable group (89% and 97% of baseline) but increased in unstable patients (104% and 122%, p = 0.038 and 0.036, respectively). The depression in the right ventricular stroke work index was significantly attenuated in the unstable group (58%, 67% and 83% in stable and 90%, 97% and 117% in unstable patients, p = 0.027, 0.010 and 0.049 at 1 and 6 h after declamping and 1st POD). The release of cardiac troponin I (CTnI) and CK-MB was significantly lower in the unstable group at 6 h after declamping (5.6 2.9 and 19.0 6.3mg/l in unstable vs 17.4 9.6 and 25.8 12.3mg/l in stable patients, p = 0.000 and 0.039, respectively). Conclusion—Recent unstable angina before CABG might act as an ischaemic preconditioning stimulus and could improve haemodynamic function and cellular viability. Delayed preconditioning most likely causes this protective effect.

Effect of ischaemic preconditioning, cardiopulmonary bypass and myocardial ischaemic/reperfusion on free radical generation in CABG patients.

OBJECTIVE To investigate the free radicals (FR) generation after ischaemic preconditioning and cardiopulmonary bypass and during reperfusion in CABG patients, and the role of ischaemic preconditioning. METHODS Forty-three CABG patients were randomised into an ischaemic preconditioning and a control group. The protocol for ischaemic preconditioning was two cycles of 2-min ischaemia followed by 3-min reperfusion. Free radicals were measured using electron spin resonance spectroscopy. Global and right heart functions were collected. RESULTS The free radicals generation in coronary sinus blood in the ischaemic preconditioning group was 9.7 and 16.6% after the ischaemic preconditioning protocol and 10 min after declamping, 6.8 and 13.3% in the controls. The free radicals in arterial samples were, respectively, 21, 14, 10 and 9% at 10 min, 1, 2 and 24 h after reperfusion. Cardiac index (CI) and right ventricular ejection fraction (RVEF) were improved by ischaemic preconditioning. CONCLUSION Both ischaemic preconditioning and cardiopulmonary bypass induced free radicals generation. Although ischaemic preconditioning had no effect on free radicals generation after the operation, it protected against postoperative stunning.

Interpleural analgesia for postoperative pain relief in renal surgery patients.

The feasibility of interpleural analgesia for postoperative pain relief after renal surgery using anterior intercostal incision was studied in 16 adult patients. 20 ml bupivacaine plain 5 mg/ml in ten patients, and the same dose of bupivacaine with epinephrine 5 micrograms/ml in six patients, was injected through epidural catheter into the pleural space of the operated side, maximally three times per 24 hours. As additional pain medication, oxycodone i.m. was given if needed. In ten control patients, oxycodone was the only pain medication. Postoperative pain relief in patients who received interpleural bupivacaine plain was excellent in four, moderate in four and poor in two cases. For supplemental pain relief the patients were given 2.1 +/- 1.1 (SEM) injections of oxycodone during the three days. Control patients received, respectively. 11.6 +/- 0.7 injections of oxycodone, and they considered the pain relief excellent in six and moderate in four cases. Median duration of interpleural analgesia was in bupivacaine plain cases 6 h (range 2-14 h) and in bupivacaine with epinephrine 7 h (range 4-15 h). The mean peak serum concentration of bupivacaine plain was 1868 +/- 168 ng/ml, and that of bupivacaine with epinephrine 1312 +/- 273 ng/ml. No complications were seen. The results suggest that interpleural analgesia obtained by 20 ml bupivacaine 5 mg/ml three times a day gives most patients good pain relief.

Dopexamine unloads the impaired right ventricle better than iloprost, a prostacyclin analog, after coronary artery surgery

OBJECTIVE To evaluate the ventricle-unloading properties of dopexamine and iloprost and to compare their effects on right ventricular (RV) function and oxygen transport in patients with low RV ejection fraction (RVEF) after cardiac surgery. DESIGN A prospective, randomized, double-blind, cross-over, clinical study. SETTING University hospital. PARTICIPANTS Twenty patients with proximal total stenosis of the right coronary artery studied immediately after coronary artery surgery. INTERVENTIONS Treatment drugs were administered in a random order in doses equipotent with respect to cardiac output response. Infusion rates were increased stepwise to induce a 25% increase in cardiac index. A washout period of 60 minutes was allowed between treatments. MEASUREMENTS AND MAIN RESULTS Central hemodynamics, RV function assessed by the EF (fast-response thermodilution), end-systolic and end-diastolic volumes, and systemic oxygenation were measured before and after the first drug, after the washout period, and after the second drug. Central filling pressures remained constant during treatments. Both drugs decreased pulmonary vascular resistance index, but iloprost was more effective (p < 0.05). Iloprost decreased mean arterial and pulmonary artery pressure, which were unaffected by dopexamine. Dopexamine increased EF significantly more than iloprost (p < 0.001). End-systolic volume index decreased subsequent to dopexamine only (p < 0.001). Iloprost increased intrapulmonary shunt more than dopexamine (p < 0.001). Changes in oxygen delivery, consumption, and extraction were similar. CONCLUSION The findings suggest that dopexamine is more effective than iloprost for support and unloading of the postoperatively disturbed RV in terms of RVEF and end-systolic volume. The reduction of pulmonary vascular resistance after administration of iloprost without a decrease in end-systolic volume might not be considered a reduction of RV afterload. Iloprost increases the pulmonary shunt fraction, however, more than dopexamine, indicating a more prominent vasodilator effect.

Combined Antegrade-Retrograde Blood Cardioplegia does not Protect Right Ventricle Better than Either Technique Alone in Patients with Occluded Right Coronary Artery

To study the hypothesis that combined antegrade-retrograde delivery of cardioplegia might overcome the limitations in myocardial protection of either technique alone, we compared the distribution of the different cardioplegic approaches by assessing myocardial cooling and evaluated the effects on right ventricular (RV) function in elective coronary artery bypass grafting (CABG) patients with occluded right coronary artery (RCA). In a randomized trial, 15 patients received exclusively antegrade (ante group), 14 patients received exclusively retrograde (retro group) and 15 patients received combined, alternating antegrade-retrograde (combi group) cold blood cardioplegia. Myocardial temperatures were measured at four sites in the heart. Right ventricular function was assessed by determining the ejection fraction (fast-response thermodilution) and preload-related RV stroke work in repeated measurements. Myocardial cooling was similarly uneven and the posterior wall of the RV remained above 20 degrees C after all three methods of delivering hypothermic (5-7 degrees C) cardioplegia. The RV ejection fraction and preload-related (right atrial pressure) RV stroke work decreased postoperatively similarly in all groups. The results suggest that combined antegrade-retrograde cold blood cardioplegia could not provide more homogeneous myocardial cooling or better RV recovery than either technique alone in three-vessel-diseased CABG patients with occluded RCA.

Off-pump surgery does not eliminate microalbuminuria or other markers of systemic inflammatory response to coronary artery bypass surgery.

Objective. To evaluate whether off-pump surgery attenuates microalbuminuria and other markers of systemic inflammatory response to coronary artery bypass surgery as compared to surgery performed using cardiopulmonary bypass. Design. Forty-three adult patients undergoing elective coronary artery bypass grafting surgery were operated on with or without cardiopulmonary bypass (CPB). Microalbuminuria, serum C-reactive protein, and oxygenation and lung function parameters were measured at several time points until the first postoperative morning. Results. The urinary albumin/creatinine ratio was low in both groups before surgery, but reached a maximum level at the end of CPB or just after opening the last coronary artery clamp in the off-pump group (p < 0.05). The urinary albumin/creatinine ratio remained slightly elevated in both groups until the morning after the operation (p < 0.05). There were no statistical differences between groups. Serum C-reactive protein remained at the initial level the evening after the operation, but increased by the first postoperative morning in both groups (p < 0.001). The alveolar-arterial gradient for oxygen partial pressure rose significantly after the operation in the intensive care unit in both groups (p < 0.0001). The shunt fraction of the pulmonary circulation did not change in either group. Conclusions. Off-pump coronary artery surgery did not prevent the acute phase inflammatory response measured in the present study. The acute phase inflammatory response after coronary artery bypass surgery is more likely a response to the surgical trauma itself rather than to CPB.

Plasma thromboxane B2 levels and thromboxane B2 production by platelets are increased in patients during spinal and epidural anesthesia.

Concentrations of thromboxane (Tx) B2 in plasma and its production by platelets were measured in 20 spinal and 10 epidural anesthesia patients scheduled for small operations in the lower extremities. The main metabolite of prostacyclin, 6-keto-PGF1 alpha and prostaglandin (PG) E2 in plasma were also determined. Plasma TxB2 and TxB2 production by platelets increased during both spinal and epidural anesthesia. Plasma TxB2 levels also remained elevated 1 h after anesthesia. The plasma concentrations of 6-keto-PGF1 alpha and PGE2 did not change during spinal or epidural anesthesia. In in vitro studies, only low concentrations of lidocaine (0.5-1.0 micrograms/ml) and bupivacaine (0.5-3.0 micrograms/ml) increased platelet TxB2 production. In platelet rich plasma, neither lidocaine nor bupivacaine in concentrations of 0.5-3.0 micrograms/ml caused constant changes in ADP-induced platelet aggregation, but they inhibited it in toxic concentrations (12 micrograms/ml). The results suggest that the increased TxB2 plasma levels and platelet TxB2 production during regional anesthesia are not caused by local anesthetics itself but by other factors, e.g. tissue trauma. In clinically found concentrations, local anesthetics do not cause any constant changes in platelet aggregation.

Biochemical Indicators of Myocardial Ischaemia During Coronary Artery Bypass Grafting

Metabolic indicators of myocardial ischaemia were measured in coronary sinus blood in six patients undergoing coronary artery bypass grafting (CABG). Five arterial and coronary sinus blood samples were taken in each case--one before cardiopulmonary bypass (CPB), and three during and one after CPB. Moderate hypothermia with topical cardiac cooling and cold cardioplegia were used. Myocardial infarction occurred perioperatively in two patients. Myocardial lactate production was not found before CPB in any patient, but it was common during CPB. Adenosine, inosine and hypoxanthine were released into the coronary sinus blood, but their release did not correlate significantly with lactate production. Myocardial noradrenaline production showed positive correlation with lactate levels (p less than 0.05). Release of adrenaline from the myocardium during CABG was also demonstrated. Myocardial catecholamine production was especially seen in the patients with myocardial infarction. Myocardial catecholamine release seemed to be the most sensitive of the studied biochemical indicators of myocardial ischaemia during CABG.