Hyper osmolality does not modulate natriuretic peptide concentration in patients after coronary artery surgery.

BACKGROUND: The heart secretes natriuretic peptides (NPs) in response to myocardial stretch. Measuring NP concentrations is a helpful tool in guiding treatment. It has been suggested that sodium ion and hyperosmolality could affect NP excretion. If this is true, peri-operative NP measurements could be inconsistent when hypertonic solutions are used. With different osmolalities but equal volumes of hydroxyethyl starch (HES)--and hypertonic saline (HS)--infusions, this double-blinded study tested the hypothesis that osmolality modulates the excretion of NPs. METHODS: Fifty coronary surgery patients were randomized to receive within 30 min 4 ml/kg either HS or HES post-operatively. Samples for analysis of atrial NP (ANP), brain NP (BNP), plasma and urine sodium and osmolality and urine oxygen tension were obtained before and 60 min after starting the infusions and on the first post-operative morning. The haemodynamic parameters were measured at the same time points. RESULTS: Plasma osmolality and sodium increased only in the HS group. Changes in plasma BNP and ANP levels did not differ between the groups (P=0.212 and 0.356). There were no correlations between NP levels and osmolality or sodium at any time point. In the HS group, urine volume was higher (3295 vs. 2644 ml; P<0.05) and the need for furosemide treatment was less (0.4 vs. 3.8 mg; P<0.01) than in the HES group. CONCLUSIONS: The absence of effects of plasma sodium content or hyperosmolality on NP release validates the value of NPs as a biomarker in peri-operative patients.

Ischemic preconditioning protects right ventricular function in coronary artery bypass grafting patients experiencing angina within 48-72 hours.

BACKGROUND: To test whether ischemic preconditioning (IP) is able to protect the myocardium in recently unstable CABG patients. EXPERIMENTAL DESIGN: prospective, randomised, controlled clinical study. SETTING: University Hospital. PATIENTS: Forty CABG patients with recent unstable angina were randomised into an IP group (n=20) and a control group (n=20). Subgroup was divided based on the time of the most recent ischemia onset before the operation. INTERVENTION: The IP group was preconditioned with 2 cycles of 2-min ischemia followed by 3-min reperfusion before cross clamping. MEASURES: Hemodynamic data were monitored till the 1st POD. Biochemical markers were measured till the 2nd POD. RESULTS: There were no differences in cardiac index (Cl) and right ventricular ejection fraction (RVEF) in patients experiencing angina within 48 hours prior to operation. The percentage changes in CI and RVEF at 1 hour after declamping were significantly better in the IP group in patients experienced angina within 48-72 hours (106% vs 88% of baseline, p=0.027 and 103% vs 81% of baseline, p=0.023). No difference in postoperative cardiac troponin I (CTnI) and CK-MB was found between the IP and controls in either subgroup. CONCLUSIONS: IP has a beneficial effect on global and right ventricular hemodynamic functional recovery in unstable CABG patients experiencing angina within 48-72 hours prior to the operation. However, IP has no additional protective effects in unstable CABG patients who experience angina within 48 hours.

The protective effects of preconditioning decline in aged patients undergoing coronary artery bypass grafting.

OBJECTIVE: We sought to investigate the effects of myocardial ischemic preconditioning in adult and aged patients undergoing coronary artery bypass grafting. METHODS: Eighty patients with 3-vessel disease undergoing coronary artery bypass grafting were randomized into one of the following groups: adult ischemic preconditioning, adult control, aged ischemic preconditioning, and aged control. Hemodynamic data and cardiac troponin I values were compared between the groups. The ischemic preconditioning groups received 2 periods of 2 minutes of ischemia, followed by 3 minutes of reperfusion. The Student t test, chi(2) test, and analysis of variance for repeated measures were used for the statistical analysis. RESULTS: The baseline for right ventricular ejection fraction and cardiac index was similar. Right ventricular ejection fraction was depressed after the operation in all groups. Ischemic preconditioning significantly improved the recovery of right ventricular ejection fraction and cardiac index after the operation in adult patients (P =.013 and.001, respectively), but in the aged group there was no difference in the changes of ejection fraction and cardiac index (P =.232 and.889, respectively). The cardiac troponin I value in the adult patients subjected to ischemic preconditioning was lower than that in the adult control subjects (P =.046), but in aged patients undergoing ischemic preconditioning, the value was similar to that in aged control subjects (P =.897). Ischemic preconditioning also resulted in a shorter postoperative mechanical ventilation time and in less inotropic use in the adult group. CONCLUSION: Ischemic preconditioning protects the heart from ischemic reperfusion injury in adult patients undergoing coronary artery bypass grafting. The beneficial effects of ischemic preconditioning are manifested as a better recovery of right ventricular and global hemodynamic function, cellular viability, and surgical outcome. The protective effect of ischemic preconditioning is diminished in aged patients undergoing coronary bypass.

Cardioprotective effect of adenosine pretreatment in coronary artery bypass grafting.

OBJECTIVE: There are several reports of the use of adenosine as a cardioprotective agent during cardiac surgery. Adenosine treatment might affect neutrophils and inflammatory mediators. The present prospective randomized study was designed to investigate the effect of adenosine pretreatment on myocardial recovery and inflammatory response in patients undergoing elective coronary artery bypass surgery. DESIGN: A prospective, randomized, controlled study. SETTING: Operative unit and ICU in a university hospital in Finland. PATIENTS: Thirty male patients undergoing primary, elective coronary revascularization. INTERVENTIONS: Patients in the adenosine group received a 7-min infusion of adenosine (total, 650 microg/kg) before the initiation of cardiopulmonary bypass. MEASUREMENTS: Postoperative creatine kinase (CK)-MB release and hemodynamics were recorded. Perioperative leukocyte and cytokine release were measured. RESULTS: Adenosine pretreatment resulted in less CK-MB release and an improved postbypass cardiac index. Similar leukocyte counts and cytokine responses were seen in both groups perioperatively. Neutrophil counts were similar between the groups before and after myocardial ischemia when measured simultaneously in arterial and coronary sinus blood. CONCLUSIONS: The present results support the hypothesis that adenosine pretreatment is cardioprotective in humans, but the present dose failed to regulate the inflammatory responses after coronary artery bypass grafting.

Myocardial lactate production is not involved in the ischemic preconditioning mechanism in coronary artery bypass graft surgery patients.

OBJECTIVE: To study the relationship between ischemic preconditioning (IP) and lactate production and their impact on coronary artery bypass graft surgery patients. DESIGN: Prospective, randomized, controlled study. SETTING: University hospital. PARTICIPANTS: Eighty 3-vessel disease coronary artery bypass graft surgery patients with stable and unstable angina pectoris. INTERVENTIONS: The IP patients were preconditioned with 2 periods of 2-minute ischemia followed by 3-minute reperfusion before aortic cross-clamping. MEASUREMENTS AND MAIN RESULTS: The cardiac index (CI) after surgery was significantly higher in the IP group than in controls among stable patients (p = 0.013). IP was not effective in CI recovery in unstable patients. The baseline values of lactate production were 11.6%, 20.3%, -7.0%, and -2.9% in stable IP, stable control, unstable IP, and unstable control patients. Compared with baseline, lactate production increased significantly after the IP protocol (39.0% and 47.5% in the stable and unstable patients), and operation (47.5%, 31.7%, 35.4%, and 35.6% in stable IP, stable control, unstable IP, and unstable control patients) but not after 10 minutes of cardiopulmonary bypass (29.7% and 19.0% in the stable and unstable patients). There were no differences among the groups in lactate production after the operation. Lactate production after the IP protocol was negatively associated with CI recovery after surgery in the IP patients (p = 0.026). CONCLUSION: The IP effects do not include modulation of lactate production. IP induces lactate production, but it seems not to be involved in the triggering process.

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.

Effect of ischemic preconditioning on myocardial protection in coronary artery bypass graft patients : can the free radicals act as a trigger for ischemic preconditioning?

OBJECTIVE: To investigate the interrelationship of free radicals (FRs), ischemic preconditioning (IP), and hemodynamic function in coronary artery bypass graft (CABG) patients. DESIGN: Prospective, randomized, and controlled clinical study. PATIENTS: Forty CABG patients were randomized into an IP group (n = 20) and a control group (n = 20). INTERVENTION: The IP group was preconditioned with two cycles of two-min ischemia followed by 3-min reperfusion before cross-clamping. MEASUREMENT AND RESULTS: FR content in coronary sinus blood was measured directly using alpha-phenyl-N-tert-butylnitrone-electron spin-trapped spectroscopy. A small amount of FRs was generated after the IP protocol (5.6% above the baseline) but not in control subjects. A larger amount was generated 10 min after declamping in both groups (8.4% in IP protocol and 7.7% in control subjects). Hemodynamic function recovered better in the IP group at 1 h and 6 h after declamping. There was a significant negative correlation between FR generation after declamping and left ventricular stroke work index (LVSWI) at 1 h and 6 h after declamping (r = -0.71 and - 0.59, respectively) in the control subjects but not in the IP group. There was a significant positive correlation between FR generation after the IP protocol and cardiac index at 1 h and 6 h (r = 0.50 and 0.61, respectively) and LVSWI at 1 h and 6 h (r = 0.56 and 0.54, respectively) after declamping in the IP group but not in the control subjects. CONCLUSION: FR generation after the operation correlates with ventricular functional depression in CABG patients. IP protects the stunning heart but does not alter FR generation. The association of better hemodynamic recovery after CABG with FR generation during the IP period suggests that FRs might act as one of the triggers for IP.

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.

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.

Right ventricle is protected better by warm continuous than by cold intermittent retrograde blood cardioplegia in patients with obstructed right coronary artery.

Preservation of the right-ventricular (RV) myocardium is a clinical challenge especially in patients with occluded right coronary artery, in whom antegrade cardioplegia cannot reach areas distal to the stenosis. Retrograde administration of cardioplegia has been thought to overcome the problem, but it has been blamed for inadequate distribution to the RV and possibly poorer functional recovery of this ventricle. Adapting the hypothesis that warm blood cardioplegia may offer better distribution and a more effective supply of oxygen to the arrested heart, we compared RV function in a randomised trial in patients with significant right and left coronary artery disease, after either warm continuous (warm group, n = 15) or intermittent cold (cold group, n = 14) retrograde blood cardioplegia. Right-ventricular function was assessed by determining the ejection fraction (fast-response thermodilution) and preload-related RV stroke work in repeated measurements. The RV ejection fraction remained steady in the warm group during the postoperative course, while it declined significantly in the cold group after operation and differed from that in the warm group until the second postoperative day (p < 0.05-0.001). The ratio of RV stroke work to right atrial pressure was greater postoperatively in the warm than in the cold group until 6 hours after cardiopulmonary bypass (p < 0.05-0.01). Creatine kinase cardiac isoenzyme release was greater in the cold group (p < 0.01). The relationship between left-ventricular stroke work and corresponding preload did not differ between the groups. It can be concluded that recovery of RV function after coronary surgery was better in terms of ejection fraction and preload-related stroke work with warm continuous cardioplegia than with intermittent cold cardioplegia, this along with lower cardiac enzyme release suggesting better RV protection.

Atrial natriuretic peptide and N-terminal atrial natriuretic peptide in plasma reflect right ventricular volumes following coronary artery surgery.

BACKGROUND: Atrial natriuretic peptide (ANP) and the more stable N-terminal fragment (N-ANP) of prohormone are peptides, released in equimolar amounts from cardiac myocytes in response to atrial stretch or ventricular overload and myocardial ischaemia. Protection of the right ventricular (RV) myocardium during ischaemia in cardiac surgery is difficult, especially in patients with severe right coronary artery (RCA) disease. This prospective study was designed to ascertain a possible relationship between changes in plasma ANP/N-ANP concentration and RV function in RCA-diseased patients. METHODS: Plasma ANP and N-ANP concentrations and RV function, measured by fast-response thermodilution, were determined serially in 15 patients with total RCA stenosis and in another 15 with no significant RCA disease (controls) before, during and after coronary surgery. RESULTS: The RV ejection fraction was lower and the RV end-systolic volume index higher in the RCA-diseased patients than in the controls (P < 0.05) on the second postoperative day, and both ANP and N-ANP were higher in the RCA patients (P < 0.05) from 6 h after cardiopulmonary bypass till the second postoperative day. At the same time the changes in N-ANP concentrations from the levels before induction of anaesthesia correlated with RV ejection fraction and RV volume indexes, but not with heart rate or parameters indirectly reflecting left-sided loading. Right atrial pressure did not differ between the groups nor did it increase significantly during the study. CONCLUSIONS: The relationships found between N-ANP and RV volume indexes and RV ejection fraction suggest ventricular expression of ANP: ANP release may be stimulated by RV distension, the more so the poorer the RV function.

Myocardial cooling and right ventricular function in patients with right coronary artery disease: antegrade vs. retrograde cardioplegia.

BACKGROUND: Protection of the right ventricular (RV) myocardium during ischaemia in cardiac surgery is difficult, especially in patients with severe right coronary artery (RCA) disease. Retrograde coronary sinus cardioplegia is thought to distribute uniformly, but doubts still remain as to its adequacy in RV preservation. This study evaluated distribution of antegrade vs. exclusively retrograde coronary sinus cold blood cardioplegia by assessing myocardial cooling and compared the effects on RV function. METHODS: Fifty-eight patients scheduled for elective coronary artery surgery-29 patients with significant RCA disease and another 29 with no significant RCA stenosis (controls)-were randomised to receive either antegrade or retrograde cold blood cardioplegia through either aortic root or conventional self-inflating coronary sinus catheter (RCA-ante, RCA-retro, C-ante and C-retro groups). RV function was assessed by fast-response thermodilution. Myocardial temperatures were measured in the anterior and posterior wall of the right and left ventricle. RESULTS: Cooling of the posterior wall of the RV was effective only in the control patients given antegrade cardioplegia (14.7 degrees C), whereas in the other groups the lowest myocardial temperatures there remained above 20 degrees C (P < 0.001). In patients with obstructed RCA both antegrade and retrograde cold cardioplegia led to uneven cooling of the myocardium. After cardiopulmonary bypass the RV ejection fraction (RVEF), RV stroke work index (RVSWI) and cardiac index (CI) were significantly reduced in the RCA-retro group, and RVSWI and CI in the C-retro group, too. Regression analysis showed an inverse relationship between the temperatures of the posterior walls of the ventricles and changes in the RVEF and CI. CONCLUSIONS: Retrograde and antegrade cardioplegia alone were not effective in reducing the temperature of the posterior wall of the RV in the patients with obstructed RCA, in whom with retrograde cardioplegia RV haemodynamics were impaired for 1 hour following bypass. Neither retrograde nor antegrade cardioplegia alone can be relied on to protect the posterior wall of the RV in the patients with obstructed RCA.

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.

Conduction disturbances after different blood cardioplegia modes in coronary artery bypass grafting. Including comparison with an earlier patient series.

One-hundred and nine patients undergoing coronary artery bypass grafting were randomized to seven groups according to cardioplegia technique (5 types) and right coronary patho-anatomy (2 types). There were no major intergroup differences in postoperative outcome. Conduction disturbances developed in 26 patients, also without intergroup difference. Factors predictive of conduction disturbances were studied by univariate and multivariate analyses. Patients with such disturbances had lower myocardial temperatures than the others and more often postoperative atrial fibrillation (10/26 vs 15/83, p < 0.05). Comparison of this case series with a prospective study from our hospital in 1988-1989 showed that myocardial protection was superior in the present study. The incidence of right bundle branch block was similar in the two studies (24% vs 23%), but that of left-side conduction disturbances (bundle branch or fascicular block) was dramatically reduced (19% vs 1%, p < 0.0001) concomitantly with improved myocardial protection, indicating that development of a left-side conduction disturbance is associated with myocardial injury.