Metabolic changes and myocardial injury during cardioplegia: a pilot study.

BACKGROUND: The timing, nature, and severity of both increased cardiac troponin I (cTn-I) levels and myocardial injury during ischemic arrest with cardioplegia are unknown. To define them more accurately, we studied myocardial metabolic activity and the release of markers of myocardial cell injury into the coronary sinus before, during, and after cardioplegia. METHODS: We simultaneously measured creatine kinase, creatine kinase-MB, cTn-I, lactate, phosphate, and blood gases in coronary sinus and systemic arterial blood from 12 patients before cardiopulmonary bypass, after removal of the aortic cross-clamp, and after discontinuation of cardiopulmonary bypass. We also measured coronary sinus flow and transmyocardial fluxes of all analytes and calculated myocardial oxygen consumption, myocardial carbon dioxide production, and myocardial energy expenditure. RESULTS: Myocardial lactate release increased 10-fold after removal of the aortic cross-clamp (p = 0.012) and was accompanied by a surge in myocardial phosphate uptake (p = 0.056). These events were associated with only partial cardioplegia-induced suppression of myocardial oxygen consumption (p = 0.0047), myocardial carbon dioxide production (p = 0.0022), and myocardial energy expenditure (p = 0.0029). Simultaneously, coronary sinus cTn-I levels increased from a mean of 0.76 to 2.43 ng/mL after removal of the aortic cross-clamp, and 2.51 ng/mL after cardiopulmonary bypass (p = 0.014), leading to an increase in arterial cTn-I concentration from 0.18 to 0.98 and 3.01 ng/mL (p = 0.0002). Thus, cTn-I release across the myocardium was absent at baseline, became detectable (p = 0.012) after removal of the aortic cross-clamp, and correlated with cross-clamp and pump times. Similar changes occurred with creatine kinase-MB. CONCLUSIONS: Metabolic myocardial stress occurs during ischemic arrest with cardioplegia and is associated with inadequate suppression of metabolism and with a surge in cTn-I and creatine kinase-MB release, which is maximal after removal of the aortic cross-clamp. These changes are likely to represent structural myocardial cell injury.     

Efficacy of esmolol as a myocardial protective agent during continuous retrograde blood cardioplegia

OBJECTIVE: Esmolol, an ultra-short-acting beta-blocker, is known to attenuate myocardial ischemia-reperfusion injury. The aim of this study was to compare the effects of esmolol and potassium on myocardial metabolism during continuous normothermic retrograde blood cardioplegia. METHODS: Forty-one patients operated on for isolated aortic valve stenosis were randomly assigned to continuous coronary infusion with either potassium or esmolol during cardiopulmonary bypass. Myocardial metabolism was assessed by measuring the transmyocardial gradient of oxygen content indexed to left ventricular mass of glucose, lactate, and nitric oxide. To do so, blood samples were simultaneously withdrawn upstream (in the cardioplegia line) and downstream of the myocardium (in the left coronary ostium) 10 and 30 minutes after aortic crossclamping. RESULTS: Although the cardioplegia flow rate and pressure were similar, esmolol markedly reduced the transmyocardial gradient of oxygen content indexed to left ventricular mass compared with potassium: 13 +/- 6 vs 20 +/- 6 mL of oxygen per liter of blood per 100 g of myocardium, respectively, at 10 minutes and 16 +/- 8 vs 24 +/- 8 mL of oxygen per liter of blood per 100 g of myocardium, respectively, at 30 minutes (P =.009). Coronary glucose and lactate transmyocardial gradients were similar in both groups, indicating adequate myocardial perfusion in all patients at all times. In addition, during retrograde cardioplegia, esmolol showed a lower nitric oxide release compared with that caused by potassium (39 +/- 49 micro mol x L(-1) for potassium vs 14 +/- 8 micro mol x L(-1) for esmolol at 10 minutes and 39 +/- 47 micro mol x L(-1) for potassium vs 6 +/- 8 micro mol x L(-1) for esmolol at 30 minutes, P =.05). However, hemodynamic parameters and plasma troponin I levels remained unchanged postoperatively between the 2 types of cardioplegia. CONCLUSION: Esmolol provides potent myocardial protection in hypertrophied hearts, at least in part, by reducing myocardial oxygen metabolism.     

Effects of calcium in continuous cardioplegia on myocardial protection

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca(0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37°C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1±2.9%, 80.6±2.0%, and 71.5±3.7% (mean±SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.     

The advantages of normocalcemic continuous warm cardioplegia over low calcemic cardioplegia in myocardial protection

The effects of changing the calcium content of a continuous warm hyperkalemic crystalloid cardioplegia (CWCP) were investigated in an isolated rat heart preparation. The hearts were divided into eight groups of six each. A control group consisted of fresh nonarrested hearts and the remaining seven groups consisted of hearts perfused with continuous hyperkalemic (20 mM) modified Krebs-Henseleit bicarbonate buffer solution with calcium concentrations of 0.1, 0.3, 0.5, 1.0, 1.5, 2.0, or 2.5 mM, for either 180 or 240 min at 37°C. In the hearts arrested for 180 min, there were no significant differences in postarrest cardiac functions between the control group and any of the groups perfused with calcium concentrations of 0.5 mM or more. With a calcium concentration of 0.1 mM, the calcium paradox was provoked. The change in the calcium content of CWCP perfused for 240 min significantly affected myocardial protection. Maximum aortic flow recovery, of 74.5%±2.7%, and minimum CK release, of 15.7±2.4IU/15 min/g dry weight, were observed in hearts perfused with a calcium concentration of 1.5 mM. The calcium paradox occurred even at a calcium concentration of 0.3 mM; therefore, normal calcium concentrations should be maintained in cardiac surgery to prevent cardiac injury.     

Continuous monitoring of myocardial acid–base status during intermittent warm blood cardioplegia

Objective: Intermittent warm blood cardioplegia (IWBC) is a well-established technique for myocardial protection during cardiac operations. According to standardized protocols, IWBC administration is currently performed every 15–20 min regardless of any individual variable and in the absence of any instrumental monitoring. We devised a new system for continuous measurement of the acid–base status of coronary sinus blood for on-line evaluation of myocardial oxygenation during IWBC. Methods: In 19 patients undergoing cardiac surgery for coronary artery bypass graft and/or valve surgery and receiving IWBC (34–37°C) by antegrade induction (3 min) and retrograde or antegrade maintenance (2 min) every 15 min, continuous monitoring of myocardial oxygenation and acid/base status was performed by means of a multiparameter PO₂, PCO₂, pH, and temperature sensor (Paratrend7 ®, Philips Medical System) inserted into the coronary sinus. Results: Mean cross-clamping time was 76±26 min; ischemic time was 13±0.2 min. pH decline was not linear, showing an initial fast decline, a point of flexus, and a progressive slow decline. After every ischemic period, the pH adaptation curve showed a complex pattern reaching step-by-step lower minimum levels (7.28±0.14 during the first ischemic period, to 7.16±0.19 during the third ischemic period – P=0.003). PO₂ decreased rapidly at 90% in 5.0±1.2 min after every reperfusion. During ischemia, PCO₂ increased steadily at 1.6±0.1 mmHg per minute, with progressively incomplete removal after successive reperfusion, and progressive increase of maximal level (42±12 mmHg during the first ischemic period, to 53±23 mmHg during the third ischemic period – P=0.05). Conclusions: Myocardial oxygen, carbon dioxide, and pH show marked changes after repeated IWBC. Myocardial ischemia is not completely reversed by standardized reperfusions, as reflected by steady deterioration of PCO₂ and pH after each reperfusion. Progressive increase of reperfusion durations or direct monitoring of myocardial oxygenation could be advisable in cases of prolonged cross-clamping time.     

End-tidal CO2 and tissue pH in the monitoring of acid-base changes: a composite technique for continuous, minimally invasive monitoring

The infrared CO2 analyzer continuously monitors the CO2 tension in exhaled air at end-tidal expiration. In experimental animals, we found a consistent relationship between PaCO2 and end-tidal CO2 (ET.CO2) in the normal steady state, and in acid-base disturbances (respiratory acidosis and alkalosis, and hypoperfusion acidosis). Paired data analyses of PaCO2 (X) and ET.CO2 (Y) yielded correlation coefficients of r = 0.98 (Y = 0.96X + 4.43) during progressive hypercarbia (PaCO2: 32----110 torr), and r = 0.93 (Y = 0.89X + 0.93) during hyperventilation hypocapnia (PaCO2: 41----14 torr). The relationship between PaCO2 and ET.CO2 was seen during hypovolemic shock if pulmonary perfusion was maintained uniform in all areas of lung. The ability of the ET.CO2 sensor to predict instantaneously the PaCO2 makes it attractive enough to be used in conjunction with the subcutaneous tissue pH(pHe) sensor in the management of acid-base disturbances. After hypercarbia (FiCO2 0.15 X 40 min; PaCO2/ET.CO2: 100/101 torr), when the dogs were returned to room air, abruptly both the ET.CO2 and pHe sensors were sensitive to the changes in Fi.CO2. But the response of the ET.CO2 was swifter. The advent of transcutaneous gas monitors has shown that intermittent blood gas analyses, however frequent, are inadequate for the monitoring of the rapidly altering blood gas status in the acutely ill. The ability of the pHe sensor to identify whole-body acidosis and alkalosis combined with the speed and ease of the ET.CO2 monitor in pinpointing hypercarbic and hypocarbic states makes this two-parameter system suitable for the continuous, noninvasive monitoring of the critically ill.     

Continuous monitoring of muscle gas tensions and pH during tissue acid-base disturbances

To evaluate the applicability of continuous muscle P_O2 and P_CO2 monitoring as indicators of physiologic abnormalities, muscle (m) P_O2 and P_CO2 was measured by mass spectrometry and pH by muscle surface probe in the limb muscle of 16 dogs subjected to hemorrhage, acid infusion, hypoxia, or hypocarbia and hypercarbia. These values were compared to arterial (a) pH, P_O2, and P_CO2.During hemorrhage, mP_O2 fell sharply; mP_CO2 rose and mpH decreased linearly in proportion to the rate and the magnitude of the bleed. mP_O2 fell with the onset of blood loss, whereas significant mP_CO2 and mpH changes resulting from tissue acidosis were evident only after a large volume loss.Metabolic acidosis produced by acid infusion caused a parallel drop in arterial and mpH, a rise in mP_CO2, and no change in mP_O2.During progressive hypoxia, aP_O2 and mP_O2 reflected the changes in inspired O₂. MpH and apH fell only when mP_O2 fell to low levels. Hypercarbia and hypocarbia caused parallel changes in mP_CO2 which were also reflected in apH and mpH.Continuous muscle gas measurements appear feasible and combined with muscle pH monitoring should help the clinician pinpoint the cause of physiologic derangements in the critically ill.     

Limitations of retrograde continuous tepid blood cardioplegia for myocardial remodeling.

OBJECTIVE: We assessed potential limitations of retrograde continuous tepid blood cardioplegia (RCTBC) for myocardial remodeling, represented by hypertrophied and/or dilated myocardium in patients with severe cardiomyopathy following single aortic valve replacement. METHODS: The study was conducted on 91 patients who underwent initial single aortic valve replacement with tepid cardiopulmonary bypass (CPB) and RCTBC. Based on the postoperative maximum creatine phosphokinase (max CPK)-MB level, the patients were allocated to Group H (>/=100 IU/mL) with severe cardiomyopathy or Group L (<100 IU/mL) to make intergroup comparisons of preoperative, intraoperative, and postoperative parameter values. RESULTS: Preoperative measurements were as follows: pressure gradient between left ventricle and aorta (DeltaPG), 92.8+/-46.2 mmHg in Group H and 57.9+/-41.6 mmHg in Group L (p<0.01); implanted valve size, 21.0+/-2.2 mm in Group H and 22.8+/-2.2 mm in Group L (p<0.01); left ventricular end-diastolic volume (LVEDV), 155.7+/-73.3 mL in Group H and 224.3+/-101.5 mL in Group L (p<0.01). The rate of RCTBC flow rate increase did not differ between the groups (17.6% in Group H and 20.7% in Group L), while the rate of concomitant use of optional antegrade coronary perfusion was significantly lower in Group H (25%) than in Group L (37%) (p<0.05). Pre- and post-perfusion lactic acid levels in the myocardial protection solution measured every 30 min after aortic cross clamping were higher in Group H than in Group L. CONCLUSION: The study suggests preoperative high DeltaPG, small aortic root diameter, and low LVEDV, namely, concentrically hypertrophied myocardium, as risk factors for severe cardiomyopathy after RCTBC. RCTBC in patients with any risk factor should be accompanied by an increase in initial continuous perfusion flow and/or aggressive use of intermittent antegrade coronary perfusion.     

Comparison of myocardial temperatures with multidose cardioplegia versus single-dose cardioplegia and myocardial surface cooling during coronary artery bypass grafting

Myocardial hypothermia with multidose cardioplegia has not been compared with single-dose cardioplegia and myocardial surface cooling with a cooling jacket in patients having coronary artery bypass grafting. In this study, 20 patients with three-vessel disease undergoing coronary bypass at 28 degrees C with bicaval cannulation, caval tapes, and pulmonary artery venting (4.9 +/- 0.7 grafts per patient) were prospectively randomized equally into group I (multidose cardioplegia) and group II (single-dose cardioplegia with a cooling jacket). The initial dose of cardioplegic solution was 1000 ml. Group I then received 500 ml of cardioplegic solution every 20 minutes, delivered into the aortic root and available grafts. In group II, after the cardioplegic solution had been administered, a cooling jacket covering the right and left ventricles was applied. In both groups temperatures were recorded every 30 seconds at five ventricular sites: (1) right ventricular epicardium; (2) right ventricular myocardium or cavity, 7 mm; (3) left ventricular epicardium; (4) left ventricular myocardium or cavity, 15 mm; and (5) septum, 20 mm. Group mean temperatures at each site at various times were compared within each group and between the two groups by analysis of variance. Aortic crossclamp time was 60.3 +/- 12.1 minutes in group I and 52.8 +/- 7.3 minutes in group II (p = 0.12); cardiopulmonary bypass time was 103.7 +/- 11.1 minutes in group I versus 87.7 +/- 12.7 minutes in group II (p less than 0.01). One minute after the cardioplegic solution was initially given, temperatures between groups at each site were not statistically different, but left ventricular epicardial temperatures within both groups were significantly higher than in the other four sites. Nineteen minutes after administration of the cardioplegic solution, temperatures in group I at all sites were higher than in group II. Similarly, throughout the entire period of aortic crossclamping, mean temperatures (except left ventricular myocardial site), maximum temperatures, and percentage of time all temperatures were 15 degrees C or higher were greater in group I than in group II. The following conclusions can be reached: 1. Initial myocardial cooling with 1000 ml of cardioplegic solution is not significantly limited by coronary artery disease but is suboptimal (16 degrees or 17 degrees C) in the inferior left ventricular epicardium because of continual warming from the aorta and subdiaphragmatic viscera. 2. Without myocardial surface cooling, excessive external myocardial rewarming to 18 degrees to 22 degrees C occurs within 20 minutes at all sites after delivery of the cardioplegic solution.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of multidose cardioplegia and cardioplegic solution buffering on myocardial tissue acidosis

Multidose administration of cardioplegic solution during cardiac operation is intended to maintain both electromechanical arrest of the heart and myocardial hypothermia as well as to remove accumulated metabolites of anaerobic glycolysis. This study was conducted to assess the effect of multidose infusion of three different types of cardioplegic solution on tissue acidosis during global myocardial ischemia. Three groups of five dogs each were placed on cardiopulmonary bypass and the aorta was cross-clamped for 3 hours. The hearts were maintained at a constant temperature (20 degrees C) and cardioplegic solution was infused at an initial dose of 500 ml and five supplementary doses of 250 ml administered every 30 minutes. Group 1 received a crystalloid solution weakly buffered with sodium bicarbonate, Group 2 received a blood-based solution, and Group 3 received a crystalloid solution strongly buffered with histidine (Bretschneider's solution). The buffering capacities of the solutions used in Groups 2 and 3 were 40 and 60 times, respectively, that of the solution used in Group 1. The average myocardial tissue pH at the end of 3 hours of ischemia was 6.54 +/- 0.07 in Group 1, 7.23 +/- 0.05 in Group 2, and 7.19 +/- 0.06 in Group 3 (Group 1 significantly lower than Groups 2 and 3). Multidose infusion of a cardioplegic solution with low buffering capacity was unable to prevent the progressive development of tissue acidosis during 3 hours of ischemia. However, the multidose infusion of either blood-based or crystalloid solutions with high buffering capacity completely prevented any further reduction of tissue pH after the first 30 minutes of ischemia.     

Pressure monitoring of the coronary sinus during retrograde cardioplegia

Though the retrograde perfusion via the coronary sinus is a useful way of myocardial protection for more complicated cardiac surgery, coronary venous injury and inadequate preservation of the right ventricle were considered to be disadvantageous. In order to deal effectively with these problems we made a 3-way balloon catheter (Retro-Higami type 12 Fr) and evaluated the importance of monitoring the perfusion pressure in the coronary sinus in 214 patients. The mean perfusion pressure during retrograde cardioplegia infused by a pump was 29.4 +/- 9.1 mmHg, and had significant relation to the left ventricular mass weight (LVMW) which was calculated by UCG method. High perfusion pressure above 40 mmHg, which could have induced coronary venous injury, was noticed in 24 patients, but proper countermeasures could avoid venous injury completely. In 16 of those the high perfusion pressure was due to inadequate position of a tip of the catheter, and in other 8 it was due to relatively high flow rate of cardioplegic solution to LVMW. Twenty-eight patients showed low perfusion pressures below 20 mmHg, due mainly to the leakage from the orifice of the coronary sinus. The coronary sinus pressure during continuous gravity retroperfusion which was 9.2 +/- 2.6 mmHg seemed to bring optimal delivery of cardioplegic solution to the myocardium. On the basis of the results obtained from this clinical study we conclude that the monitoring of coronary sinus pressure during retroperfusion is useful not only to avoid coronary venous injury but to maintain adequate perfusion.     

Tissue pH monitoring in microsurgery: a preliminary evaluation of continuous tissue pH monitoring as an indicator of perfusion disturbances in microvascular free flaps

In an experiment using a continuous tissue pH monitoring system, selective occlusion of the vessels supplying lower abdominal island flaps in Sprague-Dawley rats resulted in predictable tissue pH changes. Arterial occlusion resulted in a rapid fall in pH. In all three experimental groups, the steepest rate of pH drop occurred during the first 30 minutes postocclusion. In a series of 9 patients who underwent microvascular free flap surgery the continuous pH monitor was employed postoperatively. Tissue pH was (and remained) normal in well-perfused free flaps. Tissue pH fell almost immediately with anastomotic failures. These findings demonstrate that pH measurement offers the microvascular surgeon a new, simple, and reliable approach to perfusion assessment in free flaps. Perhaps improved survival rates will result from earlier anastomotic exploration in compromised free flaps that exhibit falling pH values.     

Preservation of myocardial ATP during cardioplegia: comparison of techniques

Preservation of myocardial ATP enhances the heart's ability to resume normal function following aortic crossclamping (AXC). Preservation of this high energy substrate during 4 cardioplegia delivery techniques was evaluated and compared with changes occurring during 4 hours of continuous coronary perfusion. Dogs (31) were placed on cardiopulmonary bypass and transmural left ventricular biopsies obtained for control ATP measurements. Animals were then divided into five groups: Group I (n = 6): 4 hrs. of continuous coronary perfusion (CCP); Group II (n = 6): 3 hrs. continuous AXC, multidose blood cardioplegia (MBC); Group III (n = 6): 3 hrs. continuous AXC, multidose crystalloid cardioplegia (MCC); Group IV (n = 6): 2 hrs. intermittent AXC, single dose BC (SBC); Group V (n = 7): 2 hrs. continuous AXC, continuous perfusion BC (CBC). In each group, where applicable, myocardial biopsies were taken at 30 minute intervals during AXC, before and after cardioplegia injection, and 30 minutes following final unclamping and rewarming. Hearts in Group II (MBC) and V (CBC) showed greatest preservation of ATP stores (increases 1.1 +/- 1.2%, increases 1.8 +/- 0.9% respectively; p greater than .05) ATP levels rose as high as 23 +/- 2% (p less than .005) above control immediately following cardioplegia injection in Group II (MBC). Group IV showed poorest preservation of ATP (decreases 26 +/- 5%, p less than .01) with levels falling as much as 37 +/- 10% (p less than .01) during the period of AXC. Hearts in Group I (CCP) demonstrated a 15.6 +/- 7.5% decrease in ATP from control (p less than .05). Group III (MCC) also showed a steady decline in ATP declining 18 +/- 3% (p less than .005) from control. These data indicate that multidose blood and continuous-blood cardioplegia techniques will maintain normal myocardial ATP stores throughout the period of AXC. These groups actually show a slight rise in ATP as compared to 4 hrs. of continuous coronary perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Improved myocardial preservation with oxygenated cardioplegic solutions as reflected by on-line monitoring of intramyocardial pH during arrest

To examine the relationship between intramyocardial pH during global ischemic arrest and subsequent functional and biochemical recovery, 40 canine hearts were subjected to 4 hours of arrest at 10 degrees C. Four groups, each containing 10 hearts, were differentiated by the oxygen concentration of a hyperkalemic crystalloid cardioplegic solution (CCS), which was infused every 20 minutes. In group 1 the CCS was equilibrated at 4 degrees C with nitrogen to remove oxygen. In group 2 the CCS was aerated at 4 degrees C. In group 3 the CCS was treated to achieve an oxygen tension (PO2) similar to group 2 but with a reduced nitrogen content to prevent bubble formation, which is theoretically possible during reperfusion ("myocardial bends"). In group 4 the CCS was fully oxygenated at 4 degrees C. The resulting PO2 of CCS measured at 10 degrees C was less than 20, 170, 170, and 750 mm Hg in groups 1, 2, 3, and 4, respectively. Left ventricular function (LVF) was assessed from function curves at constant mean aortic pressure and heart rate. Functional recovery, expressed as a percentage of prearrest LVF, was 38.1% +/- 10.7% in group 1 and 84.0% +/- 8.1% in group 4 (p less than 0.008). Functional recovery was 64.9% +/- 5.5% and 69.1% +/- 7.0% in groups 2 and 3, which had similar PO2. Differences in recovery between groups 2 and 3 and group 1 approached statistical significance (p less than 0.05, NS). The mean-integrated intramyocardial pH during arrest was higher (p less than 0.003) in group 4 (7.14 +/- 0.05) than in group 1 (6.84 +/- 0.06) or group 2 (6.86 +/- 0.07). The minimum intramyocardial pH during arrest was higher in group 4 than in any other group (p less than 0.002). Myocardial adenosine triphosphate concentration at the end of arrest, expressed as a percentage of its prearrest value, was highest in group 4 (75.9% +/- 8.1%) and lowest in group 1 (54.3% +/- 5.7%), a difference approaching statistical significance (p less than 0.05, NS). These data suggest that the measurement of intramyocardial pH is a useful on-line indicator of the adequacy of preservation during hypothermic arrest and that excess nitrogen in aerated CCS had little or no effect on recovery. The data confirm the hypothesis that oxygenation of CCS is associated with good myocardial preservation, which may be attributed to the provision of oxygen for the support of aerobic metabolism during arrest.     

Nicorandil pretreatment and improved myocardial protection during cold blood cardioplegia.

OBJECTIVE: The present study was designed to assess whether pretreatment with nicorandil enhanced myocardial protection provided by cold (15 degrees C) high-potassium (25 mmol/l) blood cardioplegia during open heart surgery. METHODS: Subjects were 40 patients with a variety of acquired heart diseases undergoing cardiac surgery involved cardiopulmonary bypass. They were randomly divided into two groups, 25 pretreated nicorandil (0.3 mg/kg) 30 minutes before aortic cross clamping, 15 not pretreated. After aortic cross clamping, the initial dose of cardioplegic solution (10 ml/kg) was administered through the ascending aorta and supplemental doses of cardioplegia (5 ml/kg) given each 30 minutes thereafter. Preoperative and postoperative cardiac troponin-T, myosin light chain 1 and cardiac enzymes were measured and hemodynamic data recorded. RESULTS: Postoperative serum creatine kinase and myosin light chain 1 were significantly lower in the nicorandil pretreatment group than in controls. Serum glutamic oxalacetic transaminase and troponin-T were lower and cardiac output was higher after surgery in the nicorandil group, although not statistically significant. CONCLUSION: This data suggests that pretreatment with nicorandil enhances the myocardial protection achieved by cold blood cardioplegia.