Orthotopic transplantation of pig hearts harvested after 30 min of normothermic ischemia: controlled reperfusion with blood cardioplegia containing the Na-H-exchange inhibitor HOE 642

Objectives: The aim of our study was to develop a surgical technique for a successful transplantation of hearts harvested after 30 min of normothermic ischemia without donor pretreatment. Successful transplantation of ischemic compromised hearts could help to expand the severely limited donor pool. We used the pig model because this species is very susceptible to myocardial ischemia. Na⁺-H⁺-exchange (NHE) inhibitors have shown excellent protective properties in several in vitro and in vivo models of myocardial ischemia and reperfusion. Methods: In group I (n=12) hearts were harvested after 30 min of normothermic ischemia following cardiac arrest induced by exsanguination. Hearts were perfused with warm blood cardioplegia and transplanted orthotopically. In group II (n=9) controlled reperfusion with cold leucocyte-depleted blood cardioplegia was performed after 30 min of normothermic ischemia. In group III (n=8) the same procedure was performed as in group II but blood cardioplegia contained 1 mmol/l HOE 642. Results: In group I massive myocardial oedema was observed and none of the animals could be weaned from cardiopulmonary bypass (CPB). In contrast, all animals in groups II and III could be weaned from CPB with low dose inotropic support. In groups II and III the contractility of the hearts, expressed as maximal left and right ventricular stroke work index was significantly impaired after transplantation as compared with the preoperative value. Supplementation of blood cardioplegia with HOE 642 resulted in a significantly better recovery of the LVSWImax (Group II vs. III). Conclusions: Successful transplantation of pig hearts is possible after 30 min of normothermic ischemia without donor pretreatment if a controlled reperfusion with cold leucocyte-depleted blood cardioplegia is performed. HOE 642 given during reperfusion only improves posttransplant left ventricular function.     

The warm versus cold perfusion controversy: a clinical comparative study

To evaluate the effects of temperature on myocardial and total body protection, we analyzed 129 consecutive patients who underwent coronary artery bypass grafting, valve replacement, or both, with continuous cardioplegia (Cp). The patients were assigned to three groups: group I (n = 37) normothermic cardiopulmonary bypass (CPB) (37°C) and warm (37°C) Cp, group II (n = 49) normothermic CPB and cold (4°C) Cp and group III (n = 43) hypothermic (28°C) CPB and cold Cp. Comparison of groups I and II showed similar serum levels of creatine kinase (CK) and its myocardialspecific isoenzyme on the first postoperative day, a similar rate of perioperative myocardial infarction, postoperative need for intra-aortic balloon pump, postoperative need for inotropic support and mortality. Comparison of groups I and III showed similar serum levels of CK, amylase, lactate dehydrogenase and creatinine on the first postoperative day, a similar complication rate and mortality rate. However, normothermic CPB resulted in a shorter bypass time (83 ± 4 vs 98 ± 7 min, P<0.05) and interval until extubation (25.0 ± 3.8 vs 40.3 ± 7.4 h, P<0.05). In conclusion, there are no differences concerning myocardial protection, however, warm CPB shortens the perfusion time and postoperative course.     

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.     

Comparison of single- and multi-dose crystalloid cardioplegia to protect the immature myocardium

The primary objective of this study was to compare the protective effects of single-dose and multi-dose St. Thomas' Hospital cardioplegic solution number 1 in the ischemic and reperfused neonatal rabbit heart. In addition, the effect of including bicarbonate (a component of St. Thomas' Hospital cardioplegic solution number 2) was also studied. Hearts (n=8 per group) were excised from rabbits (7–10 days old) and aerobically perfused in the working mode with crystalloid media for 20 min (37°C). After assessing cardiac function, the hearts were arrested by an infusion of cold cardioplegic solution (2 min at 15°C with or without the addition of bicarbonate (10 mmol). The hearts were then subjected to 6 h of hypothermic ischemia (15°C and, during this period, some hearts received multiple infusions (2 min/h at 15°C) of cardioplegic solution. All hearts were reperfused for 35 min (15 min Langendorff plus 20 min working), cardiac function was then re-assessed and expressed as a percent of the preischemic value. The coronary effluent, collected during the first 15 min of reperfusion, was assayed for creatine kinase activity. At the end of the reperfusion period, the hearts were freeze clamped and taken for metabolic analysis. With multi-dose cardioplegia (without bicarbonate) the postischemic recovery of cardiac output was 67.0±6.5% and with single-dose the value was 39.3±10.0% (NS). The same pattern of postischemic recovery (that varied between 30% and 60%) for aortic flow, stroke volume and stroke work was observed with both multi-dose and single-dose infusion. The inclusion of bicarbonate in the cardioplegic solution did not significantly alter the recovery of cardiac output with single-dose (51.7±8.9% vs 39.3±10.0%) or multi-dose infusion (60.6±7.6% vs 67.0±6.5%). Creatine kinase leakage was similar in all groups, as was the myocardial high energy phosphate content. In conclusion, in the neonatal rabbit heart, multi-dose St. Thomas' Hospital cardioplegia affords similar protection to single-dose administration and this was not modified by the addition of bicarbonate.     

Do patients want minimally invasive aortic valve replacement?

Objective: Access to aortic valve can be performed through small incisions. However, a considerable advantage of this approach has not been proven by randomized studies so far. We wanted to elucidate the opinion of patients when they are informed objectively about advantages and disadvantages of minimally invasive approach prior to operation. Methods: This prospective study was performed with 27 patients undergoing isolated aortic valve replacement. These patients were informed prior to operation by the same resident concerning objective data. A photograph was shown illustrating a patient with postoperative wound after a standard- and a mini-incision, respectively. After the interview the patient could decide between full and partial sternotomy. Results: After the interview 21/27 (78%) patients preferred to have a full sternotomy (group F) and 6/27 (22%) patients (group P) decided to have a partial sternotomy. Comments of group F: surgeon should have best exposure (n=15); cosmetics aspects unimportant (n=14); operation time as short as possible (n=7). Group P: cosmetic aspects important (n=6). Significant differences between groups (group F vs. group P): age (years), 69.1±1.5 vs. 49.2±7.3 (P=0.024); operation time (min), 142±7 vs. 189±15 (P=0.002); CK (IU/l), 111±11 vs. 374±114 (P=0.0007); CKMB (IU/l), 17±2 vs. 45±17 (P=0.006); ICU-stay (days), 2.6±0.2 vs. 3.2±0.2 (P=0.044). Pericardial effusion requiring drainage was observed in two patients of group P. One patient of group P suffered myocardial infarction. Conclusion: When patients are informed objectively about advantages and disadvantages of minimal invasive aortic valve surgery only a smaller number decides to have a mini incision. The patients preferring short incisions are significantly younger since cosmetic aspects are more important. Longer duration of operation may be due to longer hemostasis based on limited exposure. Air bubbles due to inadequate de-airing might be responsible for higher CK and CK-MB levels in group P.     

Right ventricle-to-pulmonary artery shunt and modified Blalock–Taussig shunt in preparation to hemi-Fontan procedure in children with hypoplastic left heart syndrome

Objective: The advantageous effect of right ventricle-to-pulmonary artery shunt (RV–PA) on the early postoperative hemodynamics in the Norwood procedure for hypoplastic left heart syndrome (HLHS) is well known. Numerous controversies still exist with respect to the late consequences of this new palliation method in preparation for the second stage procedure. Methods: Between September 1997 and September 2004, a consecutive series of 78 children with HLHS from a single institution underwent the hemi-Fontan procedure: Group 1 (n=27) after Blalock–Taussig shunt (BT), and Group 2 (n=51) after RV–PA. Hemodynamic, echocardiographic and clinical perioperative data were analyzed. Results: There were no significant differences in the age and operative weight (Group 1: 6.9±1.04 months, 6.22±0.99 kg; Group 2: 6.57±1.12 months, 6.36±0.86 kg). Children after RV–PA were characterized by a significantly higher preoperative hematocrit value (P=0.014), lower aortic and superior vena cava oxygen blood saturation (P<0.001, P=0.024), severe right ventricle hypertrophy more rarely diagnosed in echocardiography (P<0.004), lower Qp:Qs ratio (P=0.011), larger right (P=0.001) and left (P=0.006) pulmonary artery index and a shorter intensive care unit stay after the hemi-Fontan procedure (P=0.004). Conclusions: The Norwood procedure with the RV–PA shunt provides satisfactory late hemodynamics and improves the development of the pulmonary arteries. Children with hypoplastic left heart syndrome subjected to this new method of palliation are good candidates for the hemi-Fontan procedure.     

Leukocyte Depletion of Blood Cardioplegia Attenuates Reperfusion Injury

Background. Leukocytes are associated with myocardial injury during reperfusion after ischemia. Short periods of leukocyte depletion during reperfusion result in persistent attenuation of postischemic myocardial dysfunction.

Methods. Leukocyte depletion was examined in a canine model of regional myocardial ischemia and reperfusion. The extracorporeal circuit and cardioplegia circuits underwent leukocyte depletion by mechanical filtration. Animals were instrumented for baseline global function before 90-minute occlusion of the left anterior descending coronary artery. Global function during ischemia and at 5, 30, 60, and 90 minutes after a 60-minute cardioplegic arrest using continuous blood cardioplegia was assessed in leukocyte-depleted (n = 9) and control (n = 10) groups.

Results. No significant difference between groups was seen for systemic leukocyte counts, global function, or water content. Endothelial function was significantly protected as assessed by response to both calcium ionophore (endothelial-dependent, receptor-independent relaxation: leukocyte-depleted, 72% ± 19% of endothelin-induced constriction versus control, 46% ± 14%; p < 0.05) and acetylcholine (endothelial-dependent, receptor-dependent relaxation: leukocyte-depleted, 83% ± 11% versus control, 44% ± 15%; p < 0.05).

Conclusions. Leukocyte-mediated endothelial reperfusion injury can be attenuated by leukocyte depletion during reperfusion.     

Prospective randomized trial of single clamp technique versus intermittent ischaemic arrest: myocardial and neurological outcome

Objective: To explore the hypothesis that intermittent ischaemic arrest (IIA) provides better myocardial preservation but generates a larger number of cerebral microemboli (ME) and consequently a higher incidence of post-operative cerebral dysfunction compared with the single clamp technique (SCT). Methods: Ninety-one patients with stable angina undergoing elective CABG with no clinical evidence of aortic or cerebro-vascular or neurological disease were prospectively randomized to: IIA (n=43) or SCT with intermittent anterograde cold blood cardioplegia (n=48). Myocardial preservation was assessed by measuring serum CK-MB, Troponin-T (TnT) and Troponin-I (TnI) and from pre- and post-operative ECGs and left ventricular (LV) function by echocardiography. Intra-operative cerebral ME were counted by transcranial Doppler of the right middle cerebral artery. All patients completed the Luria Nebraska Neuropsychological Battery (LNNB) tests for motor, visual, reading, memory and intellectual processes the day before surgery and at 1 week and 6 months post-operatively. Serum levels of the neuro-specific protein S-100 were measured. Results: The two groups were comparable for age, sex, extent of coronary disease, previous myocardial infarction, diabetes, hypertension and number of arterial and venous grafts. The median number of ME detected per patient was 34 (range 4–208) and was similar in both groups. Protein S-100 levels remained normal and similar in both groups at all times except in one patient with SCT who had an operative stroke. LNNB scores were similarly depressed at 1 week and recovered in all cases at 6 months. There was no correlation between the number of ME and LNNB scores. Median peak TnI levels were 0.64 μg/l with IIA vs. 0.87 μg/l with SCT (P=NS) and TnT 0.8 μg/l vs. 1.08 μg/l (P<0.03). SCT was however associated with longer mean ischaemic (67.6±16.1 vs. 34.5±16.5 min, P<0.001) and mean bypass time (88.5±18.2 vs. 74.6±26.3min, P<0.004) than IIA. Four patients with SCT and none with IIA had ECG changes suggestive of MI (P=0.04). Conclusion: During elective CABG in patients with no clinical evidence of aortic or cerebro-vascular disease the incidence of peri-operative ME and post-operative neuropsychological disturbances are comparable with both techniques of myocardial preservation. Biochemical analysis suggests that IIA provides more effective myocardial preservation.     

Terminal Warm Blood Cardioplegia Improves Cardiac Function Through Microtubule Repolymerization

Background. To elucidate the mechanisms responsible for the beneficial effects of terminal warm blood cardioplegia, we studied dynamic change in microtubules induced by cold cardioplegia followed by rewarming. Further, we investigated the relationship between cardiac function and morphologic changes in microtubules caused by hyperkalemic, hypocalcemic warm cardioplegia during initial reperfusion.

Methods. In protocol 1 isolated rat hearts were perfused at 37°C with Krebs-Henseleit buffer (KHB). After 3 hours of hypothermic cardiac arrest at 10°C, hearts were reperfused at 37°C with one of two buffers: group C, 60-minute reperfusion with KHB (K⁺, 5.9 mmol/L; Ca²⁺, 2.5 mmol/L); and group TC, 10-minute initial reperfusion with modified KHB (K⁺, 15 mmol/L; Ca²⁺, 0.25 mmol/L), followed by 50 minutes of reperfusion with KHB. Cardiac function after reperfusion was determined as a percentage of the prearrest value. In protocol 2 hearts were perfused at 37°C with KHB containing colchicine (10⁻⁵ mol/L) for 60 minutes.

Results. There was spontaneous contractile recovery after 10 minutes of initial reperfusion in hearts from group TC as well as improved cardiac function after 15, 30, and 60 minutes of reperfusion compared with that in group C. Immunohistochemical staining and immunoblot analysis demonstrated microtubule depolymerization during hypothermic cardiac arrest and complete repolymerization after 10 minutes of reperfusion with warm buffers in both groups. Colchicine-induced microtubule depolymerization is associated with deterioration of cardiac function.

Conclusions. One mechanism responsible for improved cardiac function mediated by terminal warm blood cardioplegia is the restart of contraction after complete microtubule repolymerization.     

Aprotinin reduces injury of the spinal cord in transient ischemia

Objective: The protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit spinal cord ischemia model. Design: Randomized, controlled, prospective study. Setting: University research laboratory. Subjects: New Zealand white rabbits (36) of both sexes. Methods: In 24 animals, ischemia was induced with midline laparotomy and clamping the aorta just distal to left renal artery and proximal to aortic bifurcation for 20 min. Aprotinin was given 30 000 KIU as a short intravenous injection after anesthesia, and was followed by 10 000 KIU/h by continuous infusion in group 1 (n=12). Similar volume of saline solution was used in control group of animals (group 2, n=12). Group 3 of animals (sham group, n=12) were anesthetized and subjected to laparotomy without aortic occlusion. Physiological parameters and somatosensory evoked-potentials (SEP) were monitored in animals before ischemia, during ischemia and in the first 60 min of reperfusion. Their neurological outcome was clinically evaluated up to 48 h postischemia. Their motor function was scored, and the intergroup differences were compared. The animals were sacrificed after two days of postischemia. Their spinal cord, abdominal aorta, and its branches were processed for histopathological examination. Results: In group 3, SEP amplitudes did not change during the procedures, and all animals recovered without neurologic deficits. At the end of ischemic period, the average amplitude was reduced to 53±7% of the baseline in all ischemic animals. This was followed by a gradual return to 89±8 and 81±13% of the initial amplitude after 60 min of reperfusion in group 1 and group 2 correspondingly (P>0.05). The average motor function score was significantly higher in group 1 than group 2 at 24 and 48 h after the ischemic insult (P<0.05). Histological observations were clearly correlated with the neurological findings. Conclusion: The results suggest that aprotinin reduces spinal cord injury and preserves neurologic function in transient spinal cord ischemia in rabbits.     

Inflammatory response and myocardial injury following coronary artery bypass grafting with or without cardiopulmonary bypass

Objective: In coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) the inflammatory response is suggested to be minimized. Coronary anastomoses are performed during temporary coronary occlusion. Inflammatory response and myocardial ischaemia need to be studied in a randomized study comparing CABG in multivessel disease with versus without CPB. Methods: Following randomization 30 consecutive patients received CABG either with (n=16) or without CPB (n=14). Primary study endpoints were parameters of the inflammatory response (interleukin (IL)-6, interleukin-10, ICAM-1, P-selectin) and of myocardial injury (myoglobin, creatine kinase-MB (CK-MB), troponin I) (intraoperatively, 4, 8, 16, 24 and 48 h after surgery). The secondary endpoint was clinical outcome. Results: The incidence of major (death: CABG with CPB n=1, not significant (n.s.)) and minor adverse events (wound infection: with CPB n=2, without CPB n=1, n.s.; atrial fibrillation: with CPB n=3, without CPB n=2, n.s.) was comparable between both groups. The release of IL-6 was comparable during 8 h of observation (n.s.). Immediately postoperatively IL-10 levels were higher in the operated group with CPB (211.7±181.9 ng/ml) than in operated patients without CPB (104.6±40.3 ng/ml, P=0.0017). Thereafter no differences were found between both groups. A similar pattern of release was observed in serial measures of ICAM-1 and P-selectin, with no difference between both study groups (n.s.). Eight hours postoperatively the cumulative release of myoglobin was lower in operated patients without CPB (1829.7±1374.5 μg/l) than in operated patients with CPB (4469.8±4525.7 μg/l, P=0.0152). Troponin I release was 300.7±470.5 μg/l (48 h postoperatively) in patients without CPB and 552.9±527.8 μg/l (P=0.0213). CK-MB mass release was 323.5±221.2 μg/l (24 h postoperatively) in operated patients without CPB and 1030.4±1410.3 μg/l in operated patients with CPB (P=0.0003). Conclusions: This prospective randomized study suggests that in low-risk patients the impact of surgical access on inflammatory response may mimic the influence of long cross-clamp and perfusion times on inflammatory response. Our findings indicate that multiregional warm ischaemia, caused by snaring of the diseased coronary artery, causes considerably less myocardial injury than global cold ischaemia induced by cardioplegic cardiac arrest.     

Pulmonary preservation with Bretscheider''s HTK and Celsior solution in minipigs

Background: Pulmonary preservation with high potassium/low oncotic pressure Euro-Collins (EC) solution is associated with endothelial dysfunction and reduced surfactant function. We compared two low potassium solutions, histidine-tryptophane-ketoglutarate (HTK) and Celsior, to EC in lung ischemia-reperfusion injury. Methods: In 19 minipigs, the left lung was perfused in situ with cold preservation solution (EC, n=6; HTK, n=6; Celsior, n=7). Reperfusion was started after 90 min of warm ischemia. The right pulmonary artery and main bronchus were clamped. Bronchoalveolar lavage (BAL) was obtained before ischemia and after 2 h of reperfusion. Surfactant activity was determined from the BAL in a pulsating bubble surfactometer. Results: Animals in the EC group survived 3.7±1.4 h. Six Celsior and five HTK treated animals survived the observation period of 7 h (P<0.001). Compliance of the reperfused lung deteriorated less in both Celsior and HTK groups (P<0.001). In EC and HTK animals, the pO₂/FiO₂ ratio was lower (P=0.002), and pulmonary vascular resistance was higher (P=0.02) than in Celsior animals. Surfactant function was impaired after reperfusion in all groups. Conclusions: Compared to EC, HTK solution showed moderate and Celsior distinct improvement of post-ischemic pulmonary function. However, surfactant function was not well preserved in any group.     

Automatic connector devices for proximal anastomoses do not decrease embolic debris compared with conventional anastomoses in CABG

Objective: Emboli generated during cardiac surgery have been associated with aortic clamping and manipulation. Proximal anastomotic devices are thought to be less traumatic by eliminating partial clamping, potentially resulting in fewer adverse outcomes. Intra-aortic filtration has been shown to effectively capture particulate debris. We compared the amount of debris released using intra-aortic filtration and the clinical outcomes between conventionally handsewn and automated proximal anastomoses. Methods: Seventy-seven patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass were enrolled in a prospective randomized study. Patients were assigned to the anastomotic device Group I (Symmetry™ Aortic Connector, n=39) or the conventional handsewn anastomosis control Group II (n=38). Proximal anastomoses were performed before cardiopulmonary bypass in both groups. Intra-aortic Filter 1 (EMBOL-X^TM) was deployed prior to partial clamping or puncturing the aorta for device application and removed after the proximal anastomosis was completed. Prior to cross-clamp removal, a second filter was inserted (Filter 2). A core laboratory performed quantitative and histologic analyses of the debris captured. Clinical outcomes included adverse events, neurocognitive test scores, graft patency, and mortality. Results: Preoperative variables and risk factors were not significantly different between Groups I and II (EuroSCORE 3.9±2.6 vs. 4.2±2.5). Filter analyses showed no significant difference between Groups I and II in Filter 1 or 2 for either surface area of particles or total number of particles (P>0.05). There was a significant decrease between Filters 1 and 2 in both Groups for surface area of particles (Group I: 18.5±23.8 mm² vs. 10.7±16.3 mm², P=0.017; Group II: 15.0±15.4 mm² vs. 6.9±.6.5 mm², P=0.004), and for total number of particles in Group II (8.6±3.7 vs. 7.1±2.4, P=0.023). No significant differences were observed between Group I (device) and Group II (control) outcomes for myocardial infarction, neurocognitive deficit, stroke, length of stay, graft occlusion, or mortality. Conclusions: The application of proximal aortic connectors without partial clamping does not reduce particulate emboli or affect clinical outcomes compared with conventional anastomoses. Cross-clamping during cardiopulmonary bypass produces less particulate debris than conventional or automated proximal anastomoses performed off-pump, suggesting a major source of emboli is the anastomotic process.     

Myocardial protection in the neonatal heart. A comparison of topical hypothermia and crystalloid and blood cardioplegic solutions

Myocardial protection achieved during 2 hours of ischemic arrest was evaluated in 45 isolated, blood perfused, neonatal (1 to 5 days) piglet hearts. Comparisons were made among five methods of myocardial protection: Group I, topical cooling; Group II, hyperosmolar (450 mOsm) low-calcium (0.5 mmol/L) crystalloid cardioplegia; Group III, St. Thomas' Hospital cardioplegia; Group IV, cold blood cardioplegia with potassium (21 mmol/L), citrate-phosphate-dextrose (calcium level 0.6 mmol/L), and tromethamine; and Group V, cold blood cardioplegia with potassium alone (16 mmol/L) (calcium level 1.2 mmol/L). Hemodynamic recovery (percent of the preischemic stroke work) after 30 and 60 minutes of reperfusion was 82.9% and 86.7% in Group I, 35.7% (p less than 0.0001) and 43.7% (p less than 0.0001) in Group II, 76.1% and 77.7% in Group III, 67.4% (p less than 0.05) and 60.6% (p less than 0.05) in Group IV, and 110.7% and 100.6% in Group V. Conclusions: Topical cooling is an effective method of myocardial protection in the neonate. Cold blood cardioplegia with potassium alone and a normal calcium level provides optimal functional recovery. The improved protection obtained with both crystalloid and blood cardioplegia with normal calcium levels suggests an increased sensitivity of the neonatal heart to the calcium level of the cardioplegic solution.     

Warm reperfusion and myocardial protection

Background. The aim of this study was to determine whether warm reperfusion improves myocardial protection with cardiac troponin I as the criteria for evaluating the adequacy of myocardial protection.

Methods. One hundred five patients undergoing first-time elective coronary bypass surgery were randomized to one of three cardioplegic strategies of either (1) cold crystalloid cardioplegia followed by warm reperfusion, (2) cold blood cardioplegia followed by warm reperfusion, or (3) cold blood cardioplegia with no reperfusion.

Results. The total amount of cardiac troponin I released tended to be higher in the cold blood cardioplegia with no reperfusion group (3.9 ± 5.7 μg) than in the cold blood cardioplegia followed by warm reperfusion group (2.8 ± 2.7 μg) or the cold crystalloid cardioplegia followed by warm reperfusion group (2.8 ± 2.2 μg), but not significantly so. Cardiac troponin I concentration did not differ for any sample in any of the three groups.

Conclusions. Our study showed that the addition of warm reperfusion to cold blood cardioplegia offers no advantage in a low-risk patient group.     

The role of Na/H exchange in the efficacy of multidose hypothermic cardioplegia in immature rabbit hearts

Objectives: Recent studies have demonstrated that the use of a Na⁺/H⁺ exchange inhibitor as an additive can enhance the cardioprotective efficacy of cardioplegia in the adult heart under both normothermic and hypothermic conditions. However, few references are available as to the cardioprotective effect of acidic cardioplegia or Na⁺/H⁺ exchange inhibitors in the neonatal heart, particularly under hypothermic conditions. Methods and results: In isolated working hearts from rabbits aged 7–10 days, function was assessed prior to 10 h of ischemia (20 °C) and again after 35 min of reperfusion. All hearts received a pre-ischemic infusion (10 ml) of cardioplegic solution (20 °C) at pH 7.8, followed by nine subsequent infusions (5 ml every 1 h) of cardioplegic solution (20 °C) at pH 6.6, 7.0, 7.4, 7.8 (control) or 8.2 (n=8/group). When the pH was increased to 8.2, post-ischemic recovery of cardiac output was reduced and cumulative creatine kinase (CK) leakage during cardioplegic infusions was increased. In contrast, when the pH of the cardioplegic solution was lowered to 6.6, the post-ischemic recovery of cardiac output was maintained and CK leakage was reduced. Next, the effects of 5-(N,N-dimethyl)amiloride (DMA), an inhibitor of Na⁺/H⁺ exchange, were investigated. The inclusion of DMA in the pH 8.2 solution improved the post-ischemic recovery of cardiac output from 12.6±4.1% to 52.0±3.0% (P<0.0001) and reduced cumulative CK leakage during cardioplegic infusions from 38.0±4.0 to 26.1±3.7 IU/45 ml/g dry weight (P=0.044). In contrast, the inclusion of DMA in the pH 6.6 solution provided no added benefit. (Data are expressed as the mean±SEM.) Conclusions: These results suggest that the lesser efficacy of multidose hypothermic cardioplegia in the neonatal rabbit heart may depend on the pH of the cardioplegic solution and is likely to arise, at least in part, from activation of the Na⁺/H⁺ exchanger.     

温血停搏液术终灌注对缺血再灌注心肌的保护作用

利用猫体外循环模型观察含甘露醇的温血停搏液术终灌注对缺血再灌注心肌的保护作用。心肌缺血恢复正常血液灌注前，从主动脉根部以５～６ｋＰａ的压力注入３７℃含甘露醇的低钾温血停搏液５０ｍｌ。结果显示用含甘露醇的温血停搏液术终灌注可保护缺血后再灌注心肌的功能，提高心肌能量储备，降低线粒体丙二醛含量。结论：含甘露醇的温血停搏液术终灌注，可提高心肌对氧自由基的清除能力，减轻线粒体膜脂质过氧化，提高心肌能量储备，有利于再灌注后心肌功能的恢复     

Expression of Immediate Early Genes After Cardioplegic Arrest and Reperfusion

Background. Induction of protooncogenes such as c-fos, c-jun, and EGR-1 has been implicated in cellular growth and differentiation. Heat-shock proteins (HSPs) such as hsp 70 may mediate resistance to ischemia after heat shock and ischemic preconditioning. The effects of cardioplegia on the regulation of these immediate early genes are unclear.

Methods. Isolated rat hearts were subjected to different cold (5°C) or normothermic (35°C) cardioplegic solutions and reperfused with normothermic Krebs-Henseleit buffer. Right atrial biopsy specimens from patients undergoing coronary artery bypass grafting with cold cardioplegic arrest were taken before and after cardiopulmonary bypass. Analysis of immediate early gene messenger RNAs was performed using Northern blots. Related proteins were localized by immunohistochemistry.

Results. In rat hearts, cold cardioplegia for 40 minutes with Bretschneider or St. Thomas' II solution followed by 40 minutes' reperfusion resulted in a significant increase in left ventricular c-fos, EGR-1, and c-jun messenger RNA levels (4.0-, 3.1-, and 3.0-fold, respectively, with Bretschneider solution and 3.7-, 2.8-, and 2.1-fold, respectively, with St. Thomas' II solution) compared with control hearts perfused at 35°C with Krebs-Henseleit buffer. Normothermic cardioplegia with St. Thomas' II solution was without effect, whereas sequential perfusion with Krebs-Henseleit buffer at 5°C and 35°C resulted in a similar increase in protooncogene messenger RNA levels. Only cold Bretschneider solution was related to a 5.2-fold induction of hsp 70 messenger RNA levels. Likewise, rat atrial tissues and samples from patients after cardiopulmonary bypass displayed a significant induction of these immediate early genes. Monoclonal antibodies against c-FOS and HSP 70 proteins stained nuclei and perinuclear spaces of endothelial cells and cardiac myocytes.

Conclusions. Cold cardioplegic arrest and normothermic reperfusion are potent triggers for immediate early gene induction. Hypothermia emerged as the prime stimulus for the examined protooncogenes. In contrast, hsp 70 induction was dependent on the cardioplegic solution.     

Evaluation of myocardial protection by combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia in aorto-coronary bypass grafting.

The concept of pretreatment of the myocardium with a pharmacological agent protecting the cell against ischemic and reperfusion injury is very attractive. Lidoflazine, a calcium overload blocker, predominantly membrane stabilizing, is able to prevent cell damage during ischemic arrest and reperfusion. The purpose of this study was to determine whether the combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia can provide, in clinical practice, better myocardial protection in aorto-coronary bypass grafting than St. Thomas' Hospital cardioplegia alone. As indices for myocardial protection, recovery of cardiac function, enzyme release, and clinical outcome were registered. Ninety-three patients undergoing aorto-coronary bypass surgery were studied. These patients were randomized into two groups in a double blind fashion. Patients in group A (n = 48) received lidoflazine 1 mg/kg intravenously over a period of 20 min before initiation of cardiopulmonary bypass. Group B (n = 45) receiving placebo, acted as a control group. Myocardial protection consisted of intermittent infusion of cold 4 degrees C St. Thomas' Hospital cardioplegia, topical slush ice, and systemic hypothermia (28 degrees C rectal). No significant differences between the two groups were noted in terms of recovery of cardiac function, enzyme release, incidence of myocardial infarction, low cardiac output, rhythm, and conduction disturbances. In conclusion, our data suggest that the combination of intravenous pretreatment with lidoflazine and St. Thomas' Hospital cardioplegia did not provide significant additional myocardial protection in the clinical situation.     

Microwave and radiofrequency ablation yield similar success rates for treatment of chronic atrial fibrillation

Objective: To evaluate the influence of two different ablation devices (microwave AFx^® and radiofrequency Medtronic^®), designed to create linear lesion lines, with respect to efficacy and restoration of sinus rhythm (SR). Methods: Between February 2001 and December 2002, 42 patients with chronic, persistent atrial fibrillation (AF) >6 months were submitted to different combinations of valve surgery (mitral±tricuspid, n=30; mitral and aortic±tricuspid reconstruction, n=6; aortic±tricuspid, n=8) and concomitant Maze procedure. The biatrial Maze followed the concept of the Cox III procedure, using either microwave energy (AFx Lynx) (group I: age 65.8±11.9 years, mean duration of AF 61.9±28.9 months, n=23) or radiofrequency (Medtronic Cardioblate) (group II: age 64.1±11.1 years, mean duration of AF 53.5±49 months, n=19). Results: There was one death with group I (4%), due to liver failure. Both groups were comparable with regard to Euro Score, ejection fraction, cross clamp time, cardiopulmonary bypass time, ICU (median 1 day in both groups) and hospital stay, and type of indication. The preoperative diameter of the left atrium was 69.7±10.8 and 74.0±14.3 mm in groups I and II, respectively (P=0.359). The Maze procedure resulted in 23±2 and 17±1 min additional cross clamp time in groups I and II, respectively (P=0.013). At the 12-month follow up, freedom from AF was 81 and 80% in groups I and II, respectively. Twenty percent in group I and 21% in group II needed a pacemaker (PM), due to sick sinus syndrome (2 versus 2 cases), AV bloc (2 versus 1 case) and preoperative bradycardia (0 versus 1 case), respectively. Conclusions: The combination of complex valve surgery and Maze procedure was safe and reproducible. Following the Cox Maze III line concept, microwave and radiofrequency ablation gave similar results even in patients with more complex double or triple valve procedures.