Brain Damage and Myocardial Dysfunction: Protective Effects of Magnesium in the Newborn Pig

Background. Brain damage is associated with myocardial dysfunction resulting from excessive release of endogenous catecholamines and Ca²⁺ overload. Magnesium ion, a natural Ca²⁺ blocker, has recently been recognized as a myoprotective agent.

Methods. Myocardial function was assessed in 3- to 7-day-old piglets from pressure–volume data (obtained by the conductance catheter/micromanometer technique) before and for 4 hours after ligation of the aortic arch vessels and was correlated with ultrastructural changes. Group a (n = 6) received MgSO₄ immediately after induction of brain damage for 4 hours, whereas group b (n = 6) did not receive MgSO₄ and served as control.

Results. In both groups after induction of brain damage, there was a significant (p < 0.05) increase in end-systolic elastance and preload-recruitable stroke work that persisted for 1 hour. However, after 2 and 4 hours, there was a significant (p < 0.05) reduction in both variables in group b (end-systolic elastance, 74% ± 5% and 59% ± 6%, respectively, and preload-recruitable stroke work, 77% ± 4% and 64% ± 3%, respectively, compared with baseline), and in group a, the values returned to baseline. The chamber stiffness index rose significantly (p < 0.05) in group b 15 minutes after induction of brain damage and remained significantly (p < 0.05) higher for 4 hours versus no significant change in group a. Plasma levels of epinephrine and norepinephrine were similar in the groups before and after brain damage. Electron microscopic study showed severe ultrastructural changes in group b and significantly milder changes in group a.

Conclusions. We conclude that MgSO₄ may protect the neonatal myocardium when administered immediately after brain damage.     

Near-infrared monitoring of myocardial oxygenation during ischemic preconditioning

Background. Ischemic preconditioning has been advocated as a method of cardioprotection for minimally invasive direct coronary artery bypass. This study was performed to estimate the cardioprotective effect of ischemic preconditioning before ischemia by examining the changes in myocardial tissue oxygenation and also to examine whether adenosine triphosphate-sensitive potassium channel opener enhances the cardioprotective effect of ischemic preconditioning.

Methods. Myocardial ischemia was induced in three groups of 6 dogs by temporary occlusion of the left anterior descending coronary artery. Group 1 dogs received a 30-minute coronary occlusion and subsequent 3-hour reperfusion. Groups 2 and 3 dogs underwent three periods of 5-minute coronary occlusion and 5-minute reperfusion and then received 30-minute sustained ischemia and 3-hour reperfusion. In group 3, nicorandil was administered during the procedure. Myocardial oxygenation was measured using three-wavelength near-infrared spectroscopy. Myocardial blood flow was measured by the colored microsphere method.

Results. During ischemic preconditioning the myocardial tissue oxygen saturation decreased rapidly at coronary occlusion and increased at reperfusion. It was increased stepwise at the second and third coronary occlusion. Myocardial oxygen saturation during 30-minute sustained ischemia was significantly higher in groups 2 and 3 than in group 1 (p < 0.05). The myocardial tissue hemoglobin concentration showed similar changes to myocardial oxygen saturation. During 30-minute sustained ischemia, it was significantly higher in group 2 than in group 1 (p < 0.001), and it was significantly higher in group 3 than in groups 1 and 2 (p < 0.05). Regional myocardial blood flow showed no difference after 30 minutes of sustained ischemia among the three groups. Troponin-T levels were significantly lower in groups 2 and 3 than in group 1 (p < 0.01).

Conclusions. Ischemic preconditioning had beneficial effects on myocardial oxygenation during sustained ischemia, and the protected state of the myocardium could be monitored with the use of near-infrared spectroscopy. Ischemic preconditioning coupled with nicorandil administration might provide protection for minimally invasive direct coronary bypass.     

The Role of Platelet-Activating Factor in Regional Myocardial Ischemia-Reperfusion Injury

Background. This swine model was designed to elucidate the role of platelet-activating factor in regional myocardial ischemia-reperfusion injury.

Methods. In groups 1 and 2 (n = 12 each), the left anterior descending coronary artery was ligated for 60 minutes to induce regional myocardial ischemia followed by 6 hours of reperfusion. Group 1 received the platelet-activating factor antagonist TCV-309 before ischemia, whereas group 2 did not. Group 3 (n = 3) had a sham operation.

Results. Animals in group 2 exhibited significant (p < 0.05) hemodynamic instability and myocardial depression during the reperfusion period. Despite preventive measures, 7 of the 12 animals experienced severe dysrhythmias in the form of atrial and ventricular fibrillation leading to cardiac arrest. In contrast, animals in group 1 in whom the effects of platelet-activating factor were blocked by the specific platelet-activating factor receptor antagonist TCV-309 were hemodynamically stable and had significantly (p < 0.05) better myocardial function. This significant difference in global myocardial function between the groups was observed in the presence of similar morphologic findings and regional myocardial function.

Conclusions. These results suggest that platelet-activating factor has a definite influence on global myocardial dysfunction associated with regional myocardial ischemia-reperfusion injury.     

Excimer versus carbon dioxide transmyocardial laser revascularization: effects on regional left ventricular function and perfusion

Background. Transmyocardial laser revascularization (TMR) has been established with the carbon dioxide (CO₂) laser. The largely unstudied excimer laser creates channels through chemical bond dissociation instead of thermal ablation, thereby avoiding thermal injury. We sought to compare the effects of CO₂ and excimer TMR in a porcine model of chronic ischemia.

Methods. Pigs underwent ameroid constrictor placement on the circumflex artery to create chronic ischemia. TMR was performed with CO₂ (n = 8) or excimer (n = 8) laser 6 weeks later; controls (n = 7) had ameroid placement only. Regional myocardial blood flow (RMBF), determined by radioactive microspheres, and regional myocardial function, determined by percent segmental shortening (%SS), were assessed 18 weeks after ameroid placement.

Results. Values are mean ± SD. In the ischemic zone, RMBF (mL/min/g) was improved in the CO₂ (0.73 ± 0.19) and excimer (0.78 ± 0.22) groups when compared with controls (0.55% ± 0.12%, p < 0.05). %SS was also improved in the CO₂ (15.2% ± 5.5%) and excimer (15.3% ± 5.1%) groups when compared with controls (8.0% ± 4.2%, p < 0.05).

Conclusions. Excimer and CO₂ TMR significantly improve RMBF and regional function in this porcine model of chronic myocardial ischemia despite fundamentally different tissue interactions.     

Esmolol and cardiopulmonary bypass during reperfusion reduce myocardial infarct size in dogs

Background. Infarct size can be reduced by β-blockade in acute myocardial ischemia. However it is unknown whether myocardial salvage is still effective when β-blockade is limited to reperfusion.

Methods. After initiation of cardiopulmonary bypass, 20 dogs were submitted to 2 hours of regional left ventricular ischemia, followed by 2 hours of reperfusion. In 11 dogs β-blockade was started with the onset of reperfusion (esmolol group). The remaining dogs received no treatment (control, n = 9). Infarct size was determined by tetrazolium chloride staining. Myocardial water content (MWC) and ultrastructural damage (electronmicroscopy) were determined from transmural biopsies.

Results. Infarct size was significantly smaller in the esmolol group compared with control (49% versus 68%, p < 0.05). After 2 hours ischemia there was no difference in MWC between groups, whereas after 2 hours reperfusion MWC of ischemic myocardium was significantly lower in the esmolol group than in the control (p < 0.05). Ultrastructural changes were typical for ischemia-reperfusion injury in both groups.

Conclusions. β-Blockade may be cardioprotective during reperfusion through various mechanisms and may enhance myocardial salvage, even when treatment is initiated as late as with the onset of reperfusion.     

Transmyocardial laser revascularization: experimental studies in healthy porcine myocardium

Background. Clinical studies have demonstrated a significant reduction of cardiac index shortly after transmyocardial laser revascularization in patients with low ejection fraction. We analyzed the influence of transmyocardial laser revascularization on healthy myocardium in pigs.

Methods. Carbon dioxide channels were created in 20 pigs which were observed for 6 hours. Ten pigs received one laser channel and ten pigs two laser channels per cm² in the left anterior descending artery region. Seven pigs served as controls. Perfusion (microspheres), function, histochemical, and histologic assessments were subsequently performed.

Results. A significant deterioration of left ventricular stroke work index was observed shortly after transmyocardial laser revascularization in both laser groups (p < 0.05). After 6 hours the left ventricular stroke work index did not increase and showed significantly reduced values at rest (p < 0.05) and during stress in the laser groups (p < 0.01). Normal regional perfusion, small ischemic and necrotic areas, open laser channels in the left anterior descending artery region and significantly increased myocardial water content were observed in the laser groups (p < 0.01).

Conclusions. Carbon dioxide laser channels significantly decrease global heart function shortly after transmyocardial laser revascularization in healthy porcine myocardium. This myocardial tissue showed no recovery 6 hours postoperatively.     

Neovascularization after transmyocardial laser revascularization in a model of chronic ischemia

Background. The mechanism of clinical improvement after transmyocardial laser revascularization (TMR) is unknown. One hypothesis holds that TMR causes increased myocardial perfusion through neovascularization. This study sought to determine whether angiogenesis occurs after TMR in a porcine model of chronic myocardial ischemia.

Methods. Six miniature pigs underwent subtotal left circumflex coronary artery occlusion to reduce resting blood flow to 10% of baseline. After 2 weeks in the low-flow state, dobutamine stress echocardiography and positron emission tomography were performed to document ischemic, viable myocardium. The animals then underwent TMR and were sacrificed 6 months later for histologic and immunohistochemical analysis.

Results. Histologic analysis of the lased left circumflex region demonstrated many hypocellular areas filled with connective tissue representing remnant TMR channels. Histochemical staining demonstrated a highly disorganized pattern of neovascularization consistent with angiogenesis located predominantly at the periphery of the channels. Immunohistochemical analysis confirmed the presence of endothelial cells within neovessels. Vascular density analysis revealed a mean of 29.2 ± 3.6 neovessels per high-power field in lased ischemic myocardium versus 4.0 ± 0.3 (p < 0.001) in nonlased ischemic myocardium.

Conclusions. This study provides evidence that neovascularization is present long term in regions of ischemic, viable myocardium after TMR. Angiogenesis may represent the mechanism of clinical improvement after TMR.     

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.     

Myocardial metabolism and efficiency after warm continuous blood cardioplegia

Background. Warm continuous blood cardioplegia (WCBCP) has been recommended during prolonged cardiac arrest to minimize functional deterioration. Myocardial metabolism and efficiency after this cardioplegic modality are not well described.

Methods. Substrate oxidation, blood flow, and myocardial function were measured before, during, and after 3 hours of WCBCP in 7 pigs.

Results. Free fatty acid and glucose oxidation decreased by 60% ± 3.8% and 94% ± 1.2%, respectively, during cardioplegia (both p < 0.05) and increased to 62% ± 28% and 122% ± 62% of baseline during the early recovery phase (p < 0.05 for glucose). One hour after WCBCP oxidation rates were similar to baseline. The transient postcardioplegic increase in substrate oxidation was associated with a 43% ± 23% elevation of oxygen consumption (MVO₂) compared with baseline and a 62% ± 18% increase in myocardial blood flow. Cardiac output and mean arterial pressure did not change significantly after WCBCP, although myocardial function (stroke work, left ventricular end-systolic pressure, end-diastolic pressure, contractility, and efficiency) was depressed (p < 0.05). End-diastolic pressure and contractility improved from early to late phase of recovery, whereas the other indicators of ventricular function remained depressed.

Conclusions. Myocardial substrate oxidation was preserved after 3 hours of WCBCP, although ventricular function was moderately impaired. Thus, WCBCP with a seemingly normal substrate and oxygen supply was associated with a reduced cardiac efficiency.     

Intraaortic Balloon Counterpulsation Improves Right Ventricular Failure Resulting From Pressure Overload

Background. Right ventricular (RV) dysfunction is common after heart transplantation, and myocardial ischemia is considered to be a significant contributor. We studied whether intraaortic balloon counterpulsation would improve cardiac function using a model of acute RV pressure overload.

Methods. In 10 anesthetized sheep, RV failure was induced using a pulmonary artery constrictor. Baseline measurements included mean systemic blood pressure, RV peak systolic pressure, cardiac index, and RV ejection fraction. Myocardial and organ perfusion were measured using radioactive microspheres.

Results. After pulmonary artery constriction, there was an increase in RV peak systolic pressure (32 ± 2 to 60 ± 3 mm Hg; p < 0.01) and a decrease in mean systemic blood pressure (68 ± 4 to 49 ± 2 mm Hg; p < 0.01), RV ejection fraction (0.51 ± 0.04 to 0.16 ± 0.02; p < 0.01), and cardiac index (2.48 ± 0.04 to 1.02 ± 0.11; p < 0.01). Blood flow to the RV did not change significantly, but there was a significant reduction in blood flow to the left ventricle. The initiation of intraaortic balloon counterpulsation (1:1) using a 40-mL intraaortic balloon inserted through the left femoral artery resulted in an increase in mean systemic blood pressure (49 ± 2 to 61 ± 3 mm Hg; p < 0.01), cardiac index (1.02 ± 0.11 to 1.45 ± 0.14; p < 0.05), RV ejection fraction (0.16 ± 0.02 to 0.23 ± 0.02; p < 0.01), and blood flow to the left ventricle.

Conclusions. In a model of right heart failure, the institution of intraaortic balloon counterpulsation caused a significant improvement in cardiac function. Although RV ischemia was not demonstrated, the augmentation of left coronary artery blood flow by intraaortic balloon counterpulsation and subsequent improvement in left ventricular function suggest that left ventricular ischemia contributes to RV dysfunction, presumably through a ventricular interdependence mechanism. Therefore, study of the safety and efficacy of intraaortic balloon counterpulsation in the management of patients with acute right heart dysfunction is warranted.     

Antiinflammatory effects of colforsin daropate hydrochloride, a novel water-soluble forskolin derivative

Background. To evaluate the effects of colforsin daropate hydrochloride (colforsin), a water-soluble forskolin derivative, on hemodynamics and systemic inflammatory response after cardiopulmonary bypass, we conducted a prospective randomized study.

Methods. Twenty-nine patients undergoing coronary artery bypass grafting were randomized to receive either colforsin treatment (colforsin; N = 14) or no colforsin treatment (control; N = 15). Administration of colforsin (0.5 μg · kg⁻¹ · min⁻¹) was started after induction of anesthesia and was continued for 6 hours. Perioperative cytokine and cyclic adenosine monophosphate levels, hemodynamics, and respiratory function were measured serially.

Results. Marked positive inotropic and vasodilatory effects were observed in patients receiving colforsin. Interleukin 1β, interleukin 6, and interleukin 8 levels after cardiopulmonary bypass were significantly (p < 0.05) lower in the colforsin group. Plasma levels of cyclic adenosine monophosphate increased significantly (p < 0.05) in the colforsin group, and the levels correlated inversely (r = −0.56, p = 0.002) with the respiratory index after cardiopulmonary bypass.

Conclusions. Intraoperative administration of colforsin daropate hydrochloride had potent inotropic and vasodilatory activity and attenuated cytokine production and respiratory dysfunction after cardiopulmonary bypass. The results indicate that the technique can be a novel therapeutic strategy for the systemic inflammatory response associated with cardiopulmonary bypass.     

Screening Carotid Ultrasonography and Risk Factors for Stroke in Coronary Artery Surgery Patients

Background. The role of noninvasive carotid artery screening in relation to other clinical variables in identifying patients at increased risk of stroke after coronary artery bypass grafting was examined.

Methods. Preoperative, intraoperative, and postoperative clinical data were prospectively collected for 1,835 consecutive patients undergoing first-time isolated coronary artery bypass grafting between March 1990 and July 1995, 1,279 of whom had screening carotid ultrasonography. All patients with postoperative neurologic events were identified and reviewed in detail. Average patient age was 65.3 years (range, 33 to 92 years), and 9.3% (171 patients) had a prior permanent stroke or transient ischemic attack. Hospital and 30-day mortality was 2.2% (41 patients). Forty-five patients (2.5%) had a transient or permanent postoperative neurologic event. The data were analyzed by stepwise logistic regression to determine the independent predictors of both significant carotid stenosis and stroke.

Results. On multivariate analysis, the clinical predictors of significant carotid stenosis were age (p < 0.0001), diabetes (p = 0.0123), female sex (p = 0.0026), left main coronary stenosis greater than 60% (p < 0.0001), prior stroke or transient ischemic attack (p = 0.0008), peripheral vascular disease (p = 0.0001), prior vascular operation (p = 0.0068), and smoking (p < 0.0001). When all variables were evaluated for those patients who underwent noninvasive carotid artery screening, the independent predictors of postoperative neurologic event were prior stroke or transient ischemic attack (p < 0.0001), peripheral vascular disease (p = 0.0037), postinfarction angina pectoris (p = 0.0319), postoperative atrial fibrillation (p = 0.0014), carotid stenosis greater than 50% (p = 0.0029), cardiopulmonary bypass time (p = 0.0006), significant aortic atherosclerosis (p = 0.0054), postoperative amrinone or epinephrine use (p = 0.0054), and left ventricular ejection fraction less than 0.30 (p = 0.0744).

Conclusions. The etiology of postoperative stroke is multifactorial. Selective use of carotid ultrasonography is of value in identifying patients who are at greater risk of postoperative stroke independent of other variables and should be considered before coronary artery bypass grafting, particularly in patients with a history of neurologic event or peripheral vascular disease.     

Partial left ventriculectomy for idiopathic dilated cardiomyopathy: early results and six-month follow-up

Background. Recent reports show that partial left ventriculectomy improves hemodynamic and functional status in patients with dilated cardiomyopathy. This study sought to determine the effects of partial left ventriculectomy on clinical outcome and left ventricular function during 6-month follow-up.

Methods. Twenty-two patients underwent partial left ventriculectomy. Mitral valve repair was performed whenever possible, otherwise the valve was replaced. Hemodynamic and functional data were obtained at baseline, as well as 2 weeks and 6 months postoperatively.

Results. Overall, 7 of 22 patients died; there were three early and four late deaths. One-year survival was 68% ± 10%. Ejection fraction increased from 23.9% ± 6.8% before the operation to 40.7% ± 12.5% at 2 weeks and to 36.8% ± 7.7% at 6 months (p < 0.001, for both). The cardiac index before the operation, at 2 weeks, and at 6 months was 2.3 ± 0.8, 2.9 ± 0.6, and 3.4 ± 1.0 L/m² per minute, respectively (p = 0.035, and p = 0.009, compared with baseline). The increase in ejection fraction 2 weeks postoperatively was less in patients with left circumflex artery dominance (10.9% ± 3.2% compared with 19.9% ± 10.7%, respectively, p = 0.017). At 6-month follow up, all surviving patients except one improved New York Heart Association functional class when compared with preoperative status (from 3.8 ± 0.4 to 1.4 ± 0.6, p = 0.0002).

Conclusions. Early hemodynamic improvement after partial left ventriculectomy was maintained during midterm follow-up.     

Heat shock improves recovery and provides protection against global ischemia after hypothermic storage

Background. Improved methods of donor heart preparation before preservation could allow for prolonged storage and permit remote procurement of these organs. Previous studies have shown that overexpression of heat-shock protein 72 provides protection against ischemic cardiac damage. We sought to determine whether rats subjected to heat stress with only 6-hour recovery could acquire protection to a subsequent heart storage for 12 hours at 4°C.

Methods. Three groups of animals (n = 10 each) were studied: control, sham-treated, and heat-shocked rats (whole-body hyperthermia 42°C for 15 minutes). After 12-hour cold ischemia hearts were reperfused on a Langendorff column. To confirm any differences in functional recovery, hearts were then subjected to an additional 15-minute period of warm global ischemia after which function and lactate dehydrogenase enzyme leakage were measured.

Results. Heat-shocked animals showed marked improvements compared with controls in left ventricular developed pressure (63 ± 4 mm Hg versus 44 ± 4 mm Hg, p < 0.05) heart rate × developed pressure (13,883 ± 1,174 beats per minute × mm Hg versus 8,492 ± 1,564 beats per minute × mm Hg, p < 0.05), rate of ventricular pressure increase (1,912 ± 112 mm Hg/second versus 1,215 ± 162 mm Hg/second, p < 0.005), rate of ventricular pressure decrease (1,258 ± 89 mm Hg/second versus 774 ± 106 mm Hg/second, p < 0.005). Diastolic compliance and lactate dehydrogenase release were improved in heat-shocked animals compared with controls and sham-treated animals. Differences between heat-shocked animals and control or sham-treated animals were further increased after the additional 15-minute period of warm ischemia. Western blot experiments confirmed increased heat-shock protein 72 levels in heat-shocked animals (> threefold) compared with sham-treated animals and controls.

Conclusions. Heat shock 6 hours before heart removal resulted in marked expression of heat-shock protein 72 and protected isolated rat hearts by increased functional recovery and decreased cellular necrosis after 12-hour cold ischemia in a protocol mimicking that of heart preservation for transplantation. Protection was further confirmed after an additional 15-minute period of warm ischemia.     

Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation

Background. Reperfusion injury after pulmonary transplantation can contribute significantly to postoperative pulmonary dysfunction. We hypothesized that posttransplantation reperfusion injury would result in an increase in both in-hospital mortality and morbidity. We also hypothesized that the incidence of reperfusion injury would be dependent upon the cause of recipient lung disease and the interval of donor allograft ischemia.

Methods. We performed a retrospective study of all lung transplant recipients at our institution from June 1990 until June 1998. One hundred patients received 120 organs during this time period. We compared two groups of patients in this study: those experiencing a significant reperfusion injury (22%) and those who did not (78%).

Results. In-hospital mortality was significantly greater in patients experiencing reperfusion injury (40.9% versus 11.7%, p < 0.02). Posttransplantation reperfusion injury also resulted in prolonged ventilation (393.5 versus 56.8 hours, p < 0.001) and an increased length of stay in both the intensive care unit (22.2 versus 10.5 days, p < 0.01) and in the hospital (48.8 versus 25.6 days, p < 0.03). The incidence of reperfusion injury could not be attributed to length of donor organ ischemia (221.5 versus 252.9 minutes, p < 0.20). The clinical impact of reperfusion injury was significantly greater in patients undergoing transplantation for preexisting pulmonary hypertension (6/14) than those with chronic obstructive pulmonary disease or emphysema alone (6/54) (42.9% versus 11.1%, p < 0.012).

Conclusions. Clinically significant pulmonary reperfusion injury increased in-hospital mortality and morbidity resulting in prolonged ventilation, length of stay in the intensive care unit, and cost of hospitalization. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia but increased with the presence of preoperative pulmonary hypertension. These findings suggest that recipient pathophysiology and donor allograft quality may play important roles in determining the incidence of reperfusion injury.     

Coronary revascularization with or without cardiopulmonary bypass in patients with preoperative nondialysis-dependent renal insufficiency

Background. Preoperative renal insufficiency is a predictor of acute renal failure in patients undergoing conventional coronary artery bypass grafting. Off-pump coronary artery bypass operations have been shown to reduce renal dysfunction in patients with normal renal function, but the effect of this technique in patients with preoperative nondialysis-dependent renal insufficiency is unknown.

Methods. From June 1996 to December 1999, data of 3,250 consecutive patients undergoing coronary artery bypass grafting were prospectively entered into the Patient Analysis & Tracking Systems (PATS, Dendrite Clinical Systems, London, UK). Two hundred and fifty-three patients with preoperative serum creatinine more than 150 μmol/L were identified (202 patients on-pump, 51 patients off-pump), and clinical outcomes were analyzed. Serum creatinine and urea, in-hospital mortality, and morbidity were compared between groups. The association of perioperative factors with acute renal failure was investigated by multiple logistic regression analysis.

Results. Preoperative characteristics were similar between the groups. Mean number of grafts was 2.9 ± 0.8 and 2.3 ± 0.8 in the on-pump and off-pump groups, respectively (p < 0.0001). Comparison between groups showed a significantly higher incidence of stroke, inotropic requirement, blood loss, and transfusion of red packed cell and platelets in the on-pump group (all p < 0.05). Postoperative serum creatinine and urea were higher in the on-pump group with a significant difference at 12 hours postoperatively (p < 0.05). Logistic regression analysis identified cardiopulmonary bypass, serum creatinine level 60 hours postoperatively, inotropic requirement, need for intraaortic balloon pump, transfusion of red packed cell, and hours of ventilation as predictors of postoperative acute renal failure.

Conclusions. This study suggests that off-pump coronary artery bypass operations reduce in-hospital morbidity and the likelihood of acute renal failure in patients with preoperative nondialysis-dependent renal insufficiency undergoing myocardial revascularization.     

Intermittent Antegrade Tepid Versus Cold Blood Cardioplegia in Elective Myocardial Revascularization

Background. The ideal temperature for blood cardioplegia administration remains controversial.

Methods. Fifty-two patients who required elective myocardial revascularization were prospectively randomized to receive intermittent antegrade tepid (29°C; group T, 25 patients) or cold (4°C; group C, 27 patients) blood cardioplegia.

Results. The two cohorts were similar with respect to all preoperative and intraoperative variables. The mean septal temperature was higher in group T (T, 29.6° ± 1.1°C versus 17.5° ± 3.0°C; p < 0.0001). After reperfusion, group T exhibited significantly greater lactate and acid release despite similar levels of oxygen extraction (p < 0.05). The creatine kinase-MB isoenzyme release was significantly lower in group T (764 ± 89 versus 1,120 ± 141 U · h/L; p < 0.04). Hearts protected with tepid cardioplegia demonstrated significantly increased ejection fraction with volume loading, improvement in left ventricular function at 12 hours, and decreased need for postoperative inotropic support (p < 0.05). The frequency of ventricular defibrillation after cross-clamp removal was lower in this cohort (p < 0.05). There were no hospital deaths, and both groups had similar postoperative courses.

Conclusions. Intermittent antegrade tepid blood cardioplegia is a safe and efficacious method of myocardial protection and demonstrates advantages when compared with cold blood cardioplegia in elective myocardial revascularization.     

Effects of hyperoxia on neonatal myocardial energy status and response to global ischemia

Background. This study examines the effect of neonatal exposure to clinically relevant hyperoxia levels on both in vivo myocardial metabolism and the subsequent metabolic response to global ischemia.

Methods. Three-day-old pigs were ventilated to normoxia (80 mm Hg, 2 or 5 hours, N = 11), mild hyperoxia (250 mm Hg, 2 hours, N = 9), or severe hyperoxia (500 mm Hg, 5 hours, N = 14). Ventricular biopsies obtained at the end of the ventilation period, and at early and late ischemia were analyzed for ATP, ADP, AMP, creatine phosphate, glycogen, and lactate.

Results. Hyperoxia did not significantly alter in vivo metabolism. During early ischemia, hearts exposed to severe hyperoxia had better ATP and glycogen preservation (p < 0.003). These hearts exhibited almost complete (92%) creatine phosphate depletion, in contrast to incomplete creatine phosphate use in all other neonatal hearts, even in the face of 30% ATP reductions. However, hearts exposed to severe hyperoxia also had a higher incidence of fibrillation during ischemia, which accelerated ATP and glycogen degradation.

Conclusions. Although severe hyperoxia provided an energy-sparing effect during early ischemia, it also increased the incidence of ventricular fibrillation, which negated this beneficial effect.     

Noninvasive assessment of coronary flow reserve in the right gastroepiploic artery graft

Background. To investigate the functional capacity of the right gastroepiploic artery graft (GEA) and its ability to adapt to provide adequate flow at peak myocardial demand, we investigated the feasibility of determining coronary flow reserve (CFR) provided by this vessel using transabdominal color Doppler echocardiography and the correlation between this noninvasive determination of flow reserve and nuclear stress scintigraphy.

Methods. In 40 selected patients, who underwent complete arterial myocardial revascularization using the GEA and the internal thoracic arteries (ITAs), CFR of the GEA was measured at maximum coronary hyperemia induced by intravenous adenosine infusion, 7 months (range 3 to 20) after surgery. In the same period, in 31 of this group of patients, exercise thallium scintigraphy was performed.

Results. We succeeded in measuring CFR in 37 of 40 patients with values ranging from 1.1 to 3.6 with an average of 2.1 ± 0.7. During adenosine infusion, mean velocity in the GEA significantly increased from 48 ± 20 to 89 ± 41 cm/sec (p < 0.001), mean arterial blood pressure significantly decreased from 96 ± 11 to 87 ± 11 mm Hg (p < 0.001), and heart rate significantly increased from 74 ± 11 to 87 ± 15 beats/min (p < 0.001). In 8 of these 37 patients, the nuclear exercise test was positive (compatible with reversible ischemia in the distribution area of the GEA). Average CFR in these 8 patients with positive nuclear stress test was 1.46 ± 0.28 versus 2.27 ± 0.70 in those patients with a negative test (p < 0.001).

Conclusions. Noninvasive determination of CFR of GEAs is feasible, using transabdominal Doppler echocardiography. The present study shows that coronary vasodilator reserve and autoregulation is maintained in myocardium supplied by the GEA and that the CFR has a significant correlation with the results of noninvasive nuclear exercise testing. Therefore, noninvasive determination of CFR by transabdominal Doppler echocardiography might be a valuable contribution to functional assessment of GEAs.     

Functional comparison of transmyocardial revascularization by mechanical and laser means

Background. As a result of the clinical benefit observed in angina patients treated by transmyocardial revascularization (TMR) with a laser, interest in mechanical TMR has been renewed. Although the injury induced by mechanical TMR is similar to laser TMR, the resultant impact on myocardial contractility is unknown. The purpose of this study was to determine whether mechanical TMR improves ventricular function as compared with laser TMR in chronically ischemic myocardium.

Methods. After establishing an area of chronic myocardial ischemia, 25 domestic pigs were randomized to treatment by: excimer laser (group I), a hot needle (50°C) (group II), a normothermic needle (group III), an ultrasonic needle (40 KHz) (group IV), or no treatment (group V). All devices create a transmural channel of the same diameter; 22 ± 1 transmural channels were created in each animal. Regional myocardial contractility was assessed by measuring ventricular wall thickening at rest and with dobutamine stress echocardiography. Six weeks after revascularization, the animals were restudied at rest and with stress. Postsacrifice and histologic analysis of angiogenesis and TMR effects was then assessed.

Results. Laser TMR provided significant recovery of ischemic myocardial function. This improvement in contractility after laser TMR was a 75% increase over the baseline function of the ischemic zone (p < 0.01). Mechanical TMR provided no significant improvement in function posttreatment. In fact, TMR achieved with an ultrasonic needle demonstrated a 40% worsening of the contractility versus the pretreatment baseline (p < 0.05). Histologic analysis demonstrated a significant increase in new blood vessels in the ischemic zone after laser TMR, which was not demonstrated for any of the other groups (p < 0.05). Additionally, evaluation of the mechanical TMR channels demonstrated significant scarring, which correlated with the functional results.

Conclusions. Using devices to create an injury analogous to the laser, mechanical TMR failed to improve the function of chronically ischemic myocardium. Only laser TMR significantly improved myocardial function.