Hemodynamic effects of nitroglycerin in an experimental model of acute aortic regurgitation.

Afterload reduction is an accepted therapeutic modality for the treatment of congestive heart failure caused by chronic aortic regurgitation. However, the role of vasodilator therapy in acute aortic incompetence has not been established. To investigate this, left ventricular volume overload was produced in 18 dogs by constructing a valved conduit from the descending thoracic aorta to the left ventricular apex. The time course of aortic, pulmonary and conduit flows was analyzed in eight control studies and established stability of the experimental model. In the remaining 10 dogs, intravenous nitroglycerin, titrated to reduce mean aortic blood pressure by 40%, and placebo (ethanol) were each infused for 20 min periods. Compared with placebo, nitroglycerin significantly reduced aortic flow (3,945 +/- 324 to 3,397 +/- 362 ml/min, p less than 0.01), regurgitant flow (1,304 +/- 131 to 764 +/- 90 ml/min, p less than 0.001), septal-lateral end-diastolic diameter (47.5 +/- 1.8 to 46.5 +/- 1.8 mm, p less than 0.001), left ventricular end-diastolic pressure (6.9 +/- 0.8 to 6.0 +/- 0.6 mm Hg, p less than 0.05), left ventricular stroke work (19.0 +/- 2.6 to 10.8 +/- 1.7 g-m/beat, p less than 0.001) and systemic vascular resistance (2,253 +/- 173 to 1,433 +/- 117 dyne-s/cm5, p less than 0.001). In contrast, pulmonary flow, left anterior descending coronary flow and subendocardial pH did not change during infusion of either nitroglycerin or placebo. These data indicate that by decreasing preload and afterload, and by preserving coronary flow and tissue pH, nitroglycerin effectively reduced ventricular and regurgitant volumes in the setting of acute volume overload.(ABSTRACT TRUNCATED AT 250 WORDS)

Fate of mitral regurgitation following repair of atrioventricular septal defect.

The purpose of this study was to evaluate the fate of mitral regurgitation (MR) following repair of atrioventricular septal defects (AVSDs). Echocardiograms of all survivors of isolated AVSD surgery between 1986 and 1996, who had had > or =2 postoperative color Doppler studies (39 patients), were reviewed. On each study, MR severity was graded on a 1+ to 4+ scale, based upon the size of the MR jet. Median age at surgery was 9 months (range 3 to 169); median age at postoperative follow-up was 45 months (range 3 to 107). Mild deterioration of mitral valve function was fairly common. MR severity increased by > or =1 grade in 16 patients (41%) during the course of the study. However, the deterioration in mitral valve function occurred primarily during the early postoperative time intervals. After the initial 32 postoperative months, MR worsened on only 4 occasions and in each instance worsened by only 1 grade. Deterioration to 4+ MR occurred in only 3 patients, and was not observed after the initial 30 postoperative months. Survival curve analysis predicted a 90% probability of not having severe (4+) MR after 30 months (lower 95% confidence bound: 80%). Postoperative MR remains fairly stable following AVSD repair. Serious deterioration is rare, especially after the initial 30 postoperative months.

Intraoperative assessment of the physiologic significance of coronary stenosis in humans.

Coronary angiography is generally considered the gold standard in assessing the significance of coronary stenosis. The inadequacy of coronary angiography has frequently been demonstrated by intraoperative findings that differ from those projected by the catheterization report. To better assess the physiologic significance of coronary stenosis, we measured intramyocardial pH intraoperatively in 50 myocardial segments supplied by stenotic coronary arteries before and after revascularization in 42 patients undergoing coronary artery bypass grafting. The hemodynamic, electrocardiographic, and pH responses to atrial pacing were recorded intraoperatively before and after revascularization. The coronary angiograms, performed within 3 months before bypass grafting, were reviewed by a single independent observer. Preoperative and postoperative radionuclide ventriculograms were performed and also reviewed by an independent observer. In response to atrial pacing, a fall exceeding 0.02 pH units was considered to represent ischemia and was observed in 28 segments. Patients exhibiting this response comprised Group I. Twenty-two segments demonstrated a fall of less than 0.02 pH units or a rise in pH in response to atrial pacing. Patients having this response comprised Group II. Segments in Group I responded dramatically to revascularization, with the pH during atrial pacing rising from -0.09 +/- 0.01 to -0.02 +/- 0.01 (p less than 0.001). Nine patients demonstrated ischemic S-T changes during atrial pacing, all in Group I. Pre-pacing hemodynamic parameters were similar in both groups. Group I patients, however, demonstrated a significant fall in mean arterial pressure during atrial pacing, from 92.0 +/- 3.0 to 78.4 +/- 3.3 mm Hg (p less than 0.001) whereas Group II patients did not. Twelve segments that angiograms indicated were supplied by critically stenotic vessels (greater than 75%) failed to demonstrate a significant fall in their pH during atrial pacing. In these segments, intraoperative findings and postoperative results corroborated the metabolic findings. Coronary angiography, therefore, was only 45% specific in assessing physiologically significant obstructions. The degree of segmental wall motion abnormalities likewise correlated poorly with the pH changes. Unlike coronary angiography, the response of intramyocardial pH to pacing is an accurate metabolic tool to assess myocardial ischemia in humans.

The superiority of continuous cold blood cardioplegia in the metabolic protection of the hypertrophied human heart.

The effects of sanguineous and asanguineous cardioplegia on the generation of myocardial acid in the hypertrophied human heart during aortic clamping and reflow were elucidated by continuous intraoperative monitoring of myocardial pH in 42 patients undergoing valve replacement, with or without coronary bypass. The patients were divided into three groups: Group I (n = 14) received intermittent crystalloid cardioplegia; group II (n = 14) received intermittent blood cardioplegia; and group III (n = 14) received continuous blood cardioplegia. The groups were matched according to six previously elucidated determinants of myocardial acidosis. Measurements were made of myocardial pH, hydrogen ion concentration ([H+]), and the difference in pH units between myocardial pH and the pH of neutrality of water at the corresponding temperature (delta pHn). Throughout aortic clamping, myocardial pH in groups I and II fell significantly by 0.46 +/- 0.08 and 0.15 +/- 0.07 units, respectively (p less than 0.001) between the groups). In contrast, myocardial pH remained statistically unchanged throughout aortic clamping in group III (p less than 0.001 compared to groups I and II). Similar relationships were observed in [H+] and delta pHn during aortic clamping. During the early reflow, myocardial acidosis was observed in all three groups and delta pHn in group III increased from -0.26 +/- 0.10 at the end of aortic clamping to -0.57 +/- 0.07 during reperfusion (p less than 0.03). Patients in groups II and III required significantly less inotropic and mechanical cardiac support than patients in group I (p = 0.017). Hence, although continuous blood cardioplegia does not completely prevent acid accumulation during reflow, it provides better metabolic protection of the hypertrophied human heart than either intermittent crystalloid or intermittent blood cardioplegia.

Clinical benefits of endoscopic vein harvesting in patients with risk factors for saphenectomy wound infections undergoing coronary artery bypass grafting.

OBJECTIVE: The influence of endoscopic harvesting techniques on the prevalence of leg-wound complications after coronary artery bypass grafting remains to be defined for patients at high risk for the development of wound infections. METHODS: Among 1473 patients undergoing coronary artery bypass grafting who had the saphenous vein harvested by either a continuous incision or skip incisions leaving intact skin bridges, we determined the prevalence of wound infections to be 9.6%. The following variables were entered into logistic regression analysis to identify significant risk factors that might be predictive of wound infection: diabetes, peripheral vascular disease, obesity, renal failure, steroid use, age, sex, and type of closure. We then prospectively randomized 132 patients found to be at high risk of wound infection to either endoscopic vein harvesting or a continuous open incision. RESULTS: Univariate analysis showed female sex (P =.04), diabetes (P <.001), and obesity (P <.001) to be predictors of wound infection. In a multivariate model diabetes (P =.02) and obesity (P =.001) were independent predictors. In patients at high risk, the prevalence of wound infection was 4.5% for the endoscopic group versus 20% for the open group (P =.01). Vein procurement time was greater in the endoscopic group (65 minutes vs 32 minutes, P <.001), as was the number of vein repairs required (2.5 vs 0.6, P <.001). CONCLUSION: The use of endoscopic vein harvesting decreases the prevalence of postoperative leg-wound infections in high-risk patients with diabetes and obesity. Whether this translates into an economic benefit that justifies the additional cost of that technology requires further analysis.

Structural and metabolic correlates of cell injury in the hypertrophied myocardium during valve replacement.

To characterize the ultrastructural and metabolic changes occurring in the hypertrophied ventricle during cardiac operations in man, we studied 36 patients with valvular heart disease undergoing valve replacement, during which multiple doses of cold potassium cardioplegic solution were administered (Group I). Each patient had substantial ventricular hypertrophy according to measurements made of left ventricular mass, with a mean of 232.1 +/- 19.8 gm/m2 (normal: 92 +/- 16 gm/m2). Serial biopsy specimens were obtained from the left ventricular apex at the initiation of bypass, during the cross-clamp interval, and during reperfusion. Each specimen was scored from 0 to 4 according to ischemic changes in nuclear chromatin, mitochondrial swelling, myofibrillar edema, glycogen depletion, and overall cell morphology. Myocardial pH and temperature were measured continuously in the left ventricular free wall. During the cross-clamp period, ischemic injury was evidenced by changes in nuclear chromatin (0.38 +/- 0.10 to 1.25 +/- 0.21, p less than 0.0001), intracellular edema (0.43 +/- 0.06 to 0.97 +/- 0.14, p less than 0.002), overall cell morphology (0.37 +/- 0.06 to 0.97 +/- 0.14, p less than 0.001), and mitochondria (0.10 +/- 0.05 to 0.19 +/- 0.07, p less than 0.0001). During reperfusion, mitochondrial swelling increased further (0.19 +/- 0.07 to 0.35 +/- 0.08, p less than 0.0001) and glycogen stores were depleted (0.63 +/- 0.13 to 0.96 +/- 0.17, p less than 0.02), while the other structures remained unchanged. Myocardial pH declined during ischemic arrest from 6.89 +/- 0.04 to 6.40 +/- 0.04 (p less than 0.001). The changes in myocardial pH in Group I were compared to changes in myocardial pH in 10 patients (Group II) with no left ventricular hypertrophy undergoing isolated coronary bypass graft operations with the same protective techniques. In contrast to Group I, myocardial pH did not fall in Group II during ischemic arrest (6.98 +/- 0.06 to 6.94 +/- 0.05, p = not significant). Thus, with the use of current myocardial protective techniques, ultrastructural and metabolic changes indicative of ischemia are produced in the hypertrophied myocardium. The structural alterations consist of changes in nuclear chromatin and intracellular edema during the ischemic phase and by mitochondrial swelling during reperfusion.

Intrathoracic pressures and left ventricular configuration with respiratory maneuvers.

In 12 dogs, we examined the correspondence between esophageal (Pes) and pericardial pressures over the anterior, lateral, and inferior left ventricular (LV) surfaces. Pleural pressure was decreased by spontaneous inspiration, Mueller maneuver, and phrenic stimulation and increased by intermittent positive pressure ventilation (IPPV) and positive end-expiratory pressure (PEEP). To separate effects due to blood flow, we analyzed beating and nonbeating hearts. In beating hearts, there were no significant differences between changes in Pes and pericardial pressures. In arrested hearts, increasing LV pressure by 8 Torr increased pericardial pressures by only 3.6 Torr. With IPPV and PEEP, increases in Pes and pericardial pressures were equal in live hearts and in low-volume arrested hearts (LV pressure = 4 Torr). In high-volume arrested hearts (LV pressure = 12 Torr), the increase in pericardial pressure over the anterior LV surface was less than Pes, whereas that over the lateral and inferior LV surfaces was the same as Pes. At high LV volume, in arrested hearts pericardial pressures decreased less than Pes during negative pressure maneuvers. In another six dogs, external LV configuration and volume were measured. In beating hearts during spontaneous inspiration, Mueller maneuver, and phrenic stimulation (endotracheal tube open), septal-lateral dimension and LV volume decreased by approximately 3% (P less than 0.05). This was also true for PEEP. In arrested hearts, septal-lateral dimension and LV volume decreased only with PEEP. We conclude that 1) the relationship between Pes and pericardial pressures is complex and depends on LV volume, local pericardial compliance, and the means by which Pes is changed, 2) changes in measured pericardial pressures did not completely explain changes in LV configuration, and 3) during different respiratory maneuvers, different forces account for the same observed changes in LV volume and configuration.

Intermittent claudication. Current results of nonoperative management.

We reviewed the clinical course of 91 men with mild intermittent claudication who had been followed up for at least six months without operation. During 2.5 years' mean follow-up, 60% of the patients had more severe claudication. Actuarial analysis revealed an annual mortality of 4.5% and an annual operation rate of 9%. Historical factors, including age, race, smoking, exercise, diabetes, hypertension, and the ankle-brachial index (ABI), were analyzed to determine if these variables could predict clinical outcome. Only cigarette smoking, exercise, and the ABI were significant in this regard. Patients who had smoked at least 40 pack-years had an operation rate 3.3 times higher than those who smoked less. Major daily exercise was associated with stable claudication. The initial ABI did not correlate with clinical outcome. A subsequent decrease in the ABI of at least 0.15, however, was associated with an operation rate 2.5 times higher and a symptom progression rate 1.8 times higher than patients without this change in the ABI. When regression analysis was used, the preceding variables were only 63% to 79% accurate in predicting the clinical outcome of individual patients. Careful follow-up of patients with intermittent claudication is therefore recommended to allow timely operative intervention when required.

Intraoperative metabolic monitoring of the heart: II. Online measurement of myocardial tissue pH.

Under conditions of ischemia, the hydrogen ion [H+] accumulates in the myocardial tissue in proportion to the magnitude of the ischemic insult. The accumulation of [H+] is the result of both increased anaerobic production of [H+] secondary to decreased substrate and decreased washout of [H+] secondary to decreased coronary perfusion. The Khuri tissue pH electrode/monitoring system has been developed and validated over the past two decades. Its scientific basis and correlates have been established, and it is the only system that has been approved for use in humans. Myocardial tissue pH has been monitored in the anterior and posterior walls of the left ventricle in more than 700 patients undergoing major cardiac surgery. An understanding of the relationship between pH and temperature and between the pH and [H+] in tissues is important for the proper interpretation of the myocardial pH data generated in the course of an operation. Intraoperative monitoring of myocardial pH is the only modality available to the cardiac surgeon for online assessment and improvement of the adequacy of myocardial protection. By defining myocardial protection in terms of protection from myocardial tissue acidosis, this technology provides a new tool with which the comparative efficacy of the various myocardial protection techniques can be assessed. It also provides an online tool for assessing the adequacy of coronary revascularization, and has the potential of improving procedures and outcomes for off-pump coronary artery bypass grafting.

Repair of coarctation of the aorta during infancy minimizes the risk of late hypertension.

BACKGROUND: Recent surgical reports on coarctation of the aorta have primarily focused on the relative merits of various operative techniques. However, appropriate timing for elective repair remains unclear. METHODS: In a retrospective analysis we examined the surgical outcomes in 176 consecutive patients undergoing repair of coarctation of the aorta in our institution over a 25-year period. Ninety-nine percent of the patients had follow-up for a median of 7.5 years. RESULTS: A total of 13 patients have died (7.4% overall mortality). Nine of these patients had associated complex intracardiac anomalies. There was no mortality in the 113 patients with isolated coarctation. Residual or recurrent coarctation occurred in 27 patients (15.3%). The age at operation and the type of surgical repair did not have an effect on the incidence of recurrence. Persistent or late hypertension was identified in 18 of the 107 patients who have been followed up for more than 5 years (16.8%). A total of 48 patients operated on during infancy have been followed up for more than 5 years. Only 2 have developed late hypertension (4.2%). Both of these patients had recurrence. In contrast, 16 of the 59 patients operated on after a year of age had late hypertension (27.1%). CONCLUSIONS: To minimize the risk of persistent hypertension, elective repair of coarctation should be performed within the first year of life.

Use of an adjustable tourniquet to reverse cyanosis in the newborn pig.

BACKGROUND: Previous surgical models of cyanosis have been permanent. Because normal oxygenation was not restored in these models, it is unclear whether the metabolic changes produced by prolonged exposure to hypoxemia are irreversible. We therefore designed an experimental model of cyanosis that is reversible. METHODS: The left atrial appendage was anastomosed directly to the main pulmonary artery in 8 piglets, aged 2 to 4 weeks. RESULTS: The oxygen saturation fell from 95.3% +/- 0.8% to 72.4% +/- 3.9% (p < 0.001). A tourniquet was placed around the anastomosis to produce incremental changes in the level of cyanosis. Complete tourniquet occlusion resulted in obliteration of the right to left shunt, with return of systemic oxygen saturation to baseline levels. Systemic, left atrial, and pulmonary pressures did not change during the study. CONCLUSIONS: In this acute preparation, stable hemodynamic conditions were maintained despite substantial variations in systemic levels of oxygenation. Most important, this model allows reversal of cyanosis with the return of normal oxygenation. Application of this experimental design in a chronic model may help to determine whether the metabolic effects of prolonged hypoxemia are potentially reversible.

Placement of a permanent epicardial pacemaker in children using a subcostal approach.

BACKGROUND: Previously described techniques for epicardial pacemakers in children have generally included either a left thoracotomy approach or a subxiphoid incision. METHODS: We have recently used a single left subcostal incision for placement of both the epicardial electrodes and the pacemaker generator. We report our initial experience with this technique in 8 patients. The mean age was 4 years (range, 4 months to 12 years). The smallest patient weighed 4,100 g. RESULTS: The subcostal approach was successful in 7 patients. One patient with a narrow costal margin operated on early in our experience required conversion to a thoracotomy. The pacing thresholds were uniformly excellent in all patients. There have been no associated complications. CONCLUSIONS: Placement of epicardial leads using a left subcostal incision avoids a thoracotomy, is simpler than a subxiphoid approach, and results in acceptable thresholds with minimal morbidity.

Excision of a pulmonary valve abscess in a 61-year-old woman with single ventricle.

A 61-year-old woman with levo-transposition of the great arteries, double-inlet single left ventricle, and valvar and subvalvar pulmonary stenosis presented with a large pulmonary valve vegetation unresponsive to antibiotic therapy. The diagnostic evaluation and the surgical management are discussed. At operation the pulmonary valve was excised and an abscess cavity was obliterated with a pericardial patch. She is currently doing well 3 years after the operation.

Proper timing of blood cardioplegia in infant lambs: superiority of a multiple-dose regimen.

BACKGROUND: In the pediatric and infant age groups, it is unclear whether repeated infusions of blood cardioplegia solution during ischemic arrest are beneficial or detrimental when compared with a single-dose regimen. METHODS: Twenty lambs (aged 6 to 7 weeks) were placed on cardiopulmonary bypass. A miniature glass-tip electrode measured myocardial pH and hydrogen ion concentration, [H+], in the anterior wall. The aorta was clamped for 2 hours. Group S (n = 10) received a single dose of blood cardioplegia solution. Group M (n = 10) received multiple doses of blood cardioplegia solution at 20-minute intervals. RESULTS: The amount of [H+] generated during the cross-clamp period was greater in group S than in group M (39.2 +/- 10.1 nmol/L versus 0.4 +/- 1.4 nmol/L, p < 0.008). The percent increase in the time constant, tau, an index of diastolic relaxation, was more prolonged after cardiopulmonary bypass in group S when compared with group M (51.4% +/- 2.8% versus 6.4% +/- 3.0%, p < 0.0001). Similarly, the percent decrease in end systolic elastance, a measure of systolic contractility, was greater in group S after cardiopulmonary bypass when compared with group M (29.5% +/- 1.4% versus 7.3% +/- 1.3%, p < 0.0001). CONCLUSIONS: In this infant lamb model, multiple doses of blood cardioplegia solution provided superior metabolic preservation and hemodynamic support after 2 hours of aortic clamping when compared with a single-dose regimen.

Immediate-early gene expression in ovine brain after hypothermic circulatory arrest: effects of aptiganel.

BACKGROUND: Altered gene expression occurs in the brain after global ischemia. We have developed a model to examine the effects of cardiopulmonary bypass and hypothermic circulatory arrest (HCA) on the induction of the immediate-early gene c-fos in the brains of neonatal lambs. We then tested the effects of the noncompetitive N-methyl-D-aspartate antagonist, aptiganel hydrochloride (Cerestat), on c-fos expression and neuronal injury. METHODS: Neonatal lambs (weight, 4 to 6 kg) anesthetized with isoflurane were supported by cardiopulmonary bypass, subjected to 90 or 120 minutes of HCA at 15 degrees C, and rewarmed on bypass to 38 degrees C. One hour after cardiopulmonary bypass was terminated, the brains were perfusion fixed and removed for in situ hybridization and immunohistochemical analysis. Some animals survived 3 days before their brains were removed to examine for neuronal necrosis. One group of lambs (n = 20) received aptiganel (2.5 mg/kg). A second group (n = 25) received saline vehicle only. RESULTS: Increasing duration of HCA induced a corresponding increase in c-fos messenger RNA expression throughout the hippocampal formation and cortex. However, Fos protein synthesis peaked after 90 minutes of HCA and decreased significantly (p < 0.01) after 120 minutes of HCA. Aptiganel administration caused a significant decrease in (p < 0.001) c-fos messenger RNA expression and Fos protein synthesis after 90 minutes of HCA and preserved Fos protein synthesis after 120 minutes of HCA. Neuronal necrosis was observed in the brains of vehicle-treated lambs after 120 minutes of HCA but was significantly decreased (p < 0.05) in the lambs given aptiganel. CONCLUSIONS: These experiments indicate that the transcriptional processes of immediate-early genes remain intact, whereas translational processes are impaired after prolonged HCA. The inability to synthesize Fos proteins after 120 minutes of HCA was associated with neuronal degeneration. Aptiganel preserved translational processes and caused a significant improvement in the neurologic outcome.

Regional changes in myocardial acid production during ischemic arrest: a comparison of sanguineous and asanguineous cardioplegia.

Regional differences in myocardial acid production have not been characterized during administration of either asanguineous or sanguineous cardioplegia. To investigate this, miniature glass pH electrodes were placed in the right ventricular (RV) myocardium, the left ventricular subendocardial (LV endo) region, and the subepicardial (LV epi) region in a canine model. Multiple doses of either blood cardioplegia (Group 1; N = 11) or crystalloid cardioplegia (Group 2; N = 11) were administered during 4 hours of aortic cross-clamping. The accumulation of hydrogen ions during the cross-clamp period was greater in Group 2 than Group 1 in the LV endo region (629 +/- 79 nm/L versus 66 +/- 31 nm/L; p less than 0.001), the LV epi region (623 +/- 66 nm/L versus 72 +/- 32 nm/L; p less than 0.001), and the RV myocardium (814 +/- 296 nm/L versus 150 +/- 54 nm/L; p less than 0.05). Within each group, the time course of myocardial pH and the accumulation of hydrogen ions did not differ among the LV endo region, LV epi region, and the RV myocardium (p = not significant). These data indicate that transmural and interventricular differences in myocardial pH and hydrogen ion accumulation are not produced in the vented, arrested canine heart. In addition, when compared with asanguineous cardioplegia, blood cardioplegia globally and transmurally reduces acid accumulation during ischemic arrest.

The pathophysiology of free-fall injury.

The spectrum of injuries created by a free fall are governed by distinct physical properties, of which the height of the fall and the nature of the impacted surface are the most important factors. Other determinants include the victim's age and weight and the position at landing. Orthopedic injuries frequently are encountered in falls from two stories and less, and are largely determined by the position at landing. Visceral trauma, produced by deceleration forces, frequently involves the liver, spleen, lung, heart and aorta, and must be suspected in falls from three stories and more regardless of the landing position. Mortality from a six-story fall onto a hard surface such as concrete is almost 100% for adults, although considerably less for children. Falls onto softer surfaces, including water, are better tolerated. By appreciating the physical principles that dictate the type and degree of injury, one may correctly diagnose and manage free-fall injuries.

The effects of complement activation during cardiopulmonary bypass. Attenuation by hypothermia, heparin, and hemodilution.

Complement activation was examined prospectively in 100 cardiopulmonary bypass (CPB) patients. Plasma C3a desArg (C3a) increased (cannulation: 234 +/- 33 ng/mL; 20 minutes on CPB: 622 +/- 51; 2 hours after CPB: 1143 +/- 109, p less than 0.0001). C3a at 2 hours was higher in the 13 patients requiring mechanical ventilation for longer than 1 day (1023 +/- 274) than in the 67 without respiratory complication (568 +/- 45, p less than 0.004). Five more patients were studied for neutrophil activation to confirm that a biologic effect of complement activation occurs during CPB; in these five patients C3a increased to 317% of baseline after 10 minutes on CPB with a corresponding rise in neutrophil cell surface receptors for the complement opsonin C3b (as measured by indirect immunofluorescence) to 168% (p less than 0.05). Both increases were sustained at 30 minutes. Temperature, dilution, and heparin were studied as variables relevant to CPB. Exposure of normal neutrophils to C5a in vitro caused an increase in C3b receptors which was dependent on temperature (0 specific fluorescence at 0 C, 30 at 25 C, 180 at 30 C, and 275 at 37 C). Generation of C3a and C5a in normal serum by zymosan was also temperature-dependent (ng/mL C5a generated: 0.7 at 25 C, 200 at 30 C, and 897 at 37 C; ng/mL C3a generated: 546 at 25 C, 10,872 at 30 C, and 65,667 at 37 C). Serum dilution to 33% decreased ng/mL C5a generated in the same system from 200 to 76 with no effect on C3a. Addition of heparin to 20 U/mL decreased ng/mL C3a generated from 10,872 to 913 and C5a from 200 to 8. Thus, hypothermia, dilution, and heparin protect CPB patients from complement activation by reducing both generation of C3a/C5a and the subsequent cellular response of neutrophil activation.

Balloon angioplasty of native coarctation of the aorta in infants and neonates: is it worth the hassle?

Balloon angioplasty (BA) for native coarctation of the aorta (CA) in infants and neonates remains controversial with a high incidence of restenosis. The purpose of this study is to analyze our acute and midterm results for BA of native CA in infants and neonates and try to identify factors that may be predictive of outcome. Between September 1991 and June 1999, 17 patients with CA underwent BA at a median age of 3 months (range 2 weeks--9 months) and median weight of 4.8 kg (range 2.8--7 kg). Fourteen patients had discrete CA and 3 had tubular hypoplasia. All patients were hemodynamically stable prior to BA and no patients had critical coarctation requiring prostaglandin E(1) infusion to maintain ductus arteriosus patency. Seven patients had other associated cardiac defects. All patients had significant initial improvement. The mean peak systolic gradient across the CA improved from 43 +/- 15 mmHg to 10 +/- 8 mmHg (p < 0.001), and the mean minimum diameter of the aortic lumen increased from 2.4 +/- 0.9 mm to 5.2 +/- 1.0 mm (p < 0.001). There was no mortality or major complication. At median follow-up interval of 2.7 years (0.15-7.75 years), 10 (59%) of 17 patients are clinically well and have an upper to lower limb systolic blood pressure difference of <20 mmHg. Seven (41%) of 17 patients developed significant restenosis (5 of these patients underwent repeat BA, which was successful in 3 patients). Four (24%) patients underwent surgical repair at a median age of 4.5 months (3--6.9 months) and a median time interval of 4 months (2--6.5 months) from the initial BA. All 3 patients with tubular hypoplasia type of CA underwent surgical repair. No patients developed aortic aneurysm following initial or repeat BA. All patients who underwent surgical repair were 1 month or less in age at the time of their initial BA. We conclude that BA of native CA in infants and neonates can be performed safely with low mortality and morbidity. It appears to offer the best results in patients who are older than 1 month with discrete CA and a well-developed aortic arch. Further restenosis of the discrete CA can be managed successfully by repeat BA.

Restoration of the pulmonary valve reduces right ventricular volume overload after previous repair of tetralogy of Fallot.

BACKGROUND: Severe pulmonary regurgitation (PR) and associated right ventricular (RV) dilatation are late complications of surgical repair of tetralogy of Fallot (TOF). For the past several years, we have restored pulmonary valve competence with the exclusive use of cryopreserved allografts. METHODS AND RESULTS: Sixteen patients with symptoms of diminished exercise tolerance and echocardiographic evidence of progressive PR with severe RV dilatation underwent placement of allografts in the RV outflow tract at a median age of 12 years (10 years after TOF repair). Abnormal exercise tolerance tests were documented in 10 patients. Additional surgical procedures included pulmonary artery augmentation (n = 6), closure of residual left to right shunts (n = 3), and subendocardial resection for monomorphic ventricular tachycardia (n = 1). Six patients had either preoperative or postoperative balloon dilations of pulmonary artery stenoses. All patients had symptomatic improvement after allograft insertion. At a mean follow-up of 26.4 +/- 3.4 months, the severity of PR improved in all but one patient. In 12 patients (group 1), conduit regurgitation was either trace (n = 11) or mild (n = 1). Four patients (group 2) had moderate conduit regurgitation. In a retrospective analysis, pulmonary artery diameters and cross-sectional areas were significantly smaller in the group 2 patients compared with the group 1 patients. With the exception of one patient, RV end-diastolic diameter (RVEDD/BSA) fell after allograft insertion in each patient (P < .01). The reduction in RVEDD/BSA was significantly greater in group 1 than in group 2 (31.8 +/- 3.4% versus 21.4 +/- 11.0%, P < .05). CONCLUSIONS: Thus, restoration of the pulmonary valve with cryopreserved allografts improved exercise tolerance and diminished RV volume overload in patients with severe PR after previous repair of TOF. Optimal results were achieved in patients who did not have significant residual pulmonary artery distortion.