Steroid-eluting epicardial pacing leads in pediatric patients: encouraging early results.

OBJECTIVES: This study evaluated the pacing and sensing characteristics of a new porous-tipped steroid-eluting epicardial lead in a group of pediatric patients. BACKGROUND: Pacing in children may be complicated by small patient size, patient growth and the prevalence of structural congenital heart disease in children requiring pacing. Epicardial pacing has been associated with a high incidence of problems with sensing and capture, prompting the use of transvenous endocardial pacing when possible. In some children, epicardial pacing may still be desirable because of small patient size, potential for caval obstruction, previous cardiac surgery limiting transvenous access to the heart, or the need to repair congenital heart disease at the time of pacemaker insertion. METHODS: Twelve patients aged 3 weeks to 18 years underwent placement of 23 epicardial pacing leads (8 atrial, 15 ventricular). Pulse width thresholds, sensing thresholds and lead impedance were measured weekly for 6 weeks, then at 3, 6, 12 and 18 months after pacemaker implantation. The median duration of follow-up was 12 months. RESULTS: Ventricular pulse width thresholds did not change over time, whereas atrial pulse width thresholds improved significantly. At 6 months, the mean pulse width threshold at 2.5 V for the atrial and ventricular leads was 0.10 +/- 0.03 and 0.19 +/- 0.09 ms, respectively. The thresholds were slightly lower at 12 and 18 months. At the most recent follow-up, all atrial leads sensed appropriately at 2.5 mV and all ventricular leads at 5 mV. CONCLUSIONS: These encouraging early results suggest that steroid-eluting epicardial pacing leads may be an attractive option for children needing epicardial pacing. Their excellent pacing and sensing characteristics may allow reliable dual-chamber pacing in infants who are too small for transvenous pacing.

Absence of left ventricular volume loading in infants with coarctation of the aorta and a large ventricular septal defect.

Clinical characteristics and angiographic ventricular volume data were obtained in 25 infants aged 1 to 66 days who presented with coarctation of the aorta, ventricular septal defect and congestive heart failure to determine if left ventricular volume loading was present and if there were hemodynamic or volumetric variables that were predictive of operative mortality in this group. Pulmonary to systemic flow ratio averaged 2.8 +/- 0.8 and right ventricular/left ventricular peak pressure ratio was 0.96 +/- 0.12. Left ventricular end-diastolic volume averaged 116 +/- 49% of normal and was less than the investigators' lower limit of normal in 5 (20%) of 25 patients. In contrast, right ventricular end-diastolic volume, measured in eight patients, averaged 173 +/- 47% of normal and was greater than the investigators' upper limit of normal in seven (88%) of eight. Left ventricular ejection fraction averaged 0.47 +/- 0.17 and was below normal (less than 0.55) in 14 (58%) of 24 patients. Preoperative volume and ejection fraction data did not differ in infants with coarctation plus ventricular septal defect and a similar group of 19 infants with isolated coarctation. Abnormal left ventricular operative volume distensibility was inferred by normal or decreased left ventricular end-diastolic volume and increased left ventricular end-diastolic pressure (greater than 12 mm Hg) in 12 (55%) of 24 patients. Early plus late mortality was related to left ventricular size: 3 of 5 patients with a small left ventricular end-diastolic volume died, compared with only 4 of 20 with a normal or increased volume (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative right and left ventricular volumes and pump function in the newborn lamb.

A quantitative cineangiographic method is presented for studying neonatal lamb ventricular volumes and pump function without thoracotomy or surgical instrumentation of the heart. When this method was employed in lambs with a mean age of 24.4 hours it was found that the right and left ventricular end-diastolic volumes, ejection fractions and systolic outputs did not differ significantly at this early postnatal time. Restudy of these lambs at a mean age of 15.6 days showed that right and left ventricular end-diastolic volumes, normalized for body weight, and ejection fractions had not changed significantly. Although systolic outputs decreased, the difference was not significant. Thus there is early postnatal equalization of left and right heart volumes, and deviations from this relation should suggest abnormal hemodynamic function.

Operative repair of coarctation of the aorta in infancy: results with and without ventricular septal defect.

Coarctation of the aorta (CA) presenting in infancy is a life-threatening condition, especially if associated with intracardiac left-to-right shunts. Between 1971 and 1980, 51 infants with symptomatic CA have been diagnosed and treated. Ventricular septal defect (VSD) was present in 18 patients and patent ductus arteriosus in 24. End-to-end repair was performed in 20 patients, 17 (85%) of whom were long-term survivors. Subclavian flap angioplasty repair was used in 28 patients, of whom 25 (89%) were long-term survivors. During long-term follow-up 6 patients (35%) who underwent end-to-end repair had recurrent CA, whereas only 3 patients (12%) who underwent subclavian flap angioplasty had recurrent CA (p less than 0.05). The mortality rate in patients with associated VSD was higher (4 of 18, 22%). Pulmonary trunk banding with subsequent VSD repair was associated with a better survival (13 of 14 patients, 90%) than when banding was not performed (2 of 5 patients) (p less than 0.05). These results suggest subclavian flap angioplasty is the preferred treatment for symptomatic CA occurring in infancy. Concomitant pulmonary trunk banding in patients with VSD can be performed with the expectation of a lower mortality at subsequent VSD repair.

Congenital ostial stenosis of the right coronary artery repaired by vein patch angioplasty.

A case of congenital ostial stenosis of the right coronary artery is presented in which revascularization was performed by saphenous vein patch angioplasty.

Similar neurobehavioral outcome after valve or coronary artery operations despite differing carotid embolic counts.

OBJECTIVES: The interrelationships among coronary and valvular operations, microemboli, and neurobehavioral outcome are unclear. We hypothesized that adult patients undergoing cardiac valve operations would have more total emboli delivered to the brain than patients undergoing coronary artery bypass grafting and that this would associate with worse neurobehavioral outcomes. METHODS: One hundred ninety-three patients undergoing coronary artery bypass grafting and 73 patients undergoing cardiac valve operations were compared. Patients received neurologic, neuro-ophthalmologic, and 11 standardized neurobehavioral tests preoperatively and 5 to 7 days, 1 month, and 6 months postoperatively. Left common carotid Doppler ultrasonographic embolus detection was performed intraoperatively. Repeated measures and logistic regression analyses of outcome were performed. RESULTS: Patients undergoing either coronary or valve operations were well matched by age (61 +/- 10 and 59 +/- 12 years, respectively), but a significantly greater fraction of patients undergoing valve operations were female, diabetic, or had undergone previous cardiac operations. Neurobehavioral scores of patients undergoing either coronary artery bypass grafting or cardiac valve operations did not differ significantly at any time. Total embolus counts differed significantly: the median was 105 during coronary artery bypass grafting and 479 during cardiac valve operations (geometric means of 104 and 412, respectively; P =.0001). Significantly more emboli were detected in the patients undergoing cardiac valve operations after removal of the left ventricular vent and after separation from cardiopulmonary bypass, but comparable numbers of emboli were seen in the 2 groups before cardiopulmonary bypass. In both groups decreased neurobehavioral performance was apparent at 5 to 7 days, with improvement at 1 and 6 months. Increasing numbers of carotid emboli significantly associated with worse performance on the letter cancellation test. There were no significant differences between patients undergoing valve and coronary operations in neurobehavioral outcomes, strokes, transient ischemic attacks, or deaths. CONCLUSIONS: The significantly greater number of emboli in the group of patients undergoing cardiac valve operations is likely the result of the entrainment of intracardiac air. The greater numbers of emboli during cardiac valve operations do not appear associated with a commensurately greater risk of adverse neurologic or neurobehavioral outcome.

Response of the hypertrophied left ventricle to global ischemia. Comparison of hyperkalemic cardioplegic solution with and without verapamil.

The hypertrophied left ventricle is at considerably greater risk for injury when subjected to global ischemia than is an otherwise normal heart. We evaluated the efficacy of verapamil, a calcium-channel blocking agent, as an adjunct to standard crystalloid cardioplegic solution in animals with left ventricular hypertrophy subjected to myocardial ischemia during cardiopulmonary bypass. Infracoronary aortic stenosis was produced in 15 mongrel puppies by plication of the noncoronary cusp of the aortic valve. Studies were conducted 3 to 4 months later. Left ventricular catheter-tip pressure transducers and major and minor axis ultrasonic dimension crystals were inserted, and the animals were then supported by cardiopulmonary bypass with 30 minutes of normothermic ischemia. Animals were randomized to receive either standard hyperkalemic crystalloid cardioplegic solution (n = 8) or the same solution with verapamil, 0.1 mg/kg (n = 7). After the 30 minutes of ischemia, the animals were supported on cardiopulmonary bypass for an additional 30 minutes and then separated from bypass. They were then studied for another 2 hours by measurement of myocardial adenosine triphosphate content, myocardial blood flow, systolic function with use of the end-systolic pressure/volume ratio, and compliance with use of the natural strain coefficient of the minor axis at 15 mm Hg end-diastolic pressure. There was a better recovery of systolic function in the animals treated with verapamil (89.2% versus 63.3%). The compliance as measured with use of the minor axis natural strain coefficient returned essentially to baseline in the group of animals treated with verapamil (0.236 +/- 0.038 before ischemia and 0.254 +/- 0.043 2 hours after ischemia), but it fell markedly in the control animals (0.219 +/- 0.027 before ischemia and 0.153 +/- 0.016 2 hours after ischemia). Myocardial adenosine triphosphate levels were not significantly different at any time during the study. Likewise, myocardial blood flow was not significantly different between groups. We conclude that the addition of verapamil to hyperkalemic cardioplegic solution improves recovery of both systolic and diastolic function after global ischemia in dogs with left ventricular hypertrophy resulting from aortic stenosis. The precise mechanism for this is unknown.

The effect of positive end-expiratory pressure on regional ventilation and perfusion in the normal and injured primate lung.

Although positive end-expiratory pressure (PEEP) is being employed in the management of respiratory insufficiency, many of its physiological effects remain undetermined. The cardiopulmonary effects of PEEP as well as its effect on regional ventilation and perfusion were studied in 10 baboons before and after pulmonary injury with oleic acid. In the normal lung, there was significant improvement in oxygenation at a PEEP of 5 cm. of water secondary to improved ventilation and perfusion in all PEEP greater than 5 cm. of water produced increasing mismatch of ventilation and perfusion in all zones. After oleic acid was injected, hypoxemia was evident with a reversal of the normal ventilation-perfusion (V/Q) relationship between upper and lower lung zones. This mismatch of ventilation and perfusion was corrected at a PEEP of 15 cm. of water. It was reasonable to conclude that the use of PEEP in the injured lung exerts it beneficial effect by balancing regional ventilation and perfusion in addition to increasing functional residual capacity.

Global ischemia in the immature canine ventricle. Enhanced protective effect of verapamil and potassium.

The efficacy of the addition of verapamil to a cardioplegic solution was evaluated in immature canine hearts subjected to normothermic global ischemia. Two groups of mongrel puppies less than 10 weeks old were subjected to 30 minutes of global myocardial ischemia while on cardiopulmonary bypass. One group (Group K) was arrested with cardioplegic solution containing 20 mEq/L of KCl; the other group (Group K + V) was arrested with the same solution containing 0.2 mg/kg of verapamil. Ultrasonic crystals were placed for measurement of left ventricular dimensions, and micromanometers measured left ventricular pressures. Functional measurements included left ventricular strain, first derivative of left ventricular pressure (dP/dt), and the end-systolic pressure/volume ratio (Emax). Metabolic recovery was assessed by measuring myocardial adenosine triphosphate (ATP) content. Ninety minutes following ischemia, Group K + V exhibited greater minor axis strain at a left ventricular end-diastolic pressure of 15 and 20 mm Hg (p less than 0.05), greater dP/dt (p less than 0.05 to 0.001), and greater Emax (p less than 0.05) than Group K. ATP content in Group K + V was greater at 60 minutes (Group K + V: 12.74 +/- 1.60 mumol/gm; Group K: 8.39 +/- 1.30, p less than 0.05) and 90 minutes (Group K + V: 10.34 +/- 0.46; Group K: 7.55 +/- 1.42, p less than 0.05) after ischemia. The addition of verapamil to a cardioplegic solution containing potassium enhances the recovery of function and high-energy phosphate stores in the immature myocardium following normothermic global ischemia.

Repair of atrioventricular canal malformation in the first year of life.

Disappointing results with pulmonary artery banding and subsequent correction led to the decision in 1977 that all infants presenting to our hospital with atrioventricular (AV) canal and evidence of severe heart failure, lack of growth, or pulmonary hypertension should have early operative correction. Since that time 24 consecutive infants have undergone repair. All had refractory heart failure. Average age at operation was 18 weeks (3 to 38) and average weight was 4.3 kg (2.3 to 6.4). Only four patients were older than 6 months of age at operation. Preoperative peak pulmonary artery pressure was 81 +/- 3.3 mm Hg, which was equal to systemic arterial pressure in all cases. Mean pulmonary-to-systemic resistance ratio was 0.28 +/- 0.05. five patients had moderate mitral regurgitation and five had a ductus arteriosus. Three had significant associated malformations. Profound hypothermia and circulatory arrest were utilized in all patients. Common AV valve tissue was divided and valvular integrity was ensured by resuspension to a single Dacron patch which closed both the atrial and ventricular defects. Operative death occurred in two patients (8%) both with associated defects (one with total anomalous pulmonary venous connection and the other with coarctation). One late death occurred in a patient with associated partial anomalous pulmonary venous connection, and one patient has had a pacemaker implanted. Survivors have been followed for 7 to 60 months. All patients are growing at an increased rate postoperatively. All cardiac medications have been discontinued in 16 of 21 patients. Operative repair of complete atrioventricular canal can be performed in infancy with low operative and late death rates and will relieve signs and symptoms of heart failure and allow more normal growth and development. On the basis of this experience, it appears unnecessary to delay operative correction with the known increased risk of the development of pulmonary hypertension.

Hypoplasia of the systemic ventricle in congenitally corrected transposition of the great arteries: preoperative documentation and possible implications of operation.

This article describes the determination of small systemic ventricular volume by quantitative cineangiocardiography in two patients with congenitally corrected transposition of great arteries, Ebstein's malformation of the systemic atrioventricular valve, and ventricular septal defect. A subjectively small systemic ventricle and an Ebstein-like abnormality of the systemic atrioventricular valve have been described previously in association with congenitally corrected transposition, but in vivo quantification of ventricular size and pump function has not been reported. An initial palliative rather than a totally corrective procedure is probably desirable in patients with this combination of findings. Ventricular volume calculations may prove useful as an aid in selection of operation in this setting.

Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction.

This study tested the hypothesis that enhancement of blood cardioplegia with the nitric oxide donor agent SPM-5185 inhibits postischemic left ventricular and coronary endothelial dysfunction. Eighteen anesthetized dogs supported by total vented bypass were subjected to 30 minutes of normothermic ischemia followed by 4 degrees C multidose blood cardioplegia. Hearts received either standard blood cardioplegia (vehicle group; n = 6), blood cardioplegia with 1 mumol/L SPM-5185 (low-dose group; n = 6), or 10 mumol/L SPM-5185 (high-dose group; n = 6). After 60 minutes of cardioplegic arrest, the heart was reperfused for a total of 60 minutes, first in the beating empty state for 30 minutes and then after discontinuation of bypass for 30 minutes. Baseline and postischemic left ventricular function was assessed by the slope of the end-systolic pressure-volume (impedance catheter) relation. Postischemic end-systolic pressure-volume relation was depressed by 53.7% of preischemic values in the vehicle group (from 8.2 +/- 1.0 to 3.8 +/- 0.3 mm Hg/ml) and by 33.7% (from 9.2 +/- 1.1 to 6.1 +/- 0.5 mm Hg/ml) in the low-dose group. In contrast, there was complete postischemic functional recovery in the high-dose group (from 7.6 +/- 1.1 to 7.2 +/- 1.2 mm Hg/ml). In coronary arteries isolated from these hearts, endothelium-dependent maximal relaxation to acetylcholine was impaired by 27% in the vehicle group and by 18% in the low-dose group, whereas the high-dose group showed complete endothelium-dependent relaxation. Myeloperoxidase activity, an index of neutrophil accumulation in postischemic myocardium, was elevated in the vehicle and low-dose groups (3.36 +/- 0.58 and 2.56 +/- 0.68 U/100 mg tissue) but was significantly reduced in the high-dose group to 1.27 +/- 0.45 U/100 mg tissue. We conclude that inclusion of 10 mumol/L nitric oxide donor SPM-5185 in blood cardioplegia improves postischemic ventricular performance and endothelial function in ischemically injured hearts, possibly via inhibition of neutrophil-mediated damage.

Extrapulmonary thoracic disease caused by Blastomyces dermatitidis.

A case of blastomycosis is reported involving the mediastinum and compromising the plexus brachialis. The pathology, pathophysiology, and treatment of this patient and of a previously reported patient are discussed and compared with the characteristics of extrapulmonary thoracic disease caused by histoplasmosis. Because of the favorable response of these patients to prolonged antifungal therapy, blastomycosis should be considered in the differential diagnosis of invasive extrapulmonary thoracic disease.

Effectiveness of the Cobra aortic catheter for dual-temperature management during adult cardiac surgery.

OBJECTIVES: In animals the Cardeon Cobra catheter (Cardeon Corp, Cupertino, Calif) allows independent control of aortic arch and descending aortic temperatures and profoundly reduces cerebral embolization during bypass. This investigation describes the first clinical use of the device during adult cardiac surgery. The purpose of the study was to confirm that the Cobra catheter delivers adequate cerebral and systemic perfusion while providing simultaneous cerebral hypothermia and systemic normothermia during cardiopulmonary bypass. METHODS: In a prospective multicenter study the Cobra aortic catheter was placed in 20 adults undergoing cardiopulmonary bypass. Arch and corporeal temperatures, bypass flows, and arterial blood pressures were recorded intraoperatively. Jugular bulb and mixed venous oxygen saturation was used to assess the adequacy of cerebral and systemic perfusion. RESULTS: Surgeons at 3 institutions placed the Cobra catheter in patients undergoing coronary artery bypass grafting (n = 13), valve (n = 3), and combined valve-bypass (n = 4) operations. Mean total bypass flows of 2.1 +/- 0.2 L x min(-1) x m(-2) maintained mean arterial pressures in arch and descending aortic circulations of greater than 55 mm Hg. A mean differential of 4.3 degrees C between arch and descending aortic temperatures was established before crossclamp application, and a mean maximum temperature differential of 7 degrees C was established during bypass. A 2.4 degrees C temperature differential was maintained at crossclamp removal. Cerebral and systemic venous oxygen saturation remained greater than 65% during bypass. CONCLUSIONS: The Cobra device met all expectations for an arterial cannula with adequate perfusion to the arch and corporeal circulations. Dual perfusion with the Cobra catheter allows for independent temperature control during cardiopulmonary bypass with simultaneous cerebral hypothermia and systemic normothermia.

Supplemental L-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury.

Unenhanced hypothermic cardioplegia does not prevent postischemic endothelial and contractile dysfunction in hearts subjected to antecedent regional or global ischemia. This study tested the hypothesis that supplementing blood cardioplegic solution and reperfusion with the nitric oxide precursor L-arginine would preserve endothelial function, reduce infarct size, and reverse postcardioplegia regional contractile dysfunction by the L-arginine-nitric oxide pathway. In 23 anesthetized dogs, the left anterior descending coronary artery was ligated for 90 minutes, after which total bypass was established for surgical "revascularization." In 10 dogs, unsupplemented multidose hypothermic blood cardioplegic solution was administered for a total of 60 minutes of cardioplegic arrest. In eight dogs, L-arginine was given intravenously (4 mg/kg per minute) and in blood cardioplegic solution (10 mmol) during arrest. In five dogs, the nitric oxide synthesis blocker N omega-nitro-L-arginine (1 mmol) was used to block the L-arginine-nitric oxide pathway during cardioplegia and reperfusion. Infarct size (triphenyltetrazolium chloride) as percent of the area at risk was significantly reduced by L-arginine compared with blood cardioplegic solution (28.2% +/- 4.1% versus 40.5% +/- 3.5%) and was reversed by N omega-nitro-L-arginine to 68.9% +/- 3.0% (p < 0.05). Postischemic regional segmental work in millimeters of mercury per millimeter (sonomicrometry) was significantly better with L-arginine (92 +/- 15) versus blood cardioplegic solution (28 +/- 3) and N omega-nitro-L-arginine (26 +/- 6). Segmental diastolic stiffness was significantly lower with L-arginine (0.46 +/- 0.06) compared with blood cardioplegic solution (1.10 +/- 0.11) and was significantly greater with N omega-nitro-L-arginine (2.70 +/- 0.43). In ischemic-reperfused left anterior descending coronary arterial vascular rings, maximum relaxation responses to acetylcholine, the stimulator of endothelial nitric oxide, was depressed in the blood cardioplegic solution group (77% +/- 4%) and was significantly reversed by L-arginine (92% +/- 3%). Smooth muscle function was unaffected in all groups. We conclude that cardioplegic solution supplemented with L-arginine reduces infarct size, preserves postischemic systolic and diastolic regional function, and prevents arterial endothelial dysfunction via the L-arginine-nitric oxide pathway.

Regional myocardial dimensions following coronary artery bypass grafting in patients. Relationship of functional deterioration to graft occlusion.

The direct relationship between graft flow and regional midwall myocardial function has not been documented in patients. Therefore, the present study was designed to quantitate the effects of coronary artery bypass grafting on regional myocardial mechanics distal to a coronary artery obstruction. Twenty-one patients with subtotal or total occlusion of the left anterior descending (LAD) coronary artery underwent coronary artery bypass grafting. Following completion of the aortic and coronary anastomoses, two miniature ultrasonic dimension transducers (2.5 mm. diameter) were positioned within the minor axis of the anterior left ventricular free wall and were allowed complete freedom of movement. The transducers were placed at midwall depth, and areas of clinically apparent myocardial fibrosis were not utilized as sites of implantation. During control, 30 minutes following the termination of cardiopulmonary bypass, regional myocardial dimensions, pulmonary artery diastolic pressure, arterial pressure, and heart rate were recorded with all saphenous vein grafts open and after 30 seconds of single vein graft occlusion. These measurements were repeated during atrial pacing at a rate of 128 +/- 4 beats per minute. Data are mean +/- the standard error of the mean. During control, graft occlusion resulted in a regional decrease in systolic excursion from 1.3 +/- 0.1 to 1.0 +/- 0.2 mm. (p less than 0.01), as well as a decrease in the rate of shortening from 8.7 +/- 0.2 to 6.2 +/- 1.1 mm. per second (p less than 0.05); heart rate, mean arterial pressure, and diastolic pulmonary artery pressure remained unchanged. Graft occlusion with atrial pacing resulted in an exaggerated decrease in both regional systolic excursion, from 1.2 +/- 0.2 to 0.6 +/- 0.2 mm. (p less than 0.01), and rate of shortening, from 9.4 +/- 1.5 to 4.4 +/- 0.2 mm. per second (p less than 0.01). For the group of patients studied, end-diastolic lengths were unchanged with graft occlusion during control and atrial pacing. Moreover, with graft occlusion, isolated patients demonstrated regional dyskinesia as evidenced by holosystolic bulging. These studies in patients have documented for the first time that, despite a constant preload, afterload, and heart rate, regional myocardial function following coronary artery bypass grafting is dependent upon adequate graft flow, especially during stress.

Total anomalous pulmonary venous connection in infancy. Ten years' experience including studies of postoperative ventricular function.

The surgical experience with total anomalous pulmonary venous connection (TAPVC) at the Venderbilt Hospital between the years 1969 and 1979 was reviewed. Twenty-five patients with TAPVC were studied. All but one patient presented at less than 1 year of age, and 11 patients were operated upon in the first 2 weeks of life. Operative mortality rate was 20% (5/25). Four of the five deaths were in critically ill neonates requiring preoperative ventilatory support. All operative deaths were in patients with pulmonary venous obstruction. All operative survivors have been followed for a mean 4.5 years (6 months to 10 years). There have been no late deaths or cases of symptomatic pulmonary venous obstruction. All children have had normal growth patterns. Ten patients have been recatheterized. Pulmonary artery systolic pressure, which was markedly elevated prior to operation, fell to normal levels after operation. Ventricular function has been evaluated by quantitative angiocardiography in nine patients before and after operation. Left ventricular size and function were markedly depressed preoperatively and rose to normal levels in postoperative survivors. Left atrial maximal volume was found to be 94% of normal values. These data support the contention that preoperative pulmonary venous obstruction is the single risk factor predicting higher risk of operative death. The presence of severe depression of left ventricular size and function preoperatively does not predict a higher operative risk, and postoperative survivors can expect normal ventricular function.

Amelioration of the deleterious effects of platelets activated during cardiopulmonary bypass. Comparison of a thromboxane synthetase inhibitor and a prostacyclin analogue.

Thrombocytopenia and platelet dysfunction are commonly seen after cardiopulmonary bypass. In addition, the microvascular bed of ischemic myocardium is a potent stimulus for platelet deposition and microvascular plugging. Thus, it would appear theoretically advantageous to provide pharmacologic protection of platelets by inhibiting their response to activating agents and thereby preventing their loss into the extracorporeal circuit; this would further inhibit myocardial platelet deposition and the deleterious effects therein. Twenty-one mongrel dogs were placed on cardiopulmonary bypass with 30 minutes of normothermic global ischemia. They were randomly assigned to receive pretreatment with an infusion of saline (control, n = 8), a thromboxane synthetase inhibitor (RO-22-4679, n = 5), or a prostacyclin analogue that does not produce hypotension (ZK 36,374, n = 8). The platelet count in those animals treated with ZK 36,374 was significantly higher at the end of the experiment than in the control group (102.8 +/- 10.7 X 10(3) versus 69.7 +/- 10.6 X 10(3), p less than 0.01); the animals treated with RO-22-4679 had a platelet count between the other two groups (92.8 +/- 14.8 X 10(30)), which was not significantly different from either. Myocardial platelet deposition was measured with indium 111-labeled platelets. Those animals treated with ZK 36,374 had a much lower level of platelet deposition than the group of controls; again the RO-22-4679 group had values between the other two. Finally, myocardial blood flow after global ischemia and cardiopulmonary bypass, measured with radioactive microspheres, was significantly higher in the ZK 36,374 group than in the control group. We conclude that ZK 36,374 prevents platelet consumption during cardiopulmonary bypass over and above that seen with inhibition of thromboxane synthesis alone. It also prevents deposition of platelets into the myocardium after global ischemia and we presume by that mechanism increases myocardial blood flow.

Pathophysiology of chronic cyanosis in a canine model. Functional and metabolic response to global ischemia.

To investigate the pathophysiology of chronic cyanosis, we subjected 14 adult mongrel dogs to diversion of the inferior vena cava to the right inferior pulmonary vein. This produced a mean oxygen tension of 42 +/- 2 mm Hg and a calculated right-to-left shunt of 52.0% +/- 3.9%. These animals (Group C) and 15 normal dogs (Group N) were subjected to cardiopulmonary bypass with 20 minutes of normothermic global ischemia. Functional indices studied were rate of rise of left ventricular pressure and the end-systolic pressure/volume ratio. Metabolic status was assessed by obtaining transmural myocardial biopsy specimens for measurement of adenosine triphosphate content. Myocardial blood flow was measured with radiolabeled microspheres. There were no significant differences between Group C and Group N in either functional index or blood flow measurement prior to global ischemia. At 45 minutes after ischemia, Group N animals had a significantly greater rate of rise of left ventricular pressure (at a left ventricular end-diastolic pressure of 0, 5, 10, and 15 mm Hg, p less than 0.025 to 0.05) and subendocarial perfusion (endocardial/epicardial flow ratio 0.961 +/- 0.037 versus 0.815 +/- 0.021, p less than 0.01). At 90 minutes after ischemia, Group N animals exhibited a significantly higher end-systolic pressure/volume ratio (4.9 +/- 0.7 versus 3.0 +/- 0.4 mm Hg/ml, p less than 0.05), rate of rise of left ventricular pressure (at an end-diastolic pressure of 0 to 20 mm Hg, p less than 0.005 to 0.05), and endocardial/epicardial flow ratio (1.065 +/- 0.046 versus 0.829 +/- 0.059, p less than 0.01). No differences in adenosine triphosphate content were found at any sampling period. The Group C left ventricles exhibited no hypertrophy but were significantly dilated compared to Group N (38.8 +/- 0.3 versus 30.1 +/- 0.2 mm, p less than 0.05). Inferior vena cava to pulmonary vein diversion produces cyanosis with left ventricular dilatation but without hypertrophy. It is proposed that abnormal loading characteristics of the left ventricle are responsible for the functional derangements that result from global ischemia.

Basal nitric oxide expresses endogenous cardioprotection during reperfusion by inhibition of neutrophil-mediated damage after surgical revascularization.

Ischemia-reperfusion damages endothelium and impairs basal production of nitric oxide. Basally released nitric oxide is cardioprotective by its inhibition of neutrophil activities. Loss of endogenous nitric oxide with endothelial injury may occur during two phases: cardioplegic ischemia and reperfusion (aortic declamping). This study tested the hypothesis that inhibition of endogenously released nitric oxide in hearts subjected to regional ischemia, cardioplegic arrest, and reperfusion (1) restricts endogenous cardioprotection and permits neutrophil-mediated damage and (2) expresses damage during the reperfusion phase. L-Nitro-arginine was used to block basal nitric oxide production. In 22 anesthetized dogs, the left anterior descending artery was ligated for 90 minutes followed by 1 hour of arrest with cold multidose (every 20 minutes) blood cardioplegia. Dogs were divided into three groups: the first group received standard unsupplemented blood cardioplegia (group 1, n = 8), in the second group L-nitro-arginine was administered as an additive to blood cardioplegic solution (1 mmol) and as an infusion during reperfusion (34 mg/kg) (group 2, n = 7), and in the third group L-nitro-arginine was administered only at reperfusion (group 3, n = 7). The ligature was released during the second infusion of cardioplegic solution. Infarct size (triphenyltetrazolium chloride) was increased in group 3 (L-nitro-arginine only at reperfusion) compared with that in group 1 (standard blood cardioplegia) (49% +/- 6% vs 34% +/- 2%, respectively), but was not further extended in group 2 (L-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion) (56% +/- 3%, p > 0.05 vs group 3), which suggests primarily a reperfusion process. Polymorphonuclear neutrophil-specific myeloperoxidase activity in the area at risk was elevated comparably in groups 2 and 3 (group 2: 2.9 +/- 0.5 units/gm tissue, p = 0.06 vs group 1; group 3: 3.9 +/- 1.0 units/gm tissue, p < 0.05 vs group 1) compared with that in the standard blood cardioplegia group (1.7 +/- 0.3 units/gm tissue), suggesting polymorphonuclear neutrophil accumulation occurs primarily during reperfusion. Polymorphonuclear neutrophil adherence in ischemic-reperfused left anterior descending artery segments was comparably greater in group 2 (L-nitro-arginine as an additive to blood cardioplegic solution and at reperfusion: 195 +/- 21 polymorphonuclear neutrophils/mm2 of artery, p < 0.05 vs group 1) and group 3 (L-nitro-arginine only at reperfusion: 224 +/- 20 polymorphonuclear neutrophils/mm2 of artery, p < 0.05 vs group 1) relative to that in group 1 (108 +/- 19 polymorphonuclear neutrophils/mm2 of artery). There was no significant adherence to nonischemic circumflex arteries. We conclude that blockade of endogenous nitric oxide augments postischemic injury mediated by polymorphonuclear neutrophils, and this damage is expressed primarily during the reperfusion phase.