Ethane: a marker of lipid peroxidation during cardiopulmonary bypass in humans.

The goals of this study were to (1) determine the utility of quantification of ethane as a marker of ischemia-reperfusion during human cardiopulmonary bypass (CPB); and (2) determine, using an animal model for this surgical procedure, whether the mode of surgical approach produced increases the quantity of exhaled ethane. Human CPB was initiated following standard anesthetic and monitoring regimens. Samples of gas were collected at baseline and at multiple defined time points throughout the studies. Ethane was determined using cryogenic concentration and gas chromatography. Sternotomy increased exhaled ethane compared to baseline (p < .007; 5.8 +/- 1.7 vs. 3.0 +/- 0.7 nmol/m2 x min); ethane returned to baseline levels prior to the initiation of CPB. Aortic unclamping produced ethane elevation (p < .05; 2.3 +/- 0.8 vs. 1.5 +/- 0.4 nmol/m2 x min) with the levels being related to a lower cardiac index and a higher systemic vascular resistance post aortic unclamping. Termination of CPB significantly increased ethane levels compared to baseline (p < .002; 4.8 +/- 1.7 vs. 3.0 +/- 0.7 nmol/m2 x min). Independent variables that correlated with increased ethane measurements included a higher arterial blood pH on bypass and the change in hemoglobin pre- and post-CPB. Electrocautery, but not scalpel, incision of the porcine abdominal wall increased ethane levels significantly (p < .02). These results indicate that exhaled ethane may be a valuable marker of lipid peroxidation during and following CPB.

Cardiopulmonary bypass with profound hypothermia. An optimal preservation method for multiorgan procurement.

Numerous techniques have been devised for the harvesting of individual organs during a multiorgan procurement operation. Cardiopulmonary bypass with profound hypothermia (PH) has been employed in successful harvesting of heart-lung, kidney, pancreas, and liver grafts. This report summarizes our experience using CPB-PH for the harvesting of multiple organs from 10 brain-dead donors during the period from July 1983 to January 1988. Organs harvested included 10 heart-lungs, 17 kidneys (3 kidneys were not harvested due to anatomy and elevated creatinine), 1 liver, and 1 pancreas. Mean ischemic time for the distantly procured heart-lung grafts was 281 +/- 10 min. Adequate pulmonary function, as assessed by arterial blood gases, was observed in each heart-lung recipient (mean PO2 was 119 +/- 46 mmHg, 164 +/- 47 mmHg, 130 +/- 30 mmHg, 114 +/- 26 mmHg at immediate post-CPB, 6 hr postop, 24 hr postop, and postextubation, respectively). Mean length of intubation was 34 +/- 8 hr. Mean creatinines of kidney recipients at days 2, 7, and current creatinine were 7.4 +/- 3.6 mg%, 3.6 +/- 2.4 mg%, and 1.6 +/- 0.66 mg%, respectively. Eight kidney recipients (47%) required dialysis, (2 patients required only a single dialysis). Ninety-four percent of the kidney transplant patients are alive, and 88% (15/17) have functioning kidneys. One liver and 1 pancreas were harvested during this time period. Preservation was satisfactory in both the pancreas (Johns Hopkins Hospital) and liver (Dr. Thomas Starzl, personal communication). The technique of CPB-PH has resulted in excellent function of heart-lung grafts. Follow-up of the transplanted kidneys, liver, and pancreas utilizing this technique shows equal or better function compared with standard techniques. This technique offers other advantages in addition to satisfactory multiorgan preservation. Placement of an unstable patient on CPB ensures adequate organ perfusion and allows for a gradual yet uniform cooling of all organ systems. Cooling to a core temperature of 10-15 degrees C requires 30 min, during which time preliminary intraabdominal and mediastinal dissection can be carried out. Following cessation of CPB and subsequent exsanguination, organs can be more easily dissected in a near-bloodless field. This technique does not preclude additional crystalloid organ flushing. Since multiorgan procurement occurs with virtually every donor, this technique may be the optimal method providing excellent preservation, ease of dissection, and better control of hemodynamics during the operation.

Quality of life in octogenarians after open heart surgery.

OBJECTIVES: To determine the quality of life in octogenarians after open heart surgery. BACKGROUND: Despite an increasing number of cardiac operations on octogenarians, the outcome as measured by functional status, independence of living, and psychological parameters of quality of life remain unproved. METHODS: Two groups of octogenarians (group 1, undergoing operation in 1986; group 2 in 1991) were reviewed retrospectively to determine operative mortality and functional results. RESULTS: Group 1 (n = 15, mean age of 83.2 years) and group 2 (n = 53, mean age 83.0 years) were studied. Operations included isolated coronary artery bypass grafting (group 1, 10; group 2, 29) and valve replacements +/- coronary artery bypass grafting +/- other procedures (group 1: 5; group 2, 24). Group 1 had 9% hospital mortality and 53% actuarial survival after a mean follow-up of 6.3 years. Group 2 had 17% hospital mortality and 72% actuarial survival after a mean follow-up of 1.5 years. At follow-up, significant improvements were observed in New York Heart Association (NYHA) angina class, congestive cardiac failure class, number of cardiovascular symptoms, and indices for satisfaction with overall life and general affect in both groups. Further, group 2 also showed significant improvements in independence of living, ease of life, and Karnofsky dependency category, but these improvements were less evident in group 1 after a longer period of follow-up. At follow-up, 75% of group 1 and 84% of group 2 octogenarians would definitely have made the same decision to undergo open heart surgery in retrospect. CONCLUSION: This study demonstrates improved quality of life after open heart surgery in octogenarians.

Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion.

Leukocyte depletion improves early postischemic ventricular performance in neonatal models of global myocardial ischemia. However, the rate of leukocyte reaccumulation after cardiopulmonary bypass and its subsequent impact on myocardial function is not known. This laboratory study examined the effect of leukocyte depletion on myocardial performance during the initial 6-hour period after bypass in an in situ, in vivo porcine model of neonatal cardiac surgery. Fifteen 3- to 5-day-old piglets (eight control and seven leukocyte depleted animals) were instrumented by placement of left ventricular short-axis sonomicrometry crystals and an intraventricular micromanometer catheter. Mechanical leukocyte depletion was achieved with Pall RC100 filters (Pall Biomedical, Inc., Fajardo, Puerto Rico) in the cardiopulmonary bypass circuit. Neonatal hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Two control animals died after the operation and were excluded from data analysis. Leukocyte filtration reduced the granulocyte count during initial myocardial reperfusion to 0.8% of control values. However, circulating granulocyte counts increased in leukocyte depleted animals throughout the postoperative period, reaching 68% of control values by 6 hours. Despite this rapid return of circulating granulocytes, animals subjected to leukocyte depletion had significantly better preservation of left ventricular performance (measured by preload recruitable stroke work, p < or = 0.02), left ventricular systolic function (measured by end-systolic pressure-volume relationship, p < or = 0.05), and ventricular compliance (p < or = 0.04) during the experiment. These changes in ventricular function were associated with a significant increase in left ventricular water content (p < or = 0.02) and tissue myeloperoxidase activity (p < or = 0.005) in control animals compared with leukocyte depleted animals. This study demonstrates that leukocyte depletion during initial reperfusion results in sustained improvement in postischemic left ventricular function despite the rapid return of granulocytes to the circulation.

Leukocyte depletion ameliorates free radical-mediated lung injury after cardiopulmonary bypass.

Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of lung injury associated with cardiopulmonary bypass. To determine whether leukocyte depletion could prevent this injury, we used a dog model simulating routine cardiac operations. Mongrel dogs (11 to 17 kg) were subjected to cardiopulmonary bypass with a bubble oxygenator and cooled to 27 degrees C. After aortic crossclamping and cardioplegic arrest for 90 minutes, control animals (n = 5) were rewarmed and weaned from bypass, and their condition was then stabilized for 90 minutes. Leukocyte-depleted animals (n = 5) had a leukocyte filter incorporated in the bypass circuit. During bypass, circulating leukocyte counts decreased by 60% in control dogs, and by 97% in leukocyte-depleted animals. Free radical generation (estimated by spectrophotometric assay of plasma conjugated dienes) was significantly reduced by leukocyte depletion during and after bypass. Total hemolytic complement activity and the titer of C5 decreased markedly immediately after the onset of bypass in both the control and leukocyte-depleted animals. Pulmonary function after bypass was better preserved in leukocyte-depleted animals. These data suggest that depletion of circulating leukocytes contributes to lung injury during cardiopulmonary bypass and is associated with increased oxygen radical activity, pulmonary edema, and vasoconstriction. Leukocyte depletion substantially reduced the pulmonary injury seen after cardiopulmonary bypass.

Successful twenty-four-hour lung preservation with donor core cooling and leukocyte depletion in an orthotopic double lung transplantation model.

Donor core cooling with cardiopulmonary bypass is a valid method of clinical lung preservation. However, organ ischemia with this method is still limited to short-term intervals. Since circulating leukocytes participate in postischemic injury through the release of oxygen-derived free radicals, we examined whether leukocyte depletion by mechanical filtration could extend ischemic tolerance of the lung during preservation and subsequent double lung transplantation. Bovine donor lungs were preserved by donor core cooling (10 degrees to 15 degrees C) with cardiopulmonary bypass. Donor lungs were removed, stored in 4 degrees C donor blood for 24 hours, and transplanted. Graft function was studied for 6 hours after transplantation. Group 1 animals (n = 6) underwent standard cardiopulmonary bypass with whole blood for donor and recipient procedures. In group 2 (n = 6), leukocyte filters were incorporated into the cardiopulmonary bypass circuit in both donor and recipient operations. In group 2 recipient animals leukocyte counts decreased to 3% of mean baseline values and remained low during the experiment. Postischemic lung function (assessed by systemic arterial oxygenation, pulmonary artery pressure, pulmonary vascular resistance, airway pressure, lung water content, and end-point histologic characteristics) was significantly better preserved in the animals with leukocyte depletion. Leukocyte depletion by mechanical filtration in both donor and recipient improves the ischemic tolerance of the lung beyond that provided by donor core cooling alone, resulting in excellent lung function after 24 hours of ischemia.

A no-flush, core-cooling technique for successful cardiopulmonary preservation in heart-lung transplantation.

In order to determine whether a no-flush, core-cooling technique could provide extended heart-lung preservation, we placed donor calves on cardiopulmonary bypass and instituted rapid cooling to 15 degrees C during the continuous infusion of isoproterenol. The heart and lungs were harvested after the administration of a cardioplegic solution through the aortic root. In the control group (N = 5), heart and lungs were orthotopically allotransplanted immediately. In the preserved group (N = 5), heart and lungs were similarly excised but were stored in a normal saline bath at 4 degrees C for approximately 4 hours and then transplanted. Both groups received isoproterenol during reperfusion and were studied for 6 hours after implantation. A load independent analysis of myocardial function was done by determining with a sonomicrometer the ratio of the end-systolic pressure to the end-systolic dimension. Pulmonary preservation was evaluated by measurement of extravascular lung water with a double-indicator dilution method, arterial oxygenation on 100% inspired oxygen, and serial lung biopsies. Myocardial and pulmonary function after 4 hours of static preservation was found to be similar to controls. No-flush, core-cooling with cardiopulmonary bypass provides adequate cardiorespiratory function after acute bovine heart-lung allotransplantation. With the use of this technique, successful extended cold ischemic cardiopulmonary preservation for heart-lung transplantation may be achieved.

Cardiopulmonary bypass and the blood-brain barrier. An experimental study.

The diffuse inflammation produced by cardiopulmonary bypass might disrupt the blood-brain barrier and lead to the transient neurologic dysfunction occasionally seen after cardiac operations. To evaluate this possibility, blood-brain barrier integrity was measured by carbon 14-aminoisobutyric acid tracer technique after 2 hours of cardiopulmonary bypass in piglets. Six animals were cooled to 28 degrees C on cardiopulmonary bypass and then rewarmed to 38 degrees C before carbon 14-aminosisobutyric acid was injected intraarterially. A control group of six animals underwent median sternotomy and heparinization but were not placed on cardiopulmonary bypass. Blood-to-brain transfer coefficients for carbon 14-aminosisobutyric acid were calculated for multiple brain regions; higher coefficients reflect greater flux of carbon 14-aminosisobutyric acid and suggest loss of blood-brain barrier integrity. The brain regions examined and their transfer coefficients (cardiopulmonary bypass versus control mean +/- standard error of the mean ml/gm/min) were middle cerebral artery territory cortex (0.0032 +/- 0.0002 versus 0.0030 +/- 0.0002; p = 0.42), diencephalon (0.0031 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.50), midbrain (0.0028 +/- 0.0002 versus 0.0027 +/- 0.0002; p = 0.86), cerebellum (0.0036 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.22), and spinal cord (0.0035 +/- 0.0003 versus 0.0041 +/- 0.0008; p = 0.48). There were no significant differences in transfer coefficients between animals placed on cardiopulmonary bypass and control animals in any brain region examined. The pituitary gland lacks a blood-brain barrier and had a correspondingly high coefficient in control animals and those undergoing cardiopulmonary bypass (0.077 +/- 0.012 versus 0.048 +/- 0.008; p = 0.07). Two hours of moderately hypothermic cardiopulmonary bypass does not disrupt the blood-brain barrier.

Mitral valve operation in patients with the Marfan syndrome.

Optimal surgical treatment of mitral regurgitation in the Marfan syndrome (valve repair versus replacement) is controversial because the underlying connective tissue defect theoretically might compromise repair durability. To examine the results of mitral valve repair in these patients, we did a retrospective review of 160 patients with the Marfan syndrome who had cardiac surgical procedures between January 1983 and January 1993. Thirty-six patients had mitral procedures, 29 of which were repairs. Mitral valve replacement was necessary in seven patients because of extensive annular calcification and/or severe anterior leaflet abnormalities. The 18 men and 11 women undergoing mitral valve repair had a mean age of 26.5 +/- 2.6 years (range 9 months to 54 years); seven patients were less than 18 years of age. Twenty-four of the 29 patients had concomitant aortic root replacement because of aortic dilation or valvular insufficiency. All 29 repairs included annuloplasty, and 11 patients also required leaflet resection. There were no operative deaths. At mean follow-up of 26.6 +/- 4.8 months, there have been three late deaths, two caused by arrhythmia and one by complications of type III aortic dissection. All survivors are in New York Heart Association class I or II. In three patients recurrent mitral regurgitation developed (grade III or IV); 5-year actuarial freedom from significant mitral regurgitation was 88.3%. One patient required repeat mitral annuloplasty after endocarditis of the composite aortic graft spread to the mitral valve. No patient required late mitral valve replacement. These results demonstrate that (1) 22% of patients with the Marfan syndrome who undergo cardiac operation require a mitral valve procedure, (2) most can be treated by mitral repair rather than replacement, and (3) at early follow-up, results of mitral repair in this population are satisfactory.

Separation of craniopagus Siamese twins using cardiopulmonary bypass and hypothermic circulatory arrest.

Occipitally joined craniopagus Siamese twins were separated with the use of cardiopulmonary bypass and hypothermic circulatory arrest. The 7-month-old infants shared a large sagittal venous sinus that precluded conventional neurosurgical approach because of risk of exsanguination and air embolism. After craniotomy and preliminary exposure of the sinus, each twin underwent sternotomy and total cardiopulmonary bypass with deep hypothermia. Hypothermic circulatory arrest allowed safe division and subsequent reconstruction of the sinus remnants. Several unusual problems were encountered, including transfusion of a large blood volume from one extracorporeal circuit to the other through the common venous sinus, deleterious warming of the exposed brain during circulatory arrest, and thrombosis of both pump oxygenators. Both infants survived, although recovery was complicated in each by neurologic injury, cranial wound infection, and hydrocephalus. This case demonstrates the valuable supportive role of cardiopulmonary bypass and hypothermic circulatory arrest in the management of complex surgical problems of otherwise inoperable patients.

Glutamate excitotoxicity: a mechanism of neurologic injury associated with hypothermic circulatory arrest.

Glutamate, the major central nervous system neurotransmitter, may have potent neurotoxic activity under conditions of metabolic stress. By receptor autoradiography, we have demonstrated that brain regions most vulnerable to injury during prolonged hypothermic circulatory arrest have the highest density of glutamate receptors. To test the hypothesis that such injury could be mediated by glutamate excitotoxicity, we used dizocilpine (MK-801), a selective N-methyl-D-aspartate-glutamate receptor antagonist in a canine survival model of hypothermic circulatory arrest. Eighteen male dogs (20 to 25 kg) were supported by closed-chest cardiopulmonary bypass, subjected to 2 hours of hypothermic circulatory arrest at 18 degrees C, and rewarmed on cardiopulmonary bypass. All were mechanically ventilated and monitored for 20 hours before extubation and survived for 3 days. Group A dogs (n = 9) received a prearrest intravenous bolus of dizocilpine (0.75 mg/kg) followed by continuous infusion (75 micrograms/kg per hour), resulting in electroencephalographic silence. Dizocilpine was weaned before extubation. Group B dogs received vehicle only. According to a species-specific behavior scale that yielded a neurologic deficit score ranging from 0 (normal) to 500 (brain dead), all animals were neurologically assessed every 12 hours. After the dogs were killed at 72 hours, brains were examined by receptor autoradiography and histologically for patterns of selective neuronal necrosis; they were scored blindly from 0 (normal) to 100 (severe injury). Group A dogs had better neurologic function than group B (neurologic deficit score 21 +/- 15 versus 192 +/- 40, p < 0.001) and had less neuronal injury (7.3 +/- 3 versus 48.3 +/- 9, p < 0.0001). Densitometric receptor autoradiography revealed preservation of neuronal N-methyl-D-aspartate-glutamate receptor expression in group A only. These results represent the first direct evidence of a role for glutamate excitotoxicity in the development of hypothermic circulatory arrest-induced brain injury and suggest that selective glutamate receptor antagonists may have a neuroprotective capacity in prolonged periods of hypothermic circulatory arrest.

Aortic root replacement. Risk factor analysis of a seventeen-year experience with 270 patients.

Between September 1976 and September 1993, 270 patients underwent aortic root replacement at our institution. Two hundred fifty-two patients underwent a Bentall composite graft repair and 18 patients received a cryopreserved homograft aortic root. One hundred eighty-seven patients had a Marfan aneurysm of the ascending aorta (41 with dissection) and 53 patients had an aneurysm resulting from nonspecific medial degeneration (17 with dissection). These 240 patients were considered to have annuloaortic ectasia. Thirty patients were operated on for miscellaneous lesions of the aortic root. Thirty-day mortality for the overall series of 270 patients was 4.8% (13/270). There was no 30-day mortality among 182 patients undergoing elective root replacement for annuloaortic ectasia without dissection. Thirty-six of the 270 patients having root replacement also had mitral valve operations. There was no hospital mortality for aortic root replacement in these 36 patients, but there were seven late deaths. Twenty-two patients received a cryopreserved homograft aortic root; 18 of these were primary root replacements and four were repeat root replacements for late endocarditis. One early death and two late deaths occurred in this group. Actuarial survival for the overall group of 270 patients was 73% at 10 years. In a multivariate analysis, only poor New Year Heart Association class (III and IV), non-Marfan status, preoperative dissection, and male gender emerged as significant predictors of early or late death. Endocarditis was the most common late complication (14 of 256 hospital survivors) and was optimally treated by root replacement with a cryopreserved aortic homograft. Late problems with the part of the aorta not operated on occur with moderate frequency; careful follow-up of the distal aorta is critical to long-term survival.

The changing profile of the cardiac donor.

BACKGROUND: Expansion of traditional donor criteria has become standard in most centers. To determine how this has affected donor profiles, at our institution, we reviewed all adult (age > or = 16) cardiac donors of the past 15 years. METHODS: We separated 261 cardiac donors into 2 groups based on time periods: Group I, 1983 to 1991 (n = 131), and Group II, 1991 to 1998 (n = 130). RESULTS: The groups differed significantly in mean donor age (26.2 years vs 30.9; p < 0.001), percent older than 40 years (6% vs 27%; p < 0.001), percent female (23% vs 35%; p = 0.04), percent distant procurement (54% vs 22%; p < 0.001), and percent minority donors (14% vs 29%; p < 0.001). We found an increase in non-traumatic deaths (24% vs 40%; p = 0.008). Older donors had significantly more non-traumatic deaths than younger donors (79% vs 13%; p < 0.001). Overall 5-year survival of recipients was 64% and was not significantly different between our early and late experiences (60% vs 68%; p = not significant [NS]). Recipients with hearts from older donors had a 5-year survival similar to recipients with younger donor hearts (61% vs 64%; p = NS). Traumatic and non-traumatic donors had similar 5-year survivals (64% vs 63%, p = NS). A stepwise multivariate analysis of the entire cohort identified donor age, donor weight, recipient United Network for Organ Sharing status, and cardiopulmonary bypass time as significant independent risk factors for recipient survival. Recipients of hearts from donors < 90 kg had significantly better 5-year survivals than recipients from donors > or = 90 kg (66% vs 48%; p = 0.01). CONCLUSIONS: Our evolving cardiac donor pool now has more minorities, women, and older donors whose deaths are often non-traumatic. At our institution, donor pool expansion has had no adverse effect on the long-term survival of recipients.

Dehydroepiandrosterone and cardiac allograft vasculopathy.

BACKGROUND: Tissue culture, animal model, and epidemiologic studies suggest that dehydroepiandrosterone may inhibit atherosclerosis through its potent antiproliferative effects. Because cardiac allograft vasculopathy is predominantly a proliferative abnormality of intimal and medial smooth muscle cells, plasma levels of dehydroepiandrosterone may play an important role in the development of this disease. METHODS: Sixty-one cardiac allograft recipients who survived for 1 year or more and had at least one annual follow-up cardiac catheterization were included in the study. Plasma levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and free dehydroepiandrosterone (dehydroepiandrosterone not bound to sex hormone-binding globulin) were measured in all 61 subjects and compared with the presence or absence of cardiac allograft vasculopathy as defined by angiography. RESULTS: Plasma levels of total and free dehydroepiandrosterone were lower in subjects in whom cardiac allograft vasculopathy developed (p = 0.005 and 0.003, respectively). Furthermore, the time to development of cardiac allograft vasculopathy was shorter in subjects with low levels of total and free dehydroepiandrosterone (p = 0.062 and 0.046, respectively). This relationship was maintained after adjusting for age, gender, cholesterol, prednisone use, and blood pressure. CONCLUSIONS: Low plasma levels of dehydroepiandrosterone may facilitate and high levels may retard the development of cardiac allograft vasculopathy.

Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants.

To evaluate changes in coronary blood flow during allograft rejection, 16 beagles with cervical cardiac allografts from mongrel donors were immunosuppressed postoperatively for 7 days with cyclosporine (20 mg/kg orally) and prednisone (0.5 mg/kg orally). They were weaned from immunosuppression over 3 days and then treated with methylprednisolone (30 mg/kg/day IV), cyclosporine (20 mg/kg orally), and prednisone (0.5 mg/kg orally) for 4 days. Previous experiments with this model have suggested the utility of phosphorus 31 nuclear magnetic resonance spectroscopy (31P NMR) in the diagnosis of rejection. Therefore in 10 dogs (NMR group) bioenergetic changes during rejection were assessed using the 31P NMR index of the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). To correlate coronary blood flow and graft ischemia with allograft rejection, six dogs (FLOW group) underwent placement of a magnetic flow probe on the left anterior descending coronary artery to determine mean and peak coronary flow. In both NMR and FLOW groups, grafts were evaluated by endomyocardial biopsy (grading 0 to 8 for increasing rejection), and measurement of lactate production and left ventricular end-diastolic pressure. During the initial 7 days of immunotherapy, cellular rejection was effectively suppressed, and the bioenergetic status of the grafts remained stable (day 7: PCr/Pi = 70% of baseline, biopsy score = 2.0). During weaning of immunotherapy, however, the metabolic profile of the grafts decayed (day 10: PCr/Pi = 45% of baseline, biopsy score = 5.8; p less than 0.05 vs day 0). After 4 days of augmented immunosuppression, PCr/Pi recovered to 83% of baseline; this metabolic recovery corresponded with an improvement in mean biopsy score to 3.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of theophylline for treatment of prolonged sinus node dysfunction in human orthotopic heart transplantation.

Sinus node dysfunction may complicate heart transplantation in over 50% of cases, leading to prolonged bradyarrhythmias in 20% of recipients. Permanent pacemaker implantation, the standard treatment for such persistent rhythm disturbances, can result in significant complications in this setting. A protocol with theophylline, a methylxanthine known to reverse the sinus node electrophysiologic abnormalities observed in transplant patients, was initiated at our institution in October 1989 to treat posttransplantation bradyarrhythmias and to reduce the need for pacemaker implantation. Patients with sinus or nodal bradycardia or sinus arrest were given theophylline orally; the drug was initiated in 15 of 38 patients (39.5%), 3 to 24 days after transplantation. Mean duration of treatment was 57.4 days (range, 20 to 105 days). Normal sinus rhythm with a rate of more than 90 beats/min was restored in 14 of 15 patients (93.3%). Permanent pacing was required in one patient. Transplant recipients before October 1989 (group 1, n = 112) were compared with subsequent transplant recipients (group 2, n = 38). These groups did not differ significantly in incidence of bradyarrhythmias or potential risk factors for posttransplantation sinus node dysfunction, though a greater preoperative use of amiodarone occurred in group 2. Permanent pacemaker requirement was significantly reduced from 16.1% in group 1 to 2.6% in group 2 (p < 0.05) with the introduction of theophylline. Theophylline is effective treatment for posttransplantation bradyarrhythmias, thereby resulting in a reduced need for pacemaker implantation.

Twelve-hour cardiopulmonary preservation using donor core cooling, leukocyte depletion, and liposomal superoxide dismutase.

Because leukocytes and oxygen radical species contribute to ischemic and reperfusion injury during organ preservation, we examined the effects of a long-acting liposomal superoxide dismutase (liposomal SOD) and mechanical filtration of leukocytes on cardiopulmonary graft function after 12 hours of static preservation. Bovine heart-lung blocks were harvested, core cooled to 15 degrees C, stored in 4 degrees C donor blood for 12 hours, and then orthotopically transplanted (control group, n = 6). In the leukocyte-depletion group (n = 6), a leukocyte filter was incorporated in the bypass circuits of the donor and recipient. In the SOD group (n = 6), liposomal SOD (5000 U/kg) was administered in the cardioplegic solution, in the prime of the bypass circuits of donor and recipient, and immediately before recipient heart-lung reperfusion. In the combination group (n = 6), both leukocyte depletion (LD) and liposomal SOD were used. Only four of six control animals survived more than 2 hours after weaning from bypass, whereas all LD, SOD, and LD + SOD animals survived to be studied at 6 hours. Pulmonary function was assessed at 6 hours by arterial oxygen tension on 100% inspired oxygen (PO2), pulmonary vascular resistance (PVR), and postmortem wet/dry lung weight ratios. Arterial pO2 values (mm Hg) were as follows: control, 102 +/- 51; LD, 437 +/- 60*; SOD, 278 +/- 83; and LD + SOD, 504 +/- 54* (*p less than 0.05 vs controls). PVR values (dynes . sec . cm5) were as follows: control, 1975 +/- 697; LD, 682 +/- 131*; SOD, 607 +/- 191*; and LD + SOD 367 +/- 87* (*p less than 0.05 vs controls).(ABSTRACT TRUNCATED AT 250 WORDS)

The monosialoganglioside, GM1, reduces neurologic injury associated with hypothermic circulatory arrest.

BACKGROUND: Neurologic injury associated with prolonged hypothermic circulatory arrest (HCA) may be mediated by calcium-dependent glutamate excitotoxicity (GE). The monosialoganglioside GM1 has been shown in vitro to limit GE in conditions of metabolic stress. To test the hypothesis that gangliosides can prevent HCA-induced brain injury, GM1 was used in a canine model of HCA. METHODS: Twelve male dogs were placed on closed-chest cardiopulmonary bypass, subjected to 2 hours of HCA at 18 degrees C, and rewarmed to 36 degrees to 37 degrees C on closed-chest cardiopulmonary bypass. All were mechanically ventilated and monitored for 20 hours before extubation and survived for 3 days. Group 1 dogs (n = 6) were pretreated with GM1, 30 mg/kg/24hr for 3 days before HCA, and received continuous infusion of GM1 during the procedure and 30 mg/kg/24hr for 3 days after HCA. Group 2 dogs (n = 6) received vehicle only. With a species-specific behavior scale that yielded a neurodeficit score ranging from 0% (normal) to 100% (brain dead), all animals were neurologically assessed every 12 hours. After death at 72 hours, brains were examined by glutamate receptor autoradiography and by histologic examination for patterns of selective neuronal necrosis and were scored blindly from 0 (normal) to 100 (severe injury). RESULTS: Group 1 dogs had better neurologic function compared with group 2 (neurodeficit score, 4.2% +/- 3% vs 38.4% +/- 8%; p < 0.001) and had less neuronal injury (11.3 +/- 3 vs 48.3 +/- 9, p < 0.001). Densitometric receptor autoradiography revealed preservation of neuronal glutamate receptor expression in group 1 only. CONCLUSIONS: These results provide evidence of a role for GE in the development of HCA-induced brain injury and suggest that monosialogangliosides may have a neuroprotective capacity in prolonged periods of HCA.

Penetrating trauma to the tricuspid valve and ventricular septum: delayed repair.

Penetrating cardiac trauma can result in a wide range of injuries to intracardiac structures. Missile injury, in particular, can cause damage in more than one cardiac chamber that may be difficult to identify at initial emergent operation. We report a case of late repair of traumatic ventricular septal defect and tricuspid valve perforation from gunshot wound. This case illustrates the importance of thorough examination of intracardiac anatomy during emergent and delayed repair for penetrating cardiac trauma.