Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage.

Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by drusen deposits and thickened Bruch's membrane (BM). This study details the capacity of nanosecond laser treatment to reduce drusen and thin BM while maintaining retinal structure. Fifty patients with AMD had a single nanosecond laser treatment session and after 2 yr, change in drusen area was compared with an untreated cohort of patients. The retinal effect of the laser was determined in human and mouse eyes using immunohistochemistry and compared with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser treatment was quantified using electron microscopy and quantitative PCR. In patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr. Retinal structure was not compromised in human and mouse retina after laser treatment, with only a discrete retinal pigment epithelium (RPE) injury, and limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse 3 mo after treatment (ApoEnull treated 683 ± 38 nm, ApoEnull untreated 890 ± 60 nm, C57Bl6J 606 ± 43 nm), with the expression of matrix metalloproteinase-2 and -3 increased (>260%). Nanosecond laser resolved drusen independent of retinal damage and improved BM structure, suggesting this treatment has the potential to reduce AMD progression.

Validation of local venous sampling within the at risk left anterior descending artery vascular bed in the canine left ventricle.

The validity of using blood sampled from the anterior interventricular vein (AIV), anatomically located within the myocardium perfused by the left anterior descending (LAD) coronary artery, to represent venous drainage originating from the LAD vascular territory was studied in eight anaesthetised, open chest dogs. The LAD was cannulated and perfused from a blood reservoir isolated from the systemic circulation. To determine the presence of blood from non-LAD sources that appears in the AIV sample, 51Cr-labelled red blood cells were injected into the left atrium and distributed in the systemic circulation while the LAD was perfused by non-radioactive blood. The percentage spillover of red blood cells from non-LAD sources into the AIV drainage was determined under control, reduced LAD flow, ischaemia, and reperfusion conditions as 100 X (AIV chromium content/arterial chromium content). Spillover of red blood cells into AIV blood samples averaged only 1.5(1.3)% under control conditions and increased insignificantly to 8.6(3.5)% during reduced LAD flow. During ischaemia red blood cells in AIV blood increased insignificantly to 98.3(5.0)% but decreased to 1.9(1.3)% after reperfusion. Studies in five dogs with microspheres showed that a portion of this admixture from non-LAD sources originated from precapillary nutritional collateral or overlapping blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac transplantation in a patient with muscular dystrophy and cardiomyopathy.

A 17-year-old boy with muscular dystrophy developed a cardiomyopathy. His brother died of a cardiomyopathy, and muscle enzyme levels were elevated in asymptomatic family members. Examination revealed cardiomegaly, hepatomegaly, proximal muscle atrophy and weakness, and calf hypertrophy. Skeletal muscle and endomyocardial biopsy specimens were consistent with Becker's muscular dystrophy. Because of intractable heart failure, orthotopic cardiac transplantation was performed. Two years after transplantation, the patient has returned to work and regained previous exercise tolerance. Heart transplantation can be an acceptable treatment of patients who have muscular dystrophy, with preserved ambulation and favorable life expectancy, and also life-threatening cardiomyopathy refractory to medical management.

Decrease in hippocampal [3H]vinylidene kainic acid binding in genetically epilepsy-prone rats.

Specific [3H]vinylidene kainic acid binding to the kainate-sensitive subtype of glutamate receptor was studied in brain of 31-day-old non-epileptic Sprague-Dawley control and two colonies of genetically epilepsy-prone rats using in vitro autoradiographic techniques. At 37.5 nM [3H]vinylidene kainic acid, specific [3H]vinylidene kainic acid binding was reduced significantly by 18 and 22% in dorsal and ventral hippocampal formation stratum lucidum of 31-day-old genetically epilepsy-prone-9 rats compared with non-epileptic controls. Hippocampal [3H]vinylidene kainic acid binding was reduced in genetically epilepsy-prone-3 rats by 15 and 18%, but these reductions were not statistically significant. Saturation of [3H]vinylidene kainic acid binding studies indicated that the total number of ventral hippocampal [3H]vinylidene kainic acid binding sites was decreased by 21% in genetically epilepsy-prone-3 rats and 28% in genetically epilepsy-prone-9 rats. The reduction in ventral hippocampal [3H]vinylidene kainic acid binding in genetically epilepsy-prone rats resembles the reduction in ventral hippocampal [3H]vinylidene kainic acid binding sites observed in perinatal hypothyroid rats. As genetically epilepsy-prone rats are hypothyroid during the neonatal period, the reduction in hippocampal [3H]vinylidene kainic acid binding in the genetically epilepsy-prone rats may be a consequence of a hypothyroid-induced defect in the development or maturation of the hippocampal mossy fiber projection in genetically epilepsy-prone rats. An alternative hypothesis is that the putative occurrence of spontaneous limbic seizures in genetically epilepsy-prone rats may lead secondarily to a reduction in hippocampal [3H]vinylidene kainic acid binding sites.

Complications associated with the use of heterologous bovine pericardium for pericardial closure.

Two complications necessitating removal of bovine pericardium used as a pericardial patch graft in 60 patients are reported. These complications, plus a few others reported in the literature, suggest that caution in the clinical use of bovine pericardium remains appropriate.

Myocardial infarction complicated by myocardial rupture and Bacteroides sepsis.

A patient in whom a myocardial rupture complicated recent myocardial infarction was found to have cardiac and systemic Bacteroides sepsis; he had just completed a course of steroids. Surgical repair of the cardiac rupture, mediastinal irrigation with povidone-iodine, and broad-spectrum antibiotics resulted in the patient's recovery.

Reperfusion injury after temporary coronary occlusion.

In 24 anesthetized open-chest dogs, we examined the time course of changes in contractile function, diastolic muscle stiffness (sonomicrometry), tissue water content, and ultrastructure after 1 hour of occlusion of the left anterior descending coronary artery and after 2 hours of unmodified reperfusion. One hour of occlusion of the left anterior descending artery replaced active shortening with passive bulging (21.4% +/- 2.9% versus -5.9% +/- 0.9%, p less than 0.05) in the involved segment. There was no increase in either subendocardial water content (78.6% +/- 0.1% versus 79.7% +/- 0.7%) or operative muscle stiffness (2.80 +/- 0.72 versus 2.36 +/- 0.42 mm Hg/mm) after the occlusion period. There were only mild to moderate ultrastructural alterations suggestive of reversible injury. In sharp contrast, reperfusion was associated with a 2.48% increase in subendocardial water content (p less than 0.05), a 42% increase in diastolic muscle stiffness (3.34 +/- 0.42 mm Hg/mm, p less than 0.05), and greater ultrastructural damage. We conclude that myocardial injury is significantly extended with unmodified blood reperfusion after temporary coronary occlusion.

Is a left ventricular vent necessary for coronary artery bypass operations performed with cardioplegic arrest?

The need for ventricular venting with hypothermic cardioplegic arrest is controversial. We report an evaluation of the need for left ventricular venting in a canine model that closely simulates conditions during routine coronary artery bypass grafting (CABG). Thirty-five dogs were placed on cardiopulmonary bypass for 60 minutes of hypothermic cardioplegic arrest (18 vented, 17 nonvented) and then reperfused for 30 minutes. Myocardial temperature and left atrial pressure (LAP) were recorded continuously. Before and 30 minutes after hypothermic cardioplegic arrest, left ventricular function curves were generated (six vented, six nonvented), and biopsy specimens of the left ventricle were taken for adenosine triphosphate (ATP) determinations (11 vented, 10 nonvented) and semiquantitative grading of mitochondrial ultrastructure (six vented, six nonvented). LAP in nonvented dogs was 7.4 mm Hg during hypothermic cardioplegic arrest and 5.0 mm Hg during reperfusion. Temperature during hypothermic cardioplegic arrest was 12.3 degrees C in vented dogs and 11.3 degrees C in nonvented dogs (p = 0.5). There were no differences in left ventricular function or preservation of mitochondrial ultrastructure between vented and nonvented dogs. ATP after hypothermic cardioplegic arrest was 96.6% of control (4.30 microM/gm) in vented dogs and 94.6% (4.37 microM/gm) in nonvented dogs (p = 0.7). The absence of left ventricular venting did not lead to ventricular distention or more rapid rewarming. These data in vented dogs and nonvented dogs strongly support the belief that left ventricular venting is not necessary during routine CABG.

Clinical spectrum of blunt tracheobronchial disruption illustrated by seven cases.

Tracheobronchial disruption resulting from blunt trauma is unusual, but when it does occur it can have serious immediate and delayed consequences. A high index of suspicion for this injury and an awareness of the variety of clinical, radiographic, and bronchoscopic presentations are the key elements in diagnosis. Our experience with seven patients with blunt tracheobronchial trauma seen from 1972 through 1980 is reviewed. Emphasis is placed on the importance of early diagnosis to avoid the complications associated with delayed repair.

Malignant fibrous histiocytoma of the mediastinum and lung: a report of three cases.

One case of primary malignant fibrous histiocytoma of the lung and two cases of that tumor in the mediastinum are reported. Primary malignant fibrous histiocytoma is rare in those areas, appearing more commonly in deep fascia and skeletal muscles of the extremities and torso and in the retroperitoneum. Most of the tumors contain both fibroblast-like and histiocyte-like cells; some contain pleomorphic giant cells and inflammatory cells. They are often confused with other sarcomas, and their true biologic potential is not clearly defined. Radiation appears to be a very useful adjunct to surgical therapy and was used in the cases reported here.

Heparin dosing and monitoring for cardiopulmonary bypass. A comparison of techniques with measurement of subclinical plasma coagulation.

Subclinical plasma coagulation during cardiopulmonary bypass has been associated with marked platelet and clotting factor consumption in monkeys. To better define subclinical coagulation in man, we measured plasma fibrinopeptide A concentrations before, during, and after cardiopulmonary bypass. Patients were assigned to one of three groups of heparin management: group 1 (n = 10)--initial heparin dose 300 IU/kg, with supplemental heparin if the activated coagulation time fell below 400 seconds; group 2 (n = 6)--initial heparin dose 250 IU/kg, with supplemental heparin if activated coagulation time was less than 400 seconds; and group 3 (n = 5)--initial heparin dose 350 to 400 IU/kg, with supplemental heparin if whole blood heparin concentration was less than or equal to 4.1 IU/ml. Activated coagulation time and heparin concentration were measured every 30 minutes during cardiopulmonary bypass, and fibrinopeptide A was measured at hypothermia, normothermia, and whenever activated coagulation time was less than 400 seconds. Quantitative and qualitative blood clotting competence was assessed after cardiopulmonary bypass, including mediastinal drainage for the first 24 hours. Fibrinopeptide A values were markedly elevated during cardiopulmonary bypass but were well below the levels present before and after cardiopulmonary bypass. Fibrinopeptide A correlated inversely with heparin concentration during cardiopulmonary bypass (r = -0.46, p = 0.03), but higher fibrinopeptide A levels during cardiopulmonary bypass did not correlate with post-cardiopulmonary bypass coagulopathy. Group 3 patients received the highest heparin doses (p less than 0.05) and had the greatest postoperative blood loss (p less than 0.05). Protamine dose and heparin concentration during cardiopulmonary bypass correlated best with postoperative mediastinal drainage. Our findings support the following conclusions: (1) compensated subclinical plasma coagulation activity occurs during cardiopulmonary bypass despite activated coagulation time greater than 400 seconds or heparin concentration greater than or equal to 4.1 IU/ml; (2) post-cardiopulmonary bypass mediastinal drainage correlates strongly with increased heparin concentration during cardiopulmonary bypass (p less than 0.05) and protamine dose (p less than 0.05); and (3) during cardiopulmonary bypass at both normothermia and hypothermia, activated coagulation times greater than 350 seconds result in acceptable fibrinopeptide A levels and post-cardiopulmonary bypass blood clotting.

Cerebral injury and cardiac operations.

Cerebral complications constitute the leading source of morbidity and disability after cardiac operations. The incidence of stroke after coronary artery bypass grafting has increased in tandem with the mean age of the patient population. Although many cerebral deficits resolve with time, others remain sources of disability for otherwise functional patients and detract from an otherwise successful procedure. The clinical spectrum of cerebral complications includes both neurologic and neuropsychologic deficits. Neurologic deficits include fatal cerebral injury, stroke, impaired level of consciousness, and seizures. The incidence of these deficits is 1% to 6%. Neuropsychologic deficits refer to cognitive changes, and are quantitated with tests of memory and learning and speed of visual-motor response. The incidence of these deficits is 60% to 80% at 1 week after operation and 20% to 40% at 8 weeks after operation. Central nervous system complications after cardiac operations have been attributed in large part to the effects of cardiopulmonary bypass on the brain. Potential mechanisms include macroembolization of air or particulate matter; microembolization of gas, fat, aggregates of blood cells, platelets or fibrin, and particles of silicone or polyvinylchloride tubing; and inadequate cerebral perfusion pressure. Methods of assessment include those applied during the procedure (clinical observation, assessment of cerebral blood flow and metabolism, intraoperative electroencephalography, transcranial and carotid Doppler echography, quantitative embolic measurement, and fluorescein angiography) and those performed to measure outcome (neurologic and neuropsychologic testing, computed tomographic scans, magnetic resonance imaging, and cerebrospinal fluid studies). Much of the literature regarding cerebral injury and cardiopulmonary bypass is descriptive, relating patient risk factors to the incidence of postoperative stroke.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for cerebral injury and cardiac surgery.

Cerebral complications represent the leading cause of morbidity after cardiac operations. With the growing awareness of their social and economic importance, increasing attention is being given to their prevention. In the coronary artery bypass population, advanced age (> or = 75 years) is associated with an 8.9% neurologic deficit rate. Mortality is increased ninefold in the elderly patient with a neurologic deficit. Cardiopulmonary bypass has long been recognized as a cause of neuropsychologic deficits. Emboli are thought to be the causal agent. Retinal microvascular lesions during cardiopulmonary bypass as well as recent demonstration of widespread pathologic subcapillary arteriolar dilatations in the brain after cardiopulmonary bypass have been documented. Despite widespread interest in cerebral blood flow and neurologic deficits, there is no convincing evidence that defines a critically low or dangerously high level of flow. The ascending aorta represents a leading source of embolic neurologic injury. The use of intraoperative ultrasound to identify the diseased aorta may result in alternative operative strategies in an effort to minimize emboli and improve neurologic outcome. Existing literature offers conflicting views on optimal management of carotid artery stenosis in the coronary artery surgical patient. A trend that combined carotid endarterectomy and coronary artery bypass may often be appropriate will need confirmation through a multicenter clinical trial. Open cardiac surgical procedures, particularly in the aged population, carry a significant increased risk of adverse neurologic outcome. Postoperative arrhythmias may result in embolic neurologic deficit. A further understanding of risk factors for cerebral injury will be of value in developing therapeutic approaches to this major clinical problem.

Mitral valve operation via an extended transseptal approach.

The extended transseptal approach to the mitral valve has been used for 71 consecutive procedures. Four patients died; none had complications directly attributable to the exposure. Twenty underwent a primary reparative procedure; 30, a primary replacement procedure; and 21, a repeat procedure. Despite division of the sinus node artery, 26 of 32 patients with sinus rhythm preoperatively had sinus rhythm postoperatively; 4 had atrial fibrillation postoperatively. Twenty-seven of 37 patients with atrial fibrillation preoperatively had atrial fibrillation postoperatively; 8 had sinus rhythm postoperatively. Because the exposure provided by this extended transseptal approach is superior to that of standard approaches, we now use it routinely for mitral valve operations.

Surgical revascularization of acute evolving myocardial infarction without blood cardioplegia fails to restore postischemic function in the involved segment.

This study determines the additional protection provided by multidose hypothermic potassium blood cardioplegia over cardiopulmonary bypass alone following one hour of coronary occlusion. In 19 anesthetized dogs having an open-chest procedure, the left anterior descending coronary artery (LAD) was occluded for one hour, and this resulted in loss of active shortening in the affected zone (sonomicrometry). Cardiopulmonary bypass was established, and the dogs were divided into two groups based on the mode of reperfusion. In 10 dogs, hearts were arrested for one hour with amino acid-enhanced multi-dose blood cardioplegia; the ligatures were removed prior to the second infusion. In the 9 remaining dogs, the ligatures were removed and reperfusion was initiated with unmodified blood on total vented bypass. Both groups were reperfused for one additional hour. Postischemic levels of adenosine triphosphate (ATP) were comparable in the blood cardioplegia and bypass groups, and subendocardial levels averaged 42.8% and 45.8% of controls, respectively. Levels of creatine phosphate returned to control values. Subendocardial water content was significantly less in the blood cardioplegia hearts than the bypass hearts (79.4 +/- 0.5% vs. 81.5 +/- 0.5%; p less than .05); subendocardial water content in the blood cardioplegia group was not different from controls (78.6 +/- 0.1%). Blood cardioplegia restored significantly more fractional shortening than total vented bypass alone (39.3 +/- 9.8% vs. 6.3 +/- 9.1% of control), despite similarities in postischemic levels of ATP. We conclude that blood cardioplegia allows better myocardial salvage in the setting of evolving infarction. Therefore, attention must be directed to both the conditions (bypass, delivery pressure) and composition (cardioplegia) of reperfusion.

Surgical implications in malignant cardiac disease.

Despite the rarity of primary malignant tumors of the heart (0.0017 to 0.03% of large postmortem series) and the infrequency of clinical signs and symptoms (0 to 50%) of the more common metastatic cardiac tumors, many cardiothoracic surgeons at some time will encounter a patient with one of these two conditions. A review of the medical literature yielded 28 cases of primary cardiac tumors, 10 of secondary tumors, and 12 of carcinoid heart disease treated surgically and followed sufficiently for retrospective evaluation. We summarized those cases and made the following conclusions. Primary malignant tumors of the heart are occasionally resectable, although cure is unlikely; survival may be enhanced by postoperative irradiation but probably not by postoperative chemotherapy. For patients with secondary malignant tumors of the heart, surgical intervention is rarely of benefit except for establishing a tissue diagnosis, effecting artificial cardiac pacing, decompressing symptomatic pericardial effusions, or reducing an obstructive tumor mass. Patients with carcinoid heart disease affecting the valves may derive benefit from valve replacement or repair. Thus, in selected patients with malignant cardiac disease, surgical intervention may be feasible and should always be among the therapeutic options considered.

A prospective study of sternal wound complications.

Eight hundred seventy patients were enrolled in a prospective study to identify risk factors for sternal wound complications following open-heart operations. The 0.8% incidence of major sternal complications was similar to that reported in the literature by other centers. The effects of age, sex, weight, operative time, type of procedure, resident versus attending surgeon, prolonged ventilatory support, reoperation for bleeding, external cardiac massage, and Dacron versus wire suture for sternal closure were assessed by stepwise logistic regression. Prolonged ventilation and female sex both strongly increased the risk of major sternal complications. Age and weight exerted lesser, but statistically significant, effects on the incidence of such complications. None of the other factors was associated with an increased risk of major sternal complications.

Improved lung preservation with cold air storage.

Conventional topical slush cooling limits lung transport to 4 to 6 hours. For this canine study of an alternate air cooling system, 37 canine lungs were removed: 24 were placed in plastic bags, and inserted in a Transplanthermm container at core air temperatures (n = 6 lungs each) of (A) 4 degrees C, (B) 8 degrees C, (C) 12 degrees C, and (D) 20 degrees C; 6 were stored conventionally in ice slush (E); and 7 were transplanted immediately (F). After 8 hours, the stored lungs were transplanted and the contralateral pulmonary artery was ligated. Survival, arterial oxygen tension, and extravascular lung water were monitored at 15 minutes and every hour for 4 hours. Four-hour survival was 100% in groups A, B, and F; 83% in group C, 50% in group D, and 17% in group E. The mean arterial oxygen tension at 1 hour was lower in group E (6.4 +/- 2.4 kPa) than in group A (39.8 +/- 13.2 kPa) (p = 0.0002) or in group F (42.0 +/- 16.2 kPa) (p = 0.0035). Extravascular lung water in group E was higher at 15 minutes (15.44 +/- 5.63 mL/kg) than in group A (3.76 +/- 0.63 mL/kg) (p = 0.0001) and group F (4.69 +/- 1.65 mL/kg) (p = 0.003). Cold air storage appears to provide better lung preservation than hypothermic immersion in ice slush.

Myocardial protection with blood cardioplegia in ischemically injured hearts: reduction of reoxygenation injury with allopurinol.

Myocellular injury mediated by oxygen radicals potentially limits myocardial protection in ischemically damaged hearts. This damage may be greater with oxygen-carrying blood cardioplegic solutions. A major mechanism of oxygen radical production is the conversion of hypoxanthine to uric acid by xanthine oxidase. In 16 anesthetized dogs, we studied whether adding allopurinol, a xanthine oxidase inhibitor, to blood cardioplegia would improve recovery of left ventricular (LV) performance and oxygen consumption. Millar transducer-tipped catheters and minor axis ultrasonic crystals were placed to assess LV performance by the slope of the end-systolic pressure-minor axis diameter relationships (Emax). Following total vented bypass, the hearts underwent 30 minutes of normothermic ischemia and then hypothermic blood cardioplegia with 1 mM allopurinol (N = 8) or without allopurinol (N = 8). Postischemic LV performance was significantly better with allopurinol than without (49.5 +/- 8.0 versus 17.4 +/- 4.1% of preischemic Emax; p less than 0.004). Postischemic LV oxygen consumption in the beating working state, calculated from LV blood flow (15 microm microspheres) and oxygen extraction, was comparable to preischemic values with and without allopurinol (10.2 +/- 1.2 versus 8.6 +/- 1.2 ml O2/100 gm/min). We conclude that allopurinol enhancement of blood cardioplegia increases myocardial protection in severely ischemic ventricles.

Surgical revascularization of acute (1 hour) coronary occlusion: blood versus crystalloid cardioplegia.

This study compares blood versus crystalloid cardioplegia in restoring contractile function, and high-energy phosphate and tissue water content in a myocardial segment after 1 hour of coronary artery occlusion. Anesthetized dogs underwent instrumentation with the chest open to measure left ventricular and aortic pressures, and systolic shortening in the myocardium perfused by the left anterior descending coronary artery (LAD) was measured with ultrasonic crystals. In 21 dogs, the LAD was occluded for an hour, thereby replacing systolic shortening with passive lengthening averaging -28.7 +/- 6.2% of control shortening in both groups. The dogs were then placed on total bypass, and arrest was achieved with multidose crystalloid (N = 10) or blood cardioplegia (N = 11). The ligatures were released just prior to the second infusion of cardioplegic solution. Postischemic subendocardial levels of adenosine triphosphate were comparably depleted with crystalloid and blood cardioplegia (55.2% and 44.0%, respectively, of control). Subendocardial increases in water content were similar for crystalloid (3.62%) and blood (3.16%) cardioplegia. Recovery of segmental shortening was significantly greater with blood than crystalloid cardioplegia (31.5 +/- 8.2% versus 4.9 +/- 6.6% of control, respectively). We conclude that the composition and the delivery of blood cardioplegia used in this study restore greater postischemic function than crystalloid cardioplegia in acute evolving myocardial infarction.