Real-time SPIDER: ultrashort pulse characterization at 20 Hz.

We present an implementation of spectral phase interferometry for direct electric-field reconstruction (SPIDER) which characterizes ultrashort optical pulses in the spectral or temporal domain at a rate of 20 Hz. This apparatus was used in real-time as a diagnostic tool to optimize our 1 kHz regeneratively amplified laser system for the shortest duration pulses.

Noninvasive detection of cardiac allograft rejection by prospective telemetric monitoring.

A method for cardiac allograft surveillance that is less invasive than endomyocardial biopsy is needed. A fall in the unipolar peak-to-peak amplitude recorded from cardiac allografts has been shown to detect rejection when retrospectively compared with endomyocardial biopsy. This study was performed to assess the sensitivity and specificity of prospective telemetric unipolar peak-to-peak amplitude surveillance in detecting rejection of heterotopic canine cardiac allografts occurring through triple drug immunosuppression. Native heart and graft amplitudes were telemetrically acquired on a daily basis. A fall in normalized unipolar peak-to-peak graft amplitude to less than 85% was used as an indication for biopsy. A quantitative rejection score was calculated for each endomyocardial biopsy (rejection score greater than 0.66 = histologic rejection). Rejection was documented in all animals. Thirty-six biopsies were performed (10 control biopsies and 26 amplitude-directed biopsies); 25 of the 36 demonstrated rejection. Sensitivity and specificity were 88% and 91%, respectively. A linear correlation between unipolar peak-to-peak amplitude and rejection severity was seen (R = 0.87, p less than 0.001). The first true positive amplitude was associated with mild-to-moderate rejection (rejection score = 1.63 +/- 0.45). Unipolar peak-to-peak amplitude recorded from native hearts remained stable during allograft rejection. It is concluded that prospective, telemetric cardiac allograft surveillance can accurately detect rejection occurring through ongoing immunosuppression.

Profound systemic hypothermia protects the spinal cord in a primate model of spinal cord ischemia.

Spinal cord ischemia with resultant paraplegia or paraparesis remains an important clinical problem after operations on the thoracoabdominal aorta. Because hypothermia has a protective effect on ischemic neural tissue, we developed a baboon model of spinal cord ischemia to simulate the situation encountered clinically for resection of aneurysms of the thoracoabdominal aorta and to determine whether profound hypothermia produced by hypothermic cardiopulmonary bypass has a protective effect on spinal cord function. After cardiopulmonary bypass was established, the aorta was clamped distal to the left subclavian artery and proximal to the renal arteries for 60 minutes. Group I animals (n = 9) underwent aortic clamping at normothermia (37 degrees C), and group II animals (n = 9) were cooled to a rectal temperature of 15 degrees C before aortic clamping and underwent cardiopulmonary bypass at this temperature until the aorta was unclamped. Of the eight operative survivors in group I, six animals were paraplegic and two were paraparetic, whereas all six group II animals that survived the procedure were neurologically intact (p = 0.0002). The protective effect of hypothermia was associated with blunting of the hyperemic response of spinal cord blood flow (determined by the radioactive microsphere technique) in the lower thoracic and the lumbar segments of the spinal cord after unclamping of the aorta. Profound hypothermia produced by hypothermic cardiopulmonary bypass may be an effective method of protection of the spinal cord in patients undergoing repair of aneurysms of the thoracoabdominal aorta and may reduce the prevalence of ischemic injury to the spinal cord.

Injury in nonischemic lung after unilateral pulmonary ischemia with reperfusion.

We developed an in vivo intact canine model to study pulmonary ischemia-reperfusion (IR) injury. The surgical approach simulates that of unilateral lung transplantation but is free of technical difficulties and other factors related to lung preservation. Serial measurements of regional pulmonary blood flow (rPBF), extravascular density (EVD), and transcapillary protein flux were made with the quantitative imaging technique of positron emission tomography. Eleven experimental and six control animals were studied. After 2 h of warm ischemia followed by reperfusion, no significant change occurred in rPBF despite significantly increased EVD, which was greater on the ischemic than on the nonischemic side. Protein flux, measured as a rate constant, was also greater on the ischemic than on the nonischemic side (median 181 x 10(-4)/min, range 104-619, vs. median 90, range 33-132) immediately after reperfusion. Both sides were also significantly different from control values (median 37, range 21-57). On both sides, protein flux decreased over time and at 5 h after reperfusion was not different from that of controls. Data from the control animals showed that these findings in the experimental animals were not due to surgical technique, deterioration in the surgical preparation, or hyperperfusion of the nonischemic lung. Thus IR injury of one lung can lead to similar, but less severe, injury in the contralateral lung. Because injury in the nonischemic lung develops only after reperfusion of the ischemic lung, injury to the nonischemic lung is probably humorally mediated. The model is a useful and relevant method for studying the physiological consequences of pulmonary IR injury.

Inflammation and oxygen free radical formation during pulmonary ischemia-reperfusion injury.

In a companion study, we showed that 2 h of warm unilateral lung ischemia followed by reperfusion resulted in bilateral tissue injury, indicated by increases in extravascular density (EVD) and permeability, measured as the pulmonary transcapillary escape rate (PTCER) for radiolabeled transferrin. EVD and PTCER measurements were obtained with the quantitative imaging technique of positron emission tomography (PET). In the current study, we evaluated this increase in EVD histologically and correlated EVD and PTCER with measurements of oxidant-reactive sulfhydryls (RSH) in plasma as a marker of oxygen free radical (OFR) formation. Histologically edema, leukocyte infiltration, and hemorrhage were all present on the ischemic side, but only after reperfusion, whereas only neutrophil infiltration was observed on the nonischemic side. Histology scores correlated with EVD (r = 0.81) and PTCER (r = 0.75), but permeability was abnormal at times even in the absence of neutrophil infiltration. Plasma RSH concentration from the ischemic lung decreased significantly (P less than 0.05) during pulmonary ischemia (i.e., before reperfusion) and returned to baseline on reperfusion. The degree of RSH oxidation did not correlate with the severity of injury as measured by PET or histology. Thus pulmonary ischemia-reperfusion injury is characterized by inflammation, hemorrhage, edema, and OFR formation. Injury occurred after reperfusion, not after ischemia alone. In addition, injury to the contralateral nonischemic lung suggests a neutrophil-independent circulating mediator of injury.

Cardiac Whipple's disease without digestive symptoms.

Whipple's disease is a systemic illness that can affect the heart, causing pericarditis, myocarditis, and valvular endocarditis. We describe a 43-year-old man without gastrointestinal symptoms who underwent mitral and aortic valve replacement for endocarditis, in whom a diagnosis of Whipple's disease was made at operation.

Intracoronary ultrasound-guided CABG in patients with angiographically noncritical lesions. Cardiovascular Surgery Associates.

BACKGROUND: Coronary angiography is used to determine the severity of coronary artery disease; however, in a small group of patients, clinically significant angina and physiologic tests indicative of myocardial ischemia do not correlate with angiographically demonstrable critical coronary artery disease. In these patients intracoronary ultrasound may demonstrate the true severity of lesions. METHODS: Eight patients with angina and positive stress testing but without angiographically critical left main or left anterior descending artery stenoses were retrospectively identified. After intracoronary ultrasonic demonstration of critical left main or left anterior descending artery lesions, coronary artery bypass grafting was performed. Follow-up evaluation of clinical status and repeat stress testing were carried out. RESULTS: Intracoronary ultrasound demonstrated critical left main (n = 4) or proximal left anterior descending artery (n = 7) stenoses in all patients. Severity of angiographic versus intracoronary ultrasound-documented stenoses was (mean +/- standard error of the mean) 10% +/- 10% versus 65% +/- 10% for left main lesions and 30% +/- 5% versus 75% +/- 5% for left anterior descending artery lesions. After coronary artery bypass grafting all patients had decreased angina and normalization of stress testing. CONCLUSIONS: In patients with clinical presentations indicative of significant coronary artery disease but with angiographically noncritical lesions, intracoronary ultrasound can accurately assess the severity of stenoses. Coronary artery bypass grafting guided by intracoronary ultrasonic findings successfully treats myocardial ischemia in these patients.

Use of intraoperative mapping to optimize surgical ablation of atrial flutter.

The purpose of this study was to develop a surgical treatment for atrial flutter using intraoperative activation sequence mapping to minimize the surgical procedure necessary to ablate the flutter. A canine model (n = 10) of left atrial enlargement was developed by creating a shunt from the left subclavian artery to the left superior pulmonary vein. Sustained atrial flutter was easily induced in this model. The flutter consisted of a single reentrant circuit that rotated around one or two anatomic obstacles linked by a region of functional block. Epicardial templates, consisting of 252 bipolar electrodes, were used to record activation time maps. After localization of the reentrant circuit, surgical incisions were placed to interrupt the pathways. In all 10 animals, flutter could be induced and intraoperative mapping localized the reentrant circuit. Seven circuits were in the right atrium and three were in the left atrium. The operation ablated all of the preoperative circuits. However, in 5 of the animals, flutter originating from a new circuit could be induced. Activation sequence mapping before and after operation demonstrates that there are multiple potential reentrant pathways in this canine model of atrial flutter. Therefore, all potential pathways must be surgically interrupted to prevent inducibility of atrial flutter.

Intraoperative echocardiographic diagnosis of previously unrecognized cor triatriatum.

Cor triatriatum is a congenital heart defect resulting in abnormal septation of the left atrium by a fibromuscular membrane. Echocardiography has improved the preoperative diagnosis of this rare congenital heart defect. We report a case where transesophageal echocardiography proved useful in the intraoperative diagnosis of a previously undetected cor triatriatum.

Early cardiac allograft rejection is independent of regional myocardial blood flow.

Noninvasive telemetric monitoring of canine heterotopic cardiac allograft unipolar peak-to-peak amplitude (UPPA) has permitted prospective surveillance for rejection; moreover, this technique is able to reliably detect rejection before the development of histologic evidence of myocyte necrosis. This study was performed to determine whether early cardiac allograft rejection and the accompanying decline in allograft UPPA were associated with alterations in regional myocardial blood flow (RMBF). Seven heterotopic, intrathoracic canine cardiac transplantations were performed using triple-drug immunosuppression. Native hearts and allografts were instrumented with right ventricular and left ventricular epicardial screw-in electrodes connected to subcutaneous telemeters. Daily measurement of native and graft UPPA was performed; using radioactive microspheres, native and graft RMBF were determined during the control period and when UPPA had declined by 15%, 30%, and 45%. Graft histologic status was determined by endomyocardial biopsy at the time of RMBF determination. Mean duration of the study was 19.7 +/- 3.9 days. Rejection was documented in all animals. The UPPA was stable in native hearts; UPPA declined in the allografts after the onset of rejection. A biphasic change in allograft blood flow was seen. Initially RMBF increased as UPPA declined; a 30% to 45% reduction in UPPA was associated with a 41% increase in RMBF (p = 0.028 versus allograft control). Subsequently, a significant decline in blood flow was observed for reductions in UPPA greater than 45% (0.68 +/- 0.44 versus 1.07 +/- 0.47 mL.g-1 x min-1 for a 30% to 45% decline in UPPA; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Free radical scavengers and myocardial preservation during transplantation.

The efficacy of oxygen radical scavengers in preservation of left ventricular (LV) function after prolonged hypothermic global ischemia was investigated in a model of orthotopic cardiac transplantation in sheep. Group 1 hearts (N = 8) received hypothermic crystalloid cardioplegic solution, and were harvested and stored at 4 degrees C in balanced electrolyte solution for six hours prior to transplantation. Group 2 (N = 9) received identical treatment with the addition of 30,000 units of superoxide dismutase to the cardioplegic solution and the administration of 60,000 units of superoxide dismutase coincident with reperfusion. All animals were weaned from cardiopulmonary bypass. Preischemic and postischemic LV function was determined using sonomicrometry and a micromanometer-tipped LV catheter. Coronary blood flow was determined using standard microsphere techniques, and platelet deposition was assayed with autologous platelets labeled with indium 111. Lipid peroxidation products were measured using thiobarbituric acid assay. LV performance was significantly better (p less than .05) in Group 2 hearts when assessed by the slope of the end-systolic pressure-volume relationship and the stroke work versus end-diastolic volume relationship. There was better preservation of endocardial blood flow in the group receiving superoxide dismutase compared with controls (p less than .05). Platelet deposition, as determined by the tissue to blood ratio of scintigraphic counts, was greater (p less than .05) in controls compared with the group receiving superoxide dismutase. In addition, thiobarbituric acid reactive species were significantly less (p less than .05) in Group 2 versus Group 1 hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Intermittent reperfusion extends myocardial preservation for transplantation.

A protocol was developed to compare prolonged heart preservation by hypothermic storage with prolonged hypothermic storage interrupted by a period of reperfusion. Hearts from adult mongrel dogs were excised after administration of 4 degrees C crystalloid cardioplegia. Group A hearts (N = 7) underwent 7.5 hours of ischemia at 4 degrees C followed by 1.5 hours of reperfusion and rewarming (A0). Group B hearts (N = 8) underwent 3 hours of ischemia at 4 degrees C, 1.5 hours of reperfusion and rewarming (B1), 3 additional hours of ischemia at 4 degrees C following repeat cardioplegia, and finally 1.5 hours of reperfusion and rewarming (B2). During reperfusion, hearts were defibrillated and left ventricular (LV) function was assessed by measuring isovolumic peak systolic pressure and maximum positive rate of rise of LV pressure (+dP/dtmax) with an intraventricular balloon. LV biopsy samples for adenosine triphosphate (ATP) assay were obtained before ischemia and after each rewarming period. One Group A heart could not be defibrillated and studied. All Group B hearts completed the protocol. LV function, as assessed by peak pressure and +dP/dtmax, at B1 and B2 exceeded values obtained at A0, but the differences were not statistically significant. The mean ATP level was 63.4 +/- 7.7% of baseline at B1 and 79.7 +/- 4.3% of baseline at B2 (p less than .03). The mean ATP level was 57.9 +/- 5.9% of baseline at A0 (p less than .007, B2 vs. A0). It is presumed that intermittent reperfusion allows repletion of substrate stores, which results in improved myocardial protection.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of Toronto stentless porcine valve in patients with aortic dilation.

One of the contraindications for a stentless aortic valve is dilation of the aorta such that the sinotubular ridge is more than 2 mm larger than the annulus. Since May of 1994, 134 patients have had their aortic valve replaced with St Jude Toronto SPV valves; of these, 38 patients have required sinotubular ridge reduction. This was done by using one or more pleats in the aorta between the commisural posts. There were 20 patients with one pleat, 12 patients with two pleats, 5 patients with three pleats, and 1 patient with four pleats. In addition, three Toronto SPV valves were used in patients with significant calcification in the native coronary sinuses. All of the valves have had trace or no aortic insufficiency and have not developed aortic insufficiency in follow-up evaluation. Mean gradients remain low (<10 mm Hg). These valves have been much more versatile than originally expected and can be used in patients with mild to moderate aortic dilation and calcification.

Experimental evaluation of a new albumin-impregnated knitted dacron prosthesis.

The performance of a new albumin-impregnated, knitted vascular graft stored damp in saline was assessed by a comparative study in the canine aorta. Knitted grafts interposed into the descending thoracic aorta for 4 weeks included: albumin-coated and stored damp in saline (damp albuminated) (n = 6), albumin-coated and freeze-dried (dry albuminated) (n = 5), collagen-coated (n = 4), and uncoated (n = 4). The results of macroscopic and microscopic evaluation were subjected to one-way analysis of variance (Newman-Keuls). Damp albuminated grafts had significantly less transinterstitial blood loss than uncoated grafts (P less than 0.05). No significant differences in thrombogenicity, thrombus-free surface area, tissue ingrowth, or endothelial coverage existed between the damp albuminated and the uncoated grafts. However, significantly less thrombogenicity (P less than 0.05) and more endothelial cell coverage (P less than 0.05) were present in the damp albuminated grafts than in the collagen-coated grafts. No evidence for delayed graft hemorrhage or distal embolization was found in any group. The new damp albuminated graft is a minimally thrombogenic prosthesis combining low implantation porosity with relative ease of handling. It should function well as a low porosity graft for great vessel replacement.

Long-term assessment of a damp-stored, albumin-coated, knitted vascular graft.

In a previous study the authors reported greater endothelialization and thrombus-free surface area in albumin-coated grafts compared with collagen-coated grafts after 1 month's aortic interposition. Another study was undertaken to determine whether these differences persisted after a 6-month implantation period. A 6 cm segment of either an albumin-coated [n = 6] or a collagen-coated [n = 4] graft was implanted into a canine descending thoracic aorta for 6 months. Light micrographs from multiple sections of each explanted graft were scored from 1 to 4, least to most, for tissue ingrowth, perigraft inflammation, and capsular thickness. Using computer planimetry, luminal thrombus free surface area and endothelial coverage were calculated from gross and electron photomicrographs, respectively. The results were averaged and expressed as mean +/- standard error (SEM). After 6 months, no significant differences were noted between the albumin-coated grafts and the collagen-coated grafts, both of which were durable and served equally well as scaffolds for vascular remodeling and tissue incorporation. The authors conclude that the safety, ease of handling, low porosity, low thrombogenicity, and durability of the albuminated grafts warrant their clinical trial.

Patterns of practice in palliative radiotherapy in Africa - case revisited.

AIMS: To investigate patterns of practice in palliative radiotherapy in Africa. MATERIALS AND METHODS: Fifteen centres in Africa provided detailed information about radiotherapy in both metastatic and locally advanced disease via a questionnaire. Information included general information (institution status, equipment, staff, patient number), radiotherapy and other treatment characteristics in bone metastasis, brain metastasis, metastatic spinal cord compression, lung and liver metastasis, as well as locally advanced tumours. RESULTS: The number of patients annually seen/treated ranged from 285 to 5000. Breast, cervix, head and neck, gastrointestinal and prostate cancer were the top five cancers overall. Eight (53%) institutions were without linear accelerators, four (27%) had a single one, whereas one institution each had two, three and four linear accelerators. The number of cobalt machines ranged from 0 to 2 (median 1). Most centres still prefer to use fractionated radiotherapy regimens over single-fraction regimens in bone metastasis, although most centres are now using single-fraction radiotherapy in retreatments. Radiotherapy in brain metastasis and metastatic spinal cord compression mostly conform to worldwide standards. Lung and liver metastases are rarely irradiated, largely as a consequence of the lack of modern radiotherapy technology. Locally advanced disease in various tumour sites was mostly palliated, in agreement with current evidence-based practices. CONCLUSIONS: African countries still lack adequate staffing and equipment to adequately address their clinical burden, being palliative in most cases. Emphasis should also be made on more rationally using existing capacities by using more of the single-fraction radiotherapy regimens, especially in bone metastasis.

Eosinophil 15-lipoxygenase is a leukotriene A4 synthase.

5-Lipoxygenase is the first committed enzyme in the leukotriene biosynthetic pathway and is known to catalyze not only the first oxygenation of arachidonate to form 5(S)-hydroperoxyeicosatetraenoic acid (5(S)-HPETE), but also dehydration of this intermediate into leukotriene A4 (LTA4) by an activity termed leukotriene A4 synthase. Inhibition of cytosolic 5-lipoxygenase prepared from human blood granulocytes with zileuton (100 microM) was virtually complete, but LTA4 synthase activity was only inhibited by 47%. Structural characterization of eicosanoids synthesized in these preparations revealed an abundance of 15-lipoxygenase metabolites including 15-HETE when arachidonate was used as substrate and 5(S),15(S)-dihydroxy-6,8,11,13(E,E,Z,Z)-eicosatetraenoic acid when 5(S)-HPETE was used as substrate. When neutrophils were prepared that contained less than 1% eosinophil contamination, zileuton was found to almost completely inhibit all 5-lipoxygenase, as well as LTA4 synthase products. Immunochemical analysis of the supernatants from purified neutrophils and eosinophils confirmed the previous observation that neutrophils do not express 15-lipoxygenase. Incubation of 5(S)-HPETE with recombinant mammalian 15-lipoxygenase resulted in the formation of 6-trans-LTB4 and 6-trans-12-epi-LTB4 as LTA4 products, as well as the 12-lipoxygenase product 5(S),12(S)-diHPETE. The mechanism of action of 15-lipoxygenase acting as an LTA4 synthase is proposed to involve removing the pro-R hydrogen atom at carbon-10 of 5(S)-HPETE, which is antarafacial to the hydroperoxy group to yield LTA4.

Surgical intervention in neonates with critical pulmonary stenosis.

The surgical experience with 18 consecutive neonates with critical pulmonary stenosis (PS) and intact ventricular septum was reviewed. All patients had cardiac catheterization with calculation of right ventricular volume. Group A patients (N = 8) had a small right ventricular end-diastolic volume (RVEDV less than 72% of predicted). Group B patients (N = 10) had a normal or enlarged RVEDV. All patients had a closed pulmonary valvotomy. Five Group A patients required a systemic-pulmonary shunt or prostaglandin (PGE1) after operation; one patient died. Nine Group B patients did well after valvotomy; one moribund patient died after valvotomy and shunt. Six of 16 survivors required reoperation: valvectomy in four patients and shunt takedown in two patients. Four of the six patients who had reoperation also had a transannular patch. There was one unrelated late death. All long-term survivors are asymptomatic. Recatheterization in four patients with a small right ventricle (RV) documented significant RV growth. In conclusion, most neonates with critical PS can be managed with closed valvotomy. Patients with a small RV may require PGE1 or a shunt after operation for persistent hypoxemia. Some patients with a small RV will have significant RV growth after valvotomy.