Blood lactic acid levels after artificial heart implantation.

The aim of this study is to investigate blood lactic acid levels after the placement of the AbioCor implantable replacement heart to determine whether circulatory support with the AbioCor device results in adequate tissue perfusion. Tissue perfusion may not be adequate during cardiac surgery, especially with the use of cardiopulmonary bypass (CPB). Inadequate perfusion is usually associated with anaerobic metabolism, metabolic acidosis, and lactate accumulation. Ten calves had implantation of the AbioCor by means of a right thoracotomy. Standard cardiopulmonary bypass was performed during surgery. Lactic acid levels and blood gas analyses were measured. All animals were monitored for pressures in the aorta, pulmonary artery, and left and right atria. The output of the AbioCor was calculated based on beat rate and stroke volume. All animals were rapidly weaned off cardiopulmonary bypass to full AbioCor support and had normal hemodynamics with normal filling pressures. The lactic acid levels were elevated after surgery, peaked at 8 to 12 hours, and then gradually decreased to the normal range 24 hours after surgery. There was a positive relationship between lactate levels, oxygen consumption, and extraction rate, that is, the lactic acid levels were higher in the presence of increased oxygen consumption and increased oxygen extraction rate. There was a negative relationship between lactate levels and oxygen delivery, and arterial and venous oxygen content, that is, the lactic acid levels were higher when oxygen delivery and arterial and venous oxygen contents were low. The pathophysiology of lactic acidosis is uncertain, but is most likely due to inadequate perfusion during cardiopulmonary bypass, and lactate washout after adequate perfusion has been established. The return to aerobic metabolism with clearance of lactate demonstrates that the AbioCor is able to provide complete circulatory support with normal tissue perfusion.

Factors that predict the presence of sentinel lymph node metastasis in patients with melanoma.

BACKGROUND: This analysis was performed to identify prognostic factors that are predictive of sentinel lymph node (SLN) metastasis in melanoma. METHODS: Analysis was performed of a multi-institutional, prospective, randomized trial of SLN biopsy for melanoma. Eligibility criteria included age 18 to 70 years, Breslow thickness of 1.0 mm or more, and clinically negative regional lymph nodes. SLNs were evaluated by serial sectioning and immunohistochemistry for S100. Univariate chi-square and multivariate logistic regression analyses were performed to assess factors predictive of the presence of a positive SLN. Probability values of less than.05 were considered significant. RESULTS: SLNs were identified in 99.7% of patients. A total of 1058 patients were evaluated; 961 patients had complete data and were included in the statistical analysis. SLNs were positive for tumor in 208 of 961 patients (22%). Breslow thickness, Clark level, ulceration, and patient age were factors that were found to be independently predictive of the presence of SLN metastasis. CONCLUSIONS: Increasing Breslow thickness, Clark level of more than III, the presence of ulceration, and patient age of 60 years or less are the most important independent prognostic factors associated with the finding of positive SLN in patients with melanoma.

Sentinel lymph node biopsy for breast cancer: impact of the number of sentinel nodes removed on the false-negative rate.

BACKGROUND: Numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine axillary nodal status for breast cancer, but unacceptably high false negative rates have also been reported. Attention has been focused on factors associated with improved accuracy. We have previously shown that injection of blue dye in combination with radioactive colloid reduces the false negative rate compared with injection of blue dye alone. We hypothesized that this may be from the increased ability to identify multiple sentinel nodes. The purpose of this analysis was to determine whether removal of multiple SLNs results in a lower false negative rate. STUDY DESIGN: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multiinstitutional study. Patients with clinical stage T1-2, N0 breast cancer were eligible for enrollment. All patients underwent SLN biopsy using blue dye alone, radioactive colloid alone, or both agents in combination, followed by completion level I and II axillary dissection. RESULTS: A total of 1,436 patients were enrolled in the study from August 1997 to February 2000. SLNs were identified in 1,287 patients (90%), with an overall false negative rate of 8.3%. A single SLN was removed in 537 patients. Multiple SLNs were removed in 750 patients. The false negative rates were 14.3% and 4.3% for patients with a single sentinel node versus multiple sentinel nodes removed, respectively (p = 0.0004, chi-square). Logistic regression analysis revealed that use of blue dye injection alone was the only factor independently associated with identification of a single SLN (p<0.0001), and patient age, tumor size, tumor location, surgeon's previous experience, and type of operation were not significant. CONCLUSIONS: The ability to identify multiple sentinel nodes, when they exist, improves the diagnostic accuracy of SLN biopsy. Injection of radioactive colloid in combination with blue dye improves the ability to identify multiple sentinel nodes compared with the use of blue dye alone.

Predicting the status of the nonsentinel axillary nodes: a multicenter study.

BACKGROUND: Sentinel lymph node (SLN) biopsy is a minimally invasive procedure that provides accurate nodal staging information. The need for completion axillary dissection after finding a positive SLN for breast cancer has been questioned. HYPOTHESIS: The presence of nonsentinel node (NSN) metastases in the axillary dissection specimen correlates with tumor size, the number of SLNs removed, and the number of positive SLNs. DESIGN: Prospective, multi-institutional study. PARTICIPANTS AND METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a nationwide study involving 148 surgeons. All patients underwent SLN biopsy, followed by level I/II axillary dissection. All SLNs were evaluated histologically at a minimum of 2-mm intervals. Immunohistochemical analysis using antibodies for cytokeratin was performed at the discretion of each participating institution. All NSNs were evaluated by routine histologic examination. RESULTS: An SLN was identified in 1268 (90%) of 1415 patients. Increasing tumor size was significantly correlated with increasing likelihood of positive NSNs: T1a, 14%; T1b, 22%; T1c, 30%; T2, 45%; and T3, 57% (P =.002, chi(2) test). The presence of positive NSNs was not significantly associated with the number of SLNs removed. Patients with more than 1 positive SLN were more likely to have positive NSNs than those with only 1 positive SLN (50% vs 32%; P<.001, chi(2) test). Increasing tumor size and the presence of multiple positive SLNs were also associated with the presence 4 or more positive axillary nodes. Multivariate analysis confirmed that tumor size and the number of positive SLNs were independent factors predicting the presence of positive NSNs. CONCLUSIONS: The likelihood of positive NSNs correlates with increasing tumor size and the presence of multiple positive SLNs. However, even patients with small primary tumors have a substantial risk of residual axillary nodal disease after SLN biopsy. These data will be helpful in counseling patients regarding the need for completion axillary dissection after a positive SLN is identified.

Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: results of a multiinstitutional study.

OBJECTIVE: To determine the optimal radioactive colloid injection technique for sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: The optimal radioactive colloid injection technique for breast cancer SLN biopsy has not yet been defined. Peritumoral injection of radioactive colloid has been used in most studies. Although dermal injection of radioactive colloid has been proposed, no published data exist to establish the false-negative rate associated with this technique. METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multiinstitutional study involving 229 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed at the discretion of the operating surgeon. Peritumoral injection of isosulfan blue dye was performed concomitantly in most patients. The SLN identification rates and false-negative rates were compared. The ratios of the transcutaneous and ex vivo radioactive SLN count to the final background count were calculated as a measure of the relative degree of radioactivity of the nodes. One-way analysis of variance and chi-square tests were used for statistical analysis. RESULTS: A total of 2,206 patients were enrolled. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed in 1,074, 297, and 511 patients, respectively. Most of the patients (94%) who underwent radioactive colloid injection also received peritumoral blue dye injection. The SLN identification rate was improved by the use of dermal injection compared with subdermal or peritumoral injection of radioactive colloid. The false-negative rates were 9.5%, 7.8%, and 6.5% (not significant) for peritumoral, subdermal, and dermal injection techniques, respectively. The relative degree of radioactivity of the SLN was five- to sevenfold higher with the dermal injection technique compared with peritumoral injection. CONCLUSIONS: Dermal injection of radioactive colloid significantly improves the SLN identification rate compared with peritumoral or subdermal injection. The false-negative rate is also minimized by the use of dermal injection. Dermal injection also is associated with SLNs that are five- to sevenfold more radioactive than with peritumoral injection, which simplifies SLN localization and may shorten the learning curve.

Sentinel lymph node biopsy for melanoma: how many radioactive nodes should be removed?

BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard method of staging patients with cutaneous melanoma. Sentinel lymph node biopsy usually is performed by intradermal injection of a vital blue dye (isosulfan blue) plus radioactive colloid (technetium sulfur colloid) around the site of the tumor. Intraoperative gamma probe detection has been shown to improve the rate of SLN identification compared to the use of blue dye alone. However, multiple sentinel nodes often are detected using the gamma probe. It is not clear whether these additional lymph nodes represent true sentinel nodes, or second-echelon lymph nodes that have received radiocolloid particles that have passed through the true sentinel node. This analysis was performed to determine the frequency with which these less radioactive lymph nodes contain metastatic disease when the most radioactive, or "hottest," node does not. MATERIALS AND METHODS: In the Sunbelt Melanoma Trial, 1184 patients with cutaneous melanoma of Breslow thickness 1.0 mm or more had sentinel lymph nodes identified. Sentinel lymph node biopsy was performed by injection of technetium sulfur colloid plus isosulfan blue dye in 99% of cases. Intraoperative determination of the degree of radioactivity of sentinel nodes (ex vivo) was measured, as well as the degree of blue dye staining. RESULTS: Sentinel nodes were identified in 1373 nodal basins in 1184 patients. A total of 288 of 1184 patients (24.3%) were found to have sentinel node metastases detected by histology or immunohistochemistry. Nodal metastases were detected in 306 nodal basins in these 288 patients. There were 175 nodal basins from 170 patients in which at least one positive sentinel node was found and more than one sentinel node was harvested. Blue dye staining was found in 86.3% of the histologically positive sentinel nodes and 66.4% of the negative sentinel nodes. In 40 of 306 positive nodal basins (13.1%), the most radioactive sentinel node was negative for tumor when another, less radioactive, sentinel node was positive for tumor. In 20 of 40 cases (50%), the less radioactive positive sentinel node contained 50% or less of the radioactive count of the hottest lymph node. The cervical lymph node basin was associated with an increased likelihood of finding a positive sentinel node other than the hottest node. CONCLUSIONS: If only the most radioactive sentinel node in each basin had been removed, 13.1% of the nodal basins with positive sentinel nodes would have been missed. It is recommended that all blue lymph nodes and all nodes that measure 10% or higher of the ex vivo radioactive count of the hottest sentinel node should be harvested for optimal detection of nodal metastases.

Application of data mining for examining polypharmacy and adverse effects in cardiology patients.

This article comments upon the use of data mining tools to examine clinical data. Many cardiovascular patients have co-morbid diseases that put them at risk for polypharmacy, or severe adverse reactions from the interactions of multiple medications. Clinical trials typically use too few patients with stringent inclusion/exclusion criteria that prevent an examination of the issue of polypharmacy. However, clinical data collected in the course of patient treatment can be used in conjunction with data mining to find meaningful results.

DNA flow cytometry does not predict 5- or 10-year recurrence rates for T1-2 node-negative breast cancer.

BACKGROUND: A small proportion of T1 or T2 node-negative breast cancer tumors will recur in patients by 5 years, and more by 10 years. Results of recent studies have suggested improvement in overall survival with administration of adjuvant chemotherapy to all patients. More sensitive and specific methods are needed to identify patients at highest risk for recurrence who might benefit most from adjuvant therapy, saving others from unnecessary treatment. Some investigators have suggested DNA flow cytometry as a method to discriminate patients at greatest risk for recurrence. HYPOTHESIS: DNA flow cytometry has predictive value for breast cancer recurrence in node-negative patients. METHODS: The cancer registry of a medium-sized university-affiliated hospital was used to identify patients with T1-2 N0 M0 breast cancer treated with a uniform surgical approach and no adjuvant therapy who had completed at least 5 years of follow-up or had recurrence. Flow cytometric analysis was performed on paraffin-embedded specimens. RESULTS: Of 115 patients, 92 (80%) had disease-free survival without recurrence and 23 (20%) had recurrence. Comparison of diploid and nondiploid tumors for likelihood of recurrence revealed no association (P = .79). Furthermore, the DNA index and S-phase fraction were not significantly different between recurrent and nonrecurrent groups. CONCLUSIONS: The likelihood of recurrence of small node-negative breast cancers after mastectomy cannot be accurately predicted on the basis of DNA flow cytometric analysis. Traditional methods for determining risks-such as nuclear and histological grade, lymph node status, and tumor size-seem to be more useful. Sentinel lymph node biopsy techniques may increase the detection of micrometastases.

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group.

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.

Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used.

PURPOSE: Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS: A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS: There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P <.05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3. 9%; P <.05). CONCLUSION: In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.

Spectral analysis of graft flow for anastomotic error detection in off-pump CABG.

OBJECTIVE: Flow probes have been introduced as a non-invasive means of anastomotic quality assessment in off-pump coronary artery bypass graft (CABG). Flow waveform morphology cannot reliably be assessed visually unless severe anastomotic stenosis is present ( > 90%). We applied spectral analysis techniques to determine whether the frequency content of graft flow can improve the surgeon's ability to detect anastomotic errors. METHODS: Forty-six mammary to left anterior descending artery (LAD) anastomoses were created in mongrel dogs during off-pump CABG surgery. Graft flow was measured using transit-time flow probes with the LAD closed, and the mammary graft patent and with varying degrees of stenosis. The degree of anastomotic stenosis was created by an artificial stitch and verified by random postoperative angiography. Spectral analysis of the graft flow waveforms was performed. Differences in the magnitude and phase components of the graft flow for the first five harmonics were determined for the varying anastomosis test conditions. Differences were determined using analysis of variance and least square means techniques. RESULTS: The magnitude of the fundamental (zeroth) harmonic was statistically different in the internal mammary artery (IMA) with 0-25% stenosis compared to IMA with 50-75% stenosis (P < 0.01 ). Further, the magnitude of the first, second, and fourth harmonics were statistically different in IMA with 0-25% compared to IMA with 75% (P < 0.01). The phase of the first harmonic was statistically different in IMA with 25% stenosis than IMA with 50% stenosis (P < 0.01 ). No differences in interaction between the LAD and IMA for all ranges of stenosis were detected (P > 0.50). CONCLUSION: Spectral analysis of graft flow waveforms may be beneficial in detecting lesser degrees of anastomotic stenosis (i.e. < 90%) compared to traditional visual assessment of mean graft flow and/or graft flow waveform morphology.

Neural network pattern recognition analysis of graft flow characteristics improves intra-operative anastomotic error detection in minimally invasive CABG.

OBJECTIVE: The intra-operative assessment of the quality of anastomosis in minimally invasive coronary artery bypass surgery (CABG) is critical. Recent investigations demonstrated that flow probes used intra-operatively to assess anastomotic errors may give the surgeon a false sense of confidence as only severely stenotic anastomoses (>90%) could be reliably detected. We developed a neural network system using graft flow data and assessed its potential to improve anastomotic error detection. METHODS: Mammary to LAD grafts (n = 46) were constructed in mongrel dogs off-pump. Continuous beat-to-beat graft flow was recorded using transit-time flow probes. Various degrees of anastomotic stenoses (0-100%) were created by an additional suture. The degree of anastomotic stenosis was confirmed by postoperative angiography. A learning vector quantization neural network was created using heart rate, mean aortic pressure, mean systolic, maximum systolic, minimum systolic, mean diastolic, maximum diastolic, minimum diastolic, and mean graft flows. In addition, a spectral analysis of the flow waveforms was performed and the magnitude and phase of the first five harmonics were used to further develop the neural network. RESULTS: The neural network pattern recognition system was 94% accurate in detecting any stenosis >50%. To validate the model, a testing set was used with 20% of the data values, and the accuracy remained at 100% above chance alone. CONCLUSION: Pattern recognition of transit-time flow probe tracings using neural network systems can detect anastomotic errors significantly better than the surgeon's visual assessment, thereby improving the clinical outcome of minimally invasive CABG.

Atrioventricular discordance: results of repair in 127 patients.

OBJECTIVE: The conventional management of patients with atrioventricular discordance is directed at associated lesions, taking advantage of physiologic "correction"; however, the morphologic right ventricle and tricuspid valve support the systemic circulation. Questions surrounding survival using this approach led us to analyze our institutional results. METHODS: All patients with atrioventricular discordance undergoing biventricular repair were analyzed (n = 127, 1959-1997), excluding those with functionally univentricular hearts. The ventriculoarterial connection associated with atrioventricular discordance varied and was most commonly discordant (87%), but occasionally concordant (6%), double-outlet right ventricle (6%), or double-outlet left ventricle (1%). At initial presentation, the most common lesions associated with atrioventricular discordance were ventricular septal defect (86%), pulmonary stenosis (64%), tricuspid regurgitation (28%), and atrioventricular block (12%). Nine patients underwent a double switch procedure to create ventriculoarterial concordance and the remainder were managed conventionally without correcting discordant connections. RESULTS: Operative mortality was 6% and did not vary by associated lesion. Twenty years after repair, survival was 48%. Within 20 years, 56% of patients required reoperation, usually for atrioventricular valve incompetence (n = 16), pulmonary stenosis (n = 16), or both (n = 3). Pacemakers were required in 50 patients, 4 before repair, 40 within 2 months of repair, and 6 remotely after repair. In early follow-up, the double switch procedure (n = 9) had equivalent mortality and a high pacemaker requirement for atrioventricular block. CONCLUSIONS: Analysis of conventional management of atrioventricular discordance revealed cumulative increases in mortality, systemic atrioventricular valve (tricuspid) replacement, complete atrioventricular block, and incidence of reoperation. Alternative management should be examined.

Results after partial left ventriculectomy versus heart transplantation for idiopathic cardiomyopathy.

OBJECTIVE: Partial left ventriculectomy has been introduced as an alternative surgical therapy to heart transplantation. We performed a single-center, retrospective analysis of all patients with idiopathic dilated cardiomyopathy who underwent partial left ventriculectomy or heart transplantation or who were listed for transplantation to determine operative mortality rate, 12-month survival, freedom from death on the heart transplantation waiting list, and freedom from death or need for relisting for heart transplantation. METHODS: Patients who had partial left ventriculectomy (October 1996 to April 1998) were retrospectively compared with patients who were listed for heart transplantation (January 1995 to April 1998). Survival was assessed after the surgical procedure (partial left ventriculectomy vs heart transplantation) and from time of listing for heart transplantation to assess the additional impact of waiting list deaths. Freedom from death or relisting for heart transplantation was also compared. RESULTS: There was no difference in age or United Network for Organ Sharing status between the 2 groups. Twenty-nine patients with idiopathic dilated cardiomyopathy were listed for heart transplantation; 17 patients underwent transplantation, 6 patients died while on the waiting list, and 6 patients remain listed. One patient died after heart transplantation, and 1 patient required relisting. Sixteen patients had partial left ventriculectomy; 10 patients are in improved condition, 2 patients died (1 death early from sepsis and 1 death from progressive heart failure), and 4 patients required relisting for heart transplantation. Operative survival was 94% after partial left ventriculectomy and 94% after heart transplantation (P =.92). Postoperative 12-month Kaplan-Meier survival was 86% after partial left ventriculectomy and 93% after heart transplantation (P =.90). Twelve-month Kaplan-Meier survival after listing for heart transplantation was 75% due to death while on the waiting list (P =.76). Freedom from death or need for relisting for heart transplantation was 56% after partial left ventriculectomy and 86% after transplantation (P =.063). CONCLUSION: Operative and 12-month survival after partial left ventriculectomy and heart transplantation were comparable. However, despite their initial improvement, many patients who underwent partial left ventriculectomy required relisting for transplantation. Although partial left ventriculectomy is associated with acceptable operative and 12-month survival, it may prove to serve better as a bridge to transplantation in patients with idiopathic dilated cardiomyopathy rather than definitive therapy, given the number of patients who required relisting for transplantation.

Analysis of pulmonary microvasculature changes after photodynamic therapy delivered to distant sites.

Photodynamic therapy (PDT) can exert local damage by direct tumor cytotoxicity, by disruption of the microvasculature or by a combination of these effects. Although systemic effects after PDT of small tissue areas (< 1% total body surface area) are unlikely, treatment of larger areas may result in an accumulated effect leading to toxicity. Several investigators have described animal death after high dose PDT to tumors on the hind limb of animals and hypothesized that a toxic shock syndrome caused by vasoactive agents released after PDT is responsible. Because one of the most vulnerable organs to toxic shock injury is the lung, we studied the systemic effects of local PDT to this organ by intravital microscopy using a pulmonary window chamber. The PDT treatment conditions (25 mg/kg Photofrin, 24 h, 150 J/cm2 630 nm, maximum area 6.28 cm2) were chosen that produce systemic toxicity and lethality in rats. Adhesion of leukocytes in the lung was monitored in vivo using anti-CD-13-labeled microspheres. The progression of pulmonary edema was assessed by monitoring the leakage of rhodamine-labeled albumin and by wet-to-dry lung weight ratios. Although an increased leukocyte adherence was observed and a significant number of animals died after the extensive PDT treatment, no biologically significant lung edema could be demonstrated. These data indicate that lung edema and acute respiratory distress syndrome is not the cause of death in these animals and that the toxicity is related to other mechanisms including circulatory shock after extensive muscle damage.

Analysis of acute vascular damage after photodynamic therapy using benzoporphyrin derivative (BPD).

Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short times after injection of photosensitizer. Groups of rats with chondrosarcoma were given 2 mg kg(-1) of BPD intravenously 5 min to 180 min before light treatment of 150 J cm(-2) 690 nm. Vascular response was monitored using intravital microscopy and tumour cure was monitored by following regrowth over 42 days. For treatment at 5 or 30 min after BPD injection, blood flow stasis was limited to tumour microvasculature with lesser response in the surrounding normal microvasculature, indicating selective targeting for damage. No acute changes were observed in vessels when light was given 180 min after BPD injection. Tumour regression after light treatment occurred in all animals given PDT with BPD. Long-term tumour regression was greater in animals treated 5 min after BPD injection and least in animals given treatment 180 min after drug injection. The correlation between the timing for vascular damage and cure implies that blood flow stasis plays a significant role in PDT-induced tumour destruction.

A review of transit-time flow measurement for assessing graft patency.

Anastomotic quality is a critical issue in minimally invasive coronary artery bypass surgery, particularly "off-pump". It is important to detect a "poor" anastomosis during the procedure so future re-operation can be avoided. Methods such as intraoperative angiography, thermal angiography, probing of the anastomosis, and graft flow measurement have been used intraoperatively to help identify anastomotic errors. With the evolution of stabilizers, graft patency rates for off-pump cases have improved, but many believe they are still not as high as those of the conventional procedure. For off-pump surgery to be accepted and practiced universally, patency rates must be equivalent to those of "on-pump" cases. Transit-time flow measurement has become an increasingly popular non-invasive method for assessing anastomotic quality. However, it is difficult to establish whether an anastomosis is patent based on mean graft flow alone. Spectral analysis of graft flow waveforms reveal characteristic patterns that identify intermediate ranges of stenosis between fully patent and totally occluded. Together, these two components of graft flow have been used in the construction of a neural network to help identify "faulty" anastomoses. Transit-time flow measurement is a non-invasive tool that can be beneficial in identifying fully patent or nearly occluded grafts, and may also help in distinguishing intermediate stenoses.

Intraoperative assessment of acute hemodynamic changes after partial left ventriculectomy.

Partial left ventriculectomy (PLV) has been introduced as an alternative surgical therapy for patients with end-stage dilated cardiomyopathy. The physiological benefits of PLV are relatively unknown. Therefore, the objective of this study was to determine the acute effects of PLV by measuring cardiac function before and after PLV. Aortic and left ventricular pressures and aortic flow were measured in eight patients. Continuous, beat-to-beat data were recorded and compared pre-PLV and post-PLV with and without inferior vena cava (IVC) occlusions. PLV increased cardiac output (0.93+/-0.5, p = 0.01) as a result of increased stroke volume (5.12+/-4.24, p = 0.06) and heart rate (14.5+/-8.44, p = 0.02). Contractility (+/- dP/dt, 240.33+/-74.28, p = 0.001) and external work (650.8+/-320.4, p = 0.01) were also improved. Left ventricular end-diastolic elastance (0.15+/-0.14, p = 0.10) nearly doubled after PLV. Our results indicated an improved cardiac function as measured by increased cardiac output, stroke volume, ejection fraction (EF), and contractility.