Dan L. Serna

Survival after unilateral versus bilateral lung volume reduction surgery for emphysema.

OBJECTIVE Bilateral staple lung volume reduction surgery (LVRS) immediately improves pulmonary function and dyspnea symptoms in patients with advanced heterogeneous emphysema to a greater degree than do unilateral procedures. However, the long-term outcome after these surgical procedures needs to be critically evaluated. We compare 2-year survival of patients who underwent unilateral versus bilateral video-assisted LVRS in a large cohort treated by a single surgical group. METHODS The cases of all 260 patients who underwent video-assisted thoracoscopic stapled LVRS from April 1994 to March 1996 were analyzed to compare results after unilateral versus bilateral procedures. Overall survival was calculated by Kaplan-Meier methods; Cox proportional hazard methods were used to adjust for patient heterogeneity and baseline differences between groups. RESULTS Overall survival at 2 years was 86.4% (95% CI 80. 9%-91.8%) after bilateral LVRS versus 72.6% (95% CI 64.2%-81.2%) after unilateral LVRS (P =.001 for overall survival comparison). Improved survival after bilateral LVRS was seen among high- and low-risk subgroups as well. Average follow-up time was 28.5 months (range, 6 days to 46.6 months) for the bilateral LVRS group and 29.3 months (range, 6 days to 45.0 months) for the unilateral LVRS patients. CONCLUSIONS Comparison of unilateral versus bilateral thoracoscopic LVRS procedures for the treatment of emphysema reveals that bilateral LVRS by video-assisted thoracoscopy resulted in better overall survival at 2-year follow-up than did unilateral LVRS. This survival study, together with other studies demonstrating improved lung function after bilateral LVRS, suggests that bilateral surgery appears to be the procedure of choice for patients undergoing LVRS for most eligible patients with severe heterogeneous emphysema.

Ex vivo cardiac allograft preservation by continuous perfusion techniques.

The current technique of cardiac preservation for clinical transplantation by infusion of cold cardioplegia and immersion of the heart in an isotonic saline bath at 4°C limits safe tissue preservation time to 4 to 6 hours. The myriad of benefits to be gained by extending cardiac preservation time has prompted the search for alternatives to hypothermic immersion of the heart, the most promising of which involves techniques of coronary artery perfusion. Countless studies have shown the benefits of long-term storage of donor hearts by perfusion rather than the immersion technique. Continuous perfusion preservation has three basic advantages over simple immersion. Perfusion preservation with oxygen carrying solutions has the advantage of preventing ischemia, anaerobic metabolism, and reperfusion injury. Second, nutritional supplementation and provision of substrate can be more effectively delivered to myocardial cells. Third, continuous perfusion preservation effects the clearance of metabolic waste products from the coronary circulation. The composition of the ideal perfusion solution and optimal preservation conditions remain incompletely defined.

Noninvasive monitoring of hemodynamic stress using quantitative near-infrared frequency-domain photon migration spectroscopy

Hemorrhagic hypovolemia and inotropic agent administration were used to manipulate cardiac output (CO) and oxygen delivery in rabbits to investigate the correlation between noninvasive frequency domain photon migration (FDPM) spectroscopy and invasive hemodynamic monitoring parameters. Frequency-domain photon migration provides quantitative measurements of light absorption and reduced scattering (mu(a) and mu(s)(prime prime or minute), respectively) in tissue. Wavelength dependent mu(a) values were used to calculate in vivo tissue concentration of deoxyhemoglobin [Hb], oxyhemoglobin [HbO(2)], total hemoglobin [TotHb], and water [H(2)O] as well as mixed arterial-venous oxygen saturation (S(t)O(2)) in tissue. FDPM-derived physiologic properties were correlated with invasive measurements of CO and mean pulmonary artery pressure (mPAP), FDPM-derived [TotHb] and S(t) O(2) correlated significantly with hemorrhaged volume (HV), mPAP, and CO. Correlation coefficients for [TotHb] vs HV, mPAP, and CO were -0.77, 0.86, and 0.70, respectively. Correlation coefficients of S(t)O( 2) vs HV, mPAP, and CO were -0.71, 0.55, and 0.61, respectively. Dobutamine induced changes resulted in correlation coefficients between FDPM-derived and invasively measured physiologic parameters that are comparable to those induced by hypovolemia. FDPM spectroscopy is sensitive to changes in mPAP and CO of as little as 15%. These results suggest that FDPM spectroscopy may be used in clinical settings to noninvasively monitor central hemodynamic parameters and to directly assess oxygenation of tissues.

Cardiac function after eight hour storage by using polyethylene glycol hemoglobin versus crystalloid perfusion.

Efforts to extend myocardial preservation for transplantation by crystalloid perfusion have been limited by edema and compromised function. We hypothesized that hypothermic perfusion preservation with a polyethylene glycol (PEG) conjugated hemoglobin solution may extend preservation times. The purpose of this study was to compare cardiac function after continuous perfusion by using a hypocalcemic, normokalemic crystalloid perfusate with and without the addition of PEG-hemoglobin (Hb). The hearts of 20 anesthetized and ventilated New Zealand White rabbits were harvested after cold cardioplegic arrest. Group I (n = 10) hearts were continuously perfused with a hypocalcemic, normokalemic 3% bovine PEG-Hb solution at 20°C and 30 mm Hg for 8 hours. Group II (n = 10) hearts were continuously perfused with an identical crystalloid solution without PEG-Hb for 8 hours under the same conditions as group I hearts. Cardiac function was measured with a left ventricular force transducer after transfer to a standard crystalloid Langendorff circuit at 37°C and an aortic root pressure of 59 mm Hg. After 8 hours of perfusion preservation, heart rate was similar for groups I and II (p = not significant [NS]). Coronary blood flow after and during preservation was similar between PEG-Hb and crystalloid preserved hearts (p = NS). Left ventricular developed pressure, peak dP/d t, and peak −dP/d t were superior in hearts preserved with PEG-Hb. Percent water of total ventricular weight was 82.0% for group I and 81.6% for group II (p = NS). Continuous perfusion preservation of rabbit hearts for 8 hours with a hypocalcemic normokalemic PEG-Hb based solution at 30 mm Hg and 20°C yields left ventricular function that is superior to perfusion with a similar crystalloid solution without PEG-Hb, despite similar myocardial edema and coronary flow. Extended cardiac perfusion preservation with this PEG-Hb based solution deserves further study, including comparison with traditional cardioplegic preservation solutions.

Diffusing capacity limitations of the extent of lung volume reduction surgery in an animal model of emphysema

OBJECTIVE The purpose of this study was to investigate in an elastase-induced emphysema rabbit model the effects of increasing resection volumes during lung volume reduction surgery on pulmonary compliance, forced expiratory air flow, and diffusing capacity to assess factors limiting optimal resection. METHODS Emphysema was induced in 68 New Zealand White rabbits with 15,000 units of aerosolized elastase. Static respiratory system compliance, forced expiratory flow, and single-breath diffusing capacity were measured before the induction of emphysema, after the induction of emphysema, and 1 week after a bilateral upper and middle lobe lung volume reduction operation. RESULTS Static respiratory system compliance with 60 mL insufflation above functional residual capacity increased with emphysema induction and then decreased progressively with resection of larger volumes of lung tissue (P =.001 by analysis of variance). Expiratory flow improved after lung resection in the rabbits with large resection volumes. In contrast, diffusing capacity tended to deteriorate with larger resection volumes (P =. 18). CONCLUSION Improvements in respiratory system compliance and forced expiratory flow after lung volume reduction operations may account for the improvements seen clinically. Declines in diffusing capacity with extensive lung reduction may limit the clinical benefits associated with greater tissue resection volumes. Future investigations with animal models may reveal other physiologic parameters that may further guide optimal lung volume reduction procedures.

Relationship between amount of lung resected and outcome after lung volume reduction surgery.

BACKGROUND Lung volume reduction surgery (LVRS) is being actively investigated for palliative treatment of severe emphysema. Considerable focus is directed toward patient selection and outcomes of LVRS. However, there is little information available regarding surgical methods to guide optimal extent of resection. We hypothesized that acute improvement and long-term survival after bilateral staple LVRS would be related to the extent of tissue resected. METHODS The relationship between acute improvement in forced expiratory volume in 1 second and forced vital capacity was examined as a function of the total grams of lung tissue resected in 237 patients who underwent bilateral staple LVRS by a single group of surgeons. Overall survival was assessed based on extent of resection by quartiles of tissue weight resected using Kaplan-Meier survival methods. RESULTS Improvement in forced expiratory volume in 1 second and forced vital capacity correlated with extent of tissue resected (p < 0.01), although there was considerable variability to individual response (r = 0.3). In contrast, there was no apparent relationship between the amount of tissue resected and overall postoperative survival (p = 0.7). CONCLUSIONS There is a correlation between the amount of tissue resected and improvement in forced expiratory volume in 1 second and forced vital capacity after bilateral staple LVRS, with generally greater postoperative improvement after larger volume resections. However, there does not appear to be greater long-term survival with larger volume resections despite greater improvement in spirometry. This study suggests that factors other than improvement in spirometric variables may govern optimal LVRS resection volumes and long-term outcome. Future studies will clearly be needed in this important area of LVRS emphysema research.

Successful nonoperative management of delayed spontaneous esophageal perforation in patients with human immunodeficiency virus

Objective To describe the clinical outcome of esophageal stenting for repair of distal esophageal perforation in one patient with septic shock and human immunodeficiency virus. Design Case report. Setting Medical-surgical intensive care units of one university teaching hospital. Patient One patient with human immunodeficiency virus infection and septic shock in whom there was a delay in diagnosis of spontaneous perforation at the distal thoracic esophagus. Intervention A 10 cm × 2 cm silicone lined, partially coated, expandable metal stent was fluoroscopically placed in the distal esophagus at the perforation. Other treatment included chest tube thoracostomy, sump drainage of proximal esophagus, percutaneous gastrostomy, and antibiotics. Measurement and Main Results Septic shock and the distal esophageal perforation were successfully treated with combined esophageal stenting, thoracostomy pleural drainage and antibiotics. Esophageal stenting was accomplished fluoroscopically with a partially coated, silicone-lined, expandable metal stent. Conclusion Esophageal stenting, tube thoracostomy drainage, and antibiotics may be a management option for gravely ill patients with human immunodeficiency virus, esophageal perforation, and a delay in diagnosis. An optimal outcome requires a thoughtful, individualized approach and adherence to basic principles.

S-nitrosoglutathione preserves platelet function during in vitro ventricular assist device circulation.

Complications (severe bleeding/thromboembolism) may occur during ventricular assist device (VAD) circulation, caused mainly by platelet dysfunction from platelet activation. We hypothesized that S-nitrosoglutathione (GSNO), having platelet activity preservation properties like nitric oxide (NO), may be a titratable agent to diminish platelet activation and thus preserve platelet function. Dose-response measurement of platelet aggregation by GSNO was performed using an aggregometer. GSNO (1,000 &mgr;M) caused inhibition of collagen and ristocetin induced aggregation by approximately 50%. Next, in vitro ventricular assist device (VAD) circulation was performed (over 48 hours using human whole blood), both without (control) and with GSNO (1,000 &mgr;M), and the aggregability of perfusate was measured at 0, 0.5, 1, 3, 6, 12, 24, and 48 hours. In control VAD circuits, collagen induced platelet aggregability gradually decreased and became significantly lower after 3 hours of circulation. With GSNO, platelet function did not significantly decrease until after 12 hours. Similar results were seen for ristocetin induced aggregation; control aggregation dropped significantly after 6 hours, but not until after 24 hours with GSNO. Liquid phase measurement of total nitrogen oxides (NOT) confirmed added GSNO maintained high perfusate NOT compared with control. GSNO is effective in preserving platelet aggregation during the first 12 to 24 hours in vitro and may be effective in preserving platelet function by inhibiting platelet activation during in vivo VAD circulation.

Tirofiban administration attenuates platelet and platelet-neutrophil conjugation but not neutrophil degranulation during in vitro VAD circulation

Ventricular Assist Devices (VADs) have been used as bridges to heart transplantation. However, VAD circulation is complicated by the incidence of thromboembolism, prolonged bleeding, and activation of the inflammatory cascade. We hypothesize that platelet and neutrophil activation are inter-related and linked to the activation of the glycoprotein (GP) IIb/IIIa platelet receptor. The purpose of this study is to evaluate the effects of Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, on platelet and neutrophil activation during simulated VAD circulation. Two groups of five in vitro VAD circuits were simulated with and without Tirofiban using 450 cc of human blood. Blood samples were drawn at specific time intervals up to 72 hours, measuring leukotriene C4 (LTC4), platelet factor four (PF4), and neutrophil elastase. Tirofiban decreased serum levels of PF4 and LTC4 during VAD circulation. Neutrophil elastase secretion was not affected by Tirofiban administration. Preconditioning of VAD circulation with Tirofiban attenuated platelet activation as demonstrated by a decrease in serum PF4 levels. Tirofiban administration ameliorates the inflammatory response by altering platelet-neutrophil interaction as demonstrated by a decrease in LTC4 production. Continued elastase secretion indicates that the inflammatory response is not completely inhibited by Tirofiban administration. These results suggest that neutrophils may be activated by alternative mechanisms. Early complement activation has been demonstrated during in vivo and in vitro VAD circulation and may play a role in mediating inflammatory and thromboembolic reactions during VAD use.

Recovery of cardiac function after standard hypothermic storage versus preservation with Peg-hemoglobin.

Preservation of the heart for transplantation after infusion of cardioplegia and extirpation of a cardiac allograft results in an ischemic insult to the myocardium. This ischemic insult may lead to a loss of function in the transplanted heart. Hypothermic perfusion preservation with an oxygen hemoglobin carrying solution may avert ischemic injury and lead to improved recovery of cardiac function. The purpose of this study was to compare cardiac function after 8 hours of continuous hypothermic perfusion with a unique polyethylene-glycol-hemoglobin (PEG-Hb) solution to hearts preserved by 4 hours of hypothermic ischemic storage. Freshly extirpated hearts served as functional controls. The hearts of 26 anesthetized and intubated New Zealand white rabbits were harvested after cold cardioplegic arrest. Group I (n = 12) hearts were perfused with a PEG-Hb solution at 20°C and 30 mm Hg for 8 hours. PO2 was maintained ≥ 500 mm Hg. Group II (n = 7) hearts were preserved by cold ischemic storage for 4 hours at 4°C. Group III (n = 7) were tested immediately after harvest. Left ventricular (LV) function was measured in the nonworking state at 15 minutes, 1 hour, and 2 hours after transfer to a standard crystalloid Langendorff circuit. Measurement of LV developed pressure, peak + dP/dt and −dP/dt revealed a superior trend between Group I and Group II hearts in comparison with freshly extirpated hearts. Heart rate was similar among all groups throughout testing (p = ns). Coronary blood flow was not significantly different between groups. Continuous perfusion preservation of rabbit hearts for 8 hours with PEG-Hb solution at 30 mm Hg and 20°C yielded LV function that was similar to 4 hours of ischemic hypothermic storage. Furthermore, return of cardiac function after 8 hours of perfusion preservation using this PEG-Hb solution may be superior to that obtained in freshly extirpated hearts. These data suggest that some recovery of myocardial function may occur during perfusion preservation with this PEG-Hb solution after the ischemic insult of cardioplegic arrest. Continuous perfusion preservation using this PEG-Hb solution deserves further investigation in large animal transplant models.