In vitro study of the aortic interleaflet triangle reshaping.

Aortic interleaflet triangle reshaping (AITR) is a surgical approach to aortic valve incontinence that involves placing three stitches at half of the interleaflet triangles height. In this work, the relationship between the actual stitch height and valve functioning, and the safety margin that the surgeon can rely on in applying the stitches were systematically investigated in vitro. AITR surgery was applied to six swine aortic roots placing the stitches empirically at 50%, 60% and 75% of the triangle heights. Then the actual stitch heights were measured and the hydrodynamic performances were evaluated with a pulsatile hydrodynamic mock loop. Actual stitch heights were 45±2%, 61±4% and 79±6%. As compared to untreated conditions, the 50% configuration induced a significant variation in the effective orifice area. With stitches placed at 60%, the mean systolic pressure drop increased significantly with respect to the untreated case, but no significant changes were recorded with respect to the 50% configuration. At 75%, all the hydrodynamic parameters of systolic valve functioning worsened significantly. Summarizing, the AITR technique, when performed in a conservative manner did not induce significant alterations in the hydrodynamics of the aortic root in vitro, while more aggressive configurations did. The absence of a statistically significant difference between the 50% and 60% configurations suggests that there is a reasonably limited risk of inducing valve stenosis in the post-op scenario due to stitch misplacement.

In vitro hemodynamics and valve imaging in passive beating hearts.

Due to their high complexity, surgical approaches to valve repair may benefit from the use of in vitro simulators both for training and for the investigation of those measures which can lead to better clinical results. In vitro tests are intrinsically more effective when all the anatomical substructures of the valvular complexes are preserved. In this work, a mock apparatus able to house an entire explanted porcine heart and subject it to pulsatile fluid-dynamic conditions was developed, in order to enable the hemodynamic analysis of simulated surgical procedures and the imaging of the valvular structures. The mock loop's hydrodynamic design was based on an ad-hoc defined lumped-parameter model. The left ventricle of an entire swine heart was dynamically pressurized by an external computer-controlled pulse duplicator. The ascending aorta was connected to a hydraulic circuit which simulated the input impedance of the systemic circulation; a reservoir passively filled the left atrium. Accesses for endoscopic imaging were located in the apex of the left ventricle and in the aortic root. The experimental pressure and flow tracings were comparable with the typical in vivo curves; a mean flow of 3.5±0.1l pm and a mean arterial pressure of 101±2 mmHg was obtained. High-quality echographic and endoscopic video recordings demonstrated the system's excellent potential in the observation of the cardiac structures dynamics. The proposed mock loop represents a suitable in vitro system for the testing of minimally-invasive cardiovascular devices and surgical procedures for heart valve repair.

In vitro study of aortic valves treated with neo-chordae grafts: hydrodynamics and tensile force measurements.

Reparative surgery of the aortic root functional unit (ARFU) allows for a better preservation of the functionality of the native structure compared to prosthesis implantation. Post-operative results are satisfactory, whereas mid- and long-term results are challenging, for example in terms of cusps prolapse recurrence. At the Cardiothoracic Surgery Unit of the Sacco Hospital, a new surgical technique aimed at the stabilization in time of the results of standard ARFU repair operations has been applied. This technique, inspired by the mitral neo-chordae (NC) implantation, consists of implanting an e-PTFE suture thread between the prolapsed cusp and the sinotubular junction. Aim of this study was to assess the influence of NC implantation on the ARFU functioning by evaluating with an owned pulsatile in vitro apparatus the force magnitude acting on the NC and the dynamic behavior of porcine ARFUs treated according to the operating-room procedures. The maximum recorded values of the mean and peak diastolic forces were 0.064 and 0.186 N, respectively, and were linearly dependent upon the mean diastolic pressure across the valve. In addition, the measurements of the opening-closing times and valve leakage volumes, performed at pre- and post-surgeries, yielded that the valve functionality was not significantly influenced by NC implantation.

Hybrid aortic arch repair procedure: reinforcement of the aorta for a safe and durable landing zone.

OBJECTIVES: Hybrid aortic arch repair procedure was introduced to reduce invasiveness in high-risk patients with aortic arch pathology. The good results are expanding its application, but endoleak, particularly type I, remains its Achilles' heel. DESIGN: We describe our experience with hybrid treatment of aortic arch diseases focussing on techniques and results to avoid type I endoleak. MATERIALS AND METHODS: A total of 15 high-risk patients with zone 0-2 aortic arch pathology underwent supra-aortic debranching on ascending aorta and proximal aortic arch reinforcement with a Dacron prosthesis. Metachronously, the procedure was completed with endovascular stent grafting (ESG). RESULTS: Median age was 70 years with a mean European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 12.7±6.8. One patient died between aortic debranching and ESG. Mean time between surgical debranching and ESG was 32±27.7 days. No major neurological events occurred. Mean length of the landing zone for ESG was 3.8±0.8 cm. Computed tomography (CT) angiography scan performed soon after operation, and at 3, 6, and 12 months did not show any type I endoleak. CONCLUSIONS: Supra-aortic debranching on ascending aorta with proximal aortic arch reinforcement is a useful step to ensure a safe landing zone for ESG, reducing risk early to midterm of endoleak. Longer term follow-up is required to confirm the viability of this technique.

Combination cytotoxic chemotherapy with cisplatin or doxorubicin and photodynamic therapy in murine tumors.

This study was designed to evaluate the interaction of photodynamic therapy (PDT) and chemotherapy in an animal model. PDT is based on the interaction of hematoporphyrin derivative and red light of the appropriate wavelength (630 nm) and intensity. Two tumor models were utilized: C3H/Km mice bearing the RIF-1 tumor and BALB/c mice bearing the EMT-6 tumor. Tumor-bearing mice were treated with either cisplatin (DDP), doxorubicin (ADM), PDT, or a combination of drug and PDT. It was demonstrated that the RIF-1 tumor was sensitive to DDP and insensitive to both PDT and ADM. There was no additional antitumor effect when either drug was combined with PDT. The EMT-6 tumor was moderately sensitive to PDT and mildly sensitive to both DDP and ADM. Although the addition of DDP did not potentiate tumor destruction, the addition of ADM significantly enhanced the effect of PDT (P = .01). The enhanced activity of the combination of PDT and ADM appeared to be the result of increased activity of ADM alone, when illuminated with red (630 nm) light. This potentiation may be due to a photochemical process or may be secondary to the mild hyperthermia generated by illumination with the laser. This study demonstrates that PDT combined with cytotoxic chemotherapy is well tolerated in these animals and that certain combinations of PDT and chemotherapy may result in an enhanced tumoricidal effect.

Heterogeneity of soluble suppressor factors in rat malignant ascites.

A study was undertaken to enumerate and partially characterize soluble factors generated by tumor-bearing animals capable of suppressing PHA-induced splenocyte proliferation. Sprague-Dawley rats were induced to form malignant ascites by the intraperitoneal injection of the Walker 256 carcinoma. Intact ascites suppressed splenocyte proliferation by 96%. Molecular sieving of the ascites by means of ultrafiltration (10-kilodalton particle cutoff) revealed suppressor activity to reside in both the ultrafiltrate and retentate. Further enumeration of suppressor factors was achieved by preparative polyacrylamide gel electrophoresis of the ascites ultrafiltrate and retentate. Five discrete bands of suppressor activity were resolved in the ultrafiltrate, three of which were heat-labile. Three discrete bands of suppressor activity were resolved in the retentate, none of which were heat-labile. This study underscores the complexity and heterogeneity of soluble factors elaborated in a cancer-bearing animal.

Sequential elaboration of lymphocyte-enhancing and -suppressing factors in the sera of tumor-bearing animals.

Serum-mediated impairment of lymphocyte function was studied in an animal model. Sprague-Dawley rats inoculated intraperitoneally or subcutaneously with the Walker 256 carcinoma underwent sequential sampling of blood. The effect of these serum samples upon phytohemagglutinin-induced blastogenesis of normal rat splenocytes was monitored in an assay utilizing incorporation of (3H)-thymidine. The effect of serum samples from both the subcutaneously and the intraperitoneally inoculated tumor-bearing animals was biphasic. Early on, serum enhanced blastogenesis and later suppressed blastogenesis. Separation of sera into high and low molecular weight components by ultrafiltration demonstrated the enhancing activity to reside in the high molecular weight fraction. The enhancing activity of sera decreased over time from tumor inoculation. Conversely, suppressor activity increased over time from tumor inoculation. This study demonstrated that suppressor activity of sera obtained from animals with advanced tumors is the result of the lack of enhancing activity coupled with the elaboration of suppressor activity.