Strategies to Improve Survival from Surgery for Heart Valve Implantation in Sheep

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by difficulties in restarting the heart, causing significant on-table mortality. Therefore, optimal cardioprotective management during heart valve implantation in sheep is essential. However, little is known about successful cardioprotective management techniques in sheep. This article reports our experience in the cardioprotective management of 20 female sheep that underwent surgical aortic valve replacement with a stented tissue-engineered heart valve prosthesis. During this series of experiments, we modified our cardioprotection protocol to improve survival. We emphasize the importance of total body hypothermia and external cooling of the heart. Furthermore, we recommend repeated cardioplegia administration at 20 min intervals during surgery, with the final dosage of cardioplegia given immediately before the de-clamping of the aorta. To reduce the number of defibrillator shocks during a state of ventricular fibrillation (VF), we have learned to restart the heart by reclamping the aorta, administering cardioplegia until cardiac arrest, and de-clamping the aorta thereafter. Despite these encouraging results, more research is needed to finalize a protocol for this procedure.

Sheep are a commonly used and well-validated model for cardiovascular research, particularly for heart valve research, as blood pressure, heart rate, cardiac output, and intracardiac pressures are similar between sheep and humans. Sheep are particularly useful for heart valve research because observable changes in implanted heart valve bioprostheses that would take several years to develop in humans are apparent after only a few months in sheep.^3,11 This feature allows the ovine model to provide relevant and important information about heart valve prostheses in a relatively short time span. The first preclinical step in developing novel heart valves is to test the valve in the pulmonary position in sheep. This surgical technique is relatively easy, as the procedure can be performed on a beating heart in a low-pressure circulation. However, aortic valve surgery is the most frequently performed valvular surgical intervention in human patients.¹² Thus, an important next step is to prove the clinical applicability of a new valve by testing the valve in-vivo in the aortic position in an animal model. In contrast to pulmonary valve replacement, aortic valve replacement must be performed on an arrested heart, which makes the surgical procedure significantly more complex. The sheep is a difficult model for aortic valve replacements due to its narrow annulus, short distance between the annulus and coronary ostia, a short ascending aorta, and difficulty in de-airing of the heart prior to suturing the aortotomy.¹⁹ Consequently, high on-table mortality rates, ranging from 9% to 33%, have been reported.^1,18,21,24 Furthermore, the incidence of mortality during the first 30 d after surgery, directly related to the surgical procedure, is often high, ranging from 17% to 50%.^1,2,16,18,21 Therefore, optimizing cardioprotective strategies during surgery would improve postoperative survival. However, little is known about protective strategies in sheep. In the current series of experiments, we implanted stented, tissue engineered, aortic heart valve prostheses in 20 adult domestic sheep and developed cardioprotective techniques to increase survival rates. In this observational study, we share our experience and insights regarding cardioprotective management to potentially improve the outcome of future surgeries that require an arrested heart in sheep.     

Fertility changes in surface waters during the Aalenian (mid-Jurassic) of the Western Tethys as revealed by calcareous nannofossils and carbon-cycle perturbations

In Aalenian times, the South Iberian Palaeomargin was part of the westernmost Tethys Ocean. The Median Subbetic palaeogeographic domain of the Betic Cordillera was a relatively deep trough in the South Iberian Palaeomargin during the Early Jurassic–Late Cretaceous interval, where mainly pelagic and hemipelagic limestones and marls were deposited. A semiquantitative study of nannofossil assemblages was performed in sediments from the upper Toarcian–lowest Bajocian from two Median Subbetic sections (Agua Larga and Cerro de Mahoma). Nannofossil assemblages are composed mainly of cosmopolitan and Tethyan taxa. The NJ8a, NJ8b and NJ9 Zones as well as other useful biohorizons (FOs of Triscutum tiziense and Carinolithus magharensis and LO of Similiscutum finchii) were identified and directly correlated to ammonite zones. The analysis of the relative abundances of some common to abundant taxa including Biscutum, Carinolithus superbus, Crepidolithus crassus, Lotharingius, Schizosphaerella and Watznaueria display noticeable fluctuations that can be correlated between the two sections. The comparison of these fluctuations with the δ¹³C_carb curves and the interpretation of the palaeoecologic significance of some of these taxa provided an outline of the palaeoceanographic trophic regime throughout the interval studied. During the latest Toarcian–Early Aalenian, the high proportions of oligotrophic Schizosphaerella, moderately high proportions of C. crassus and low proportions of eutrophic Biscutum, correlate with low to moderate values in the δ¹³C_carb curves. Radiolarians display low abundance throughout this interval. This is interpreted as an interval where mesotrophic to oligotrophic and stable conditions occurred in surface waters. The Middle Aalenian, characterized by high proportions of Schizosphaerella and C. crassus and low proportions of Biscutum, correlates with low values in the δ¹³C_carb curves, and was interpreted to correspond to an episode when stable oligotrophic conditions occurred in surface waters. Radiolarians moderately increased throughout this interval. Finally, the Late Aalenian–earliest Bajocian interval, with lower proportions of Schizosphaerella and C. crassus, and higher proportions of Biscutum, also correlates with a significant positive excursion in the δ¹³C_carb curve, suggesting a shift from oligo- to eutrophic conditions in surface waters. This change in productivity is also revealed by a conspicuous increase in radiolarian abundance, at the same time as a quasi-complete replacement of Early Jurassic radiolarian fauna took place. The analysis of faunal-flora turnovers reveals a causal link between the global carbon-cycle and the pelagic response. This noticeable faunal-flora change throughout the Late Aalenian–Bajocian can be interpreted as a major biological response to the drastic modification in the western Tethys palaeogeography as consequence of the Atlantic opening, which in turn caused a new pattern in the oceanic circulation.