Quinaprilat during cardioplegic arrest in the rabbit to prevent ischemia-reperfusion injury

AbstractObjectives: This study evaluated intracardiac angiotensin-converting enzyme inhibition as an adjuvant to cardioplegia and examined its effects on hemodynamic, metabolic, and ultrastructural postischemic outcomes. Methods: The experiments were performed with an isolated, erythrocyte-perfused, rabbit working-heart model. The hearts excised from 29 adult New Zealand White rabbits (2950 ± 200 g) were randomly assigned to four groups. Two groups received quinaprilat (1 μg/mL), initiated either with cardioplegia (n = 7) or during reperfusion (n = 7). The third group received l-arginine (2 mmol/L) initiated with cardioplegia (n = 7). Eight hearts served as a control group. Forty minutes of preischemic perfusion were followed by 60 minutes of hypothermic arrest and 40 minutes of reperfusion. Results: All treatments substantially improved postischemic recovery of external heart work (62% ± 6%, 69% ± 3%, and 64% ± 5% in quinaprilat during cardioplegia, quinaprilat during reperfusion, and l-arginine groups, respectively, vs 35% ± 5% in control group, P <.001) with similarly increased external stroke work and cardiac output. When administered during ischemia, quinaprilat significantly improved recovery of coronary flow (70% ± 8%, P =.028 vs quinaprilat during reperfusion [49% ± 5%] and P =.023 vs control [48% ± 6%]). l-Arginine (55% ± 7%) showed no significant effect. Postischemic myocardial oxygen consumption remained low in treatment groups (4.6 ± 1.2 mL · min−1 · 100 g−1, 6.0 ± 2.2 mL · min−1 · 100 g−1, and 4.7 ± 1.6 mL · min−1 · 100 g−1 in quinaprilat during cardioplegia, quinaprilat during reperfusion, and l-arginine groups, respectively, vs 4.2 ± 0.8 mL · min−1 · 100 g−1 in control group), even though cardiac work was markedly increased. High-energy phosphates, which were consistently elevated in all treatment groups, showed a significant increase in adenosine triphosphate with quinaprilat during ischemia (2.24 ± 0.14 μmol/g vs 1.81 ± 0.12 μmol/g in control group, P =.040). Ultrastructural grading of mitochondrial damage revealed best preservation with quinaprilat during ischemia (100% [no damage], P =.001 vs control). Conclusion: These experimental findings have clinical relevance regarding prevention of postoperative myocardial stunning and low coronary reflow in patients undergoing heart surgery.J Thorac Cardiovasc Surg 2002;124:352-6

Impact of the coronavirus disease 2019 (COVID-19) pandemic on the care of patients with acute and chronic aortic conditions

OBJECTIVES To evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on acute and elective thoracic and abdominal aortic procedures. METHODS Forty departments shared their data on acute and elective thoracic and abdominal aortic procedures between January and May 2020 and January and May 2019 in Europe, Asia and the USA. Admission rates as well as delay from onset of symptoms to referral were compared. RESULTS No differences in the number of acute thoracic and abdominal aortic procedures were observed between 2020 and the reference period in 2019 [incidence rates ratio (IRR): 0.96, confidence interval (CI) 0.89-1.04; P = 0.39]. Also, no difference in the time interval from acute onset of symptoms to referral was recorded ( 12 h 68% in 2020, 12 h 66% in 2019 P = 0.29). Conversely, a decline of 35% in elective procedures was seen (IRR: 0.81, CI 0.76-0.87; P < 0.001) with substantial differences between countries and the most pronounced decline in Italy (-40%, P < 0.001). Interestingly, in Switzerland, an increase in the number of elective cases was observed (+35%, P = 0.02). CONCLUSIONS There was no change in the number of acute thoracic and abdominal aortic cases and procedures during the initial wave of the COVID-19 pandemic, whereas the case load of elective operations and procedures decreased significantly. Patients with acute aortic syndromes presented despite COVID-19 and were managed according to current guidelines. Further analysis is required to prove that deferral of elective cases had no impact on premature mortality

Permian-Triassic extinction and recovery: results from the Muscat -Gutech field meeting

International audienceThe Permian–Triassic transition has been surveyed in the Oman Mountains and new detailedsections have been presented (Baud and Bernecker, 2010), from autochthonous shallow-waterunits (Saih Hatat and Al Jabal al-Akhdar) to slope deposits in the Jabal Sumeini area (WadiMaqam units), from distal tilted block (Wadi Wasit) to oceanic deep-water deposits(Buday’ah).Middle Permian TransgressionAt the dawn of the Wordian (Middle Permian), the "Fusulinid Sea" transgressed over most ofOman with the exception of Jabal Ja'alan and the Huqf-Dhofar High. This transgressionenabled the establishment of a vast carbonate platform in Al Jabal al-Akhdar, a 700 m-thicksuccession of cyclic shallow-marine carbonate, the Saiq Formation (Middle and Late Permian,basal Triassic (Baud et al., 2001a, b, 2005; Richoz et al., 2005; Richoz, 2006). A similarsuccession occurs in Saih Hatat (Le Métour, 1988; Weidlich and Bernecker, 2003; Chauvet,2007), in the Musandam (Bih Formation, Maurer et al., 2009), as well as in the Interior Omanand in the Haushi area (Khuff Formation, Angiolini et al. 1998, 2003). Clearly, for us, thistransgression was the result of the break-up of the Neo-Tethyan rift and the associatedthermal subsidence.Following the peak of the thermal subsidence in the Wordian–Capitanian, a stable carbonateplatform became established on the Arabian Peninsula. The Saiq, Khuff and Hagil formationsshow a strong regressive tendency at the end of the Guadalupian (Middle Permian), withrestricted environment facies and a reduced biophase, mainly associated with a global fall insea level at this time and climate changes (Isozaki, 2009). During the Lopingian (LatePermian), the subsidence as recorded in the Saiq mega-cycle B (up to 300 m of shallowingupward cycles) was still well active.The most striking effect of the climax of the Neo-Tethyan extension was the formation of acontinental slope (Sumeini) and a basin (Hawasina) that constituted with the adjacentArabian Platform, the southern continental passive margin of the Neo-Tethys Ocean.Furthermore early-rifted blocks detached from the edge of the Arabian Shield formed isolatedproximal platforms along the continental slope (later they were incorporated in the HawasinaNappes). The continental margin slope deposits are clearly identified (with slumps and intraformationalbreccia) in the northwestern part of the Oman Mountains (Jabal Sumeini), wherethey form the basal part of the Maqam Formation dated as Roadian (Middle Permian).The distal isolated platform identified as nappes in Baid and Jabal Qamar areas by Béchennec(1988), Béchennec et al. (1992), Pillevuit (1993) and Pillevuit et al. (1997) are mainly made ofMiddle–Late Permian open-shelf carbonates. The Jabal Qamar unit includes a fragment of thepre-Middle Permian Basement (Rann, Ayim and Asfar formations, Pillevuit, 1993) overlain inunconformity by the late Early to early Middle Permian shallow-marine carbonate QamarFormation with its quartz-sandstone basal member. The Baid unit is truncated at the base andis made of about 100 m of the Middle–Late Permian (Capitanian–Wuchiapingian) shallowmarinecarbonate (Baid Formation, Béchennec, 1988; Pillevuit, 1993; Pillevuit et al., 1997;Baud et al., 2001b). The distal paleogeographic position of these Permian tilted blocks inregard with the Arabian Platform is documented by: (1) the differences in terms of facies(open marine with ammonoids) with those restricted to the others parts of the OmanMountains (Al Jabal al-Akhdar, Saih Hatat and Musandam); and (2) the presence of reworkedboulders originating from these isolated platforms in the calcirudites of the proximal units ofthe basinal Hawasina Nappes.Basinal facies of the Middle Permian are present in the Hawasina Nappes at the base ofnumerous tectonics units, made up of formations from the Hamrat Duru Group. Thesesuccessions generally start with thick volcanic sequences (Al Jil and Buday’ah formations).These volcanic rocks are either of MORB type or alkali basalt-related (Maury et al., 2003;Lapierre et al., 2004). The volcanic succession is filled and overlain by red ammonoidlimestones dated as Middle Permian (Capitanian) followed by radiolarian chert and shalesnewly dated as Lopingian in Buday'ah. In the Wadi Wasit area, the volcanic series is cappedby red cephalopods-bearing carbonate, dated Middle Permian (Wordian, Blendinger et al.,1992; Pillevuit et al., 1997; Baud et al., 2001b), by shales and breccia with reworked blocks ofMiddle Permian to basal Triassic platform carbonate (Béchennec et al., 1992b; Pillevuit, 1993;Pillevuit et al., 1997; Krystyn et al., 2003; Weidlich and Bernecker, 2007).Near Nahkl the volcanic series includes blocks of Middle Permian shallow-marine carbonateand is overlain by pelagic limestone (Weidlich, 2007). In the Rustaq area the volcanicsuccession is also capped by a condensed carbonate sequence (Hallstatt facies type) dated asMiddle Permian (Wordian, Blendinger et al., 1992; Pillevuit et al., 1997; Baud et al. 2001b;Richoz et al., 2005).Different types of deep-water black limestones are also identified in the basinal units of theBatain Plain (southeastern part of the Oman Mountains), the "Qarari Limestone" with a basedated as Roadian (Middle Permian, Immenhauser et al., 1998) and the top as Changhsingian.From the Permian/Triassic Transition to the Basal Triassic (Figure 1)At the end of the Permian (top of KS3 sequence of Koehrer et al., 2010), regressive conditionsup locally to emersion (?) are recorded as well on the Arabian carbonate platform (Al Jabal al-Akhdar, Saih Hatat and Musandam). On the slope of the continental margin, we observe ashallowing in the Sumeini unit deposits.Shallow tidal influenced carbonate platform is the main component of the Induandolomitized deposit in the Al Jabal al-Akhdar (Units C1 to C4 of the Saiq Formation in Baudand Bernecker, 2010, correlated with Khuff sequences KS2–KS1) that is now dated byconodonts. During the Dienerian, part of the margin was affected by a renewed extensionalregime, tilting and drowning resulting in erosive deposition and accumulation of carbonatebreccia (Unit C2 of the Saiq Formation) followed in the Al Jabal al-Akhdar by high-energy,partly oolitic dolomitized shallow-water deposits, Dienerian in age (Unit C3) and renewedbreccias (Unit C4). The Saiq-Mahil transition (correlated with the Khuff-Sudair transition) isprobably of late Induan age (chemostratigraphical correlations, Richoz, 2006).On the slope of the continental margin, a continuous carbonate deposition and shale has beenrecently precisely dated from Changsingian to Spathian. Overlying the Wuchiapingian–Changhsingian, deep-water chert and dolostone (upper Member B of the Maqam Formation),we note the deposition of upper Changsingian shallowing siliceous strongly bioturbated limemudstones. A major facies change occurs with the Griesbachian papery, laminatedcalcimicrobial mudstone overlying the boundary clay (base of C1c Member of the MaqamFormation). The calcarenite, calcirudite turbidites and avalanches with shallow water upperPermian lime clasts start in the Dienerian (instability period). The incredible thickness of theSmithian deposits (platy limestones, shales and megabreccia up to 900 m of thickness, middleand upper Member C of the Maqam Formation) indicate high carbonate productivity on theplatform and a very active subsidence at the base of slope (Watts, 1985; Baud et al., 2001b;Richoz et al., 2005; Richoz, 2006).On the Baid Exotic block, after karstification of part of the tilted Permian carbonate platformand the Dienerian drowning event, the Dienerian-Smithian deep-water red ammonoidlimestone is filling fissures and cavities (Hallstatt breccia) and is deposited over the Permianlimestones (Tozer and Calon, 1990; Pillevuit, 1993; Pillevuit et al., 1997; Baud et al., 2001a;Richoz, 2006; Wood and Baud, 2008).In the proximal deep-water basin (Wadi Wasit units) the Lopingian allodapic limestones arepartly eroded by a submarine avalanche breccia (Dienerian) containing Permian to basalTriassic mega-blocks. One of these blocks with a unique Permian–basal Triassic record hasbeen analyzed in Krystyn et al. (2003). Upper Dienerian–Smithian deep-water platy limestoneoverlay the Lower Dienerian mega-block breccia.In the distal Hawasina basin (Buday’ah), the Upper Permian radiolarian chert deposits areoverlain by Changhsingian siliceous shales and calcareous shales followed by Griebachianlaminated platy limestones and shales and Dienerian–Smithian papery limestones.ConclusionsThe Neo-Tethys Ocean opened with the northward drifting of the Iran/Mega-Lhasamicrocontinent followed a rifting extensional phase in the Roadian–Wordian. Thermalsubsidence, with the development of the continental margin, is well recorded in theWordian–Capitanian carbonate succession and continued during the Lopingian. Tectonicinstability of the margin, with block tilting, platform drowning and (fault) breccia depositsstarted at the dawn of the Triassic with the main climax during the Dienerian and theSmithian

Cardiac-Specific Gene Expression Facilitated by an Enhanced Myosin Light Chain Promoter

Background: Adenoviral gene transfer has been shown to be effective in cardiac myocytes in vitro and in vivo. A major limitation of myocardial gene therapy is the extracardiac transgene expression. Methods: To minimize extracardiac gene expression, we have constructed a tissue-specific promoter for cardiac gene transfer, namely, the 250-bp fragment of the myosin light chain-2v (MLC-2v) gene, which is known to be expressed in a tissue-specific manner in ventricular myocardium followed by a luciferase (luc) reporter gene (Ad.4 × MLC250.Luc). Rat cardiomyocytes, liver and kidney cells were infected with Ad.4 × MLC.Luc or control vectors. For in vivo testing, Ad.4 × MLC250.Luc was injected into the myocardium or in the liver of rats. Kinetics of promoter activity were monitored over 8 days using a cooled CCD camera. Results: In vitro: By infecting hepatic versus cardiomyocyte cells, we found that the promoter specificity ratio (luc activity in cardiomyocytes per liver cells) was 20.4 versus 0.9 (Ad.4 × MLC250.Luc vs. Ad.CMV). In vivo: Ad.4 × MLC250.Luc significantly reduced luc activity in liver (38.4-fold), lung (16.1-fold), and kidney (21.8-fold) versus Ad.CMV (p = .01); whereas activity in the heart was only 3.8-fold decreased. The gene expression rate of cardiomyocytes versus hepatocytes was 7:1 (Ad.4 × MLC.Luc) versus 1:1.4 (Ad.CMV.Luc). Discussion: This new vector may be useful to validate therapeutic approaches in animal disease models and offers the perspective for selective expression of therapeutic genes in the diseased heart

Cardiac-Specific Gene Expression Facilitated by an Enhanced Myosin Light Chain Promoter

Background: Adenoviral gene transfer has been shown to be effective in cardiac myocytes in vitro and in vivo. A major limitation of myocardial gene therapy is the extracardiac transgene expression. Methods: To minimize extracardiac gene expression, we have constructed a tissue-specific promoter for cardiac gene transfer, namely, the 250-bp fragment of the myosin light chain-2v (MLC-2v) gene, which is known to be expressed in a tissue-specific manner in ventricular myocardium followed by a luciferase (luc) reporter gene (Ad.4 × MLC 250 .Luc). Rat cardiomyocytes, liver and kidney cells were infected with Ad.4 × MLC.Luc or control vectors. For in vivo testing, Ad.4 × MLC 250 .Luc was injected into the myocardium or in the liver of rats. Kinetics of promoter activity were monitored over 8 days using a cooled CCD camera. Results: In vitro: By infecting hepatic versus cardiomyocyte cells, we found that the promoter specificity ratio (luc activity in cardiomyocytes per liver cells) was 20.4 versus 0.9 (Ad.4 × MLC 250 .Luc vs. Ad.CMV). In vivo: Ad.4 × MLC 250 .Luc significantly reduced luc activity in liver (38.4-fold), lung (16.1-fold), and kidney (21.8-fold) versus Ad.CMV ( p = .01); whereas activity in the heart was only 3.8-fold decreased. The gene expression rate of cardiomyocytes versus hepatocytes was 7:1 (Ad.4 × MLC.Luc) versus 1:1.4 (Ad.CMV.Luc). Discussion: This new vector may be useful to validate therapeutic approaches in animal disease models and offers the perspective for selective expression of therapeutic genes in the diseased heart

Resources Solid Science Workshop Zurich

Here you can find a number of resources that I mentioned during class