Routing of western Canadian Plains runoff during the 8.2 ka cold event

The collapse of the Laurentide Ice Sheet over Hudson Bay ∼8.47 ka allowed the rapid drainage of glacial Lake Agassiz into the Labrador Sea, an event identified as causing a reduction in Atlantic meridional overturning circulation (AMOC) and the 8.2 ka cold event. Atmosphere-ocean models simulations based on this forcing, however, fail to reproduce several characteristics of this event, particularly its duration. Here we use planktonic foraminifera U/Ca records to document the routing of western Canadian Plains runoff that accompanied ice-sheet collapse. Geochemical modeling of the ∼7 nmol/mol increase in U/Ca at the opening of Hudson Bay indicates an increase in freshwater discharge of 0.13 ± 0.03 Sverdrups (106 m3 s−1) from routing, a sufficient magnitude to cause an AMOC reduction. We suggest that this routing event suppressed AMOC strength for several centuries after the drainage of Lake Agassiz, explaining multi-centennial climate anomalies associated with the 8.2 ka cold event

Effects of Hydrographic Variability on the Spatial, Seasonal and Diel Diving Patterns of Southern Elephant Seals in the Eastern Weddell Sea

Weddell Sea hydrography and circulation is driven by influx of Circumpolar Deep Water (CDW) from the Antarctic Circumpolar Current (ACC) at its eastern margin. Entrainment and upwelling of this high-nutrient, oxygen-depleted water mass within the Weddell Gyre also supports the mesopelagic ecosystem within the gyre and the rich benthic community along the Antarctic shelf. We used Conductivity-Temperature-Depth Satellite Relay Data Loggers (CTD-SRDLs) to examine the importance of hydrographic variability, ice cover and season on the movements and diving behavior of southern elephant seals in the eastern Weddell Sea region during their overwinter feeding trips from Bouvetøya. We developed a model describing diving depth as a function of local time of day to account for diel variation in diving behavior. Seals feeding in pelagic ice-free waters during the summer months displayed clear diel variation, with daytime dives reaching 500-1500 m and night-time targeting of the subsurface temperature and salinity maxima characteristic of CDW around 150–300 meters. This pattern was especially clear in the Weddell Cold and Warm Regimes within the gyre, occurred in the ACC, but was absent at the Dronning Maud Land shelf region where seals fed benthically. Diel variation was almost absent in pelagic feeding areas covered by winter sea ice, where seals targeted deep layers around 500–700 meters. Thus, elephant seals appear to switch between feeding strategies when moving between oceanic regimes or in response to seasonal environmental conditions. While they are on the shelf, they exploit the locally-rich benthic ecosystem, while diel patterns in pelagic waters in summer are probably a response to strong vertical migration patterns within the copepod-based pelagic food web. Behavioral flexibility that permits such switching between different feeding strategies may have important consequences regarding the potential for southern elephant seals to adapt to variability or systematic changes in their environment resulting from climate change

Holocene Cyclic Records of Ice-Rafted Debris and Sea Ice Variations on the East Greenland and Northwest Iceland Margins

The dynamics of the Greenland Ice Sheet and drift of sea ice from the Arctic Ocean reaching Denmark Strait are poorly constrained. We present data on the provenance of Fe oxide detrital grains from two cores in the Denmark Strait area and compare the Fe grain source data with other environmental proxies in order to document the variations and potential periodicities in ice-rafted debris delivery during the Holocene. Based on their Fe grain geochemistry, the sediments can be traced to East Greenland sources and to more distal sites around the Arctic Basin. On the Holocene time scales of the two cores, sea ice biomarker (IP25) data, and quartz weight percent reveal positive associations with T°C and inverse associations with biogenic carbonate wt%. Trends in the data were obtained from Singular Spectrum Analysis (SSA), and residuals were tested for cyclicity. Trends on the environmental proxies explained between 15 and 90% of the variance. At both sites the primary Fe grain sources were from Greenland, but significant contributions were also noted from Banks Island and Svalbard. There is a prominent cyclicity of 800 yrs as well as other less prominent cycles for both Greenland and arctic sources. The Fe grain sources from Greenland and the circum-Arctic Ocean are in synchronization, suggesting that the forcings for these cycles are regional and not local ice sheet instabilities

Decadal fingerprints of freshwater discharge around Greenland in a multi-model ensemble

The recent increase in the rate of the Greenland ice sheet melting has raised with urgency the question of the impact of such a melting on the climate. As former model projections, based on a coarse representation of the melting, show very different sensitivity to this melting, it seems necessary to consider a multi-model ensemble to tackle this question. Here we use five coupled climate models and one ocean-only model to evaluate the impact of 0.1 Sv (1 Sv = 106 m3/s) of freshwater equally distributed around the coast of Greenland during the historical era 1965–2004. The ocean-only model helps to discriminate between oceanic and coupled responses. In this idealized framework, we find similar fingerprints in the fourth decade of hosing among the models, with a general weakening of the Atlantic Meridional Overturning Circulation (AMOC). Initially, the additional freshwater spreads along the main currents of the subpolar gyre. Part of the anomaly crosses the Atlantic eastward and enters into the Canary Current constituting a freshwater leakage tapping the subpolar gyre system. As a consequence, we show that the AMOC weakening is smaller if the leakage is larger. We argue that the magnitude of the freshwater leakage is related to the asymmetry between the subpolar-subtropical gyres in the control simulations, which may ultimately be a primary cause for the diversity of AMOC responses to the hosing in the multi-model ensemble. Another important fingerprint concerns a warming in the Nordic Seas in response to the re-emergence of Atlantic subsurface waters capped by the freshwater in the subpolar gyre. This subsurface heat anomaly reaches the Arctic where it emerges and induces a positive upper ocean salinity anomaly by introducing more Atlantic waters. We found similar climatic impacts in all the coupled ocean–atmosphere models with an atmospheric cooling of the North Atlantic except in the region around the Nordic Seas and a slight warming south of the equator in the Atlantic. This meridional gradient of temperature is associated with a southward shift of the tropical rains. The free surface models also show similar sea-level fingerprints notably with a comma-shape of high sea-level rise following the Canary Current

DETERMINANTS OF 6-MONTH MORTALITY IN SURVIVORS OF MYOCARDIAL-INFARCTION AFTER THROMBOLYSIS - RESULTS OF THE GISSI-2 DATA-BASE

none647Background. Current knowledge of risk assessment in survivors of myocardial infarction is largely based on data gathered before the advent of thrombolysis. It must be determined whether and to what extent available information and proposed criteria of prognostication are applicable in the thrombolytic era. Methods and Results. We reassessed risk prediction in the 10 219 survivors of myocardial infarction with follow-up data available (ie, 98% of the total) who had been enrolled in the GISSI-2 trial, relying on a set of prespecified variables. The 3.5% 6-month all-cause mortality rate of these patients compared with the higher value of 4.6% found in the corresponding GISSI-1 cohort, originally allocated to streptokinase therapy, indicates a 24% reduction in postdischarge 6-month mortality. On multivariate analysis (Cox model), the following variables were predictors of 6-month all-cause mortality: ineligibility for exercise test for both cardiac (relative risk [RR], 3.30; 95% confidence interval [CI], 2.36-4.62) and noncardiac reasons (RR, 3.28; 95% CI, 2.23-4.72), early left ventricular failure (RR, 2.41; 95% Cl, 1.87-3.09), echocardiographic evidence of recovery phase left ventricular dysfunction (RR, 2.30; 95% CI, 1.78-2.98), advanced (more than 70 years) age (RR, 1.81; 95% Cl, 1.43 -2.30), electrical instability (ie, frequent and/or complex ventricular arrhythmias) (RR, 1.70; 95% Cl, 1.32-2.19), late left ventricular failure (RR, 1.54; 95% Cl, 1.17-2.03), previous myocardial infarction (RR, 1.47; 95% CI, 1.14-1.89), and a history of treated hypertension (RR, 1.32; 95% Cl, 1.05-1.65). Early post-myocardial infarction angina, a positive exercise test, female sex, history of angina, history of insulin-dependent diabetes, and anterior site of myocardial infarction were not risk predictors. On further multivariate analysis, performed on 8315 patients with the echocardiographic indicator of left ventricular dysfunction available, only previous myocardial infarction was not retained as an independent risk predictor. Conclusions. A decline in 6-month mortality of myocardial infarction survivors, seen within 6 hours of symptom onset, has been observed in recent years. Ineligibility for exercise test, early left ventricular failure, and recovery-phase left ventricular dysfunction are the most powerful (RR, >2) predictors of 6-month mortality among patients recovering from myocardial infarction after thrombolysis. Qualitative variables reflecting residual myocardial ischemia do not appear to be risk predictors. The lack of an independent adverse influence of early post-myocardial infarction angina on 6-month survival represents a major difference between this study and those of the prethrombolytic era.noneVOLPI A; DEVITA C; FRANZOSI MG; GERACI E; MAGGIONI AP; MAURI F; NEGRI E; SANTORO E; TAVAZZI L; TOGNONI G; FERUGLIO GA; LOTTO A; ROVELLI F; SOLINAS P; TAVAZZI L; TOGNONI G; BRUNO M; CAPPELLO T; COPPINI A; FINCATI F; MANTOVANI G; PANGRAZZI J; POGNA M; TURAZZA FM; ANSELMI M; BARBONAGLIA L; BIGI R; CAVALLI A; FRIGERIO M; GIORDANO A; GUALTIEROTTI C; TORTA D; CAROLA R; GIORDANO F; BARLOTTI R; LOPARCO G; VIGLINO GL; RUGGERI G; GIAMUNDO L; DANESI A; PACIARONI E; GAMBINI C; URBANO G; PURCARO A; FRANCESCONI M; FIGLIOLIA S; CANNONE M; ANTOLINI R; DEVOTI G; CRISTALLINI P; PORCIELLO PI; TEONI P; BURALI A; ZUCCONELLI V; DEMATTEIS C; IERVOGLINI A; SCATASTA M; AMABILI S; CARATTI CA; ZOLA G; FERRAGUTO P; SALICI G; CENTARO A; ROTIROTI D; GENOVESE M; GINEVRINO P; DAMATO N; ALTAMURA CM; COLONNA L; CASTELLANETA G; BOVENZI F; MESSINA D; GALANTINO A; CAMPOREALE N; CUCCHINI F; CAMPOSTELLA L; MALACRIDA R; GENONI M; PELLEGRINI P; BRIDDA A; RIGGI L; ACONE L; MOSCATIELLO G; BRUNO A; INVERNIZZI G; TESPILI M; GUAGLIUMI G; CASARI A; ALBANO T; TOMASSINI B; TORTA D; DIBIASE G; SCARAMUZZINO G; RUGGERO S; BRACCHETTI D; DECASTRO U; FULVI M; BRAITO E; ERLICHER A; OBERLECHNER W; GAGLIARDI RS; BIGHIGNOLI L; BONIZZATO G; RIZZI GM; SCAZZINA L; PERRINI A; STRANEO G; STRANEO U; SCIRE A; VERRIENTI A; GUADALUPI M; STORELLI A; ZUCCA L; DABUSTI M; ALBONICO B; DEPETRA V; TABACCHI GC; SCERVINO R; MEREU D; MAXIA P; BIANCO A; CRABU E; MANGIAMELI S; CENTAMORE G; MALFITANO D; AMICO C; VANCHERI F; SANTOPUOLI G; BALDINI F; PANTALEONI A; CONTESSOTTO F; TERLIZZI R; MERIGHI A; TURCHI E; TEGLIO V; PIGNATTI F; PEZZANA A; GOZZOLINO G; GIGLIO M; PETTINATI G; IEVA M; CIRICUGNO S; CORREALE E; ROMANO S; DIFUCCIA A; CASTELLANO B; NATALE A; CERNETTI C; CELEGON L; CANDELPERGHER G; ARIENZO F; RUSSO F; DEVIVO L; MAY L; ACHILLI G; BLASI A; SORRENTINO F; DATO A; GALLONE P; PALUMBO C; DELLAMONICA R; PAGANO L; ALBERTI A; ORSELLI L; DEPONTI C; PARMIGIANI ML; FERRARI M; ACITO P; BUSI F; DELLAVITTORIA G; BELLET C; BORTOLINI F; ROSSI A; CORONA C; BONDI S; NICCOLINI D; GAMBERI G; ARCURI G; MAIOLINO P; CARROZZA A; DELIO U; CAPRETTI G; MARINONI C; GUASCONI C; SONNINO S; PAGLIEI M; FERRARI G; LOMBARDI R; AGNELLI D; DERINALDIS G; CALCAGNILE A; SIGNORELLI S; BENDINELLI S; LUSETTI L; MOLLAIOLI M; COSMI F; PLASTINA F; VENNERI N; FERACO E; CATELLI P; POLUZZI C; DISTANTE S; BIANCHI C; COPPETTI S; ZAMPAGLIONE G; GATTO C; ZURLO R; USLENGHI E; MARGARIA F; MILANESE U; LOMANTO B; ZIACCHI V; RIVA D; BERTOCCHI P; TIRELLA G; DAULERIO M; SAURO G; BINI A; MAZZONI V; POGGI P; MARESTA A; JACOPI F; PATRONCINI A; PUPITA F; GAGGI S; FRAUSINI G; ANTONIOLI GE; MALACARNE C; CODECA L; CAPPATO R; ANDREOLI L; VARACCA S; BUIO E; FAZZINI PF; PUCCI P; SARRO F; VERGASSOLA R; BARCHIELLI M; DEMATTEIS D; CARRONE M; BRUNOZZI LT; MENICONI L; LIBERATI R; RADOGNA M; TALLONE M; CONTE R; IERI A; ZIPOLI A; SANSONI M; CANZIANI R; GUIDALI P; CRISTALLO E; MARIELLO F; MUZIO L; BENVENUTO MR; BALDINI MR; VECCHIO C; CHIARELLA F; FALCIDIENO M; CECCHI A; GIULIANO G; SEU V; PERUGINI P; TOSELLI A; BASSO F; CORTI E; ROSSI P; DELFINO R; CAPONNETTO S; GNECCO G; GHIGLIOTTI G; PENNESI A; LOMBARDI G; RUGGIERI A; BERTOLO L; SLOMP L; LANZETTA T; MAZZARONE L; CRESTI A; BELLODI G; ZUARINI AM; VENERI L; PARCHI C; GIOVANELLI N; NEGRONI S; DETHOMATIS M; BARGHINI A; MARINO E; RICCI D; LEMME P; DIGIACOMO U; AQUARO G; RONZANI G; OTTELLO B; VONTI V; MORETTI S; PALERMO R; MARSILI P; SIDERI F; RAGAZZINI G; GRAMENZI S; BATTISTINI S; DIODATO T; VALERIO A; TUCCI C; DEPASQUALE B; GELFO PG; BERTULLA A; BOLLINI R; DEMARCHI E; BACCA F; DEGIORGI V; LOCATELLI V; SAVOIA MT; FERRACINI C; BARBARESI F; COTOGNI A; FRANCO G; ROMANO S; PASSONI F; DURBANO M; MORETTI G; PEROTTI S; CAPRETTI M; DELBENE P; CASCONE M; BALDINI U; ORLANDI M; ODDONE A; CAIZZI V; MASINI G; LAZZARI M; BALLERINI B; BOZZI L; MOCETTI T; BERTOLINI A; PASOTTI E; SANGUINETTI M; MANTOVANI R; TOGNOLI T; MAGGI A; TUSA M; CAMERONI E; GUERRA GP; REGGIANI A; REDAELLI S; GIUSTI S; TANTALO L; RIZZI A; DIGIOVANNI N; GUZZO V; GABRIELE M; COLOMBO G; ALBERZONI A; SALVIOLI G; GALFETTI F; DOVICO E; BELLUZZI F; GOLA E; CASELLATO F; LECCHI G; CONSOLO F; SACCA CB; CONSOLO A; PICCOLO E; GASPARINI G; DEVITA C; ALBERTI A; MASSA D; BELLI C; DOSSENA MG; CORSINI C; SANNA GP; AZZOLLINI M; TRUAZZA F; LOTTO A; NADOR F; DEMARTINI M; BOZZI G; SEREGNI R; PASTINE I; MORPURGO M; CASAZZA F; REGALIA F; MAGGIOLINI S; RIGO R; PANCALDI S; POZZETTI D; PASCOTTO P; FRANCESCHI L; DAINESE F; MELINI L; CAPPELLI C; BERNARDI C; PALMIERI M; BORGIONI L; ZILIO G; SANDRI R; ALITTO F; MASARO G; VALAGUSSA F; SCHIAVINA R; RAVESI D; DANIELLO L; PIANTADOSI FR; BARRA P; ROMEO D; MININNI N; SEVERINO S; MOSTACCI M; CASTELLARI M; BANDA D; ROLANDI R; VILLA WD; CARBONE V; ALLEGRI M; FASCIOLO L; PITTALIS M; MUREDDU V; SORO F; DELEDDA MG; MARRAS E; MARCHI SM; DELUCA C; MANETTA M; VOLTA SD; SPERANDEO V; DONZELLI M; VITRANO MG; GERACI E; PITROLO F; LAMONICA S; BELLANCA G; MESSINA G; MIRTO U; RAINERI A; TRAINA M; DIBENEDETTO A; RIBAUDO E; DIFRANCESCO M; RONCHITELLI R; CARONE M; DIGREGORIO D; DIPAOLO G; PASQUALE M; COREA L; COCCHIERI M; ALUNNI G; PAPI L; CHIRIATTI G; LUPETTI M; GAZZOLA U; ARRUZZOLI S; VILLANI GQ; MELLINI M; MADRUZZA L; PIAZZA R; MICHELI G; FRANCHINI C; BECHI S; MARTINES C; MARCHESE D; GABBIA G; BIGALLI A; CIUTI M; CABANI E; DELCITERNA F; ALFIERI A; CHITI M; LONGHINI J; CODELUPPI P; NEGRELLI M; ZANUTTINI D; NICOLOSI GL; MARTIN G; PETRELLA A; BARDAZZI L; BIANCO GA; CELLAMARE G; GIANNELLI F; LICITRA G; LICITRA R; LETTICA GV; TUMIOTTO G; BELLANTI G; BOSI S; CASALI G; MONDUCCI I; BARONE A; PARENTI F; HEYMAN J; COZZI E; BALDACCI G; BACCOS D; BRIGHI F; DESANCTIS A; BOCK R; PALMIERI M; ROSSI F; AMATI P; SEMPRINI P; NARDELLI A; BOTTERO G; VARTOLO C; MILAZZOTTO F; DICROCE G; DIMARIO F; ANGRISANI G; AZZOLINI P; NEJA CP; MANZOLI U; ROSSI E; TRANI C; MASINI V; SEBASTIANI F; TOPAI M; BORGIA MC; LUCIANI C; FERRI F; DEPAOLA D; CAPURSO S; TUGNOLI F; VETTA C; ALTIERI T; BORZI M; VISCOMI A; STRIANO U; SALITURI S; ZONZIN P; FIORENCIS R; BADIN A; RAVERA B; BALDI C; SILVESTRI F; ALLEMANO P; REYNAUD S; SANSON A; MILANI L; DESIMONE MV; RUSSO A; VILLELLA A; GRAZINI M; AMIDEI S; ANSELMI L; PICCANICOLINO R; MASCELLI G; TAGLIAMONTE A; MESSINA V; TEDESCHI C; BOSSI M; BISIOLI M; TACCHI G; PAGNI G; VIVALDI F; IBBA GV; SANNIA L; PEDRAZZINI F; BAGNI E; FABII S; ALVINO A; ANTONIELLI E; DORONZO B; MARTINENGO E; BECCHI G; SALMOIRAGHI A; DIGIOVANNA F; CARAMANNO G; CAPORICCI D; BRUN M; GIANI P; FERRARIO G; PECI P; RONCONI G; SKOUSE D; BIANCHI C; GIUSTINIANI S; CUCCHI GF; TAVASCI E; SILVERII A; MARCELLINI G; SPECA G; STANISCIA D; CIMINO A; SERAFINI N; DEBONIS P; CERRUTI P; BAZZUCCHI M; DALPRA F; SPEROTTO C; MOLE GD; BARBANO G; POMARI F; GASCHINO G; PARIGI A; GANDOLFO N; RONDONI F; BRUSCA A; DILEO M; GOLZIO PG; ABRATE M; SCLAVO MG; ROCCI R; POGGIO G; GIANI S; CUZZUCREA D; BRASCHI GB; SCIACCA R; SAMMARTANO A; FURLANELLO F; BRAITO G; CUZZATO V; TOTIS O; FAURETTO F; LEO F; GALATI A; PALMA P; CAMERINI F; MORGERA T; BARBIERI L; FERUGLIO GA; SLAVICK GA; FRESCO C; CUDA A; SARNICOLA P; ARZILLO P; BINAGHI G; MACCHI G; CALVERI G; DIMARCO G; LEVANTESI G; PANERAI C; CATURELLI G; FACCHIN L; SARTORE G; ZARDINI P; MARINO P; CARBONIERI E; NAVA S; MAZZINI C; NAVA R; SERRA N; SASSARA M; NICROSINI F; GANDOLFI P; BERGOGNONI G; BALLESTRA AM; VIOLO CVOLPI A; DEVITA C; FRANZOSI MG; GERACI E; MAGGIONI AP; MAURI F; NEGRI E; SANTORO E; TAVAZZI L; TOGNONI G; FERUGLIO GA; LOTTO A; ROVELLI F; SOLINAS P; TAVAZZI L; TOGNONI G; BRUNO M; CAPPELLO T; COPPINI A; FINCATI F; MANTOVANI G; PANGRAZZI J; POGNA M; TURAZZA FM; ANSELMI M; BARBONAGLIA L; BIGI R; CAVALLI A; FRIGERIO M; GIORDANO A; GUALTIEROTTI C; TORTA D; CAROLA R; GIORDANO F; BARLOTTI R; LOPARCO G; VIGLINO GL; RUGGERI G; GIAMUNDO L; DANESI A; PACIARONI E; GAMBINI C; URBANO G; PURCARO A; FRANCESCONI M; FIGLIOLIA S; CANNONE M; ANTOLINI R; DEVOTI G; CRISTALLINI P; PORCIELLO PI; TEONI P; BURALI A; ZUCCONELLI V; DEMATTEIS C; IERVOGLINI A; SCATASTA M; AMABILI S; CARATTI CA; ZOLA G; FERRAGUTO P; SALICI G; CENTARO A; ROTIROTI D; GENOVESE M; GINEVRINO P; DAMATO N; ALTAMURA CM; COLONNA L; CASTELLANETA G; BOVENZI F; MESSINA D; GALANTINO A; CAMPOREALE N; CUCCHINI F; CAMPOSTELLA L; MALACRIDA R; GENONI M; PELLEGRINI P; BRIDDA A; RIGGI L; ACONE L; MOSCATIELLO G; BRUNO A; INVERNIZZI G; TESPILI M; GUAGLIUMI G; CASARI A; ALBANO T; TOMASSINI B; TORTA D; DIBIASE G; SCARAMUZZINO G; RUGGERO S; BRACCHETTI D; DECASTRO U; FULVI M; BRAITO E; ERLICHER A; OBERLECHNER W; GAGLIARDI RS; BIGHIGNOLI L; BONIZZATO G; RIZZI GM; SCAZZINA L; PERRINI A; STRANEO G; STRANEO U; SCIRE A; VERRIENTI A; GUADALUPI M; STORELLI A; ZUCCA L; DABUSTI M; ALBONICO B; DEPETRA V; TABACCHI GC; SCERVINO R; MEREU D; MAXIA P; BIANCO A; CRABU E; MANGIAMELI S; CENTAMORE G; MALFITANO D; AMICO C; VANCHERI F; SANTOPUOLI G; BALDINI F; PANTALEONI A; CONTESSOTTO F; TERLIZZI R; MERIGHI A; TURCHI E; TEGLIO V; PIGNATTI F; PEZZANA A; GOZZOLINO G; GIGLIO M; PETTINATI G; IEVA M; CIRICUGNO S; CORREALE E; ROMANO S; DIFUCCIA A; CASTELLANO B; NATALE A; CERNETTI C; CELEGON L; CANDELPERGHER G; ARIENZO F; RUSSO F; DEVIVO L; MAY L; ACHILLI G; BLASI A; SORRENTINO F; DATO A; GALLONE P; PALUMBO C; DELLAMONICA R; PAGANO L; ALBERTI A; ORSELLI L; DEPONTI C; PARMIGIANI ML; FERRARI M; ACITO P; BUSI F; DELLAVITTORIA G; BELLET C; BORTOLINI F; ROSSI A; CORONA C; BONDI S; NICCOLINI D; GAMBERI G; ARCURI G; MAIOLINO P; CARROZZA A; DELIO U; CAPRETTI G; MARINONI C; GUASCONI C; SONNINO S; PAGLIEI M; FERRARI G; LOMBARDI R; AGNELLI D; DERINALDIS G; CALCAGNILE A; SIGNORELLI S; BENDINELLI S; LUSETTI L; MOLLAIOLI M; COSMI F; PLASTINA F; VENNERI N; FERACO E; CATELLI P; POLUZZI C; DISTANTE S; BIANCHI C; COPPETTI S; ZAMPAGLIONE G; GATTO C; ZURLO R; USLENGHI E; MARGARIA F; MILANESE U; LOMANTO B; ZIACCHI V; RIVA D; BERTOCCHI P; TIRELLA G; DAULERIO M; SAURO G; BINI A; MAZZONI V; POGGI P; MARESTA A; JACOPI F; PATRONCINI A; PUPITA F; GAGGI S; FRAUSINI G; ANTONIOLI GE; MALACARNE C; CODECA L; CAPPATO R; ANDREOLI L; VARACCA S; BUIO E; FAZZINI PF; PUCCI P; SARRO F; VERGASSOLA R; BARCHIELLI M; DEMATTEIS D; CARRONE M; BRUNOZZI LT; MENICONI L; LIBERATI R; RADOGNA M; TALLONE M; CONTE R; IERI A; ZIPOLI A; SANSONI M; CANZIANI R; GUIDALI P; CRISTALLO E; MARIELLO F; MUZIO L; BENVENUTO MR; BALDINI MR; VECCHIO C; CHIARELLA F; FALCIDIENO M; CECCHI A; GIULIANO G; SEU V; PERUGINI P; TOSELLI A; BASSO F; CORTI E; ROSSI P; DELFINO R; CAPONNETTO S; GNECCO G; GHIGLIOTTI G; PENNESI A; LOMBARDI G; RUGGIERI A; BERTOLO L; SLOMP L; LANZETTA T; MAZZARONE L; CRESTI A; BELLODI G; ZUARINI AM; VENERI L; PARCHI C; GIOVANELLI N; NEGRONI S; DETHOMATIS M; BARGHINI A; MARINO E; RICCI D; LEMME P; DIGIACOMO U; AQUARO G; RONZANI G; OTTELLO B; VONTI V; MORETTI S; PALERMO R; MARSILI P; SIDERI F; RAGAZZINI G; GRAMENZI S; BATTISTINI S; DIODATO T; VALERIO A; TUCCI C; DEPASQUALE B; GELFO PG; BERTULLA A; BOLLINI R; DEMARCHI E; BACCA F; DEGIORGI V; LOCATELLI V; SAVOIA MT; FERRACINI C; BARBARESI F; COTOGNI A; FRANCO G; ROMANO S; PASSONI F; DURBANO M; MORETTI G; PEROTTI S; CAPRETTI M; DELBENE P; CASCONE M; BALDINI U; ORLANDI M; ODDONE A; CAIZZI V; MASINI G; LAZZARI M; BALLERINI B; BOZZI L; MOCETTI T; BERTOLINI A; PASOTTI E; SANGUINETTI M; MANTOVANI R; TOGNOLI T; MAGGI A; TUSA M; CAMERONI E; GUERRA GP; REGGIANI A; REDAELLI S; GIUSTI S; TANTALO L; RIZZI A; DIGIOVANNI N; GUZZO V; GABRIELE M; COLOMBO G; ALBERZONI A; SALVIOLI G; GALFETTI F; DOVICO E; BELLUZZI F; GOLA E; CASELLATO F; LECCHI G; CONSOLO F; SACCA CB; CONSOLO A; PICCOLO E; GASPARINI G; DEVITA C; ALBERTI A; MASSA D; BELLI C; DOSSENA MG; CORSINI C; SANNA GP; AZZOLLINI M; TRUAZZA F; LOTTO A; NADOR F; DEMARTINI M; BOZZI G; SEREGNI R; PASTINE I; MORPURGO M; CASAZZA F; REGALIA F; MAGGIOLINI S; RIGO R; PANCALDI S; POZZETTI D; PASCOTTO P; FRANCESCHI L; DAINESE F; MELINI L; CAPPELLI C; BERNARDI C; PALMIERI M; BORGIONI L; ZILIO G; SANDRI R; ALITTO F; MASARO G; VALAGUSSA F; SCHIAVINA R; RAVESI D; DANIELLO L; PIANTADOSI FR; BARRA P; ROMEO D; MININNI N; SEVERINO S; MOSTACCI M; CASTELLARI M; BANDA D; ROLANDI R; VILLA WD; CARBONE V; ALLEGRI M; FASCIOLO L; PITTALIS M; MUREDDU V; SORO F; DELEDDA MG; MARRAS E; MARCHI SM; DELUCA C; MANETTA M; VOLTA SD; SPERANDEO V; DONZELLI M; VITRANO MG; GERACI E; PITROLO F; LAMONICA S; BELLANCA G; MESSINA G; MIRTO U; RAINERI A; TRAINA M; DIBENEDETTO A; RIBAUDO E; DIFRANCESCO M; RONCHITELLI R; CARONE M; DIGREGORIO D; DIPAOLO G; PASQUALE M; COREA L; COCCHIERI M; ALUNNI G; PAPI L; CHIRIATTI G; LUPETTI M; GAZZOLA U; ARRUZZOLI S; VILLANI GQ; MELLINI M; MADRUZZA L; PIAZZA R; MICHELI G; FRANCHINI C; BECHI S; MARTINES C; MARCHESE D; GABBIA G; BIGALLI A; CIUTI M; CABANI E; DELCITERNA F; ALFIERI A; CHITI M; LONGHINI J; CODELUPPI P; NEGRELLI M; ZANUTTINI D; NICOLOSI GL; MARTIN G; PETRELLA A; BARDAZZI L; BIANCO GA; CELLAMARE G; GIANNELLI F; LICITRA G; LICITRA R; LETTICA GV; TUMIOTTO G; BELLANTI G; BOSI S; CASALI G; MONDUCCI I; BARONE A; PARENTI F; HEYMAN J; COZZI E; BALDACCI G; BACCOS D; BRIGHI F; DESANCTIS A; BOCK R; PALMIERI M; ROSSI F; AMATI P; SEMPRINI P; NARDELLI A; BOTTERO G; VARTOLO C; MILAZZOTTO F; DICROCE G; DIMARIO F; ANGRISANI G; AZZOLINI P; NEJA CP; MANZOLI U; ROSSI E; TRANI C; MASINI V; SEBASTIANI F; TOPAI M; BORGIA MC; LUCIANI C; FERRI F; DEPAOLA D; CAPURSO S; TUGNOLI F; VETTA C; ALTIERI T; BORZI M; VISCOMI A; STRIANO U; SALITURI S; ZONZIN P; FIORENCIS R; BADIN A; RAVERA B; BALDI C; SILVESTRI F; ALLEMANO P; REYNAUD S; SANSON A; MILANI L; DESIMONE MV; RUSSO A; VILLELLA A; GRAZINI M; AMIDEI S; ANSELMI L; PICCANICOLINO R; MASCELLI G; TAGLIAMONTE A; MESSINA V; TEDESCHI C; BOSSI M; BISIOLI M; TACCHI G; PAGNI G; VIVALDI F; IBBA GV; SANNIA L; PEDRAZZINI F; BAGNI E; FABII S; ALVINO A; ANTONIELLI E; DORONZO B; MARTINENGO E; BECCHI G; SALMOIRAGHI A; DIGIOVANNA F; CARAMANNO G; CAPORICCI D; BRUN M; GIANI P; FERRARIO G; PECI P; RONCONI G; SKOUSE D; BIANCHI C; GIUSTINIANI S; CUCCHI GF; TAVASCI E; SILVERII A; MARCELLINI G; SPECA G; STANISCIA D; CIMINO A; SERAFINI N; DEBONIS P; CERRUTI P; BAZZUCCHI M; DALPRA F; SPEROTTO C; MOLE GD; BARBANO G; POMARI F; GASCHINO G; PARIGI A; GANDOLFO N; RONDONI F; BRUSCA A; DILEO M; GOLZIO PG; ABRATE M; SCLAVO MG; ROCCI R; POGGIO G; GIANI S; CUZZUCREA D; BRASCHI GB; SCIACCA R; SAMMARTANO A; FURLANELLO F; BRAITO G; CUZZATO V; TOTIS O; FAURETTO F; LEO F; GALATI A; PALMA P; CAMERINI F; MORGERA T; BARBIERI L; FERUGLIO GA; SLAVICK GA; FRESCO C; CUDA A; SARNICOLA P; ARZILLO P; BINAGHI G; MACCHI G; CALVERI G; DIMARCO G; LEVANTESI G; PANERAI C; CATURELLI G; FACCHIN L; SARTORE G; ZARDINI P; MARINO P; CARBONIERI E; NAVA S; MAZZINI C; NAVA R; SERRA N; SASSARA M; NICROSINI F; GANDOLFI P; BERGOGNONI G; BALLESTRA AM; VIOLO

MEDICAL SCIENCE. GISSI-2: A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction

A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1\ub75 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12 500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study was the combined estimate of death plus severe left ventricular damage. 12 490 patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA alone, tPA plus heparin). No specific differences between the two thrombolytic agents were detected as regards the combined end-point (tPA 23\ub71%; SK 22\ub75%; relative risk 1\ub704, 95% Cl 0\ub795-1\ub713), nor after the addition of heparin to the aspirin treatment (hep 22\ub77%, no hep 22\ub79%; RR 0\ub799, 95% Cl 0\ub791-1\ub708). The outcome of patients allocated to the four treatment groups was similar with respect to baseline risk factors such as age, Killip class, hours from onset of symptoms, and site and type of infarct. The rates of major in-hospital cardiac complications (reinfarction, post-infarction angina) were also similar. The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0\ub75%, SK 1\ub70%, RR 0\ub757, 95% Cl 0\ub738-0\ub785; hep 1\ub70%, no hep 0\ub76%, RR 1\ub764, 95% Cl 1\ub709-2\ub745), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8\ub78% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI. \ua9 1990