SEPSIS AND BuwlD DISSEMINATED INTRAVASCULAR COAGULATION: A MODIFIED THERAPEUTIC APPROACH (LOW DOSE IIEPARIN AND IN DIPIRIDAMOLE) WITH TWO SUCCESSFUL CASES.

Games OM. Magaihh hM, Fmj M, P&a F&o WC, Junqueira Neves H, Carvalbo JI, Gumcs ES,

Ftmda@o Cardiovascular So Francisa, de A&s - Sew&r Be.10 Horizoate - MG, Brazil

‘Ihe bqarm is used in DIC io attempt to stop the sugmcnted consumptim of c4mgulation &tax The Hqarindipyridamole assodicm would be enolha f&a&e aknative since tie hwio

pathways and the dip&idamoIe e&d woold bc. added iu the treatment. Two patients (WhiB, male, 17 years old wd WAC, male, 12 years old) with sepsis and clinical and labor&q s&u&of DICweretrcatedwith6OOWKg/24hofhcparioand 20 mgKg of dipyridamole by continoos intision and spar&d way3 for a mediom time of 14 days. The diagnostic of WMB patiad was septic athrih and the blood adtures revealed Stuphyl~cexs aweus bacteria. His initial platelet count was 65OOOhm and only 24 hours a&r the beghmii of heparin- diwole asso&tion in&&a it rose to 105EMom3. ‘Ihe diagnostic of WAC patimt was a big hepatic abscess end his blood culture also revealed str&vlmlxcus t?wew bcteria. The anticoegutatiar treatmmt perded 18daystitbe6rstpatieot and 10 days for the scamd. ‘Iheir medium time of critical care unit staying was twenty-one days, and botb patients were dkdmrged in good hemodyoamic amditia~s. The hqarin- dipyridamole association may be an important akwative to treat DIG induced by sepsis, mainly by Staphylococcus aureus.

BENEFICIAL EFFECTS OF SARPOGRALATE IN MYOCARDIAL INFARCTION Xiaobing Guo, David Brasil, Kanwal Kumar, Hide0 Kumamoto, Nobuakira Takeda & Naranjan S. Dhalla. Institute of Cardiovascular Sciences, University of Manitoba, Winnipeg, Canada.

Earlier we have reported that sarpogralate, a 5-HT,A receptor antagonist, exerts cardioprotection against ischemia-perfusion induced injury in isolated perfused rat hearts. This study was undertaken to examine if sarpogralate has any beneficial effects in a rat model of acute myocardial infarction. The drug (5 mg/kg; daily) was given orally for 3 weeks 1 hr after starting occlusion of coronary artery in rats. The 24 hr mortality in these animals was markedly reduced. The surviving experimental drug treated animals showed a significant reduction in cardiac hypertrophy and infarct size at 21 days of inducing myocardial infarction. Hemodynamic assessment of animals revealed that the increase in left ventricular end diastolic pressure as well as depression in the rate of pressure development and rate of pressure decay in drug treated-infarcted hearts were less than those seen in the untreated-infarcted group. These results showing the beneficial effects of sarpogralate indicate that 5-HT may be involved in the pathogenesis of acute myocardial infarction. (Supported by CIHR Group in Experimental Cardiology)

ION CONCENTRATION-DEPENDENCE OF RAT CARDIAC UNITARY L-TYPE CALCIUM CHANNEL CONDUCTANCE Ant6nio Guia, Michael D. Stern, Edward G. Lakatta, and Ira R. Josephson. Laboratory of Cardiovascular Sciences, GRC bldg, National Institute on Aging, N.I.H., Baltimore, MD, U.S.A. 21224-6825

Little is known about the native physiological properties

of unitary cardiac L-type calcium currents (ica) measured with physiological calcium (Ca) ion concentration, and their role in excitation-contraction (E-C) coupling. Our goal was

to chart the concentration-dependence of unitary

conductance (y) of iCa down to physiological ion concentrations and compare it to barium (Ba) conductance in the absence of agonists. In isolated, K-depolarized rat myocytes, iCa amplitudes were measured using cell-attached patches with 2 to 70 mM Ca or 2 to 105 mM Ba in the

pipette. At 0 mV, 2 mM Ca produced 0.12 pA and 2 mM Ba produced 0.19 pA unitary currents. Unitary conductance was described by a Langmuir Isotherm relationship with a

maximum ‘/ca of 5.3 f 0.2 pS (N = l5), and YBa of 15 i I pS

(N = 27). The concentration producing half-maximal y, Kd(+

was not different between Ca (1.7 i 0.3 mM) and Ba (I .9 * 0.4 mM). We found that quasi-physiological concentrations of Ca produced currents that were as easily resolvable as those obtained with the traditionally used

higher concentrations. This study leads to future work on the molecular basis of E-C coupling under more physiological conditions.

EXERCISE-INDUCED LATE PRECONDITIONING IS TRIGGERED BY GENERATION OF NITRIC OXIDE. Yiru Guo, Wen-Jian Wu, Xiao-Ping Zhu, Qianhong Li, Xian- Liang Tang, and Roberto Bolli. Division of Cardiology, University of Louisville, Louisville, KY, USA,

~htdefboutsofphysical exmisehavekens-lmvntoelicit clsiepd techdon in infad size (exerdseinduead tale PC), the d-a?dcalsignela~fcf~thii~remain unknchvn. Wetestedihehypulhe&thatgenet&nofNOviaeNOSis lEsponsblefwbiggsfillg-letepc. MilwletraitlE!dto runontfie~~llfwfwrdays,afferwhichthqrwwesubjecledta foursessionsofexerdse(2sessionsldayfortwo~days). Twenty-four ~NZUIS later, rnkz um a 30-r& connary ocdusion followedby24hofreperfusion. lnfarctsbewaareducedbyex&se (24.7 f 2.2 % of the risk region vs. 62.1 f 1.9 % of the risk region) in conh-d njce (groups I and II). When the NOS inhibitor Af’-nilrd- arginine(LNA)wasg~npriortoeachof~efourboutsofexercise @Cup IV), the infard size was indistinguishable fmm that observed in controlandshamexerdsedmice. bheneNosLmieevefaeubjected toemciae,egehn0protedhwasabserved. In&&ingty,infa&size in eNosc shamexercised mice was indiiu@-&le frcm v&j+pe -Y mice,

iridiing that eNOS does not rrcduiate rrfyowrd’~l infard size in this model. We conclude that 1) exe induces late PC in the mouse2)NOisanecessary b%ggeroflhiseclapWm, and 3) U-e NOS lsofwm i-espw&lefor~ heNOismstlikelyeNOS.

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