Evaluacin de los efectos de la diabetes mellitus sobre la circulacin menor en un modelo experimental inducido por estreptozotocina

Evaluacin de los efectos de la diabetes mellitus sobre la circulacin menor en un modelo experimental inducido por estreptozotocina.

Alejandro Len Palacios, Jos Luis Flores Guerrero, Gonzalo Vancini BecerraDr. Fausto Atonal Flores, Dr. Jos Gustavo Lpez y Lpez

1Wild S., et al., Global Prevalence of Diabetes, Diabetes Care ,2004International Diabetes Federation.The IDF Diabetes Atlas.Fifth Edition, 2012Rull Ja., et al., Epidemiology of type 2 diabetes in Mexico, Arch Med Res 20051 TOTAL:2000 : 171 millones 2030 : 366 millones 2 TOTAL:2011 : 366 millones 2030 : 552 millones Amrica2000: 33 millones2030: 66.8 millonesfrica2000: 7 millones2030: 18.2 millonesEuropa2000: 33.3 millones2030: 48 millonesMedio Este2000: 15.2 millones2030: 42.6 millonesAsia y Australia2000: 82.7 millones2030: 190.5 millones3MXICO2025: 11.7 millones2 MORTALIDAD:2011 : 4.6 millones8.6 % de todas las causas 2No ano de 2000 haviam 151 milhes de diabticos no mundo. O crescimento previsto deste nmero em 10 anos varia entre 23 e 57% nas diferentes reas. Em 2010 o nmero de pacientes diabticos dever ser de 221 milhes. Alguns autores consideram estes nmeros subestimados.

Zimmet et al. Nature, 414: 782-787, 2001

Circulacin Pulmonar3Relacin Diabetes Mellitus Circulacin Pulmonar

CHEST 2005; 128:2568-35714Relacin Diabetes Mellitus Circulacin Pulmonar

5Relacin Diabetes Mellitus Circulacin Pulmonar

6

CHEST 2009; 136:31-36Relacin Diabetes Mellitus Circulacin Pulmonar7Evaluacin de la comorbilidadDiabetes Mellitus Hipertensin Pulmonaren un modelo experimental

Reactividad vascularMedicin de presin pulmonarndice FultonTcnica de LangerdoffElectrocardiograma8Caracterizacin delmodelo experimental de diabetesCONTROLDIABETICOGlucemia114.6 1 mg/dL443.2 21.5 mg/dLPeso corporal346.6 6 g183.4 2 gIngesta de agua33.75 1.6ml/24 hrs117.85 7.6ml/24 hrsOrina excretada3.60 0.27ml/24 hrs83.784.2ml/24 hrsIngesta de alimento24.64 1.6g /24 hrs38.391 1.5g/24 hrs

9

Sprague Dawley2-3 mCONTROLDME - STPZSacrificio

A

Registro de tensin isomtricaReactividad vascular10

11

12Efecto de un inhibidor de la eNOSEndotelioMsculo lisoeNOSL-CitrulinaL-ArgininaNOVasodilatacinCa2+AcetilcolinaGMPc

X13NO

M2IP3Ca2+RSL-arginina + O2 eNOS NO+L-citrulinaCa2+_CaMCa2+ClulaEndotelial

Guanilato ciclasasolubleGTPGMPcCa2+Relajacin

107.7 11% 115.9 11% ONONONONONONONONNPNAcetilcolinaCLMVEfecto de un donador de ON14EndotelioMsculo lisoeNOSL-CitrulinaL-ArgininaNOVasodilatacinCa2+AcetilcolinaGMPcO2-ONOO-+SODH2O2XH2O

Efecto de un dismutador de O2-

15EndotelioMsculo lisoeNOSL-CitrulinaL-ArgininaNOVasodilatacinCa2+AcetilcolinaGMPcO2-O2-NADPH oxidasaXO2-X

Efecto de un inhibidor de la NADPH oxidasa

16

17Diabetes MellitusHipertensin Pulmonar< Vasodilatacin> Vasoconstriccin18

Medicin dePresin Pulmonar

CTRLDMEPAP

PRESIN (mmHg)05101520253035(n=7)19

ndice Fulton20ndice Fulton

0.30840.010.37280.02*Ctrl DM21El modelo de DM por estreptozotocina como un modelo experimental de HAP22

23

24Diabetes MellitusMiocardiopata DiabticaHipertensinPulmonarVentrculoIzquierdoVentrculoDerecho?Anlisis temporal25

26 Respuesta del miocardio a la hipertensin pulmonar generada por DM

27Langendorff

28close-up

29

perspectivas30

Electrocardiograma31ElectrocardiogramaControlDME32Variabilidad de la Frecuencia CardiacaFCFC

ControlDME33Variabilidad de la Frecuencia CardiacaControlDME34Dianas terapeticasInsulinaSildenafiloQuercetina35EndotelioClulas msculo lisoeNOSL-CitrulinaL-ArgininaVasodilatacinNOVasoconstriccinHAPSerotonina+O2-X-Insulina+

36Sildenafilo

37Dr. Jos Gustavo Lpez y LpezResponsable del laboratorio

Dr. Fausto Atonal FloresDr. Ricardo Prez FuentesFM BUAPEstudiantes de LicenciaturaEduardo Limn MelladoEmmanuel GuizarGonzalo Vancini BecerraAlejandra CoyopotlIlse Lucero MerinoEmanuel Castro Onofre

MPSSJose Luis Flores GuerreroAlejandro Len PalaciosColaboracionesInstituto de Fisiologa BUAPUniversidad Computense de Madrid

Estudiante postgradoEsther JuarezLaboratorio de Farmacia ClnicaFacultad de Ciencias QumicasBenemrita Universidad Autnoma de Puebla38Grfico30.30840.37280.010.010.020.02

Promedio CtrPromedio DM

Por fechaFechaRataPeso rata (gr.)Glucosa mg/dlPeso corazn (gr.)Cociente VD / CuerpoCociente VD / VIVI + TVD9/23/08SHR Wistar304-0.82360.25120.000830.305010/3/08SHR Wistar324-0.77340.23250.000720.300610/10/08SHR Wistar--0.69430.32110.000000.462510/17/08SHR Wistar--0.67480.44910.000000.665511/18/08Ctr Sprague Dawley #103201040.53700.17240.000540.321011/18/08DM Sprague Dawley #12353420.47450.14820.000630.312311/19/08DM Sprague Dawley #52654340.64240.26350.000990.410211/19/08Ctr Sprague Dawley #2320740.54600.17740.000550.324912/1/08Ctr Sprague Dawley248-0.44830.14360.000580.320312/2/08Ctr Sprague Dawley--0.49150.16210.000000.329812/3/08Ctr Sprague Dawley--0.49640.14860.000000.29941/13/09Ctr Sprague Dawley310990.53720.13700.000440.25501/15/09DM Sprague Dawley #10-201604060.30850.09870.000620.31991/19/09DM Sprague Dawley #152604150.37560.17300.000670.46061/21/09DM Sprague Dawley #211805940.46630.16830.000940.36092/2/09Ctr (Osvaldo) Sprague Dawley70 das-0.37220.09130.000000.24532/3/09Ctr Wistar #432781050.50170.07090.000260.14132/5/09Ctr (Osvaldo) Sprague Dawley70 das-0.32030.09800.000000.30602/16/09Ctr Sprague Dawley322-0.47250.16150.000500.34182/19/09Ctr (Osvaldo) Sprague Dawley70 das-0.48560.14910.000000.30702/19/09Ctr Sprague Dawley620-0.56440.16100.000260.28532/20/09Ctr Sprague Dawley312-0.57580.17170.000550.2982Segunda Parte4/2/09Ctr Wistar #454101480.81580.22880.000560.28054/3/09DM Wistar #412605600.69090.21620.000830.31294/3/09DM Wistar #462403600.45420.12610.000530.27764/16/09DM Wistar #312655120.51460.16350.000620.31774/17/09Ctr Wistar #513251070.63260.20400.000630.32254/20/09Ctr Wistar #494701500.96250.34060.000720.35394/21/09Ctr Wistar #533211540.55410.13270.000410.23954/23/09DM Wistar #582643900.54370.19090.000720.35114/24/09DM Wistar #422234330.62110.28600.001280.4605

Por grupoRataPeso rata (gr.)Glucosa (mg/dl)Peso corazn (gr.)Cociente VD / CuerpoCociente VD / VIVI + TVDSHR Wistar304-0.82360.25120.00082630.3050SHR Wistar324-0.77340.23250.00071760.3006SHR Wistar--0.69430.32110.00000000.4625SHR Wistar--0.67480.44910.00000000.6655Ctr Sprague Dawley3201040.53700.17240.00053880.3210Ctr Sprague Dawley3203420.54600.17740.00055440.3249Ctr Sprague Dawley2484340.44830.14360.00057900.3203Ctr Sprague Dawley-740.49150.16210.00000000.3298Ctr Sprague Dawley--0.49640.14860.00000000.2994Ctr Sprague Dawley310-0.53720.13700.00044190.2550Ctr Sprague Dawley322-0.47250.16150.00050160.3418Ctr Sprague Dawley620990.56440.16100.00025970.2853Ctr Sprague Dawley3124060.57580.17170.00055030.2982DM Sprague Dawley2354150.47450.14820.00063060.3123DM Sprague Dawley2655940.64240.26350.00099430.4102DM Sprague Dawley160-0.30850.09870.00061690.3199DM Sprague Dawley2601050.37560.17300.00066540.4606DM Sprague Dawley180-0.46630.16830.00093500.3609Ctr Wistar278-0.50170.07090.00025500.1413Ctr (Osvaldo) Sprague Dawley70 das-0.37220.09130.00000000.2453Ctr (Osvaldo) Sprague Dawley70 das-0.32030.09800.00000000.3060Ctr (Osvaldo) Sprague Dawley70 das-0.48560.14910.00000000.3070Segunda ParteRataPeso rata (gr.)Glucosa (mg/dl)Peso corazn (gr.)Cociente VD / CuerpoCociente VD / VIVI + TVDCtr Wistar #454101480.81580.22880.000560.2805Ctr Wistar #513251070.63260.20400.000630.3225Ctr Wistar #494701500.96250.34060.000720.3539Ctr Wistar #533211540.55410.13270.000410.2395DM Wistar #412605600.69090.21620.000830.3129DM Wistar #462403600.45420.12610.000530.2776DM Wistar #312655120.51460.16350.000620.3177DM Wistar #582643900.54370.19090.000720.3511DM Wistar #422234330.62110.28600.001280.4605

VD-CuerpoRataCociente VD / CuerpoSHR Wistar0.0008263SHR Wistar0.0007176SHR Wistarno se pes rataSHR Wistarno se pes rataCtr Sprague Dawley0.0005388Ctr Sprague Dawley0.0005544Ctr Sprague Dawley0.0005790Ctr Sprague Dawleyno se pes rataCtr Sprague Dawleyno se pes rataCtr Sprague Dawley0.0004419Ctr Sprague Dawley0.0005016Ctr Sprague Dawley0.0002597Ctr Sprague Dawley0.0005503DM Sprague Dawley0.0006306DM Sprague Dawley0.0009943DM Sprague Dawley0.0006169DM Sprague Dawley0.0006654DM Sprague Dawley0.0009350Ctr Wistar0.0002550Ctr (Osvaldo) Sprague Dawleyno se pes rataCtr (Osvaldo) Sprague Dawleyno se pes rataCtr (Osvaldo) Sprague Dawleyno se pes rataSegunda ParteCtr Wistar #450.00056Ctr Wistar #510.00063Ctr Wistar #490.00072Ctr Wistar #530.00041DM Wistar #410.00083DM Wistar #460.00053DM Wistar #310.00062DM Wistar #580.00072DM Wistar #420.00128

VD-VIRataCociente VD / VISHR Wistar0.3050SHR Wistar0.3006SHR Wistar0.4625SHR Wistar0.6655Ctr Sprague Dawley0.3210Ctr Sprague Dawley0.3249Ctr Sprague Dawley0.3203Ctr Sprague Dawley0.3298Ctr Sprague Dawley0.2994Ctr Sprague Dawley0.2550Ctr Sprague Dawley0.3418Ctr Sprague Dawley0.2853Ctr Sprague Dawley0.2982DM Sprague Dawley0.3123DM Sprague Dawley0.4102DM Sprague Dawley0.3199DM Sprague Dawley0.4606DM Sprague Dawley0.3609Ctr Wistar0.1413Ctr (Osvaldo) Sprague Dawley0.2453Ctr (Osvaldo) Sprague Dawley0.3060Ctr (Osvaldo) Sprague Dawley0.3070Segunda ParteCtr Wistar #450.28046Ctr Wistar #510.32248Ctr Wistar #490.35387Ctr Wistar #530.23949DM Wistar #410.31293DM Wistar #460.27763DM Wistar #310.31772DM Wistar #580.35111DM Wistar #420.46047

VD-Cuerpo Prom. n=7Ctr Sprague Dawley0.00053880.5388n=5DM Sprague Dawley0.00063060.63062.6457513111Ctr Sprague Dawley0.00055440.55442.2360679775DM Sprague Dawley0.00099430.9943Ctr Sprague Dawley0.00057900.5790DM Sprague Dawley0.00061690.6169Ctr Sprague Dawley0.00044190.4419DM Sprague Dawley0.00066540.6654Ctr Sprague Dawley0.00050160.5016DM Sprague Dawley0.00093500.9350Ctr Sprague Dawley0.00025970.2597Ctr Sprague Dawley0.00055030.5503Promedio Ctr0.00048940.4893776Promedio DM0.00076840.7684475Desviacin Estndar0.00011070.1107365Desviacin Estndar0.00018120.1812143Error estndar de la media0.00004190.0418545Error estndar de la media0.00008100.0810415Prueba T (CTR vs DM)0.00762680080.0076Promedio Ctr0.00048940.4894Promedio Ctr0.48940.0400Promedio DM0.00076840.7684Promedio DM0.76840.0800Prueba T (CTR Sprague vs CTR Wistar)0.24644980260.8636833327Promedio Ctr0.4894Promedio DM0.7684Segunda Parte n=4Ctr Wistar #450.00056 n=5DM Wistar #410.000832Ctr Wistar #510.000632.2360679775DM Wistar #460.00053Ctr Wistar #490.00072DM Wistar #310.00062Ctr Wistar #530.00041DM Wistar #580.00072DM Wistar #420.00128Promedio Ctr0.0005810Promedio DM0.0007959Desviacin Estndar0.0001309482Desviacin Estndar0.0002951833Error estndar de la media0.0000655Error estndar de la media0.0001320Prueba T (CTR vs DM)0.2219441058Promedio Ctr0.000581Promedio DM0.000796

VD-Cuerpo Prom.0.040.040.040.08

Promedio CtrPromedio DM

VD-VI Prom.

Cociente VD/Peso Corporal

VD-VI--Glucosa

GRAFICAS n=7Ctr Sprague Dawley0.3210 n=5DM Sprague Dawley0.31232.6457513111Ctr Sprague Dawley0.32492.2360679775DM Sprague Dawley0.4102Ctr Sprague Dawley0.3203DM Sprague Dawley0.3199Ctr Sprague Dawley0.3298DM Sprague Dawley0.4606Ctr Sprague Dawley0.2994DM Sprague Dawley0.3609Ctr Sprague Dawley0.2550Ctr Sprague Dawley0.3418Ctr Sprague Dawley0.2853Ctr Sprague Dawley0.2982Promedio Ctr0.3084Promedio DM0.3728Desviacin Estndar0.0267360Desviacin Estndar0.0626Error estndar de la media0.0101Error estndar de la media0.0280Promedio Ctr0.30840.01Promedio DM0.37280.02Prueba T (CTR vs DM)0.0181912745Promedio Ctr0.3084Promedio DM0.3728Segunda Parte n=4Ctr Wistar #450.28046 n=5DM Wistar #410.312932Ctr Wistar #510.322482.2360679775DM Wistar #460.27763Ctr Wistar #490.35387DM Wistar #310.31772Ctr Wistar #530.23949DM Wistar #580.35111DM Wistar #420.46047Promedio Ctr0.2991Promedio DM0.3440Desviacin Estndar0.0498Desviacin Estndar0.0701Error estndar de la media0.0249Error estndar de la media0.0314Prueba T (CTR vs DM)0.3179402943Promedio Ctr0.2991Promedio DM0.3440

GRAFICAS

Cociente VD/VI

Cociente VD/VI

0.010.010.020.02

Promedio CtrPromedio DM

RataGlucosaCociente VD / VIRataGlucosaCociente VD / VICtr Wistar #451480.28046DM Wistar #415600.31293Ctr Wistar #511070.32248DM Wistar #463600.27763Ctr Wistar #491500.35387DM Wistar #315120.31772Ctr Wistar #531540.23949DM Wistar #583900.35111DM Wistar #424330.46047

&APage &PGlucosaCociente VD / VI

GlucosaCociente VD / VI

vd/corporalvd/corporalvd/vivd/viPromedio Ctr VD/Peso Corporal0.4894Promedio Ctr VD/VI0.3084Promedio DM VD/Peso Corporal0.7684Promedio DM VD/VI0.3728Promedio Ctr0.4894Promedio Ctr0.3084Desviacin Estndar0.1107Desviacin Estndar0.0267Error estndar de la media0.0419Error estndar de la media0.0101Promedio DM0.7684Promedio DM0.3728Desviacin Estndar0.1812Desviacin Estndar0.0626Error estndar de la media0.0810Error estndar de la media0.0280

0.04185446870.04185446870.08104151510.08104151510.01010524050.01010524050.02801602470.0280160247

Promedio Ctr VD/Peso CorporalPromedio DM VD/Peso CorporalPromedio Ctr VD/VIPromedio DM VD/VI