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Yochai Birnbaum - One of the best experts on this subject based on the ideXlab platform.

  • acute coronary syndromes amplification of the myocardial infarct size limiting effects of exenatide with cilostazol a Phosphodiesterase III Inhibitor
    2012
    Co-Authors: Yochai Birnbaum, Alexander C Castillo, Ling Shukuan, Mandeep Bajaj, J R Perezpolo
    Abstract:

    Asrac Caegor: 6. Acue Coroar Sromes: Basicreseaio umer: 1177-583Auhors: Yochai Birnbaum, Alexander C. Castillo, Ling Shukuan, Mandeep Bajaj, Jose R. Perez-Polo, Yumei Ye, University of Texas Medical Branch, Galveston, TX, USA, Baylor Collge of Medicine, Houston, TX, USABackground: Glucago-lie eie (G1) aalogues reuce mocarial ifarc size (IS) i oiaeic aimals. Ischemic a harmacological recoiioig of iaeic aimals is limie. Acivaio of he G1 receors icreases iracellular cAM wih owsream acivaio of roei iase A (KA). Cilosazol (CI), a hoshoieserase III ihiior reves he egraaio of cAM a augmes he IS-limiig effecs of sais. We assesse wheher CI augmes he IS-limiig effecs of exeaie (EX), a G1 aalogue, icreasig iracellular cAM i mice wih e-2 iaees mellius. Methods: D/D mice fe a Weser Die receive oral CI (10 mg/g) or vehicle oral gavage 24h efore surger. Oe hour efore surger mice receive S.C. EX (1 mcg/g) or vehicle. Aiioal mice receive H89, a KA ihiior, aloe or wih CI+EX. Mice were sujece o 30 mi coroar arer occlusio a 24h reerfusio. Ischemic area a ris (AR) was assesse lue e a IS TTC. Results: Bo weigh, lef vericular weigh a he size of he AR were comarale amog grous. Boh EX a CI reuce IS. IS was he smalles i he CI+EX grou (Figure). IS i he H89 grou was 48.2±4.6% of he AR a i he CI+EX+H89 45.8±1.4% (=.117). Boh EX a CI icrease cAM. cAM levels were sigiical higher i he CI+EX grou. Conclusion: EX a CI have aiive IS-limiig effecs i iaeic mice. The aiive effecs are relae o cAM iuce KA acivaio, as H89 loce he effec of CI+EX.

  • protecting against ischemia reperfusion injury antiplatelet drugs statins and their potential interactions
    Annals of the New York Academy of Sciences, 2010
    Co-Authors: J R Perezpolo, Yochai Birnbaum
    Abstract:

    Statins and antiplatelet agents are currently used as therapeutic agents for patients with acute myocardial infarction. Statins limit myocardial infarct size by activating phosphatidylinositol-3-kinase (PI3K), ecto-5'-nucleotidase, Akt/endothelial nitric oxide synthase (eNOS), and the downstream effectors inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Inhibition of PI3K, adenosine receptors, eNOS, iNOS, or COX-2 abrogates the protective effects of statins. At >5 mg/kg, aspirin attenuates the myocardial infarct-size-limiting effect of statins. In contrast, the combination of low-dose atoravastatin with either the Phosphodiesterase-III Inhibitor cilostazol or the adenosine reuptake Inhibitor dipyridamole synergistically limits infarct size. Low-dose aspirin with dipyridamole started during ischemia augmented the infarct-size-limiting effects of simvastatin. In contrast, high-dose aspirin blocked the protective effect of simvastatin. The combination of dipyridamole with low-dose aspirin and simvastatin resulted in the smallest infarct size. According to the most current data available, we believe that antiplatelet regimens may require modification for patients who are receiving statins.

Frank Isgro - One of the best experts on this subject based on the ideXlab platform.

  • the prophylactic use of the beta blocker esmolol in combination with Phosphodiesterase III Inhibitor enoximone in elderly cardiac surgery patients
    Anesthesia & Analgesia, 2004
    Co-Authors: Joachim Boldt, Christian Brosch, Andreas Lehmann, Stephan Suttner, Frank Isgro
    Abstract:

    We assessed the influence of the prophylactic use of a combination of the IV beta-adrenergic blocker, esmolol, and the Phosphodiesterase III Inhibitor, enoximone, on postbypass hemodynamic status, inflammation, and endothelial and organ function in a prospective, randomized, placebo-controlled study in 42 patients aged >65 yr undergoing aortocoronary bypass grafting. In 21 patients, esmolol (aim: heart rate <70 bpm) plus enoximone (initial bolus of 0.5 mg/kg followed by a continuous infusion of 2.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and continued until the morning of the first postoperative day; another 21 patients received saline solution as placebo. Hemodynamics, splanchnic perfusion (gastric-arterial CO(2) gap), liver function (glutathione transferase-alpha plasma levels), renal function (creatinine clearance, urine concentrations of N-acetyl-beta-D-glucosaminidase), myocardial ischemia (creatine-kinase MB and troponin T plasma levels), inflammation (elastase, interleukin-6 and -8 plasma levels), and endothelial integrity (adhesion molecules plasma levels) were assessed at baseline, before and after cardiopulmonary bypass (CPB), and in the intensive care unit until the first postoperative day. Catecholamine requirements were significantly less in the treated than in the nontreated patients. Heart rate was significantly slower, cardiac index was higher, and gastric-arterial CO(2) gap was significantly lower in the treatment group. Troponin T, beta-N-acetyl-beta-D-glucosaminidase, glutathione transferase-alpha, and soluble adhesion molecules increased significantly in the untreated control, but remained almost normal in the esmolol+enoximone patients. Inflammatory responses (elastase/interleukins) were attenuated by esmolol+enoximone. We conclude that, in comparison to an untreated control, the prophylactic use of a combination of esmolol and enoximone in elderly patients undergoing cardiac surgery with cardiopulmonary bypass resulted in overall beneficial effects on postbypass hemodynamic status, organ function, inflammatory response, and endothelial integrity.

  • the prophylactic use of the β blocker esmolol in combination with Phosphodiesterase III Inhibitor enoximone in elderly cardiac surgery patients retracted
    Anesthesia & Analgesia, 2004
    Co-Authors: Joachim Boldt, Christian Brosch, Andreas Lehmann, Stephan Suttner, Frank Isgro
    Abstract:

    We assessed the influence of the prophylactic use of a combination of the IV β-adrenergic blocker, esmolol, and the Phosphodiesterase III Inhibitor, enoximone, on postbypass hemodynamic status, inflammation, and endothelial and organ function in a prospective, randomized, placebo-controlled study in 42 patients aged >65 yr undergoing aortocoronary bypass grafting. In 21 patients, esmolol (aim: heart rate <70 bpm) plus enoximone (initial bolus of 0.5 mg/kg followed by a continuous infusion of 2.5 μg . kg -1 min -1 ) was started after induction of anesthesia and continued until the morning of the first postoperative day; another 21 patients received saline solution as placebo. Hemodynamics, splanchnic perfusion (gastric-arterial CO 2 gap), liver function (glutathione transferase-a plasma levels), renal function (creatinine clearance, urine concentrations of N-acetyl-β-D-glucosaminidase ), myocardial ischemia (creatine-kinase MB and troponin T plasma levels), inflammation (elastase, interleukin-6 and -8 plasma levels), and endothelial integrity (adhesion molecules plasma levels) were assessed at baseline, before and after cardiopulmonary bypass (CPB), and in the intensive care unit until the first postoperative day. Catecholamine requirements were significantly less in the treated than in the nontreated patients. Heart rate was significantly slower, cardiac index was higher, and gastric-arterial CO 2 gap was significantly lower in the treatment group. Troponin T, β-N-acetyl-β-D-glucosaminidase, glutathione transferase-a, and soluble adhesion molecules increased significantly in the untreated control, but remained almost normal in the esmolol+enoximone patients. Inflammatory responses (elastase/interleukins) were attenuated by esmolol+enoximone. We conclude that, in comparison to an untreated control, the prophylactic use of a combination of esmolol and enoximone in elderly patients undergoing cardiac surgery with cardiopulmonary bypass resulted in overall beneficial effects on postbypass hemodynamic status, organ function, inflammatory response, and endothelial integrity.

Kiyonori Harii - One of the best experts on this subject based on the ideXlab platform.

  • clinical use of amrinone a selective Phosphodiesterase III Inhibitor in reconstructive surgery
    Plastic and Reconstructive Surgery, 2001
    Co-Authors: Shigeru Ichioka, Takashi Nakatsuka, Yuko Sato, Norihiko Ohura, Kiyonori Harii
    Abstract:

    Amrinone is a selective Phosphodiesterase III Inhibitor that increases cyclic adenosine monophosphate by preventing its breakdown. It is effective in the treatment of congestive heart failure because of its ability to increase myocardial contractility and vascular smooth muscle relaxation. This study was designed to clarify the potential efficacy of amrinone in plastic surgery by clinically assessing its ability to enhance flap blood flow after reconstructive surgery and relieve intraoperative vasospasm. Its effects were compared with those of prostaglandin E1 and lidocaine, which are widely approved agents for improving the hemodynamics of flaps. In the first clinical study, the effects on flap blood flow after flap transfers were investigated. Twenty-six patients underwent reconstructive surgery with vascularized free or pedicled flaps. Blood flow was measured before and 60 minutes after intravenous infusion of lactated Ringer solution (control), amrinone (10 microg/kg/min), or prostaglandin E1 (10 ng/kg/min) using a laser Doppler flowmeter. In the second study, the effects on relief of vasospasm during operation were evaluated. The blood flow of 28 island flaps was measured by laser Doppler flowmetry immediately after flap elevation and 10 minutes after topical application of saline (control), amrinone (5 mg/ml), or lidocaine (10%) to the pedicle in an attempt to resolve the vasospasm. In both clinical studies, the effects of amrinone were statistically no less than those of prostaglandin E1 and lidocaine. The results show that amrinone positively influences the microcirculatory blood flow of transferred flaps and relieves intraoperative vasospasm in clinical cases. The present study suggests that amrinone could be useful for postoperative and intraoperative care in reconstructive surgery.

  • Topical application of amrinone (a selective Phosphodiesterase III Inhibitor) for relief of vasospasm.
    The Journal of surgical research, 2000
    Co-Authors: Shigeru Ichioka, Takashi Nakatsuka, Yuko Sato, Norihiko Ohura, Kiyonori Harii
    Abstract:

    Background. Amrinone, a selective Phosphodiesterase III Inhibitor, is an agent that possesses a combination of positive inotropic and vasodilating properties as a result of preventing the degradation of cAMP, and it has recently been licensed for the treatment of heart failure. The aim of this study was to investigate the potential therapeutic application of amrinone to resolve vasospasm, which is the major problem in reconstructive surgery. In this study its effect was compared with that of lidocaine, the most commonly used topical vasodilating agent clinically. Materials and methods. The probe of an ultrasonic transit-time volume flowmeter was applied to the femoral artery of rats to measure blood flow. After a baseline recording was obtained, 0.03 ml of epinephrine was applied topically to induce vasospasm. The vessels were then immersed in 1 ml of amrinone (5 mg/ml), 10% lidocaine hydrochloride, or normal physiological saline solution for 1 min in an attempt to resolve the spasm. In another group of animals, no solution was used following administration of epinephrine to allow observation of spontaneous resolution of the vasospasm over time. Results. The results showed an essentially immediate spasm-resolving effect in both the amrinone group and the lidocaine group. The amrinone group showed a significantly greater degree of maximum increase in blood flow than the lidocaine group. The effect of lidocaine decreased with time, whereas amrinone had a more lasting effect. Conclusions. The findings suggest that amrinone could be used as an effective topical vasodilating agent to resolve vasospasm in reconstructive surgery.

  • amrinone a selective Phosphodiesterase III Inhibitor improves microcirculation and flap survival a comparative study with prostaglandin e1
    Journal of Surgical Research, 1998
    Co-Authors: Shigeru Ichioka, Takashi Nakatsuka, Yuko Sato, Masahiro Shibata, Akira Kamiya, Kiyonori Harii
    Abstract:

    Background. Amrinone, a selective Phosphodiesterase (PDE) III Inhibitor, is a newly developed agent that possesses a combination of positive inotropic and vasodilating properties as a result of preventing the degradation of cAMP and it has recently been licensed for treatment of heart failure alone. Amrinone is expected to be useful for the treatment not only of heart failure but also of peripheral circulatory disorders, including vascular disease, and for ischemic flaps, because it improves microcirculatory hemodynamics. To investigate potential therapeutic applications of amrinone, we evaluated its ability to improve microcirculatory hemodynamics and flap survival. Materials and methods. The rat skinfold chamber technique was employed to quantify microcirculation directlyin vivo.The improved survival area of random flaps in rats treated with amrinone was examined to assess therapeutic efficacy of this drug. Its effects were compared with those of prostaglandin E1(PGE1), which has been widely approved as an agent for improving hemodynamics. Results. Microcirculatory blood flow and flap survival area were significantly increased in both amrinone- and PGE1-treated animals, compared to the saline-treated controls. The ameliorating effects of amrinone were comparable to those of PGE1. Conclusions. The results of this study suggest amrinone to be a potentially useful drug not only for treating heart failure but also for improving microcirculation in patients with vascular diseases and for postoperative care after reconstructive surgery.

P. A. J. Janssen - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of human cardiac cyclic amp Phosphodiesterases by r 80122 a new selective cyclic amp Phosphodiesterase III Inhibitor a comparison with other cardiotonic compounds
    Journal of Pharmacology and Experimental Therapeutics, 1992
    Co-Authors: D De Cheffoy De Courcelles, K De Loore, E Freyne, P. A. J. Janssen
    Abstract:

    Four cyclic AMP (cAMP)-Phosphodiesterases (PDE) belonging to families I, II, III and IV were identified in homogenates from human failing hearts. On fractionation of cardiac membranes, the cyclic GMP (cGMP)-inhibitable cAMP-PDE III copurified with the sarcoplasmic reticulum. cAMP-PDE activities were separated from the soluble fraction by DEAE-ion exchange chromatography and identified as belonging to the four different families of cAMP-PDEs. Various cAMP-PDE Inhibitors, mostly cardiotonic compounds, were tested for their Inhibitory potency on the different cAMP-PDEs and their selectivity for the type III isoenzyme was determined. Isobutylmethylxanthine, papaverine, theophylline and dipyridamole inhibited PDE activity in a weak and nonselective manner. Milrinone, enoximone, adibendan, pimobendan, bemoridan and the newly synthesized 1,2,3,5-tetrahydro-2-oxoimidazo[2,1-b]quinazoline derivatives, R 81267 and R 80122 were selective PDE III Inhibitors. However, the IC50 values on this enzyme varied from 10 microM for enoximone to 0.036 microM for R 80122. The selectivity of the drugs for PDE III was calculated by division of the IC50 value for PDE I, II or IV by the IC50 value for PDE III. PDE I/PDE III ratio ranged from 95 for enoximone to near 28,000 for R 80122; the PDE II/PDE III ratios ranged from 95 for enoximone to 3,500 for R 80122. Although there was strong variation between the drugs, most of them showed a high selectivity for PDE III in comparison to PDE I and to PDE II. In contrast, PDE IV appeared to be more sensitive to these substances.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Cardiac and hemodynamic effects of intravenous R80122, a new Phosphodiesterase III Inhibitor, in a canine model of myocardial ischemia and heart failure.
    Journal of cardiovascular pharmacology, 1992
    Co-Authors: A. Van De Water, R. Xhonneux, R. S. Reneman, P. A. J. Janssen
    Abstract:

    The cardiac and hemodynamic effects of R80122, a new specific Phosphodiesterase III Inhibitor, were studied in a closed-chest canine model of acute global left ventricular ischemia complicated by heart failure. The results obtained were compared with those obtained with milrinone. Intravenous infusion of the compounds (0.005 mg/kg/min for both) was started when stable heart failure had developed and was continued for 50 min followed by a washout period of 60 min. Both R80122 and milrinone improved the function of the acutely failing heart, as indicated by the increase in the values of the variables related to left ventricular function, but differences existed. The most striking differences were the normalization of the left ventricular external mechanical efficiency with R80122, but not with milrinone, and the maintenance of aortic blood pressure during infusion of R80122, which decreased during infusion of milrinone. Milrinone tends to induce ventricular tachycardia more frequently than R80122. It can be concluded that R80122 and milrinone improve the function of the acutely failing heart, but that the changes induced by R80122 are better balanced, i.e., enhancement of external mechanical efficiency with maintenance of aortic blood pressure.

Masatoshi Makuuchi - One of the best experts on this subject based on the ideXlab platform.

  • effects of amrinone on hepatic ischemia reperfusion injury in rats
    Journal of Hepatology, 2002
    Co-Authors: Takashi Kobayashi, Yasuhiko Sugawara, Takao Ohkubo, Hiroshi Imamura, Masatoshi Makuuchi
    Abstract:

    Abstract Background/Aims : The present study was designed to investigate the effect of amrinone, a Phosphodiesterase III Inhibitor, on hepatic ischemia – reperfusion injury in rats. Methods : Amrinone was infused at a rate of 20 or 100 μ g/kg/min, and 60-min partial ischemia was induced. The effects of amrinone on hemodynamic status, hepatic tissue cyclic adenosine 5 ′ -monophosphate (cAMP), hepatic tissue blood flow, platelet aggregation and plasma levels of transaminase were examined. The expression of intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase activity were analyzed and histological examination was performed in the injured liver. The cumulative survival rates for 14 days were also examined. Results : Hemodynamic status was not affected by amrinone. The levels of cAMP during reperfusion were significantly higher in rats with amrinone. Hepatic tissue blood flow during reperfusion was increased and platelet aggregation was inhibited by amrinone. The expression of ICAM-1 mRNA and protein in the injured liver was suppressed in rats with amrinone. The levels of transaminase, necrotic changes and myeloperoxidase activity were suppressed after reperfusion and higher survival was achieved in the rats treated with amrinone. Conclusions : Amrinone protected against ischemia – reperfusion injury of the liver in the present model.

  • effects of amrinone on ischaemia reperfusion injury in cirrhotic patients undergoing hepatectomy a comparative study with prostaglandin e1
    BJA: British Journal of Anaesthesia, 2000
    Co-Authors: Ryo Orii, Yasuhiko Sugawara, Masatoshi Makuuchi, Kyungho Chang, Masakazu Hayashida, Yoshitsugu Yamada, Tadatoshi Takayama, Kazuo Hanaoka
    Abstract:

    The effects of amrinone, a selective Phosphodiesterase III Inhibitor, on liver ischaemia reperfusion injury have not yet been clarified. Forty-five patients with hepatocellular carcinoma who underwent partial liver resection using Pringle's manoeuvre were studied. Patients were divided into three groups: those given amrinone, those given prostaglandin E1 (PGE1) and those not treated (controls). An indocyanine green (ICG) clearance test was performed before the operation and three times during surgery: just before induction of liver ischaemia, just after liver resection and 60 min after reperfusion. Blood lactate and base excess were measured at the same times. Systolic and diastolic arterial pressure, heart rate, cardiac index and oesophageal temperature were monitored. Aminotransferase levels were recorded the day before surgery, 1 h after operation and on the first and third postoperative days. These data were compared between groups. The ICG elimination rate, lactate and base excess in the amrinone group differed significantly from those in controls during the observation period (P=0.03, P=0.04 and P=0.03, respectively). The differences between the PGE1 and control groups were not significant. There were no significant differences between the groups in perioperative vital signs, cardiac index or postoperative aminotransferase. Amrinone enhanced intraoperative ICG elimination in cirrhotic patients who underwent liver resection.