piperidines and Coronary-Stenosis

Patients with type 2 diabetes are at high risk for developing coronary artery disease (CAD). Noninvasive anatomic assessment by coronary computed tomography angiography (CCTA) is being increasingly used for detecting or excluding CAD. Recently, fractional flow reserve (FFR) using routinely acquired CCTA datasets (FFR. This study will be a prospective, non-randomized, multicenter trial performed in Japan. Patients with type 2 diabetes who have intermediate coronary artery stenosis (diameter stenosis <70%) as evaluated by CCTA will be treated with 25mg/day of alogliptin. After 48 weeks' treatment, CCTA will be repeated. The primary endpoint will be changes in FFR. This study will be the first multicenter trial to evaluate the effects of alogliptin on coronary atherosclerosis using the newly developed FFR

Topics: Aged; Carotid Intima-Media Thickness; Computed Tomography Angiography; Coronary Angiography; Coronary Stenosis; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Fractional Flow Reserve, Myocardial; Humans; Hypoglycemic Agents; Japan; Male; Middle Aged; Piperidines; Plaque, Atherosclerotic; Prospective Studies; Uracil

A 56-year-old man with 3 coronary vessel disease (#5, HL, #13), underwent OPCABG. Anesthesia was induced with propofol (PRO), fentanyl and vecuronium, and maintained with continuous infusion of remifentanil (REM), PRO and vecuronium. After the revascularization of 3 vessels, we changed the infusion anesthetics from REM to dexmedetomidine (DEX), and 40 minutes later we extubated immediately after the operation in the operating room with no problems. Ultra fast-track anesthesia in off-pump coronary artery bypass grafting is controversial, largely because of a concern about increased risk of derangement in respiratory mechanics. But this method, general anesthesia by combination of propofol-remifentanil-dexmedetomidine without epidural analgesia, was very stable in the operative period, and respiration was well maintained after extubation in the operating room. There were no critical hypercapnea, hypoxia, ventilatory problems and any cardiac complications. This method provided suitable conditions for maintenance and emergence of anesthesia, and enabled a shorter stay in ICU of below 24 hours.

Topics: Anesthesia Recovery Period; Anesthesia, General; Coronary Artery Bypass, Off-Pump; Coronary Stenosis; Dexmedetomidine; Humans; Intubation, Intratracheal; Male; Middle Aged; Operating Rooms; Perioperative Care; Piperidines; Propofol; Remifentanil; Ventilator Weaning

Both beta-adrenergic blockade and bradycardia may contribute to the therapeutic effect of beta-blockers in chronic heart failure (CHF). This study tested the relative importance of bradycardia by comparing cilobradine (Cilo), a sinus node inhibitor, with a beta-blocker, metoprolol (Meto), in an established canine model of CHF. Dogs were chronically instrumented for hemodynamic and left ventricular (LV) volume measurements. CHF was created by daily coronary embolization via a chronically implanted coronary (left anterior descending coronary artery) catheter. After establishment of CHF, control (n=6), Meto (30 mg/day, n=5), Cilo (low) (1 mg/kg/day, n=5), or Cilo (high) (3 mg/kg/day, n=5) was given orally for 12 weeks. Systemic hemodynamics, echocardiography, and pressure volume analysis were measured at baseline, at CHF, and 3 months after treatment in an awake state. Protein levels of cardiac sarcoplasmic reticulum calcium-ATPase (SERCA2a), ryanodine receptor (RyR2), and Na+-Ca2+ exchanger (NCX1) were measured by Western blot. RyR2 protein kinase A (PKA) phosphorylation was determined by back-phosphorylation. After 12 weeks, Meto and Cilo (high and low) produced similar bradycardic effects, accompanied by a significantly improved LV dP/dt versus control [Meto, 2602+/-70; Cilo (low), 2517+/-45; Cilo (high), 2579+/-78; control, 1922+/-115 mm Hg/s; p<0.05]. Both Meto and Cilo (high) normalized protein levels of SERCA2a and NCX1 and reversed PKA hyperphosphorylation of RyR2, in contrast to controls. High-dose cilobradine effectively produced bradycardia and improved cardiac function after CHF, comparable with metoprolol. Restored protein levels of SERCA2a and improved function of RyR2 may be important mechanisms associated with cilobradine therapy.

Topics: Adrenergic beta-Antagonists; Animals; Benzazepines; Calcium; Coronary Stenosis; Dogs; Echocardiography; Female; Heart Failure; Heart Rate; Male; Metoprolol; Piperidines; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Sodium-Calcium Exchanger; Ventricular Function, Left; Ventricular Remodeling

A paradoxical microcirculatory constriction has been observed in hearts of patients with ischemia, secondary to coronary stenosis. Here, using the isolated mouse heart (Langendorff), we examined the mechanism of this response, assuming involvement of nitric oxide (NO) and endothelin-1 (ET-1) systems. Perfusion pressure was maintained at 65 mmHg for 70 min (protocol 1), or it was reduced to 30 mmHg over two intervals, between the 20- and 40-min marks (protocol 2) or from the 20-min mark onward (protocol 3). In protocol 1, coronary resistance (CR) remained steady in untreated heart, whereas it progressively increased during treatment with the NO synthesis inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME) (2.7-fold) or the ET(A) antagonist BQ-610 (2.8 fold). The ET(B) antagonist BQ-788 had instead no effect by itself but curtailed vasoconstriction to BQ-610. In protocol 2, hypotension raised CR by 2.2-fold. This response was blunted by reactive oxygen species (ROS) scavengers (mannitol and superoxide dismutase plus catalase) and was converted into vasodilation by l-NAME, BQ-610, or BQ-788. Restoration of normal pressure was followed by vasodilation and vasoconstriction, respectively, in untreated and treated preparations. In protocol 3, CR progressively increased with hypotension in the absence but not presence of L-NAME or BQ-610. We conclude that the coronary vasculature is normally relaxed by two concerted processes, a direct action of NO and ET-1 curtailing an ET(B2)-mediated tonic vasoconstriction through ET(A) activation. The negative feedback mechanism on ET(B2) subsides during hypotension, and the ensuing vasoconstriction is ascribed to ET-1 activating ET(A) and ET(B2) and reactive nitrogen oxide species originating from ROS-NO interaction.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Coronary Stenosis; Coronary Vessels; Endothelins; Enzyme Inhibitors; Hemodynamics; Hypotension; Mice; Mice, Inbred C57BL; Microcirculation; Models, Cardiovascular; Myocardial Ischemia; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oligopeptides; Piperidines; Reactive Oxygen Species; Vasoconstriction; Vasodilation; Vasomotor System