Postconditioning, i.e., brief intermittent episodes of myocardial ischemia-reperfusion performed at the onset of reperfusion, reduces infarct size after prolonged ischemia. Our goal was to determine whether postconditioning is protective against myocardial stunning. Accordingly, conscious chronically instrumented dogs (sonomicrometry, coronary balloon occluder) were subjected to a control sequence (10 min coronary artery occlusion, CAO, followed by coronary artery reperfusion, CAR) and a week apart to postconditioning with four cycles of brief CAR and CAO performed at completion of the 10 min CAO. Three postconditioning protocols were investigated, i.e., 15 s CAR/15 s CAO (n=5), 30 s CAR/30 s CAO (n=7), and 1 min CAR/1 min CAO (n=6). Left ventricular wall thickening was abolished during CAO and similarly reduced during subsequent stunning in control and postconditioning sequences (e.g., at 1 h CAR, 33+/-4 vs. 34+/-4%, 30+/-4 vs. 30+/-4%, and 33+/-4 vs. 32+/-4% for 15 s postconditioning, 30 s postconditioning, and 1 min postconditioning vs. corresponding control, respectively). We confirmed this result in anesthetized rabbits by demonstrating that shortening of left ventricular segment length was similarly depressed after 10 min CAO in control and postconditioning sequences (4 cycles of 30 s CAR/30 s CAO). In additional rabbits, the same postconditioning protocol significantly reduced infarct size after 30 min CAO and 3 h CAR (39+/-7%, n=6 vs. 56+/-4%, n=7 of the area at risk in postconditioning vs. control, respectively). Thus, contrasting to its beneficial effects on myocardial infarction, postconditioning does not protect against myocardial stunning in dogs and rabbits. Conversely, additional episodes of ischemia-reperfusion with postconditioning do not worsen myocardial stunning.

BackgroundFurosemide is the only loop diuretic recommended by the ACVIM consensus guidelines for treatment of congestive heart failure (CHF) in dogs related to degenerative mitral valve disease (DMVD). Torasemide is another potent loop diuretic with a longer half‐life and a higher bioavailability.Objectives(1) To demonstrate that torasemide given once a day (q24h) is noninferior to furosemide given twice a day (q12h) for treating dogs with CHF; (2) and to compare the effect of the 2 drugs on the time to reach a composite cardiac endpoint “spontaneous cardiac death, euthanasia due to heart failure or CHF class worsening.”AnimalsA total of 366 dogs with CHF attributable to DMVD.MethodsAnalysis of 2 prospective randomized single‐blinded reference‐controlled trials was performed. Dogs orally received either torasemide q24h (n = 180) or furosemide q12h (n = 186) in addition to standard CHF therapy over 3 months. The primary efficacy criterion was the percentage of dogs with treatment success assessed in each study. The time to reach the composite cardiac endpoint was used as secondary criterion in the overall population.ResultsTorasemide was noninferior to furosemide (P torasemide − P furosemide = +7%; 95% CI [−8%; +22%] and P torasemide − P furosemide = +1%; 95% CI [−12%; +14%], respectively, in Study 1 and Study 2). Torasemide (median dose = 0.24 mg/kg/d q24h; range = 0.10–0.69 mg/kg/d) was associated with a 2‐fold reduction in the risk of reaching the composite cardiac endpoint (adjusted HR = 0.47; 95% CI = 0.27–0.82; P = 0.0077) as compared with furosemide (median dose = 1.39 mg/kg q12h; range = 0.70–6.30 mg/kg q12h).Conclusions and Clinical ImportanceTorasemide q24h is an effective oral diuretic in dogs with CHF.

Selective heart rate reduction with ivabradine converts PSWT into ejectional thickening but not with atenolol secondary to its negative inotropism.