Effects of a sustained-release form of isosorbide dinitrate on left atrial pressure in dogs with experimentally induced mitral valve regurgitation.

BACKGROUND: The effects of isosorbide dinitrate (ISDN) have not been sufficiently investigated in conscious dogs with mitral valve regurgitation (MR). OBJECTIVE: The objective was to investigate the effects of a sustained-release form of ISDN (sr-ISDN) on hemodynamics and the autonomic nervous system in dogs with MR. ANIMALS: Six healthy Beagles weighing 11.2 ± 2.2 kg (2 years of age; 2 males and 4 females) were used. METHODS: Experimental, crossover, and interventional study. Dogs with experimentally induced MR were administered placebo, 2, 5, and 10 mg/kg sr-ISDN PO on separate days with a 7-day washout period between randomized dosings. Left atrial pressure (LAP) had been recorded continuously from 30 minutes before administration of sr-ISDN to 12 hours after administration. RESULTS: LAP was significantly decreased after administration in the 5 and 10 mg/kg groups. Significant decrease was observed at 3 and 4 hours after administration in the 5 mg/kg group. In the 10 mg/kg group, significant decrease was observed at 2, 3, 4, 5, 6, 7, 10, and 11 hours after administration. The lowest value was observed at 4 hours after administration in the 5 and 10 mg/kg groups (20.9 ± 4.2 to 15.9 ± 3.9 mmHg, P < .01, and 21.3 ± 4.0 to 13.6 ± 4.2 mmHg, P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Sustained-release form of ISDN showed significant decrease of LAP in the 5 mg/kg and 10 mg/kg groups, and duration of effect was dose related.

A basic consideration for porcine liver preservation using a novel continuous machine perfusion device.

INTRODUCTION: The aims of this study were to compare extracellular and intracellular-type University of Wisconsin (UW) solutions for liver grafts and to assess oxygenation in this perfusion system. MATERIALS AND METHODS: The organ preservation system consisted of 3 circulating systems for the portal vein, hepatic artery, and maintenance of the perfusion solution. The portal vein or hepatic artery system had a roller pump, a flow meter, and a pressure sensor. In this study, we perfused livers with UW or extracellular type UW-gluconate at 4°C-6°C for 4 hours. The flow rates at the entrance were 0.5 mL/min/g liver in the portal vein and 0.2 mL/min/liver in the hepatic artery. Orthotopic liver transplantation was performed in pigs: group 1-a, grafts procured after acute hemorrhagic shock were preserved by a solution without O(2); group 1-b, grafts were preserved with O(2); group 2-a, grafts were perfused using intracellular type solution (UW); and group 2-b, grafts were perfused using extracellular-type solution (UW-gluconate). RESULTS: Effluent aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in group 1-b were lower than those in group 1-a. Survival rates in group 2-a and group 2-b were 1/4 and 3/3, respectively. Effluent AST and LDH levels in the perfusate of group 2-b were lower than group 2-a. Histological study revealed necrosis of hepatocytes and sinusoidal congestion in group 2-a. CONCLUSION: A beneficial effect of extracellular-type solution with oxygenation in a novel continuous machine preservation system yielded well-preserved liver graft function.

Pretransplant screening and evaluation of liver graft viability using machine perfusion preservation in porcine transplantation.

A novel method using machine perfusion for pretransplant screening and evaluation of the viability of liver grafts has been proposed, seeking to prevent severe ischemia-reperfusion injury and to reduce the risk of primary graft nonfunction. This study sought to evaluate the viability of critical grafts, which were obtained from expanded criteria donors or donation after cardiac death donors during preservation with a new machine preservation perfusion system (NES-01). The normalized pressure transition in the hepatic artery was employed as an evaluation index for liver viability. As a result, the normalized pressure (p/p(0)) in the hepatic artery showed a distinctive transition under each experimental conditions controlled by warm ischemic time (WIT). The high viability graft, obtained under the condition of WIT as 0 minutes (WIT0), showed a quick response to hepatic artery pressure after initiating perfusion, whereas the normalized pressure showed a sudden decrease. In contrast, the normalized pressure among WIT60, which may cause the graft to lose viability, showed a poor hepatic artery response. These findings corresponded to the cumulative release of enzymes. The findings of our study suggest that monitoring of the pressure drop rate in the hepatic artery during machine perfusion can be used to evaluate liver graft viability.

The effect of pimobendan on left atrial pressure in dogs with mitral valve regurgitation.

BACKGROUND: The effects of pimobendan on left atrial pressure (LAP) in dogs with mitral valve disease (MR) have not been documented in a quantitative manner. OBJECTIVE: The objective was to document and study the short-term effects of pimobendan on LAP and echocardiographic parameters in MR dogs. ANIMALS: Eight healthy Beagle dogs weighing 10.0-14.7 kg (3 males and 5 females; aged 2 years) were used. METHODS: Experimental, cross-over, and interventional study. Dogs with surgically induced MR received pimobendan at either 0.25 mg/kg or 0.50 mg/kg p.o. q12h for 7 days and then, after a 7-day wash-out period, the other dosage. LAP was measured for 30 minutes at baseline and again on days 1, 2, 4, and 7 of pimobendan administration. RESULTS: Mean LAP was significantly decreased after the administration of 0.25 mg/kg (15.81 ± 5.44 mmHg to 12.67 ± 5.71 mmHg, P < .001) and 0.50 mg/kg (15.76 ± 5.45 mmHg to 10.77 ± 5.23 mmHg, P < .001). Also, the 0.50 mg/kg group led to a significantly lower LAP (P < .01) compared with the 0.25 mg/kg group. Significant reduction was seen for the first time 4 days after the administration of 0.25 mg/kg and a day after the administration of 0.50 mg/kg. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan decreased LAP in a dose-dependent manner in dogs with acute MR caused by experimental chordal rupture. This study did not evaluate adverse effects of high-dose pimobendan, and additional studies in clinical patients are warranted.

The effect of furosemide on left atrial pressure in dogs with mitral valve regurgitation.

BACKGROUND: The effects of furosemide on left atrial pressure (LAP) in dogs with mitral regurgitation (MR) have not been documented in a quantitative manner and between different routes of administration. OBJECTIVE: To document LAP and echocardiographic parameters in MR dogs administered furosemide IV or PO, in order to document changes in LAP after furosemide treatment. ANIMALS: Five healthy Beagle dogs (3 males and 2 females; aged 2 years) were used. METHODS: Experimental, cross-over, and interventional study. LAP was measured before the administration of furosemide, and 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours after administration. Furosemide 1, 2, or 4 mg/kg IV, PO or placebo was administered. RESULTS: LAP was significantly decreased with all administrations of furosemide but not after placebo (P < .05, respectively). The max reduction was observed 1 hour (1 mg/kg IV, 15.04 ± 7.02 mmHg), 3 hours (2, 4 mg/kg IV, 13.28 ± 8.01, 9.23 ± 4.92 mmHg), 4 hours (1 mg/kg PO, 14.68 ± 11.51 mmHg), and 5 hours (2, 4 mg/kg PO, 13.19 ± 10.52, 10.70 ± 7.69 mmHg). E wave and E/Ea were significantly decreased corresponding to the reduction of LAP after administration of 2 and 4 mg/kg (P < .05, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: LAP was decreased in proportion to the dosage of furosemide, which did not significantly differ between IV and PO of the same dosages. E wave and E/Ea might be useful for the treatment evaluation of furosemide.