Jau- Chang

Hemodynamic effect of inhaled nitric oxide in dilated cardiomyopathy patients on LVAD support.

Recently it has been shown that inhaled nitric oxide (NO), which has been proven to contribute to improvement in critical pulmonary hypertension, may provide a favorable effect early after left ventricular assist device (LVAD) support. To improve right ventricular function, inhalation of NO was added to treatment with conventional catecholamines for four consecutive dilated cardiomyopathy (DCM) patients following institution of LVAD. In two patients 1 hr after inhalation of NO, central venous pressure (CVP), mean pulmonary arterial pressure (PAm), and pulmonary vascular resistance (PVR) were improved. These results led to better LVAD output and resulted in an adequate cardiac index. On the other hand, a right VAD (RVAD) was implemented in one patient whose high CVP, PAm, and PVR continued; he was weaned after 8 days of RVAD support. Another patient who had a high CVP but normal PAm and PVR before and after inhalation of NO had no improvement in his hemodynamic state. These data suggest that inhaled NO may improve systemic circulation by reducing right ventricular afterload and may become a promising and convenient therapy before placing RVAD in DCM patients under LVAD support. RVAD should be conducted in patients with right ventricular failure or when pulmonary hypertension is associated with impaired right ventricular reserve, even after inhalation of NO. ASAIO Journal 1997;43:M418-M421.

Hepatic sinusoid endothelial dysfunction plays a role in hyperbilirubinemia in patients following implantation of an LVAD.

To clarify the mechanism of hyperbilirubinemia in the setting of a left ventricular assist device (LVAD), the change in hepatocellular function, hepatic sinusoid endothelial microcirculation, and inflammatory response before and after LVAD implantation were evaluated. Eight consecutive patients underwent the placement of an LVAD, and serum levels of total bilirubin (TB), transaminases [alanine transaminase (ALT), aspartate transaminase (AST)], interleukin (IL-6, IL-8), and hyaluronic acid (HA), an indicator of hepatic sinusoidal circulation, were measured before and after LVAD implantation. The TB of all patients increased significantly in the first post operative week (p < 0.05 vs. pre-operatively). In five patients, the elevated TB (4.6 ± 4.1 mg/dl) returned to pre-operative levels (2.7 ± 2.0 mg/dl) by the 14th post operative day (Group R), but in the other three patients who died of multiple organ failure, the level of TB increased to 39.9 ± 16.4 mg/dl (Group A). Levels of HA and IL-8 had good correlation with the level of TB (HA: r = 0.60, p < 0.05; IL-8: r = 0.55, p < 0.05). However, AST, ALT, and IL-6 were not related to changes in TB. These results suggest that hepatic sinusoid endothelial dysfunction and inflammatory reaction may play a significant role in hepatic failure in patients following implantation of an LVAD.

Portable cardiopulmonary support system as a bridge to left ventricular assist system implantation. A new strategy for the treatment of end stage cardiac disease.

The key to the successful implantation of a left ventricular assist system (LVAS) for patients with end stage cardiac disease is whether the functions of other vital organs are irreversibly damaged or not. The portable cardiopulmonary support system (PCPS) is not only as convenient as, but is more powerful than, the intra-aortic balloon pump (IABP) in resuscitating impaired end organ function. To investigate the efficacy of PCPS in end stage cardiac disease, end organ function before and after the application of PCPS was retrospectively analyzed for end stage cardiac disease. From 1992 to 1996, five cardiomyopathy patients with deterioration in end organ function, despite application of IABP, underwent PCPS support before implantation of LVAS. Urine volume and levels of liver enzymes (sAST and sALT) and serum creatinine were determined before and after institution of PCPS. After the start of PCPS, the urine output increased significantly (1,840 ± 450–4,340 ± 470 ml/day, p < 0.01), and levels of sAST, sALT, and serum creatinine decreased significantly (630 ± 220–150 ± 50 IU/L, 630 ± 260–260 ± 130 lU/L, and 2.9 ± 0.5–1.2 ± 0.1 mg/dl, respectively; p < 0.05). All five patients were successfully bridged to LVAS implantation, and none died of multiple organ failure caused by pre-existing cardiac failure. These results indicate that PCPS before LVAS implantation is useful in resuscitating impaired end organ function and improving the survival rate with LVAS implantation for end stage cardiac disease.

The Effects of a New Ultra-Short-Acting β-Adrenergic Blocker, ONO-1101, on Cardiac Function During and After Cardiopulmonary Bypass

The administration of an ultra-short-acting β-adrenergic antagonist, esmolol, has been introduced as a novel method for beating-heart surgery. In the present study, a new ultra-short-acting β-blocker, ONO-1101, was administered during cardiopulmonary bypass (CPB) to investigate its effects on cardiac function and hemodynamics. Nine adult mongrel dogs underwent 60 min of CPB during which they were given either ONO-1101 (ONO group;n=4) or saline (control group;n=5). In the ONO group, the hearts became flaccid enough for surgery to be performed without cardiac standstill within 10min after the commencement of ONO-1101 with significant decreases in the heart rate, the preload recruitable stroke work (PRSW), and the slope of the endsystolic left ventricular pressure-volume relationship (Emax). The mean arterial pressure and systemic vascular resistance also decreased, but were maintained above 50 mmHg during CPB without catecholamine. These indices increased to the control group level 20 min after the discontinuation of ONO-1101. The serum concentration of ONO-1101 decreased from the maximum level of 121±15 μg/ml soon after infusion to 11 ±5 μg/ml within 30 min after discontinuation. These data suggest that ONO-1101 may be useful to enable beating-heart surgery to be performed without aortic cross-clamp as an ultra-short-acting β-adrenergic blocker.

SUCCESSFUL EXPERIMENTAL MULTIORGAN TRANSPLANT FROM NON-HEART-BEATING DONORS USING PERCUTANEOUS CARDIOPULMONARY SUPPORT

Organ procurement from non-heart-beating donors (NHBDs) may expand donor pools. In this study, the method of reanimation of heart, lung, and kidney in NHBDs by percutaneous cardiopulmonary support (PCPS) was evaluated. Thirteen beagles were asphyxiated after being given prostacyclin analogue, verapamil, propranolol, and nafmostat mesilate intravenously. Thirty minutes after cardiac arrest, the body was reperfused by PCPS for 1 hr. PCPS priming fluid contained the four drugs above and KCl. Eight hearts immersed in University of Wisconsin (Madison, WI) solution for 24 hr were transplanted orthotopically using leukocyte depleted blood cardioplegia, five left lungs immersed in modified Collins solution were transplanted orthotopically, and five kidneys immersed in University of Wisconsin solution were transplanted heterotopically. All donor hearts arrested without ventricular fibrillation. All transplanted hearts beat spontaneously, and all animals were weaned from cardiopulmonary bypass without inotropic support. The oxygen and carbon dioxide pressure of pulmonary vein blood in the donor lung were no different from those in the recipient lung. All transplanted kidneys made urine soon after reperfusion. These data suggested that hearts, lungs, and kidneys from NHBDs pretreated with four drugs and reanimated with PCPS can be transplanted successfully and that this method may expand the donor pool.

NITRIC OXIDE GAS INFUSION TO THE OXYGENATOR ENHANCES THE BIOCOMPATIBILITY OF HEPARIN COATED EXTRACORPOREAL BYPASS CIRCUITS

Heparin coated bypass circuits have been reported to improve the biocompatibility of extracorporeal circulation, although it is still insufficient and improvable. Nitric oxide (NO) is known to inhibit platelet activation and inflammatory reactions. In this study, the authors evaluated exogenous NO infusion in enhancing the effect of a heparin coated bypass circuit on the biocompatibility of an extracorporeal circuit, especially in view of the attenuation of the inflammatory response. A miniature closed bypass circuit, including an oxygenator (BioActive surface; Carmeda, Stockholm, Sweden) was primed with fresh human heparinized blood and perfused with a centrifugal pump. Either pure N2 gas (control group: n = 7) or NO gas (NO group [100 ppm in N2]: n = 7) was infused to the oxygenator. NO metabolites (nitrite and nitrate), platelet count, thrombin-antithrombin III complex (TAT), alpha2-plasmin-plasminogen inhibitor complex (PIC), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), serotonin, complement 3 activation products (C3a), granulocyte elastase, and bradykinin were measured at 0, 30, 60, 120, and 180 min after starting perfusion. At every sampling point, platelet counts were significantly higher, and TAT, beta-TG, and bradykinin were lower in the NO group than in the control group. PF4, C3a, and granulocyte elastase were significantly lower in the NO group at 60, 120, and 180 min. These results suggest that NO gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal circuits.

Percutaneous cardiopulmonary support system as a bridge to left ventricular assist system (LVAS) implantation: Analysis of its role in the treatment of end-stage cardiac disease

The key to the successful implantation of a left ventricular assist system (LVAS) for patients with endstage cardiac disease is whether the functions of other vital organs are irreversibly damaged or not. The percutaneous cardiopulmonary support system (PCPS) is not only equal in convenience to the intra-aortic balloon pump (IABP), it is more powerful in resuscitating impaired end-organ function. To investigate the efficacy of PCPS for end-state cardiac disease, we retrospectively analyzed end-organ function before and after the application of PCPS. From 1992 to 1996, five cardiomyopathy patients with deteriorated end-organ function despite the application of IABP underwent PCPS support before implantation of LVAS. Urine volume and levels of liver enzymes (sAST and sALT) and serum creatinine were determined before and after the application of PCPS. After the application of PCPS, the urine output increased significantly (1840±450 to 4340±470 ml/day,P<0.01) and levels of sAST, sALT, and serum creatinine decreased significantly (630±220 to 150±50IU/l, 630±260 to 260±130IU/l, and 2.9±0.5 to 1.2±0.1 mg/dl, respectively) (P<0.05). All five patients were successfully bridged to LVAS implantation and none of them died of multiple organ failure caused by pre-existing cardiac failure although one out of five patients died on device ultimately. These results indicated that PCPS before LVAS implantation is useful to resuscitate impaired end-organ function and to improve the survival rate of LVAS implantation for end-stage cardiac disease.