Efficacy of siloenafil in the management of severe pulmonary hypertension in patients with rheumatic mitral valve disease undergoing mitral valve surgery

Rheumatic heart disease remains a major health issue in developing countries, and is commonly complicated with pulmonary hypertension. Phosphodiesterase 5 inhibitors selectively inhibit PDE5 abundantly located in the pulmonary vasculature, leading to pulmonary vasodilatation without significant systemic effects. This study aims to investigate the effect of sildenafil, given in a single dose through the nasogastric tube after induction of anesthesia, on hemodynamic parameters in patients with severe pulmonary hypertension secondary to rheumatic mitral valve disease. Thirty adult patients, males and females, with severe pulmonary hypertension [PASP > 60 mmHg] secondary to mitral valve disease and scheduled for mitral valve surgery were randomly allocated to receive either 50 mg of sildenafil [group S] or placebo [group C] through the nasogastric tube immediately after induction of anesthesia. Mean arterial pressure [MAP], systolic [PASP] and mean [MPAP] pulmonary artery pressure values, pulmonary vascular resistance index [PVRI], systemic vascular resistance index [SVRI], and cardiac index [Cl] were assessed before sildenafil administration [Tl], 30 min after administration [T2], 30 min after weaning from cardiopulmonary bypass [T3], 1, 2, and 6 hours postoperatively [T4, T5, and T6 respectively]. Right ventricular fractional area change [RVFAC] was assessed by transesophageal echocardiography at the same timings. PASP was significantly lower in group S compared to group C at T2, T3, and 4 [p<0.05]. Similarly, MPAP was significantly lower in group S compared to group S at T2 and T3 [p<0.05]. PVRI was significantly lower in group S compared to group C at T2 and T3 [p<0.05]. RVFAC was significantly higher in group S compared to group C at T2 and T3 [p<0.05]. There was no difference between both groups in SVRI or Cl. Sildenafil has resulted in a significant reduction in systolic and mean pulmonary artery pressures, as well as PVRI. This has resulted in improvement in right ventricular systolic function without any systemic effects. It is concluded that sildenafil can be very useful in patients with severe pulmonary hypertension undergoing valve surgery

impact of preemptive phosphodiesterase III inhibition on left ventricular diastolic performance after valve replacement for aortic stenosis

Left ventricular diastolic dysfunction [LVDD] in aortic stenosis is an important independent risk factor for early and late postoperative mortality. We hypothesized that enoximone or milrinone, administered after releasing the aortic cross-clamp improved the diastolic function of the left ventricle as assessed by transesophageal echocardiography [TEE] in patients with aortic stenosis undergoing aortic valve replacement. Forty-five adult patients with valvular aortic stenosis and preserved systolic function scheduled for primary aortic valve replacement were randomly assigned to one of three equal groups; in group M [milrinone group, n = 15] patients received milrinone with a loading dose of 50 microg/kg followed by an infusion of 0.5 microg/kg/min for 6 hours. In group E [enoximone group, n = 15] patients were given enoximone after release of aortic cross-clamp, with an initial bolus of 0.5 mg/kg followed by a continuous infusion of 2.5 microg/kg/min for 6 hours, and in group C [control group, n = 15] patients received saline bolus and infusion at the same time and interval as the first two groups. Hemodynamic parameters and transesophageal echocardiographic assessment of left ventricular end-diastolic area [EDA], transmitral inflow velocity, and tissue doppler imaging [TDI] of the mitral annulus parameters were assessed pre-bypass [Tl], post-bypass [12] after administration of the test drug and separation from CPB, and at the end of the operation after chest closure [T3]. Cardiac index showed a statistically significant increase [p < 0.05], while the systemic vascular resistance showed statistically significant decrease [p < 0.05] in T2 and T3 compared to Tl in the three groups. Cardiac index was significantly higher [p < 0.05] and the systemic vascular resistance was significantly lower [p < 0.05] in T2 and T3 in both the milrinone and enoximone groups compared to the control group at the same intervals. Left ventricular end-diastolic area showed a decrease in all groups which was statistically significant [p < 0.05] comparing T2 and T3 to Tl but without intergroup difference. Peak E-wave velocity, peak A-wave velocity and E/A ratio of the transmitral flow were comparable in the three groups. E-wave deceleration time was significantly decreased [p < 0.05] in T2 and T3 in the three groups. Tissue Doppler analysis of the peak early mitral annular velocity revealed no significant difference between the three groups. The administration of milrinone or enoximone after release of aortic cross-clamp in valve replacement for aortic stenosis did not improve ventricular diastolic function and failed to show increase in the indices of compliance and relaxation compared to the control

Effect of lung insufflation with oxygen or air during cardiopulmonary bypass on post-bypass pulmonary dysfunction

Cardiopulmonary bypass [CPB] causes various abnormalities in the physical and functional properties of the lungs that initiate increases in pulmonary capillary endothelial permeability, decreases in lung compliance, and impaired gas exchange during the immediate postoperative period. This prospective randomized clinical trial was designed to investigate the effect of insufflating the lungs with 100% oxygen or air versus totally disconnecting the lungs and leaving them to collapse during cardiopulmonary bypass. Fifty-six adult patients undergoing CABG surgery with total CPB and aortic cross-clamping were included. Patients were randomly allocated to 1 of 3 groups that differed only in respiratory management during CPB; Group I [O [2] group, n=19] received 100% oxygen insufflation at 4 L/min. Group II [Air group, n=19] received air [FiO[2] 0.2] at the same flow rate. Group III [Collapse group, n=18] were totally disconnected from the anesthesia machine, and their lungs were left to collapse. PaO[2]/FiO[2] was significantly reduced in O2and Collapse groups in the post-CPB measurement compared to baseline but not in Air group [p<0.05]. In the postoperative period PaO[2]/FiO[2] was significantly higher in Air group compared to O[2] group, measured at 1 hour and 4 hours postoperatively [473 + 60 vs 407 + 90, and 476 +/- 39 vs 416 +/- 73 respectively, p<0.05] denoting a more rapid recovery of the lungs. Static and dynamic lung compliance were significantly reduced in the post-CPB and postoperative measurements in 0[2] and Collapse groups, but not in Air group [p<0.05]. Bronchoalveolar lavage [BAL] cytolines [TNF-alpha and IL-8] were significantly elevated in the post-CPB measurement in 02 group compared to baseline [12.1 [0 -42.1] vs 1 [0 - 17] pg, and 674 [50 - 8767] vs 217 [<10 - 2076] pg respectively, p<0.05], but not in Air or Collapse groups. TNF-alpha and IL-8 were significantly higher in O[2] group in the post-CPB measurement compared to both other groups [p<0.05]. Lung insufflation with air [without the application of mechanical ventilation or CPAP] during CPB has attenuated post-CPB pulmonary dysfunction compared to insufflation with 100% oxygen or disconnecting the lungs and leaving them to collapse. Oxygen on the other hand has caused an inflammatory response as evident by an increase in BAL cytokines