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Biomedical subjects

Guido Van Nooten

Publications and source records attributed to Guido Van Nooten.

At least 19 recordsLinked to original sources
PubMed2006

Stentless and stented aortic valve replacement in elderly patients: Factors affecting midterm clinical and hemodynamical outcome.

OBJECTIVE: To report on the midterm results of aortic valve replacement (AVR) with stented and stentless bioprosthesis in an elderly population by analyzing the factors affecting survival and hemodynamical performance. METHODS: In a retrospective study, 145 patients with a Toronto stentless prosthesis are compared with 110 patients with a stented Carpentier-Edwards valve. The 5- to 10-year clinical outcome, transprosthetic gradients, and early and late left ventricular mass (LVM) regression are analyzed in view of specific prosthesis- and patient-related factors. RESULTS: Actuarial survival at 5 years is 82% after stentless AVR versus 68% after stented AVR (p < 0.001) in elderly patients. However, there was no difference in survival at 8 years, being 55.9% and 59.5%, respectively. Univariate analysis revealed that advanced age at the time of operation, NYHA class IV, use of a stented xenograft, presence of patient-prosthesis mismatch (PPM) (IEOA < or = 0.85 cm2/m2), and severe preoperative left ventricular (LV) hypertrophy (LVMI > 180 g/m2) affected survival adversely. But multivariate analysis determined only age, NYHA class IV and excessive LV hypertrophy as independent predictors of late mortality. Stented and stentless xenografts were equally effective in terms of transprosthetic gradients and LVMI regression. The use of a stentless valve significantly reduced the occurrence of PPM (18% vs 41%, p < 0.01). Early LVMI regression at 1 year was optimized by the avoidance of PPM, indicated by a higher absolute (43.7+/-28.3 g/m2 vs 58.6+/-33.8 g/m2, p = 0.003) and relative (25.0+/-12.7% vs 31.4+/-14.9%, p=0.004) mass regression. However, late LV remodeling was predominantly affected by systemic hypertension and severe preoperative LV hypertrophy, resulting in the incomplete LVMI resolution in 61.3% and 66.7% of these patients, respectively. CONCLUSION: In elderly patients, aortic valve replacement appears to be equally effective with a stentless or stented bioprosthesis. Midterm clinical outcome is mainly determined by patient-related factors such as age, advanced NYHA class, and severity of preoperative LV hypertrophy. Regarding post-AVR left ventricular remodeling, patient-prosthesis mismatch influences the early phase, whereas arterial hypertension affects the late regression more. However, the left ventricular remodeling is continuously compromised by the preoperative presence of excessive hypertrophy, despite the efficacy of the aortic valve replacement.

Aged↗
PubMed2006

Readily available porcine aortic valve matrices for use in tissue valve engineering. Is cryopreservation an option?

The clinical use of acellular biological valves as scaffolds in tissue valve engineering would require them to be readily available. This study examines the feasibility of cryopreserving porcine aortic valve matrices for use in tissue valve engineering. Matrices prepared using an enzymatic-detergent decellularization protocol were examined before and after cryopreservation. The biochemical status of tissues were evaluated by collagen and uronic acid (proteoglycan) determination and their mechanical properties were determined using a burst test. The histological and ultrastructural properties were evaluated by light and electron microscopy. Cryopreservation did not significantly affect the collagen and uronic acid content of aortic leaflet matrices. Histological and ultrastructural sections, however, confirmed extensive disruption of the extracellular collagen matrix and inter-fibrillar proteoglycan associations following cryopreservation. Although neither the breakage force nor the maximum force at failure was significantly different in matrices before and after cryopreservation, the strain observed in matrices was significantly higher after cryopreservation. To our knowledge this is the first study to investigate the effects of cryopreservation on aortic valve matrices. Cryopreservation did not significantly alter the biochemical properties of porcine aortic valve matrices. Nevertheless, cryopreservation had significant adverse effects on the structural and mechanical properties of matrices. Cryopreserved matrices showed significantly higher strain when stressed compared to non cryopreserved matrices. While, theoretically matrices are only expected to be functional for a limited time until regenerated in vivo, further mechanical testing is necessary to evaluate the effects of these changes on the durability of porcine aortic valve matrices for use in tissue valve engineering.

Animals↗
PubMed2005

Randomized comparison of stentless versus stented valves for aortic stenosis: effects on left ventricular mass.

BACKGROUND: Aortic valve replacement (AVR) is the established treatment for severe aortic stenosis. In response to the long-term results of aortic homografts, stentless porcine valves were introduced as an alternative low-resistance valve. We conducted a randomized trial comparing a stentless with a stented porcine valve in adults with severe aortic stenosis. METHODS AND RESULTS: The primary outcome was change in left ventricular mass index (LVMI) measured by transthoracic echocardiography and, in a subset, by cardiovascular MR. Measurements were taken before valve replacement and at 6 and 12 months. Patients undergoing AVR with an aortic annulus < or =25 mm in diameter were randomly allocated to a stentless (n=93) or a stented supra-annular (n=97) valve. There were no significant differences in mean LVMI between the stentless versus stented groups at baseline (176+/-62 and 182+/-63 g/m2, respectively) or at 6 months (142+/-49 and 131+/-45 g/m2, respectively), although within-group changes from baseline to 6 months were highly significant. Changes in LVMI measured by cardiovascular MR (n=38) were consistent with the echo findings. There was a greater reduction in peak aortic velocity (P<0.001) and a greater increase in indexed effective orifice area (P<0.001) in the stentless group than in the stented group. There were no differences in clinical outcomes between the 2 valve groups. CONCLUSIONS: Despite significant differences in indexed effective orifice area and peak flow velocity in favor of the stentless valve, there were similar reductions in left ventricular mass at 6 months with both stented and stentless valves, which persisted at 12 months.

Aged↗
PubMed2005

Can autologous thrombin with a rest fraction of ethanol be used safely for activation of concentrated autologous platelets applied on nerves?

The use of concentrated platelet-rich plasma (cPRP) as a source of growth factors is reported to be beneficial for an enhanced osteogenesis in spine surgery. Today both bovine and autologous thrombin is used for activating the platelets and thus releasing the growth factors. In order to prevent transmission of organisms and the development of antibodies, autologous thrombin seems to be the logical choice. However, the preparation of autologous thrombin is cumbersome and consumes a part of the cPRP. In order to overcome this problem, a commercial autologous thrombin kit (activAT, Dideco, a Sorin Group company, Italy) has been developed which produces autologous thrombin out of platelet-poor plasma. A possible disadvantage of this kit could be the rest fraction of 1.18% of ethanol in the platelet gel. In a pig model, the influence of different ethanol concentrations on the ischiadic nerve was studied. The study consisted out of four groups; a control group (n=6), a group with platelet gel 0% ethanol (n=6), a group with platelet gel 1.18% ethanol (n=6) and a group with platelet gel 3.8% ethanol (n=7). In all the groups, the ischiadic nerve was dissected and the myelin sheet opened after which the wound was closed (control group) or one of the three therapies was applied. After 12 h, the animal was sacrificed and the ischiadic nerve was submitted for histological examination. Myelin sheaths appeared normal in all cases. No axonal swelling was observed. No statistically significant differences were observed for neutrophilic and eosinophilic infiltration nor for collagen necrosis between groups. Platelet gel prepared by the use of a commercial autologous thrombin kit and containing 1.18% of ethanol can be safely used on nerves.

Animals↗
PubMed2005

Relation between neurocognitive impairment, embolic load, and cerebrovascular reactivity following on- and off-pump coronary artery bypass grafting.

OBJECTIVES: To evaluate the effect of on-pump and off-pump coronary artery bypass grafting (CABG) on postoperative cognitive impairment and cerebrovascular reactivity, with attention for the perioperative high-intensity transient signals (HITS). DESIGN: A prospective comparative study. SETTING: Urban university hospital. PATIENTS: Candidates for cardiac surgery. METHODS: Measurement of HITS as a reflection of embolic load was performed in 50 patients (on-pump CABG, n = 32; off-pump CABG, n = 18). To measure cognitively induced cerebrovascular reactivity, cerebral blood flow velocity (BFV) was measured preoperatively in 66 patients, early postoperatively (after 6 days) in 63 patients, and late postoperatively (after 6 months) in 44 patients during five cognitive tasks. In the same session, seven standardized neuropsychological tests were administered. RESULTS: A higher embolic load was found in the on-pump group (p < 0.01). In the on-pump group, aortic cannulation was the most important HITS-prone surgical maneuver. Repeated-measures multivariate analysis of variance (using surgical technique as between-subjects factor and significant differences between both groups as covariates) on the group data revealed no significant differences in neuropsychological performance and BFV immediately after surgery or at 6 months after surgery, compared with preoperative performance. No main effect of surgery was found for neuropsychological performance and BFV. No significant correlations were found between the number of HITS and the degree of postoperative neuropsychological impairment. Individual comparisons revealed that 60% (59.4% in the on-pump group; 61.1% in the off-pump group) of the patients undergoing CABG showed evidence of cognitive impairment soon after surgery. In 24.2%, the cognitive sequelae persisted at 6 months follow-up (31.8% in the on-pump group; 9.1% in the off-pump group). The cognitive impairment index (sum of impaired neuropsychological tests) showed a significant difference after 6 months between both surgery groups with fewer neurocognitive tests that remained impaired in the off-pump group. CONCLUSIONS: In off-pump surgery, significantly fewer HITS were observed. On an individual level, more favorable results in neuropsychological test performance were demonstrated in the off-pump group after 6 months. The number of HITS showed no correlation with degrees of early and late postoperative neuropsychological impairment.

Age Distribution↗
PubMed2004

Outcome analysis of major cardiac operations in low weight neonates.

BACKGROUND: From June 1995 to January 2003, 49 consecutive neonates of less than 2,500 g underwent early surgery for congenital heart disease. A retrospective analysis was performed to evaluate the early to medium term outcome. METHODS: Major cardiac surgery for congenital heart defects included a complete correction in 31 patients (group I) and a palliative procedure in 18 patients (group II). Mean age at operation was 15.2 days (1 day-90 days) and mean weight was 2,190 g (1,300 g-2,500 g). Twenty-four children (49%) were born prematurely. All neonates were critically ill and 47% were already ventilated preoperatively. Heart defects included mainly ventricular septal defect (10), tetralogy of Fallot complexes (8), aortic coarctation (8), transposition complexes (7), single ventricle anomalies (4), pulmonary atresia with intact septum (4), interrupted aortic arch (3), totally anomalous pulmonary venous return (3), and common atrioventricular septal defect (2). RESULTS: Overall surgical mortality was 18%: 4 neonates died after definitive repair and 5 after palliation; representing, respectively, 13% and 28% of each group. Postoperative morbidity occurred in half of the patients (53%). Age, weight, prematurity, type of first surgical procedure, and use of cardiopulmonary bypass did not influence the early outcome. After a mean follow-up of 2.82 years (2 months to 6 years), survival was 87% in the correction group and 54% in the palliation group. All children were in NYHA class I-II. Freedom from reintervention at 18 months was 68% after correction versus 8% after palliation. CONCLUSIONS: Cardiac surgery for congenital malformations in critically ill, low weight neonates can be achieved with acceptable mortality, at the cost of an increased morbidity. Early outcome seems independent of age, weight, prematurity, use of extracorporeal perfusion, and type of first intervention. Moreover, primary correction appears to result in an early survival benefit, remaining constant over time.

Birth Weight↗
PubMed2004

Prediction of the clinical performance of adult arterial cannulas.

The choice of an arterial cannula for cardiac surgery is often difficult. The clinician has to rely on the pressure-flow diagrams provided by the manufacturer that are all produced using water. The conversion of these water data to representative clinical conditions is often difficult if not impossible. In this in vivo study the theory of dynamic similarity is applied to scale the manufacturer's data to the clinical situation, in order to predict the pressure drop desired by the cardiac surgeon. Three hundred and forty-seven samples of pressure drop are obtained in 58 patients. Patients are grouped according to cannula size (20, 22, and 24 Fr). Very good correlation is found between measured and predicted values (r = 0.93; 0.86; 0.87 for 20; 22; 24 Fr). As a result, windows of optimal performance are constructed for each cannula diameter. This technique also allows the construction of an online recommendation for signaling abnormal cannula performance during cardiac surgery.

Adult↗
PubMed2004

Transforming growth factor-beta-induced transition of fibroblasts: a model for myofibroblast procurement in tissue valve engineering.

BACKGROUND AND AIM OF THE STUDY: The selection of a suitable cell type for scaffold seeding, its isolation and adequate expansion in vitro remains a major challenge in tissue valve engineering. The study aim was to establish a model for efficient procurement of myofibroblasts for in-vitro seeding using fibroblasts as progenitor cells. METHODS: Dermal and arterial mesenchymal cells from human (hDMC1.1 and hAMC1.1) and sheep (sDMC1.1 and sAMC1.1) were isolated by sequential culture. Cell isolates were characterized by stringent criteria based on morphology, immunocytochemistry using antibodies to vimentin, cytokeratin, prolyl 4-hydroxylase, smooth muscle alpha-actin (alpha-SMA) and smooth muscle myosin, and by Western blotting for alpha-SMA and N-cadherin. Cultures with less than 10-20% alpha-SMA-positive cells were considered to be fibroblastic. Cells were subsequently transdifferentiated with the cytokine transforming growth factor-beta1 (TGF-beta1) during five days, and then evaluated morphotypically, by immunocytochemistry, and by Western blotting. The metabolic and functional properties of TGF-beta1-treated and untreated colonies were compared by measuring the expression of extracellular proteins (collagen type 1 and tenascin-C) and by a collagen matrix contraction assay. RESULTS: TGF-beta1 successfully transformed both human and sheep fibroblasts to metabolically active and functional myofibroblasts based on stringent criteria for myofibroblast characterization. Alpha-SMA positivity of 100% was obtained in all cases (hDMC1.1, hAMC1.1, sDMC1.1, and sAMC1.1) after transformation compared to less than 50% in the non-transformed state (hAMC1.1, 17%; hDMC1.1, 10%; sAMC1.1, 43%; and sDMC1.1, 30%). This observation was further supported by increased contractility and an up-regulation of extracellular protein production in transdifferentiated cells. CONCLUSION: Untreated arterial cell isolates were, at best, less than 50% alpha-SMA-positive. By allowing procurement of high densities of myofibroblasts in a relatively short time, the model was seen to be a potentially useful tool in tissue valve engineering, at least in investigations using autologous cells in the sheep model.

Actins↗
PubMed2003

Successful management of a large pulmonary cement embolus after percutaneous vertebroplasty: a case report.

Percutaneous vertebroplasty is increasingly used for the treatment of vertebral compression fractures. Local leakage of polymethylmethacrylate cement into the perivertebral space is a common complication, but important systemic effects have rarely been reported. The authors describe the case of a 52-year-old patient with central pulmonary embolism after percutaneous vertebroplasty of the eleventh thoracic vertebral body. The large cement embolus was removed from the right pulmonary artery with a hybrid technique combining an interventional catheter procedure with an open heart operation. The patient made an uneventful recovery. The authors review how appropriate arthroplasty techniques might minimize the risk of this dreadful complication.

Acenocoumarol↗
PubMed2003

Modified stentless porcine valve enhances accelerated cuspal calcification in the juvenile sheep model.

OBJECTIVE: Stent mounting of any bioprosthesis, induces a loss of mobility and reduces the effective valve orifice. By contrast, for stentless procedures, the higher surgical technicality remains a major obstacle for many surgeons. In an attempt to facilitate the insertion of the stentless porcine aortic valve (Toronto SPV), we tried to alter the design by lowering the invasive profile at the depth of the sinuses on both coronary sites. This could theoretically facilitate the implant of the modified stentless valve with an easygoing single layer suture at the challenging subcoronary level and make it more attractive for every surgeon. METHODS: Modifications of the standard model were done by lowering the profile at the depth of the sinuses on both coronary sites, whether by plication or excision of the protruding porcine aortic wall at the nadir of each coronary sinus. Nine juvenile sheep underwent implantation of stentless porcine aortic valves in pulmonary position: 3 standard Toronto SPV, 3 plicated Toronto SPV and 3 excised Toronto SPV. In each series, valves were explanted after 3 months. Valves were analyzed. RESULTS: The cusps of standard Toronto SPV were perfectly functioning and pliable, without visible calcification after three months. The calcium content of the cusps was less than those in the plicated and excised Toronto SPV (2.4 +/- 0.7 microg/mg versus 10.8 +/- 5.9 and 6.7 +/- 3.4 microg/mg). In the plicated and excised valves, calcification of the cusp was more pronounced in the commissural region (3.9 +/- 1.9, 29.0 +/- 16.7, 13.8 +/- 9.5 microg/mg in the standard, plicated and excised Toronto SPV, respectively). On the other hand, the aortic wall from the plicated Toronto SPV had more calcium than that from the other groups (53.6 +/- 6.3, 41.2 +/- 7.1, 45.2 +/- 7.4 microg/mg in the plicated, standard and excised Toronto SPV, respectively). CONCLUSIONS: The modification of stentless porcine valve enhanced accelerated cuspal calcification in the commissural region. It accentuated that the correct implantation technique for stentless procedures is extremely important in order to prevent early degeneration.

Animals↗
PubMed2003

Outcome in a post-cardiac surgery population with acute renal failure requiring dialysis: does age make a difference?

BACKGROUND: Acute renal failure (ARF), requiring dialysis (ARF-d), develops in 1-5% of patients undergoing cardiac surgery and is associated with higher in-hospital mortality. Age is one of the known risk factors for the development of ARF. As the ageing population is increasing, the nephrologist will be faced with a large population of elderly patients requiring dialysis following cardiac surgery. The aim of our study was to evaluate the influence of age on and the risk factors for in-hospital mortality. METHODS: Eighty-two patients with ARF following cardiac surgery and requiring dialysis between January 1997 and October 2001 were included. Two groups of patients were studied: the younger population (<70 years, 42 patients, mean age 59+/-10) and an elderly population (>/=70 years, 40 patients, mean age 76+/-4). Severity of disease was evaluated using the SAPS (Simplified Acute Physiology Score), the Liano score and the SHARF (Stuivenberg Hospital Acute Renal Failure) score. RESULTS: Overall mortality in the population with ARF-d was 56.1%. No difference in mortality rate was found between the younger (61.9%) and elderly patient group (50.0%). The two groups were very similar in baseline and procedural characteristics with exception of body weight (P=0.02) and preoperative glomerular filtration rate (P=0.0001). No significant difference was found in the scoring systems between the old and the young (SAPS P=0.52; Liano P=0.96; SHARF T0 P=0.06; SHARF T48 P=0.15). Mortality in the elderly was significantly correlated with hypotension before starting renal replacement therapy (RRT) (P=0.002), mechanical ventilation (P=0.002), presence of multiorgan failure (MOF) (P=0.0001) and higher scores in the severity models (SAPS: P=0.01; Liano: P<0.0001 and SHARF: P<0.0001). CONCLUSION: The outcome in the elderly requiring dialysis due to ARF post-cardiac surgery is comparable with the outcome in a younger population. No significant difference was found in severity of disease between the elderly and the younger. Variables predicting mortality in the elderly are the presence of MOF, mechanical ventilation and hypotension 24 h before starting RRT. These findings indicate that at the time the nephrologist is called for an elderly patient requiring dialysis due to ARF following cardiac surgery, age per se is not a reason to withhold RRT.

Acute Kidney Injury↗
PubMed2003

Intermittent nitric oxide combined with intravenous dipyridamole in a piglet model of acute pulmonary hypertension.

UNLABELLED: Continuous administration of inhaled nitric oxide is now widely used as a potent and selective pulmonary vasodilator. We have evaluated the effects of IV dipyridamole, a cyclic guanosine monophosphate (cGMP) phosphodiesterase inhibitor, on the magnitude and duration of action of inhaled nitric oxide (NO)-mediated pulmonary vasodilation. We hypothesized that inhibition of cGMP degradation could augment and prolong the pulmonary vasodilating effects of NO and allow for intermittent NO inhalation. In eight anesthetized and mechanically ventilated piglets, IV U-46619, a thromboxane A(2) analog, was used to induce pulmonary hypertension. The effects of 2, 5, and 10 ppm of NO, delivered during 4 min for each concentration and followed by a 10-min NO-free interval after each NO concentration, were evaluated without and with dipyridamole. Pulmonary vascular resistance decreased from 825 +/- 49 dynes. s. cm(-5) (U-46619) to 533 +/- 48 dynes. s. cm(-5) (10 ppm NO) (P < 0.05 versus U-46619) and 396 +/- 42 dynes. s. cm(-5) (dipyridamole 10 microg kg-1x min-1 and 10 ppm NO) (P <0.05 versus NO), and cardiac output increased from 1.93 +/- 0.09 L/min to 2.03 +/- 0.13 L/min and 2.60 +/- 0.30 L/min (P < 0.05 versus NO). Mean arterial blood pressure decreased from 90 +/- 5 mm Hg (10 ppm NO) to 75 +/- 3 mm Hg (dipyridamole plus 10 ppm NO) (P < 0.01). The pulmonary vasodilation obtained with NO alone could be prolonged from 12 to 42 min when inhaled NO was combined with IV dipyridamole, accounting for a time-weighted reduction in NO exposure by 72%. We conclude that dipyridamole augments the effects of NO on right ventricular afterload, allows for intermittent NO inhalation, and can significantly reduce exposure to NO. IMPLICATIONS: IV dipyridamole prolongs the action of inhaled nitric oxide (NO) in a piglet model of acute pulmonary hypertension. Intermittent NO inhalation combined with IV dipyridamole decreases pulmonary artery pressure for a prolonged period of time and reduces exposure to NO.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2002

Short-term and long-term neurocognitive outcome in on-pump versus off-pump CABG.

OBJECTIVE: Neuropsychological dysfunctions are considered to be important complications of coronary artery bypass graft surgery (CABG). We examined the frequency of neuropsychological abnormalities occurring in patients undergoing CABG with (on-pump) and without (off-pump) cardiopulmonary bypass. METHODS: Neuropsychological assessment with seven cognitive tasks was performed one day before, 6-7 days after (n=49) and 6 months after (n=35) surgery. The subgroup undergoing on-pump surgery (n=30 at 7 days and n=22 at 6 months) was demographically comparable to the off-pump subgroup. The on-pump group included more multiple vessel disease. RESULTS: Repeated measures multivariate analysis of variance (using surgical group as a between-subjects factor) on the group data revealed no significant differences neither immediately after surgery nor at 6 months after surgery, compared with the preoperative performance. There were no significant differences between the on-pump and off-pump groups in post-operative neuropsychological performance soon after surgery. A significant difference was found between the two groups 6 months after surgery, with more favorable results for the off-pump group. Individual comparisons revealed that 59% of the patients of both groups undergoing CABG showed evidence of cognitive impairment soon after surgery. In 11% of the patients (all on-pump), the cognitive sequelae persisted at follow-up. CONCLUSION: This study showed no short-term difference between the on-pump and off-pump CABG groups. The long-term cognitive outcome revealed more favorable results for the off-pump group. Although a preference to operate multiple vessel disease with classical cardiopulmonary bypass (CPB) has to be considered, the present study shows evidence for a different pattern of early decline and late recovery of cognitive functions in patients undergoing CABG with and without CPB.

Aged↗
PubMed2002

Mock loop testing of On-x prosthetic mitral valve with Doppler echocardiography.

Previous in vitro testing (mainly in aortic position) and clinical experience (often based on Doppler echocardiographic observations) demonstrated an excellent hemodynamic behavior of the On-X valve. However, integrative studies including simultaneous hemodynamic pressure and flow measurements and Doppler echocardiography are lacking. Using our computer-controlled mock loop system, two samples of the Mitral 27/29 and one sample of the Conform-X Mitral 25/33 are tested in mitral position. Data include transvalvular pressure gradient and flow as well as transthoracic Doppler echocardiography. The valves are tested under three pressure conditions (ventricular systolic pressure of 100, 130, and 160 mm Hg) at three different heart rates (60, 100, and 140 beats/min). In addition, ventricular pressure conditions simulating fibrillation are imposed. Both valve types show similar hydrodynamic characteristics and have an effective orifice area of 2.1 cm2 and a performance index of 0.56 for a cardiac output of 3.5 L/min. Regurgitant volumes remain below 6 ml.

Coronary Circulation↗
PubMed2002

Diagnosis of myocardial perforation by a Greenfield filter made by transesophageal echocardiography.

Greenfield filters have been successfully used to prevent pulmonary embolism in selected patients. However, various complications have been described. A patient is presented in whom a Greenfield filter migrated to the right atrium, and subsequently perforated the right atrial wall. The diagnosis was made by transesophageal echocardiography and the filter removed surgically. This case emphasizes the role of transesophageal echocardiography in the management of migrated Greenfield filters.

Aged↗
PubMed2002

Intravenous dipyridamole enhances the effects of inhaled nitric oxide and prevents rebound pulmonary hypertension in piglets.

Inhaled nitric oxide (NO) is increasingly used in the treatment of pulmonary hypertension, despite its potential toxicity and the risk of life-threatening rebound pulmonary hypertension upon its discontinuation. We investigated whether i.v. dipyridamole, a cGMP phosphodiesterase inhibitor, increased the effects of inhaled NO and prevented rebound pulmonary hypertension. In 14 anesthetized and mechanically ventilated piglets, pulmonary hypertension was induced with U-46619, a thromboxane A(2) analogue. Response to NO and rebound pulmonary hypertension were evaluated without and with i.v. dipyridamole. Low-dose dipyridamole (10 micro g/kg/min) increased cardiac output and augmented the effects of inhaled NO on pulmonary vascular resistance, with marginal additive effect on mean pulmonary artery pressure. Pulmonary vascular resistance decreased from 904 to 511 (20 parts per million NO) (p < 0.0005) and 358 dyne s cm(-5) (20 parts per million NO + dipyridamole) (p < 0.001 versus NO alone), and mean pulmonary artery pressure decreased from 29.0 to 20.5 (p < 0.0001) and 19.3 mm Hg (NS versus NO), respectively. Mean arterial pressure decreased from 85 to 74 mm Hg (dipyridamole + NO) (p < 0.01). High-dose dipyridamole (100 micro g/kg/min) with inhaled NO reduced pulmonary vascular resistance to 334 dyne s cm(-5) but also decreased mean arterial pressure to 57 mm Hg. Eight piglets developed rebound pulmonary hypertension. Two died of acute right ventricular failure and, in five, rebound pulmonary hypertension was prevented by low-dose dipyridamole. In conclusion, low-dose i.v. dipyridamole augments the effects of inhaled NO on right ventricular afterload with moderate changes in systemic hemodynamics, and can prevent rebound pulmonary hypertension.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗