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P F Cardoso

Publications and source records attributed to P F Cardoso.

16 recordsLinked to original sources
PubMed1992

Production and reversibility of right ventricular hypertrophy and right heart failure in dogs.

Combined heart-lung transplantation has been used for end-stage primary pulmonary hypertension. Experience with single-lung transplantation for other conditions suggested that associated severe right ventricular dysfunction resulting from increased afterload would recover after placement of a satisfactory lung allograft. Early experience with the application of single-lung transplantation for pulmonary hypertension supports this contention. We devised a reversible canine model of chronic progressive pressure-overloaded right heart failure by pulmonary artery banding to study the echocardiographic, hemodynamic, and pathological reversibility of the failing right heart. Clinical right heart failure was defined as the development of ascites and pleural effusions. Right heart failure developed in 23 dogs 67 to 348 days after banding, and they were divided into two groups to determine its early and long-term effects. Group 1 dogs (n = 11) were either sacrificed immediately after the onset of right heart failure (n = 5) or unbanded (n = 6); group 2 dogs (n = 12) were maintained in right heart failure for 3 months and then either sacrificed (n = 6) or unbanded. Unbanded dogs in both groups were observed for 4 additional months before sacrifice. A control group of 6 normal dogs was sacrificed for pathological comparisons. After unbanding, the right ventricular systolic pressure fell from 97 +/- 17 mm Hg (group 1) and 88 +/- 31 mm Hg (group 2) to 44 +/- 11 mm Hg and 47 +/- 13 mm Hg, respectively. Despite this persistent gradient across the pulmonary artery, echocardiographic and hemodynamic measures of right ventricular function returned to normal, albeit more slowly in the group 2 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The role of dextran 40 and potassium in extended hypothermic lung preservation for transplantation.

We have previously demonstrated that a low-potassium dextran solution provides superior and more reliable preservation of lungs for 12 hours than that provided by the commonly used Euro-Collins solution. This study was designed to examine the individual contributions of dextran 40 and a low (extracellular) potassium concentration to lung preservation. In a randomized, blinded study using an in vivo canine single-lung transplant model, lungs preserved with low-potassium dextran solution (K+, 4 mmol/L; dextran 40, 20 gm/L) were compared to lungs preserved with low-potassium, no-dextran solution (K+, 4 mmol/L) and high-potassium dextran solution (K+, 123 mmol/L; dextran 40, 20 gm/L). The lungs were assessed immediately and 3 days after transplantation. The low-potassium dextran solution provided excellent immediate pulmonary function with little variability (arterial oxygen tension, 519 +/- 12 mm Hg, measured on the transplanted lung alone, inspired oxygen fraction = 1.0, n = 6). Removing the dextran 40 from the flush solution (low-potassium group) led to a significant deterioration in pulmonary function (arterial oxygen tension, 243 +/- 78 mm Hg, n = 6, p less than 0.01). The high-potassium dextran solution provided extremely poor preservation (arterial oxygen tension, 176 +/- 79 mm Hg; n = 6; p less than 0.01). Two animals in this group died within 6 hours of operation. Viability of the transplanted bronchus was significantly improved with the two solutions containing dextran 40. These results indicate that dextran 40 and low potassium concentration both contribute significantly to the uniformly excellent 12-hour lung preservation seen with the low-potassium dextran solution.

Animals↗
PubMed1992

The effect of basic fibroblast growth factor and omentopexy on revascularization and epithelial regeneration of heterotopic rat tracheal isografts.

Donor airway ischemia is a significant problem after clinical lung transplantation despite the use of omentopexy for accelerated local bronchial revascularization. Several growth factors have been shown to induce angiogenesis in vitro and in vivo. In the present study the quantitative effects on tracheal revascularization and epithelial regeneration of omentopexy and continuous local administration of basic fibroblast growth factor were investigated in a heterotopic rat tracheal isograft model. Tracheas were harvested from donor rats and heterotopically implanted into the omentum of syngeneic recipient rats. Animals were randomly assigned to study groups differing only in treatment of the tracheal segments: omental wrap for 2, 7, or 14 days; omental wrap plus continuous local administration of basic fibroblast growth factor for 7 or 14 days; or omental wrap plus local application of saline for 7 or 14 days. Two, 7, or 14 days after the animals were put to death, the vascularity of the tracheal segments and attached omentum and the tracheal epithelial morphology were assessed in a blinded fashion with use of light microscopy and morphometric image analysis. Vascularity in tracheal segments treated with basic fibroblast growth factor was significantly (p less than 0.05) greater than in control tracheas after 7 and 14 days. Epithelial regeneration was also improved in the basic fibroblast growth factor-treated groups at days 7 and 14 (p less than 0.05). We conclude that continuous local administration of basic fibroblast growth factor enhances early revascularization of tracheal segments induced by omentopexy and accelerates epithelial regeneration in a heterotopic rat tracheal isograft model.

Animals↗
PubMed1992

Equivalent eighteen-hour lung preservation with low-potassium dextran or Euro-Collins solution after prostaglandin E1 infusion.

Improved techniques of pulmonary preservation would help alleviate the critical shortage of donor organs in lung transplantation and would improve early graft function. A previous study demonstrated that cold pulmonary artery flush with low-potassium dextran solution was superior to Euro-Collins solution in preservation of canine lung allografts stored for 12 hours when no pulmonary vasodilator was used before donor lung flush. The present study was designed to determine whether donor pretreatment with prostaglandin E1 would affect the superiority of low-potassium dextran as a preservation solution. Prostaglandin E1 was infused (50 micrograms/min) in 12 donor dogs until potent vasodilation was demonstrated. Low-pressure pulmonary artery flush (50 ml/kg) with either Euro-Collins or low-potassium dextran solution (n = 6 for each group) was performed at 4 degrees C in a randomized, blinded fashion. Heart-lung blocks were extracted and stored at 4 degrees C for 18 hours before left lung allografting. Inflatable cuffs were placed around each pulmonary artery, allowing independent study of the native and transplanted lungs. All 12 recipient dogs survived the 3-day assessment period. Lungs flushed and stored in Euro-Collins or low-potassium dextran solution provided equivalent gas exchange function on day 0 (arterial oxygen tension: Euro-Collins 289 +/- 105 mm Hg versus low-potassium dextran 265 +/- 111 mm Hg; mean +/- standard error of the mean) and on day 3 (Euro-Collins 516 +/- 45 mm Hg versus low-potassium dextran 354 +/- 77 mm Hg; p = 0.10). Mean pulmonary artery pressures in the transplanted lung were not significantly different in the Euro-Collins and low-potassium dextran groups on day 0 (21.4 +/- 2 mm Hg versus 33.7 +/- 5 mm Hg, respectively; p = 0.09) or on day 3 (20.2 +/- 2.7 mm Hg versus 24.2 +/- 5.1 mm Hg, respectively; p = 0.50). We conclude that there was no advantage of low-potassium dextran over Euro-Collins as a flush solution in this 18-hour canine single lung allograft model in which prostaglandin E1 was administered before pulmonary artery flush.

Alprostadil↗
PubMed1992

Reliable eighteen-hour lung preservation at 4 degrees and 10 degrees C by pulmonary artery flush after high-dose prostaglandin E1 administration.

Pulmonary preservation is improved by hypothermia, but the optimal preservation temperature is not known. The effects of two different preservation temperatures, 4 degrees and 10 degrees C, on lung function were studied in a canine left lung allograft survival model allowing selective perfusion of either lung. After donor treatment with high-dose prostaglandin E1, (25 micrograms/kg), lungs were flushed with modified Euro-Collins solution (50 ml/kg) and stored in Euro-Collins solution for 18 hours at 4 degrees C in group I (n = 8) and 10 degrees C in group II (n = 6). Pulmonary gas exchange and hemodynamics were compared on the day of transplantation (day 0) and 3 days later (day 3). Rapid, high-flow, low-pressure flush was achieved uniformly in both groups (flush time: group I, 35.1 +/- 2.4 second; group II, 35.3 +/- 3.0 seconds; p = 0.96; flush pressure: group I, 9.8 +/- 0.7 mm Hg; group II, 10.1 +/- 1.1 mm Hg; p = 0.8). Transplanted lungs provided similar excellent oxygenation in both groups on day 0 (arterial oxygen tension, group I, 451 +/- 82 mm Hg; group II, 497 +/- 37 mm Hg; p = 0.61; inspired oxygen fraction = 1.0) and day 3 (arterial oxygen tension, group I, 551 +/- 57 mm Hg; group II, 587 +/- 19 mm Hg; p = 0.55), with a statistically significant improvement from day 0 to day 3 in both groups (group I, p = 0.034; group II, p = 0.038). There was no difference in arterial carbon dioxide tension, base excess, cardiac output, blood pressure or pulmonary artery pressure between the two groups. We conclude that a large bolus of prostaglandin E1 into the pulmonary artery produces a high-flow, low-pressure flush with modified Euro-Collins solution; with this technique, equivalent, reliable 18-hour lung preservation can be achieved at 4 degrees and 10 degrees C flush and storage temperatures.

Alprostadil↗
PubMed1992

[Revascularization of heterotopic isotransplants of the rat trachea using an omentum flap].

Donor airway ischemia remains a significant problem following lung transplantation. An acceleration of local bronchial revascularization would be advantageous for bronchial healing. In the present study, the quantitative effects of omentopexy on tracheal revascularization and epithelial regeneration were investigated in a heterotopic rat tracheal isograft model. Tracheal segments were harvested from donor rats and heterotopically implanted into the omentum of syngeneic recipient rats. Tracheal segments were wrapped for 2 days (group 2), 7 days (group 3) or 14 days (group 4). Tracheal segments in group 1 were harvested and not re-implanted. Following sacrifice of the animals after 2, 7 or 14 days, the vascularity of the tracheas and the tracheal epithelial morphology were assessed histologically using morphometric image analysis. The vascularity of tracheal segments was significantly higher in group 1 (native tracheas) compared to all other groups. Vascularity in group 4 segments (omental wrap for 14 days) was significantly greater than in group 3 segments (omental wrap for 7 days). Tracheal epithelial morphology was characterized by non-confluent single epithelial cells at day 2, a confluent multilayered nonciliated epithelium after 7 days of omental wrap and a morphologically normal epithelium after 14 days of omental wrap. Our new heterotopic rat tracheal isograft model allows histologic assessment and quantification of local revascularization and epithelial regeneration of tracheal segments by omentopexy.

Anastomosis, Surgical↗
PubMed1991

Low-potassium UW solution for lung preservation. Comparison with regular UW, LPD, and Euro-Collins solutions.

University of Wisconsin solution has been used successfully in clinical kidney and liver preservation. The object of this study was to determine if low-potassium UW (LPUW) solution could be applied to pulmonary preservation. Rabbit lungs were stored after hypothermic pulmonary artery (PA) flush with four different solutions (group 1: low-potassium dextran (LPD) solution, group 2: high-potassium UW (HPUW) solution, group 3: LPUW solution, group 4: modified Euro-Collins (E-C) solution). The lungs were preserved at 10 degrees C for 30 hr and evaluated in an ex vivo ventilation/perfusion apparatus using fresh pooled venous rabbit blood. Mean PA flush pressures (MFP) during harvesting were significantly lower in groups 1 and 3 (8.1 +/- 1.0 mmHg and 7.3 +/- 0.6 mmHg, respectively; mean +/- SEM) than in groups 2 and 4 (15.5 +/- 1.7 mmHg and 12.3 +/- 0.9 mmHg, respectively). Lungs in groups 1 and 3 showed significantly higher PaO2 (103.5 +/- 8.0 mmHg and 89.3 +/- 7.2 mmHg) than groups 2 and 4 (48.3 +/- 7.7 mmHg, 66.7 +/- 4.7 mmHg). Groups 1 and 3 showed significantly lower wet/dry weight (W/D) ratios after reperfusion (6.21 +/- 0.15 and 6.39 +/- 0.23) than groups 2 and 4 (7.70 +/- 0.57 and 7.13 +/- 0.21, respectively). There were no significant differences in MFP, PaO2, PaCO2, mean pulmonary artery pressure, or W/D ratio between groups 1 and 3. These results suggest that LPUW solution may be as beneficial as LPD solution for pulmonary arterial flush and lung preservation.

Adenosine↗
PubMed1991

Use of an isolated in situ canine lung perfusion model to evaluate dopamine clearance by the lung.

An isolated in situ lung perfusion model was used to assess dopamine clearance by the lungs in 12 dogs. The preparation consisted of a closed perfusion system in situ, in which systemic arterial blood supply was interrupted. Blood flow to the lungs was maintained at presurgery flow rates. The inflow was restricted to the lungs by the pulmonary arteries and outflow was limited to the pulmonary veins. Pulmonary artery pressure, temperature and pO2 were maintained at physiological levels. After confirmation of a stable base line, one of 3 doses (1, 2, or 5 micrograms/kg/min) of dopamine was infused over 30 min to achieve steady-state blood concentrations, then blood samples were drawn at specified times during and after the infusion. Dopamine plasma concentrations were analyzed by high performance liquid chromatography with electrochemical detection. Dose-dependent disposition of dopamine was observed in both plasma concentration-time profiles and in clearance (20.3 +/- 9.6 ml/min/kg at 5 micrograms/kg/min vs. 41.6 +/- 19.1 ml/min/kg at 1 micrograms/kg/min, P = 0.038). A sham experiment revealed that the blood in this experimental preparation contributed less than 10% to the total clearance of dopamine. This study revealed that our isolated in situ model is an excellent method to evaluate the role of the lungs in drug removal. Furthermore, it confirmed that the lungs contribute to the clearance of dopamine from the body.

Animals↗
PubMed1991

The effect of pulmonary arterial flow and positive end-expiratory pressure on retrograde bronchial mucosal blood flow.

Bronchial viability within the first few days after lung transplantation depends on collateral blood flow from the pulmonary to the bronchial circulation. In the present study the relationship between pulmonary arterial flow and retrograde bronchial blood flow, and the effect of positive end-expiratory pressure on bronchial blood flow were evaluated by laser Doppler velocimetry in an isolated in situ lung perfusion model. Nine adult mongrel dogs were exsanguinated by way of a left atrial cannula. Blood was pumped by a roller pump into the main pulmonary artery. Lungs were perfused at random flow (in 0.5 L/min increments) at rates of 1 to 3 L/min. Steady-state laser Doppler velocimetric measurements at each level of flow were made at the tracheal carina and both bronchial carina. Pump flow was then set at baseline cardiac output and positive end-expiratory pressure was applied. Steady-state laser Doppler velocimetric measurements were obtained at each level of positive end-expiratory pressure (5 cm H2O and 10 cm H2O). Bronchial blood flow correlated well with pulmonary arterial flow (for the tracheal carina; rs = 0.912 and p less than 0.0005; for the right bronchial carina, rs = 0.799, p less than 0.0005; for the left bronchial carina, rs = 0.917, p less than 0.0005; where rs is the common correlation coefficient). The bronchial blood flow at the left bronchial carina and the right bronchial carina were significantly higher than at the tracheal carina (p less than 0.005 and p less than 0.05, respectively). At baseline cardiac output, bronchial blood flow in the in situ model was approximately 50% lower than observed in the intact animals. Positive end-expiratory pressure increased the bronchial blood flow at the tracheal carina and both bronchial carina (p less than 0.05).

Animals↗
PubMed1991

Plasma atrial natriuretic factor concentrations in a canine model of right heart pressure overload.

Two studies were carried out in order to evaluate the plasma atrial natriuretic factor (ANF) concentrations, as well as hemodynamic and renal profiles in a chronic canine model of right heart pressure overload induced by pulmonary artery (PA) banding. In study I (n = 6), the animals were submitted to a gradual increase in pressure to clarify whether an increase in pressure or atrial distension was the main stimulus to ANF secretion. In study II (n = 6), right heart pressure overload was produced more rapidly, resulting in fluid retention and weight gain, thereby completing the model of right heart failure, and allowing an evaluation of the mechanisms involved in ANF resistance. In study I there were significant increases in right atrial pressure over baseline at 20 weeks, ANF levels at 24 weeks and right atrial area at 28 weeks following PA banding. In study II right heart pressures and ANF levels were higher than baseline at 12 weeks (p less than 0.0001), and fluid retention developed between 12-24 weeks in all dogs. The results suggest that increased right heart pressure, rather than atrial size, is a primary stimulus to ANF secretion in chronic right heart pressure overload. Despite the increases in right atrial pressure, clinical fluid retention occurred only with elevations of renin and aldosterone.

Aldosterone↗
PubMed1991

A reevaluation of heparin requirements for cardiopulmonary bypass.

We wished to determine if reduction in the standard heparin administration for cardiopulmonary bypass could be accomplished safely with the use of membrane oxygenators. An experimental study was designed to evaluate two different heparin administration protocols for cardiopulmonary bypass with hollow-fiber membrane oxygenators. Two groups of six pigs were submitted to hypothermic cardiopulmonary bypass (28 degrees C) for 3 hours, then rewarmed, decannulated, and reassessed after 1 hour. In group I (control) heparin was administered to maintain the activated clotting time in excess of 450 seconds; in group II activated clotting time was maintained between 250 and 300 seconds. The mean total heparin administered was 41,000 units in group I and 25,000 units in group II. Concentration of coagulation factors II, V, and VIII, fibrinogen, and platelet count were determined before, during, and 1 hour after bypass. No significant difference in any of these coagulation parameters was observed between the groups. The performance of the oxygenators was similar in both groups, with no evidence of thrombosis. Thus reduced heparin administration, enough to keep activated clotting time between 250 and 300 seconds, was not related either to major coagulation factors and platelet consumption or to derangements in the oxygenator's performance.

Animals↗
PubMed1990

The superiority of an extracellular fluid solution over Euro-Collins' solution for pulmonary preservation.

Limited donor supply is the major factor restricting the application of lung transplantation. A uniformly reliable method of lung preservation would improve donor organ availability. At present, Euro-Collins' solution, an intracellular fluid-type solution, is most widely used in organ preservation. However, we have previously shown that initial pulmonary flush with an extracellular-type solution (low-potassium dextran solution [LPD]) provided better pulmonary preservation than Euro-C. In the present study, we used an in vitro-ventilated, blood-perfused rabbit lung model to examine whether the mechanism for this improvement was related to the effect of LPD during pulmonary flush or its effect during storage. Rabbit lungs were harvested and stored after pulmonary flush with different solutions (group 1: 400 ml of LPD; group 2: 400 ml of Euro-C; group 4: 300 ml of Euro-C followed by 100 ml of LPD; n = 5 in each group). The lungs were then preserved at 10 degrees C for 18 hr and reperfused with fresh venous blood. After 10 min of reperfusion, lungs in group 1 showed the highest PO2 (group 1: 124.4 +/- 7.7 mmHg; group 2: 46.2 +/- 9.4 mmHg P less than 0.01). Lungs in both group 3 and group 4 showed better lung function and lower wet/dry weight ratio than those in group 2. We conclude that LPD provides better lung preservation by its effects both on pulmonary flush and on storage.

Animals↗
PubMed1989

Recovery of elevated atrial natriuretic peptide in pressure-overload right heart failure.

Elevation of the plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) was observed in canine chronic right heart failure (RHF) secondary to right ventricular (RV) pressure overload. Pressure overload on the right heart was gradually increased using an inflatable cuff. The interval between banding and the onset of RHF was 152 +/- 52 days. Seventeen RHF dogs were produced and divided into Group I (n = 11) and Group II (n = 6). At the onset of RHF, Group I dogs were either sacrificed for study of the heart, or unbanded to allow recovery from RHF. The dogs in Group II were maintained in RHF for 3 additional months before being either sacrificed or unbanded. Following unbanding, the ANP level of Group I recovered from 108 +/- 36 (n = 11) to 20 +/- 6 pg/ml (n = 6) at 1 month and was maintained at 27 +/- 7 pg/ml (baseline, 21 +/- 5 pg/ml, n = 11) at 4 months. ANP levels of Group II declined from 165 +/- 55 (n = 6) to 87 +/- 2 pg/ml (n = 3) at 1 month and further decreased to 42 +/- 14 pg/ml (n = 3) 4 months after unbanding. Thus, compared to Group I, Group II had a high ANP level before unbanding and a delay in recovery of the ANP levels despite normalization of the right atrial pressure (RAP). Four months after release of pressure overload, the right atrial hypertrophy persisted in the unbanded dogs; however, Group I unbanded dogs showed a better reversal of the right atrial hypertrophy than Group II unbanded dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A method for safe twelve-hour pulmonary preservation.

The clinical application of lung transplantation is severely limited by the shortage of suitable donor organs. Current techniques of lung preservation allow a maximum of 4 to 6 hours of safe ischemic time. The function of canine left lung allografts stored for 12 hours after being cooled by pulmonary artery flush was studied. Two types of flush solution were used: group I; Euro-Collins solution; group II, low-potassium-dextran solution. Lung function was studied immediately and 3 days after transplantation. This protocol enables study of acute preservation-related lung injury and the delayed manifestations of ischemic and reperfusion injury after a 3-day period of recovery. Inflatable cuffs were placed around each pulmonary artery at operation and were attached to subcutaneous injection ports. Temporarily occluding either pulmonary artery allowed independent study of the native or transplanted lung. Using this model, we were able to demonstrate reliable and reproducible preservation of lungs for 12 hours. The low-potassium-dextran solution provided significantly better immediate function of the preserved lung than the Euro-Collins solution: arterial oxygen tension 509 +/- 15 mm Hg versus 111 +/- 16 mm Hg (p less than 0.0001). Function on the third day was excellent for both groups. Pulmonary artery pressure, pulmonary vascular resistance, and carbon dioxide tension were not significantly different between the groups immediately or on day 3.

Animals↗