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Biomedical subjects

R Pifarre

Publications and source records attributed to R Pifarre.

At least 37 records · Page 2Linked to original sources
PubMed1993

Sensorineural hearing loss associated with aortocoronary bypass surgery: a prospective analysis.

A prospective, clinical study was undertaken to assess the relationship between aortocoronary bypass surgery (ACBS) and sensorineural hearing loss (SNHL). Between August 1, 1988 and July 31, 1989, 1458 patients underwent ACBS and 181 volunteers were entered into the study based on availability and capability to complete preoperative and postoperative questionnaires and audiometric testing. One hundred forty-five patients completed the study. Intraoperative audiant brainstem response (ABR) testing was performed on 7 patients with essentially normal hearing. Although 4 patients (2.8%) reported a subjective change in hearing on postoperative questionnaires, objective testing did not confirm a significant hearing change in pure-tone, speech discrimination, or speech reception threshold testing. Acute or sudden SNHL within 2 weeks following ACBS was not identified in any patient completing the study. This study did not provide evidence to support a causal relationship between SNHL and ACBS. However, if SNHL does occur following ACBS, the well-established etiology of ototoxic therapy and subsequent SNHL demands exclusion in the absence of conflicting histopathologic information.

Aged↗
PubMed1993

Investigation of a thrombin inhibitor peptide as an alternative to heparin in cardiopulmonary bypass surgery.

BACKGROUND: This study was undertaken to determine if a newly developed synthetic peptide thrombin inhibitor (DuP 714; DuPont-Merck, Wilmington, Del) could be used as an anticoagulant in cardiopulmonary bypass (CPB) surgery. METHODS AND RESULTS: Anesthetized mongrel dogs were placed on CPB for 1 hour and then observed for 2 hours. Following a dose-finding study, the optimal dose (DuP 714 group) and an overdose (DuP-HI group) were studied. The DuP 714 group received 0.25 mg/kg i.v. bolus plus 0.5 mg.kg-1 x h-1 infusion of DuP 714 (n = 10) and the DuP-HI group received 0.5 mg/kg i.v. bolus plus 1.0 mg.kg-1 x h-1 infusion of DuP 714 (n = 6). No neutralizing agent was used. The control group received 2.0 mg/kg intracardiac bolus of heparin with 0.15 mg/kg i.v. bolus injections as needed to maintain the activated clotting time (ACT) at > 300 seconds during CPB (n = 6). Protamine sulfate (2.0 mg/kg) was used to reverse heparin after CPB. Postoperative blood loss for both DuP 714 groups was less than that for heparin (177 +/- 40 and 297 +/- 36 versus 318 +/- 99 g, P = NS). The DuP 714 group revealed higher pump line filter fibrin deposits (15.5 +/- 3.6 mg, P < .032 ANOVA) compared with the heparin group (4.2 +/- 2.4 mg), whereas the DuP-HI group showed equivalent deposits (9.3 +/- 5.3 mg). The ACT levels recorded during and 30 minutes after CPB were 638 +/- 52 and 160 +/- 9 seconds in the DuP 714 group and > 800 and 436 +/- 75 seconds in the DuP-HI group; however, the ACT level only in the DuP-HI group remained elevated 2 hours after CPB. Platelet counts were significantly higher (P < .05) in both DuP 714 groups after CPB. There was nearly complete elimination of all peptide in the urine. No statistical difference was observed in hemodynamics (cardiac index and systemic vascular resistance) in any of the groups. CONCLUSIONS: This study reveals that the peptide inhibitor DuP 714 can effectively function as an anticoagulant in a canine CPB model. The efficacy and safety, even when overdosed, are demonstrated by reduced blood loss and lack of platelet count reduction. Clinical monitoring can be achieved by the use of ACT levels. No evidence of hemodynamic compromise was noted with the drug administration.

Animals↗
PubMed1993

Risk/benefit ratio of perioperative OKT3 in cardiac transplantation.

This study shows that perioperative OKT3 provides no benefit in terms of the time of onset or frequency of rejection or patient survival. However, it does result in an increased incidence of infection, particularly CMV infection. Thus, the risk/benefit ratio of perioperative OKT3 does not appear favorable. However, a multicenter, randomized trial including a larger number of patients and longer patient follow-up will be required to definitively answer the question.

Azathioprine↗
PubMed1992

Cardiac adaptation to obesity and hypertension after heart transplantation.

Obesity and hypertension frequently develop after heart transplantation. The cardiac adaptation to obesity and hypertension was studied by determining hemodynamic and echocardiographic indexes in 10 obese hypertensive patients (body mass index greater than or equal to 27.8 kg/m2 in men or greater than or equal to 27.3 kg/m2 in women) matched by mean arterial pressure, age and gender with 10 nonobese hypertensive patients 1 year after cardiac transplantation. Cardiac output was 30% greater (p less than 0.02) and systemic vascular resistance 25% lower (p less than 0.01) in the obese than in the nonobese patients. Right ventricular systolic and pulmonary artery systolic, diastolic and mean pressures were also significantly higher (p less than 0.05) in the obese patients. Left ventricular end-diastolic diameter was 25% greater (p less than 0.05), left ventricular mass 28% greater (p less than 0.02) and left ventricular end-diastolic volume 20% higher (p less than 0.01) in the obese subjects. Left ventricular ejection fraction was significantly lower in the obese than in the nonobese subjects (34% vs. 51%, p less than 0.05). These results indicate that the cardiac adaptation to obesity and hypertension after heart transplantation consists of left ventricular dilation and an increase in left ventricular mass associated with an increased cardiac output and lower peripheral vascular resistance. These adaptive changes that occur in obese hypertensive patients after heart transplantation might increase the long-term risk of graft failure, as suggested by their lower left ventricular ejection fraction 1 year after transplantation.

Adaptation, Physiological↗
PubMed1992

Successful treatment of heart transplant rejection with photopheresis.

Photopheresis is a potential therapy for rejection in which reinfusion of mononuclear cells exposed to ultraviolet-A light ex vivo, after treatment with 8-methoxypsoralen in vivo, initiates host immune responses that specifically inhibit the cytotoxicity of the photomodulated mononuclear cells. Between May 1990 and January 1991, 7 heart transplant (HT) patients (age 42.2 +/- 16.7 [mean +/- SD] years) on triple immunosuppression (cyclosporine, corticosteroids, and azathioprine) had 9 episodes of non-hemodynamically compromising moderate rejection that were treated with photopheresis. These episodes of rejection occurred at an average of 114.4 +/- 180.5 (range 8-575) days after HT. After oral administration the mean serum level of 8-methoxypsoralen achieved was 129.0 +/- 72.4 ng/ml. An average of 10.4 +/- 9.6 x 10(9) mononuclear cells were treated with each photopheresis procedure. Photopheresis was performed twice when less than 5 x 10(9) mononuclear cells had been treated with the first procedure. Of 9 rejection episodes treated with photopheresis, 5 required 1 procedure and 4 required 2 procedures. Photopheresis was used to treat a single episode of rejection in 5 pts. and 2 separate rejection episodes in 2 additional pts. Eight of 9 episodes of rejection were successfully reversed by photopheresis as assessed by endomyocardial biopsy (EMB) performed 7 days after treatment. Immunohistochemical analysis of EMB samples revealed that postphotopheresis cell counts for T cells, B cells, and macrophages were reduced compared to pretreatment values and correlated with the histopathologic resolution of rejection. Hemodynamics were normal prephotopheresis and remained unchanged at the time when the postphotopheresis EMB showed no evidence rejection No adverse effects have been observed with photopheresis. Over a follow-up period of 5.3 +/- 4.0 months, rejection and infection rates/pt./follow-up months were 0.3 +/- 0.4 and 0.04 +/- 0.07, respectively. The preliminary, short term results of this pilot study indicate that photopheresis may be efficacious in the treatment of moderate rejection in hemodynamically stable HT patients and thus may be an alternative to corticosteroid pulses.

Adult↗
PubMed1992

Photopheresis versus corticosteroids in the therapy of heart transplant rejection. Preliminary clinical report.

BACKGROUND: Photopheresis is a technique in which reinfusion of mononuclear cells exposed to UV-A light ex vivo after in vivo treatment with 8-methoxypsoralen initiates host-immunosuppressive responses. METHODS AND RESULTS: To determine if photopheresis safely reverses International Society for Heart and Lung Transplantation (ISHLT) rejection grades 2, 3A, and 3B without hemodynamic compromise, 16 heart transplant patients with ISHLT rejection grades 2, 3A, and 3B were randomized to photopheresis or corticosteroid therapy. The average number of mononuclear cells treated with each photopheresis procedure was 9.8 +/- 9.1 x 10(9) (mean +/- SD). Photopheresis and corticosteroids reversed eight of nine and seven of seven episodes of rejection, respectively. The median time from initiation of treatment to rejection reversal was 25 days (range, 6-67 days) in the photopheresis group and 17 days (range, 8-33 days) in the corticosteroid group. Hemodynamics were normal before either treatment and did not change after reversal of rejection. No adverse reactions occurred with photopheresis, and all patients in either treatment group are alive. CONCLUSIONS: These preliminary, short-term results in prospectively randomized patients indicate that photopheresis may be as effective as corticosteroids for treating ISHLT rejection grades 2, 3A, and 3B. The apparently low toxicity and potential efficacy of photopheresis warrant further analysis of its role in the prevention and treatment of heart transplant rejection.

Adult↗
PubMed1992

Repeat median sternotomy for the automatic implantable cardioverter and defibrillator.

Forty-four patients with a repeat sternotomy for the implantation of the automatic implantable cardioverter and defibrillator are presented. Thirty-three of the patients had placement of the device only and 11 had a concomitant open heart procedure--nine for aorto-coronary bypass (mean of 1.6) and two for mitral valve replacement. Twenty-two complications occurred in 17 patients. Arrhythmia was the most common problem. Two deaths occurred perioperatively in the group (mortality rate of 4.5 per cent) and were caused by gram-negative pneumonia and pulmonary embolus. There were no specific complications related to the sternotomy. It is, therefore, concluded that the repeated sternotomy is an excellent method to insert the automatic cardioverter and defibrillator.

Aged↗
PubMed1991

Atrial natriuretic peptide responses during anaesthesia in patients with refractory cardiomyopathies.

In patients with congestive heart failure, the release of atrial natriuretic peptide (ANP) is decreased. This study sought to determine the extent of ANP, sympathetic and haemodynamic responses to acutely increased atrial pressure in patients with cardiomyopathies undergoing orthotopic cardiac transplantation. Haemodynamic variables, plasma ANP, norepinephrine, and epinephrine concentrations were measured in 17 patients at five times before and after induction of anaesthesia using either ketamine 1.5 micrograms.kg-1 or sufentanil 3.6 +/- 0.3 micrograms.kg-1. Preinduction values in the ketamine and sufentanil groups were not significantly different. Compared with preinduction values, increases in mean arterial pressure (26%), pulmonary capillary wedge pressure (90%), right atrial pressure (107%), and heart rate (24%) occurred in the ketamine group while cardiac index decreased by 19% (P less than 0.05). Haemodynamic variables in the sufentanil group did not change at any of the times studied. Plasma concentrations of atrial natriuretic peptide were not different within or between treatment groups. Following tracheal intubation plasma norepinephrine levels increased by 116% in the ketamine group (P less than 0.05), but did not change in the sufentanil group. Plasma norepinephrine concentrations differed significantly between the ketamine and sufentanil groups. There were no differences in epinephrine concentrations in either group. Despite the anticipated haemodynamic and catecholamine differences found between the ketamine and sufentanil groups, the levels of plasma ANP were similar. Based upon these results, it is concluded that ANP exerts little influence in the control of fluid volume or blood pressure in patients with refractory cardiomyopathy.

Adult↗
PubMed1991

Potential use of recombinant hirudin as an anticoagulant in a cardiopulmonary bypass model.

Recombinant (r) hirudin is a potent thrombin-specific inhibitor derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared with heparin in a canine model of cardiopulmonary bypass operations. Two administration regimens were used for r-hirudin: group 1, 1.0 mg/kg intracardiac bolus then intravenous bolus at 30 minutes (n = 10); and group 2, 1.0 mg/kg intracardiac bolus with 1.25 +/- 0.04 mg.kg-1.h-1 intravenous infusion (n = 8). Group 3 was given an intracardiac bolus of heparin, 1.66 mg/kg (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (p = 0.02). Decreases in platelets, fibrinogen, and hematocrit due primarily to hemodilution were the same in each group. The bleeding time assay showed less prolongation for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life all coagulation variables returned to baseline within 30 minutes after cardiopulmonary bypass. Because r-hirudin lacks effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in cardiopulmonary bypass. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.

Animals↗
PubMed1991

Combined myocardial revascularization and abdominal aortic aneurysm repair.

Myocardial infarction remains the leading cause of early and late deaths after abdominal aortic reconstruction in patients with abdominal aortic aneurysm. Our approach for the past 4 years has been combined myocardial revascularization with abdominal aortic aneurysm repair in patients with good left ventricle performance. From July 1984 through June 1989, 128 patients underwent abdominal aortic aneurysm repair. Seventeen patients underwent combined abdominal aortic reconstruction with coronary artery bypass grafting. One patient died (5.9%). The remaining patients are all well at current follow-up. Our experience shows that patients with coronary artery disease and abdominal aortic aneurysm may have both lesions safely repaired as a single operative procedure.

Aorta, Abdominal↗
PubMed1991

Comparative studies on various assays for the laboratory evaluation of r-hirudin.

Several laboratory methods are available to measure r-hirudin, including clot-based, amidolytic, immunologic, and physicochemical techniques. The global tests, such as the PT, APTT, and Heptest, did not show an adequate response to r-hirudin in the range of 0.5 to 10.0 micrograms/ml, where full anticoagulation is achieved, as determined by animal models of thrombosis. The 10 U/ml thrombin time assay was very sensitive to r-hirudin, whereas the 10 U/ml calcium thrombin time gave a dose-dependent response from 0.15 to 10.0 micrograms/ml. Whole blood clotting assays (ACT, TEG) effectively measured r-hirudin levels up to 25 micrograms/ml. The amidolytic anti-Factor IIa assay, specific for evaluating direct thrombin inhibition, was very effective, particularly when modified to decrease the sample: thrombin ratio for higher r-hirudin concentrations. This assay may be useful in quality control, since it is biochemically defined and reagents are easily standardized. Thrombin generation assays based on synthetic substrates showed limited effect of r-hirudin; however, assays based on TAT complex and prothrombin fragment F1+2 generation showed a dose-dependent response. Immunologic methods (ELISA) are under development. Since these assays measure both complexed and noncomplexed hirudin, and since they are only sensitive to submicrogram levels, they may only be useful for the direct quantitation of absolute levels of r-hirudin but not for monitoring clinical anticoagulation. Thus, thrombin-based clotting, amidolytic, and immunologic assays can be used to evaluate and measure r-hirudin. However, optimization of each assay to respond to high and low concentrations of r-hirudin and their application to clinical monitoring, batch control, and standardization needs to be determined.

Animals↗
PubMed1991

Use of recombinant hirudin to increase the patency rate of microanastomosis in a rabbit model.

Microvascular surgical techniques now play an extremely important role in reconstructive surgery. Failures still persist and are most commonly due to thrombotic occlusion of the microvascular anastomosis. Five to 20% of all free tissue transfers and replants are affected. A logical step in the effort to resolve this problem would be the infusion of the newly available recombinant hirudin (r-hirudin). The value of r-hirudin in microvascular surgery has not been investigated. An animal model mimicking the thrombotic mechanisms similar to those in the clinical situation has been described in which a length of rabbit femoral artery is excised, turned inside out and reinserted into the vessel with two standard microvascular anastomoses. The major factors in clinical anastomosis failure are represented in this animal model by medial disruption, imperfect vessel wall alignment, needle holes, trauma, foreign suture material and changes in flow. The type III adventitial collagen turned inward reproduces the clinical problem of adventitial strands becoming caught in the anastomosis. A predictable rate of thrombosis results depending on inversion graft length: a 2 mm segment has an occlusion rate at one week of about 30%. Using this model heparin infusions significantly decrease thrombosis rates compared to saline. Using an almost identical model we have begun a study the effect of r-hirudin on microvascular patency. New Zealand White male rabbits were anaesthetized with ketamine and xylazine. Through a groin incision the femoral vein was catheterized and tubing connected to an infusion pump. The femoral artery was exposed, and the adventitia aggressively removed since it is difficult to minimally debride adventitia in a reproducible fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1991

Comparison of recombinant hirudin and heparin as an anticoagulant in a cardiopulmonary bypass model.

Recombinant (r) hirudin is a potent thrombin-specific inhibitor originally derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared to heparin in a dog model of cardiopulmonary bypass (CPB) surgery. Two administration regimens were used for r-hirudin: Group I received 1.0 mg/kg intracardiac (i.c.) bolus then intravenous (i.v.) bolus at 30 min (n = 10); Group II received 1.0 mg/kg (i.c.) bolus with 1.25 +/- 0.04 mg/kg/h (i.v.) infusion (n = 8). Group III was given heparin 1.66 mg/kg (i.c.) bolus (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (P = 0.02). Decreases in platelets, fibrinogen and haematocrit due primarily to haemodilution were the same in each group. The bleeding time was less prolonged for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life, all coagulation parameters returned to baseline within 30 min after CPB. Since r-hirudin has no effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in CPB. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.

Animals↗
PubMed1991

An objective perspective on recombinant hirudin: a new anticoagulant and antithrombotic agent.

Leeches have been in medical use for many years. Hirudin, the anticoagulant obtained from the medicinal leech has been purified, characterized and can now be produced by recombinant (r) technology. R-hirudin is a potent inhibitor of thrombin and is therefore a potentially valuable anticoagulant and antithrombotic drug. This article reviews the current status of r-hirudin in this role and compares the pharmacokinetics, mechanism of action and clinical efficacy of this agent with heparin. The methods available for laboratory assessment and clinical monitoring of r-hirudin and the possible ways of antagonizing its effects are also discussed. Finally, the potential clinical applications of r-hirudin are outlined, although further laboratory and clinical studies, together with a fall in the cost of this compound are required before r-hirudin can be more widely accepted as an anticoagulant and antithrombotic agent.

Amino Acid Sequence↗