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Peritoneal fibrinolytic activity and intra-abdominal adhesions
1120
Peritoneal fibrinolytic activity and intra-abdominal adhesions
The mechanisms leading to reduction of peritoneal fibrinolytic activity in conditions that are associated with the formation of intra-abdominal adhesions were studied. Tissue plasminogen activator was found, by antibody inhibition techniques, to be the activator of fibrinolysis in homogenates of control peritoneum (n=6). Homogenates of control (n=10) and inflamed
peritoneum (n=10) were analysed. Plasminogen activating activity was much lower in inflamed peritoneum (median 0·07 IU/cm2) than in control tissue (median 12·0 IU/cm2) (p<0·001). Levels of tissue plasminogen activator and &agr;2-antiplasmin were
similar in both control and inflamed tissue.
Plasminogen activator inhibitor-1, not detectable in control peritoneum, was present in inflamed tissue and might be the reason for the reduction in functional fibrinolytic activity. Introduction Intra-abdominal adhesions, a frequent occurrence after abdominal surgery and peritoneal inflammation, are the commonest cause of small bowel obstruction in developed countries.1 The presence of such adhesions complicates further abdominal surgery. After peritoneal injury a fibrin-rich inflammatory exudate is released into the peritoneal cavity.2 The resulting delicate fibrinous adhesions are either lysed by the fibrinolytic system or are organised into permanent fibrous adhesions by the incorporation of collagen.3 Reduction in peritoneal fibrinolytic activity, as occurs after injury or bacterial peritonitis,2-4 is associated with adhesions. Peritoneal plasminogen activating activity is also reduced by ischaemia and inflammation.5 We have studied the principal activators and inhibitors of fibrinolysis in control and inflamed peritoneum.
Patients and methods Patients 10 patients undergoing emergency surgery (appendicitis 7, perforated viscus 3), who had peritoneal inflammation, and 10 control patients, presumed to have normal peritoneum, having
Green, UK) as soon as possible after opening the peritoneal cavity. was dissected off the underlying tissue. The specimen was wrapped in aluminium foil, frozen in dry ice, and then
The disc of tissue transferred to
a
freezer
at -
80°C.
Preparation of peritoneal homogenate. The peritoneal biopsy specimens were thawed at room temperature and weighed. Each sample was washed with 0-5 ml rinsing solution (5 mmol/I sodium dihydrogen phosphate, 0-15 mol/l sodium chloride, pH 74) and placed into 1 ml homogenising solution (2-5 mmol/l sodium dihydrogen phosphate, 0-075 mol/1 sodium chloride, 025% ‘Triton X100’, [Sigma, UK] pH 78) in a small plastic tube on ice. The tissues were then homogenised in an ’Ultra-Turrax’ (Janke and Kunzel, Staufen, West Germany) homogeniser for 30 s. The homogenates were centrifuged at 12 000 xg for 20 min at 4°C. Aliquots of 0-25 ml of supernatant were stored at - 20°C until assay. All samples were assayed within 4 weeks. Determination of plasminogen activator. Lyophilised polyclonal goat anti-tissue plasminogen activator antibody and antiurokinase plasminogen activator antibody (Biopool, Umea, Sweden) were reconstituted with 1 ml of buffer (20 mol/l sodium dihydrophosphate, 100 mol/1 sodium chloride, pH 7-3). The reconstituted antibody was serially diluted with 100 ui amounts of buffer to a maximum dilution of 1 in 2.16 Tissue homogenates from 6 samples of control perioneum were brought to room temperature. 20 ltl from each of the samples was incubated with 20 µlfrom each of the serial antibody dilutions for 30 min at 37°C. From each peritoneal homogenate/antibody dilution sample, 20 ul of solution was placed in the central well of a plasminogen-containing fibrin plate.5 The following sample controls were also analysed: dilution buffer, anti-tissue plasminogen activator antibody, anti-urokinase plasminogen activator antibody, peritoneal homogenate with goat serum, and peritoneal homogenate alone (the last for assay of plasminogen activating activity). Standard solutions of human tissue plasminogen activator (2nd international standard, National Institute for Biological Standards and Controls, Mill Hill, UK), reconstituted in sterile water, were also placed on fibrin plates. The fibrin plates were then incubated for 24 h at 37°C. Maximum and minimum diameters of the zone of lysis around the central well were measured and the mean value calculated. A standard plot of diameter of fibrin plate lysis against log tissue plasminogen activator concentration was constructed for the tissue plasminogen activator standards and the line of best fit was calculated by least squares regression analysis. From this standard curve the plasminogen activating activity of the control and sample solutions was calculated. For samples incubated with anti-tissue plasminogen activator antibody and anti-urokinase plasminogen activator antibody the titre inhibiting fibrin plate lysis by 50% or greater, by comparison with peritoneal homogenates alone, was recorded.
elective surgery were studied. Patients gave informed consent to inclusion in this study, which was approved by the hospital ethical committee.
Methods 6
Biopsy technique. Parietal peritoneum was biopsied (disposable, diameter biopsy punch, Stiefel Laboratories, Woobum
mm
ADDRESS Academic Surgical Unit, St Mary’s Hospital (M. N. Vipond, FRCS, S. A. Whawell, BSc, H. A F. Dudley, FRCS), and Department of Surgery, Hammersmith Hospital, London, UK (J N. Thompson, FRCS) Correspondence to Mr M N Vipond Academic Surgical Unit, St Mary’s Hospital, London W2 1NY, UK
1121
Fig 1- -log2 titre of tissue plasminogen activator antibody (anti-tPA) and anti-urokinase plasminogen activator antibody (anti-uPA) required to give 50% inhibition of plasminogen activating activity in control peritoneum Fig 3-Concentration of plasminogen activator inhibitor-1 (PAI-1) in control and inflamed peritoneum. Molecular changes in inflammation. Tissue homogenates from all control and inflamed peritoneal biopsy specimens were brought to room temperature. For each sample the following assays were carried out in duplicate. Plasminogen activating activity was determined by the fibrin plate technique described above. The results for plasminogen activating activity were expressed in international units of tissue plasminogen activator per cm2 peritoneum (IU I crn2). The lower limit of sensitivity of the assay was 0 04 IU/cm2. Both tissue plasminogen activator and plasminogen activator inhibitor-1 were measured by enzyme-linked immunosorbent assay (Tintelize, Fluorochem, Old Glossop, UK). a2-antiplasmin was measured by chromogenic assay (KabiVitrum, Uxbridge, UK). The lower limits of sensitivity for the assays were 0-05
ng/ml (tissue plasminogen activator), 2-5 ng/ml (plasminogen
activator inhibitor-1) and 0-05 µM/1 (&agr;2-antiplasmin). The coefficients of variation of the tissue plasminogen activator assay were 6% (intra-assay) and 10% (inter-assay), and for plasminogen activator inhibitor-1 were 4% (intra-assay) and 9% (inter-assay).
Statistical methods. For graphic presentation of antibody titres, Iog2 was used so that titres could be represented as linear integers without unwieldy large numbers. For example, — log21indicates a titre of 1 in 2, and -logzl6 a titre of 1 in 65 536. The Mann-Whitney U and Spearman rank correlation tests were used. -
Results Determination of plasminogen activator The control samples (dilution buffer, anti-tissue plasminogen activator antibody, and anti-urokinase plasminogen activator antibody) did not lyse fibrin plates. Plasminogen activating activity of peritoneal homogenate with goat serum and peritoneal homogenate alone were similar. The antibody titre required to inhibit plasminogen activating activity by 50% or greater is shown in fig 1. Median titres of 1 in 2 12 s anti-tissue plasminogen activator antibody and 1 in 2anti-urokinase plasminogen activator antibody were required to inhibit plasminogen activating Tissue activity of control peritoneum (p<0-01). activator concentration correlated with plasminogen for the 10 control peritoneal plasminogen activating activity data not samples (correlation coefficient 0-75, p<005, shown).
Molecular changes in inflammation
Plasminogen activating activity
of control
(median
12-0
IU/cm2) and of inflamed peritoneum (median 0 07 IVlcm2) (p < 0-001) determined by fibrin plate lysis is shown in fig 2. Tissue plasminogen activator assay was similar in control (median 1-03 ng/ml) and inflamed peritoneum (median 0-97 ng/ml, data not shown). &agr;2-antiplasmin was detected in neither control nor inflamed peritoneum. Plasminogen activator inhibitor-1was not present in control peritoneum but was detected in all samples of inflamed peritoneum
(median 8-45 ng/ml, p < 0-001, fig 3). Discussion Fig 2-Plasminogen activating activity (PAA) of control inflamed peritoneum.
and
In 1969,
peritoneal
and colleagues’6 suggestion that mesothelial cells can activate plasminogen led to
Myhre-Jensen
1122
the hypothesis that the plasminogen activating activity of the peritoneum determines whether inflammation is followed
by fibrinolysis or organisation. Our study has shown that tissue plasminogen activator is the principal physiological plasminogen activator in peritoneal tissue and that the reduction in functional fibrinolytic activity seen in inflammation is mediated by plasminogen activator inhibitor-1. These changes in the peritoneum are similar to those that occur in plasma.7 Although the cellular origin of tissue plasminogen activator and plasminogen activator inhibitor-1in peritoneal tissue has not been ascertained, mesothelial cells may produce tissue plasminogen activator, as do the morphologically similar endothelial cells.8 Mesothelial tissue plasminogen activator might, by complexing with fibrin and plasminogen, prevent the adhesion of peritoneal surfaces. Various pharmacological agents, including heparin, streptokinase, and urokinase, have been investigated for use in the prophylaxis of adhesions9,10 but results have been disappointing. Locally active preparations of tissue plasminogen activator might prevent adhesion formation,11,12 possibly by competitive inhibition of plasminogen activator inhibitor-1. Our studies suggest that intraperitoneal plasminogen activator inhibitor-1 monoclonal antibody or other plasminogen activator inhibitor-1 inhibitors might also be effective in the prophylaxis of adhesions.
REFERENCES 1. Bevan PG. Adhesive obstruction. Ann R Coll Surg Engl 1984; 66: 164-69. 2. Ellis H, Harrison W, Hugh TB. The healing of peritoneum under normal and pathological conditions. Br J Surg 1965; 52: 471-76. 3. Raftery AT. Regeneration of peritoneum: A fibrinolytic study. J Anat 1979; 129: 659-64. 4. Hau T, Payne D, Simmons RL. Fibrinolytic activity of the peritoneum during experimental peritonitis. Surg Gynecol Obstet 1979; 148: 415-18. 5. Thompson JN, Paterson-Brown S, Harbourne T, Whawell SA, Kalodiki E, Dudley HAF. Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation. Br J Surg 1989; 76: 382-84. 6. Myhre-Jensen O, Larsen SB, Astrup T. Fibrinolytic activity in serosal and synovial membranes. Arch Pathol 1969; 88: 623-30. 7. Rånby M, Brändström A. Biological control of tissue plasminogen activator-mediated fibrinolysis. Enzyme 1988; 40: 130-43. 8. Hanss M, Collen D. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by cultured human endothelial cells: modulation by thrombin, endotoxin, and histamine. J Lab Clin Med
1987; 109: 97-104.
HA, Otubo JAM. Value of a single intraperitoneal dose of heparin in prevention of adhesion formation: an experimental evaluation in rats. Int J Fertil 1987; 32: 332-35. 10. Rivkind AI, Lieberman N, Durst AL. Urokinase does not prevent abdominal adhesion formation in rats. Eur Surg Res 1985; 17: 9. Al-Chalabi
254-58. 11. Menzies D, Ellis H. Intra-abdominal adhesions and their prevention by topical tissue plasminogen activator. J R Soc Med 1989; 82: 534-35. 12. Doody KJ, Dunn RC, Buttram VC. Recombinant tissue plasminogen activator reduces adhesion formation in a rabbit uterine horn model. Fertil Steril 1989; 51: 509-12.
Preliminary report: follow-up after dynamic cardiomyoplasty
Five patients were studied 5-13 months after dynamic cardiomyoplasty for refractory heart failure. In two, muscle flap stimulation caused a pronounced increase in cardiac index (mean 55%) and ejection fraction (mean 75%); no patient showed improvement in cardiac filling pressure. 2 years after surgery, one of the patients with died from improvement haemodynamic ventricular fibrillation, and histochemistry of the stimulated muscle flap revealed predominantly fatigue-resistant type I fibres, without evidence of fibrosis. In selected cases, dynamic cardiomyopathy could be of long-term benefit.
notion that, with a progressive pacing protocol, glycolytic fatigue-prone muscle fibres can be transformed into oxidative fatigue-resistant fibres. The operation has been proposed not only for ventricular reinforcement but also for ventricular substitution. In some instances it has been proposed as an alternative to cardiac transplantation, but few long-term results have been reported.4-6 The technique is illustrated in fig 1. We record here our findings in five consecutive patients who underwent successful dynamic cardiomyoplasty, after
Introduction
ADDRESSES: Department of Cardiology, Boucicaut Hospital, 75015 Paris, France (A. A. Hagege, MD, M Desnos, MD, F. Fernandez, MD, F. Fontaliran, MD, C. Guerot, MD); Department of Cardiovascular Surgery, Broussais Hospital, 75014 Paris, France (J. C. Chachques, MD, A. Carpentier, MD). Correspondence to Dr Albert A. Hagege, Department of Cardiology, Boucicaut Hospital, 78 rue de la convention, 75015 Paris, France.
Dynamic cardiomyoplasty is a new technique for assisting the failing heart. A latissimus dorsi muscle flap is wrapped around the ventricles and stimulated in synchrony with cardiac systolic activity.1-3 The method is based on the
long-term follow-up.
Peritoneal fibrinolytic activity and intra-abdominal adhesions
The mechanisms leading to reduction of peritoneal fibrinolytic activity in conditions that are associated with the formation of intra-abdominal adhesions were studied. Tissue plasminogen activator was found, by antibody inhibition techniques, to be the activator of fibrinolysis in homogenates of control peritoneum (n=6). Homogenates of control (n=10) and inflamed
peritoneum (n=10) were analysed. Plasminogen activating activity was much lower in inflamed peritoneum (median 0·07 IU/cm2) than in control tissue (median 12·0 IU/cm2) (p<0·001). Levels of tissue plasminogen activator and &agr;2-antiplasmin were
similar in both control and inflamed tissue.
Plasminogen activator inhibitor-1, not detectable in control peritoneum, was present in inflamed tissue and might be the reason for the reduction in functional fibrinolytic activity. Introduction Intra-abdominal adhesions, a frequent occurrence after abdominal surgery and peritoneal inflammation, are the commonest cause of small bowel obstruction in developed countries.1 The presence of such adhesions complicates further abdominal surgery. After peritoneal injury a fibrin-rich inflammatory exudate is released into the peritoneal cavity.2 The resulting delicate fibrinous adhesions are either lysed by the fibrinolytic system or are organised into permanent fibrous adhesions by the incorporation of collagen.3 Reduction in peritoneal fibrinolytic activity, as occurs after injury or bacterial peritonitis,2-4 is associated with adhesions. Peritoneal plasminogen activating activity is also reduced by ischaemia and inflammation.5 We have studied the principal activators and inhibitors of fibrinolysis in control and inflamed peritoneum.
Patients and methods Patients 10 patients undergoing emergency surgery (appendicitis 7, perforated viscus 3), who had peritoneal inflammation, and 10 control patients, presumed to have normal peritoneum, having
Green, UK) as soon as possible after opening the peritoneal cavity. was dissected off the underlying tissue. The specimen was wrapped in aluminium foil, frozen in dry ice, and then
The disc of tissue transferred to
a
freezer
at -
80°C.
Preparation of peritoneal homogenate. The peritoneal biopsy specimens were thawed at room temperature and weighed. Each sample was washed with 0-5 ml rinsing solution (5 mmol/I sodium dihydrogen phosphate, 0-15 mol/l sodium chloride, pH 74) and placed into 1 ml homogenising solution (2-5 mmol/l sodium dihydrogen phosphate, 0-075 mol/1 sodium chloride, 025% ‘Triton X100’, [Sigma, UK] pH 78) in a small plastic tube on ice. The tissues were then homogenised in an ’Ultra-Turrax’ (Janke and Kunzel, Staufen, West Germany) homogeniser for 30 s. The homogenates were centrifuged at 12 000 xg for 20 min at 4°C. Aliquots of 0-25 ml of supernatant were stored at - 20°C until assay. All samples were assayed within 4 weeks. Determination of plasminogen activator. Lyophilised polyclonal goat anti-tissue plasminogen activator antibody and antiurokinase plasminogen activator antibody (Biopool, Umea, Sweden) were reconstituted with 1 ml of buffer (20 mol/l sodium dihydrophosphate, 100 mol/1 sodium chloride, pH 7-3). The reconstituted antibody was serially diluted with 100 ui amounts of buffer to a maximum dilution of 1 in 2.16 Tissue homogenates from 6 samples of control perioneum were brought to room temperature. 20 ltl from each of the samples was incubated with 20 µlfrom each of the serial antibody dilutions for 30 min at 37°C. From each peritoneal homogenate/antibody dilution sample, 20 ul of solution was placed in the central well of a plasminogen-containing fibrin plate.5 The following sample controls were also analysed: dilution buffer, anti-tissue plasminogen activator antibody, anti-urokinase plasminogen activator antibody, peritoneal homogenate with goat serum, and peritoneal homogenate alone (the last for assay of plasminogen activating activity). Standard solutions of human tissue plasminogen activator (2nd international standard, National Institute for Biological Standards and Controls, Mill Hill, UK), reconstituted in sterile water, were also placed on fibrin plates. The fibrin plates were then incubated for 24 h at 37°C. Maximum and minimum diameters of the zone of lysis around the central well were measured and the mean value calculated. A standard plot of diameter of fibrin plate lysis against log tissue plasminogen activator concentration was constructed for the tissue plasminogen activator standards and the line of best fit was calculated by least squares regression analysis. From this standard curve the plasminogen activating activity of the control and sample solutions was calculated. For samples incubated with anti-tissue plasminogen activator antibody and anti-urokinase plasminogen activator antibody the titre inhibiting fibrin plate lysis by 50% or greater, by comparison with peritoneal homogenates alone, was recorded.
elective surgery were studied. Patients gave informed consent to inclusion in this study, which was approved by the hospital ethical committee.
Methods 6
Biopsy technique. Parietal peritoneum was biopsied (disposable, diameter biopsy punch, Stiefel Laboratories, Woobum
mm
ADDRESS Academic Surgical Unit, St Mary’s Hospital (M. N. Vipond, FRCS, S. A. Whawell, BSc, H. A F. Dudley, FRCS), and Department of Surgery, Hammersmith Hospital, London, UK (J N. Thompson, FRCS) Correspondence to Mr M N Vipond Academic Surgical Unit, St Mary’s Hospital, London W2 1NY, UK
1121
Fig 1- -log2 titre of tissue plasminogen activator antibody (anti-tPA) and anti-urokinase plasminogen activator antibody (anti-uPA) required to give 50% inhibition of plasminogen activating activity in control peritoneum Fig 3-Concentration of plasminogen activator inhibitor-1 (PAI-1) in control and inflamed peritoneum. Molecular changes in inflammation. Tissue homogenates from all control and inflamed peritoneal biopsy specimens were brought to room temperature. For each sample the following assays were carried out in duplicate. Plasminogen activating activity was determined by the fibrin plate technique described above. The results for plasminogen activating activity were expressed in international units of tissue plasminogen activator per cm2 peritoneum (IU I crn2). The lower limit of sensitivity of the assay was 0 04 IU/cm2. Both tissue plasminogen activator and plasminogen activator inhibitor-1 were measured by enzyme-linked immunosorbent assay (Tintelize, Fluorochem, Old Glossop, UK). a2-antiplasmin was measured by chromogenic assay (KabiVitrum, Uxbridge, UK). The lower limits of sensitivity for the assays were 0-05
ng/ml (tissue plasminogen activator), 2-5 ng/ml (plasminogen
activator inhibitor-1) and 0-05 µM/1 (&agr;2-antiplasmin). The coefficients of variation of the tissue plasminogen activator assay were 6% (intra-assay) and 10% (inter-assay), and for plasminogen activator inhibitor-1 were 4% (intra-assay) and 9% (inter-assay).
Statistical methods. For graphic presentation of antibody titres, Iog2 was used so that titres could be represented as linear integers without unwieldy large numbers. For example, — log21indicates a titre of 1 in 2, and -logzl6 a titre of 1 in 65 536. The Mann-Whitney U and Spearman rank correlation tests were used. -
Results Determination of plasminogen activator The control samples (dilution buffer, anti-tissue plasminogen activator antibody, and anti-urokinase plasminogen activator antibody) did not lyse fibrin plates. Plasminogen activating activity of peritoneal homogenate with goat serum and peritoneal homogenate alone were similar. The antibody titre required to inhibit plasminogen activating activity by 50% or greater is shown in fig 1. Median titres of 1 in 2 12 s anti-tissue plasminogen activator antibody and 1 in 2anti-urokinase plasminogen activator antibody were required to inhibit plasminogen activating Tissue activity of control peritoneum (p<0-01). activator concentration correlated with plasminogen for the 10 control peritoneal plasminogen activating activity data not samples (correlation coefficient 0-75, p<005, shown).
Molecular changes in inflammation
Plasminogen activating activity
of control
(median
12-0
IU/cm2) and of inflamed peritoneum (median 0 07 IVlcm2) (p < 0-001) determined by fibrin plate lysis is shown in fig 2. Tissue plasminogen activator assay was similar in control (median 1-03 ng/ml) and inflamed peritoneum (median 0-97 ng/ml, data not shown). &agr;2-antiplasmin was detected in neither control nor inflamed peritoneum. Plasminogen activator inhibitor-1was not present in control peritoneum but was detected in all samples of inflamed peritoneum
(median 8-45 ng/ml, p < 0-001, fig 3). Discussion Fig 2-Plasminogen activating activity (PAA) of control inflamed peritoneum.
and
In 1969,
peritoneal
and colleagues’6 suggestion that mesothelial cells can activate plasminogen led to
Myhre-Jensen
1122
the hypothesis that the plasminogen activating activity of the peritoneum determines whether inflammation is followed
by fibrinolysis or organisation. Our study has shown that tissue plasminogen activator is the principal physiological plasminogen activator in peritoneal tissue and that the reduction in functional fibrinolytic activity seen in inflammation is mediated by plasminogen activator inhibitor-1. These changes in the peritoneum are similar to those that occur in plasma.7 Although the cellular origin of tissue plasminogen activator and plasminogen activator inhibitor-1in peritoneal tissue has not been ascertained, mesothelial cells may produce tissue plasminogen activator, as do the morphologically similar endothelial cells.8 Mesothelial tissue plasminogen activator might, by complexing with fibrin and plasminogen, prevent the adhesion of peritoneal surfaces. Various pharmacological agents, including heparin, streptokinase, and urokinase, have been investigated for use in the prophylaxis of adhesions9,10 but results have been disappointing. Locally active preparations of tissue plasminogen activator might prevent adhesion formation,11,12 possibly by competitive inhibition of plasminogen activator inhibitor-1. Our studies suggest that intraperitoneal plasminogen activator inhibitor-1 monoclonal antibody or other plasminogen activator inhibitor-1 inhibitors might also be effective in the prophylaxis of adhesions.
REFERENCES 1. Bevan PG. Adhesive obstruction. Ann R Coll Surg Engl 1984; 66: 164-69. 2. Ellis H, Harrison W, Hugh TB. The healing of peritoneum under normal and pathological conditions. Br J Surg 1965; 52: 471-76. 3. Raftery AT. Regeneration of peritoneum: A fibrinolytic study. J Anat 1979; 129: 659-64. 4. Hau T, Payne D, Simmons RL. Fibrinolytic activity of the peritoneum during experimental peritonitis. Surg Gynecol Obstet 1979; 148: 415-18. 5. Thompson JN, Paterson-Brown S, Harbourne T, Whawell SA, Kalodiki E, Dudley HAF. Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation. Br J Surg 1989; 76: 382-84. 6. Myhre-Jensen O, Larsen SB, Astrup T. Fibrinolytic activity in serosal and synovial membranes. Arch Pathol 1969; 88: 623-30. 7. Rånby M, Brändström A. Biological control of tissue plasminogen activator-mediated fibrinolysis. Enzyme 1988; 40: 130-43. 8. Hanss M, Collen D. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by cultured human endothelial cells: modulation by thrombin, endotoxin, and histamine. J Lab Clin Med
1987; 109: 97-104.
HA, Otubo JAM. Value of a single intraperitoneal dose of heparin in prevention of adhesion formation: an experimental evaluation in rats. Int J Fertil 1987; 32: 332-35. 10. Rivkind AI, Lieberman N, Durst AL. Urokinase does not prevent abdominal adhesion formation in rats. Eur Surg Res 1985; 17: 9. Al-Chalabi
254-58. 11. Menzies D, Ellis H. Intra-abdominal adhesions and their prevention by topical tissue plasminogen activator. J R Soc Med 1989; 82: 534-35. 12. Doody KJ, Dunn RC, Buttram VC. Recombinant tissue plasminogen activator reduces adhesion formation in a rabbit uterine horn model. Fertil Steril 1989; 51: 509-12.
Preliminary report: follow-up after dynamic cardiomyoplasty
Five patients were studied 5-13 months after dynamic cardiomyoplasty for refractory heart failure. In two, muscle flap stimulation caused a pronounced increase in cardiac index (mean 55%) and ejection fraction (mean 75%); no patient showed improvement in cardiac filling pressure. 2 years after surgery, one of the patients with died from improvement haemodynamic ventricular fibrillation, and histochemistry of the stimulated muscle flap revealed predominantly fatigue-resistant type I fibres, without evidence of fibrosis. In selected cases, dynamic cardiomyopathy could be of long-term benefit.
notion that, with a progressive pacing protocol, glycolytic fatigue-prone muscle fibres can be transformed into oxidative fatigue-resistant fibres. The operation has been proposed not only for ventricular reinforcement but also for ventricular substitution. In some instances it has been proposed as an alternative to cardiac transplantation, but few long-term results have been reported.4-6 The technique is illustrated in fig 1. We record here our findings in five consecutive patients who underwent successful dynamic cardiomyoplasty, after
Introduction
ADDRESSES: Department of Cardiology, Boucicaut Hospital, 75015 Paris, France (A. A. Hagege, MD, M Desnos, MD, F. Fernandez, MD, F. Fontaliran, MD, C. Guerot, MD); Department of Cardiovascular Surgery, Broussais Hospital, 75014 Paris, France (J. C. Chachques, MD, A. Carpentier, MD). Correspondence to Dr Albert A. Hagege, Department of Cardiology, Boucicaut Hospital, 78 rue de la convention, 75015 Paris, France.
Dynamic cardiomyoplasty is a new technique for assisting the failing heart. A latissimus dorsi muscle flap is wrapped around the ventricles and stimulated in synchrony with cardiac systolic activity.1-3 The method is based on the
long-term follow-up.