Experimental assessment of thrombogenicity in vascular prostheses before and during prostaglandin E1 treatment.

The effect of prostaglandin E1 (PGE1; Prostavasin), a powerful platelet blocking agent, was assessed on various new synthetic or biological prostheses in a 6-min in vivo extra corporal arterio-venous (AV) shunt. In eight anaesthetised and heparinised minipigs (weight 25.1 +/- 1.9 kg) the following materials were tested before and during PGE1 infusion (alprostadil-alpha-CD; 40 micrograms/50 ml NaCl/50 min or 0.8 microgram/min): PTFE, (Gore-tex, TW, 4 mm ID); Xenograft, Biologic (Solcograft, 5 mm ID), (non-porous) and Dacron (Atrium, 4 mm ID); polyurethane 1 (Braun-Melsungen, 4 mm ID); polyurethane 2 (S. Gogolewski, 4 mm ID), (porous). Technetium-labelled platelet deposition and blood flow were measured; morphology was assessed by scanning electron microscopy (SEM) and histology. Compared to control levels, PGE1 infusion had a significant systemic effect on mean arterial pressure required by the protocol (MAP 82.6 vs. 66.6 mm Hg; p < 0.001) and flow (173.6 vs. 134.8 mm/min; p < 0.001). Standardised platelet counts per area showed a marked overall decrease from 197 to 130 counts/min/mm2; NS). The morphological assessment by SEM showed a slight increase of surface cellular deposition (score: 6.7 vs. 8.3), the histology score being unchanged (3.9 vs. 3.7). Looking at deposition of platelets for each prosthesis, the porous materials showed a net improvement after PGE1 treatment as compared to non-porous materials. We conclude that PGE1 may be of benefit by reducing platelet deposition in synthetic porous vascular prostheses in the early phase.

[Heart sounds--a mathematical transformation of blood pressure? On the origin of heart sounds]. / Der Herzschall--eine mathematische Transformation des Blutdrucks? Uber den Ursprung der Herztöne.

Two main theories exist concerning the origin of the heart sounds. The first proposes that rapid pressure fluctuations cause the cardiac valve leaflets to vibrate and produce the sound. The second theory suggests that sudden pressure perturbations cause the entire cardiohemic mass to vibrate as a whole. In 35 patients (26 men and 9 women, aged 18 to 73) with various heart diseases microtransducer catheters (Millar) were used to simultaneously record aortic pressures and aortic internal phonocardiograms in order to determine if they had a common mode of origin and propagation. The propagation velocities of the first heart sound and the foot of the aortic pressure pulse were found to be similar, 5.24 +/- 0.61 m/s and 5.97 +/- 1.87 m/s respectively (+/- SE). It was possible to derive facsimiles of the aortic internal phonocardiogram by double differentiation of the corresponding aortic pressure pulse and conversely to derive the pressure pulse by double integration of the phonocardiogram. These data support the concept that the low-frequency pressure variations produced by the entire cardiohemic mass, which predominate in the aortic pressure pulse waveforms, are generated and propagated in the same manner as the high-frequency pressure variations, which are the first and second heart sounds.

2,3-butanediol in experimental myocardial ischaemia in pigs.

To investigate the role of 2,3-butanediol in myocardial ischaemia we analysed this compound in pig's myocardium and blood. Ischaemia was induced by ligation of a coronary artery. In the first study we found significantly higher levels of 2,3-butanediol in the homogenate of ischaemic myocardium than in non-ischaemic myocardium. The lactate concentration was also significantly elevated. In the second study, where ischaemia was similarly induced, and where reperfusion was achieved by re-opening the ligated coronary artery after 20 min, 2,3-butanediol in peripheral blood was found to increase significantly. In the pigs in which the coronary artery was not re-opened, the 2,3-butanediol level in peripheral blood was unchanged. We conclude that in pigs' anaerobic myocardia accumulation of 2,3-butanediol occurs; if the myocardium is reperfused this metabolite also appears in the blood.

90Y-resin particles--animal experiments on pigs with regard to the introduction of superselective embolization therapy.

Resin particles (diameter 45-75 microns) were labelled with 90Y, suspended in a glucose/dextran solution and infused into the kidneys of 3-month-old pigs (tumour model). Both kidneys of each animal were embolized with particles, but only one with active (90Y loaded) particles and the other, for comparison, with inactive particles. The organ measurements showed less than 1% of injected activity in bone, bone marrow, liver and lung compared to greater than 99% retention by the kidneys. Only minimal shunted activity was found in blood (less than 0.27%) and urine (less than 0.07%). There was a clear shrinkage of the 90Y-treated kidneys with a reduction in weight of up to 50%. Histologically, the ischaemic lesions (infarcts and atrophy) were clearly more pronounced and extensive in the 90Y-embolized kidneys than in the non-radioactive embolized kidneys. Furthermore, severe arterial wall changes and fibrotic necrosis due to radiation damage were observed in the 90Y-treated kidneys. It is concluded that with intra-arterially applied particles a dose of about 100 Gy is sufficient to completely destroy tissue-specific structures. Complications due to acute necrosis or inflammatory reactions were not observed, and there were no shunt related alterations seen in the liver or lungs. The 90Y-loaded resin particles are considered suitable for a super selective intra-arterial radioembolization.

[Evaluation of recent vascular prostheses in the arteriovenous shunt]. / Erprobung neuer Gefässprothesen im arterio-venösen Shunt.

Prosthetic vascular replacement materials are still suboptimal especially for distal peripheral and coronary bypass grafts due to the small caliber and high occlusion rates. Therefore new vascular grafts have been assessed with respect to blood compatibility, thrombogenicity and host pretreatment. In 12 heparinized minipigs (25 kg), a total of 120 small caliber grafts (i.d. 3.0 mm) were perfused (6 min) in a femoro-femoral arteriovenous shunt (AVS). Materials included: Dacron (Atrium), PTFE (Gore), Polyurethanes (PU), Auto- and Xenografts. Animals were treated preoperatively with fishoil (3 g EPA/QD x 3 weeks = group I), perioperatively with prostaglandins (PGE1 = group II) or with fishoil and graft incubation in plasma proteins (= group III) and compared to controls without pretreatment (= group 0). We measured flow, deposition of marked thrombocytes (HMPAO-Tc* per area and per weight). - Blood flow was similar in AVS for all groups and materials (168 +/- 86 ml/min, p = NS). There was no significant correlation in deposition of marked thrombocytes and host pretreatments (group 0: controls = 7356 counts/area, group I: fishoil = 6807. group II: PGE1 = 7864). However graft incubation in plasma proteins significantly lowered deposition of marked thrombocytes (1766 in group III vs. 7356 in group 0: p less than 0.05). And significant differences of thrombocyte counts where found between the different materials: Autografts less than PTFE less than Xenografts less than Small Pore PU less than Dacron less than Large Pore PU.--AVS is a useful tool to determine early thrombogenicity in prosthetic vascular replacement materials and to assess the effect of different host pretreatments.

[Energy metabolism of the brain, detected with 31-P magnetic resonance spectroscopy during extracorporeal circulation in the rabbit]. / Energiestoffwechsel des Hirns, erfasst mit 31-P Magnet-Resonanz-Spektroskopie während des extrakorporalen Kreislaufes beim Kaninchen.

The question of a possible brain damage during open heart surgery using extracorporeal circulation is still a problem, especially in infants with circulatory arrest under deep hypothermia. During the last years Magnetic Resonance Spectroscopy was developed, and with this method we have now a possibility to study brain energy metabolism non-invasively and continuously. Our aim was to develop an animal model (rabbit) for studying brain energy metabolism by 31-P Magnetic Resonance Spectroscopy during extracorporeal circulation. In a first step we have shown that the influence of hypothermia on energy metabolism in the brain can be measured in the intact animal by MR-Spectroscopy. In a second step a non-magnetic heart-lung machine for rabbits was constructed and is described here. We get a completely normal brain spectrum in the beginning and after two hours of extracorporeal circulation. The spectrum is also normal on extracorporeal circulation at 35 degrees C and during cooling down to 18 degrees C. With this animal model it will be possible to study different variables of extracorporeal circulation such as duration of circulatory arrest under deep hypothermia or changes of the priming including pharmacological changes.

Low-energy He-Ne-laser irradiation of the bovine mammary gland.

The bovine mammary gland was used to examine the effects of low-energy laser irradiation. Laser irradiation with 25 mW on an area of 7.5 cm in diameter on the right front quarter lasted 30 minutes daily for five consecutive days. Six cows were used to assess the effects of this treatment on the healthy mammary gland. Subclinical mastitis was induced in twelve quarters of the same six cows with oyster glycogen and the same laser protocol was followed on the right front quarters. In both experiments the left hind quarter served as a control. Four cases of spontaneous subclinical mastitis were treated in the same way. Parameters measured included milk yield, somatic cell count, conductivity, Na/K-ratio in milk serum, and fat, protein and lactose concentrations in milk. The bovine mammary gland was chosen in view of its particular suitability for the assessment of changes in biosynthetic capacity and inflammation course. In several respects, mastitis may be compared to currently recommended indications. No evidence for any stimulation of the healthy mammary gland or therapeutic effects on mastitis by low-energy He-Ne-laser could be found.

Experimental pancreaticosplenic composite transplantation in the pig. Operative technique and assessment of graft function.

A large animal model for substitutive pancreaticosplenic composite transplantation with urinary drainage to the bladder has been developed in the pig. Transplantations were performed in 7 nontissue-typed donor-recipient combinations without immunosuppressive medication. Six recipients showed perfect graft function at least until the 5th postoperative day. Blood glucose, intravenous glucose tolerance tests and urine amylase concentrations proved to be sensitive markers of graft function. Scintigraphic follow-up examination with 99mTc tin colloid could only record perfusion of the splenic transplantation. With this model the role of the spleen in pancreaticosplenic composite transplantations can be studied in forthcoming experiments.

Surgical repair of the kidney after blunt lesions of intermediate degree using a Vicryl mesh: an experimental study.

Twelve experimentally induced blunt renal lesions in pigs were treated either with an alloplastic renal capsule made of semi-elastic Vicryl mesh or with homologous pig fibrin adhesive or with through-and-through chromic catgut sutures as controls. The Vicryl mesh capsule was made by the Ethnor Company (Paris, France) to our specifications. The postoperative isotope nephrograms, which were repeated until the Vicryl had been fully resorbed, showed good renal function in every case. However, when compared to the controls, the kidneys which had been repaired with Vicryl mesh contained considerably less scar tissue at the site of parenchymal rupture and showed neither perirenal fibrosis nor atrophy of the parenchyma in the vicinity of the capsule. Our preliminary results seem to confirm that simple and rapid surgical treatment of moderately severe blunt renal lesions is possible using the alloplastic Vicryl mesh capsule. The method may also be suitable for reconstruction of the parenchyma following multiple nephrotomies, such as for removal of staghorn calculus, and experimental investigations are under way to clarify this point.

Perfusate oncotic pressure during cardiopulmonary bypass. Optimum level as determined by metabolic acidosis, tissue edema, and renal function.

Current practice with respect to the use of a dilutional prime for cardiopulmonary bypass (CPB) varies widely, and the safe lower limit of perfusate protein content has not been defined. We studied this question in 75 rabbits subjected to a 1-hour CPB with a perfusate colloid osmotic pressure (COP) ranging from 26 to 4 mm Hg. Metabolic acidosis was inversely related to COP; acid-base equilibrium is thus best maintained with a high perfusate protein content. Tissue edema rapidly increased at COP levels below 16 mm Hg, i.e. with a protein level less than 4.2 g%. Urinary excretion during CPB was antagonized by the COP, the reason being that glomerular filtration rate was proportional to the difference between perfusion pressure and COP. The safety margin for renal function during CPB thus widens with a decreasing perfusate protein content. We conclude that the optimum levels of perfuste oncotic pressure and protein content during experimental cardiopulmonary bypass are 16 mm Hg and 4.2 g%.

Tolerance and resistance of myocardium to anoxia: experimental studies.

We shall emphasize the notion of wide variability in the tolerance and resistance to anoxia of the myocardium, although the most important parameters are temperature and time. They can be modified widely by accompanying physical or biochemical conditions: --Cardiac distension and drugs inducing cardiac arrest; --Resuscitative perfusion; --The effect of some biochemical components is more likely explained by their possible action on the mitochondriae (glyoxilic acid-Isoproterenol). The study of the mitochondriae alone can explain the different behaviours of hearts subjected to anoxia in various situations.