Platelet Volume: Density Relationships in Normal and Acutely Bled Dogs

The relationship between platelet volume and platelet density was studied in normal dogs and in dogs subjected to acute blood loss.
Frequency distribution histograms of platelet densities were obtained by centrifuging diluted whole blood over a series of 13 silicone solutions varying in specific gravity from 1.007 to 1.065 and determining the percentage of platelets that remained in the supernatants above the silicone after centrifugation for 2 min at 9500 g. Frequency distribution histograms of platelet volumes were obtained using the Model B Coulter Counter with the Coulter Model H particle size analyser.
Platelets of normal dogs have a skewed distribution of densities. The mean density is approximately 1.020 but the plateau region on the cumulative distribution of platelet densities is not reached until specific gravity 1.045-1.050. Mean platelet volume increases as density increases.
When platelet production was increased following acute blood loss, both mean density and mean volume increased abruptly, but the change in density histograms was more prolonged as well as more striking than change in mean density. Results of serial observations suggest that the large dense platelets produced following acute blood loss represent an aberrant population and that these platelets do not decrease in volume as they age.     

The Effect of Ellagic Acid on Coagulation in Vivo

Ellagic acid shortens the silicone and glass clotting times of the blood ofdogs, cats, rabbits and rats. The silicone clotting time is reduced so as tomake it almost equal to the normal glass clotting time for 5 to 30 minutesafter the injection of the agent. There is occasional acceleration of thromboplastin generation in dogs. No other clotting factors were altered significantlyin our experiments.

There were no obvious toxic effects of ellagic acid, and it appears to decrease bleeding in normal animals.

Submitted on February 15, 1965 Accepted on May 8, 1965     

Vicryl-scarf-induced scarring around esophagogastric junction as treatment of esophageal reflux disease

A ringlike structure around the cardia has proven to be sufficient in preventing gastroesophageal reflux, as seen with the Angelchick prosthesis. To avoid the insertion of a nonabsorbable foreign body, a scarring was induced by implanting a Vicryl scarf around the esophagogastric junction. Reflux disease was induced in 18 dogs by circular cardiomyomectomy. In 12 dogs, a Vicryl scarf was laid around the cardia; six dogs served as controls. All of the dogs in the control group either died or had to be sacrificed due to severe reflux esophagitis. All animals receiving the scarf survived the entire duration of the experiment. Endoscopically, only one case of temporary reflux esophagitis could be detected. Long-term pH-metry demonstrated complete reflux suppression after the third postoperative month. Radiographically, esophagogastric transit was always unimpaired. On autopsy, the scarf was found to have changed into a slim scarring after the sixth postoperative month and then remained unaltered. We conclude that inducing scarring around the cardia is as effective in reflux prevention as the silicone ring.     

Voluntary control of an ileal pouch by coordinated electrical stimulation

Ileal reservoirs were constructed in four dogs under general anesthesia and stimulated by means of a constant current generator that produced pulse trains at frequencies between 6 Hz and 1.67 kHz. Stimulation at 6 Hz with 50 ms pulses between amplitudes of 15 and 25 mA uniformly produced pouch contraction and reservoir emptying. Stimulation at other frequencies did not cause pouch emptying although pressure increases were sometimes observed. Such electrical stimulation may be useful for voluntary control of intestinal reservoirs when used as replacement for urinary bladder or colon. The mechanism by which the intestinal contraction is produced appears to be different than that produced by slow wave pacing.     

A regurgitant jet and echocardiographic abnormalities in aortic regurgitation: an experimental study

Acute aortic regurgitation was created experimentally in 21 mongrel dogs to examine the relationship of the regurgitant jet to observed echocardiographic findings. The direction of the regurgitant jet was studied by echo contrast injections in the aortic root. Diastolic fluttering of the anterior mitral leaflet (AML) was noted in all 21 dogs irrespective of direction of the jet. Diastolic fluttering of the interventricular septum (IVS) was noted in six of the seven dogs with a tear of the noncoronary cusp and in one of seven dogs with lesions in the left coronary cusp. In all seven dogs with echocardiographically demonstrated IVS fluttering, a regurgitant jet impinged on the anterior part of the IVS. Amplitude of the AML excursion was not significantly different from control when the lesions involved the noncoronary or the left coronary cusps. However, all seven dogs that had a lesion in the right coronary cusp demonstrated a significant reduction in the amplitude of the AML excursion. The regurgitant jet in these dogs impinged uniformly on the AML. We conclude that diastolic fluttering of the AML is uniformly observed and unrelated to the direction of the regurgitant jet, diastolic fluttering of the IVS is caused by the regurgitant jet impinging upon the IVS, and amplitude of the AML may be reduced as a result of a jet impingement of the AML.     

Functional dendritic cells are required for transfusion-induced sensitization in canine marrow graft recipients

Untransfused dogs given 9.2 Gy total-body irradiation and hematopoietic grafts from DLA-identical littermate donors uniformly achieve sustained engraftment, whereas dogs given three transfusions (Tx) of whole blood from the intended marrow donor 24, 17 and 10 days pretransplant uniformly reject their graft. Sensitization appears to be mediated by peripheral blood mononuclear cells and can be prevented by prior irradiation of the Tx product with UV light, known to inactivate leukocytes, in particular, cells with accessory function. In the present study we investigated which leukocyte population was responsible for Tx-induced sensitization and subsequent marrow graft rejection. Surprisingly, neither monocytes nor macrophages or dendritic cells induced sensitization, and all dogs so treated achieved engraftment; however, all four evaluable dogs transfused with UV- exposed blood to which small numbers of normal dendritic cells (12.5 x 10(3)/kg) were added rejected their marrow graft. Among five dogs given UV-exposed blood and normal monocytes (12.5 x 10(3)/kg) only one rejected its graft, and four achieved sustained engraftment. We conclude that donor dendritic cells are necessary, albeit not sufficient for in vivo sensitization. Sensitization is prevented by elimination or inactivation of dendritic cell.     

Determination of Mechanical and Tribological Properties of Silicone-Based Composites Filled with Manganese Waste

High-tonnage industrial processes generate high amount of waste. This is a growing problem in the whole world. Neutralizing such waste can be time consuming and costly. One of the possibilities of their reuse is to use them as fillers in polymer composites. Introduction of the filler in polymer matrix causes change in its mechanical and tribological properties. In the article, the effect of introducing fillers from post-production waste, and its effect on changing the physical properties of silicone-based composites filled with manganese (II) oxide and waste manganese residue was investigated. The composites were made by gravity casting. Composites with 2.5, 5, 7.5, and 10 wt% of the fillers were examined. The composite materials were subjected to tests such as: density, hardness, resilience, tensile test, abrasion resistance, and ball-on-disc. Microscopic images showed that, the particles of the fillers are uniformly distributed in silicone matrix with the formation of smaller agglomerates. Such agglomerates introduced a discontinuity in the structure of the polymer material, which caused a decrease in the tensile strength and elongation at break for all tested compositions in comparison with the mechanical properties of the silicone used as the matrix. However, it was found that all silicone-based composites filled with manganese (II) oxide and manganese residue showed a reduction in abrasive wear, compared to the reference sample.     

Ultraviolet irradiation of blood prevents transfusion-induced sensitization and marrow graft rejection in dogs

In a canine model using DLA-identical littermate pairs, we have shown that a regimen of three transfusions of donor blood given 24, 17, and 10 days before transplant uniformly leads to marrow graft rejection, presumably due to sensitization to minor (non-DLA) histocompatibility antigens. Untransfused dogs uniformly achieve sustained engraftment. In the present study, we investigated whether the exposure of blood to ultraviolet (UV) light (220-300 nm) prior to transfusion prevented sensitization of the recipient and allowed for successful marrow engraftment. Ten dogs were each given three pretransplant transfusions from the marrow donor. Each transfusion consisted of 50 mL of whole blood exposed in vitro to UV light for a total of 1.35 J/cm2. All ten dogs achieved engraftment. In contrast, all four dogs that had received sham-exposed transfusions rejected their grafts. In vitro studies revealed that although cell viability was not affected, leukocytes contained in UV-exposed blood were unable to function as stimulator cells in mixed leukocyte cultures or as accessory cells in mitogen- stimulated cultures. These data are consistent with the hypothesis that accessory cells are involved in transfusion-induced sensitization. We conclude that in vitro exposure of blood to UV light before transfusion prevents sensitization and allows for subsequent marrow engraftment.     

Ceruletide-induced acute pancreatitis in the dog and its amelioration by exogenous secretin

Large pharmacological doses of ceruletide administered to conscious dogs by intravenous (i.v.) infusion uniformly induce a severe acute necrotizing pancreatitis within 4 h. High-dose i.v. secretin administered for a period of 24 h after cessation of ceruletide infusion resulted in a significant amelioration of the acute pancreatitis compared to non-secretin-treated dogs with acute pancreatitis. Light microscopy of the pancreas in secretin-treated dogs revealed a significant decrease in edema, polymorphonuclear leukocyte infiltration, cell necrosis and acinar cell vacuolization. Serum amylase levels in secretin-treated dogs were significantly decreased compared to non-secretin-treated dogs. The results of this study suggest that high-dose i.v. secretin exerts a beneficial effect on pre-established, ceruletide-induced acute pancreatitis in dogs.     

Ceruletide-induced acute pancreatitis in the dog and its amelioration by exogenous secretin

Summary Large pharmacological doses of ceruletide administered to conscious dogs by intravenous (i.v.) infusion uniformly induce a severe acute necrotizing pancreatitis within 4 h. High-dose i.v. secretin administered for a period of 24 h after cessation of ceruleetide infusion resulted in a significant amelioration of the acute pancreatitis compared to non-secretin-treated dogs with acute pancreatitis. Light microscopy of the pancreas in secretin-treated dogs revealed a significant decrease in edema, polymorphonuclear leukocyte infiltration, cell necrosis and acinar cell vacuolization. Serum amylase levels in secretin-treated dogs were significantly decreased compared to non-secretin-treated dogs. The results of this study suggest that high-dose i.v. secretin exerts a beneficial effect on pre-established, ceruletide-induced acute pancreatitis in dogs.     

Characterization of host cells involved in resistance to marrow grafts in dogs transplanted from unrelated DLA-nonidentical donors

A canine model of marrow transplantation was used to further define the host cells mediating resistance to marrow engraftment. Recipient dogs were given 9.2 Gy of total body irradiation followed by marrow infusion from unrelated DLA-nonidentical donors. No postgrafting immunosuppression was given. At three and ten days posttransplantation recipient marrow and peripheral blood cells were obtained and characterized by the following in vitro studies: morphologic analysis; phenotypic analysis with monoclonal antibodies; assays for natural killer cell (NK) activity; and cocultures with donor marrow to study the effect on donor CFU-GM growth. Daily differential cell counts revealed a proliferation of peripheral blood mononuclear cells approximately eight days posttransplant. By day 10 surviving host cells were uniformly large granular lymphocytes which were phenotypically of T cell lineage, had NK activity, and were capable of suppressing donor marrow CFU-GM growth. Mononuclear cells from dogs given total body irradiation only and no marrow infusion (radiation control group), did not suppress CFU-GM growth when cocultured with marrow from unrelated DLA-mismatched dogs. These results suggest that radioresistant host cells with the morphology of large granular lymphocytes and NK activity and which proliferate in response to the infused donor marrow cells mediate resistance to DLA-nonidentical marrow grafts. It remains to be determined, however, whether in vitro functional studies reflect the mechanisms involved in vivo.     

Myocardial infarct size threshold for two-dimensional echocardiographic detection: sensitivity of systolic wall thickening and endocardial motion abnormalities in small versus large infarcts

This study evaluated the ability of 2-dimensional echocardiography to detect myocardial infarcts of varying sizes. Echocardiography was performed in 29 closed-chest, conscious dogs 2 days after circumflex coronary artery occlusion, and the ultrasonic recordings were analyzed for regional abnormalities in either wall thickening or endocardial motion. Acute myocardial infarct (AMI) size and extent were assessed by morphologic examination. In 5 dogs, coronary occlusion failed to produce AMI; in these dogs wall thickening analysis showed no abnormalities (100% specificity), and endocardial motion analysis yielded 1 false-positive result (80% specificity). In 24 dogs an AMI developed; infarcts larger than 18% of left ventricular mass uniformly resulted in echocardiographically detectable contraction abnormalities. When the AMI was small (1 to 6% of left ventricular mass) and primarily subendocardial, the sensitivity of echocardiography was poor: Only 3 of 10 of the dogs with a small AMI had abnormalities by wall thickening, and only 1 of 10 by endocardial motion. Thus, in this canine model of AMI, 2-dimensional echocardiography was insensitive to small, subendocardial AMI. If this is so in humans as well, it is a potential limitation of the clinical use of echocardiography in the detection of AMI.     

Polyisobutylene and Silicone in Warm Edge Glazing Systems—Evaluation of Long-Term Performance

This article describes the characteristics of one type of sealing system used in warm edge glazing units and analyses the possible causes of damage. Attention was focused on the performance of the dual seal, PIB/silicone system. This type of glazing is widely used for modern curtain walls and roofs of office buildings and shopping centres. Study was focused on PIB displacement defects, which affects both the appearance and thermal performance of the curtain wall system. Wide-ranging field surveys were conducted to examine the problems identified in some office buildings. The information gathered in this way was used to identify the critical areas and causes of seal displacement in the analysed insulating glass units (IGUs). Laboratory tests were conducted on PIB and silicone seals retrieved from the removed defective units. The properties of these materials were determined and used to evaluate the applied edge sealing system and build a representative numerical model. Due to the problems encountered in deriving accurate analytical formulas, finite element (FE) approximation was used as a problem solving tool. The generated FE model and strain analysis were the key parts to obtaining a true representation of the actual behaviour of IGUs subjected to various environmental loads, taking into account the influence of the air cavity. Results of computer simulations and laboratory tests were compared for model validation. The effect of changes in ambient pressure was examined, showing the development of tensile strains in the silicone and PIB, which can lead to debonding. The greatest principal strains occur at the silicone/butyl rubber interface and this location should be considered to be the most susceptible to failure. The observations are summarised in the final conclusions. Additionally, as field study showed, after ten years in service, the percentage of damaged units is considerable. More frequent IGUs inspection should cover both appearance and thermal imaging to detect unsealed panels. From the standpoint of both durability and appearance, dual silicone/PIB should be phased out in favour of modern seal systems.     

A nonflow basis for the vulnerability of the subendocardium

The functional consequences of a transmural gradient of metabolism in the heart were studied in 19 dogs. The technique of retrograde blood flow diversion after coronary occlusion was used to deplete the ischemic myocardium of blood flow. Blood flow was uniformly and equally depleted in all layers, averaging 0.044 ml/min per g. With oxygen supply a controlled variable, transmural differences in metabolic demand can be addressed. In groups of dogs severe myocardial ischemia was induced for periods of 20 to 90 minutes. No necrosis was noted after 20 minutes of ischemia. Beginning at 30 minutes of blood flow depletion, necrosis progressed from the endocardium toward the epicardium in a "wave front" pattern. At 90 minutes of ischemia, approximately 70% of the area at risk was necrotic. Thus, the relative vulnerability of the endocardium as compared with the epicardium is due to nonflow factors, and probably dictated by transmural differences in metabolic activity. It would appear that myocardial metabolism as compared with blood flow occupies a primary and overriding role during the first 20 minutes of ischemia. Furthermore, differences in transmural metabolism also dictate subendocardial vulnerability for ischemic periods greater than 20 minutes, irrespective of blood flow. The role of blood flow in these events may be to modulate the rate of the transmural wave front of progressing necrosis after 20 minutes of ischemia.     

Early and late outcome following deployment of a new flexible tantalum intracoronary stent in dogs.

A new radiopaque, highly flexible balloon-expandable tantalum stent was tested. Thirty-six of 40 stents were successfully deployed percutaneously in the coronary arteries of 31 dogs. The dogs were given aspirin before, intravenous heparin during, and aspirin alone after the procedure. One dog died at 24 hours because of coronary occlusion following traumatic implantation. Four dogs were put to death early, revealing re-endothelialization by 9 days. Eleven dogs were put to death from 2 weeks to 9 months during long-term follow-up, showing all vessels widely patent with the stent uniformly embedded within a stable neointimal layer. Follow-up arteriography showed patency in all remaining stents up to 1 year, with no perforation or aneurysm formation. Four stents were placed into canine peripheral arteries and were removed percutaneously after deployment. Pathology revealed no significant trauma to involved vessels. This tantalum stent exhibits feasibility of percutaneous deployment, early neointimal formation, low thrombogenicity on long-term aspirin therapy alone, and patency up to 1 year in this canine model.     

猫小型血巴尔通氏体人工感染犬初步研究

目的探讨猫、犬血巴尔通氏体的传播关系。方法从确诊为单独感染猫小型血巴尔通氏体的原发病猫无菌抽取血液,接种到无特定病原体的健康犬、脾脏摘除犬及对照猫,以外周血液镜检和特异性PCR检测作为感染的评价方法。结果健康犬和脾脏摘除犬均没有获得感染,对照猫获得了长达21天感染。结论猫小型血巴尔通氏体具有较强宿主特异性,通过血液接种的方式可以在本动物间传播,但不能通过血液接种的方式传播给健康犬或脾脏摘除犬。     

The association between silicone implants and both antibodies and autoimmune diseases

Silicones are widely used materials in many fields of medicine and largely are believed to be biologically inert. However, some investigators have reported that silicone implants are associated with an increased incidence of autoimmune disorders. In this study, we evaluated the capsular tissue of silicone implants and the sera of implant patients and controls for antisilicone antibodies and nonspecific immunoglobulins (IgG, IgA, IgM, and IgE). Our study group included 15 patients (eight men and seven women) undergoing reconstructive procedures for burn scars, in whom we used silicone implants, and 15 sex-matched controls undergoing reconstructive surgery for burn scars without using silicone implants. By immunofluorescence, we discovered strong capsular binding of IgG and weak capsular binding of IgM; antisilicone antibody levels were significantly higher in capsular tissue than elsewhere. Serum IgE also was higher in patient vs control subject sera. In conclusion, silicone materials do lead to an immune response consisting of antisilicone antibodies most evident immediately adjacent to the implant itself.     

Factors influencing the distribution of antibacterial agents in interstitial tissue fluid: Molecular size and protein binding

The distribution of two aminoglycosides and three penicillins was studied in dogs. Serial samples of interstitial tissue fluid were obtained from subcutaneous silicone rubber capsules and compared with simultaneous serum samples. The results showed the reproducibility of the method both between animals and between experiments. Tobramycin showed a trend to higher serum and tissue fluid concentrations compared to gentamicin but these differences were not statistically significant. The striking differences between the tissue fluid concentrations of ampicillin and cloxacillin were related to the high protein binding of the latter. It is concluded that an adequate tissue fluid concentration requires an adequately maintained serum concentration; drugs that are rapidly excreted and especially those that are highly protein bound, should be given in doses sufficient to produce such a serum concentration.     

Mechanisms of termination of reentrant atrial arrhythmias by class I and class III antiarrhythmic agents

We studied atrial flutter due to circus movement in chronically instrumented conscious dogs to identify the mechanism by which class I and class III antiarrhythmic drugs terminate reentrant excitation. We used a crossover experimental design administering five class I agents and one class III agent, by intravenous bolus followed by intravenous infusion. The class I agents other than lidocaine were almost uniformly effective in terminating the arrhythmia (disopyramide in six of seven dogs, propafenone in six of six, flecainide in seven of seven, and SC-40230 in seven of seven). Termination was preceded by a marked increase in cycle length (ranging from +78% with propafenone to +55% with disopyramide), but with the exception of disopyramide, class I agents did not significantly shorten the excitable gap. With disopyramide the gap decreased from 49 +/- 3% to 28 +/- 3% of the cycle length. With no class I agent did the wavelength of effective refractoriness increase to approach the cycle length of the arrhythmia. Lidocaine, used as a negative control, terminated the reentry in one dog with modest prolongation of the cycle length. Terminations with class I agents correlated with depression of conduction rather than prolongation of refractoriness. In contrast with class I agents, D-sotalol prolonged the cycle length minimally (+10%) and terminated the arrhythmia in six of seven dogs. It decreased the excitable gap from 42 +/- 4% to 26 +/- 6% of the cycle, but it still did not cause the wavelength of effective refractoriness to equal the cycle length. Terminations by D-sotalol seemed to result from either failure of the lateral boundaries of the circus path or reflection within the path.     

Lead Fixation in Dogs Achieved with RF Energy

Lead Fixation in Dogs Achieved with RF Energy. Introduction : The purpose of this study was to test whether radiofrequency (RF) energy could be used to fixate leads to the endocardium.
Methods and Results : In six dogs we measured the dislodgment force and pacing threshold before and after RF Fixation in the coronary sinus (CS) and right ventricle (RV). RF fixation was achieved with a CardioRhythm Atakr* ablation unit. The dislodgment force of CS leads fixed with RF energy was 1.63 ± 0.65 oz, compared with < 0.1 oz for similar leads placed in the CS of six separate dogs. In the RV, leads fixed with RF energy had a dislodgment force of 1.29 ± 0.27 oz, compared with 0.48 ± 0.28 oz. for urethane ( P < 0.01) and 1.01 ± 0.21 oz for silicone ( P = 0.41) tined leads. In the CS, the pacing threshold for RF fixed leads increased significantly from 2.2 ± 1.1 V (0.5 msec) before fixation to 4.2 ± 1.3 V after fixation ( P < 0.01), while in the RV, the pacing threshold increased from 0.41 ± 0.05 V (0.5 msec) before fixation to a mean of 2.03 ± 0.44 V after fixation ( P < 0.01). In another group of six dogs studied for 12 weeks. 5 of 6 RF fixed CS leads remained attached, as did 8 of 10 RF fixed RV leads. For the RV leads, the mean pacing threshold was 0.90 ± 0.35 V, compared with 0.53 ± 0.18 V (0.5 msec) for similar tined leads ( P = 0.02) and 1.2 ± 0.30 V (0.5 msec) for screw leads ( P = 0.18) in the RV.
Conclusion : We conclude that RF energy can be used to attach leads to the RV and CS endocardium. While the RV pacing thresholds increased acutely, the mean chronic thresholds were not significantly different for RF fixed leads and standard tined or screw leads.