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J St Cyr

Publications and source records attributed to J St Cyr.

12 recordsLinked to original sources

Platelet storage solution improves the in vitro function of preserved platelet concentrate.

BACKGROUND AND OBJECTIVES: Stored platelets develop biochemical lesions, manifest as depressed haemostatic function, clot retraction and wound healing. ViaCyte trade mark, a proprietary experimental preservative solution (comprising D-ribose, D-glucose, Hanks solution, Hepes solution, bovine serum albumin, tic anticoagulant peptide and sterile water), was tested in comparison with the presently accepted storage solution, citrate-dextrose-phosphate-plasma (CDP-P), to evaluate its ability to preserve platelet function during storage. MATERIALS AND METHODS: Platelets stored in ViaCyte and platelets suspended in CDP-P were transferred to polypropylene tubes with PL732 covers and analysed for adenine nucleotide levels (ATP molecules), in vitro agonist-mediated P-selectin expression and aggregation. RESULTS: After 5 days of storage at room temperature, 12.2% of platelets stored in ViaCyte exhibited P-selectin expression at rest, and 64.2% exhibited P-selectin expression upon activation with thrombin challenge, an increase of 52%. Platelets stored in CDP-P exhibited 44.4% P-selectin expression at rest, suggesting significant activation during storage, and thrombin stimulation resulted in P-selectin expression of 47.9%, an increase of only 2.5% (P< or =0.002, untreated vs. treated). ViaCyte also maintained ATP levels throughout the storage period, while these levels became depressed in platelets stored in CDP-P (P< or =0.02, untreated vs. treated). Storing platelets in the experimental preservative solution maintained their ability to aggregate, while control platelets lost their ability to aggregate in response to agonist. CONCLUSIONS: ViaCyte appears to protect platelets during storage, reflected by a low level of induced lesions. Platelets stored in ViaCyte maintain energy levels at their resting state, which preserves their ability to aggregate and secrete granule contents, and ensures the availability of additional platelets for activation upon in vitro challenge.

Adenosine Triphosphate↗

Chronic orthotopic aortic valve implantation model.

BACKGROUND AND AIM OF THE STUDY: The ideal animal model to assess implanted prosthetic aortic valves has yet to be universally accepted. The majority of mechanical valves are used for aortic valve replacement (AVR), yet historically animal models have provided data mainly after mitral valve implantation, due to the poor survival of animals undergoing AVR. Proposed regulations will require data from site-specific models. Thus, we modified previously reported chronic ovine models used for orthotopic implantation of aortic valves, to conduct preclinical aortic valve evaluation and to establish a predictive animal model needed for safety, hemodynamics, pathology and handling. METHODS: Fourteen sheep underwent AVR with 19 mm mechanical valves. Each animal was placed on cardiopulmonary bypass and the prosthetic valve implanted using a complete transverse ascending aortic transection. Hemodynamic data and aortography were obtained intraoperatively and again after 20 weeks, at which time hemodynamic studies, aortography, and pathological examination were performed. RESULTS: There were two operative deaths, but no significant complications in the other 12 sheep, 11 of which survived for 20 weeks. One animal died two weeks before sacrifice due to valve thrombosis. Chronic hemodynamic and aortographic data were within normal limits for all 11 sheep, and gross pathology of the implanted valve revealed no abnormalities. CONCLUSION: This study demonstrated the feasibility of the ovine model for orthotopic AVR, thus allowing greater confidence in the predictive value of in vivo hemodynamic and angiographic data gathered before clinical trials. Compared with other species, this ovine model provided improved rates of morbidity and mortality, reproducibility, ease of postoperative care, availability and acceptable anatomical similarities to humans. Future aortic valve studies at Medtronic will build on this knowledge base, making ovines - with this surgical technique - our animal model of choice.

Animals↗

Improved cannulation method for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation has been shown to be useful for patients in reversible cardiogenic shock. Effective arterial cannulation techniques for infants have been developed that are simple to use and require minimal subsequent vascular repair or reconstruction after removal. Groin cannulation in adults frequently requires bidirectional arterial cannulation to ensure adequate distal perfusion as well as frequent complex arterial repairs after discontinuation. We describe a simple arterial cannulation technique using a single right-angle, high-flow arterial cannula. With this technique adequate bidirectional arterial perfusion is maintained with a single arterial cannula while the need for vascular repairs or reconstruction is minimized.

Catheterization, Peripheral↗

Bronchial anomaly of the right upper lobe.

This case report presents a rare anomaly of right upper lobe bronchial anatomy. During routine right upper lobe resection for carcinoma, a common right upper and middle lobe bronchus was found. The resection was completed as a right upper and middle bilobectomy. Knowledge of this uncommon variant was beneficial in performing the pulmonary resection. A review of the literature is presented.

Adenocarcinoma↗

Long term model for evaluation of myocardial metabolic recovery following global ischemia.

Myocardial ATP levels remain depressed following significant periods of ischemia (Isc) despite reperfusion (Rpf). Neither the rate of in vivo ATP return following global Isc nor the factors which influence recovery have been defined. In order to determine the time course to complete the return of ATP levels and evaluate methods of enhancing recovery of ATP levels, we have devised a chronic canine model of global Isc. In this model serial ventricular biopsies can be taken in the awake animal over several days without reoperation which allows an investigation of the recovery of the myocardium following a uniform global insult to be performed. Recovery of ATP levels has been shown to depend, at least in part, on the availability of precursors and the activity of the ATP regenerating enzymes. Because complete recovery of ATP levels takes days, short term (hours) models have limitations. Previous attempts at enhancing ATP recovery following Isc have been only partially successful because either the degree of depression was not great or the period of observation was short, resulting in incomplete return. To identify the best precursor choice, we previously measured the activity of the AMP regenerating enzymes, adenosine kinase (AdK) (adenosine----AMP) and adenine phosphoribosyl transferase (APRT) (adenine----AMP). Because APRT activity was 20 fold higher than AdK with similar Km values for substrates, it appeared that adenine (A) is preferred to adenosine for AMP regeneration in the dog's myocardium. The formation of 5-phosphoribosyl 1-pyrophosphate (PRPP) may also be rate limiting and, therefore, the effect of ribose (R) on ATP recovery was also evaluated. Recovery of ATP levels was assessed in three groups: (1) normal saline (NS), (2) A (20 mM) in normal saline (A/NS) or (3) A with R (80 mM) in normal saline (A/R) were infused (1.0 ml/min) into the right atrium of dogs for 48 hours following Isc. In all groups, ATP levels fell to between 46-60% of pre-Isc levels during Isc. In the NS dogs, ATP levels continued to fall slightly to 46% pre-Isc levels during the first four hours of Rpf after Isc. By 24 hours no appreciable recovery had occurred and the measured ATP was only 51% of the pre-Isc value. Even by seven days, ATP had not returned fully, and by extrapolation, complete recovery required 9.9 +/- 1.4 days. Treated dogs showed, however, that ATP recovery could be significantly enhanced.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗

Myocardial high-energy phosphate levels in cardiomyopathic turkeys.

A congestive cardiomyopathy (CCM) model occurs in inbred broad-breasted turkeys and is manifested by reduced hatchability and a high mortality within a week of hatching. In the survivors, cardiac dilation begins by 3-4 weeks of age and further mortality occurs from chronic congestive heart failure. The mechanisms behind these changes is unknown, and, therefore, we investigated what role, if any, myocardial energy metabolism might play in these events. Ventricular myocardial samples were obtained for analysis of adenine nucleotides (ATP, ADP, AMP) and creatine phosphate (CP) in control and CCM turkeys, 1-31 days old. The adenine nucleotide energy charge (EC) was calculated using the formula EC = ATP + 1/2ADP/(ATP + ADP + AMP). We found the myocardial ATP levels and EC in CCM hearts at 1-2 days were reduced. In control turkeys, no significant age-related differences were found in myocardial high-energy phosphate compounds or in the EC. This depression in the energy metabolism of CCM turkeys may also be reflected in their poor hatchability. By 6-10 days, however, ATP levels had recovered and remained normal despite the onset of cardiac dilation and failure at 3-4 weeks of age in CCM turkeys. Because CP levels in control and CCM turkey hearts were similar in all age groups, significant ischemia did not appear to be present after hatching in CCM turkeys. Our results suggest, therefore, that an insult probably prior to hatching produced depressed myocardial energy levels in CCM turkeys and led to reduced hatchability. This early insult appears to be significant, in that late cardiac dysfunction resulted despite the recovery of myocardial ATP levels.

Adenine Nucleotides↗

Extracorporeal whole body hyperthermia treatment of HIV patients, a feasibility study.

The literature supports that the retrovirus, Human Immunodeficiency Virus (HIV), which is thought to cause Acquired Immunodeficiency Syndrome (AIDS), is heat sensitive at temperatures which can be achieved in man. Invasive or non-invasive induction of whole body hyperthermia (WBH) has been used to treat an array of illnesses, primarily in the field of oncology, until recently. Non-invasive methods have proven to be less toxic than invasive means. However, new technology and refined patient management have shown a dramatic decrease in the side effects with extracorporeal whole body hyperthermia (EWBH). The Food and Drug Administration granted a prospective trial for six HIV positive/AIDS patients to undergo a single treatment of EWBH, with patients randomized to a core temperature of either 41 or 42 degrees C. All patients had failed antiretrovirals and experienced at least one episode of an opportunistic infection. Organetics, Ltd., PS-1 extracorporeal, centrifugal pump device was used to induce EWBH. Results of this feasibility study demonstrated the ability of this equipment and technique to induce EWBH with acceptable toxicity. It was not possible to assess efficacy in this small study.

Adult↗

Long-term evaluation of prosthetic mitral valves in sheep.

We have developed an in vivo model for chronic evaluation of prosthetic heart valves using juvenile domestic sheep. This report summarizes the results of a study conducted to assess a new bileaflet prosthetic valve. Nine juvenile sheep underwent mitral valve replacement using standard cardiopulmonary bypass techniques including mild hemodilution, systemic hypothermia, and cold fibrillatory arrest. The average time on cardiopulmonary bypass was 57 min. There were no surgical or anesthetic complications. Two (22%) early deaths occurred due to prosthetic annular size disproportion (1) and preexisting pneumonitis (1); postmortem examination of both implanted devices revealed normal function. The remaining seven animals (78%) remained clinically well and underwent left and right heart catheterization, angiography, and sacrifice after the 150th postoperative day. Left ventriculograms demonstrated normal valve function in all cases. The average mitral transvalvular gradient, as determined by simultaneous pulmonary capillary wedge and left ventricular and diastolic pressure, was 5.4 mm Hg. Thus we have developed a new in vivo model that provides a successful model for chronic evaluation of prosthetic valves using a sheep model. There are several features contributing to the success of our model. First, to decrease the possibility of bacteremia and seeding of the prosthesis, a single incision is used and intraoperative monitoring lines minimized. Second, we use a short cardiopulmonary bypass run (range 52-62 min), with no period of ischemia. Third, fresh sheep blood is transfused immediately following bypass to prevent anemia. Fourth, gastric decompression is used to prevent ruminal bloating, with the resulting vena caval compression that decreases blood return while on bypass.

Animals↗