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Biomedical subjects

Krzysztof Karnicki

Publications and source records attributed to Krzysztof Karnicki.

9 recordsLinked to original sources
PubMed2006

In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity: implications for thrombotic risk.

Gram-negative bacteria release LPS, which activates Toll-like-receptor-4 (TLR4) in the host, initiating an inflammatory response to infection. Infection increases risk for thrombosis. Platelets contribute to defense from infection and to thrombosis. Experiments were designed to determine whether LPS, through TLR4 signaling, affects platelet phenotype. Platelet responses in wild-type (WT) mice and mice that lack the TLR4 gene (dTLR4) were compared following a single nonlethal injection of LPS (0.2 mg/kg iv). Compared with WT mice, mice without TLR4 had fewer circulating platelets with lower RNA content and were less responsive to thrombin-activated expression of P-selectin but were equally sensitive to aggregation or ATP secretion. One week following the LPS injection, the time it takes for the circulating platelet pool to turnover, the number of circulating platelets, thrombin-induced expression of P-selectin, and collagen-activated aggregation were increased comparably in both groups of mice. Therefore, the change of the platelet pool to an activated phenotype 1 wk after a single exposure to LPS appears to arise from a process that is independent of TLR4. The persistence of the effect 1 wk after the injection suggests that the changes reflect an action of LPS on megakaryocytes and their platelet progeny rather than on circulating platelets, which would have been cleared.

Animals↗
PubMed2006

Immunohistochemistry of thrombi following iliac venous stenting: a novel model of venous thrombosis.

Stenting has become a common intervention for venous occlusive disease. Little is known regarding the composition of venous thrombi complicating stent placement. The optimal design of antithrombotic agents in this setting requires this knowledge. Quantitative immunohistochemistry was undertaken to define the platelet, fibrin(ogen) and leukocyte composition and spatial orientation of venous thrombi following percutaneous iliac stent placement in pigs. Venous stent thrombus size was measured by weight and scintillation detection of autologous (111) In-platelets. Thrombi were divided in segments (cephalad to caudad), sectioned and stained with monoclonal anti-platelet glycoprotein Ib or polyclonal anti-fibrin(ogen) fluorescent antibodies. Thrombus platelet content was 100-fold greater than paired whole blood samples. The caudal-most segments contained platelet-rich aggregates (p < 0.05) with abundant leukocytes (p < 0.0001) relative to more cephalad segments. Platelet and fibrin(ogen) content varied over an eight-fold range between segments but were directly correlated with each other (r = 0.77; p < 0.0001). The platelet co-localization with fibrin(ogen) is consistent with the phospholipid dependence of prothrombin activation. The abundance and caudal distribution of platelet-leukocyte aggregates indicate their preferential accretion from flowing blood early in the genesis of venous stent thrombi. These may represent novel cellular targets for the prevention and treatment of venous thrombosis.

Animals↗
PubMed2005

Platelet characteristics change with aging: role of estrogen receptor beta.

Estrogen receptor beta (betaER) is the predominant estrogen receptor in platelets. Experiments were designed to define phenotypic changes in platelets with aging following deletion of betaER (betaERKO). Blood was collected from wild-type and betaERKO female mice at 4-7 (young) and 24-25 (aged) months of age. In young animals, total number of platelets, number of platelets containing RNA (reticulated platelets), aggregation, dense body adenosine triphosphate secretion, and alpha granular secretion were the same in both groups. With aging, total number of platelets decreased but reticulated platelets increased in betaERKO mice; aggregation and dense granule adenosine triphosphate secretion decreased whereas basal expression of fibrinogen receptors increased with age in wild-type and betaERKO mice. Basal expression of P-selectin and annexin V binding increased with aging only in betaERKO mice; thrombin did not increase expression in these mice. Therefore, deletion of betaER is associated with specific platelet functions, which are expressed only with age-associated reproductive senescence.

Adenosine Triphosphate↗
PubMed2004

The impact of peripheral arterial disease on circulating platelets.

INTRODUCTION: To test the hypothesis that circulating platelets display evidence of reversible interactions with atherosclerotic lesions, platelet alpha-granule content and propensity for microaggregate formation were measured in samples from normal donors (n=65) and from patients with either peripheral arterial disease (n=47) or renovascular hypertension (n=22). To measure the effect of a defined arterial injury on platelet function, platelet samples were compared before and 30 min after elective angioplasty. MATERIALS AND METHODS: P-selectin was measured after strong stimulation of ultra-dilute platelets with thrombin (10 nM). Microaggregation was measured as a platelet count deficit in citrate-anticoagulated platelet-rich plasma (PRP) relative to that predicted from the count in EDTA-anticoagulated blood. RESULTS: Platelet alpha-granule P-selectin was significantly lower from platelets of patients compared to normal donors. In addition, platelets from patients have a significantly greater propensity to form microaggregates in citrate anticoagulant. In contrast to atherosclerotic renovascular hypertension, platelets from patients with fibromuscular dysplasia, a distinct non-inflammatory cause of arterial stenosis, do not differ significantly from normal donors. Other than the PRP platelet count, which rose transiently following angioplasty, other platelet measures were unchanged by the injury. CONCLUSIONS: Atherosclerotic arterial disease is associated with an increased share of platelets unable to express P-selectin and an increased fraction of platelets that microaggregate in citrate anticoagulant. These platelet alterations are not completely explained by either focal arterial injury or abnormal rheology associated with arterial stenosis but appear to be an effect of the atherosclerotic process.

Age Factors↗
PubMed2002

Factors contributing to individual propensity for arterial thrombosis.

OBJECTIVE: Occurrence of arterial thrombosis secondary to vascular disease in an individual is not easily predicted. After establishing that this poor predictability arises at least in part from an intrinsic thrombosis propensity of the individual, we sought to determine whether the propensity for arterial thrombosis is governed by blood or arterial wall factors. METHODS AND RESULTS: To evaluate the variability arising from the blood, autologous 111In-labeled platelet deposition was measured after high-shear perfusion of compressed aortic strips, prepared from a single pig, with heparinized blood from 25 pigs. To evaluate the variability arising from the vessel wall, aortic strips from 8 pigs were superfused with blood from a single animal. Blood samples from 25 animals superfused over aortic substrate from a single source yielded a 24-fold range of platelet deposition. In contrast, when aortic substrates from 8 different animals were superfused with blood from a single animal, platelet deposition spanned a 3-fold range. Platelet deposition was significantly correlated with whole-blood lymphocyte counts and with platelet counts. CONCLUSIONS: Individual propensity for arterial thrombosis in pigs is more greatly influenced by blood components than by elements within the arterial wall.

Animals↗
PubMed2002

Influence of anatomical location on arterial thrombosis.

Atherosclerosis manifests as a systemic disease with near global involvement of the named segments of the arterial tree. Acute thrombotic arterial occlusion, however, is not equally distributed. To evaluate intra-individual regional differences in arterial thrombogenicity, we compared (111)In-platelet deposition in porcine carotid and femoral arteries after a standardized crush injury. Within the unidirectional flow conditions of elastic carotid arteries, platelet deposition was more than 3-fold higher compared with predominantly muscular femoral arteries with triphasic arterial flow. To determine the influence of rheology on platelet deposition after crush injury, carotid arteries were transplanted into the femoral position and compared with the paired native carotid and femoral arteries. Similarly, femoral arteries transposed to the carotid position were compared with the paired native carotid artery. In each of these experiments, arterial transposition to a new anatomic location imparts a predilection for platelet deposition indigenous to the new location. In the controlled environment of two high-shear thrombin-independent and -dependent flow chambers, porcine carotid and femoral arterial substrates were indistinguishable from one another with respect to platelet deposition. Regional differences in arterial hemodynamics may account for substantial differences in thrombosis arising from deep arterial injury.

Animals↗
PubMed2002

A new platelet preservative.

A new platelet preservative, ViaCyte trade mark (balanced salt solution, physiological buffer, D-ribose, bovine serum albumin, D-glucose, sterile water) was tested against the presently used storage solution (citrate-phosphate-dextrose; CPD) and results revealed that ViaCyte demonstrated added protection for platelets during storage-induced activation. Following five days of storage at room temperature, only 12.2% of platelets stored in ViaCyte exhibited P-selectin expression at rest and, upon thrombin challenge, 64.2% were activated, an increase of 42%. In control platelets (platelets stored in CDP), 44.4% were activated due to storage-induced lesions, and thrombin stimulation resulted in 47.9% P-selectin expression, an increase of only 2.5%. ViaCyte storage maintained the resting state and preserved platelet function, making more platelets available for activation upon agonist challenge. This preliminary study demonstrated that the presently used standard preservative does not offer protection from storage-induced lesions. Partially dysfunctional platelets do not contribute significantly to hemostasis in vivo and play little role, if any, in clot retraction and wound healing processes.

Blood Platelets↗
PubMedDate not supplied

Stapled aortic anastomoses: a minimally invasive, feasible alternative to videoscopic aortic suturing?

Widespread applications of totally laparoscopic aortic reconstructions have been limited by the long cross-clamp time required to suture the aortic anastomosis despite improvement in instrumentation. The authors' hypothesis was that a "one-step anastomosis concept" using an intraluminal stapler would allow shorter cross-clamp time but similar patency and imperviousness as videoscopic suturing techniques. An intraluminal stapler (Endopath-ILS, Ethicon) with a modified anvil was used to perform videoscopic-assisted thoracic aorta-to-iliac artery bypass with a 21 mm by 8 mm polytetrafluoroethylene (PTFE) graft in 22 sheep through a minimally invasive approach using a 5 cm thoracotomy. The graft-to-iliac artery anastomoses were hand sutured through a flank incision. Twelve sheep were used to establish the technique and 10 subsequent animals constituted the study group. Aortic cross-clamp time, imperviousness, and need for additional sutures were recorded and compared to previously reported data using videoscopic suturing in pigs. Patency was assessed by comparing lower limb arterial pressures. Macroscopic and microscopic examinations of the anastomoses were performed at different time-points within the first 3 months. Videoscopic-assisted stapled anastomoses were also performed on atherosclerotic aortas of 3 human cadavers. Stapled anastomoses between the thoracic aorta and PTFE graft were completed in 8 of 10 animals. Two animals were euthanized after stapler failure and anastomotic bleeding. Sutures to strengthen the anastomosis had to be used in 4 cases. Mean aortic cross-clamp time in 8 successful cases was 4.3 +/-2.9 minutes (range 2-11 minutes) and was significantly shorter than clamp time of videoscopic suturing technique (48.7 +/-9.4 minutes, p < 0.0001). Imperviousness was good or excellent in 4 animals and fair in 4 animals. All anastomoses were patent at the end of the procedure. Examination of the anastomosis of the 2 failed interventions showed medial aortic tear surrounding the anastomosis in 1 case and misfired staples in the other. No graft occlusion was noted during follow-up ranging from 0 to 12 weeks. At the time of harvest, no bleeding was noted after epinephrine and volume infusion to increase mean arterial pressure to 200 mm Hg for 15 minutes. Macroscopic examination of the anastomoses revealed adequate healing with circumferential stapling of the prosthesis to the aortic wall and no stenosis or thrombus except in 1 false aneurysm (1/7, 14%). Surface electron microscopy showed cells coverage of the anastomosis surface. When applied on human cadaver thoracic and abdominal aorta with atherosclerotic changes, clamping times of less than 5 minutes were achieved. However, imperviousness tested with saline was poor. An automatic stapling device allows performance of a graft-to-aorta anastomosis through a minimally invasive approach with shorter clamping time than a videoscopic suturing technique. However, the current technique of aortic stapling is unreliable and further improvements are needed.

Anastomosis, Surgical↗