Acetylcholine and chronic vasculopathy in rat renal allografts.

BACKGROUND: Chronic allograft vasculopathy (CAV) is an important aspect of chronic allograft injury, which limits the long-term success of renal transplantation. The pathogenesis of CAV is ill defined, and no effective therapies exist. Acute rejection episodes are a major risk factor for CAV. Recently, we demonstrated that leukocytes, which strongly accumulate in allograft blood vessels during fatal acute rejection, produce acetylcholine (ACh), which has the potential to provoke CAV. Herein, we test the hypothesis that ACh is also produced by leukocytes during the development of CAV. METHODS: Kidneys were transplanted in the Fischer 344 to Lewis rat strain combination, an established experimental model for CAV. Isografts were performed in Lewis rats. The capacity of intravascular graft leukocytes to synthesize ACh was investigated during reversible acute rejection on day 9 posttransplantation and during the process of vascular remodeling on day 42. Furthermore, allograft recipients were treated with rivastigmine, which blocks enzymatic degradation of ACh. RESULTS: The protein expression of the high-affinity choline transporter-1 and choline acetyltransferase was increased in leukocytes from allografts on day 9 and 42 posttransplantation. In addition, leukocytes accumulating in the lumina of allograft blood vessels were by far more numerous compared with isografts. In line with our hypothesis, ACh itself was detected by high-pressure liquid chromatography in graft leukocytes but not in leukocytes from untreated kidneys. Treatment with rivastigmine drastically exacerbated CAV compared with placebo. CONCLUSION: We suggest that endogenous ACh contributes to the pathogenesis of CAV and may be a promising target for novel therapies preventing CAV.

Leukocyte accumulation in graft blood vessels during self-limiting acute rejection of rat kidneys.

During self-limiting acute rejection preceding chronic vasculopathy, large amounts of leukocytes, predominantly monocytes, interact with the endothelium of renal allografts. We aim to characterize them and to identify targets for functional and interventional studies. Leukocytes were harvested by vascular perfusion from Fischer 344 to Lewis renal allografts or Lewis isografts, followed by flow cytometry, quantitative RT-PCR and genome-wide transcriptional profiling. Leukocyte accumulation peaked in allografts on day 9. The percentage of monocytes expressing MHC class II and CD161 was increased whereas CD4, CD11a, CD43, and CD71 expression remained unchanged. IFN-γ, IL-1ß, IL-2, IL-10, TNF-α, and iNOS mRNA increased in allograft leukocytes but IL-4, IL-6, IL-12, TGF-ß, and tissue factor did not. During acute rejection, 1783 genes were differentially expressed. In conclusion, graft blood leukocytes display a unique state of partial activation during self-limiting rejection. Numerous differentially expressed genes deserve further investigation as potential factors in deciding the fate of the allograft.

The prevalence of potentially unstable coronary lesions in patients with coronary artery disease--virtual histology study.

BACKGROUND: Histopathological studies indicate that coronary artery lesions with a thin fibrous cap and large necrotic core (thin-cap fibroatheromas, TCFA) are characterised by a high risk of rupture and can potentially trigger acute coronary syndrome (ACS). Atherosclerotic lesions with a well preserved fibrous cap (fibroatheromas, FA) are considered to be more stable ones. Intravascular ultrasound virtual histology (IVUS-VH) enables identification of FA and TCFA in vivo. There are no published data regarding IVUS-VH derived occurrence of both FA and TCFA in patients with different clinical presentation. AIM: To determine IVUS-VH derived occurrence of FA and TCFA in coronary arteries of patients with chronic stable angina in comparison with recent or acute ACS subjects. METHODS: Intravascular ultrasound examination was performed in 60 patients, who were prospectively enrolled to three groups: group A--chronic stable angina, without a history of ACS within the previous 12 months; group B--recent ACS (4 weeks-3 months); group C--acute phase of ACS. RESULTS: The final analysis included 75 non-culprit lesions (group A: n=29 lesions; group B: n=22; group C: n=24). There were no significant differences in lesions' angiographic and ultrasound characteristics between the studied groups. There was no significant difference in the occurrence of FA lesions between the studied groups (20.7 vs. 22.7 vs. 4.2, respectively; NS). There was a significant difference in TCFA occurrence between the studied groups (31.0 vs. 50.0 vs. 79.2%; p <0.01). CONCLUSIONS: The present study confirms higher occurrence of thin-cap fibroatheromas in patients with clinically confirmed coronary instability. It also indicates that IVUS-VH can be a valuable tool for rupture prone lesion identification, which might help in better risk stratification in coronary artery disease patients.

Acute coronary syndrome caused by left main coronary artery plaque rupture and thrombosis - resolution after pharmacological treatment.

The article presents a case of a 68-year old male admitted to coronary care unit because of acute coronary syndrome without ST segment elevation. In coronary angiography a lesion in the left main coronary artery (LMCA) is found. Intravascular ultrasound (IVUS) examination confirms the diagnosis of the ruptured plaque with the presence of thrombus. Because of the well preserved lumen area a decision to continue intensive pharmacotherapy is made. Follow-up angiography and IVUS show a complete resolution of thrombus. The article discusses different management strategies in patients with confirmed ruptured plaque in LMCA.

[Unfortunate outcome of subsequent vascular complications in female patients assigned to percutaneous coronary intervention -- case report]. / Niekorzystny przebieg kolejnych powiklan naczyniowych u chorej poddanej zabiegowi planowej angioplastyki wiencowej -- opis przypadku.

We present a case of a 58-year-old female who underwent elective PCI of the left anterior descending coronary artery. The procedure was complicated by vessel dissections and myocardial infarction. Cardiogenic shock complicated acute coronary syndrome required intraaortic balloon pumping what led to descending aortic dissection successfully treated with stent-graft implantation. However, the patient died due to intractable cardiogenic shock.

Mean platelet volume on admission predicts impaired reperfusion and long-term mortality in acute myocardial infarction treated with primary percutaneous coronary intervention.

OBJECTIVES: We sought to determine the prognostic value of mean platelet volume (MPV) for angiographic reperfusion and six-month mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). BACKGROUND: Mean platelet volume is predictive of unfavorable outcome among survivors of STEMI when measured after the index event. No data are available for the value of admission MPV in patients with STEMI treated with primary PCI. METHODS: Blood samples for MPV estimation, obtained on admission in 398 consecutive patients presenting with STEMI, were measured before primary PCI. Follow-up up to six months was performed. RESULTS: No-reflow was significantly more frequent in patients with high MPV (> or =10.3 fl) compared with those with low MPV (<10.3 fl) (21.2% vs. 5.5%, p < 0.0001). The MPV was correlated strongly with corrected Thrombolysis In Myocardial Infarction frame count (CTFC) (r = 0.698, p < 0.0001). Kaplan-Meier survival analysis showed six-month mortality rate of 12.1% in patients with high MPV versus 5.1% in low MPV group (log rank = 6.235, p = 0.0125). After adjusting for baseline characteristics, high MPV remained a strong independent predictor of no-reflow (odds ratio [OR] 4.7, 95% confidence interval [CI] 2.3 to 9.9, p < 0.0001), CTFC > or =40 (OR 10.1, 95% CI 5.7 to 18.1, p < 0.0001), and mortality (OR 3.2, 95% CI 1.1 to 9.3, p = 0.0084). Abciximab administration resulted in significant mortality reduction only in patients with high MPV values (OR 0.02, 95% CI 0.01 to 0.48, p = 0.0165). CONCLUSIONS: Mean platelet volume is a strong, independent predictor of impaired angiographic reperfusion and six-month mortality in STEMI treated with primary PCI. Apart from prognostic value, admission MPV may also carry further practical, therapeutic implications.

[Patient with stable ischaemic heart disease and essential thrombocythemia in Invasive Cardiology Laboratory -- role of the automated systems for estimation of platelet aggregation]. / Chory ze stabilna choroba wiencowa i wspólistniejaca nadplytkowoscia samoistna w pracowni kardiologii inwazyjnej. Rola zautomatyzowanych systemów oceny stopnia agregacji plytek.

Patient with stable ischaemic heart disease and essential thrombocythemia in Invasive Cardiology Laboratory -- role of the automated systems for estimation of platelet aggregation. A case of a 63-year-old male patient with essential thrombocythemia and coronary artery disease is presented. The patient underwent elective coronary angiography and subsequent angioplasty of the intermediate branch. The procedure was complicated by a massive thrombosis of the right coronary artery. Tirofiban and subsequent stenting relieved anginal symptoms. Next, platelet activity was monitored using the platelet function analyser PFA-100 which enabled optimisation of the antiplatelet agent dosages. The usefulness of this device in the catheterisation laboratory is discussed.

[Prevalence of respiratory viruses in elderly people]. / Wystepowanie wirusów oddechowych u ludzi w podeszlym wieku.

We analysed the presence of respiratory tract viruses in 206 elderly people (more than 65 years old). To identify viruses we used immunofluorescence method. The study revealed respiratory virus infection in about one third of examined patients. We found the most frequent infection with parainfluenza viruses. We found also more frequent prevalence of respiratory viruses in the oldest subgroup (more than 75 years old). No correlation between presence of respiratory viruses and smoking, diabetes or congestive heart failure was found.