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Biomedical subjects

Roland Prondzinsky

Publications and source records attributed to Roland Prondzinsky.

7 recordsLinked to original sources
PubMed2006

Proteome analysis of myocardial tissue following ischemia and reperfusion--effects of complement inhibition.

Myocardial ischemia-reperfusion injury can be related to complement activation with generation of chemotactic mediators, release of cytokines, leukocyte accumulation, and subsequent severe tissue injury. In this regard, activation of transcription factors (i.e., NFkappaB) and de novo protein synthesis or inflammatory protein degradation seems to play an important role. In the present study, we analyzed the cardiac protein expression following myocardial ischemia (60 min) and reperfusion (180 min) in a rabbit model utilizing two-dimensional electrophoresis and nanoHPLC/ESI-MS/MS for biochemical protein identification. To achieve cardioprotective effects, we used a novel highly selective small molecule C1s inhibitor administered 5 min prior to reperfusion. The reduction of myocardial injury was observed as diminished plasma creatine kinase activity in C1s-INH-248-treated animals (65.2+/-3 vs. 38.5+/-3 U/g protein after 3 h of reperfusion, P<0.05). With proteome analysis we were able to detect 509+/-21 protein spots on the gels of the 3 groups. A pattern of 480 spots with identical positions was found on every gel of myocardial tissue of sham animals, vehicle and C1s-INH-248-treated animals. We analyzed 11 spots, which were identified by mass spectrometry: Superoxide dismutase, alpha-crystallin-chain-B, mitochondrial stress protein, Mn SOD, ATP synthase A chain heart isoform, creatine kinase, and troponin T. All of these proteins were significantly decreased in the vehicle group when we compared to sham-treated animals. Treatment with C1s-INH-248 preserved levels of these proteins. Thus, blocking the classical complement pathway with a highly specific and potent synthetic inhibitor of the activated C1 complex archives cardio-protection by altering and preserving different anti-inflammatory and cytoprotective cascades.

Amino Acid Sequence↗
PubMed2006

Temporary trans-coronary pacing by coated guidewires: a safe and reliable method during percutaneous coronary intervention.

Relevant bradycardias during percutaneous coronary intervention (PCI) are a rare event, but they require immediate therapy by temporary pacing. However, transvenous pacing is associated with frequent and severe complications. Therefore, we wanted to evaluate the safety and reliability of trans-coronary pacing by means of a PCI guidewire. Coronary pacing was applied to 70 consecutive patients undergoing PCI. Pacing was performed before and after PCI in a unipolar setting using standard guidewires as a cathode and a skin electrode as an anode. Both were connected to an external pacemaker. Coronary pacing (maximum output at 10 V, impulse duration 2.5 ms) was effective in 60 of 70 patients (85.7%). Successful pacing was achieved in the LAD and diagonal branches in 90% (27 of 30 Pts.), in the LCX and marginal branches 84.2% (16 of 19 Pts.) and in the RCA in 81% (17 of 21 Pts.). Pacing thresholds were comparable in all vessels within a range of 1-10 V averaging 6.6 +/- 2.3 V before and 6.6 +/- 2.2 V after PCI. The impedance ranged from 190-544 Omega with mean pacing impedance for coronary pacing of 424 Omega before and 416 Omega after PCI, respectively. Significant bradycardias during PCI occurred in 7 cases (10%). In three cases (4.3%) temporary coronary pacing became necessary at a maximum pacing duration of 3 min. There were no severe side effects. Coronary spasm occurred in 3 cases (4.3%) after pacing and was promptly reversible after intracoronary application of nitroglycerine. It is concluded that coronary pacing is a safe and feasible method for the treatment of bradycardias during PCI. It avoids additional venous puncture under hemodynamically unstable conditions and subsequent transvenous pacing, which is accompanied by potentially severe complications and additional costs.

Acute Disease↗
PubMed2006

Attenuated autonomic function in multiple organ dysfunction syndrome across three age groups.

Multiple organ dysfunction syndrome (MODS) is the failure of several organs after a trigger event. The mortality is high, at up to 70%. We hypothesize that autonomic dysfunction may substantially contribute to the development of MODS and speculate that there is an age dependence of autonomic dysfunction in MODS. A total of 90 consecutively admitted MODS patients were assigned to this study. Three variables of autonomic function were analyzed: heart rate variability (HRV), baroreflex sensitivity (BRS) and chemoreflex sensitivity (CRS). The patient cohort was divided into three age groups. The main finding was that BRS, CRS and almost all indices of HRV were attenuated in comparison to normal range data and there was no age dependence for HRV indices or CRS, but there was for BRS. In conclusion, autonomic function in MODS is attenuated. The influence of MODS on autonomic function overwhelms the age dependence of autonomic function observed in healthy subjects.

Aging↗
PubMed2005

Surgical trauma affects the proinflammatory status after cardiac surgery to a higher degree than cardiopulmonary bypass.

OBJECTIVES: Cytokines contribute to the development of the systemic inflammatory response syndrome or multiple-organ failure frequently observed after cardiopulmonary bypass-supported cardiac surgery. To quantify the contribution of bypass-induced versus trauma-induced inflammatory response after coronary artery bypass grafting, we examined plasma cytokine levels in 120 patients with coronary artery disease who were treated with or without cardiopulmonary bypass-assisted procedures. METHODS: Patients were treated in accordance with one of the following protocols: (1) elective percutaneous coronary intervention without cardiopulmonary bypass (n = 69), (2) cardiopulmonary bypass-supported percutaneous coronary intervention (cardiopulmonary bypass-percutaneous coronary intervention; n = 10), and (3) cardiopulmonary bypass-supported coronary artery bypass grafting (cardiopulmonary bypass-coronary artery bypass grafting; n = 41). Cytokine levels (picograms/milliliter) were measured by enzyme-linked immunosorbent assay from plasma samples obtained at various time points. RESULTS: Interleukin-6 was measured in blood samples from all 3 patient populations. The maximum interleukin-6 level was 13.6 +/- 22.3 pg/mL in the percutaneous coronary intervention group, 170.4 +/- 165.4 pg/mL in the cardiopulmonary bypass-percutaneous coronary intervention group, and 640.3 +/- 285.7 pg/mL in the cardiopulmonary bypass-coronary artery bypass grafting group. Interleukin-6 levels were significantly different, and the 95% confidence intervals did not overlap. In the cardiopulmonary bypass-percutaneous coronary intervention group, bypass duration correlated well with interleukin-6 production ( r = 0.915; P < .001), whereas these parameters did not correlate in patients who underwent cardiopulmonary bypass-coronary artery bypass grafting ( r = 0.307; P = .054). CONCLUSIONS: These findings support the suggestion that surgical trauma and cardiopulmonary bypass contribute to the inflammatory response after cardiac surgery, although trauma may contribute to a higher degree.

Angioplasty, Balloon, Coronary↗
PubMed2005

Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups.

OBJECTIVE: Multiple organ dysfunction syndrome (MODS) is the sequential failure of several organ systems after a trigger event, like sepsis or cardiogenic shock. Mortality rate is high, up to 70%. Autonomic dysfunction may substantially contribute to the development of MODS. Our study aimed to characterize a) the spectrum of autonomic dysfunction of critically ill MODS patients; b) whether autonomic dysfunction is different in patients receiving sedation, mechanical ventilation, or catecholamines; c) the age dependency of autonomic dysfunction in MODS; and d) whether autonomic dysfunction predicts mortality in MODS. DESIGN: Prospective cohort study. SETTING: Twelve-bed medical intensive care unit in a university center. PATIENTS: Ninety consecutively admitted score-defined MODS patients. INTERVENTIONS: Assessment of heart rate variability, baroreflex sensitivity, and chemoreflex sensitivity as markers of autonomic dysfunction. The patients were followed for 28-day mortality. MEASUREMENTS AND MAIN RESULTS: Baroreflex sensitivity, chemoreflex sensitivity, and almost all indexes of heart rate variability were attenuated in comparison to normal range data. There was no association between the assessed heart rate variability variables, baroreflex sensitivity or chemoreflex sensitivity, and the presence of sedation or catecholamine therapy. Except for frequency-domain variables, pNN50 (percentage of differences of successive RR intervals differing >50 msecs) and rMSSD (root mean square of successive difference of N-N intervals), none of the measured variables were related to the presence of mechanical ventilation. Age dependency was detected for baroreflex sensitivity but not for heart rate variability indexes or chemoreflex sensitivity (across ages 24-96 yrs). lnVLF predicted 28-day mortality best in the entire cohort of patients and in a subgroup of patients with cardiogenic-triggered MODS. CONCLUSIONS: Autonomic function of MODS patients is blunted, and this attenuation has prognostic implications. The extensive influence of MODS on autonomic function overwhelms and masks the well-known age dependency of autonomic function seen in healthy persons.

Adult↗
PubMed2002

Dysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression.

OBJECTIVES: Activity of mitochondrial respiratory chain complexes with and without mitochondrially encoded subunits was assessed in failing human myocardium together with parameters of mitochondrial gene expression. BACKGROUND: Mutations and deletions in mitochondrial genome (mtDNA) sporadically accumulate in the aging myocardium. In experimental heart failure, they are discussed to be a generalized problem resulting in disturbances of mitochondrial gene expression and mitochondrial function. METHODS: In left ventricular specimens from 43 explanted failing hearts and 10 donor hearts, enzyme activities of respiratory chain complexes, messenger ribonucleic acid (mRNA) expression of mitochondrially and nuclear encoded mitochondrial components (reverse transcriptase-polymerase chain reaction, Northern blot), undeleted wildtype mtDNA (Southern blot), and nuclear encoded mitochondrial transcription factor A (mtTFA) (Western blot) were quantified. RESULTS: Citrate synthase normalized activity of mitochondrial respiratory chain complex I, which contains seven mitochondrially encoded subunits, was decreased by 28% in terminally failing myocardium, whereas the activity of the exclusively nuclear encoded complex II was unchanged. However, the amount of intact mtDNA, the mRNA of all mitochondrially encoded subunits of the entire respiratory chain, the amount of mtTFA, and the enzymatic activity of complex III and complex IV, which also contain mitochondrially encoded subunits, were normal compared with donor hearts, excluding generalized disturbance of mitochondrial gene expression. Retrospective analysis of drug therapy before transplantation identified beta-blockers as one putative protection against this disturbance. CONCLUSIONS: In terminally failing human myocardium of patients receiving drug therapy, complex I depression is not caused by mtDNA damage and disturbed mitochondrial gene expression. The absence of mtDNA damage should facilitate recovery of the overloaded myocardium, if effective unloading could be achieved.

Adrenergic beta-Antagonists↗