Short term effects of milrinone on biomarkers of necrosis, apoptosis, and inflammation in patients with severe heart failure

<p>Abstract</p> <p>Introduction</p> <p>Inotropes are associated with adverse outcomes in heart failure (HF), raising concern they may accelerate myocardial injury. Whether biomarkers of myocardial necrosis, inflammation and apoptosis change in response to acute milrinone administration is not well established.</p> <p>Methods</p> <p>Ten patients with severe HF and reduced cardiac output who were to receive milrinone were studied. Blood samples were taken just before initiation of milrinone and after 24 hours of infusion. Dosing was at the discretion of the patient's attending physician (range 0.25–0.5 mcg/kg/min). Plasma measurements of troponin, myoglobin, N-terminal-pro-BNP, interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand were performed at both time points.</p> <p>Results</p> <p>Troponin was elevated at baseline in all patients (mean 0.1259 ± 0.17 ng/ml), but there was no significant change after 24 hours of milrinone (mean 0.1345 ± 0.16 ng/ml, p = 0.44). There were significant improvements in interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand (all p < 0.05) indicative of reduced inflammatory and apoptotic signaling compared to baseline.</p> <p>Conclusion</p> <p>In conclusion, among patients with severe HF and low cardiac output, ongoing myocardial injury is common, and initiation of milrinone did not result in exacerbation of myocardial injury but instead was associated with salutary effects on other biomarkers.</p

Levels and sources of PCDDs, PCDFs and dl-PCBs in the water ecosystems of central Poland — A mini review

Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) are unwanted by-products in a variety of industrial and thermal processes. They have been present on Earth long before the human era, since they may be also formed as a result of forest fires or volcanic explosions. Polychlorinated biphenyls (PCBs) in turn, have been intentionally produced by humans. Poland was a minor producer of PCB mixtures (Chlorofen and Tarnol), which were a source of direct and indirect environmental diffusion with PCB and less with PCDDs/PCDFs. Industrial accidents with PCDDs/PCDFs were absent in Poland. Their stability and resistance to thermal breakdown made them very dangerous for environment and, in consequence, due to their environmental persistence, bioaccumulation and biomagnification in the terrestrial and aquatic food chains, to humans. Humans may become affected by PCDDs/PCDFs and PCBs through environmental (soil and water contamination, fish and food), occupational (incinerators; pulp, paper and metallurgy industry; copper production), or accidental (Seveso accident) exposure. The aim of this review was to evaluate environmental hazard caused by PCDDs, PCDFs and dioxin-like-PCBs in the central region of Poland based on the accessible data on diffusion of those compounds in sediments and riverine, reservoir and storm water from our previous studies and discussed in the context of other achievements in Poland and elsewhere

Inotropic effects of angiotensin II on human cardiac muscle in vitro

The direct effects of angiotensin II (Ang II) on human cardiac muscle were investigated using isolated trabecular muscles from failing and functionally normal hearts. Atrial and ventricular trabeculae were studied. Results demonstrated a positive inotropic effect of Ang II on human cardiac muscle. Comparison of the effects of Ang II among groups indicated that the responsiveness tended to be greater in atrial and normal muscle compared with failing muscle. Results of this study also demonstrated heterogeneity in the responsiveness to Ang II among human muscles, which was not correlated with patient age, sex, diagnosis, prior treatment with angiotensin converting enzyme inhibitor, or heart function. A significant correlation between response to Ang II and response to isoproterenol was demonstrated in failing ventricular trabeculae, which may suggest that defects in beta-adrenergic responsiveness in the failing human ventricle are accompanied by a loss of responsiveness to Ang II. Studies were extended to the Syrian cardiomyopathic hamster and its control. A dose-dependent inotropic response occurred in normal hamster ventricular muscle but was significantly diminished in cardiomyopathic muscle. Ang II did not shorten the timing of contraction, and pretreatment with adrenergic-blocking agents did not shift the dose-response curve, indicating that the response was not cyclic AMP mediated. This study demonstrates for the first time that Ang II can exert an inotropic effect directly on human cardiac muscle and confirms that there is a direct effect of Ang II on hamster cardiac muscle. The study further suggests, however, that the inotropic response to Ang II in cardiac muscle is heterogeneous and may be diminished by heart failure

Continuous aortic flow augmentation - A pilot study of hemodynamic and renal responses to a novel percutaneous intervention in decompensated heart failure

Background - Diminished aortic flow may induce adverse downstream vascular and renal signals. Investigations in a heart failure animal model have shown that continuous aortic flow augmentation ( CAFA) achieves hemodynamic improvement and ventricular unloading, which suggests a novel therapeutic approach to patients with heart failure exacerbation that is inadequately responsive to medical therapy. Methods and Results - We studied 24 patients ( 12 in Europe and 12 in the United States) with heart failure exacerbation and persistent hemodynamic derangement despite intravenous diuretic and inotropic and/or vasodilator treatment. CAFA ( mean +/- SD 1.34 +/- 0.12 L/min) was achieved through percutaneous ( n = 19) or surgical ( n = 5) insertion of the Cancion system, which consists of inflow and outflow cannulas and a magnetically levitated and driven centrifugal pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular resistance decreased from 1413 +/- 453 to 1136 +/- 381 dyne (.) s (.) cm(-5) at 72 hours ( P = 0.0008). Pulmonary capillary wedge pressure decreased from 28.5 +/- 4.9 to 19.8 +/- 7.0 mm Hg ( P < 0.0001), and cardiac index ( excluding augmented aortic flow) increased from 1.97 +/- 0.44 to 2.27 +/- 0.43 L (.) min(-1) (.) m(-2) ( P = 0.0013). Serum creatinine trended downward during treatment ( overall P = 0.095). There were 8 complications during treatment, 7 of which were self-limited. Hemodynamics remained improved 24 hours after CAFA discontinuation. Conclusions - In patients with heart failure and persistent hemodynamic derangement despite intravenous inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a reduction in serum creatinine. CAFA represents a promising, novel mode of treatment for patients who are inadequately responsive to medical therapy. The clinical impact of the observed hemodynamic improvement is currently being explored in a prospective, randomized, controlled trial

Evaluation of the stability profile of anticancer drugs: a review of Ifosfamide and Mesna regimen for the treatment of metastatic soft tissue sarcoma

Purpose: This paper aims to summarise and critically review the existing published literature with regard to clinical considerations as well as stability testing studies of Ifosfamide and Mesna. It also aims to highlight the factors that should be considered when designing and conducting stability testing experiments. Summary: Ifosfamide and Mesna are currently given to patients for 14 days continuous home-based infusion for the treatment of soft tissue sarcoma. No previous work has evaluated their stability for more than 7 days under real-life conditions so the current regimen involves patients visiting hospital twice during the 14-day treatment. This may create extra disruption to patients’ life style as well as increasing the workload for cancer services. Conclusion: There is a need to conduct stability testing experiments for Ifosfamide and Mesna taking into consideration all of the highlighted factors to mimic standard clinical practice