Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP).Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups.Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction

Effects of volatile anesthetics on elastic stiffness in isometrically contracting ferret ventricular myocardium

of halothane, isoflurane, and sevoflurane on elastic stiffness, which reflects the degree of cross-bridge attachment, were studied in intact cardiac muscle. Electrically stimulated (0.25 Hz, 25°C), isometrically twitching right ventricular ferret papillary muscles (n 15) at optimal length (Lmax) were subjected to sinusoidal length oscillations (40 Hz, 0.25– 0.50 % of Lmax peak to peak). The amplitude and phase relationship with the resulting force oscillations was decom-posed into elastic and viscous components of total stiffness in real time. Increasing extracellular Ca2 concentration in the presence of anesthetics to produce peak force equal to control increased elastic stiffness during relaxation, which suggests a direct effect of halothane and sevoflurane on cross bridges. sinusoidal length oscillations; cross bridges; calcium THERE IS EVIDENCE THAT the volatile anesthetics halo

British Journal of Clinical Pharmacology / Cefuroxime plasma and tissue concentrations in patients undergoing elective cardiac surgery: Continuous vs bolus application. A pilot study

Aims Surgical site infections contribute to morbidity and mortality after surgery. The authors hypothesized that higher antibiotic tissue concentrations can be reached for a prolonged time span by continuous administration of prophylactic cefuroxime compared to bolus administration. Methods Twelve patients undergoing elective cardiac surgery were investigated. Group A received 1.5 g cefuroxime as bolus infusions before surgery, and 12 and 24 hours thereafter. In group B, a continuous infusion of 3.0 g cefuroxime was started after a bolus of 1.5 g. Cefuroxim levels were determined in blood and tissue (microdialysis). T test, Wilcoxon signed rank test and test were used for statistical analysis. Results The area under the curve (AUC) of plasma cefuroxime concentrations was greater in group B (399 [333518]) as compared to group A (257 [177297] h mg L, [median and interquartile range], P = .026). Furthermore, a significantly longer percentage of time > minimal inhibitory concentrations of 2 mg L (100% vs 50%), 4 mg L (100% vs 42%), 8 mg L (100% vs 17%) and 16 mg L (83% vs 8%) was found for free plasma cefuroxime in group B. In group B, area under the curve in subcutaneous tissue (78 [61113] h mg L) and median peak concentration (33 [2638] mg L) were markedly higher compared to group A (P = 0.041 and P = .026, respectively). Conclusions Higher cefuroxime concentrations were measured in plasma and subcutaneously over a prolonged period of time when cefuroxime was administered continuously. The clinical implication of this finding still has to be elucidated.(VLID)509872