Toward the optimal lead system and optimal criteria for exercise electrocardiography

To define the optimal lead system for exercise electrocardiography, data of the whole body surface potential distribution were analyzed in 25 normal subjects and in 25 patients with coronary artery disease at rest and during exercise. All patients had a normal electrocardiogram at rest. The sensitivity of the standard chest leads was 60 percent; it improved to 84 percent with the body surface map whereas both methods had a 100 percent specificity. On the basis of these data, and reports from other centers, it is concluded that a single bipolar lead from the right subclavian area to lead V5 is adequate in those laboratories that are restricted to testing subjects with a normal electrocardiogram at rest. In patients with a previous infarction or other abnormalities in the electrocardiogram at rest three (pseudo) orthogonal leads or several standard leads are necessary. Recommendations for optimal measurements from the exercise electrocardiogram are based on quantitative computer analysis of the selected leads in larger groups of patients. Best results were obtained with a combination of S-T amplitude, S-T slope and heart rate. The improvement in sensitivity from 50 percent with visual analysis to 85 percent with computer was similar to that obtained with body surface mapping. Changes of the P wave and QRS complex during exercise appeared to be of little diagnostic value. The pathophysiologic mechanisms that contribute to the changes of the electrocardiogram during exercise are discussed

In Vitro Evaluation of Anti-Aggregation and Degradation Behavior of PEGylated Polymeric Nanogels under In Vivo Like Conditions

The in vivo stability and biodegradability of nanocarriers crucially determine therapeutic efficacy as well as safety when used for drug delivery. This study aims to evaluate optimized in vitro techniques predictive for in vivo nanocarrier behavior. Polymeric biodegradable nanogels based on hydroxyethyl methacrylamide-oligoglycolates-derivatized poly(hydroxyethyl methacrylamide-co-N-(2-azidoethyl)methacrylamide) and with various degrees of PEGylation and crosslinking densities are prepared. Three techniques are chosen and refined for specific in vitro evaluation of the nanocarrier performance: (1) fluorescence single particle tracking (fSPT) to study the stability of nanogels in human plasma, (2) tangential flow filtration (TFF) to study the degradation and filtration of nanogel degradation products, and (3) fluorescence fluctuation spectroscopy (FFS) to evaluate and compare the degradation behavior of nanogels in buffer and plasma. fSPT results demonstrate that nanogels with highest PEGylation content show the least aggregation. The TFF results reveal that nanogels with higher crosslink density have slower degradation and removal by filtration. FFS results indicate a similar degradation behavior in human plasma as compared to that in phosphate buffered saline. In conclusion, three methods can be used to compare and select the optimal nanogel composition, and these methods hold potential to predict the in vivo performance of nanocarriers