Background-Hypertension treatment and control remain low worldwide. Strategies to improve blood pressure control have been implemented in the United States and around the world for several years. This study was designed to assess improvement in blood pressure control over a 10-year period in a large cohort of patients in the Department of Veterans Affairs.

Myocardial cells isolated from 8-day chick embryos were grown in monolayer culture under conditions that produce "standard embryonic" and "adult-type" cells. These cells were subjected to electric field stimulation that had a waveshape and intensities similar to those used in clinical electric countershock procedures. Photocell mechanograms obtained before, during, and after stimulation were correlated with simultaneously measured transmembrane potentials to determine the relationship between membrane polarization and arrhythmia production that occured after the stimulus. The results of these experiments demonstrate that a predictable sequence of mechanical responses occurs after stimuli ranging in intensity from 6 to 200 V/cm. This sequence, which closely resembles that observed in vivo after similar stimulation intensities, consists of a single response (activation), tachyarrhythmia, relaxed arrest followed by transient tachyarrhythmia, arrest with contracture, and cellular fibrillation. This diverse pattern of arrhythmias is associated with a prolonged depolarization of the cell membrane which increases with the intensity of the applied stimulus. It is probable that this depolarization is caused by a transient electromechanical deformation of the cell membrane during the shock. These findings contribute to a better understanding of the causes of the arrhythmias that appear after clinical and experimental electric countershock procedures.

Arrhythmias, S-T segment changes, immediate refibrillation, and other signs of dysfunction are often observed after clinical and experimental transthoracic defibrillation. In vitro studies suggested that shock-induced dysfunction is induced by sarcolemmal dielectric breakdown accompanied by ionic exchanges through transient, shock-induced microlesions in the sarcolemma. To test this hypothesis, cultured chick embryo myocardial cells were shocked in media containing fluorescein isothiocyanate-labeled dextrans (FITC-dextrans) ranging in molecular mass from 4 to 70 kDa, using electric field stimulation 5 ms in duration and ranging in intensity from 0 to 200 V/cm. Results showed that the percentage of cells incorporating 4- to 20-kDa dextrans increased in a dose-dependent manner. The 4- and 10-kDa dextrans were incorporated beginning at intensities of 50-100 V/cm. Dextran incorporation corresponded with shock intensities which produced a shock-induced arrest of spontaneous contraction lasting 1 min. The 20-kDa dextrans were incorporated following 150- and 200-V/cm shocks. Shocks of these intensities also produced a transient postshock contracture. Larger dextrans (40 and 70 kDa) were not incorporated. These results suggest the formation of transient sarcolemmal microlesions having a diameter of 45-60 A during high-intensity electric field stimulation.

According to the most commonly accepted hypothesis, ventricular defibrillation is produced by exciting cells in a critical mass of the ventricle. For monophasic defibrillator waveforms, this hypothesis correctly predicts a direct correlation between defibrillation threshold in the transthoracic calf model and excitation threshold for extracellular field stimulation in the cultured cell model. To further test the hypothesis, we determined whether symmetrical biphasic waveforms, which reduce defibrillation threshold in the calf to approximately 65% of that of the corresponding monophasic waveform (14), decrease excitation threshold in the cultured cell model. Experiments were performed on 100- to 250-microns aggregates from 10- to 12-day-old chick embryos. Excitation threshold strength-duration curves obtained at extracellular potassium (Ko) = 6.5 mM and pacing interval of 1,000 ms showed a significant reduction for symmetrical biphasic rectangular waveforms, when compared with the corresponding monophasic waveforms for durations greater than 3 ms. At the rheobase, the threshold ratio between the biphasic and monophasic waveforms was 0.63 (SE = 0.02). Transmembrane potentials during stimulation showed that excitation takes place during the second portion of the biphasic waveform for intensities that are subthreshold for the monophasic waveform. The relative effectiveness of the biphasic waveform (5-ms duration) increases under "fibrillation conditions" of short pacing interval (300 ms) and high extracellular potassium (10.5 mM). These results show that symmetrical biphasic waveforms decrease excitation threshold in the cultured cell model and that the degree of threshold reduction is dependent on Ko and beat rate.

Excitation thresholds and arrhythmias were studied in "adult-type" cultured chick embryo myocardial cells after electric field stimulation with biphasic, truncated, and rectified underdamped RLC (resistance-inductance-capacitance) type waveforms, to test the hypothesis that the negative phase of biphasic waveforms ameliorates membrane dysfunction induced by the initial positive portion. Photocell mechanograms and intracellular microelectrodes monitored extrasystoles and depolarization-induced arrhythmias. Rectifying or truncating biphasic waveforms did not alter the excitation threshold. However, shock intensities producing specific postshock arrhythmias or a specific severity of postshock prolonged depolarization differed significantly when biphasic waveforms were truncated or rectified. The voltage gradient producing a specific dysfunction was 12-14% lower for the truncated version than for the biphasic; that for the rectified version was 17-27% lower than for the biphasic version (although both contained the same energy). Safety factor, the ratio between shock intensity producing specific dysfunction and that producing excitation, was determined for each waveform. Biphasic waveforms had larger safety factors than truncated or rectified waveforms. Since safety factor, as measured in cultured myocardial cells, closely corresponds with in situ defibrillating effectiveness (14), the significantly higher safety factors of biphasic waveforms suggest that carefully shaped biphasic waveforms might improve the efficacy and safety of cardiac defibrillation procedures.

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High-intensity electric shocks used for cardiac defibrillation produce arrhythmias, S-T segment changes, and a low percent success in situ. Cultured myocardial cells exhibit similar postshock arrhythmias that are caused by a prolonged depolarization of the cell membrane. Since this dysfunction is ameliorated by biphasic RLC-type waveforms, we examined rectangular biphasic waveforms to maximize this beneficial effect and clarify the dysfunction-inducing mechanism. Cultured myocardial cells were subjected to electric field stimulation with monophasic 5-ms rectangular waveforms of about 80 V/cm to produce a postshock arrest of contractile activity lasting 4 s. Shocks given with this control waveform were alternated with biphasic test waveforms having the same initial portion followed by negative "tails" 1-100 ms in duration and 5-100% of the initial positive portion in amplitude. Results from 31 biphasic waveforms demonstrated significant alterations in postshock dysfunction. Waveforms with up to 10% undershoot and ranging from 5 to 100 ms in duration decreased arrest time by up to 50%; waveforms with greater than 20% undershoot led to protracted postshock arrest times. These results strengthen the hypothesis that electromechanical breakdown of the myocardial cell membrane underlies postshock dysfunction and show that biphasic waveforms with low amplitude tails ameliorate this dysfunction.

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