Ronald E. Jones

Conditioning prepulse of biphasic defibrillator waveforms enhances refractoriness to fibrillation wavefronts.

The mechanism of biphasic waveform defibrillation threshold reduction is unknown. We tested the hypothesis that, during refractory period stimulation, sarcolemmal hyperpolarization by the first pulse of biphasic waveforms facilitates excitation channel recovery, which enhances graded responses produced by the second depolarizing pulse. This prolongs cellular refractoriness to fibrillation wavefronts when compared with a monophasic depolarizing stimulus. Monophasic (10 msec, rectangular wave) or symmetrical biphasic (10 msec, each pulse) current injection S2 stimuli at 1.5 and two times S1 threshold were used to scan the S1 action potential refractory period (S1 cycle length, 600 msec) in myocardial cell aggregates. S2 waveforms were delivered with normal and reversed polarity to test the hyperpolarizing action of biphasic waveforms. Responses to an S3 stimulus, which simulated a potential incoming fibrillation wavefront, were also determined. Results showed that biphasic S2 waveforms produced longer graded responses during and immediately after the S1 refractory period than did corresponding monophasic S2 waveforms. The maximum difference in response duration produced by the biphasic and monophasic waveforms was 58.6 +/- 10.0 msec (p less than 0.001). This maximum difference occurred 10 msec before the end of the S1 refractory period. The longer response durations produced by biphasic S2 also produced longer refractoriness to the S3 stimulus. The maximum difference in total refractoriness to S3 of 51.8 +/- 2.8 msec (p less than 0.002) occurred at the same S1S2 coupling interval as the maximum difference in S2 response duration. Prolonged refractoriness may protect ventricular cells from refibrillation wavefronts and act as the cellular basis for greater biphasic waveform defibrillation efficacy.

Increasing fibrillation duration enhances relative asymmetrical biphasic versus monophasic defibrillator waveform efficacy.

Biphasic waveforms reduce defibrillation threshold compared with corresponding monophasic waveforms. However, effects of fibrillation duration on relative efficacy of monophasic and biphasic waveforms are unknown. This study used a newly developed defibrillation model, the isolated right- and left-sided working rabbit heart, with epicardial defibrillation electrodes, to compare threshold for a monophasic waveform (5 msec rectangular) and an asymmetrical biphasic waveform (5 msec each pulse, V2 = 50% V1). Mean voltage defibrillation threshold (V50) was determined from sigmoidal probability of successful defibrillation versus shock intensity curves after 5, 15, and 30 seconds of fibrillation in a paired study with 10 hearts. Results showed that biphasic waveforms had significantly lower voltage and energy thresholds at all fibrillation durations and that their relative efficacy improved with increasing fibrillation duration. Biphasic voltage threshold was 38.2 +/- 2.2, 44.7 +/- 4.8, and 46.6 +/- 3.2 V after 5, 15, and 30 seconds of fibrillation compared with monophasic thresholds of 51.7 +/- 4.4 (p less than 0.002), 63.0 +/- 7.6 (p less than 0.05), and 72.1 +/- 3.9 V (p less than 0.005). Biphasic waveform energy threshold was 0.67 that for the monophasic waveform after 5 seconds of fibrillation (0.12 +/- 0.01 versus 0.18 +/- 0.03 J, p less than 0.05). The ratio between biphasic waveform threshold and monophasic waveform threshold (B/M) decreased to 0.62 at 15 seconds. At 30 seconds, B/M was 0.52 (0.17 +/- 0.02 versus 0.33 +/- 0.04 J, p less than 0.02). This study also showed that biphasic waveform threshold was a nonlinear function of monophasic waveform threshold so that improved biphasic defibrillator waveform efficacy was greatest for hearts having higher monophasic thresholds.(ABSTRACT TRUNCATED AT 250 WORDS)

Refractory period prolongation by biphasic defibrillator waveforms is associated with enhanced sodium current in a computer model of the ventricular action potential

Mechanisms through which biphasic waveforms lower defibrillation threshold are unknown. Previous work showed that low-intensity biphasic shocks (BS2), delivered during the refractory period of a control action potential (S1), produced significantly longer responses than monophasic shocks (MS2). To test the hypothesis that longer responses are due to hyperpolarization-induced excitation channel recovery during the first portion of the biphasic waveform, the authors used the Beeler-Reuter ventricular action potential computer model with the Drouhard-Roberge (BRDR) modification to study refractory period stimulation with MS2 (10 msec) and symmetrical BS2 (10 msec each pulse). At 1.5 times diastolic threshold, BS2 prolonged action potential duration when delivered 50 msec into the S1 refractory period, and produced a maximum BS2 versus MS2 response duration difference of 62 msec. Longer BS2 responses corresponded to enhanced BS2-induced sodium current compared to MS2. Maximum BS2 vs MS2 sodium current difference was 400 uA/cm/sup 2/. These results show that, in a computer model of the ventricular action potential, hyperpolarization by the first phase of a biphasic waveform enhances S2 sodium current and prolongs duration of refractory-period responses. This effectively shortens the cellular refractory period. Prolonged refractory period responses, produced by biphasic defibrillator waveforms, may underlie enhanced defibrillating efficacy at low shock intensities.<<ETX>>

Blood Pressure Control Among US Veterans A Large Multiyear Analysis of Blood Pressure Data From the Veterans Administration Health Data Repository

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. Methods and Results— A cohort of 582 881 hypertensive patients and 260 924 normotensive individuals treated in 15 Department of Veterans Affairs medical centers between 2000 and 2010 were examined. Strategies used system-wide included blood pressure control as a performance measure, automatic notification to healthcare providers, electronic reminders, and a systematic revisit schedule. The main outcome measure was the percentage of hypertensive patients whose hypertension was controlled and the level of blood pressure each month. In the hypertensive cohort (mean age 62.9±13.4 years, 96.0% male), 52.3% of patients were white, 25.1% were black, and 21.1% were Hispanic. Blood pressure control rates improved from 45.7% in September 2000 to 76.3% in August 2010. Improvements were similar across ethnic, racial, age, and sex groups. Average systolic/diastolic blood pressure decreased from 142.6/77.1 mm Hg in 2000 to 131.2/74.8 mm Hg in 2010, a decrease of 11.3/2.3 mm Hg ( P <0.0001 for both). Systolic and diastolic blood pressures were lower in summer than in winter, and this trend continued through 2010. On average, control rates increased by 3.0% per year and were 6.8% higher in summer than in winter. Conclusions— High rates of blood pressure control can be achieved in all age and ethnic groups and in both sexes. # Clinical Perspective {#article-title-17}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. Methods and Results— A cohort of 582 881 hypertensive patients and 260 924 normotensive individuals treated in 15 Department of Veterans Affairs medical centers between 2000 and 2010 were examined. Strategies used system-wide included blood pressure control as a performance measure, automatic notification to healthcare providers, electronic reminders, and a systematic revisit schedule. The main outcome measure was the percentage of hypertensive patients whose hypertension was controlled and the level of blood pressure each month. In the hypertensive cohort (mean age 62.9±13.4 years, 96.0% male), 52.3% of patients were white, 25.1% were black, and 21.1% were Hispanic. Blood pressure control rates improved from 45.7% in September 2000 to 76.3% in August 2010. Improvements were similar across ethnic, racial, age, and sex groups. Average systolic/diastolic blood pressure decreased from 142.6/77.1 mm Hg in 2000 to 131.2/74.8 mm Hg in 2010, a decrease of 11.3/2.3 mm Hg (P<0.0001 for both). Systolic and diastolic blood pressures were lower in summer than in winter, and this trend continued through 2010. On average, control rates increased by 3.0% per year and were 6.8% higher in summer than in winter. Conclusions— High rates of blood pressure control can be achieved in all age and ethnic groups and in both sexes.

Postcountershock fibrillation in digitalized myocardial cells in vitro

Postcountershock arrhythmias are potentiated in patients receiving digitalis; and these arrhythmias frequently lead to irreversible ventricular fibrillation and death. The mechanisms underlying this potentiation are largely unknown. The purpose of this study was to determine whether an accentuation of electric shock induced arrhythmias was produced in in vitro myocardial cells by ouabin, a fast-acting digitalis glycoside. Such an accentuation would suggest that the in vivo potentiation occurred in the individual myocardial cell rather than through some secondary mechanism such as action on the nervous system as had been previously suggested. Myocardial cells grown in vitro were subjected to 5 msec square wave electric field stimulation of varying intensity. Pre- and postshock arrhythmias were evaluated using a photovoltaic cell mounted on a closed-circuit television monitor. The photocell converted the change in light intensity produced by cellular contraction to an electrical signal which was then processed and displayed on a strip chart recorder. Fibrillation of the cell sheet and of portions of individual myocardial cells could be observed visually on the television monitor. “Therapeutic” (antiarrhythmic) concentrations of ouabain were observed in the range of 1 x 10−6M to 5 x 10−6M; “toxic” (arrhythmia producing) concentrations were above, 1 x 10−5M. Electric shocks of intensities which produced a short postshock arrest in nondigitalized cells, produced an increased duration of arrest proportional to the ouabain concentration in the range of 5 x 10−8M to 7 x 10−6M. Cellular fibrillation has been previously observed in in vitro myocardial cells after extremely high shock intensities in the absence of ouabain or after toxic concentrations of ouabain in the absence of electric shock. Similar cellular fibrillation was observed in this study after low intensity electric shocks in cells exposed to low concentrations of ouabain, neither of which produced cellular fibrillation alone. Because this cellular fibrillation in vitro appears to be related to “irreversible” fibrillation in vivo, these results suggest that the deleterious interactions between digitalis and electric countershock occur directly in the myocardial cell and that postshock cellular fibrillation may be the basis for the “unmasking” of digitalis toxicity by electric countershock which has been of clinical concern.

Effects Of Monophasic Defibrillator Waveform Intensity On Graded Response Duration In A Computer Simulation Of The Ventricular Action Potential

This study uses a computer model of the ventricular action potential to examine the ionic basis for the increase in graded response duration with increasing stimulus intensity which is observed experimentally. A 10 msec monophasic defibrillator waveform with intensity ranging fiom 1 to 5 times diastolic threshold was used to produce graded responses during the cellular refractory period. Response duration was a sigmoidal function of stimulus intensity which reached a plateau at three times threshold. Prolonged responses were associated with increased sodium channel activation. Prolonged graded responses, by protecting cells from approachin fibrillation wavefronts, may cause successd defibrillation by high intensity electric field shocks.

GUIDELINES ALLOWING CONTROL OF HYPERTENSION IN NON-DIABETICS GREATER THAN 60 YEARS OLD AT UP TO 150 MMHG AVERAGE SYSTOLIC BLOOD PRESSURE INCREASES PATIENT MORTALITY IN VETERANS

Background: The Veterans Affairs (VA) Electronic Health Record (EHR) contains the vital signs of over 8,000,000 patients, allowing comparisons between blood pressure (BP) control and mortality. Methods: We reviewed changes in blood pressure (BP) over 15 years (2000-2014). Hypertension (HTN) was