Histological remodeling in an ovine heart failure model resembles human ischemic cardiomyopathy.

Staged coronary embolization, causing myocardial microinfarctions, has been shown in dogs and sheep to cause chronic ischemic heart failure (HF) that resembles the hemodynamics of the human condition. However, its histopathological basis remains unclear. We examined the hypothesis that the ventricular remodeling seen in such sheep resembles the histopathology of human ischemic cardiomyopathy (ICM). Understanding the pathophysiology of this model will determine its place in the development of treatment strategies for HF. Global left ventricular (LV) damage resulting in HF was induced by staged coronary embolization in 11 sheep. Six others served as controls (normal control, NC). In HF sheep, the heart was harvested 6 months after LV ejection fraction (EF) had stabilized at <35%. Histopathological profiles were compared in biventricular transverse sections at midpapillary level using computed image analysis. LV end-diastolic volume increased in the HF group from 84.9+/-29 to 122.4+/-30.3 ml (n=11, P<.05), but myocytes across the LV wall in noninfarcted zones decreased (435.7+/-38.2 NC; 297.8+/-48.4/unit area HF; n=11, P<.0001) as did myocyte nuclear density (990.5+/-51.5 NC; 677.5+/-121.1/mm(2) HF, n=11, P<.0001). In contrast, LV replacement and interstitial fibrosis increased as did myocyte diameter in noninfarcted zones: 0.1+/-0.1 to 6.2+/-4.5% (P=.0049); 2.0+/-1.0 to 7.6+/-4.9% (P=.0149); and 10.0+/-0.5 to 15.9+/-2.2 microm (P<.0001), respectively. Although LV myocyte nuclear length increased (10.2+/-1.0 NC; 12.2+/-0.9 microm HF, n=11, P=.0006), right ventricular (RV) myocyte nuclear density and length did not alter. In this ovine chronic HF model, LV dilation and interstitial and myocyte remodeling resemble human ICM.

Ventricular remodeling after cardiomyoplasty in heart failure sheep: passive and dynamic effects.

BACKGROUND: Recent reports claim that cardiomyoplasty (CMP) has a girdling effect on the left ventricle, to prevent dilatation and functional deterioration, but the mechanism of its long-term effects on the native heart is not known. We compared the relative role of CMP's active squeezing and passive girdling in chronically failing hearts. METHODS: After induction of stable heart failure (left ventricular ejection fraction = 27% +/- 7%) by staged coronary microembolization, CMP was performed in 11 of 18 sheep. After 8 weeks pacing training of the latissimus dorsi muscle (LDM), cardiac assist was begun with 1:2 synchronous bursts in 6 sheep (d-CMP, n = 6), and the LDM in the passive group (p-CMP, n = 5) remained unstimulated. Four (base line) and 30 weeks after induction of heart failure, the pressure-volume relationship was derived. RESULTS: After 30 weeks in d-CMP the slope (Emax) of the end-systolic pressure-volume relationship increased by 66% +/- 55% (p < 0.05) and external work efficiency by 48% +/- 41% (p < 0.01). In the passive CMP and control groups, slope and external work efficiency were unchanged. Conversely, left ventricular end-diastolic volume decreased (-14% +/- 12%, p < 0.05) in the dynamic CMP group compared with a static course in the passive CMP group (3% +/- 10%, p > 0.05) and an increase (18% +/- 15%, p < 0.05) in controls. CONCLUSIONS: Dynamic CMP improved native heart's contractility and external work efficiency. In addition, whereas passive CMP has simply a girdling effect, dynamic CMP also induces reverse left ventricular chamber remodeling.

In situ measurements of skeletal muscle power output using new capacitive strain gauge.

Experiments are described in which a fatigue index is determined for the latissimus dorsi muscle of sheep in situ, using capacitive strain gauges. Parallel experiments for invasive and non-invasive measurements are conducted, measuring global contraction and relaxation rates and shortening duration for paced muscle. The results show that, above one pulse per burst (5 V, 100 microseconds pulsewidth), contraction rates (62 +/- 11 mm s-1) and relaxation rates (50 +/- 7 mm s-1) are constant for unloaded muscle. For one animal, fatigue testing with a 2.5 kg load at six pulses per burst shows shortening rates increasing to a maximum (80 mm s-1) after 30 s and reducing to 5 mm s-1 after 150 s. The decrease in shortening amplitude is used as a fatigue index, log displacement against time. Power output is load dependent, measuring 4.7 W kg-1 with a 2.5 kg load. There is good agreement between the invasive and non-invasive measurements, thus providing a method for monitoring changes in muscle parameters non-invasively during future pacing transformation.

The effect of home training with direct blood pressure biofeedback of hypertensives: a placebo-controlled study.

BACKGROUND: Home training in self-lowering of blood pressure using continuous blood pressure feedback has not previously been reported. Enhancement of laboratory-learned skills was hypothesized on the basis of outcomes from other intellectual, emotional and physical endeavours. OBJECTIVE: To examine the supplementary effect of home blood pressure biofeedback training. DESIGN: Thirty unmedicated, mild hypertensives participated in a randomized, double-blinded, modified contingency placebo-controlled study. METHOD: After suitable screening and baseline blood pressure measurements subjects undertook eight laboratory biofeedback sessions and then 12 home training sessions over 4 weeks using continuous finger blood pressure monitoring. RESULTS: In the laboratory those being administered active therapy (n=16) lowered systolic pressures by 5 +/- 5.4 mmHg compared with a lowering of 4 +/- 4.2 mmHg with placebo (NS). During the fourth week at home lowering for the active group (11 +/- 8 mmHg) was greater than that with placebo (4 +/- 6.2 mmHg, P=0.017). Arm-cuff blood pressures were not statistically different for groups and with time but that of the active group was lower by 9 +/- 15.4/7 +/- 10.2 mmHg, which is a clinically relevant change, after home biofeedback. CONCLUSIONS: The efficacy of self-lowering of systolic blood pressure in mild hypertensives by continuous feedback was enhanced by 6 mmHg with 4 weeks of practice at home. Standard arm-cuff blood pressure was reduced by a clinically relevant amount. The home environment proved cost effective for this 'high-tech' approach.

Improved efficiency of energy transfer to external work in chronic cardiomyoplasty based on the pressure-volume relationship.

OBJECTIVE: Cardiomyoplasty is a surgical procedure to support the failing heart, in which a burst-stimulated latissimus dorsi muscle flap is transposed and wrapped around the ventricles. The effect of dynamic cardiac compression, implemented as cardiomyoplasty, on left ventricular performance remains controversial; the mechanism by which clinical symptoms are improved remains unclear. To investigate the mechanism for improvement of patients' symptoms, it is important to evaluate the effects of cardiomyoplasty on left ventricular energetics and on left ventricular systolic and diastolic function. We therefore evaluated the efficiency of energy transfer from the native pressure-volume area to external work under conditions of 1:3 skeletal muscle burst pacing in an animal model with chronic heart failure. METHODS: In seven Merino-Wether sheep, cardiomyoplasty was performed after stable heart failure was induced by staged coronary embolizations (ejection fraction < 35%). Hemodynamic assessment including the assessment of the pressure-volume relationship was performed 8 weeks after cardiomyoplasty when the latissimus dorsi muscle was fully trained. Instantaneous left ventricular pressure and volume were measured with a catheter-tipped manometer and a conductance catheter during steady-state conditions and after a transient inferior vena cava occlusion. The effect of dynamic cardiac compression on left ventricular systolic function was assessed by comparing pre-assisted and assisted beats and on diastolic function by comparing assisted and post-assisted beats. RESULT: The slope of the end-systolic pressure-volume relationship decreased by 30.5% +/- 27.8% (p = 0.02) during assisted beats. However, left ventricular pump performance improved by increasing stroke volume and external work by 35.9% +/- 36.0% (p = 0.03) and 9.7% +/- 6.8% (p = 0.03), respectively, resulting in a reduction of the volume intercept. As a result, the end-systolic pressure-volume relationship shifted to the left. The efficiency of energy transfer from the native pressure-volume area to the overall external work improved by 7.6% +/- 8.2% (p = 0.04). Cardiomyoplasty did not affect the time constant of left ventricular isovolumic pressure decline or the maximal rate of pressure decay, which suggested that cardiomyoplasty did not affect left ventricular relaxation. CONCLUSIONS: Dynamic cardiac compression in the form of cardiomyoplasty enhanced left ventricular pump performance without interrupting left ventricular filling. The ratio of energy transfer from the native pressure-volume area to the overall external work suggests a myocardial oxygen-sparing effect of cardiomyoplasty.

Effect of feedback signal and psychological characteristics on blood pressure self-manipulation capability.

Blood pressure presentation mode and personality are likely to influence biofeedback outcome. Thirty-six normotensive subjects were randomly assigned to visual or auditory continuous systolic feedback. "Distracting speech" and "broad band noise" were also superimposed and the effect on the biofeedback response was investigated. Psychological influence was also investigated. Systolic pressure reduction of 4 +/- 4.3 mmHg (visual, p = .04) and 5 +/- 5.5 mmHg (visual + auditory, p = .03) were achieved compared with auditory feedback (2 +/- 4.7 mmHg), which was less effective. The addition of noise or speech had no effect on the systolic response, but speech adversely affected diastolic reduction (p = .04). Mood (p = .003) was associated with systolic lowering, whereas increased trait anxiety (p = .06) and expectation (p = .03) had trends for opposite effects. Increased anger-hostility, state-anxiety, and expectation (p = .06) had links with systolic raising capability. We conclude that feedback modality and psychological characteristics have implications for studies investigating blood pressure manipulation capability.

A stable ovine congestive heart failure model. A suitable substrate for left ventricular assist device assessment.

Similarities in coronary circulation and heart size of sheep to that of humans are specific advantages of a sheep model of congestive heart failure (CHF). CHF was created in 11 sheep (51 +/- 4 kg) by selective sequential intracoronary injection of 90 microns microspheres under 1.5% isoflurane anesthesia. Hemodynamic characteristics were assessed at baseline, 4 weeks after establishment of CHF (ejection fraction [EF] < 35%, n = 11), and 26 weeks (n = 7) later. Baseline echocardiographic EF was 59 +/- 5% and fell to 26 +/- 5% after 5 +/- 2 embolizations. The left ventricular (LV) pressure-volume relationship showed stable decreases in LV end-systolic elastance (Ees) and preload recruitable stroke work. Intravenous infusion of dobutamine increased Ees from 2.8 +/- 1.7 to 4.3 +/- 2.2 and 4.5 +/- 1.4 mmHg/ml at heart rates of 140 and 160/min, respectively, at baseline. Increases of Ees (from 1.3 +/- 0.5 to 2.3 +/- 0.7 and 1.9 +/- 0.5 mmHg/ml at heart rates of 140 and 160/min, respectively) with dobutamine under CHF conditions did not exceed Ees values at baseline without dobutamine. This response to dobutamine infusion did not change 26 weeks after establishment of CHF. This stable ovine CHF model is proposed for studies on the long-term effects of cardiac assist devices.

Placebo-controlled biofeedback blood pressure effect in hypertensive humans.

The role of biofeedback in blood pressure control remains ill-defined because of nonspecific (placebo) effects, small study numbers, and the technical limitations of continuous pressure feedback. Clarification of its potential is awaited by those seeking a nonpharmacological approach to blood pressure control. This study examines the capability for systolic pressure lowering of 5 mm Hg or more using continuous pressure feedback in a statistical sample of untreated, well-characterized, mildly hypertensive individuals. Subjects were randomized in a double-blind study to active or placebo biofeedback. Placebo consisted of a modified contingency approach, using a partial disguise based on a digital high pass filter with 15 elements. Blood pressure-lowering capability was assessed during two laboratory sessions. Continuous visual feedback resulted in 11 of 28 subjects on active treatment and 12 of 28 on placebo treatment lowering their systolic pressure by 5 mm Hg or more (11 +/- 5.6 and 12 +/- 8.4 mm Hg, respectively; P = NS). Prestudy pressure was well-matched (153 +/- 9/97 +/- 4 and 154 +/- 8/98 +/- 4 mm Hg, respectively). An initial small difference in diurnal profile did not change. These findings indicate that among mildly hypertensive individuals, almost half can lower systolic pressure at will for short periods. This capability is independent of the real or placebo nature of the feedback signal. We conclude that there is no specific short-term biofeedback pressure-lowering capability in hypertensive individuals. Further exploration is needed to determine whether specific components of the placebo effect can be delineated, whether personality characteristics influence the response, and whether further biofeedback training can alter the outcome.

Physiological influences on continuous finger and simultaneous intra-arterial blood pressure.

Because of the clinical and experimental utility of continuous finger blood pressure measurements and the need for accuracy, we tested the performance of a new hydraulic device in 22 consecutive hypertensive subjects during physiological and pharmacological interventions. Ipsilateral brachial intra-arterial pressure was monitored during rest, Valsalva's maneuver, static handgrip, and mental arithmetic and after sublingual glyceryl trinitrate. In excess of 40,000 blood pressure values were analyzed. Average bias (intra-arterial minus finger blood pressure) was 8.2 +/- 17.0 mm Hg (mean +/- SD, P = NS) for systolic and 2.8 +/- 10.4 mm Hg (P = NS) for diastolic pressure. Two-way ANOVA of biases with subject and task factors showed a subject effect (P < .001). Intersubject and intrasubject standard deviations of bias were 13.8 and 9.8 mm Hg systolic and 8.7 and 5.7 diastolic, respectively. Linear drift (millimeters of mercury per minute) of finger pressure was greater (P < .001) for systolic than diastolic pressure during static exercise and math and after glyceryl trinitrate. Coefficients of determination for blood pressure ranged from 0.4 +/- 0.3 to 0.8 +/- 0.3 during the tasks. We conclude that (1) noninvasive finger blood pressure faithfully follows intra-arterial changes but with clinically relevant offsets, (2) this technique is best suited for assessing pressure changes, (3) physiological and pharmacological interventions do not consistently affect finger pressure accuracy, (4) many reports of finger blood pressure measuring devices are based on direct readings obtained with inadequate system response characteristics, and (5) the tested instrument falls short of the standard requirements (bias < or = 5 +/- 8 mm Hg) for devices that measure intermittently.

Environmental noise and sleep--a study of arousals, cardiac arrhythmia and urinary catecholamines.

Nine adult subjects with documented cardiac arrhythmia were studied during 4 nights of sleep in a laboratory. A sleep polygraph and single-channel electrocardiogram were recorded continuously throughout each night. After the 1st night's familiarization, the subjects were presented with 1 night each of 50 calibrated aircraft or truck noise events. One other night was noise-free. Intervals containing noise and paired quiet intervals were examined for sleep stage at interval onset, number of sleep stage changes and ventricular premature contractions (VPCs). Overnight urinary catecholamines were also assayed. It was found that noise increased the likelihood of arousal responses to the same extent in all sleep stages (p < 0.05). Four subjects showed frequent VPCs during the experiment. These VPCs were significantly related to sleep stage (p < 0.05) but not to noise events. Excretion of urinary catecholamines did not differ between noise and quiet nights.

Structural adaptation of the heart in borderline hypertensives in response to blood pressure lowering with captopril.

OBJECTIVE: To determine whether treatment of borderline hypertension reverses the cardiac 'amplifier' effect associated with increased left ventricular mass. DESIGN: Randomized, double-blind, placebo-controlled trial involving treatment for 6 months. SETTING: Ambulant outpatients in a teaching hospital. PARTICIPANTS: Recruited by local doctor referral or worksite screening. Average of two readings of entry blood pressures taken 1 week apart 140-160 mmHg (systolic) or 90-95 mmHg diastolic, or both. Twenty-six previously untreated males, mean +/- SD age 33 +/- 9.2 years with mean +/- SD blood pressure 138 +/- 7.4/90 +/- 7.0 mmHg entered and completed the study. INTERVENTIONS: Twelve subjects received captopril, average dose 72 mg/day for 24 weeks, the remainder receiving placebo. MAIN OUTCOME MEASURES: Echocardiographic left ventricular dimensions, mass and transmitral Doppler flow, as well as office, ambulatory and exercise blood pressure. RESULTS: In the captopril group blood pressure was reduced significantly. Left ventricular mass decreased significantly from 205 to 195 g at 8 weeks and to 202 g at 24 weeks, returning to 232 g 4 weeks after treatment. Interventricular septum thickness fell significantly at 24 weeks. Doppler parameters did not alter. Baseline 8-h ambulatory blood pressure did not change with treatment. The reduction in peak exercise systolic blood pressure in the captopril group was not different from the change in the placebo group. CONCLUSION: Blood pressure can be effectively lowered using captopril in young subjects with borderline hypertension. Treatment is well tolerated and leads to regression of left ventricular wall thickness and mass, suggesting that treatment of blood pressure elevations may be advisable at lower levels than currently recommended.

Continuous, non-invasive volume-clamp blood pressure: determinants of performance.

OBJECTIVE: To test a prototype hydraulic, non-invasive, continuous finger blood pressure monitor based on the volume-clamp principle for procedure-related factors likely to influence precision. DESIGN: The influence of these factors was determined by repeatability of finger blood pressure measurement and the relationship to contralateral arm-cuff blood pressure. METHODS: Repeated blood pressure measurements from three different fingers were made in 60 subjects following re-initialization of the device and re-insertion of the finger into the cuff. Repeatability was assessed in relation to simultaneous arm-cuff readings. Drift in arm-finger discrepancy was measured over a 1-h period. Finger diameter, drug therapy and presence of peripheral vascular disease were correlated with arm-finger blood pressure difference. RESULTS: Repeatability coefficients (twice the SD of the arm-finger difference) across device re-initialization were large, but similar to parallel repeated arm blood pressure determinations: 17.6 and 17.1 mmHg for systolic blood pressure (SBP) and 13.9 and 13.6 mmHg for diastolic blood pressure (DBP), respectively. Withdrawing and re-inserting the finger reduced repeatability substantially, with a 50% increase in repeatability coefficient. A trend towards a progressive 9-mmHg increase was observed in overestimation of SBP over the 1-h period. Mean +/- SD pooled arm-finger blood pressure differences were -10.8 +/- 14.6 mmHg for SBP and 4.5 +/- 9.4 mmHg for DBP. Blood pressure measured in different fingers was similar on average, with repeatability no poorer than for re-insertion of the same finger. The presence of peripheral vascular disease in 15 subjects correlated with a smaller arm-finger difference for DBP. CONCLUSIONS: Variations in positioning of the finger within the cuff influences blood pressure measurement during volume-clamp plethysmography, reducing its precision. Finger SBP exceeds brachial auscultatory readings and has similar precision.

Quantitative photoplethysmography: Lambert-Beer law or inverse function incorporating light scatter.

Finger blood volume is commonly determined from measurement of infra-red (IR) light transmittance using the Lambert-Beer law of light absorption derived for use in non-scattering media, even when such transmission involves light scatter around the phalangeal bone. Simultaneous IR transmittance and finger volume were measured over the full dynamic range of vascular volumes in seven subjects and outcomes compared with data fitted according to the Lambert-Beer exponential function and an inverse function derived for light attenuation by scattering materials. Curves were fitted by the least-squares method and goodness of fit was compared using standard errors of estimate (SEE). The inverse function gave a better data fit in six of the subjects: mean SEE 1.9 (SD 0.7, range 0.7-2.8) and 4.6 (2.2, 2.0-8.0) respectively (p < 0.02, paired t-test). Thus, when relating IR transmittance to blood volume, as occurs in the finger during measurements of arterial compliance, an inverse function derived from a model of light attenuation by scattering media gives more accurate results than the traditional exponential fit.