Systemic neurohumoral activation and vasoconstriction during pacing-induced acute myocardial ischemia in patients with stable angina pectoris

To identify the effect of myocardial ischemia on systemic neurohormones and vascular resistance, 32 untreated, normotensive patients with coronary artery disease underwent incremental atrial pacing until angina. Arterial and coronary venous lactate and arterial values of catecholamines and angiotensin II were determined at control, at maximal pacing rates, and at 1, 2, 5 and 30 minutes after pacing. Based on pacing-induced ST-segment depression (greater than or equal to 0.1 mV) or myocardial lactate production, or both, patients were selected as ischemic (n = 25) or nonischemic (n = 7). Baseline clinical and hemodynamic data were comparable. During pacing, chest pain was similar (20 ischemic vs 7 nonischemic patients). Also, hemodynamic measurements were comparable, except for contractility, which did not improve, and left ventricular end-diastolic pressure, which significantly increased in ischemic patients. Moreover, during ischemia arterial pressures increased significantly (13%) and systemic resistance increased from 1,470 +/- 60 (control) to 1,632 +/- 76 dynes.s.cm-5 5 minutes after pacing (p less than 0.05) in ischemic but not in nonischemic patients. Pacing did not affect neurohormones in nonischemic patients. In contrast, norepinephrine in ischemic patients increased significantly from 1.7 +/- 0.2 (control) to 2.6 +/- 0.3 (maximal pacing) and to 3.0 +/- 0.4 nmol/liter (1 minute after pacing), whereas angiotensin II levels increased from 6.2 +/- 1.4 (control) to 9.3 +/- 2.1 pmol/liter (1 minute after pacing, p less than 0.05). Epinephrine only increased during maximal rates (0.9 +/- 0.1 vs 0.6 +/- 0.1 nmol/liter at control, p less than 0.05). Thus, myocardial ischemia activates circulating catecholamines and angiotensin II, accompanied by systemic vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of left ventricular residual function using postextrasystolic potentiation. Relation between systolic time intervals and angiographic study

The effects of postextrasystolic potentiation (PESP) on systolic time intervals and left ventricular wall motion were studied during diagnostic cardiac catheterization in 20 patients (4 normal individuals, 11 patients with coronary artery disease and 5 patients with idiopathic dilated cardiomyopathy). Postextrasystolic changes in the aortic pressure and systolic time intervals were measured from the electrocardiogram and aortic pressure tracing. After a micromanometer-tipped catheter was positioned in the ascending aorta just above the aortic valve, a single ventricular premature beat was introduced using an R-wave coupled stimulator. PESP was then studied during left ventriculography which was undertaken simultaneously in the right anterior oblique 30 degrees and left anterior oblique 60 degrees positions. Following two or three normal sinus beats, a right ventricular extrastimulus was delivered again under the same stimulating condition. PESP in all patients caused a decrease in the ratio of the preejection period to the left ventricular ejection time (PEP/ET). The average percent decrease was 21% (from 0.429 +/- 0.162 to 0.339 +/- 0.102, p less than 0.001). The left ventricular ejection fraction (EF) increased in all patients with PESP from 0.52 +/- 0.20 to 0.61 +/- 0.17 (p less than 0.001). The postextrasystolic changes in the PEP/ET ratio and EF were greater in patients with low cardiac performance. There was a good correlation (r = -0.85, p less than 0.001) between the changes in the EF and those in PEP/ET in PESP. Thus, it is possible to determine left ventricular residual function (the postextrasystolic change in the global EF) using the postextrasystolic change in PEP/ET in patients with coronary artery disease and dilated cardiomyopathy.     

Alpha-receptor restriction of coronary blood flow during atrial fibrillation

The effects of atrial fibrillation (AF) on coronary circulation before and after alpha-receptor blockade were studied in 14 anesthetized, open-chest dogs. AF was induced by electrical stimulation of the left atrial appendage; identical rhythmic heart rates were adjusted by left atrial pacing. During atrial pacing, coronary vascular resistance (CVR) was 0.97 +/- 0.10 mm Hg X min X 100 g/ml (resistance units [RU]), coronary blood flow (CBF) 125 +/- 14 ml/min X 100 g, and oxygen saturation 30 +/- 2%; plasma epinephrine was 193 +/- 42 pg/ml and norepinephrine 584 +/- 111 pg/ml. During AF, CVR was higher (1.16 +/- 0.11 RU, p less than 0.0005), whereas CBF (92 +/- 9 ml/min X 100 g, p less than 0.001) and coronary sinus oxygen saturation (24 +/- 2%, p less than 0.0025) were lower than during atrial pacing. When AF was induced, epinephrine increased to 333 +/- 98 pg/ml (p less than 0.05) and norepinephrine to 1,005 +/- 214 pg/ml (p less than 0.005). The large increase in plasma catecholamines suggested an activation of the sympathoadrenal system during AF. In addition, the alpha-receptor blocker phenoxybenzamine (10 mg/kg, intravenously) abolished the differences in CVR, CBF and oxygen saturation between AF and atrial pacing. The data suggest that the decrease in CBF and increase in CVR during experimentally induced AF are caused by coronary vasoconstriction, mediated by sympathetic activation of alpha receptors in the coronary vascular bed.     

Energy cost of postextrasystolic potentiation in man

The energetic costs of post-extrasystolic potentiation (PEP) were assessed by evaluating left ventricular function and coronary blood flow in 16 patients with different forms of cardiac disease during cardiac catheterisation under basal conditions and sustained coupled right ventricular pacing. The coronary blood flow was measured by thermodilution techniques with sampling in the aorta and coronary sinus to measure O2 concentration, glucose, and plasma lactate and catecholamine levels. Parameters of LV function were calculated from data obtained from biplane left cineventriculography. During PEP, the ejection fraction increased from 0.48 +/- 0.8 to 0.62 +/- 0.22, the mean velocity of circumferential fibre shortening from 0.79 +/- 0.37 to 1.12 +/- 0.45 circ/s (p less than 0.001) and systolic work from 97 +/- 46 to 139 +/- 67 g/m2 (p less than 0.05). Coronary blood flow increased from 176 +/- 60 to 305 +/- 155 ml/min; myocardial oxygen consumption per potentialized beat rose from 0.15 +/- 0.07 to 0.50 +/- 0.33 ml/beat (p less than 0.001) whilst cardiac efficiency fell from 19.1 +/- 8 to 9.2 +/- 4% (p less than 0.001). PEP was associated with increased myocardial noradrenaline secretion (-3.1 +/- 31.5 ng/min under basal conditions to 30.2 +/- 42.8 ng/min, p less than 0.05). Therefore, the inotropic effect of PEP imposes a high metabolic demand and is associated with increased myocardial noradrenaline secretion.     

Response of the left ventricle in idiopathic dilated cardiomyopathy to postextrasystolic potentiation

The effectiveness of postextrasystolic potentiation (PESP) was assessed to detect residual function of the left ventricle in seven patients with idiopathic dilated cardiomyopathy (IDC). The postextrasystolic changes in the aortic pressure pulse, global left ventricular function, and quantitative regional left ventricular wall motion were investigated. PESP caused an increase in the peak systolic aortic pressure (116 +/- 17 to 130 +/- 25 mm Hg, p less than 0.01), a decrease in the peak diastolic aortic pressure (74 +/- 12 to 61 +/- 11 mm Hg, p less than 0.001), a decrease in preejection period/left ventricular ejection time (PEP/LVET) ratio (0.637 +/- 0.136 to 0.457 +/- 0.097, p less than 0.001), and an increase in the global left ventricular ejection fraction (LVEF) (0.26 +/- 0.09 to 0.40 +/- 0.12, p less than 0.01). Postextrasystolic changes in LVEF were inversely related to changes in PEP/LVET (r = -0.76, p less than 0.05). The postextrasystolic patterns of the regional wall motion of the left ventricle were different in each patient. The results of this study suggest that residual left ventricular function can be detected in patients with IDC by their response to PESP.     

Dissociation of sympathetic responses to baroreceptor loading and unloading in compensated congestive heart failure secondary to ischemic or nonischemic dilated cardiomyopathy.

This study tested the hypothesis that abnormalities of baroreceptor-mediated suppression of sympathetic activity may persist in chronic congestive heart failure (CHF) despite pharmacologic treatment and clinical stability. Plasma norepinephrine and norepinephrine kinetics (using 3HNE infusions) were measured during head-up and head-down tilt in 8 patients with chronic CHF and 6 normal control subjects. In response to upright tilt, normal subjects increased plasma norepinephrine (270 +/- 45 to 413 +/- 60 pg/ml, p less than 0.001) and norepinephrine spillover (540 +/- 103 to 781 +/- 124 ng/min, p less than 0.001). Patients also increased plasma norepinephrine (436 +/- 105 to 600 +/- 112 pg/ml, p less than 0.05) and norepinephrine spillover (802 +/- 180 to 1,037 +/- 370 ng/min). During head-down tilt, plasma norepinephrine decreased in normal subjects (from 413 +/- 60 to 256 +/- 26 pg/ml, p less than 0.001). The decrease was due entirely to a decrease in norepinephrine spillover (781 +/- 124 to 466 +/- 40 ng/min, p less than 0.001). In contrast, there was no significant change in norepinephrine spillover (1,037 +/- 370 to 949 +/- 338 ng/min) during head-down tilt in patients with CHF. These data suggest that suppression of sympathetic activity during baroreceptor loading may be defective in CHF despite relative preservation or correction of the response to baroreceptor unloading.     

Catecholamine metabolism during pacing-induced angina pectoris and the effect of transcutaneous electrical nerve stimulation

The arterial levels of norepinephrine and epinephrine were estimated in 14 patients with severe coronary artery disease in order to assess the catecholamine metabolism during pacing-induced angina pectoris and to evaluate the effects of transcutaneous electrical nerve stimulation (TENS). Arterial levels of epinephrine and norepinephrine increased significantly during pacing to angina pectoris (p less than 0.05 and p less than 0.001, respectively), indicating that maximal atrial pacing induced an increase in sympathetic tone. At the corresponding pacing rate during TENS, myocardial lactate production was improved (p less than 0.01) and the ST segment depression was less pronounced (p less than 0.05). The maximal pacing rate during TENS was 141 +/- 24 compared to 123 +/- 19 (p less than 0.01) and the heart rate-blood pressure product was also significantly higher (p less than 0.01), suggesting an elevation of the anginal threshold by TENS. Systemic vascular resistance and systolic blood pressure were significantly reduced (both p less than 0.01). These beneficial results may be caused by a decrease in left ventricular afterload as reflected by a fall in systolic blood pressure and may be explained by reduced sympathetic activity. TENS may decrease the sympathetic activity either directly or indirectly as a consequence of pain inhibition. This hypothesis is supported by the fact that arterial levels of epinephrine and norepinephrine dropped during TENS in TENS responders.     

"Isolength" postextrasystolic potentiation as a predictor of functional restoration following surgical revascularization for myocardial ischemia

A previously developed method of programmed postextrasystolic potentiation (PESP) was assessed in eight patients with medically refractory unstable angina, as a predictor of functional restoration resulting from surgical revascularization. Prior to coronary arteriography, left ventricular segmental wall motion was determined during ventricular pacing and the first postextrasystolic beat following an extrasystole. The postextrasystole was induced at an interval calculated to occur at a time where ventricular preload was identical to the regular paced beat (isolength interval). The left ventricular wall was divided into six segments, each subscribing one area of the ventriculogram, and correction for rotation during systole was made. Of 48 segments, 21 were considered "jeopardized," due to greater than 70% reduction in cross-sectional lumen of the serving coronary arteries. Fifteen of these 21 responded to PESP, increasing their segmental area ejection fraction from 44 +/- 5 (paced "normal" beat) to 56 +/- 6 (postextrasystolic beat) (p less than 0.05). Following surgical revascularization, these segments showed an improvement in their baseline area ejection fraction from 44 +/- 6 to 58 +/- 5 (p less than 0.05). Six jeopardized segments that failed to respond to PESP prior to revascularization showed functional deterioration after revascularization. The 27 non-jeopardized segments (which were not revascularized) also showed functional improvement, suggesting improved collateral flow. This study demonstrates that isolength postextrasystolic potentiation obtained with a standardized pacing protocol may be used to predict the potential for improvement in cardiac function following surgical revascularization. Our results also show that lack of PESP predicts loss of left ventricular myocardial function following revascularization.     

Changes in arterial levels and myocardial metabolism of catecholamines during pacing-induced angina pectoris.

In order to elucidate the effects of atrial pacing on cardiac catecholamine metabolism, 11 patients were studied during cardiac catheterization. Blood samples were drawn from a peripheral artery and the coronary sinus for estimation of catecholamine concentrations. Heart rate was increased by 10 beats/min each minute, and all patients experienced chest pain at maximal pacing rate. Coronary sinus blood flow rose from 122 +/- 19 at rest to 208 +/- 25 ml/min at final pacing rate, and myocardial lactate extraction ratio decreased. There was no significant change in arterial epinephrine levels, whereas the extraction ratio decreased (p less than 0.05). The norepinephrine arterial levels increased at the final pacing rate (p less than 0.01). The calculated myocardial release increased as well, but not to a statistically significant degree. The exact mechanisms of the rise in sympathetic activity and arterial norepinephrine levels cannot be ascertained with the present study design. Myocardial ischemia with subsequent chest pain seems to be a probably cause for the increased sympathetic outflow.     

Experimental myocardial infarction. XVI. The detection of inotropic contractile reserve with postextrasystolic potentiation in acutely ischemic canine myocardium.

Postextrasystolic potentiation after a single closely coupled extrasystole may identify residual ventricular contractile performance in acutely ischemic myocardium without producing sustained secondary ischemic depression of myocardial function. Postextrasystolic potentiation was systematically used in eight open chest dogs to assess the progression of regional contraction abnormalities during a 10 minute occlusion of the left anterior descending coronary artery. Segment function was determined from pressure-length loop areas inscribed during right ventricular pacing at 128 +/- 3 (mean +/- standard error of the mean) beats/min, and after single closely coupled (179 +/- 3 msec) extrasystoles. Despite a 50 percent decrease in border zone segment function, postextrasystolic potentiation consistently augmented mechanical performance to control levels throughout the ischemic period. Central ischemic zone segment function deteriorated more profoundly, with the development of holosystolic aneurysmal bulging within 30 seconds after occlusion. Nonetheless, postextrasystolic potentiation produced marked inotropic augmentation, but not to control levels, for up to 10 minutes of ischemia. These results suggest that latent viability and contractile reserve may exist during brief periods of coronary occlusion.     

Mechanism of postextrasystolic potentiation in the right ventricle.

The mechanism of postextrasystolic potentiation (PESP) has been studied in the left ventricle in humans; however, this phenomenon has not been evaluated in the right ventricle. Accordingly, 18 sinus beats were compared to postextrasystolic beats during the same cineventriculogram using simultaneous high-fidelity right ventricular (RV) and pulmonary artery pressures and cast-validated biplane cineventriculographic volumes in normal patients. The increase in cycle length was 22 +/- 12% (standard deviation) in the postextrasystolic beats. Right ventricular ejection fraction increased from 61 +/- 10 to 68 +/- 4% (p less than 0.001) and RV stroke volume increased from 99 +/- 18 to 128 +/- 20 ml (p less than 0.001) due to an increase in RV end-diastolic volume (165 +/- 34 to 189 +/- 30 ml, p less than 0.001) as RV end-systolic volume (65 +/- 24 to 61 +/- 17 ml, difference not significant) and RV end-systolic pressure (16 +/- 7 to 17 +/- 6 mm Hg, difference not significant) remained unchanged. Despite an increase in RV systolic pressure from 29 +/- 7 to 31 +/- 7 mm Hg (p less than 0.01) and an increase in RV end-diastolic pressure from 8 +/- 4 to 10 +/- 5 mm Hg (p less than 0.001), RV +dP/dtmax did not change (318 +/- 102 to 294 +/- 82 mm Hg/s, difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of bucindolol in systemic hypertension

The hemodynamic effects of oral bucindolol, a non-selective beta-adrenergic blocking agent with intrinsic sympathomimetic activity and direct vasodilating properties, were studied at rest and during handgrip exercise with a flotation-directed pulmonary artery catheter in 12 patients with mild to moderate essential hypertension. After the initial dose of 150 mg of bucindolol, blood pressure (BP) was significantly reduced and cardiac output was increased (from 5.9 +/- 0.8 to 6.8 +/- 1.6 liters/min) in the supine position and during exercise (p less than 0.05). Systemic vascular resistance was reduced (from 1,555 +/- 339 to 1,311 +/- 467 dynes s cm-5, p less than 0.01) at rest and without significant changes during exercise. There were increases in heart rate (13 +/- 13%, p less than 0.01) and right atrial (69 +/- 77%, p less than 0.05), pulmonary arterial (38 +/- 24 %, p less than 0.001) and pulmonary artery wedge pressures (62 +/- 46%, p less than 0.001) during exercise. Bucindolol did not change these variables at rest or during exercise. Bucindolol increased plasma norepinephrine levels both at rest (from 330 +/- 151 to 588 +/- 320 ng/liter, p less than 0.01) and during exercise (from 468 +/- 220 to 685 +/- 390 ng/liter, p less than 0.05). After 4 weeks of bucindolol with doses of 50 to 200 mg 3 times daily, BP was reduced in both supine and standing positions (mean arterial BP of 11 +/- 7% [p less than 0.001] and 11 +/- 6% [p less than 0.001], respectively), without changes in cardiac output, systemic vascular resistance or plasma norepinephrine level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Potentiation of atrial contractility by paired pacing augments ventricular preload and systolic performance

BACKGROUND: Paired electrical stimulation and postextrasystolic potentiation (PESP) of contractility has been extensively studied in ventricular myocardium, but less is known about PESP of atrial contractility. Our aim was to determine whether PESP of atrial contractility could augment left ventricular (LV) preload and improve LV systolic performance. METHODS AND RESULTS: A paired electrical stimulus closely following the pacing stimulus was applied to isolated atrial and ventricular myocardium from 4 dog hearts, and the interval dependent force potentiation was examined. In isolated atrial myocardium, paired pacing increased the active tension from a baseline of 1.36 +/- 0.23 to 2.60 +/- 0.57 g/mm(2); in ventricular myocardium active tension increased from 2.58 +/- 0.42 to 3.81 +/- 0.27 g/mm(2) (both P <.01). Then, LV pressure (micromanometer) and segment length (ultrasonic crystals) were measured in the intact hearts of 7 anesthetized dogs in which premature stimuli were applied to the atrium. In intact hearts, paired pacing of the atrium (coupling interval 200 ms) increased LV end-diastolic pressure from 3.8 +/- 1.0 to 6.4 +/- 1.0 mm Hg; systolic pressure increased from 105 +/- 6 to 112 +/- 7 mm Hg (both P <.05). LV pressure-length loop area (regional stroke work) increased 10.5 +/- 0.2%. CONCLUSIONS: Isolated atrial myocardium exhibits substantial PESP of contractility, which is similar to ventricular myocardium. In the intact heart, atrial PESP augments LV systolic performance by effecting an increase in LV preload. This technique may provide a means of improving cardiac performance in patients with heart failure.     

Adrenergic coronary vasoconstriction in acute right ventricular hypertension

This study tested the hypothesis that alpha-adrenergically mediated coronary vasoconstriction during the haemodynamic stress of right ventricular hypertension antagonises the effect of adenosine. Myocardial blood flow and plasma catecholamines were measured in 12 awake, but mildly sedated, chronically instrumented dogs during acute pulmonary artery constriction (PAC) before and during an infusion of adenosine (1 mg X kg-1 iv), with and without prior alpha blockade with phenoxybenzamine (10 mg/kg iv). PAC was performed by gradual inflation of a pulmonary artery hydraulic occluder until aortic pressure began to fall, after which aortic pressure was restored to control levels by aortic constriction. Heart rate was held constant by pacing. Two distinct patterns of response to adenosine during PAC were observed. Six dogs (group A) demonstrated attenuation of adenosine induced coronary vasodilatation; left ventricular (LV) myocardial flow fell from 7.35 +/- 1.14 ml X min-1 . g-1 (+/- SE) during adenosine to 3.63 +/- 0.81 during PAC and adenosine (p less than 0.05). In the six remaining dogs (group B) attenuation was not observed (LV flow = 6.51 +/- 0.92 during adenosine; 8.14 +/- 1.11 during PAC and adenosine). During PAC, both the severity of RV hypertension and levels of circulating catecholamines were greater in group A than in group B. Alpha-blockade partially restored adenosine responsiveness in group A during PAC, and LV flow increased to 6.23 +/- 0.80 (p less than 0.05). We propose that attenuation of the coronary flow response to adenosine infusion during PAC is related to the severity of PAC and alpha-adrenergically mediated coronary vasoconstriction.     

Postextrasystolic potentiation and its contribution to the beat-to-beat variation of the pulse during atrial fibrillation.

BACKGROUND. Beat-to-beat variations in the pulse during atrial fibrillation (AF) have conventionally been attributed to time-dependent changes in filling. We have explored the possibility that they are dependent on the intrinsic myocardial interval force relation. METHODS AND RESULTS. Left ventricular (LV) contractility (maximum rate of rise of pressure, LV dP/dtmax) and ascending aortic blood velocity were measured during cardiac catheterization in 15 patients with AF. Beats preceded by an interval of less than 500 msec were excluded from analysis to reduce the confounding influence of incomplete mechanical restitution. The LV dP/dtmax was then related to the prepreceding interval. An inverse relation consistent with postextrasystolic potentiation was obtained in all 15 patients (Spearman's rank correlations, -0.56 to -0.86; p less than or equal to 0.0001). This relation was confirmed in three patients during pacing that overrode the AF and introduced single-interval variations into steady-state pacing. The ECG sequences from six of the AF patients were used to drive isometrically contracting guinea pig papillary muscle and human right ventricular tissue (n = 7); the same inverse relation was demonstrated. On a beat-by-beat basis, the maximum rate of rise of force in the isolated muscle correlated well with LV dP/dtmax in the patients (r = 0.50-0.86, p less than or equal to 0.0001). The relation of the integral of aortic velocity (AVI, proportional to stroke volume) to prepreceding interval was also inverse, whereas important correlations were demonstrated between LV dP/dtmax and AVI (Spearman's rank correlations, 0.27-0.95; p less than or equal to 0.0001). CONCLUSIONS. This study demonstrates that postextrasystolic potentiation contributes to the characteristic beat-to-beat variation of the pulse in AF.     

Reduced cardiovascular responsiveness to exercise-induced sympathoadrenergic stimulation in patients with cirrhosis

Cardiovascular responsiveness to sympathoadrenergic activation obtained by muscle exercise in the supine position was evaluated in 22 patients with cirrhosis (11 alcoholic, 11 postnecrotic/cryptogenic; 14 with ascites) and 10 controls of comparable age. Plasma norepinephrine, heart rate, diastolic arterial pressure and cardiac function, as evaluated by systolic time intervals, were monitored. At rest, cirrhotics had higher norepinephrine (154 +/- 19 S.E.M. ng/l) and heart rate (79 +/- 2 beats per min) than controls (71 +/- 3 ng/l, p less than 0.01; 67 +/- 2 beats per min, p less than 0.001), whereas diastolic arterial pressure was similar. Among systolic time intervals, electromechanical systole, pre-ejection period, electromechanical delay and pre-ejection period to left ventricular ejection time ratios were prolonged (p less than 0.05 or less). Exercise led to significant increases in plasma norepinephrine, heart rate and diastolic arterial pressure in both controls and patients. In the latter, however, whereas the increase in norepinephrine was greater (p less than 0.001), those in heart rate and diastolic arterial pressure were less (p less than 0.005). As expected, most systolic time intervals shortened, but the decrease in pre-ejection period (p less than 0.05), isometric contraction time (p less than 0.02) and pre-ejection period to left ventricular ejection time ratio (p = 0.06) was less in patients than in controls. Direct correlations between exercise-induced changes in norepinephrine and both diastolic arterial pressure (r = 0.81; p less than 0.005) and heart rate (r = 0.85; p less than 0.002) were observed in controls, while inverse correlations (r = -0.67, p less than 0.001 and r = -0.44; p less than 0.05) were found in cirrhotics. These results suggest that cardiovascular reactivity to the sympathetic drive is impaired in cirrhotics. The impairment of cardiac contractility may be due to altered electromechanical coupling.     

Effect of postextrasystolic potentiation on systolic bulging of ischemic myocardium

Because the extent of myocardial bulging after acute coronary occlusion is primarily dependent on wall tension, this study examined whether the decrease in systolic bulging with postextrasystolic potentiation was due to contractile reserve or to changes in loading conditions. Seven dogs were atrially paced at 100 beats/min after the sinus node was crushed and atrial extrasystoles were generated. The left ventricular minor axis diameter and segment lengths in the ischemic and nonischemic zones were measured with sonomicrometers. Wall tension was estimated using Laplace's law, and regional tension-length loops were determined. By 5 min after the left anterior descending coronary artery was occluded, there was regional bulging. Postextrasystolic potentiation diminished the extent of bulging by increasing both isovolumic and ejection percent systolic shortening (isovolumic -9.1 +/- 2.0% to -5.9 +/- 1.7%, p less than 0.008; ejection 2.2 +/- 0.7% to 4.3 +/- 2.0%, p less than 0.008). The tension-length loops after coronary occlusion showed an exponential upstroke and almost superimposed downstroke consistent with passive movement. The loops were unchanged by postextrasystolic potentiation. Wall tension data showed that bulging was reduced because of a shift down the tension-length curve as end-systolic wall tension was reduced by augmented nonischemic contraction. Similar results were seen at 60 min of coronary occlusion. This study demonstrates that the decrease in bulging seen with postextrasystolic potentiation is due to changes in loading conditions and not to contractile reserve.     

Thromboxane release in coronary artery disease: spontaneous versus pacing-induced angina

To determine thromboxane A2 release in coronary artery disease, we measured its stable metabolite thromboxane B2 by radioimmunoassay in 20 patients. In 15 patients with stable disease (last angina episode greater than 96 hours before study), coronary venous thromboxane B2 concentrations were lower than in aortic blood (mean 109 +/- 36 vs 194 +/- 40 pg/ml, p less than 0.001). In contrast, in five other patients with spontaneous angina, coronary venous thromboxane B2 concentrations were higher than aortic thromboxane B2 concentrations during the angina episode (mean 1716 +/- 316 vs 875 +/- 388 pg/ml, p less than 0.02). Plasma thromboxane B2 levels were in the normal range (mean 175 +/- 35 pg/ml) in patients with stable angina but significantly (p less than 0.02) higher in patients with spontaneous angina. With atrial pacing to the point of chest pain and/or ECG changes in patients with stable coronary artery disease, aortic thromboxane B2 concentrations increased in 10 of 13 patients (mean 283 +/- 70 pg/ml, p less than 0.02). Coronary venous thromboxane B2 concentrations increased in seven patients at peak pacing rates (mean 223 +/- 76 pg/ml) and in three other patients after termination of pacing. These data indicate that release of thromboxane A2 is much greater during spontaneous angina than with pacing stress in patients with coronary artery disease. Thromboxane A2 released during spontaneous or pacing-induced angina may modulate coronary and systemic vascular tone. Enhanced thromboxane A2 activity may either precede or follow myocardial ischemia and could be a factor in the initiation and propagation of the ischemic episode.     

Alterations in serum sodium in relation to atrial natriuretic factor and other neuroendocrine variables in experimental pacing-induced heart failure

The pathophysiologic role of atrial natriuretic factor and other neuroendocrine variables in relation to serum sodium and renal function was evaluated in 15 conscious dogs with severe chronic ventricular pacing-induced heart failure (250 beats/min for 5.1 +/- 0.4 weeks). Six sham-operated dogs observed over an 8 week period served as controls. Development of heart failure was characterized by a progressive increase in plasma norepinephrine, renin activity and aldosterone from control values of 293 +/- 15 pg/ml, 1.4 +/- 0.4 ng/ml per h and 124 +/- 42 pg/ml, respectively, to 1,066 +/- 96 pg/ml, 10.2 +/- 2.4 ng/ml per h and 577 +/- 151 pg/ml (all p less than 0.01), respectively, at severe heart failure. In contrast to other neuroendocrine variables, plasma atrial natriuretic factor increased from a control level of 243 +/- 74 pg/ml to a peak concentration of 724 +/- 149 pg/ml (p less than 0.01) at 2 weeks, then declined and plateaued at twice the level of the control value as severe heart failure developed. At severe heart failure, serum sodium decreased from 147 +/- 0.6 to 141.8 +/- 2.1 mmol/liter (p less than 0.05), whereas urea increased from 6.0 +/- 0.5 to 7.8 +/- 0.6 mmol/liter (p less than 0.05). The change in serum sodium concentration correlated with plasma renin activity and aldosterone (r = -0.77, -0.88, respectively, both p less than 0.01), but not with norepinephrine or atrial natriuretic factor. When sinus rhythm was restored, 14 dogs were observed for 48 to 72 h and 8 dogs were followed up for another 4 weeks after cessation of pacing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics in humans

Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics were examined in 11 patients with angiographically normal coronary arteries and without variant angina or resting angina. Selective H1-receptor stimulation was achieved by infusing histamine into the left coronary artery at a rate of 2.0 micrograms/min for 5 minutes after pretreatment with cimetidine (25 mg/kg). Plasma histamine concentration in the coronary sinus, coronary sinus blood flow, heart rate, and aortic pressure were measured before, during, and after the histamine infusion. Coronary arterial diameter was measured by cinevideodensitometric analysis of coronary arteriograms performed before and immediately after the histamine infusion. During the histamine infusion, plasma histamine concentration in the coronary sinus increased from 0.33 +/- 0.06 to 5.86 +/- 0.71 ng/ml (p less than 0.01); coronary sinus blood flow increased from 98 +/- 12 to 124 +/- 13 ml/min (p less than 0.01), and coronary vascular resistance decreased from 1,113 +/- 117 to 851 +/- 91 mm Hg.min/l (p less than 0.01). Heart rate and aortic pressure remained unchanged. The mean luminal diameters of the proximal, middle, and distal left anterior descending artery increased by 9.4 +/- 3.6% (p less than 0.05), 19.2 +/- 3.8% (p less than 0.001), and 31.5 +/- 5.6% (p less than 0.001), respectively, after the histamine infusion. The mean luminal diameters of the proximal, middle, and distal left circumflex artery increased by 15.2 +/- 3.6% (p less than 0.01), 17.5 +/- 5.2% (p less than 0.01), and 20.6 +/- 4.3% (p less than 0.001), respectively, after the histamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)