Effects of chronic oral quinidine on left ventricular performance

We studied the effects of 10 to 14 days of oral quinidine administration (200 mg every 8 hrs) on left ventricular (LV) $\text{dP}\text{dt}$ max and shortening fraction (%ΔD) in seve preinstrumented consclous dogs in the resting state, during atrial pacing at 120 bpm, and during an acute pressure load produced by intravenous phenylephrine. Dogs were studied before, during, and after oral quinidine administration with control measurements varying by < 10%. In the resting state, heart rate (85 ± 6 SEM vs 88 ± 7 bpm), LV end-diastolic pressure (7.2 ± 1.4 vs 6.7 ± 1.1 mm Hg), LV end-diastolic diameter (39.6 ± 3.2 vs 38.9 ± 2.7) did not differ (p > 0.05) before or during quinidine, respectively. During atrial pacing LV $\text{dP}\text{dt}$ increased similarly during the control and quinidine periods (+ 13 and + 11%), and %ΔD decreased equally (?26% and ?21%) during phenylephrine infusion off and on quinidine. Thus chronic oral quinidine administration in clinically therapeutic doses (serum quinidine levels 2.3 to 7.5 μg/ml) produced no depression in LV performance at rest or during an acute pressure load.     

Effect of the undisturbed pericardium on left ventricular size and performance during acute volume loading

Studies in instrumented dogs have suggested that the pericardium alters left ventricular diastolic pressure-volume relations and thus may influence systolic performance. However, the instrumentation used in these studies disrupts the pericardium and may have influenced the results. We therefore studied five conscious dogs by methods not traumatic to the pericardium, before and after pericardiectomy. Although heart rate and left ventricular systolic and end-diastolic pressures were not different before or after pericardiectomy, either at rest or during volume loading, end-diastolic volume measured by biplane two-dimensional echocardiography increased post pericardiectomy at rest from 38 ± 4 (SE) to 61 ± 4 ml (p < 0.05) and during volume loading from 68 ± 5 to 79 ± 5 ml (p < 0.005). After pericardiectomy, ejection fraction was unchanged, but the peak value of the first derivative of left ventricular systolic pressure ($\text{dP}\text{dt}$) increased significantly at rest from 17 ± 2 to 26 ± 4.0 × 10² mm Hg/sec. We conclude that pericardiectomy shifts the left ventricular end-diastolic pressure-volume curve to the right and increases the systolic isovolumic index of $\text{dP}\text{dt}$ in the basal state.     

Alterations in left ventricular relaxation during atrioventricular pacing in humans

To determine whether the asynchronous left ventricular contraction-relaxation sequence that exists during right ventricular pacing alters left ventricular relaxation, measurements of both the maximal rate of decline of left ventricular pressure (peak negative dP/dt) and the time constant of left ventricular relaxation were obtained during atrial and atrioventricular (AV) pacing in 25 patients referred for diagnostic cardiac catheterization. Heart rate was maintained at 10 to 15 beats/min above the sinus rate at rest, and relaxation was assessed during atrial pacing, AV pacing and repeat atrial pacing. The patients were classified into two groups. Group 1 included 10 patients with normal left ventricular systolic function at rest (ejection fraction greater than 0.55) and without evidence of prior myocardial infarction. Group 2 included 15 patients with a depressed left ventricular ejection fraction or akinesia of one or more left ventricular segments on the contrast ventriculogram, or both. Heart rate, peak left ventricular systolic pressure, end-systolic pressure and end-diastolic pressure remained constant during atrial, AV pacing and repeat atrial pacing in all patients. In group 1 patients, the decrease in peak negative dP/dt (1,507 +/- 200 versus 1,424 +/- 187 mm Hg/s) and the increase in the time constant of left ventricular relaxation (48 +/- 11 versus 51 +/- 11 ms) during AV pacing was not significantly different when compared with values during atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unloading effects of prazosin in patients with chronic aortic regurgitation

Seventeen patients with chronic aortic regurgitation (AR) were examined by echocardiography and left and right heart catheterization. Cardiac output and regurgitation volume were measured by the dye dilution method. Administration of single and four repeated doses of prazosin (PZ) led to reductions of left ventricular (LV) end-diastolic, end-systolic, and left atrial end-systolic diameters, and decrease of left ventricular filling pressure. Regurgitation fraction, regurgitation flow, and volume indexes decreased significantly (p < 0.01). Total left ventricular output decreased (p < 0.001) as did derived parameters of left ventricular work and performance. Fractional shortening, ejection fraction, and mean circumferential fiber shortening velocity increased as did LV $\text{dP}\text{dt}$ and dP/dt/P. Changes in heart rate and cardiac and stroke indexes after PZ were not significant. Preload reduction (dilation of the venous bed and reduction of regurgitation) seems to be the most important effect of PZ in AR. We found PZ to be a suitable and effective drug for oral treatment of chronic AR.     

Acute effects of doxorubicin (adriamycin) on left ventricular function in dogs

Although chronic doxorubicin (adriamycin) cardiotoxicity often is attributed to repeated episodes of acute myocardial injury, the acute effects of doxorubicin on in vivo left ventricular performance have not been studied in a carefully controlled setting. Accordingly, we recorded high-fidelity left ventricular pressures and segmental dimensions before and after either intravenous or intracoronary doxorubicin in twelve open-chest dogs. Propranolol was administered to prevent reflex sympathetic stimulation, and heart rate was held constant by atrial pacing. Intravenous doxorubicin (1.5 mg/kg) (n = 6) caused significant decreases in all measured indices of myocardial contractility, in association with a large decrease in left ventricular systolic pressure (125 ± 28 and 81 ± 23 mm Hg before and 5 min after doxorubicin, respectively, P < 0.01). Intracoronary doxorubicin (0.075 to 0.3 mg/kg) (n = 6) caused similar decreases in percent segment shortening (from 19 ± 7 to 16 ± 8, P < 0.05), mean normalized shortening rate (from 0.87 ± 0.34 to 0.71 ± 0.37 segment lengths/sec, P < 0.05), and peak positive left ventricular $\text{dP}\text{dt}$ (by 10 ± 11%, P < 0.07), although left ventricular systolic pressure was only modestly decreased (126 ± 20 and 113 ± 17 mm Hg before and after doxorubicin, respectively, P < 0.01). Intracoronary doxorubicin also slowed the rate of left ventricular relaxation, as evidenced by an increase in the time constant for isovolumic pressure fall from 32.0 ± 9.0 to 36.9 ± 7.5 msec, and significantly altered the relationship between left ventricular pressure and dimension at end-diastole.We conclude that a single dose of doxorubicin can acutely alter both systolic and diastolic left ventricular function in dogs. These effects are nearly immediate in onset, and are independent of potential functional alterations due to drug-induced systemic hypotension.     

Left ventricular dimensions and function during exercise in dogs with chronic right ventricular pressure overload

Left ventricular (LV) dimensions and shortening at rest and during treadmill exercise were examined before and after 4 weeks of pulmonary artery (PA) constriction in 6 conscious dogs. The dogs were preinstrumented with LV and right ventricular (RV) catheters, an LV micromanometer, a PA inflatable cuff occluder and ultrasonic crystals to measure an LV anteroposterior, a septal-lateral, an apex-base and a free wall segment chord. With PA constriction, RV pressures increased from $\text{49 ±}\text{4}\text{2}\text{± 1 mm}$ Hg (systolic/end-diastolic) to $\text{104 ±}\text{5}\text{2}\text{± 1}$ at rest and from $\text{71 ±}\text{9}\text{2}\text{± 1}\text{to}\text{133 ±}\text{8}\text{14}\text{± 2}$ at peak exercise (mean ± standard error of the mean). Heart rate, LV pressure and LV dP/dt were similar before and after RV pressure overload at rest and with exercise. During exercise at control, systolic shortening increased significantly in all chords. With chronic PA constriction at rest, shortening of all chords also remained normal despite decreases in end-diastolic dimensions, which were most marked in the septal-lateral chord (23% decrease, p <0.01). However, during exercise in the presence of RV pressure overload, septal-lateral shortening decreased 46% (p <0.01) despite increases in systolic shortening in the other chords similar to the control response. Therefore, although LV function at rest in chronic RV pressure overload is normal, exercise may induce regional abnormalities of LV contraction that appear to be mediated by a reduced contribution of the ventricular septum to LV ejection.     

Modification of left ventricular response to pacing tachycardia by nifedipine in patients with coronary artery disease

The calcium blocking agent nifedipine was shown to protect the isolated left ventricle against the development of altered diastolic compliance during severe global ischemia. To assess the influence of nifedipine during myocardial ischemia in human subjects, we studied the effect of nifedipine (20 mg sublingually) on the hemodynamic response to pacing tachycardia (heart rate 66 ± 4 to 143 ± 4 beats per minute) in 17 patients with multivessel coronary artery disease. Typical anginal pain occurred in all patients during pacing tachycardia before nifedipine, but in only 3 of 17 patients during pacing after nifedipine. In 11 patients a significant (≥ 5 mm Hg) increase in postpacing left ventricular end-diastolic pressure (LVEDP, 15 ± 2 mm Hg to 28 ± 2 mm Hg, p < 0.01) developed, and was associated with an upward shift of the left ventricular diastolic pressure-volume curve. In these patients, pretreatment with nifedipine did not alter resting LVEDP or aortic pressure, but did attenuate or abolish the increase in LVEDP and the shift in left ventricular diastolic pressure-volume curves after pacing tachycardia to the same rate and for the same duration. The antianginal effect of nifedipine was not associated with a reduction in contractility, because there was no change in LV + dp/dt after nifedipine. However, the increase in left ventricular systolic pressure achieved in response to pacing tachycardia was less after nifedipine. We conclude that nifedipine favorably modifies the symptomatic and hemodynamic response to pacing tachycardia in patients with coronary artery disease. The mechanism is uncertain and could involve a direct myocardial effect, peripheral vasodilation, coronary vasodilation or a combination of these effects.     

Effect of increasing heart rate on left ventricular performance in patients with normal cardiac function

The influence of an increase in heart rate on left ventricular (LV) contractile performance was assessed in patients with normal LV function. In 19 patients (3 men, 16 women) ages 55 +/- 9 years (mean +/- standard deviation) with normal global and segmental LV function and normal coronary arteries, LV dP/dt max was measured at baseline heart rate and during atrial pacing at baseline +5, baseline +25 and baseline +45 beats/min. In 10 of the patients, intravascular volume was not altered during pacing and, as a result, echocardiographically measured LV end-diastolic dimension decreased (5.4 +/- 0.4 at baseline vs 4.9 +/- 0.5 cm at baseline +45 beats/min, p less than 0.05). In these patients, LV dP/dt max increased modestly (1,571 +/- 237 at baseline vs 1,760 +/- 199 mm Hg/s at baseline +45 beats/min, p less than 0.05). In the other 9 patients, intravascular volume was expanded rapidly (by saline infusion) during pacing and, as a result, LV end-diastolic dimension was held constant (5.2 +/- 0.6 at baseline vs 5.1 +/- 0.6 cm at baseline +45 beats/min, difference not significant). In these patients, LV dP/dt max increased substantially with pacing (1,505 +/- 228 at baseline vs 2,050 +/- 258 mm Hg/s at baseline +45 beats/min, p less than 0.05). Thus, an increase in heart rate induces a modest increase in LV dP/dt max in patients in whom LV preload (as reflected by end-diastolic dimension) is allowed to decrease; in contrast, it causes a marked increase in LV dP/dt max in those in whom LV preload is maintained constant.     

Inotropic responsiveness of the heart in catecholamine cardiomyopathy

Inotropic responsiveness to norepinephrine (NE) or Ca²⁺ was studied in 15 rabbits with catecholamine cardiomyopathy (CM) and the results were compared with 11 controls. The former group was prepared by infusing NE (2 μg/min/kg) for 90 minutes, 2 to 3 days prior to study, and injury was confirmed and quantified histologically. Comparison of NE dose-response curves relating percent increase of left ventricular (LV) $\text{dP}\text{dt}$ max to NE dose in six controls and 10 CM hearts revealed significant depression of CM contractility. Responses to graded infusions of Ca²⁺ were also determined in five controls and in five CM animals. With the increases in serum Ca²⁺ identical in the two groups, the percent increases in $\text{dP}\text{dt}$ max were less in CM hearts. Further, NE dose-response curves obtained during continuous CaCl₂ infusion were sharply attenuated in CM hearts and initial LV end-diastolic pressure (LVEDP) in the CM hearts was considerably higher than in the controls. It is concluded that inotropic sensitivity to NE is reduced in CM hearts. This cannot be ascribed to altered β-receptors alone, because responsiveness to Ca²⁺ was also reduced. Myocardial damage was indicated by histology and elevated LVEDP. Moreover, the normalized percent data suggest that the remaining viable fibers in the CM hearts were functioning subnormally and thus reduced performance was not due solely to the decreased number of contracting units.     

Intra-ventricular resynchronization for optimal left ventricular function during pacing in experimental left bundle branch block

oBJECTIVES: We sought to investigate to what extent intra-ventricular asynchrony (intraVA) and inter-ventricular asynchrony (interVA) determine left ventricular (LV) function in canine hearts with left bundle branch block (LBBB) during ventricular pacing. BACKGROUND: Pacing therapy improves LV pump function in patients with heart failure and abnormal ventricular conduction supposedly due to resynchronization. However, the relationship between LV pump function and measures of asynchrony is not well established. METHODS: In 15 experiments, LV (various sites) and biventricular (BiV) pacing was performed at atrioventricular (AV) delays of 20 to 140 ms. Measured were the maximum rate of increase (dP/dt(max)) of LV pressure and LV stroke work (SW) (conductance catheter), interVA (time delay between the upslope of LV and RV pressures), and intraVA (from endocardial electrical activation maps). RESULTS: Induction of LBBB increased interVA (-6.4 +/- 8.6 to -28.4 +/- 8.5 ms [RV earlier]) and intraVA (4.9 +/- 2.4 to 18.0 +/- 3.3 ms), whereas LV dP/dt(max) and SW decreased (-13 +/- 18% and -39 +/- 24%, respectively). During LBBB, LV and BiV pacing increased LV dP/dt(max) and SW (mean increases 14% to 21% and 11% to 15%, respectively) without changing diastolic function or preload. Optimal improvement in LV function was obtained consistently when intraVA returned to pre-LBBB values, while interVA remained elevated. Normalization of intraVA required AV delays shorter than the baseline PQ time during LV apex and BiV pacing, thus excluding endogenous LV activation, but AV delays virtually equal to the baseline PQ time (difference 4 +/- 9 ms, p = NS) during pacing at (mid)lateral LV sites to obtain fusion between pacing-induced and endogenous activation. CONCLUSIONS: In LBBB hearts, optimal restoration of LV systolic function by pacing requires intra-ventricular resynchronization. The optimal AV delay to achieve this depends on both the site of pacing and baseline PQ time.     

Changes in left ventricular wall dimensions during regional myocardial ischemia

The relation between changes in left ventricular wall systolic thickening and other measures of left ventricular function were studied during regional ischemia in 14 open chest pigs. A fixed decrease in coronary peak blood flow from 46 ± 5 (standard error) to 13 ± 2 ml/min was produced using a screw clamp and flow probe placed around the left anterior descending coronary artery. Myocardial wall thickness was measured with a calibrated harpoon mercury strain gauge placed through the apical portion of the left ventricle and recorded continuously with left ventricular systolic pressure, the first derivative of left ventricular pressure rise ($\text{dP}\text{dt}$) and pressure-derived peak velocity of contraction. During systole, the left ventricle thickened by 10.7 ± 2.1 percent of its total average thickness of 12.7 ± 0.7 mm. Within 6 seconds of the onset of ischemia total myocardial wall thickness decreased from 1.356 ± 0.135 to 0.592 ± 0.081 mm (P < 0.001) or to 45.2 ± 5.1 percent of the control value. During ischemia, changes were noted in both the isovolumic and the ejection phases of systole in addition to left ventricular wall thinning of 0.282 ± 0.02 mm at enddiastole. There was no significant change in left ventricular pressure or its derived values. In two experiments isolated wall thickness alternans was observed. These studies indicate that myocardial wall thickness is more sensitive than ventricular pressure as a measure of local changes in myocardial function during regional myocardial ischemia.     

The effect of noradrenaline on blood flow and oxygen consumption in normal and ischemic areas of myocardium

The effects of infusions of noradrenaline (1.0 μg/Kg./min.) were studied in dogs 2 to 3 hr. after acute ligation of the anterior descending branch of the left coronary artery. The model allowed blood flow to be simultaneously measured in the ischemic (infarcting) region and in the normal myocardium. Sampling blood from a local vein (draining the ischemic region) and from the coronary sinus (draining the normal myocardium) allowed comparisons to be made of oxygen consumption by the two regions.Coronary artery ligation resulted in a marked decrease in cardiac output and external cardiac work and an increase in left ventricular end-diastolic pressure with an unchanged LV $\text{dP}\text{dt}$. This is indicative of reduced myocardial contractility. Blood flow in the area supplied by the ligated vessel fell to a mean of 17.6 ± 2.7 ml./100 Gm./min., which is about 20 per cent of the normal flow in this region.Infusing noradrenaline 2 to 3 hr. after ligation increased systemic arterial pressure, LV $\text{dP}\text{dt}$ max, external cardiac work, and blood flow and oxygen consumption in normal areas of the myocardium. There was some evidence that pulmonary shunting was increased by the drug.Noradrenaline also markedly increased peripheral coronary pressure and blood flow in the ischemic region, as assessed by ¹³³Xenon clearance and by retrograde flow from the ligated vessel. Oxygen consumption in the ischemic region was also increased by noradrenaline. It is suggested that part of the increase in flow occurs in the endocardial region since the effective subendocardial perfusion pressure is increased by noradrenaline. This increase in flow would account for the reduction in infarct size which has been observed by other workers when the systemic arterial pressure is raised.     

Left ventricular function in systole and diastole in constrictive pericarditis

Left ventricular function was studied in systole and diastole in 30 patients with constrictive pericarditis. Left ventricular end-diastolic volume was used to divide the patients into three arbitrary groups: severe constriction (EDV < 25 ml./M.²), moderate constriction (EDV 25 to 50 ml./M.²), and mild constriction (EDV > 50 ml./M.²).The patients had high ventricular diastolic and venous filling pressures (mean LVEDP = 23 ± 7 mm. Hg, mean RVEDP = 20 ± 7 mm. Hg). Measurements related to absolute fiber shortening (stroke index, stroke work index, and left ventricular ejection rate) were reduced and linearly related to the degree of constriction as assessed by the end-diastolic volume.Measurements of relative fiber shortening or lengthening (ejection and filling fraction and circumferential fiber shortening) were normal despite great reduction in ventricular volumes.Velocity measurements, peak LV $\text{dp}\text{dt}$ and mean velocity of circumferential fiber shortening were normal or slightly reduced.These changes were reflected in the systolic time interval measurements pre-ejection phase, left ventricular ejection time, and the ratio $\text{PEP}\text{LVET}$.Diastolic function of the ventricle was abnormal; the distensibility index of the ventriculo-pericardial system ($\text{ΔV}\text{ΔP}$) was low and the passive elastic modulus in-increased. The change in compliance correlated with the degree of constriction and there was a linear relationship between compliance and EDV.The ventricle was underloaded despite the high filling pressure and stroke work index was reduced; extrinsic compression raised the diastolic pressure and reduced left ventricular volumes.     

Assessment of left ventricular systolic function using echocardiography in patients with preserved ejection fraction and elevated diastolic pressures

There is controversy regarding the nature of systolic function in patients with elevated filling pressure and preserved left ventricular (LV) ejection fraction. In this study, tissue Doppler variables and 2-dimensional echocardiographic systolic strain (SS) and systolic strain rate (SSr) were measured in patients who underwent cardiac catheterization to determine correlations with invasively measured LV end-diastolic pressure (LVEDP), dP/dt, and LV mass. Forty patients were studied. Their mean age was 55.9+/-9.9 years, and their mean LV ejection fraction was 59.8+/-5.2%. Tissue Doppler systolic annular velocity (5.4+/-1.1 vs 6.4+/-1.0 cm/s, p=0.04), SS (13.4+/-3.7% vs 18.8+/-2.3%, p <0.001), and SSr (0.73+/-0.17 vs 0.98+/-0.14 s(-1), p <0.001) were significantly lower in patients with LVEDP >20 mm Hg compared with those with LVEDP <20 mm Hg. Tissue Doppler systolic velocity, SSr, and SS were correlated with LV mass (R=0.58, R=0.57, and R=0.52, respectively, all p values <0.001) and with LVEDP (R=0.49, p=0.002; R=0.79, p<0.001; and R=0.70, p<0.001, respectively). However, dP/dt was not significantly different between patients with LVEDP >20 mm Hg and those with LVEDP <20 mm Hg (1,387+/-520 vs 1,495+/-594 mm Hg/s, respectively, p=0.55) and was not correlated with LV mass (R=0.18, p=0.25). The optimum cut-off values for LVEDP >20 mm Hg were SSr <0.85 s(-1) (area under the curve 0.88, p<0.001, positive predictive value 89%, negative predictive value 86%) and SS<16% (area under the curve 0.84, p=0.002, positive predictive value 88%, negative predictive value 79%). In conclusion, as opposed to invasively measured dP/dt, tissue Doppler systolic velocity and 2-dimensional echocardiographic SS and SSr are significantly depressed in patients with preserved LV ejection fraction and LVEDP >20 mm Hg, suggesting that systolic abnormalities are present in at least some of these patients. These differences are likely because invasively measured dP/dt and these echocardiographic variables measure different systolic properties in patients with preserved LV ejection fraction.     

Preferred left ventricular lead position for upgrade from right ventricular pacing to cardiac resynchronization therapy

Introduction

Cardiac resynchronization therapy (CRT) is well-established for treating symptomatic heart failure with electrical dyssynchrony. The left ventricular (LV) lead position is recommended at LV posterolateral to lateral sites in patients with left bundle branch block; however, its preferred region remains unclear in patients being upgraded from right ventricular (RV) apical pacing to CRT. This study aimed to identify the preferred LV lead position for upgrading conventional RV apical pacing to CRT.

Methods

We used electrode catheters positioned at the RV apex and LV anterolateral and posterolateral sites via the coronary sinus (CS) branches to measure the ratio of activation time to QRS duration from the RV apex to the LV anterolateral and posterolateral sites during RV apical pacing. Simultaneous biventricular pacing was performed at the RV apex and each LV site, and the differences in QRS duration and LV dP/dt_max from those of RV apical pacing were measured.

Results

Thirty-seven patients with anterolateral and posterolateral LV CS branches were included. During RV apical pacing, the average ratio of activation time to QRS duration was higher at the LV anterolateral site than at the LV posterolateral site (0.90 ± 0.06 vs. 0.71 ± 0.11, p < .001). The decreasing ratio of QRS duration and the increasing ratio of LV dP/dt_max were higher at the LV anterolateral site than at the posterolateral site (45.7 ± 18.0% vs. 32.0 ± 17.6%, p < .001; 12.7 ± 2.9% vs. 3.7 ± 8.2%, p < .001, respectively) during biventricular pacing compared with RV apical pacing.

Conclusion

The LV anterolateral site is the preferred LV lead position in patients being upgraded from conventional RV apical pacing to CRT.     

Cardiac dose response relationship for intravenously infused glucagon in normal intact dogs and men

The mechanism of glucagon's cardiac effects is not well understood. As the cardiac dose response to glucagon in intact animals has not been elucidated, this was determined in normal men and dogs. In man, heart rate, blood pressure, systolic time intervals and echocardiographic indices of ventricular wall motion were determined. Plasma glucagon levels (PGL) were measured by radioimmunoassay. Men received 3 glucagon infusions of 10^?10 to 10^?8 moles/minute followed by a bolus of 0.5 mg. or 1.0 mg. Small but significant changes were observed in ejection fraction and left ventricular posterior wall displacement at the 10^?9 moles/minute infusion rate (mean PGL 1.9 ng./ml.), a PGL close to that of some pathophysiologic states such as burns, ketoacidosis, and acute myocardial infarction, while cardiac output, heart rate, and other indices of cardiac performance were significantly changed only at the 10^?8 moles/minute and bolus injections. Some indices, notably stroke volume, were unchanged.In dogs, left ventricular (LV) pressure, LV pressure derivative (LV $\text{dP}\text{dt}$), and aortic flow were measured with implanted LV solid state pressure transducers and electromagnetic flow probes. Dogs received six infusions from 2.7 × 10^?11 to 2.7 × 10^?8 moles/minute followed by a bolus of 2 mg. In dogs, significant changes occurred in LV $\text{dP}\text{dt}$ at 2.7 × 10^?9 moles/minute (mean PGL 31.5 ng./ml.) and in heart rate at 2.7 × 10^?8 moles/minute only. It appears that substantial hemodynamic effects do not appear in man or dogs until PGL 10 to 100 times those seen in pathophysiologic states are achieved. Thus, it seems unlikely that glucagon contributes substantially to the hyperdynamic circulatory conditions observed in these states. Significant hemodynamic response to glucagon was noted in normal men, however, at a PGL less than that achieved by usual pharmacologic doses of glucagon and this lower PGL was not associated with the gastrointestinal symptoms commonly observed clinically.     

Effect of dual-chamber pacing on systolic and diastolic function in patients with hypertrophic cardiomyopathy Acute doppler echocardiographic and catheterization hemodynamic study

Objectives. This study sought to evaluate prospectively the acute hemodynamic effect of dual-chamber pacing by using a combined hemodynamic approach of high fidelity pressure and Doppler velocity measurements.Background. Dual-chamber pacing has been proposed recently as an alternative in the symptomatic treatment of patients with hypertrophic obstructive cardiomyopathy. Although early reports documented a decrease in left ventricular outflow tract gradient and symptomatic improvement, questions remain about the hemodynamic effects of dual-chamber pacing on systolic and diastolic function.Methods. Twenty-nine patients with hypertrophic cardiomyopathy underwent a combined cardiac catheterization and Doppler echocardiographic study during normal sinus rhythm and P-synchronous pacing at various atrioventricular (AV) intervals. High fidelity pressure measurements of left ventricular inflow and left atrial pressures, ascending aortic pressure, thermodilution cardiac output and Doppler mitral flow velocity curves were obtained to evaluate both systolic and diastolic left ventricular function.Results. During AV pacing at the shortest delay of 60 ms, there was a significant decrease in cardiac output (p < 0.05) and peak positive dP/dt (p < 0.05), an increase in mean left atrial pressure (p < 0.05) and a prolongation of τ, the time constant of relaxation (p < 0.05), compared with that during normal sinus rhythm. During pacing at the optimal AV delay (longest AV interval with pre-excitation), there was a similar trend, with deterioration in both systolic and diastolic function variables but of lesser magnitude than that during pacing at the shortest AV intervals. The deterioration in both systolic and diastolic function was present in 21 patients with and 8 without left ventricular outflow obstruction. There was a modest decrease in left ventricular outflow tract gradient from 73.3 ± 45.0 (mean ± SD) to 61.3 ± 40.5 mm Hg (p = 0.03) during dual-chamber pacing at the optimal AV delay compared with that during normal sinus rhythm.Conclusions. The acute effect of pacing the right atrium and ventricle may be detrimental to both systolic and diastolic function of the left ventricle, particularly at the short AV intervals. Further studies of the long-term effects of dual-chamber pacing in carefully performed randomized studies are needed.     

Effect of coronary vasodilation on ventricular fibrillation threshold: Role of exogenous vasodilators and perfusion conditions

Even without myocardial ischemia, coronary blood flow (CBF) constitutes a major determinant of ventricular fibrillation threshold (VFT). To clarify whether abnormal distribution of normal or increased CBF plays any additional role, 14 open-chest chloralose-anesthetized dogs with fixednormalized heart rate, cardiac output, and systemic arterial pressure and separate servocontrolled left main coronary artery perfusion were studied as follows: VFT was determined first with coronary perfusion pressure (CPP) set at systemic level (80 mm Hg). Then CBF index was fixed at control levels (134.0 ± 9.5 ml/min · 100 gm^?1 LV) and coronary vasodilation was induced by intracoronary infusion of adenosine until CPP decreased to 49.0 ± 2.0 mm Hg. Myocardial O₂ consumption, LV pressure, LV $\text{dp}\text{dt}$, and surface ECG remained unchanged. However, VFT decreased in all trials by about 45% (p < 0.001). When CPP was reset to 80 mm Hg while maintaining vasodilation, CBF index increased by 90% to 255.4 ± 15.4 ml/min · 100 gm^?1 LV and VFT by 26% (p < 0.005) from control. Yet these VFT increases in response to intraluminal pharmacologic vasodilation were about 19% (p < 0.002) lower than expected for similar CBF index increases occurring physiologically. We conclude that intraluminal coronary vasodilation not matched by appropriate CBF increase results in substantial decrease of VFT. Moreover, at comparable increase of CBF, spontaneous physiologic vasodilation is more effective than intraluminal pharmacologic coronary vasodilation in increasing VFT.     

Gender Differences in Cardiac Dysfunction and Remodeling due to Volume Overload

BackgroundThis study examined the sex differences for hemodynamic and echocardiographic changes in hypertrophied and failing hearts induced by arteriovenous (AV) shunt.Methods and ResultsEchocardiographic and hemodynamic alterations were determined in male and female rats at 4 and 16 weeks after AV shunt. Ovariectomized females treated with estrogen for 16 weeks post-AV shunt were also used. Both genders developed cardiac hypertrophy at 4 and 16 weeks post-AV shunt; however, the increase in cardiac muscle mass was greater in females than males at 16 weeks. At 4 weeks post-AV shunt, increases in ventricular dimensions and left ventricular end-diastolic pressure (LVEDP) as well as a decrease in fractional shortening occurred in males only. Unlike the females, the rates of pressure development (+dP/dt) and decay (-dP/dt) were depressed and LVEDP increased in male rats at 16 weeks post-AV shunt. An increase in cardiac output was seen in both genders, but this was more marked in the males at 4 and 16 weeks post-AV shunt. Although mRNA levels for ACE were increased in both male and female rats at 4 and 16 weeks, mRNA levels for angiotensin II type 1 receptor were increased in males at 16 weeks only. Furthermore, increases in plasma catecholamines were elevated in males but were decreased or unchanged in females at 16 weeks of AV shunt. LV internal diameters as well as depressed fractional shortening occurred in males whereas increases in posterior wall thickness were seen in the female rats at 16 weeks of AV shunt. Ovariectomy resulted in depressed +dP/dt, -dP/dt, and fractional shortening, whereas a marked increase in cardiac output as well as increased LVEDP and LV internal diameters were observed at 16 weeks post-AV shunt. Although treatment with 17-β estradiol normalized ±dP/dt, LVEDP remained elevated.ConclusionGender differences in cardiac function may be due to differences in the type of cardiac remodeling as a consequence of AV shunt. Furthermore, estrogen appears to play an important role in preventing cardiac dysfunction and adverse ventricular remodeling in female rats.     

Acute effects of ethanol on myocardial blood flow in the nonischemic and ischemic heart

To determine the effects of ethanol on myocardial blood flow in the non-ischemic and ischemic heart, coronary blood flow was measured with radionuclide-tagged microspheres in the anesthetized dog before and after intravenous administration of 1.7 g/kg body weight of ethanol. In non-ischemic dogs, at an average peak blood ethanol level of 225 ± 8 mg/dl (mean ± standard error of the mean), left atrial pressure increased from 5.7 ± 0.6 to 7.7 ± 0.8 mm Hg (p <0.01) and heart rate slowed from 179 ± 8 to 171 ± 8 min^?1 (p <0.001) but mean aortic pressure and cardiac output were unchanged. Average myocardial blood flow increased from 122 ± 5 to 143 ± 8 ml/min per 100 g (p <0.001). In dogs given ethanol after coronary occlusion, at an average peak blood ethanol level of 201 ± 13 mg/dl, left atrlal pressure increased from 6.3 ± 0.6 to 7.4 ± 1.4 mm Hg (p <0.05) but there was no significant change in heart rate, mean aortic pressure or peak positive first derivative of left ventricular pressure ($\text{dP}\text{dt}$). In these dogs, there was a significant change (F = 6.47, p <0.001) in the distribution of myocardial blood flow. In the nonischemic zone, blood flow increased from 118 ± 7 to 148 ± 14 ml/min per 100 g (p <0.005), whereas in the ischemie zone it declined from 30 ± 6 to 20 ± 5 ml/min per 100 g (p <0.02). Myocardial tissue demonstrating myocardial perfusion equal to or greater than 80 percent of preligation levels showed a significant increment of blood flow after ethanol; by contrast, myocardial tissue having blood flow levels equal to or less than 60 percent of preligation levels showed a significant decline in blood flow.Thus, ethanol increases coronary blood flow in the nonischemic myocardium. However, in the acutely ischemic heart, ethanol produces an unfavorable redistribution of myocardial blood flow with flow in the non-ischemic myocardium increasing, at least in part, at the expense of blood flow to ischemic myocardium, producing in effect a “coronary steal.”