Thomas R. Porter

Autonomic pathophysiology in heart failure patients. Sympathetic-cholinergic interrelations.

We conducted this study in an effort to characterize and understand vagal abnormalities in heart failure patients whose sympathetic activity is known. We measured sympathetic (peroneal nerve muscle sympathetic recordings and antecubital vein plasma norepinephrine levels) and vagal (R-R intervals and their standard deviations) activities in eight heart failure patients and eight age-matched healthy volunteers, before and after parasympathomimetic and parasympatholytic intravenous doses of atropine sulfate. At rest, sympathetic and parasympathetic outflows were related reciprocally: heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows. Low dose atropine, which is known to increase the activity of central vagal-cardiac motoneurons, significantly increased R-R intervals in healthy subjects, but did not alter R-R intervals in heart failure patients. Thus, our data document reciprocal supranormal sympathetic and subnormal parasympathetic outflows in heart failure patients and suggest that these abnormalities result in part from abnormalities within the central nervous system.

Myocardial contrast echocardiography for the assessment of coronary blood flow reserve: Validation in humans☆

OBJECTIVES The aim of this study was to validate the use of myocardial contrast echocardiography to determine coronary blood flow reserve in humans. BACKGROUND Although myocardial contrast echocardiography has been used to accurately quantify coronary flow reserve in animals, validation for its use in humans to measure flow reserve is lacking. METHODS We analyzed the time-intensity curve from the anteroseptal region of the left ventricular short axis produced after a left main coronary artery injection of sonicated albumin before and after intracoronary administration of papaverine in 16 patients without angiographically significant coronary artery disease. The ratio of half-time of video intensity disappearance from peak intensity, variable of curve width, area under the time-intensity curve and corrected peak contrast intensity after papaverine compared with baseline were correlated with coronary flow reserve measured simultaneously with an intracoronary Doppler probe in the left anterior descending coronary artery. RESULTS There was a strong inverse correlation with half-time of contrast washout and coronary flow reserve (r = -0.76, p = 0.0007) and a strong positive correlation between the variable of curve width (which is inversely proportional to curve width) and coronary flow reserve (r = 0.71, p = 0.002). There was a weak but significant inverse correlation between area under the time-intensity curve and coronary flow reserve (r = -0.54, p = 0.03) but no correlation between corrected peak contrast intensity and coronary flow reserve (r = -0.36, p = NS). Despite the strong correlation for the ratios for half-time of contrast washout and variable of curve width and actual coronary flow reserve measured with intracoronary Doppler probe, the transit time ratios consistently underestimated coronary flow reserve. CONCLUSIONS Myocardial contrast echocardiography performed with left main coronary artery injections of sonicated albumin can be utilized to measure coronary flow reserve in humans. Transit time variable ratios (half-time of contrast washout and variable of curve width) derived from the time-intensity curve correlate most strongly with coronary flow reserve.

Transesophageal echocardiography to assess mitral valve function and flow during cardiopulmonary resuscitation

This study further defines the mechanism of blood flow during closed-chest compression using transesophageal Doppler echocardiography. Although the echocardiographic demonstration of mitral valve closure during closed-chest compression has been used as evidence of direct cardiac compression, mitral valve closure has also been documented to occur during resuscitation by selectively increasing intrathoracic pressure. Transesophageal Doppler echocardiography was used to assess mitral valve position and flow in 17 adult patients undergoing cardiopulmonary resuscitation with a mechanical piston compression device. Left and right ventricular fractional shortening, mitral valve position with chest compression, timing and magnitude of transmitral flow, and anteroposterior chest diameter were recorded. In 12 patients (group I), the mitral valve closed during the down-stroke of chest compression; in the remaining 5 (group II), it opened further. Peak transmitral flow occurred during the release phase and was significantly higher (p < 0.05) in group I (39.5 +/- 9.3 cm/s) than the peak flow in group II (21.3 +/- 5.9 cm/s), which occurred during the downstroke of chest compression. Left ventricular fractional shortening inversely correlated (r = -0.68; p = 0.02) with the anteroposterior chest diameter, but did not correlate with peak transmitral flow (r = 0.34; p = not significant). It is concluded that the mitral valve closes during the downstroke of chest compression in most adult patients during resuscitation. The absence of a relation between mitral valve flow and left ventricular fractional shortening supports the hypothesis that other factors such as nonuniform increases in intrathoracic pressure cause the mitral valve to open or close during chest compression.

Ischemia-induced regional wall motion abnormality is improved after coronary angioplasty: Demonstration by dobutamine stress echocardiography

OBJECTIVES The purpose of this study was to examine whether dobutamine stress echocardiography can detect reversal of ischemia-induced left ventricular regional wall motion abnormality immediately after percutaneous transluminal coronary angioplasty. BACKGROUND Although angioplasty is routinely performed as a means of coronary revascularization, at present there is a question whether this results in an immediate improvement in ischemia-induced left ventricular regional function. METHODS Thirty-five patients underwent dobutamine stress echocardiography 24 h before and 24 to 48 h after angiographically successful coronary angioplasty. Only patients with normal wall motion at rest were included. Dobutamine infusion was begun at 5 micrograms/kg per min and increased at 5-min intervals (10, 20, 30, 40 micrograms/kg per min). Echocardiographic images were stored into cine loops and analyzed off line with simultaneous comparison of images acquired at baseline, 5 micrograms/kg per min, peak infusion and recovery. Echocardiographic images were interpreted independently, without knowledge of other data, by two experienced cardiologists using the 16-myocardial segment model. RESULTS Before angioplasty, dobutamine stress echocardiography induced wall motion abnormalities in 31 patients (88%). Wall motion score at peak dobutamine infusion improved in 28 (90%) of the 31 patients after angioplasty. Wall motion score at peak dobutamine infusion for the group improved from 20 +/- 3 before angioplasty to 17 +/- 2 after angioplasty (p < 0.001). There was no change in the rate-pressure product achieved for the group before and after angioplasty (20,038 +/- 6,415 beats/min x mm Hg before versus 20,775 +/- 5,435 after angioplasty, p = NS). Before angioplasty, dobutamine stress echocardiography induced angina in 13 patients (37%), whereas angina occurred only once after angioplasty. Electrocardiographic changes diagnostic of ischemia occurred seven times, all before angioplasty. CONCLUSIONS We conclude that dobutamine stress echocardiography is an excellent method to demonstrate an immediate improvement in stress-induced regional left ventricular dysfunction in the distribution of the vessel undergoing successful angioplasty.

Direct in vivo evaluation of pulmonary arterial pathology in chronic congestive heart failure with catheter-based intravascular ultrasound imaging

Abstract Patients with chronic congestive heart failure (CHF) frequently develop secondary pulmonary hypertension. This development is a poor prognostic indicator.1 In addition, secondary pulmonary hypertension that does not improve in response to vasodilators identifies a group of patients who will have a poor outcome after orthotopic heart transplantation.2,3 The structural abnormalities of the pulmonary artery that occur in CHF have been described in autopsy specimens,4 and human studies have demonstrated indirectly that there are alterations in pulmonary vascular impedance and stiffness.5,6 Intravascular ultrasound using high-frequency catheter-based imaging has been performed to quantify pulmonary artery area and diameter in humans.7 It also has been validated as a method of detecting plaque in both elastic and muscular arteries.8 We hypothesized that intravascular ultrasound could be used to characterize the changes in pulmonary vascular morphology and elasticity in CHF.

Usefulness of myocardial contrast echocardipgraphy in detecting the immediate changes in anterograde blood flow reserve after coronary angioplasty

Myocardial contrast echocardiography has revealed that successful coronary angioplasty results in an immediate decrease in the amount of collateral blood flow to the perfusion bed supplied by the dilated vessel. This information could potentially be used with pharmacologic stress in the catheterization laboratory to also assess the improvement in coronary flow reserve after angioplasty. The immediate changes in area under the time intensity curve produced by a 1 ml slow injection of sonicated albumin immediately proximal to a stenosis before and after 14 angiographically successful angioplasties was studied in 12 patients. Area under the curve was assessed before and after an 8 mg selective injection of papaverine. The changes in area under the curve were correlated with percent improvement in epicardial area stenosis. Visually successful angioplasty resulted in > 30% improvement in area under the curve after papaverine in 9 of 14 studies. There was a significant correlation between improvement in area under the curve after papaverine and percent improvement in epicardial area stenosis (r = 0.75; p < 0.01). No patient had left ventricular wall motion abnormalities after papaverine before or after angioplasty. These changes suggest that quantitatively successful angioplasty results in decreased collateral blood flow to the involved myocardium during pharmacologic stress. These improvements in coronary flow reserve cannot be predicted by visual analysis of angioplasty results.

In Vitro Study of the Effects of Volume Changes on Parameters of the Radiofrequency Amplitude Versus Time Curve With Sonicated Albumin

The ultrasound time intensity curve parameters obtained from an intracoronary injection of either sonicated albumin or Albunex are used to quantify coronary flow changes. How much the volume changes that accompany the flow changes affect various time intensity curve parameters is unknown. Accordingly, we designed a variable-volume in vitro chamber connected to a flow pump operating at four predetermined flow settings (44 to 184 ml/minute). Injections of either sonicated albumin or Albunex were given proximal to a mixing chamber, which then passed through the scanning chamber at three different volume settings. The parameters studied were area under the curve, corrected peak contrast intensity, ascending and descending slopes of the curve, time to peak radiofrequency signal, the time required to reach half peak intensity (half time up), the time required to decay to half peak intensity (half time down), and total transit time (the time from appearance to disappearance of 10% of peak intensity). Although area, half time up, half time down, and transit time all correlated with flow when volume was held constant, only transit time (and the natural logarithm of the transit time) correlated strongly with flow changes when simultaneous changes in volume occurred. Transit time also correlated with volume changes when flow was held constant, but was more sensitive to flow changes. These data may explain why transit time variables may still be able to detect flow changes in the coronary circulation despite a simultaneous change in myocardial blood volume.