Pramod K. Mohanty

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.

Arterial baroreflex abnormalities in heart failure. Reversal after orthotopic cardiac transplantation.

Arterial baroreflex control of the heart and peripheral circulation is markedly impaired in humans and animals with congestive heart failure. After reversal of heart failure in animal models, arterial baroreflex control of heart rate remains impaired for up to 8 months. Cardiac transplantation restores normal ventricular function and completely reverses heart failure, but does it normalize arterial baroreflex control of heart rate in humans? We studied baroreflex sensitivity in 11 patients with severe heart failure, six normal control patients, and 23 patients at 2 weeks to 4 years after orthotopic cardiac transplantation. Baroreflex sensitivity was assessed with intravenous bolus injections of phenylephrine and is expressed as change in RR or PP interval (msec) per millimeters of mercury rise in systolic arterial pressure. Atrial rate of both donor (denervated) and recipient (innervated) atria were measured in the transplant group. Baroreflex sensitivity in patients with severe heart failure was 2.0 +/- 0.3 msec/mm Hg, but in patients after cardiac transplantation, it was 13.0 +/- 0.9 msec/mm Hg (p less than 0.001). The responses in the transplant group were similar to those observed in normal controls (10 +/- 1.2 msec/mm Hg, p = NS). Our data indicate that patients with severe congestive heart failure have marked abnormalities of baroreflex control, which are reversed as early as 2 weeks after cardiac transplantation. In view of this rapid reversal, we consider it unlikely that abnormal baroreflex sensitivity seen in heart failure is due to structural alterations in the baroreceptors. We speculate that neurohumoral rather than structural abnormalities account for depressed baroreflex sensitivity in heart failure.

Impairment of cardiopulmonary baroreflex after cardiac transplantation in humans.

There is ample evidence for efferent cardiac denervation in patients after cardiac transplantation. However, little is known regarding the effects of the cardiac deafferentation that also results. We examined responses to graded lower-body negative pressure and thus cardiopulmonary baroreceptor unloading in 23 patients 3 to 12 months after cardiac transplantation and compared their responses with those of nine normal subjects. Responses of mean arterial pressure, forearm vascular resistance, and plasma norepinephrine were assessed during lower-body negative pressure and the cold pressor test. Reflex increases in forearm vascular resistance (1.5 +/- 1, 5.0 +/- 1.4, and 6.4 +/- 2.1 vs 14.5 +/- 4.5, 20.3 +/- 6.5, and 34 +/- 11 units) and plasma norepinephrine (42 +/- 12, 58 +/- 15, and 62 +/- 13 vs 49 +/- 14, 94 +/- 25, and 173 +/- 36 pg/ml) during lower-body negative pressure (at -10, -20, and -40 mm Hg) were strikingly smaller in cardiac transplant patients than in normal subjects. The impaired responses of the cardiac transplant patients were not the result of a nonspecific depression of cardiovascular reflexes, since increases in mean arterial pressure (12 +/- 3 vs 10 +/- 2 mm Hg), forearm vascular resistance (19.5 +/- 3.4 vs 18 +/- 5.8 units), and plasma norepinephrine (56 +/- 8 vs 42 +/- 11 pg/ml) during cold pressor test were not significantly different in the two groups. Furthermore, the impaired responses were not caused by the immunosuppressive agents used to treat the cardiac transplant patients, since patients with renal transplants on similar regimens had augmented forearm vasoconstrictor responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular diastolic collapse. An echocardiographic sign of regional cardiac tamponade.

BackgroundCardiac tamponade after cardiac surgical procedures is often associated with hemodynamically significant localized pericardial effusions. The localized collection of pericardial effusion in the postoperative period and the atypical presentation of cardiac tamponade limit the use of conventional clinical and echocardiographic signs usually seen with a circumferential pericardial effusion. Observation of left ventricular diastolic collapse in the echocardiogram of a patient with postoperative regional cardiac tamponade prompted us to explore the frequency of this sign in regional cardiac tamponade. Methods and ResultsWe retrospectively analyzed the echocardiograms of 18 patients with postoperative cardiac tamponade for the following echocardiographic findings: right atrial collapse, right ventricular diastolic collapse, left atrial collapse, and left ventricular diastolic collapse. Three of the 18 patients had circumferential pericardial effusion, and 15 had loculated pericardial effusion; in 10, the effusion was predominantly posterior, and in the other five, it extended laterally or inferiorly. The conventional echocardiographic signs of cardiac tamponade such as right atrial collapse, right ventricular diastolic collapse, and left atrial collapse were present in only 3, 1, and 3 of these 15 patients, respectively, but all exhibited leftcv ventricular diastolic collapse. Increasing pressure within the compartment of a loculated pericardial effusion reaching the limit of penicardial distensibility and consequent transient reversal of transmural left ventricular pressure during diastole are most likely the basis for diastolic collapse of the thick-walled ventricle in a setting of regional cardiac tamponade. ConclusionsWe conclude that left ventricular diastolic collapse is a frequent sign of regional cardiac tamponade and could be a useful marker of tamponade in postoperative patients. (Circulation 1991;83:1999—2006)

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.

Dobutamine Stress Echocardiography Early After Heart Transplantation Predicts Development of Allograft Coronary Artery Disease and Outcome

OBJECTIVES This study sought to determine the prognostic significance of serial dobutamine stress echocardiography (DSE) in new heart transplant recipients and to examine the relation between persistent wall motion abnormalities and the eventual development of coronary artery disease (CAD) as assessed by angiography. BACKGROUND Allograft CAD is a major cause of graft failure. However, clinical diagnosis of the early disease remains difficult. The reasons for this include the diffuse nature of the disease and its predilection for the microvasculature, which are not easily detected by coronary angiography. Identifying patients at risk for the development of angiographic CAD early after transplantation may allow such patients to be targeted for aggressive treatment options to prevent subsequent cardiac events and early graft failure. METHODS Twenty-two new heart transplant recipients were selected to undergo serial DSE at the time of their regularly scheduled endomyocardial biopsy. In addition, patients underwent scheduled annual coronary angiography. DSE was performed in 5-min stages with infusion of intravenous dobutamine at 5, 10, 20, 30 and 40 microg/kg body weight per min. RESULTS Twenty-two patients had 91 DSE studies and 45 coronary angiograms. The patients were categorized into three groups based on the echocardiographic results. Group 1 (n = 7) had normal serial stress echocardiographic studies. Group 2 (n = 4) had transient inducible wall motion abnormalities. Group 3 (n = 11) developed persistent wall motion abnormalities. During a mean follow-up time of 32 +/- 11 months (range 5 to 50), 8 (73%) of 11 patients in Group 3 developed events. The events included angiographic CAD (n = 7), myocardial infarction (MI) (n = 1) and cardiac death (n = 3). The patient who developed an MI had a normal coronary angiogram. No cardiac event or angiographic disease occurred in either Group 1 or 2 patients. CONCLUSIONS These results suggest that dobutamine-induced wall motion abnormalities, which are persistent in new heart transplant recipients, are predictive of the development of angiographic CAD, MI or death.

New insights into pacemaker syndrome gained from hemodynamic, humoral and vascular responses during ventriculo-atrial pacing

Ventricular pacing is performed during programmed electrical stimulation and during normal functioning of single chamber (VVI or VVIR) pacemakers. In many patients, retrograde ventriculoatrial (V-A) conduction may occur and evoke hemodynamic and reflex neurohumoral responses, which are unique to this pacing mode. Accordingly, forearm blood flow, forearm vascular resistance, mean and phasic arterial pressure, cardiac output and plasma norepinephrine, epinephrine and dopamine were measured during atrial, ventricular and V-A pacing at a cycle length of 600 ms (100 beats/min) before and after regional alpha blockade with intraarterial phentolamine in 16 patients with a left ventricular ejection fraction greater than 35% and little or no symptoms of congestive heart failure. During V-A pacing, cardiac output decreased by 10%, whereas forearm vascular resistance increased from 52 +/- 7 to 70 +/- 9 U (p less than 0.001) and plasma norepinephrine increased from 183 +/- 27 to 232 +/- 27 pg/ml (p less than 0.01). Phentolamine nearly abolished the increase in forearm vascular resistance in response to V-A pacing (18 +/- 4.1 U before vs 5.8 +/- 1.5 U after, p less than 0.05). The change in forearm vascular resistance with V-A pacing correlated with systolic arterial pressure, but not with changes in mean arterial pressure, pulse pressure, cardiac output, mean or peak right atrial pressure, pulmonary artery or pulmonary capillary wedge pressure. These results suggest that forearm vascular resistance responses to V-A pacing are mediated mainly by alpha-adrenergic receptors, through the arterial baroreflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of cardiac tamponade after cardiac surgery: Relative value of clinical, echocardiographic, and hemodynamic signs

Early detection and treatment of cardiac tamponade is crucial in management of patients after cardiac surgery. Because of the atypical features of this condition and paucity of data on relative frequency of different signs, we evaluated the sensitivity of various clinical, echocardiographic, and hemodynamic signs. We retrospectively evaluated the relative frequency of clinical, echocardiographic, and hemodynamic signs in 29 patients with cardiac tamponade after cardiac surgery. In our study 66% had a localized, posterior pericardial effusion, and the other 34% had circumferential pericardial effusion. In the whole group 24% of patients had hypotension, and pulsus paradoxus was noted in 48%, right atrial collapse in 34%, right ventricular diastolic collapse in 27%, left ventricular diastolic collapse in 65%, and left atrial collapse in 13%. Elevation with equalization of pressures was noted in 81% patients. In the patient group with circumferential pericardial effusion and cardiac tamponade 40% patients were hypotensive and 50% patients had pulsus paradoxus. RA collapse was present in 70%, RV diastolic collapse in 70%, and LV diastolic collapse in 20%. Elevated diastolic pressures with equalization of these pressures was present in 71%. In the group with regional pericardial effusion and cardiac tamponade hypotension was present in 16% and pulsus paradoxus in 47%. RA collapse was present in 16%, RV diastolic collapse in 5%, LV diastolic collapse in 89%, and LA collapse in 21% of the patients with regional tamponade. Elevated diastolic pressures with equalization of these pressures was noted in 86% of the patients. Our observations indicate that among patients who have undergone cardiac surgery the presentation of cardiac tamponade is usually atypical.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Afferent reinnervation of the autotransplanted heart in dogs.

Patients have been observed with a chest pain syndrome after cardiac transplantation. For this pain to be cardiac in origin the afferent nerves carrying sensory information from the heart would have to reinnervate the heart. A previous study in dogs indicated that afferent reinnervation is uncommon during the first 2 years after transplantation. The purpose of this study was to determine whether afferent reinnervation of the heart occurs in the long term. The decreases in arterial pressure and renal nerve activity resulting from chemical stimulation of left ventricular sensory receptors with vagal afferents with cryptenamine (veratrum alkaloid) were assessed in three dogs 8 to 12 years and in four dogs 6 to 8 weeks after cardiac autotransplantation and in six sham-operated dogs (thoracotomy-pericardiotomy 6 to 8 weeks before study). Responses of renal nerve activity to physiologic stimulation of cardiac receptors by volume expansion were also determined. Left ventricular cryptenamine inhibited renal nerve activity by 72 +/- 8% in dogs with long-term and by 10 +/- 6% in dogs with short-term autotransplantation and by 92 +/- 5% in sham-operated dogs. Decreases in mean arterial pressure in these groups were 34 +/- 4, 11 +/- 3 and 67 +/- 16 mm Hg, respectively. Volume expansion inhibited renal nerve activity in long-term autotransplant (43%) and sham-operated (48%) groups but less in the short-term transplant group (33%) for comparable increases in cardiac filling pressure. It is concluded that in dogs there is extensive afferent reinnervation of the long-term autotransplanted heart that results in relatively normal cardiopulmonary baroreflex responses to volume expansion.(ABSTRACT TRUNCATED AT 250 WORDS)