Effects of cardiac hypertrophy secondary to hypertension on the coronary circulation.

For many years clinicians have suspected that hypertrophied ventricles have an inadequate coronary circulation. Recent studies have confirmed early observations that flow per gram in hypertrophied ventricles is normal at rest. However, coronary vascular resistance is greatly increased when hypertension is the cause of left ventricular hypertrophy. Studies that have employed labeled microspheres to assess regional myocardial perfusion have shown that the transmural distribution of myocardial perfusion is often abnormal in dogs with left ventricular hypertrophy. In addition, studies of cardiac hypertrophy in many animal models have shown that maximal coronary vasodilatation is limited substantially. Furthermore, when hypertrophied hearts are subjected to a physiologic stress that induces coronary vasodilatation, endocardial underperfusion occurs frequently. Thus, studies in animals suggest that cardiac hypertrophy adversely affects the coronary circulation. The availability of new techniques for estimating phasic and transmural coronary blood flow in man should make it possible to extend these studies to patients with cardiac hypertrophy.     

Coronary reserve in volume-induced right ventricular hypertrophy from atrial septal defect

To assess coronary reserve in patients with right ventricular (RV) hypertrophy secondary to volume overload, the quantitative characteristics of coronary reactive hyperemia were examined in 20 patients with a large atrial septal defect (ASD). The control group consisted of 13 patients who had undergone elective cardiac surgery for abnormalities that did not involve the right ventricle or its blood supply. Coronary blood flow velocity was measured in RV branches of the right coronary artery at cardiac surgery. Echocardiographic measurements of RV diameter in ASD and in control patients (2.3 +/- 0.2 and 1.1 +/- 0.2 cm, respectively, p less than 0.05) documented the presence of substantial RV enlargement in patients with ASD. In patients with ASD and in control subjects, a 20-second coronary occlusion produced maximal coronary dilation. After release of a 20 second coronary occlusion, the peak-to-resting velocity ratio in ASD and in control patients was 3.1 +/- 0.2 and 5.5 +/- 0.1, respectively (p less than 0.05). The 50% decrease in the ratio of peak-to-resting coronary blood flow velocity, a measure of relative coronary reserve, in patients with ASD suggests that coronary reserve is compromised in volume-induced RV hypertrophy. These studies support the concept that in humans, volume-induced RV hypertrophy substantially decreases coronary reserve.     

Prospective study of surgery for left ventricular aneurysm

To assess the effects of surgery for ventricular aneurysm on left ventricular performance 18 consecutive patients referred for such surgery were Studied prospectively. The patients had the following preoperative findings: ejection fraction by Isotope ventriculogram 28± 4 percent (mean ± standard error), New York Heart Association functional class 3.6 ± 0.1 and left ventricular noncontractile area 28 ± 3 percent by the graphic integration method. Thirteen patients had both angina pectoris and congestive heart failure, two had angina alone and three had congestive heart failure alone. All patients were studied before and after operation with isotope ventriculograms at rest and during exercise and treadmill exercise tolerance tests if their clinical status permitted these studies. Five patients also had postoperative cardiac catheterization. Catheterization data were in close agreement with the results of imaging studies. In 11 patients the aneurysm was resected and in 4 H was plicated; in 3, no discrete aneurysm was found. Sixteen patients including the three with no discrete aneurysm had concomitant coronary bypass grafting. There was no operative death and one late death.After operation, all patients had significant improvement in functional class (postoperative class 2.3 ± 0.1, p < 0.005). The amount of tissue resected (percent of total left ventricular surface area) was about 50 percent of the noncontractile area visualized on contrast angiography and there was a poor correlation between these two values (r = 0.56). Only four patients (22 percent) had either an increase in ejection fraction (range 8 to 13 percent) or a greater than 10 percent reduction in end-diastolic volume. Postoperative left ventricular end-diastolic pressure was unchanged. Thus, surgery for ventricular aneurysm can be accomplished with relatively small risk. Although functional Improvement is very common, it is not related to substantial improvement in global left ventricular function.     

Comparison of three methods of evaluating coronary obstructive lesions: Postmortem arteriography,pathologic examination and measurement of regional myocardial perfusion during maximal vasodilation

Numerous studies of coronary obstructive lesions in patients by angiographic and pathologic techniques have concluded that the severity of obstruction is seriously underestimated by angiography. It has generally been assumed that morphologic examination of an undistended coronary vessel is a reasonable reference standard. To test this assumption, three methods of examining coronary arteries were compared in cynomolgus monkeys with diet-induced coronary atherosclerosis. Total and regional myocardial perfusion during maximal coronary vasodilation were measured, postmortem coronary arteriography was performed with contrast medium injected at systemic pressure and the undistended coronary vessels were extended pathologically. In these atherosclerotic monkeys, there were widespread intimai changes in the epicardial arteries ranging from fatty streaks to large plaques with medial atrophy; morphometric studies showed a mean (± standard error of the mean) luminal stenosis of 57 ± 3 percent (range 38 to 76). Postmortem coronary arteriograms showed no evidence of localized obstruction. Under resting conditions, global and transmural left ventricular perfusion were normal. During maximal coronary vasodilation, minimal coronary vascular resistance was higher (p <0.07) in these monkeys with atherosclerosis than in normal control monkeys (0.21 ± 0.04 versus 0.13 ± 0.07 mm Hg/ml × ml/min × 100 g). No evidence of localized perfusion deficits was observed in either group of monkeys under control conditions or during maximal coronary vasodilation.The findings of unobstructed coronary angiograms and only modest impairment of perfusion, despite moderate obstructive lesions, suggest that at normal distending pressures coronary atherosclerotic lesions are outwardly displaced; medial atrophy may allow dilation and preservation of luminal size. Thus, in cynomolgus monkeys with diet-induced coronary atherosclerosis, pathologic examination of the undistended coronary vessel appears to overestimate the hemodynamic significance of the lesions. The relevance of these experimental findings to the evaluation of atherosclerotic coronary lesions in patients remains to be determined.     

The Bezold-Jarisch reflex revisited: Clinical implications of inhibitory reflexes originating in the heart

The concept of depressor reflexes originating in the heart was introduced by von Bezold in 1867 and was later revived by Jarisch. The Bezold-Jarisch reflex originates in cardiac sensory receptors with nonmyelinated vagal afferent pathways. The left ventricle, particularly the inferoposterior wall, is a principal location for these sensory receptors. Stimulation of these inhibitory cardiac receptors by stretch, chemical substances or drugs increases parasympathetic activity and inhibits sympathetic activity. These effects promote reflex bradycardia, vasodilation and hypotension (Bezold-Jarisch reflex) and also modulate renin release and vasopressin secretion. Conversely, decreases in the activity of these inhibitory sensory receptors reflexly increase sympathetic activity, vascular resistance, plasma renin activity and vasopressin.Long regarded as pharmacologic curiosities, it is now clear that reflexes originating in these inhibitory cardiac sensory receptors are important to the pathophysiology of many cardiovascular disorders. This paper reviews the role of inhibitory cardiac sensory receptors in several clinical states including 1) bradycardia, hypotension and gastrointestinal disorders with inferoposterior myocardial ischemia and infarction, 2) bradycardia and hypotension during coronary arteriography, 3) exertional syncope in aortic stenosis, 4) vasovagal syncope, 5) neurohumoral excitation in chronic heart failure, and 6) the therapeutic effects of digitalis.     

Carotid sinus baroreflex influence on electrophysiologic properties of the canine atrioventricular node and ventricle

This study examines the efferent mechanisms of carotid sinus baroreflex influence on ventricular repolarization and refractory period compared with effects on atrioventricular (AV) nodal conduction. Pressure was controlled in both carotid sinuses by the Moisejeff technique in 16 chloralose-anesthetized dogs. Increases in carotid sinus pressure during pacing produced graded prolongation of AV nodal conduction, ventricular repolarization and refractory period with a threshold at a carotid sinus pressure of 120 mm Hg and a peak response at 200 mm Hg. Atropine, 0.4 mg/kg, attenuated the peak percent change in ventricular repolarization interval by only 12 ± 14% (± standard error of the mean) despite a significantly greater attenuation (48 ± 11%, p <0.05) in peak percent change in AV nodal conduction. However, stellate ganglionectomy attenuated the peak percent change in ventricular repolarization (42 ± 19%), similar to effects on AV nodal conduction (59 ± 21%, p >0.25). Changes in mean arterial pressure, ventricular end-diastolic segment length or segment length shortening with systole (sonomicrometer technique) did not account for the electrophysiologic responses. Latency to peak effect on ventricular repolarization (43 ± 7 seconds) was slower than that on AV nodal conduction (23 ± 6 seconds, p <0.05). This difference in time course was not abolished by atropine. Thus, the carotid sinus baroreflex prolongs ventricular repolarization and refractoriness mainly by withdrawal of sympathetic influence; AV nodal conduction is prolonged by both vagal activation and sympathetic withdrawal. In addition, differences in time course between ventricular and AV nodal electrophysiologic responses are not explained by different efferent autonomic mechanisms.     

Artifactual regional gray level variability in contrast-enhanced two-dimensional echocardiographic images: effect on measurement of the coronary perfusion bed

The purpose of this study was to determine the extent of regional variability of image echocardiographic amplitude (expressed as gray level variability) in contrast-enhanced two-dimensional echocardiographic images, and to assess the effect of such baseline gray level variability on quantitation of the coronary perfusion bed. In 10 anesthetized closed chest dogs, short-axis papillary muscle echocardiographic images were obtained during control preinjection conditions and during injection of three contrast agents into the left main coronary artery with and without circumflex artery occlusion. Regional echocardiographic amplitude variation was measured by computer-based videodensitometric analysis of mean gray levels in four myocardial regions after cavity (background) gray level subtraction. To determine the effect of regional gray level variability on quantitation of the coronary perfusion bed, the contrast-enhanced left anterior descending artery perfusion bed was measured by two methods. The circumferential method ignored myocardial contrast inhomogeneity by measuring the circumferential extent of contrast enhancement, whether or not the enhancement by contrast medium extended transmurally. The exact method measured only the area of myocardium actually enhanced by contrast medium, which often did not extend transmurally. The perfusion beds determined by the two echocardiographic methods were compared with the anatomic perfusion bed determined by postmortem barium-gelatin coronary arteriography. Regional gray levels varied qualitatively and quantitatively in the control state (before contrast injection), with lateral regions being less bright than axial regions. After injection of contrast medium, brightness increased in all regions, the axial regions brightening most.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the volume conductor on the apparent orientation of a known cardiac dipole

The surface electrocardiogram (EKG) is dependent on two major factors: the cardiac generator and the volume conductor. This investigation assessed the effects of the volume conductor in man on the apparent orientation of a simulated cardiac dipole. The apparent orientation of the dipole was calculated from measured surface potentials from about 60 locations on the body of five patients with implanted cardiac pacemakers. The real orientation of the dipole (an implanted pacemaker) was determined radiographically. The effects of both inhomogeneity and boundary characteristics of the volume conductor on the apparent orientation of the dipole were assessed using a new inverse algorithm. The difference between the orientation of the real and the calculated dipoles averaged 30 degrees (range 15 degrees--40 degrees) when the torso was assumed to be an infinite-homogeneous volume conductor. When the configuration of the torso was accounted for, however, the difference between the orientation of the real and calculated dipoles was reduced to 9 degrees (range 5 degrees--13 degrees). Thus, by taking into account the geometry of the torso and neglecting the inhomogeneities in the volume conductor, it is possible to calculate the orientation of a dipole in the cardiac region with an accuracy of about 9 degrees. It is reasonable to assume that the orientation of real activation wave fronts from localized areas of the heart could be calculated with a similar degree of accuracy.     

Left atrial myxoma: Demonstration by stop-action cardiac ultrasonography

A case of left atrial myxoma masquerading as a cardiomyopathy is presented; the unsuspected tumor was diagnosed by stop-action cardiac ultrasonography and echocardiography. The stop-action technique complements standard echocardiography by enhancing the delineation of anatomic and spatial orientation. It has previously been applied to congenital cardiac lesions and should prove to be a valuable noninvasive technique in the precatheterization evaluation of acquired heart disease as well.     

Anuloaortic ectasia: angiographic, hemodynamic and clinical comparison with aortic valve insufficiency

Thirty-five patients with angiographically diagnosed anuloaortic ectasia were compared with 18 patients with isolated aortic valve insufficiency to study differences between the presentation, hemodynamic or angiographic findings and clinical course in the two groups. The maximal aortic root diameter in anuloaortic ectasia was 7.6 +/- 2.4 cm (mean +/- 1 standard deviation) versus 4.2 +/- 0.6 in aortic insufficiency. Dissection was a common complication of anuloaortic ectasia (44 percent) but was not seen in aortic insufficiency. Neither the size nor the configuration of the aortic aneurysm was a reliable predictor of dissection. Despite surgical therapy, patients with anuloaortic ectasia have a worse prognosis than those with aortic valve insufficiency.     

Diastolic blood flow into the pulmonary artery in carcinoid heart disease

A patient with carcinoid heart disease manifested by mild pulmonary stenosis, severe tricuspid incompetence and mild tricuspid stenosis had unequivocal evidence of blood flow from the right ventricle into the pulmonary artery during ventricular diastole. Simultaneous right ventricular and pulmonary arterial pressure curves demonstrated that right ventricular diastolic pressure exceeded pulmonary arterial pressure during mid-diastole, indicating consistent mid-diastolic opening of the pulmonary valve. This was followed by a parallel increase in right ventricular and pulmonary arterial pressures throughout the rest of diastole. Right heart cineangiograms, obtained with right atrial dye injection, substantiated the pattern of flow from the right ventricle to the pulmonary artery during ventricular diastole. This previously unrecognized phenomenon is probably due to the combined effects of increased right atrial pressure, decreased right ventricular compliance and normal pulmonary arterial pressure.     

Cardioselective and nonselective beta-adrenoceptor blocking drugs in hypertension: a comparison of their effect on blood pressure during mental and physical activity

The ability of cardioselective and nonselective beta-adrenoceptor blocking drugs, with and without partial agonist activity, to control increases in blood pressure associated with mental and physical activity was compared in 35 subjects with hypertension. Direct measurements of blood pressure and radioenzymatic determinations of plasma norepinephrine were obtained before, during and after four activities, and were repeated after random allocation to treatment with atenolol, metoprolol, pindolol or propranolol. Cardioselective and nonselective drugs modestly reduced the pressor response to reaction time testing, but not to mental arithmetic or isometric exercise. The increase in systolic blood pressure during bicycling was attenuated significantly by the cardioselective drugs atenolol (by 23 mm Hg, or 38%) and metoprolol (21 mm Hg, or 41%), but not by the nonselective agents pindolol (with partial agonist activity) (13 mm Hg, or 20%) and propranolol (10 mm Hg, or 17%) (p less than 0.02 cardioselective versus nonselective; p = NS pindolol versus propranolol). Only bicycle exercise increased plasma norepinephrine concentrations (by 80%). These results suggest that beta-adrenoceptor blocking drugs will not attenuate increases in blood pressure during mental or physical activities unless intense sympathoadrenal activation also occurs. Marked elevations in circulating epinephrine, with or without norepinephrine, and peripheral beta 2-blockade appear necessary for alpha-mediated vasoconstriction to predominate and for the contrasting effects of cardioselective and nonselective drugs to be appreciated.     

Systemic markers of fibrinolysis after unsuccessful intracoronary streptokinase thrombolysis for acute myocardial infarction: Does nonreperfusion indicate failure to achieve a systemic lytic state?

Reasons for the failure of intracoronary streptokinase (STK) to result in coronary thrombolysis were examined in 45 patients with acute myocardial infarction presenting with angiographic evidence of total coronary occlusion. In 25 patients (group A), clot lysis was initially successful; in 20 (group B), reperfusion was unsuccessful. The STK dosage in group A ranged from 84,000 to 310,000 units (mean 188,000 +/- 12,000); STK dosage in group B ranged from 160,000 to 360,000 units (mean 267,000 +/- 11,000 [p less than 0.05]). Before therapy, levels of fibrin degradation products and serum fibrinogen were normal in all patients. After intracoronary STK, fibrin degradation products and serum fibrinogen levels changed similarly in both groups. Eight-five percent of patients in group B had evidence of a systemic fibrinolytic state. These data suggest that higher doses of STK administered in the same manner are unlikely to result in an increased reperfusion rate. Systemic hematologic markers of fibrinolysis are not helpful in explaining the success or failure of intracoronary thrombolysis.     

Use of an ultrasonic contrast method in the diagnosis of valvular regurgitation and intracardiac shunts

Injection of normal saline solution or indocyanine green dye through intracardiac catheters results in ultrasonic reflections from the site of injection. To evaluate the diagnostic usefulness of this observation, ultrasonic transducers were first placed directly on the pulmonary artery or ascending aorta of six open chest dogs. The rapid injection of 5 ml of normal saline solution into the femoral vein or left atrium produced a “cloud” of contrast echoes filling the pulmonary artery or ascending aorta. Thus, the echo-reflecting phenomenon persists during the passage of blood across two cardiac valves. Sixty-two patients aged 2 months to 70 years were then studied during cardiac catheterization; recordings were made during injection of indocyanine green dye or normal saline solution. Contrast echoes appeared in the left atrium after left ventricular injection in 14 of 16 patients with mitral regurgitation. Aortic root injection produced contrast echoes in the left ventricle in 13 of 16 patients with aortic regurgitation. Valvular regurgitation as small as 10 percent by angiographic determination was detected. Shunting was detected In patients with atrial and ventricular septal defects, patent ductus arteriosus and tetralogy of Fallot. Catheter-induced mitral regurgitation was demonstrated in one patient. This method is a sensitive and accurate qualitative technique for detecting intracardiac shunts and valvular regurgitation.