The effect of severity of coronary artery obstructive disease and the coronary collateral circulation on local histopathologic and electrographic observations in man.
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Biopsy↗
Biomedical subjects
R H Helfant
Publications and source records attributed to R H Helfant.
Propranolol in mitral stenosis during sinus rhythm.
Patients with early symptomatic mitral stenosis usually suffer from pulmonary congestion on the basis of left atrial and pulmonary venous hypertension. They are often in sinus rhythm, and cardiac output is usually well maintained. Symptoms occur most often when heart rate, cardiac output, or both are increased. In this study, intravenous propranolol administered to patients with pure mitral stenosis in sinus rhythm resulted in significant reductions in mitral diastolic gradient (-7.1 mm. Hg +/- 1.6 SED), mean pulmonary wedge pressure (--6.9 mm. Hg +/- 1.2) and mean pulmonary artery pressures (--9.0 mm. Hg +/- 1.2). This was due to simultaneous reduction of heart rate (--13.0 beats/minute +/- 2.6 and cardiac output (--0.5 L./minute +/- 0.2). A small associated reduction of left ventricular systolic pressure (--5.1 mm. Hg +/- 2.6) was not accompanied by adverse clinical effects. A potential role for propranolol in medical management of pure mitral stenosis in the presence of sinus rhythm is suggested.
Adult↗
The use of echocardiography in determination of reversible posterior wall asynergy.
Recent studies have indicated that nitroglycerin can be delineate potentially reversible asynergic zones depicted ventriculographically. To assess the ability of the echocardiogram to detect reversible asynergy, posterior wall motion was assessed in 19 patients both echocardiographically and ventriculographically before and after nitroglycerin. Thirteen of the 19 patients demonstrated abnormal posterior wall motion both by echocardiography and ventriculography while six were normal by both techniques. In 4 of the 13 asynergic areas, posterior wall excursion improved following nitroglycerin (from 0.99 +/- .07 to 1.30 +/- .07 cm. by echocarciography (p less than .025) with a corresponding improvement in hemiaxis shortening from 12.0 +/- 6.1 per cent to 29.0 +/- 6.7 per cent (p less than .02). In contrast, in nine patients in whom inferior segment hemiaxis shortening was unchanged following nitroglycerin, posterior wall excursion by echocardiography was similarly not improved (1.01 +/- .03 cm. before and 1.02 +/- .03 cm. after nitroglycerin). The effect of nitroglycerin on posterior wall velocity paralleled changes in posterior excursion. The six patients with initially normal posterior excursion showed no significant change by either echocardiography or ventriculography following nitroglycerin. Thus, the echocardiogram is of considerable value in detecting both the presence and potential for improvement of asynergic posterior wall segments.
Cardiomyopathies↗
Contrasting effects of dopamine and isoproterenol in experimental myocardial infarction.
The comparative effects of dopamine and isoproterenol on local myocardial contraction and ischemic injury after coronary occlusion were evaluated in 10 dogs. Dopamine (2.5 to 5 mug/kg per min) and isoproterenol (0.125 to 0.25 mug/kg per min) were randomly infused for 20 minutes, and segmental tension (Walton-Brodie gauge) of central ischemic, border and nonischemic myocardial zones and epicardial electrograms (10 to 12 sites) were simultaneously recorded. After coronary occlusion, tension in border zones decreased to 73.5 +/- 6.4 percent (mean +/- standard error of the mean) and tension in central zones to 60.6 +/- 9.9 percent (P less than 0.001) of control level, whereas total S-T elevation (sigmaST) rose from 10.8 +/- 1.6 to 98.4 +/- 14.0 mv and average S-T elevation (ST) from 1.6 +/- 0.2 to 10.8 +/- 1.6 mv (P less than 0.001). Isoproterenol increased heart rate from 148.7 +/- 6.9 to 170.6 +/- 7.7 beats/min (P less than 0.010) and improved tension in the border zone to 110.5 +/- 8.5 percent (P less than 0.010) and improved tension in the border zone to 110.5 +/- 8.5 percent (P less than 0.005) and nonischemic zone to 128.4 +/- 6.7 percent (P less than 0.02). Tension in the central zone was unchanged. However, sigmaST increased from 98.4 +/- 14.0 to 126.9 +/- 14.7 mv (P less than 0.005) and ST from 10.8 +/- 1.6 to 14.2 +/- 1.6 mv (P less than 0.001). Dopamine did not change heart rate but increased tension in the border zone from 72.4 +/- 7.9 to 124.4 +/- 16.8 percent (P less than 0.001) and tension in the nonischemic zone from 86.0 +/- 10.0 to 133.3 +/- 10.0 percent (P less than 0.01). Tension in the central zone was unimproved. However, sigmaST and ST did not increase (sigmaST from 99.8 +/- 10.8 to 97.7 +/- 13.9 mv and ST from 11.1 +/- 1.3 to 10.8 +/- 1.5 mv). Atrial pacing was used to increase heart rate during infusion of dopamine to 180.0 +/- 7.6 beats/min but neither sigmaST nor ST increased. In summary, both dopamine and isoproterenol decrease contraction abnormalities in the border and nonischemic zones after after acute coronary occlusion. Although isoproterenol increases both heart rate and S-T segment elevation, dopamine does not adversely affect either variable.
Animals↗
Pathophysiologic significance of S-T and T wave abnormalities in patients with the intermediate coronary syndrome.
The frequent association of new ST-T wave changes without Q waves in the surface electrocardiogram of patients with the intermediate coronary syndrome necessitates a better understanding of the pathophysiologic significance of this finding. A previous study in patients with stable coronary artery disease indicated that the surface electrocardiogram is insensitive in detecting epicardial Q waves. This relation was evaluated in 21 patients with the intermediate syndrome, characterized by recurrent chest pain at rest associated with significant new S-T or T wave abnormalities, or both, and no new Q waves in the surface electrocardiogram at the time of open heart coronary bypass surgery. Unipolar electrograms were recorded from the epicardial surface of the left ventricle before the bypass procedure. In 19 patients, epicardial electrograms revealed initial R waves over areas of the left ventricle in which the acute S-T and T wave abnormalities were evident in the surface electrocardiogram. Two patients had epicardial Q waves (one laterally and one inferiorly). In seven patients, a transmural biopsy specimen was also obtained from the ischemic area. All showed histologically normal myocardium without evidence of early inflammatory or necrotic tissue. Of the 19 patients discharged, only one demonstrated new postoperative Q waves that had been detected by epicardial recordings before bypass. In summary, patients with the intermediate syndrome exhibiting S-T or T wave abnormalities, or both without new Q waves in the surface electrocardiogram generally do not have Q waves either in the intraoperative epicardial or postoperative surface electrocardiogram. In addition, no histopathologic abnormalities are apparent in biopsy specimens taken from the ischemic area.
Adult↗
Contrasting effects of nitroprusside and phentolamine in experimental myocardial infarction.
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Animals↗
Asynergy in coronary heart disease. Evolving clinical and pathophysiologic concepts.
The widespread use of cardiac ventriculography has focused interest on the frequency with which asynergy accompanies coronary heart disease as well as on its clinical and prognostic implications and dynamic nature. Recently, "intervention ventriculography" using nitroglycerin or postextrasystolic potentiation has indicated that asynergic zones may be more accurately classified as reversible (implying viable myocardium) or irreversible (nonviable or scarred myocardium), and thus the ventriculographic definition of aneurysm must reflect not only the severity of asynergy but its contractile reserve. Surface electrocardiogram Q waves, the severity of asynergy, and degree of coronary occlusion all adversely affect the potential for reversibility, whereas coronary collaterals enhance it. Important clinical applications include assessment of the potential utility of coronary bypass surgery in improving asynergy and of vasodilators in the treatment of patients with left ventricular failure. With refractory sequelae of aneurysms (heart failure, ventricular tachyarrhythmias, and systemic emboli) and a discrete aneurysm, surgical resection has been increasingly used with generally good results.
Arrhythmias, Cardiac↗
Determination of lead III Q waves significance. Utility of deep inspiration.
The relative clinical significance of lead III Q waves and the effect of inspiration has received added impetus after the finding that Q waves have predictive value for coronary artery disease and asynergy. We studied the effect of deep inspiration on Q waves in leads III and aVF in 31 patients and correlated it with the findings at cardiac catheterization. We found that phasic respiration can alter Q-wave duration significantly in leads III and aVF, regardless of the presence or absence of significant associated coronary artery disease and asynergy, and is therefore of no clinical value in this regard.
Cardiac Catheterization↗
Q waves in coronary heart disease: newer understanding of their clinical implications.
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Action Potentials↗
Nitroprusside therapy. Treatment of hypertensive patients with recurrent resting chest pain, ST-segment elevation, and ventricular arrhythmias.
Five hypertensive patients with acute myocardial infarction and persistent postinfarction hypertension who experienced severe and recurrent resting chest pain, ST elevations, and severe ventricular arrhythmias refractory to conventional treatment with bed rest, sedation, oxygen inhalation, nitrates, and antiarrhythmic agents received sodium nitroprusside by continuous intravenous infusion, titrated to reduce systolic blood pressure to 100 to 110 mm Hg. Treatment resulted in noticeable improvement in symptoms, reduction in ST elevations, and abolition of ventricular arrhythmias in all five patients. In four patients, cessation of nitroprusside infusion after 48 hours resulted in prompt recurrence of hypertension, chest pain, ST-segment elevations, and ventricular arrhythmias. These were all rapidly reversed following reinstitution of the nitroprusside therapy for seven to eight days, strongly suggesting a cause-and-effect relationship. Nitroprusside infusion in these patients suggests a potentially important use for such therapy in this clinical setting.
Acute Disease↗
Nitroglycerin: new concepts about an old drug.
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Arrhythmias, Cardiac↗
Temporal relation of epicardial electrographic, contractile and biochemical changes after acute coronary occlusion and reperfusion.
The increasing use of changes in the S-T segment of local epicardial electrograms to quantitate myocardial infarct size has led to the need for a better understanding of this method. Accordingly, we studied the local electrographic, tension and biochemical changes that occurred after coronary occlusion and subsequent reperfusion in 44 dogs using epicardial electrograms from 10 to 12 sites, Walton-Brodie strain gauge arches and myocardial ratios of potassium ion to sodium ion (K+/Na+). After coronary occlusion for 1 hour, total S-T segment elevation increased from 10.2 +/- 2.4 to 78.3 +/- 13.7 mv (P less than 0.001) and tension development decreased to 63.6 +/- 7.0% of control value (P less than 0.001); occlusion for 3 hours resulted in a total S-T segment elevation increase from 5.8 +/- 3.4 to 56.7 +/- 8.7 mv (P less than 0.001) and a tension decrease to 61.4 +/- 5.3% (P less than 0.001) of control value. After reperfusion two types of response were observed. In nine experiments new local pathologic Q waves appeared in an average of 5.3 of 8.2 ischemic electrode sites within 5 to 10 minutes of reperfusion concomitant with a marked further decrease in total tension from 67.3 +/- 5.5% to 42.4 +/- 6.0% of control value (P less than 0.001). Simultaneously, total S-T elevation decreased from 66.1 +/- 8.2 to 25.3 +/- 3.4 mv (P less than 0.001). In seven experiments no Q waves appeared after reperfusion and there was no significant change in tension. Total S-T elevation again decreased from 58.3 +/- 12.7 to 27.1 +/- 5.7 mv (P less than 0.025). When normal saline solution was perfused distal to the coronary arterial occlusion total S-T elevation decreased from 68.0 +/- 3.6 to 36.3 +/- 5.2 mv (P less than 0.001). After 3 hours of coronary occlusion, myocardial K+ decreased and Na+ increased in the ischemic zone, resulting in a significant decrease in the K+/Na+ ratio (P less than 0.005). Reperfusion for 2 hours resulted in a further depletion of K+ and an increase in Na+ with a resultant complete reversal of the K+/Na+ ratio (P less than 0.001). In summary, after reperfusion the S-T segment abnormalities rapidly decreased in all experiments despite the appearance of new Q waves in more than half of these studies concomitant with either a decrease or no change in contractile ability and continuing myocardial K+ loss and Na+ accumulation. S-T segment mapping therefore appears to be of limited value in assessing the effect of reperfusion on infarct size. The decrease in S-T segments that occurred with perfusion of either blood or saline solution suggests a "washout" phenomenon.
Animals↗
Effect of nitroprusside on local contractile performance after coronary ligation and reperfusion.
To study the effects of nitroprusside infusion on the regional contractile performance of the left ventricle after coronary occlusion, local tension and segment length of the ischemic, border and nonischemic zones were studied using Walton-Brodie strain gauge arches and mercury-in-Silastic tubing segment length gauges in open chest dogs. The effect of this intervention on the time period for functional reversibility of the affected areas after revascularization was also examined. Fifteen minutes after occlusion of the left anterior descending coronary artery, nitroprusside (4 to 11 mug/kg per min) was infused to keep systolic pressure 20 to 25% below control levels for 2 hours after occlusion and then 1 hour after reperfusion. The ischemic zone showed no change in either tension or length although there was a gradual continuing decrease in tension. However, in the border zone total tension which had decreased to 81.4 +/- 9.6 (standard error of the mean) percent of control level 15 minutes after coronary occlusion, increased to 87.5 +/- 11.3% immediately after nitroprusside infusion and continued at that level for 2 hours. Preejection tension rate of tension rise and ejection tension demonstrated parallel increases. Segment length, which had increased to 144.1 +/- 4.5% of control level after coronary occlusion, declined to 115 +/- 10.7% (P less than 0.02) immediately after the onset of infusion. The nonischemic zone showed a sustained increase in all tension variables (P less than 0.01) and a decrease in segment length during the period of nitroprusside infusion with a return to control value after discontinuation of the infusion. The immediate deterioration in tension in the ischemic zone caused by reperfusion after 2 hours of occlusion was prevented by nitroprusside. The border zone continued to maintain improved tension after reperfusion but exhibited an immediate decrease from 84.1 +/- 7.8% to 69.1 +/- 11.7% (P less than 0.05) after discontinuation of nitroprusside. In summary, nitroprusside infusion provides a sustained increase in tension and decrease in length of the border and the nonischemic zones after acute coronary occlusion whereas the ischemic zone remains unaffected. Although administration of nitroprusside fails to prolong the time period for functional reversibility of the affected zones with reperfusion, it appears to prevent further deterioration.
Animals↗
Evaluation of left ventricular performance in coronary heart disease: use of isometric handgrip stress test.
The usefulness of isometric handgrip exercise in the assessment of left ventricular function was studied in 27 patients, all of whom had angiographically documented coronary artery disease. The effect of extensiveness of coronary disease and presence or absence of collaterals (both delineated by coronary arteriography) on the response to handgrip stress was also evaluated. Of 11 patients with a normal handgrip response, 4 exhibited a normal left ventriculogram and 7 were abnormal. Of these 7, 6 had inferior hypokinesis. Conversely, of 16 patients with an abnormal response to handgrip, 15 had abnormal ventriculograms. Of these, 9 had anterior akinesis. Of patients with a normal handgrip response 82% had two- or three-vessel coronary disease, and 94% with an abnormal response exhibited two- or three-vessel obstruction. There was no observed correlation between the presence or absence of collaterals and the response to handgrip. This study indicates that (1) handgrip stress, when combined with left ventriculography, often yields important additional information regarding the effect of localized contraction abnormalities on overall left ventricular performance; (2) the extent of coronary obstructive disease or the presence of collaterals per se do not appear to be the primary determinants of left ventricular performance; (3) it is possible that the location as well as severity and extent of left ventricular contraction abnormality may play an important role in determining overall left ventricular performance.
Adult↗
Guanabenz effects on blood pressure and noninvasive parameters of cardiac performance in patients with hypertension.
Guanabenz (2,6 dichlorobenzylidene amino guanidine acetate) is a new antihypertensive whose mechanism of action appears to involve both central alpha adrenergic stimulation leading to suppression of sympathetic nervous system activity from bulbar vasoconstriction centers as well as peripheral adrenergic neuron blockade. In this study, the drug was shown to produce a statistically and clinically significant decrease in blood pressure during a 4-wk placebo-controlled double-blind study. For three additional months continued efficacy and safety were shown under open conditions in 17 hypertensive patients. Mild sedation occurred, but there were no postural hypotension, tachycardia, evidence of sodium retention, gastrointestinal disturbances, or electrocardiographic (ECB) abnormalities. Noninvasive parameters of cardiac performance in 10 patients after single doses of guanabenz showed no significant changes. Although the numbers of patients were relatively small, the data suggest that this new drug may be a useful antihypertensive agent that warrants further investigation.
Adult↗
Local characteristics of the normal and asynergic left ventricle in man.
The significance of ventricular asynergy in determining medical prognosis and surgical risk in patients with coronary artery disease and its delineation by ventriculography have been of increasing interest. To determine the underlying histopathologic and electrographic features of left ventricular asynergy, 39 patients undergoing open heart surgery were studied. Thirty-six histopathologic specimens were obtained in 31 patients (26 as transmural needle biopsies and 10 as aneurysm resections). In four normally contracting areas and 12 hypokinetic areas, neither fibrosis nor early changes of myocardial damage was evident. In contrast, of eight akinetic areas there was more than 50 per cent muscle loss in four and from 30 to 35 per cent muscle loss in three, in only one area was there less than 10 per cent muscle loss. Of 12 dyskinetic zones there was more than 75 per cent muscle loss in 10 zones, 35 per cent in one and no pathologic abnormalities in one. Epicardial electrograms were obtained from 35 areas in 29 patients. Of 10 normally contracting ventricles, in one, pathologic Q waves were demonstrated only over the inferior area. Progressive increases in the severity of asynergy were associated with a progressive increase in frequency of initial abnormal Q waves. In only one of nine hypokinetic areas were epicardial Q waves exhibited, but they were present in six of 10 akinetic and five of six dyskinetic areas. Both histopathologic and electrographic data were available from 20 asynergic areas in 16 patients. Initial epicardial R waves were associated with normal biopsy specimens in seven of eight hypokinetic areas. Of seven akinetic areas, initial R waves were associated with 30 to 35 per cent muscle loss in three; of four areas with initial Q waves, there was a 35 per cent muscle loss in one and more than 50 per cent muscle loss in three. Similarly, of five dyskinetic segments, a QS pattern was associated with more than 75 per cent fibrosis in four. In one dyskinetic area there was an intial R wave in association with a normal appearing biopsy specimen. In summary, a good correlation exists between the severity of asynergy by ventriculography, the degree of muscle loss and the presence of epicardial Q waves. However, a significant amount of histologically and electrographically normal myocardium may be present even in severely asynergic areas.
Cardiac Catheterization↗
Propranolol in experimental myocardial ischemia: dissociation of effects on contraction and epicardial ST segments.
Recent studies have suggested that propranolol decreases the extent of myocardial injury in acute ischemia. Although other studies have shown that global myocardial performance is depressed, zonal effects of propranolol in this setting are unknown. Therefore, the effect of propranolol (1.0 mg. per kilogram) was investigated in nine dogs with the use of Walton-Brodie strain gauge arches and local epicardial electrograms (10 to 12 sites). The heart rate effects of propranolol were controlled by atrial pacing. After coronary occlusion, heart rate increased slightly without a significant change in blood pressure. Following the infusion of propranolol, heart rate decreased significantly from 165.0 +/- 3.5 to 126.2 +/- 4.7 beats per minute (p less than 0.001) while both the systolic and diastolic blood pressures showed insignificant changes. After coronary occlusion, nonischemic zone tension showed no significant changes; however, propranolol decreased total tension from 105.2 +/- 2.5 per cent to 66.8 +/- 4.7 (p less than 0.001). Similarly, propranolol further decreased total tension in the border zone from 84.4 +/- 6.7 per cent (p less than .02) to 50.6 +/- 5.1 (p less than 0.01). Ischemic zone tension also fell further (p less than 0.025) after propranolol. Restoration of prepropranolol heart rate had no significant effect on tension development. Following coronary occlusion, sigmaST increased from 5.7 +/- 2.2 to 72.9 +/- 20.1 mv. (p less than 0.001). Coincident with the decrease in heart rate and tension development induced by propranolol, sigmaST decreased to 60.8 +/- 18.8 mv. (p less than 0.05). When the heart rate was restored to prepropranolol level, sigmaST again rose to 73.2 +/- 16.9 mv. (p less than .005). Thus, propranolol does effect an improvement in ischemic injury which is related, at least in part, to the induced decrease in heart rate. A concomitant substantial decrease in local tension development also occurs, however. The latter observations may limit the potential usefulness of propranolol in this setting.
Animals↗
Effect of heart rate on zonal tension and ischaemia following coronary occlusion: optimal rate for Treppe versus ischaemia.
The optimal heart rate in the immediate period following acute coronary occlusion has been controversial from the standpoint of arrhythmias and the extent of ischaemic injury. In the present study we have examined the effect of heart rate on both local myocardial contractile ability and ischaemia in 10 open chested dogs using strain gauge arches and epicardial electrograms. After sinus node destruction, atrial pacing was instituted for rate control at 100/min and increased randomly to 150, 175, and 200/min. Before coronary occlusion, total tension and rate of tension rise progressively increased at higher rates while ST segments demonstrated no significant changes. After coronary artery occlusion, total tension and rate of tension rise in the ischaemic zone decreased markedly and showed no significant change with increments in pacing rate. In the border zone, after the initial decrease in tension, pacing at 150 beats/min improved tension without a change in ST segments. However, when the rate was increased to 175 and 200 beats/min, although border zone tension increased further, ST segments rose significantly. Thus, a heart rate between 100-150/min provides the optimal range for increasing contractile ability in the nonischaemic and border zones without adversely affecting the degree of ischaemic injury.
Acute Disease↗