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Biomedical subjects

R H Helfant

Publications and source records attributed to R H Helfant.

At least 73 records · Page 4Linked to original sources

Influence of nitroglycerin on collateral blood flow during acute ischaemia in the dog.

To investigate the effects of nitroglycerin on collateral blood flow 10 open chest dogs underwent coronary occlusion followed by nitroglycerin infusion (80 to 300 micrograms . min-1) to lower mean systemic blood pressure by 20 mmHg, followed by phenylephrine infusion (10 to 40 micrograms . min-1) to restore blood pressure to the pre-nitroglycerin level. Myocardial blood flow was measured with microspheres. The contribution of overlapping normal zone tissue in the ischaemic zone was evaluated with the balloon perfusion technique. Collateral flow was measured with microspheres in the most ischaemic tissue. In addition "load line" analysis was used to calculate collateral flow from retrograde flow. Nitroglycerin lowered blood flow to non-ischaemic tissue, and tended to lower blood flow to ischaemic tissue. Phenylephrine restored blood flow to the value after coronary occlusion. Load line analysis data was similar to data on myocardial blood flow from the microspheres. Collateral resistance changed little during the experiment. Th effects of nitroglycerin on collateral blood flow are, thus, minimal. While it is possible that under special circumstances there may be some decrease in collateral resistance, the bulk of data from this study and others do not support the idea that systemic infusion of nitroglycerin in the setting of an acute myocardial infarction will affect collateral flow.

Animals↗

Evaluation of "ischemia at a distance": effects of coronary occlusion on a remote area of left ventricle.

The effect of coronary occlusion on blood flow and function in a remote zone of the left ventricle was studied in 21 open-chest dogs. Group A consisted of 6 dogs not undergoing left circumflex (LC) coronary artery cannulation. The other 15 dogs underwent cannulation of the LC artery followed by partial occlusion to 40 mm Hg diastolic perfusion pressure. Of these dogs, 7 with constant perfusion pressure (group B) were separately evaluated from 8 with declining perfusion pressure (group C). Sequentially more proximal left anterior descending (LAD) occlusions were performed in each group. Blood flow in the LC zone remained unchanged in group A after sequential LAD occlusions, whereas in groups B and C distal and proximal LAD occlusions caused progressive reduction in LC flow. Although in group A segment shortening improved in the LC zone after distal LAD occlusion, in groups B and C progressive impairment in segmental shortening was observed in the LC zone after distal and proximal LAD occlusions. Thus, in the setting of critical coronary stenosis in a zone, total occlusion in another coronary artery can initiate a series of events leading to decreased blood flow in the territory of the stenotic coronary artery, resulting in ischemia and impaired segmental function.

Animals↗

Critical analysis of the application of Bayes' theorem to sequential testing in the noninvasive diagnosis of coronary artery disease.

The utility of Bayes' theorem in the noninvasive diagnosis of coronary artery disease (CAD) was analyzed in 147 patients who underwent electrocardiographic stress testing, thallium-201 perfusion imaging and coronary angiography. Eighty-nine patients had typical anginal chest discomfort and 58 had atypical chest pain. Sensitivity and specificity of the tests and prevalence of CAD at each level of testing were tabulated and compared with the results generated from Bayes' theorem. The sensitivity of electrocardiographic stress was higher in patients with multivessel CAD than in patients with 1-vessel CAD. Sensitivity, but not specificity, of each test was dependent, in part, on the result of the other test. However, the probabilities calculated from Bayes' theorem when used for sequential testing are remarkably close to the tabulated data. Thus, Bayes' theorem is useful clinically despite some evidence of test dependence. Sequential test analysis by Bayes' theorem is most useful in establishing or ruling out a diagnosis when the pretest prevalence is approximately 50% and when the 2 tests are concordant.

Aged↗

Pseudocoarctation of the aortic arch in a patient with Turner's syndrome.

Pseudocoarctation of the aortic arch is a rare congenital anomaly which resembles true coarctation by the presence of a narrowing in the descending thoracic aorta immediately distal to the origin of the left subclavian artery. However, it is differentiated from that entity by the absence of a significant hemodynamic obstruction and by the presence of aneurysmal dilatation proximal and distal to the area of narrowing. As a result, the commonly observed clinical findings of coarctation such as a prominent collateral circulation and decreased blood pressure in the lower extremities are not observed. "Kinking" or "buckling" are common adjectives used to describe the roentgenographic appearance of the aortic arch in this condition. The association of various congenital cardiac abnormalities with pseudocoarctation has been reported, and are similar to those commonly seen with true coarctation. We now present the first reported case of pseudocoarctation associated with a probable bicuspid aortic valve in a patient with Turner's syndrome.

Aortic Coarctation↗

Variable effects of intracoronary nitroglycerin on myocardial blood flow and segmental shortening according to dose and degree of coronary occlusion.

The effects of intracoronary nitroglycerin were determined in 21 open-chest dogs. Six dogs with severe stenosis (25 mm Hg diastolic perfusion pressure) and nine dogs with moderate stenosis (40 mm Hg) received a 12 micrograms bolus followed by 44 micrograms/min intracoronary nitroglycerin. In addition, six dogs with moderate stenosis (40 mm Hg) received 5 micrograms followed by 5 micrograms/min nitroglycerin. Myocardial blood flow was measured with radioactive microspheres and segment shortening with ultrasonic crystals. At 40 mm Hg, high-dose but not low-dose nitroglycerin raised epicardial blood flow, while at 25 mm Hg nitroglycerin had no effect. Subendocardial blood flow was not affected in any group. Partial occlusion resulted in a decrease in segment shortening in the 25 mm Hg group but not at 40 mm Hg. High-dose nitroglycerin had no effect on shortening at either level of occlusion. Thus, in the presence of coronary vascular reserve, high-dose nitroglycerin may overcome coronary autoregulation. A dose equivalent to one that simulates the amount of nitroglycerin delivered to the coronary circulation by a systemic infusion did not affect myocardial blood flow. In addition, even a large dose of nitroglycerin did not affect segment shortening.

Animals↗

Contrasting incidence, inducibility, and transmural sites of origin of ventricular arrhythmias during acute coronary occlusion and reperfusion.

The incidence, inducibility, and sites of origin of ventricular arrhythmias were studied in 16 open-chest dogs. The dogs were placed on cardiopulmonary bypass. Electrograms from ischemic endocardium and epicardium and normal epicardium were recorded with bipolar composite electrodes. Burst pacing was used to induce arrhythmias. Dogs were studied in the control state, 15 minutes after left anterior descending coronary artery occlusion, and during reperfusion performed after 20 minutes of occlusion. Ventricular fibrillation was seen more commonly (in 8 of 14 dogs) during reperfusion than during occlusion (in 4 of 13 dogs). Continuous fragmented electrical activity was first recorded on the ischemic zone epicardium in six of eight episodes during occlusion arrhythmias and on the endocardium in 25 of 33 episodes during reperfusion. These data may relate to the effects of varying degrees of ischemia and reperfusion on conduction characteristics of the respective layers.

Animals↗

Quantitative thallium-201 imaging: limitations in detecting pathophysiologically significant obstructive coronary artery disease.

Washout of thallium-201 after stress testing has been proposed as a method of detecting abnormal zonal myocardial perfusion without relating it to a reference "normal" area. Therefore, 18 patients with single-vessel coronary artery disease, undergoing percutaneous transluminal coronary angioplasty, underwent maximum stress testing and thallium imaging. A myocardial perfusion defect was seen in the immediate postexercise images in all 19 zones (one patient studied twice) supplied by the vessel with the obstructive lesion. Delayed images showed improvement in 15 of the 19 segments. Of the four zones which did not improve, three had evidence of a prior nontransmural myocardial infarction. Quantitative analysis of washout curves showed that counts decreased in 17 of 19 zones after background subtraction and in all 19 zones if background was not subtracted. In the corresponding normal zones directionally similar decreases in counts were seen. Thus washout characteristics were similar for both diseased and normal zones. These data indicate that washout curves are limited in their ability to detect the presence of a physiologically significant lesion.

Adult↗

Influence of nifedipine on collateral blood flow during acute ischemia in the dog.

Vasodilators have been found effective in increasing blood flow in the lateral border surrounding a central zone of infarction, but any change in blood flow to this border zone may be to the normal tissue in this zone, rather than to the ischemic tissue. In this study of the effects of nifedipine on collateral blood flow, 31 open chest dogs underwent coronary occlusion followed by nifedipine infusion, either 3 or 1 microgram/kg per min. A balloon perfusion microsphere labeling device was used to separate the influence of normally perfused tissue overlapping with ischemic tissue in the lateral border zone. Nifedipine increased blood flow in the border zone, but this increase could be accounted for by the effect of nifedipine on admixed normal tissue. In the central ischemic zone, nifedipine administration resulted in a decrease in collateral blood flow. Thus, to fully understand the effect of a vasodilator on ischemic zone blood flow, it is necessary to account for flow in overlapping normal tissue.

Animals↗

Epicardial, endocardial and transmural mapping in assessing electrophysiological effects of 14-C lidocaine and 14-C propafenone on activation times in experimental chronic myocardial infarction. Correlations with myocardial drugs concentrations.

The electrophysiological effects of lidocaine (L) and propafenone (P) in chronic myocardial infarction in relation to tissue drug concentrations (TDC) are unknown. Thus of 16 dogs with one week old myocardial infarction, 8 received propafenone 2 mg/kg and 8 lidocaine 5 mg/kg followed by 0.2 mg/kg/min of either drug for 60 min. Epicardial (EPI) mapping (greater than 30 points) was performed with a bipolar electrode. Endocardial (ENDO) and transmural (TRANS) mapping (greater than 20 points) were performed with 4 pairs of needle mounted bipolar electrodes. The % change in activation times (% delta AT) in EPI, ENDO and TRANS was evaluated in normal (N) and infarcted (I) zones at control and 60 min after drugs. Ventricular arrhythmias (VA) were studied with programmed extra stimulation. Results (P less than 0.01 to L, P less than 0.01 to N zone, # P less than 0.05 to ENDO): (Table: see text) At 60' ventricular tachycardia and ventricular fibrillation were both still inducible in 50% in the lidocaine group (37% in control), while only in 16% in the propafenone group (62% in control). Despite lower drug concentrations in the infarct, the effects on AT are comparable to normal zones for both drugs. In conclusion lidocaine reduces and propafenone increases AT, affecting in opposite directions the inducibility of reentrant ventricular arrhythmias.

Animals↗

Contrasting effects of nifedipine and verapamil on myocardium and vascular smooth muscle at two levels of coronary occlusion in the dog.

The calcium flux inhibitors nifedipine and verapamil have recently been used in the setting of both classical Heberden's and variant angina. It has also been suggested that these agents may preserve function and viability of threatened myocardium. The effects of these agents on the relationship between myocardial blood flow and contraction in the setting of partial coronary occlusion is unknown. Thus 39 open-chest dogs underwent partial coronary occlusion to diastolic perfusion pressures of 25 or 40 mm Hg. The dogs then received intracoronary infusions of 10 micrograms nifedipine or 100 micrograms verapamil. Myocardial blood flow was measured with tracer microspheres and myocardial shortening was assessed with ultrasonic crystals. At 25 mm Hg nifedipine improved myocardial shortening while blood flow did not change. In contrast, verapamil caused shortening to be abolished but also did not change blood flow. At 40 mm Hg nifedipine, while not affecting shortening, caused a "redistribution" of blood flow from endocardium to epicardium; in contrast, verapamil again caused shortening to be abolished, but only increased epicardial blood flow leaving endocardial flow intact. Thus verapamil and nifedipine have differing effects. Nifedipine is a potent vasodilator at doses having no negative inotropic effects. In addition, nifedipine can cause a transmural "redistribution" of blood flow from endocardium to epicardium. In contrast, verapamil is also a potent vasodilator, but has profound negative inotropic effects.

Animals↗

Localization and mechanism of ventricular tachycardia by ice mapping 1 week after the onset of myocardial infarction in dogs.

We developed a new technique of "ice mapping" to localize the site of termination of ventricular tachycardia in dogs 4 to 8 days after the onset of myocardial infarction. During programmed stimulation-induced ventricular tachycardia, the epicardium was mapped by moving an ice probe with a 1 cm tip over the infarct, lateral border, and normal areas. In 31 of 46 morphologically distinct sustained ventricular tachycardias, a specific area could be found that reproducibly terminated ventricular tachycardia. During ventricular tachycardia, bridging or late diastolic electrical activity was recorded from ice termination sites. In vitro microelectrode studies of 10 ice termination sites revealed slow conduction, but no spontaneous or triggered automaticity or delayed afterdepolarizations. Conduction slowed to complete block when the Tyrode perfusate was cooled from 37 degrees to 27 degrees C. We conclude that ice mapping can physiologically localize a site responsible for maintenance of ventricular tachycardia by termination of the arrhythmia, and that the presence of bridging or late diastolic electrical activity, slow conduction with cooling-induced block, and absence of spontaneous or triggered automaticity or delayed afterdepolarizations suggest that local cooling terminates ventricular tachycardia by slowing or blocking conduction in a reentrant loop.

Action Potentials↗

Inpatient treatment of unstable angina: clinical perspective and sequential management.

In the last decade, increasing information has become available to the effect that an increase in coronary artery tone and coronary artery spasm play an important role in patients with various ischemic heart disease syndromes. Coronary spasm may be superimposed on a coronary vessel already severely obstructed by atherosclerosis. Conversely, spasm may occur in an artery that is only minimally involved with atherosclerosis. The majority of patients studied in the United States with both stable and unstable angina pectoris have underlying severe organic obstructive coronary artery disease. There has now emerged a considerable amount of information from several centers showing that the calcium-channel blockers or calcium-flux antagonists are highly effective in the treatment of stable and unstable angina pectoris. This report focuses on the uses and limitations of one of these agents, nifedipine, in patients with unstable angina and provides a sequential approach to their management.

Angina Pectoris↗

Comparative effects of nitroglycerin and nifedipine on myocardial blood flow and contraction during flow-limiting coronary stenosis in the dog.

Both nifedipine and nitroglycerin are used to treat angina pectoris. The comparative effects of these agents on myocardial blood flow and contraction in the setting of flow-limiting coronary stenosis are poorly understood. Thus 24 open chest dogs underwent carotid to left anterior descending coronary arterial perfusion with coronary flow probe and perfusion pressure monitoring. Segment length was measured with ultrasonic crystals in the subendocardial ischemic and nonischemic zones. Myocardial blood flow was measured with radioactive microspheres. Partial coronary occlusion was performed to attain a diastolic perfusion pressure of 40 mm Hg. Twelve dogs received intravenous nifedipine, 3 micrograms/kg per min, and 12 received intravenous nitroglycerin to reduce aortic pressure by 20 mm Hg. Partial occlusion resulted in a slight but significant decrease in segment shortening in the ischemic zone. Neither nitroglycerin nor nifedipine affected shortening in the ischemic zone. After occlusion, blood flow decreased in the subendocardial ischemic zone but was unchanged in the subepicardium. Nifedipine increased subendocardial blood flow in the nonischemic zone and decreased it in the ischemic zone but caused no change in subepicardial flow in the ischemic zone. In contrast, nitroglycerin decreased subendocardial and subepicardial blood flow in both the ischemic and nonischemic zones. In the setting of coronary stenosis, different classes of vasodilators may have varying effects on myocardial blood flow, suggesting different sites and mechanisms of action. In addition, segment function may not always reflect changes in myocardial blood flow.

Animals↗

Reversal of regional myocardial depressant effects of propranolol with nitroglycerin.

Use of propranolol in acute myocardial infarction is limited by its cardiodepressant effects. The effects of nitroglycerin (0.4 mg intravenously) on regional myocardial dysfunction produced by total or partial (50 percent) coronary occlusion and intravenous administration of propranolol (1.0 mg/kg) were evaluated using pairs of ultrasonic crystals implanted subendocardially in the nonischemic and ischemic zones in 14 open chest dogs. During partial coronary occlusion, systolic shortening (% delta L) in the ischemic zone decreased from 20.9 +/- 5.3 to 7.2 +/- 6.4 (p less than 0.001). Propranolol did not change it significantly. Nitroglycerin increased % delta L from 6.7 +/- 4.5 to 11.2 +/- 5.3 (p less than 0.01). The nonischemic zone was unaffected by partial coronary occlusion but showed a decrease in % delta L from 18.6 +/- 6.2 to 15.6 +/- 5.1 (p less than 0.01) with propranolol. Nitroglycerin increased % delta L from 15.6 +/- 5.1 to 17.3 +/- 5.9 (p less than 0.02). During total coronary occlusion, nitroglycerin administration after propranolol improved % delta L in the nonischemic but not in the ischemic zone. Nitroglycerin caused a significant decrease in left ventricular systolic and end-diastolic pressures. Heart rate remained unchanged. It is concluded that nitroglycerin reversed myocardial depressant effects of propranolol in both the partially ischemic and the nonischemic zones after acute coronary occlusion.

Animals↗