Showing papers in "American Journal of Cardiology in 1973"

Quadricuspid semilunar valve.

Abstract: Clinical and necropsy findings are described in 10 patients with quadricuspid semilunar valves, and previous reports of 197 cases are reviewed. Quadricuspid semilunar valves occur infrequently, and usually the pulmonic valve is affected. The quadricuspid pulmonic valve typically functions normally. The quadricuspid aortic valve was functionally abnormal in 5 of 11 cases studied.

Clinical features of unrecognized myocardial infarction—Silent and symptomatic: Eighteen year follow-up: The framingham study

Abstract: The occurrence, prognosis and characteristics of persons with nonfatal unrecognized myocardial infarction were studied prospectively in a population of 5,127 men and women followed up biennially for 18 years. Of 259 electrocardiographically documented myocardial infarctions, 60 (23 percent) were discovered only by routine electrocardiogram at the time of biennial examination. Of these unrecognized infarctions, 32 (53 percent) were actually silent. In the other 47 percent of cases, the patients gave a history of interim symptoms judged to be compatible with acute infarction. In addition, of the 32 patients judged to have a silent infarction, 22 reported interim illnesses that could have been compatible with myocardial infarction. Only 10 of the 60 patients (17 percent) reported no interim illnesses or symptoms. Of the 28 patients with symptomatic infarction, 6 (21 percent) did not visit their physician despite severe symptoms; 20 gave a history of interim chest pain, 1 a history of epigastric pain and 7 a history of severe dyspnea. Patients who subsequently had unrecognized myocardial infarction typically visited physicians infrequently. Unrecognized myocardial infarction was distinctly rare in patients with prior angina pectoris. Patients with prior diabetes or high blood pressure appeared more likely to have unrecognized infarction. Unrecognized myocardial infarction appears to be as prevalent in the 1970's as it was in the 1950's. The reasons for this prevalence and possible solutions to the problem are discussed.

Quantitative electron microscopic description of heart muscle cells. Application to normal, hypertrophied and thyroxin-stimulated hearts.

Abstract: Mathematical techniques can be used to extract quantitative information from tissue electron micrographs of heart muscle With these methods it has been possible to measure the fractions of myocardial cell volume made up of myofibrils, mitochondria, sarcotubules, T system and sarcoplasm, as well as the membrane areas per unit of cell volume of plasma membrane, sarcotubular membrane and mitochondrial cristae The techniques have been used to quantitate the changes in the ultrastructure of myocardial cells in experimental left ventricular hypertrophy and in experimentally induced hypothyroidism before and after treatment with thyroxin These measurements have demonstrated striking and physiologically significant changes in the ultrastructural composition of the cells The pattern of ultrastructural change in ventricular hypertrophy differs in characteristic ways from the pattern during thyroxin-stimulated cardiac cellular growth These observations have suggested certain generalizations about the constraints to which growing myocardial cells are subject New and simple microchemical methods have been developed to determine the cardiac contents of myofibrils and mitochondrial cristae The methods are applicable to samples of heart muscle obtained at autopsy, surgery or biopsy, as well as to experimental material Application of these techniques to the study of experimental left ventricular hypertrophy and thyroxin-stimulated growth of myocardial cells has confirmed and extended the results of quantitative measurements on electron micrographs It is suggested that the approaches described can form the basis of a quantitative electron microscopic and microchemical pathology of heart muscle

Impaired left ventricular relaxation during pacing-induced ischemia.

Abstract: Rapid atrial pacing was performed in 15 patients at the time of cardiac catheterization. The results indicate that tachycardia may produce incomplete left ventricular relaxation in patients with disorders characterized by ischemia, but not in those with a normal left ventricle. This phenomenon was characterized by (1) a decrease in the peak negative value for first derivative of left ventricular pressure (dP/dt), which was used in the study as an index of left ventricular relaxation rate, (2) an increase in left ventricular diastolic pressure, and (3) a decrease in left ventricular internal diameter. These findings suggest that ventricular relaxation is an important determinant of left ventricular diastolic pressure-volume relations and that an impairment of ventricular relaxation may be partly responsible for the apparent decrease in left ventricular diastolic compliance observed during pacing-induced angina pectoris.

Cell proliferation during cardiac growth

Abstract: During the embryonic development of the myocardium both undifferentiated cells and cells containing muscle-specific proteins divide. As the heart grows and approaches maturity, its muscle cells progressively lose their mitotic activity; myocardial cell enlargement then becomes the principal process by which the heart as a whole enlarges. Mitotic figures in nuclei of heart muscle cells are frequent in the neonatal rat but become very rare at about the third month of postnatal life. Both in the developing and adult animal the work load is one of the determinants of cardiac size. The cytologic features of cardiac enlargement depend on the stage of development of the heart at the time when the stimulus to growth occurs. A work load imposed on embryonic or early neonatal hearts results in enlargement characterized by an increase in both the number and size of myocardial cells. The adult heart enlarges only by enlargement of its component muscle cells. Division of ventricular muscle cells in mammals is not activated after cardiac injury. The inability of ventricular myocardial cells to regenerate stands in sharp contrast to skeletal muscle, which is capable of considerable tissue repair, involving both regeneration of individual fibers and reconstitution of the whole muscle.

Antihypertensive action of propranolol: Specific antirenin responses in high and normal renin forms of essential, renal, renovascular and malignant hypertension*

Abstract: The antihypertensive effect of propranolol was evaluated in 96 patients with various forms of hypertension preclassified according to plasma renin activity considered in relation to urinary sodium excretion. In essential hypertension (no = 74) 74 percent of high-renin patients (14 of 19) exhibited striking blood pressure reductions and 66 percent of normal-renin patients (25 of 38) achieved diastolic pressures less than or equal to 95 mm Hg. In sharp contrast, propranolol was completely ineffective in 17 low-renin patients. In all 11 patients with unilateral renal artery or parenchymal disease propranolol also lowered blood pressure in proportion to control renin levels. The response was predictive of the antihypertensive benefit of surgery even in six “normal” renin patients. In eight patients with high-renin malignant hypertension, propranolol normalized renin, aldosterone and potassium levels and produced dramatic though often incomplete blood pressure correction. In one low-renin patient with the malignant syndrone propranolol was ineffective. Regardless of etiology, antihypertensive effectiveness of propranolol correlated with control renin levels and with the decrement in renin secretion. Thus, a simple biochemical measurement indexed against sodium excretion predicted antihypertensive drug responsiveness. These observations expose, for the first time, a role for renin in a major fraction of patients with essential hypertension. Renin-induced vasoconstriction appears to cause the hypertension in high renin and also in some normal renin patients in whom renin may be inappropriately high for sodium balance. The antihypertensive action of propranolol strikes at both vasoconstrictor and volume components of hypertension since inhibition of renin secretion naturally retards aldosterone secretion, thus preventing compensatory salt and water retention which often vitiates hypotensive therapy. Accordingly, propranolol added to either vasodilator or diuretic agents ought to improve hypotensive effect by curtailing reactive increases in renin and aldosterone: this should also reduce diuretic-induced potassium loss. Propranolol given alone may prove effective in a sizeable fraction of all hypertensive disorders and without inducing the dehydrated hyperreninemic state caused by diuretics. Therefore propranolol may prove to be an alternate first approach, except in lowrenin hypertensions where this type of therapy is ineffective and contraindicated.

Diabetes and hypertensive vascular disease

Abstract: Population studies indicate that hypertension occurs with greater frequency in diabetic than in nondiabetic subjects. The hypertension associated with diabetes may be of three types: (1) essential hypertension usually complicating diabetes of late onset, (2) systolic hypertension secondary to atherosclerosis, and (3) "diabetic hypertension" which is a form of renal hypertension accompanying the clinical syndrome of diabetic nephropathy most commonly observed in patients with diabetes of juvenile onset. Surgically curable forms of hypertension including renal vascular hypertension are probably no more frequent in patients with diabetes than in the general population. Evidence is presented suggesting that there is suppression of the renin-angiotensin system accompanied by hypertension in uncontrolled diabetes in the rat treated with alloxan. Additionally, suppression of this system has been observed in patients with long-term diabetes and evidence of diabetic renal disease and hypertension, a finding that may explain the rarity of malignant hypertension in long-term diabetes. Possible mechanisms involved in both the suppression of the renin-angiotensin system and in the "diabetic hypertension" are discussed. Since "diabetic hypertension" may be a form of hyporeninemic hypertension, elucidation of the mechanism involved may yield valuable information concerning the large group of patients with essential hypertension with suppression of the renin-angiotensin system. The agents used for antihypertensive therapy in the diabetic patient are similar to those used in other hypertensive patients, but certain considerations must be given to their use, especially in the diabetic patient with complications.

Myocardial function during atrial pacing in patients with angina pectoris and normal coronary arteriograms. Comparison with patients having significant coronary artery disease.

Abstract: Right atrial pacing at 140 beats/min for 8 minutes induced an electrocardiographic “ischemic pattern” in 10 patients with normal coronary arteriograms and chest pain usually typical of angina pectoris (group X). The findings were compared with those in 11 patients with demonstrable coronary arterial stenosis who had the same electrocardiographic “ischemic pattern” during pacing (group C). Six patients of group X and eight patients of group C experienced angina during pacing. In addition, a low level of myocardial extraction (less than 10 percent) or production of lactate was observed during pacing in five patients of group X and in seven of group C. Patients of group X showed a significant rise in cardiac index ( P P P P P

Tachycardia-bradycardia syndrome (so-called “sick sinus syndrome”): Pathology, mechanisms and treatment

Abstract: The tachycardia-bradycardia syndrome consists of paroxysmal atrial fibrillation, flutter or tachycardia followed by sinoatrial block or sinus arrest resulting in Stokes-Adams attacks. Detailed histologie findings of the conduction system of 2 patients with this entity correlated well with the clinical observation of cardiac rhythm disturbances in the sinus node, atria and atrioventricular (A-V) junction. Eight other patients with the syndrome were studied clinically. The mechanisms (as revealed by the electrocardiogram) producing the bradycardia phase include depression of pacemaker function (arrest) or of conduction (exit block) of the sinus impulse, or both, plus depression of A-V junctional impulse formation. Proper therapy usually requires electrical pacing in conjunction with administration of digitalis or propranolol, or both. Our findings suggest that the term “sick sinus syndrome” is an inaccurate and inappropriate synonym for the tachycardia-bradycardia syndrome.

Volume factor in low and normal renin essential hypertension

Abstract: The blood pressure response to spironolactone or chlorthalidone was studied in 71 patients with essential hypertension exhibiting either low or normal plasma renin activity. The patients with low renin activity were more responsive to both of these diuretic agents, but neither drug was uniquely or uniformly effective in this group. Blood pressure became normal in only 57 percent of patients with reduced renin activity receiving spironolactone therapy, whereas 24 percent maintained a diastolic pressure greater than 105 mm Hg; 44 percent of them responded to chlorthalidone, but 31 percent did not. In patients with normal renin values the blood pressure was normalized in 36 percent by spironolactone and in 37.5 percent by chlorthalidone. Responses to spironolactone were usually manifested with a dose of 100 mg/day; an increased dose rarely had an additional antihypertensive effect. The similar effectiveness of both drugs in 27 patients treated sequentially with each agent suggests that volume depletion is a common mechanism of action. The sustained induced elevations of plasma renin activity and aldosterone excretion, and the chronic elevations of blood urea nitrogen induced by both agents, indicate that a persistent shift or loss of body sodium or water occurs during therapy. Thus, the antihypertensive action of either diuretic agent appears to result from a reduction of a possibly excessive sodium or volume content relative to capacity of the vascular bed. Patients failing to respond may have had inadequate volume depletion or a hypertensive state that was maintained by a relatively greater vasoconstrictor (renin) response for the degree of volume depletion induced by the drug. Altogether the data suggest that diuretic therapy with either spironolactone or a sulfonamide is primarily indicated in low renin essential hypertension. In patients with normal renin activity diuretic therapy could be reserved for those in whom beta adrenergic blockade proves inadequate. Such sequential single-drug antihypertensive therapy offers the potential for further characterization and understanding of hypertensive disorders while affording a simpler and more specific long-term drug regimen for some patients.

Biochemical and morphologic correlates of cardiac ischemia

Abstract: Functions of membrane-linked myocardial systems and morphology of the myocardial cell were examined in normal and acutely and chronically ischemic myocardium. Hemodynamic measurements of ischemic tissue showed depressed force development as well as decreased (and variable) ventricular peak pressures. Mitochondrial respiratory function was reduced, with state 3 (phosphorylating) respiration showing the most marked impairment. Losses in cytochromes c and a 3 were observed. Diminished mitochondrial calcium uptake with subsequent release of the calcium taken up during continued respiratory activity was characteristic of severely ischemic tissue, that is, 7 days after ligation. Defects in the carnitine-mediated oxidation of palmitic acid in isolated mitochondria were severe between 1 and 8 days after ligation. Losses in tissue carnitine also occurred simultaneously with decreased mitochondrial carnitine palmityltransferase activity. During this period the oxidation of hexanoic acid was unaffected. The binding and release cycle of calcium was studied in sarcoplasmic reticulum (cardiac relaxing system) isolated from control tissues and from acutely and chronically ischemic heart. An early impairment in the release phase of calcium from an acutely ischemic preparation occurred at times (12 to 60 minutes after ligation) when the other membrane-associated functions maintained normal integrity. In the chronically ischemic dog, there was marked impairment of calcium-binding variables in the first 2 weeks after ligation. This impairment occurred at times when both mitochondrial and sodium, potassium adenosine triphosphatase (Na + ,K + -ATPase) activity levels were severely impaired. The Na + ,K + -ATPase activity level was consistently lower than the control level by 7 days after ligation. However, there was no change in kinetic indexes or in the ouabainbinding characteristics in the functional enzyme remaining. Morphologic studies of tissue taken from left posterior papillary muscle 3 to 8 days after ligation revealed significant and specific changes in ultrastructure (disrupted Z and I bands, appearance of pseudo-N band and appearance of dense bodies in mitochondria); the greatest occurrence of damaged cells occurred 7 to 8 days after ligation.

Atrioventricular and intraventricular conduction. Revised nomenclature and concepts.

Abstract: Under the organizing chairmanship of the late Hans Hecht, a symposium on Atrioventricular and Intraventricular Conduction was held in Chicago on May 28–29, 1970 under the auspices of the American College of Chest Physicians and the Center for Continuing Education, University of Chicago. After an extended discussion on nomenclature in this area by more than 150 participants, the present authors convened themselves as a self-appointed committee to create a framework for a revised nomenclature.

Unstable angina pectoris: morbidity and mortality in 57 consecutive patients evaluated angiographically.

Abstract: Fifty-seven consecutive patients presenting with unstable angina pectoris or so-called pre-infarction angina were prospectively evaluated by clinical and angiographic studies. One patient died during angiography and another died of acute myocardial infarction 11/2 hours after cardiac catheterization. Forty-five patients had significant obstruction in two or three coronary arteries. The average left ventricular ejection fraction was 59 percent. Of 15 patients treated medically, 10 were potential candidates for surgery. One of these 10 died during hospitalization and 9 survived. The nine survivors were followed up for an average of 10 months; six reported symptomatic improvement, and one had an uncomplicated myocardial infarction 6 months after study. Aortocoronary saphenous vein bypass was performed in 40 patients, of whom 9 died during hospitalization and 31 survived operation. Of the 31 survivors, 1 had an uncomplicated myocardial infarction 9 months postoperatively; there were no late deaths in this group during a follow-up period averaging 16.7 months. Thirty of the 31 survivors reported marked symptomatic improvement, and 21 of these survivors were pain-free.

Relation of age, diastolic pressure and known duration of hypertension to presence of low renin essential hypertension

Abstract: Plasma renin activity and aldosterone secretion rates were measured in 100 patients with essential hypertension in response to a low sodium diet and upright posture. Plasma renin activity showed a subnormal response in 22 percent of patients, and a greater than normal response in 4 percent. In contrast to findings in 50 normal subjects, there was a significant positive correlation between the incidence of subnormal renin response and patient age and level of diastolic blood pressure. There was no correlation between renin response and known duration of hypertension. Comparison of several clinical and biochemical variables among the renin study subgroups revealed no differences except that the group with a low level of renin activity excreted a greater amount of sodium. These data support the hypothesis that a low renin activity level may evolve with time in patients with essential hypertension.

Electrocardiographic, arteriographie and ventriculographic correlations in transmural myocardial infarction

Abstract: To determine if significant interrelations exist between the electrocardiographic diagnosis of transmural myocardial infarction, sites of coronary arterial obstruction, and left ventricular asynergy, 235 patients with angiographically documented coronary artery disease were subdivided according to the electrocardiographic location of the myocardial infarction, the coronary arterial system involved and the site of ventricular asynergy. Of 82 instances of anterior myocardial infarction, the left anterior descending artery demonstrated significant disease in 79 (96 percent). Of 100 instances of inferior myocardial infarction, the right coronary artery was significantly diseased in 87 and the left circumflex in 55. When multiple infarctions were present, multivessel disease was found in 93 percent of patients. Left ventricular asynergy was present in 81 percent, including 84 percent of those with anterior infarction, 74 percent of those with inferior infarction, and 93 percent of those with multiple infarctions. The results of our study suggest that the electrocardiogram is often of value in indicating sites of coronary arterial obstruction and ventricular asynergy in patients with coronary artery disease and transmural myocardial infarction.

Renovascular hypertension: Mechanisms, natural history and treatment

Abstract: Hypertension with atheromatous or fibromuscular renal artery stenosis was studied prospectively in 214 cases for 7 to 14 years. After 3 months or less of medical management proved unsuccessful, 100 patients, were submitted to surgical management. At latest follow-up examination, 84 of these survived and 51 were normotensive without medication. The survivors included 26 of 37 with artheromatous stenosis and 58 of 63 with fibromuscular stenosis. Medical management was continued in the other 114 patients (except for 16 transferred after 6 months to 5 years to surgical care but are not reported on here). Of these 114 patients, 44 had atheromatous disease, of whom 10 were surviving with medication at latest follow-up examination (7 others having been transferred to surgical management); and 70 had fibromuscular stenosis, of whom 49 survived with continuing medication (9 others having been transferred to surgery). At the latest follow-up study (December 1972), 55 of the 214 patients had died. Myocardial infarction, stroke and renal failure were the most common causes of death. Renal artery stenosis may be demonstrated by current angiographic techniques. Functional significance of proved lesions can be determined by renal vein renin activity, differential renal function study or demonstration of a systolic-diastolic or continuous abdominal bruit; and it can be suggested by intravenous urography and isotope renography. In carefully selected patients, definite amelioration or long-term relief of existing hypertension may be accomplished by appropriate surgical management; in the severe cases thus managed, the mortality rate appears to be decidedly reduced.

Exercise-induced ventricular arrhythmias in patients with coronary artery disease: Their relation to angiographic findings

Abstract: Ventricular extrasystoles occurring before, during or after graded exercise testing were related to extent of coronary artery disease and to ventricular motion disorders in 81 symptomatic patients undergoing selective coronary and left ventricular angiography; the results were compared with data in 89 similar age-matched patients without arrhythmias. Compared with arrhythmia-free patients, 67 patients with exercise-induced arrhythmias had a significantly greater incidence of prior myocardial infarction, double or triple vessel disease and overall abnormal ventricular contractile patterns. Exercise induced extrasystoles occurred in only 11 percent of patients with insignificant coronary disease. Abolition of resting extrasystoles by exercise was not associated with less extensive coronary disease. Our study suggests that exercise-precipitated arrhythmias may represent a form of subclinical ischemia, signify more advanced degrees of coronary and left ventricular disease, and serve as an aid in detecting potentially high-risk patients.

Experimental production of hypoplastic left heart syndrome in the chick embryo.

Abstract: The hypothesis is examined that hemodynamic alterations at the site of the primordial mitral valve may induce malformations that simulate the clinical findings of hypoplastic left heart syndrome. Surgical placement of a nylon device, approximately 90 μ in diameter, into the region of the left atrioventricular (A-V) canal was accomplished in 192 embryos (Hamburger-Hamilton stages 23 to 25). Thirty-nine pairs of experimental and control embryos survived more than 12 days. Twenty-six experimental embryos exhibited various malformations: hypoplastic left atrium and ventricle, mitral valvular atresia, aortic valvular stenosis and tubular hypoplasia of the aorta and brachlocephalic vessels. These findings reemphasize the probable morphogenetic role of blood flow pathways. The findings further implicate involvement of the left A-V canal as well as premature closing of foramen ovale and aortic valvular abnormalities in the hypoplastic left heart syndrome.

Coronary sinus lactate measurements in assessment of myocardial ischemia: Comparison with changes in lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios and with release of hydrogen, phosphate and potassium ions from the heart

Abstract: The value of measurements of lactate in coronary venous blood as a sign of myocardial anaerobiosis is reassessed. Lactate was measured after coronary arterial ligation in dogs in (1) local venous blood draining from ischemic tissue, (2) coronary sinus blood, and (3) myocardial tissue. There was an estimated lactate concentration gradient of 2- to 4-fold from ischemic tissue (epicardial biopsy specimens) to local venous blood, whereas the gradient from epicardial tissue to coronary sinus blood was 8- to 16-fold. Differences in pyruvate concentrations between ischemic tissue and local venous or coronary sinus blood were not marked. Increases in tissue lactate concentration and in lactate/pyruvate values in anaerobic tissue occurred simultaneously. Whether such tissue changes are reflected in coronary venous blood depends on the degree to which the heart cell membrane impairs egress of lactate or pyruvate, and on the venous sampling site. With coronary sinus sampling, the production of small ischemic lesions (less than 10 percent of the volume of the whole heart) caused a readily detected decrease of lactate extraction by the heart, whereas the changes in the lactate/pyruvate ratio across the heart were less marked. When lesions were larger or when highly selective coronary venous sampling techniques were used, lactate/pyruvate changes were readily detectable; changes in the ratio beta-hydroxybutyrate/acetoacetate were not very helpful in detecting ischemia. Although lactate changes in coronary venous blood are a very sensitive index of regional myocardial ischemia after coronary arterial ligation, a knowledge of changes in lactate/pyruvate ratios, potassium ion, inorganic phosphate and hydrogen ion allows a more complete description of intracellular events. These additional measurements should also help to exclude unusual circumstances in which lactate discharge from the heart occurs in the presence of apparently normal oxygenation.

Hemodynamic study of 85 patients with borderline hypertension.

Abstract: Hemodynamic changes in supine and upright position (50 ° head-up tilt) and during exercise were studied in 40 normal subjects and 85 patients with borderline hypertension. The latter were classified in 2 groups, according to the level of cardiac index. In group I, with patients in the supine position, cardiac index, stroke index, heart rate and plasma volume were normal, but total peripheral resistance was increased (P < 0.01). During upright tilt, orthostatic decrease of mean arterial pressure (P < 0.05) was observed, and the increase in total peripheral resistance was not greater than in normal subjects. The hemodynamic response to exercise was similar to that of normal subjects. In patients in group II, cardiac index, stroke index and heart rate were increased (P < 0.001), but plasma volume was decreased (P < 0.01) and total peripheral resistance was below normal (P < 0.001). With patients in the upright position, diastolic orthostatic hypertension was observed (P < 0.001) and total peripheral resistance was greater than normal (P < 0.01) despite an abnormal fall of cardiac index (P < 0.05). The hemodynamic response to exercise indicated that total peripheral resistance did not decrease as in normal subjects and in patients of group I (P < 0.001). This study provides evidence that (1) total peripheral resistance is abnormal in patients with borderline hypertension, but only during upright tilt and exercise in patients with high cardiac index, and (2) 2 main disorders seem to be important in the early stage of hypertension: abnormality of blood volume (or blood volume distribution, or both) and impaired neurogenic activity.

Quantitative evaluation of cineaortography in the assessment of aortic regurgitation

Abstract: Cineaortography, quantitative biplane left ventricular angiocardiography and Fick cardiac output studies were performed in 69 patients with aortic regurgitation to evaluate the usefulness of the aortogram in quantitating regurgitation. Thirteen patients had coexistent aortic stenosis and 12 had coexistent mitral stenosis. Patients with concomitant mitral regurgitation were excluded because their aortic regurgitant flow cannot be separately quantified with biplane ventriculography. Twenty-eight other patients without valvular regurgitation were also studied to assess further the accuracy of the quantitative ventriculography, and the stroke volumes derived from Fick and angiographic methods were found to correlate well (r = 0.97). Aortic regurgitation in the 69 patients, graded on a 1 to 5 scale from the aortogram, correlated significantly with the percent and volume of regurgitation (r = 0.56 and 0.65, P < 0.01), respectively). However, there was a wide range in amount of regurgitant flow within the aortographic grades, especially in grades 4 and 5, and there was considerable overlap between the grades. The degree of aortic regurgitation was more commonly overestimated than underestimated from the aortogram, but the correlation tended to be better in the patients with a large end-diastolic volume and normal ejection fraction and without aortic or mitral stenosis.

In vitro length-tension relations of human ventricular aneurysms: Relation of stiffness to mechanical disadvantage

Abstract: This study was designed to quantitate the length-tension relations of surgically resected human ventricular aneurysms in order to calculate the degree of paradoxical systolic expansion and mechanical disadvantage produced by various types of aneurysms. The in vitro length-tension relations of the 11 aneurysms studied closely conformed to an exponential equation. In vivo wall stress in each aneurysm was calculated from ventricular pressure and the ventriculogram utilizing the Laplace relation. In the four fibrous aneurysms the calculated increase in circumference averaged 2.4 percent in systole; in five aneurysms with fibrous and muscular tissue, average circumference increased 6.3 percent; in two muscular aneurysms (from patients with acute myocardial infarction and shock), average circumference increased by 14.6 percent. Thus, chronic fibrous aneurysms appear to produce their primary mechanical disadvantage by a loss of contractile tissue since systolic paradox is minimal. An acute muscular aneurysm produces mechanical disadvantage not only by loss of contractile tissue but also by significant paradoxical systolic expansion.

Effects of ischemia on the contractile processes of heart muscle.

Abstract: Myocardial contractility declines precipitously after coronary arterial occlusion The efficient cause of this phenomenon is probably the hypoxia-induced decrease in aerobic adenosine triphosphate (ATP) production by the ischemic myocardium The formal and material causes of this negative inotropic effect are less clearly understood A decrease in influx of calcium ion, due to sodium pump inhibition in the ischemic heart, is difficult to reconcile with evidence that Ca ++ influx is enhanced under other conditions (for example, administration of cardiac glycosides) that also impair this ion pump Shortening of the plateau of the action potential after coronary arterial occlusion may be associated with decreased systolic Ca ++ influx from the extracellular fluid, but additional evidence is needed to corroborate this view A state of acidosis, resulting from the lactate production that occurs when the ischemic myocardium shifts to anaerobic pathways of energy production, may impair contractility by increasing the tightness of Ca ++ binding to the sarcoplasmic reticulum of the heart The increased intracellular hydrogen ion concentration could also exert a negative inotropic effect by displacing Ca ++ from its binding site on troponin, which is the Ca ++ -sensitizing protein of the contractile apparatus The final cause of the early depression in mechanical energy production by the ischemic myocardium may be the conservation of chemical energy for the more important task of delaying irreversible rigor and necrosis, thereby preserving myocardial integrity

Effectiveness of dopamine in patients with cardiogenic shock.

Abstract: Dopamine was evaluated in 24 patients with cardiogenic shock of various causes (systolic blood pressure less than 90 mm Hg or 60 mm Hg below the patient's usual level as recorded by intraarterial needle, average urinary flow less than 20 ml/hour without diuretic therapy). Dopamine was not given until hypovolemia was corrected, as judged by left ventricular filling pressure (18 patients) or central venous pressure. Twelve patients survived the shock episode, 5 of whom are alive 7 to 24 months later. The 12 survivors of shock included all 6 patients (100 percent) with shock after open heart surgery; 3 of 10 (30 percent) with acute myocardial infarction; 1 of 4 (25 percent) with severe heart failure; and 2 of 4 (50 percent) with shock after noncardiac surgery. Seven patients, including 6 of the 12 survivors, received no pressor agent other than dopamine. In 12 nonsurvivors hourly urinary flow increased from 10 ± 2.3 (standard error of the mean) to a maximum of 101 ± 55 ml/hour (not significant), but 8 of these patients had virtually no change in urinary flow during dopamine therapy. In the 12 survivors, there was a larger increment in urinary flow [from 25.7 ± 11 to 250 ± 59 ml/hour ( P P μ g/kg per min. In 3 of 4 patients receiving intraaortic balloon counter-pulsation, 2 of whom survived, dopamine augmented urinary flow from an average of 20 to 208 ml/hour. We conclude that dopamine is useful, either alone or in conjunction with other pressor agents, for the treatment of cardiogenic shock, particularly in patients with diminished urinary flow and hypotension after cardiopulmonary bypass.

Platelet abnormalities in ischemic heart disease

Abstract: Forty-seven patients with well documented ischemic heart disease were studied with tests designed to detect “hypercoagulability”: platelet count, platelet aggregation response to dilutions of adenosine diphosphate (ADP) and collagen, determination of fibrinolytic activity and thromboelastography. No abnormalities were found in the thromboelastograms, fibrinolytic activity, platelet count or response of platelets to ADP. Most patients demonstrated abnormal platelet reactivity to collagen soon after myocardial infarction. Five patients (but none of the normal subjects or patients with nonischemic heart disease) had a persistent marked abnormality, with platelet hyperresponsiveness to collagen still present 10 to 16 months after infarction. These five patients differed from others with myocardial infarction by being younger, having a paucity of the recognized risk factors and having either normal coronary arteriograms or single obstructive arterial lesions. Each had significantly decreased 51chromium platelet survival time many months after infarction, during an asymptomatic period. One of eight patients with chest pain of the anginal type and normal coronary arteriograms showed similar platelet hyperaggregability. We suggest that some patients with ischemic heart disease, perhaps as many as 10 percent, have chronic abnormal platelet function, best detected by the platelet aggregation response to dilutions of collagen and by platelet survival studies. This may be a primary abnormality in patients with ischemic heart disease whose arteriograms show no advanced coronary atherosclerotic obstructive lesions.

Hypomagnesemia and refractory cardiac arrhythmia in a nondigitalized patient.

Abstract: A case of hypomagnesemia and refractory cardiac arrhythmia is presented. The patient had no evidence of clinical heart disease and was not receiving digitalis therapy. The cardiac arrhythmia was refractory to all usual forms of therapy but was instantly abolished with intravenous magnesium therapy. The unusual nature of this relation and a possible hypothesis to explain its occurrence are discussed.

Evaluation of performance of selected devices for measuring blood pressure

Abstract: Standardization of blood pressure measurements is critical for the implementation of screening programs, and especially so for a multicenter, collaborative investigation of community blood pressure control. This need arises from numerous well known sources of variability in blood pressure measurements, some of which are attributable to performance characteristics of instruments and observers. A number of instruments have been developed in recent years with the aim of overcoming certain aspects of this measurement variation. Consequently, the Coordinating Center of the National Heart and Lung Institute Hypertension Detection and Follow-up Program (HDFP) undertook to evaluate several of these devices in order to permit selection for this Program of optimal methods of blood pressure measurement. The mercury sphygmomanometer, which is the basis of most available epidemiologic data on blood pressure, was taken as the standard. In the first experiment, based upon a Graeco-Latin square design, none of the five automated devices tested compared favorably with the standard mercury sphygmomanometer, as judged by the mean values of multiple readings for each of the two specimens of each device. In a series of paired readings, all but one of the automated devices showed marked deviation from readings by the standard mercury sphygmomanometer. Qualitative observations on machine performance were also recorded and indicated serious operating difficulties with several devices—including, unfortunately, the device that had performed well in the second experiment. For the purposes of the Program, none of the automated devices tested performed adequately to recommend their substitution for the standard mercury sphygmomanometer. A modified type of mercury sphygmomanometer, designed to reduce observer bias, was included in this evaluation, did compare well, and will be used by the Program in conjunction with the standard device.

Correlation of pathophysiology and pharmacotherapy in primary hypertension

Abstract: Patients with primary hypertension vary in the extent to which abnormalities of peripheral vascular resistance, cardiac output, intravascular volume, and the functional state of the renin-angiotensin-aldosterone and sympathetic nervous system contribute to their hyperpiesis. Antihypertensive drugs can specifically counteract most of these pressor mechanisms. Through choice of appropriate drugs one can selectively correct existing disturbances and increase the effectiveness and acceptance of antihypertensive therapy. Increased vascular resistance of patients with mild hypertension can be reversed by diuretic agents. In all others more effective vasodilators are required. These should be coadministered with a diuretic and propranolol to prevent expansion of intravascular and extracellular volumes and reflex increases in cardiac output and plasma renin activity. This combination of drugs can control all degrees of hypertension. Because it reduces cardiac output and depresses plasma renin activity, propranolol is indicated for hypertensive patients with elevated cardiac output or hyperreninemia. Sympathoplegic drugs are most specific for patients whose hypertension is maintained by excessive sympathetic stimulation of the circulation. Low renin essential hypertension responds well to the natriuretic effects of spironolactone and other diuretic agents. Since the arterial compliance of hypertensive subjects decreases with increasing pressure, they have more systolic than diastolic hyperpiesis. Systolic hypertension at least equals diastolic as a risk factor for cardiovascular complications. Drug therapy of hypertension decreases systolic pressure more than diastolic, but the former often remains elevated when diastolic normotension has been achieved. In patients with decreased arterial compliance, normalization of systolic pressure requires induction of diastolic hypotension, and the safety and effectiveness of such therapy remain unknown.

Electrophysiologic studies in the syndrome of short P-R interval, normal QRS complex.

Abstract: Eighteen subjects with a short P-R interval (<0.12 second) and normal QRS complex were studied by means of His bundle recordings and programmed atrial premature depolarizations. Eight subjects had a history of supraventricular tachycardia. During sinus rhythm, the A-H interval was less than or at the lower limits of normal values (45 to 80 msec), and the H-V interval was normal (30 to 50 msec). Atrial pacing at rates of up to 160/min produced 3 types of responses. Thirteen subjects showed a progressive increase in A-H interval similar to that of normal subjects but to a lesser degree. Three subjects showed an initial increase at low pacing rates, followed by a plateau response and further increase at higher rates. Two subjects showed no significant increase in the A-H interval. In 6 of 8 subjects with supraventricular tachycardia, atrial premature depolarizations produced atrial echo beats and sustained supraventricular tachycardia in 4, indicating atrioventricular (A-V) nodal reentry as the mechanism for the supraventricular tachycardia. In 10 subjects, refractory periods of the various components of the A-V conducting system were found to be similar to those of subjects with a normal P-R interval. The data suggest the following possible explanations for the short P-R interval: (1) total or partial bypass of the A-V node; (2) an anatomically small A-V node; (3) a short or rapidly conducting intranodal pathway; or (4) isorhythmic A-V dissociation.