A retraction of two papers on cardiomyopathy.
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Ethics, Medical↗
Biomedical subjects
J R Darsee
Publications and source records attributed to J R Darsee.
Decreased myocardial taurine levels and hypertaurinuria in a kindred with mitral-valve prolapse and congestive cardiomyopathy.
In a 46-member kindred with consanguineous ancestry, eight progeny in two generations had congestive cardiomyopathy and markedly elevated urinary taurine levels (range, 411 to 536 mg per gram of creatinine [normal +/- S.D., 89 +/- 32]). Ten other family members had late or holosystolic mitral-valve prolapse, and elevated urinary taurine values (range, 215 to 265 mg). In two with mitral-valve prolapse, congestive cardiomyopathy eventually developed while the amounts of urinary taurine doubled. One member with mitral-valve prolapse died suddenly; histologic examination revealed myocardial fibrosis in the papillary muscles and myocardial taurine values of 16.9 +/- 3.0 mumol per gram of protein (normal +/- S.E., 33.2 +/- 3.6). Four other family members with congestive cardiomyopathy had myocardial fibrosis at autopsy or biopsy and mean myocardial taurine levels of 9.2 +/- 2.2 mumol. We conclude that hypertaurinuria and depressed levels of taurine in the myocardium may be associated with one type of mitral-valve-prolapse syndrome and a rapidly progressive form of congestive cardiomyopathy.
Adolescent↗
The hypertrophic heart syndromes: a glance at the chromosome.
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Cardiomegaly↗
Dependency of location of salvageable myocardium on type of intervention.
The purpose of this study were (1) to determine the location of the salvageable border zone in relation to the ischemic coronary bed, and (2) to determine whether the location of salvaged tissue differs depending on the mechanism of salvage and the type of intervention. Forty-four open chest dogs were subjected to either 6 hours of occlusion of the left anterior descending coronary artery or 4 hours of occlusion of this artery followed by 2 hours of reperfusion. Dogs with 6 hours of occlusion received either saline solution (Group I, n = 9), ibuprofen, 12.5 mg/kg body weight, (Group II, n = 7), flurbiprofen, 1 mg/kg (Group III, n = 10), or L-hydroxyphenylglycine, 10 mg/kg (Group IV, n = 8) intravenously 30 minutes and 3 hours after coronary occlusion. Dogs in Group V (n = 10) were subjected to 4 hours of coronary occlusion followed by 2 hours of reperfusion, but received no drugs. Although from 17 to 42 percent of the myocardium at risk did not become infarcted in Groups II through V compared with only 6 percent in Group I, the location of salvaged tissue was different in dogs receiving reperfusion (Group V) from that of dogs receiving drug interactions (Groups II, III and IV). In Group V, the salvaged tissue was primarily subepicardial with virtually no lateral zone of salvaged tissue (ratio of salvaged subepicardium to salvaged subendocardium 14.8 +/- 1.9 to 1). In Groups II, III and IV, there was a portion of the myocardium at risk at both lateral margins that did not become infarcted, as well as a portion of subepicardial tissue (ratio of subepicardium to subendocardium salvaged 3.3 +/- 0.4 in Group II, 2.5 +/- 0.1 in Group III and 2.0 +/- 0.2 in Group IV). Thus, infarct size reduction by ibuprofen, flurbiprofen and L-hydroxyphenylglycine is accompanied by lateral and subepicardial zones of salvage, whereas tissue salvaged by reperfusion is located primarily in the subepicardium. These observations should help to resolve the controversy regarding the existence and location of the various zones of ischemic myocardium that can be salvaged by drugs or reperfusion.
Animals↗
Recovery from prolonged abnormalities of canine myocardium salvaged from ischemic necrosis by coronary reperfusion.
The purpose of this study was to determine whether or not the biochemical, functional, and ultrastructural abnormalities produced by brief temporary coronary occlusions (unassociated with necrosis) ever resolve and, if so, when they do. Anesthetized open-chest dogs were subjected to 15 min of coronary artery occlusion followed by 72 hr, 7 days, or 14 days of reperfusion. Serial in vivo myocardial biopsies were performed for measurement of ATP and for ultrastructural analysis. Regional function was evaluated by sonomicrometry. Mean (+/- SEM) myocardial ATP concentration was 36.6 +/- 1.2 nmol/mg of cardiac protein in nonischemic subendocardium and 18.9 +/- 1.5 in ischemic subendocardium after 15 min of ischemia. ATP remainede performed for measurement of ATP and for ultrastructural analysis. Regional function was evaluated by sonomicrometry. Mean (+/- SEM) myocardial ATP concentration was 36.6 +/- 1.2 nmol/mg of cardiac protein in nonischemic subendocardium and 18.9 +/- 1.5 in ischemic subendocardium after 15 min of ischemia. ATP remainede performed for measurement of ATP and for ultrastructural analysis. Regional function was evaluated by sonomicrometry. Mean (+/- SEM) myocardial ATP concentration was 36.6 +/- 1.2 nmol/mg of cardiac protein in nonischemic subendocardium and 18.9 +/- 1.5 in ischemic subendocardium after 15 min of ischemia. ATP remained depressed in the reperfused previously ischemic subendocardium at both 90 min (68% of nonischemic value) and 72 hr (78% of nonischemic value) but returned to normal at 7 days. Regional systolic function and cardiac ultrastructural abnormalities required 7 days for full recovery. Histologic and histochemical analysis did not reveal necrosis at any time. Therefore, biochemical, functional, and ultrastructural abnormalities induced by brief periods of transient coronary occlusion not associated with necrosis do resolve completely but the recovery period is prolonged.
Adenosine Triphosphate↗
Hemodynamics of LeVeen shunt pulmonary edema.
In order to characterize the circulatory changes which may lead to pulmonary edema following the surgical placement of a LeVeen peritoneovenous shunt, intraoperative hemodynamic studies were performed on five consecutive patients without clinical evidence of cardiac disease undergoing shunt insertion. Within 30 minutes after opening the peritoneovenous shunt, there was a marked increase in pulmonary capillary wedge pressure, cardiac output, and stroke work index, and a sharp decline in both pulmonary and systemic vascular resistances. In three patients, pulmonary edema did not occur; in one patient, pulmonary edema occurred transiently but responded to furosemide administration. In these four patients, systemic vascular resistance continued to drop over the ensuing hours and the elevated pulmonary capillary wedge pressure also decreased appropriately with furosemide. The fifth patient developed persistent pulmonary edema. In this subject, systemic vascular resistance continued to rise and the elevated pulmonary capillary wedge pressure did not respond to intravenous furosemide. This study suggests that uncomplicated LeVeen peritoneovenous shunt insertion may result in a drop in systemic vascular resistance which lowers left ventricular afterload, and, thus, may protect most patients from pulmonary edema. In contrast, a continued rise in systemic vascular resistance and afterload may contribute to pulmonary edema refractory to diuretic therapy and should probably be treated with a parenteral afterload-reducing agent.
Ascites↗
Observations on the experimental reduction of infarct size and on the delayed consequences of transient myocardial ischemia.
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Animals↗
Time course of regional function after coronary occlusions of 1- to 120-min duration.
The purpose of this study was to characterize the degree and duration of functional impairment in previously ischemic tissue following coronary artery occlusions of varying duration. Open-chest dogs with left ventricular pressure transducers and ultrasonic segment length crystals were subjected to coronary artery occlusions of 1 (n = 22), 5 (n = 8), 10 (n = 7), 15 (n = 8), 20 (n = 7), 30 (n = 6), 60 (n = 10), or 120 (n = 8) min and segment length motion was measured during 6 h of reperfusion. Active shortening was replaced by passive lengthening during coronary occlusion and regional myocardial blood flow within the ischemic zone was always less than 0.4 ml . min-1 . g-1. Following reperfusion, the improvement of ischemic segment length function was inversely proportional to the duration of coronary occlusion. Function in previously ischemic segment lengths recovered rapidly after 1- and 5-min coronary occlusions, but after occlusions of 10-20 min, there was slow, though incomplete, return of some degree of active shortening yet no evidence of myocardial infarction. With occlusions exceeding 20 min there was persistence of systolic passive lengthening for 6 h despite the absence of infarction in the segment lengths in which function was being evaluated, although infarcted tissue was present ranging from 16.5 +/- 2.6% of the area of ischemia in dogs with 60-min coronary occlusions to 37.2 +/- 4.6% of the area of ischemia in dogs with 120-min occlusions.
Animals↗
Prolonged abnormalities of myocardium salvaged by reperfusion.
The purpose of this study was to determine if biochemical, functional, and ultrastructural abnormalities persist in nonnecrotic postischemic myocardium salvaged by coronary reperfusion. Anesthetized dogs were subjected to 15 min of occlusion of the left anterior descending (LAD) coronary artery followed by 3 days of reperfusion. Biopsies were obtained for measurement of adenosine 5'-triphosphate (ATP) and creatine phosphate (CP) nmol/mg protein), and regional function was evaluated using sonomicrometry. Myocardial ATP concentration after 15 min of occlusion was 37 +/- 1 nmol/mg cardiac protein in nonischemic subendocardium and 19 +/- 2 nmol/mg in ischemic subendocardium. After the hearts underwent 90 min and 72 h of reperfusion, ATP remained significantly depressed in reperfused subendocardium with values of 25 +/- 5 and 29 +/- 2 nmol/mg, respectively (P less than 0.05 and P less than 0.01 compared with the nonischemic zone in which ATP remained normal). CP levels fell during ischemia but returned to normal by 90 min of reperfusion. Percent systolic shortening of myocardial segments fell from +18 +/- 1% (active shortening) to -13 +/- 2% (passive lengthening) during ischemia and was still significantly depressed at +11 +/- 1% (P less than 0.05 vs. preocclusion) at 72 h of reperfusion. Histological examination showed no necrosis, but ultrastructural abnormalities were present. Therefore brief periods of myocardial ischemia are not associated with necrosis but result in functional, biochemical, and ultrastructural abnormalities, which are present for at lest 3 days after coronary reperfusion.
Adenosine Triphosphate↗
Demonstration of lateral and epicardial border zone salvage by flurbiprofen using an in vivo method for assessing myocardium at risk.
The purposes of this investigation were (1) to develop an in vivo method of determining the myocardium at risk after experimental coronary occlusion; (2) to define the spatial geometry of the salvageable ischemic border zone; an (3) to assess the ability of flurbiprofen, an antiinflammatory agent, to protect ischemic myocardium from necrosis. Twenty-two open-chest dogs underwent left anterior descending coronary artery occlusion and were randomized to treated (flurbiprofen 1 mg/kg i.v. at 30 minutes and 4 hours after occlusion; n = 11) or control (saline; n = 11) groups. Six hours after occlusion, methylene blue, 3 ml/lg, was injected into the left atrium, and immediately thereafter the hearts were removed and sliced transversely. Areas not perfused by methylene blue (area at risk [Ar]) were traced, planimetered, and compared to the area of necrosis (An) after incubation in triphenyltetrazolium chloride. The Ar for the two groups were similar (control 28.2 +/- 2.6%; treated 25.2 +/- 2.3% of total left ventricle; NS). In control dogs, An/Ar was 96.2 +/- 0.7%, with similar values for the epicardium and endocardium. In treated dogs, An/Ar was 66.9 +/- 8.9% (p < 0.001), with greater epicardial than endocardial salvage. Topographic superimposition of the An on the Ar showed that salvage occurred both on the epicardial and lateral aspects of the infarct. We conclude that (1) the in vivo methylene blue method of assessing myocardium at risk is useful in standardizing experimental infarct size; (2) flurbiprofen, administered 30 minutes and 4 hours after occlusion, is a potent agent for reducing infarct size; and (3) salvage of myocardium occurs both at the lateral and epicardial borders of the infarct in dogs treated with flurbiprofen.
Animals↗
Paradoxical rise in left ventricular filling pressure in the dog during positive end-expiratory pressure ventilation. A reversed Bernheim effect.
Controversy exists whether positive end-expiratory pressure (PEEP) ventilation lowers cardiac output by reducing left ventricular preload, or by a combination of mechanisms. Sixteen open-chest dogs were instrumented for measurement of left and right ventricular pressure, aortic flow, and left ventricular dimensions. With the pericardium intact, PEEP caused the interventricular septum to bulge toward the left ventricular chamber, increased right and left ventricular end-diastolic pressures, but decreased the average of the three left ventricular dimensions. When right ventricular filling pressure was suddenly reduced, the interventricular septum moved back toward the right ventricle, and left ventricular filling pressure fell. With the pericardium removed, PEEP was associated with a decrease in all three left ventricular end-diastolic dimensions but no significant change in left ventricular filling pressure. Although several indices of contractility were decreased during PEEP, all returned to baseline values when left ventricular preload was normalized during PEEP by a rapid infusion of heparinized blood into the left atrium. In conclusion, PEEP decreases preload and significantly alters the shape and compliance of the left ventricle with the pericardium intact. With the pericardium removed, PEEP produces proportional decreased in major and minor axis dimensions, does not appear to affect left ventricular contractility independent of preload, and alters left ventricular compliance to only a small degree.
Animals↗
Early recovery of regional performance in salvaged ischemic myocardium following coronary artery occlusion in the dog.
Although numerous agents have been shown experimentally to protect ischemic myocardium, a critical unanswered question is whether function is preserved in the salvaged tissue. Accordingly, 38 openchest dogs had measurements of percent segment length shortening (%SS) and velocity of segment length shortening either in midmyocardial or subepicardial and subendocardial ischemic segments before and after 60 min of left anterior descending coronary artery occlusion during 5 h of reperfusion; 10 additional dogs were subjected to 3 h of coronary occlusion followed by 72 h of reperfusion. 15 min after coronary artery occlusion, radiolabeled microspheres were injected into the left atrium for measurement of regional myocardial blood flow, and dogs were treated with 1 mg/kg i.v. (n = 23) of an anti-inflammatory drug, flurbiprofen or an equal volume of saline (n = 25). The ischemic myocardium-at-risk for necrosis was determined by injecting methylene blue dye into the left atrium with the coronary artery reoccluded at the end of the reperfusion period, slicing the left ventricle into thin transverse sections, and measuring the areas of each slice that were not perfused (pink unstained tissue) by methylene blue. The quantity of necrotic tissue in each transverse section was measured by planimetry after incubation of the slices in triphenyltetrazolium chloride, and by direct histological examination in dogs with 72 h of reperfusion. Regional myocardial blood flow of the ischemic segments between the ultrasonic dimension crystals was similar in treated (0.34+/-0.03 ml/min per g) and control dogs (0.35+/-0.03 ml/min per g). In saline-treated control dogs subjected to a l-h coronary occlusion, 17.9+/-1.8% of the myocardium-at-risk became necrotic but in flurbiprofen-treated dogs none of the tissue became necrotic. In saline-treated dogs passive lengthening of the previously ischemic segments persisted through 5 h of reperfusion in all three regions of myocardium after a 1-h coronary occlusion. In flurbiprofen-treated dogs regional function returned to normal within 5 min of reperfusion in both the subendocardium (%SS preocclusion = 17.2+/-2.0%; 5 min reperfusion = 17.8+/-3.1%; P = NS) and in the midmyocardium (%SS preocclusion = 17.8+/-2.2%; 5 min reperfusion = 17.9+/-2.3%; P = NS) and was not significantly different after 5 h of reperfusion from what it was before coronary occlusion. In the subepicardium of treated dogs regional function began to improve within 15 min of drug administration even during coronary occlusion. Regional function was not different from preocclusion values after either 5 min or 5 h of reperfusion (%SS preocclusion = 21.0+/-2.4%; 5 min reperfusion = 20.6+/-3.8%; P = NS). In dogs subjected to 3 h of coronary occlusion and 72 h of reperfusion, the administration of flurbiprofen was also associated with significantly smaller infarcts and a significantly more rapid rate of functional recovery than in control dogs.Thus, it appears that flurbiprofen not only decreased the quantity of necrosis in tissue made ischemic after coronary occlusion and then reperfused, but also allowed more rapid recovery of segmental function in ischemic but nonnecrotic tissue and in tissue with patchy necrosis; such recovery did not occur in equally ischemic myocardium in untreated control dogs. Earlier functional recovery of reversibly injured tissue following prolonged periods of ischemia is an additional important role for agents that protect ischemic myocardium from necrosis.
Animals↗
Early pathologic detection of acute myocardial infarction.
The use of tetrazolium stains for identifying myocardial infarction during the early stages of ischemic injury has become increasingly popular in both experimental and clinical studies. However, the accuracy of these stains in delineating infarctions prior to the onset of well-defined histologic necrosis is unknown. Therefore, eight open-chested, anesthesized dogs were subjected to high left anterior descending coronary artery occlusions for six hours. The hearts were then excised and "breadloafed' into 5mm-thick transverse slices that were incubated in triphenyltetrazolium chloride (TTC) for ten minutes. Three to five tissue samples were obtained from each of three areas of two transverse ventricular slices: from TTC-unstained areas (infarction) and TTC-stained areas, both close to the infarct and remote from the infarct, for electron microscopy. All eight dogs had well-defined areas of unstained tissue that appeared pale gray next to the brick-red TTC-stained tissue. Ultrastructure of the TTC-stained tissue both close to and remote from the infarct showed only modest loss of glycogen and relaxation of myofibers. Ultrastructure of the TTC-unstained tissue in all eight dogs showed numerous mitochondrial amorphous dense bodies, intracellular edema, nuclear chromatin clumping and margination, sarcolemmal disruption, and interstitial edema. Therefore, TTC is a reliable stain for localizing myocardial cells that ultrastructurally appear irreversibly injured by ischemia.
Animals↗
The no reflow phenomenon: a time-limiting factor for reperfusion after coronary occlusion?
A study was performed in 33 dogs to ascertain (1) whether the "no reflow" phenomenon is a critical factor determining the time beyond which revascularization can no longer salvage ischemic myocardium, and (2) whether reperfusion damages tissue not otherwise destined to become necrotic. Twelve dogs were subjected to 2 hours of coronary occlusion followed by 4 hours of reperfusion, 10 dogs to 4 hours of occlusion followed by 2 hours of reperfusion and 11 dogs to 6 hours of coronary occlusion alone. The area of "no reflow" was determined by injecting a fluorescent dye into the left atrium at the end of 6 hours with the coronary artery patent, and the ischemic area at risk by injecting methylene blue dye into the left atrium with the coronary artery reoccluded. The area of necrosis on all 5 mm transverse ventricular sections was determined by incubation in triphenyltetrazolium chloride stain and compared with its respective area at risk and area of no reflow. In all dogs the no reflow area was always significantly smaller than, and contained topographically within, the area of necrosis. Furthermore, the area of necrosis expressed as a percent of the area at risk was significantly smaller for dogs with 2 or 4 hours of occlusion and reperfusion than for dogs with longer periods of occlusion and briefer periods of reperfusion. It is concluded that (1) the no reflow phenomenon does not determine the critical time for salvageability of myocardium by revascularization because the area of no reflow is surrounded by necrotic but reperfusable tissue, and (2) reperfusion does not increase the quantity of ischemic tissue that becomes necrotic.
Animals↗
Transcutaneous method of measuring Doppler cardiac output--I. Comparison of transcutaneous and juxta-aortic Doppler velocity signals with catheter and cuff electromagnetic flowmeter measurements in closed and open chest dogs.
Cardiac output values obtained by thermodilution technique in 20 closed and open chest dogs were compared with values obtained by multiplying the integral of Doppler systolic velocity signals of aortic flow in 1 minute by the cross-sectional area of the aortic root. Doppler velocity signals were measured either from immediately outside the proximal aortic wall or from outside the chest wall during (1) the baseline state, (2) after 500 ml of hemorrhage, and (3) after reinfusion, (4) after administration of propranolol, and (5) during infusion of dopamine. In addition, Doppler "stroke volume" waveforms were compared with those obtained by electromagnetic flowmeter. Results showed a close similarity between Doppler signals and electromagnetic waveforms, and a close correlatin between Doppler and thermodilution values for cardiac output except at heart rates exceeding 160 beats/min. The studies showed the transcutaneous Doppler method of measuring cardiac output to be an accurate and reliable technique with application to clinical heart disease.
Animals↗
Transcutaneous Doppler method of measuring cardiac output--II. Noninvasive measurement by transcutaneous Doppler aortic blood velocity integration and M mode echocardiography.
In 15 patients with acute myocardial infarction (group I) and in 14 patients undergoing routine cardiac catheterization (group II) cardiac output values obtained by multiplying the 1 minute sum of the systolic integral of aortic blood flow velocity by the average systolic diameter of the aortic root were compared with values obtained with the thermodilution and Fick methods, respetively. Patients in group I were studied under various hemodynamic conditions, whereas those in group II were studied in the baseline state conditions, whereas those in group II were studied in the baseline state only. In group I, the correlation between the two methods was excellent (r values ranged from 0.96 to 0.99) except in one severely anemic patient whose Doppler signals were noisy, but at heart rates exceeding 150 beats/min it was not as good. In group II, the correlatin between the two methods was r = 0.96 with a standard error of the estimate of 0.226 liter. The Doppler method is totally noninvasive and is useful for monitoring changes in cardiac output in patients with acute myocardial infarction.
Adult↗
Mitral valve prolapse and ophthalmoplegia: a progressive, cardioneurologic syndrome.
Disorders characterized by both neurologic (ataxia, ophthalmoplegia, ptosis, neuromyopathy) and cardiologic (heart block, cardiomyopathy) abnormalities have been previously called the "ophthalmoplegia plus" syndromes. Most are not due to a specific enzyme defect or metabolic abnormality and thus may be similar phenotypic expressions of diverse causes. We studied seven patients with progressive external ophthalmoplegia and variable ataxia, with mitral valve prolapse and mitral regurgitation that progressed in severity as did the neuromuscular manifestations. Abnormal skeletal muscle biopsies showed "ragged-red" fibers or congenital fiber type disproportion; serum alanine levels were elevated; in-vivo and in-vitro tests of pyruvate metabolism gave abnormal results; C4 complement was decreased; and the patients' fibroblasts bound immunoglobulin when incubated with autologous serum. These data suggest a distinct neuromuscular disorder with metabolic and immunologic features associated with mitral valve prolapse and progressive mitral regurgitation.
Adult↗
Hypertrophic cardiomyopathy.
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Cardiomyopathies↗