Reduced cardiac myofibrillar Mg-ATPase activity without changes in myosin isozymes in patients with end-stage heart failure.

In this study we tested the hypothesis that reduced myofibrillar ATPase activities in end-stage heart failure are associated with a redistribution of myosin isozymes. Cardiac myofibrils were isolated from left ventricular free wall from normal human hearts and hearts at end-stage heart failure caused by coronary artery diseases, cardiomyopathy or immunological rejection. The hearts had been excised in preparation for a heart transplant. Myofibrillar Ca2(+)-dependent Mg-ATPase and myosin Ca2(+)- and K+EDTA-ATPase activities were compared. Possible changes in myosin isozyme distribution in the diseased heart were investigated using polyacrylamide gel electrophoresis of native myosin in the presence of pyrophosphate. Significant reduction in myofibrillar Ca2(+)-dependent Mg-ATPase with no changes in the sensitivity of the myofibrils to Ca2+ was observed in heart with coronary artery diseases (25.2 to 27.1% at pCa 5.83 to pCa 5.05), cardiomyopathy (21.1 to 25.5% at pCa 5.41 to pCa 5.05), and in the immunologically rejected heart (18.4 to 22.8% at pCa 5.41 to pCa 5.05). Significantly lower myosin Ca2(+)-ATPase was observed with coronary artery diseases only and myosin K-EDTA activities did not differ in diseased and normal hearts. Polyacrylamide gel electrophoresis of native myosin from the normal and three models of end-stage heart failure revealed two distinct bands in the human left ventricle and one diffuse band in the human right atria. No apparent differences in myosin isoenzyme pattern were observed between the normal and diseased hearts. Further evaluation is needed to clarify the ATPase nature of the two bands.

Threshold, enzymatic, and pathologic changes associated with prolonged transcutaneous pacing in a chronic heart block model.

Previous studies have shown that 30 minutes of transcutaneous cardiac pacing (TCP) can induce mild, clinically insignificant myocardial damage. Longer use of TCP may cause more severe cardiac damage which might result in an increase in the capture threshold for subsequent transvenous cardiac pacing (TVP). To assess this possibility, we examined changes induced by TCP in a canine chronic heart block model. Heart block was induced in conditioned dogs (n = 8) by His bundle ablation. Seven to 10 days after induction of heart block, six animals were paced. Cardiac enzymes were drawn before pacing and at 4, 24, 48, and 72 hours after pacing. Although there was a significant rise in CK at 4 and 24 hours (P less than 0.05), there was no detectable rise in the MB fraction in any of the paced animals. There was no elevation of LDH after pacing, although three animals did develop an LDH1/LDH2 isoenzyme flip indicative of myocardial damage. Animals were sacrificed 72 hours after pacing and their hearts were examined for gross and microscopic changes. The hearts of the paced animals revealed subendocardial, subepicardial, and perivascular areas of basophilic degeneration involving less than 1% of the myocardium in four of six animals. No evidence of such damage was seen in two heart-blocked control animals not undergoing pacing. TVP and TCP capture thresholds assessed before and after a 60-minute TCP pacing period showed no significant change. Hence, use of TCP for a 60-minute period prior to TVP appears to be a safe emergency pacing technique.

Efficacy and safety of constant-rate intravenous cyclosporine infusion immediately after heart transplantation.

Oral cyclosporine therapy immediately after heart transplantation is erratic and difficult to predict. The purpose of this study was to evaluate the relative efficacy and safety of cyclosporine when administered by constant-rate infusion immediately after transplantation. Nineteen patients (17 men and two women) aged 50 years (range 25 to 61 years) who weighed 71 +/- 9 kg, participated in the study and received cyclosporine, 7 to 10 mg/hr (117 +/- 15 micrograms/kg/hr). The infusions were initially maintained for 26 +/- 5 hours (range 18 to 42 hours) without adjustments in dosage. Whole blood samples were obtained at hourly intervals for the first 8 to 12 hours and then daily throughout the 7-day study period and were analyzed by high-performance liquid chromatography. Constant-rate cyclosporine infusion resulted in therapeutic blood levels (350 to 450 ng/ml) at 6 hours. These levels remained relatively steady throughout the 7-day infusion, requiring only minimal dosage adjustments. Kidney function was not altered significantly after 7 days of intravenous cyclosporine therapy as evidenced by a mean serum creatinine level of 1.3 mg/dl before therapy and 1.4 mg/dl after therapy. There, however, was a transient rise in serum creatinine level in most patients on the second or third day after transplantation that resolved without a reduction in cyclosporine dosage. The mean endomyocardial biopsy score at 1 week after transplantation was 0.1, and only four of the patients required additional immunosuppressive therapy to treat rejection during the first 6 weeks after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Marfan syndrome presenting as aortic rupture in a young athlete: sudden unexpected death?

A 20-year-old man had a spontaneous rupture of the ascending aorta while exercising. The diagnosis of Marfan syndrome, established by the gross and microscopic autopsy findings, was further supported by review of the autopsy report of the father, who had died at age 26 of a nearly identical aortic rupture. To avoid occurrences such as the above, the responsibility of the forensic pathologist should extend beyond the autopsy to appropriate counseling of families in instances where medically treatable hereditary conditions may be present in the survivors.

A maternal death due to thrombotic disease associated with anticardiolipin antibody.

We report a case of fetal death at 30 weeks' gestation followed by the unexpected death of the mother 28 1/2 hours later. At postmortem examination, extensive small-vessel thrombi were found in the maternal organs, including the uterus, kidney, and heart. In retrospect the mother had evidence of chronic pericarditis and myocarditis. Laboratory tests of antemortem serum demonstrated elevated titers of anti-double-stranded DNA and of anticardiolipin antibodies.

Effects of Nd:YAG laser energy on the arterial wall: evaluation of a new contact delivery system.

Although there has been much recent interest in the application of lasers to arterial occlusive disease, a detailed understanding of the effects of laser energy on vessel walls is lacking. This study compared the effect of a conventional, non-contact delivery system of Nd:YAG laser energy to a contact system using a 600 microns, artificial sapphire tip in eight mongrel dogs. A small section of the luminal surface of the carotid and femoral arteries was exposed to 10 or 15 joules of Nd:YAG laser power and flow was restored in the vessel. The animals were sacrificed at 0, 1, 2, 4, 7, 14, 21, and 30 days and the vessels were removed. The surface area of the laser injury for each artery was quantitated by computerized planimetry and all histologic sections were examined under light microscopy by an independent observer. Transmural necrosis occurred in 64% (20/31) of the non-contact lesions versus only 29% (9/31) of the contact lesions (P less than 0.01). Both types of laser injuries followed a predictable course with initial medial necrosis followed by formation of a fibrin erythrocyte coagulum overlying the lesions at 24 hr. The usual zones of vaporization, coagulation necrosis, and thermal damage were noted with both types of delivery systems, but the contact system resulted in more intimal vaporization. Healing of all lesions was rapid with complete endothelial coverage at two weeks. Thrombosis occurred in only 1 of 32 (3%) arteries, and there were no false aneurysms. Contact delivery of Nd:YAG laser energy produces significantly less transmural injury than does non-contact.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatal nonatherosclerotic myocardial infarction in a young man with allergic bronchial asthma.

A 34-year-old man with allergic asthma died an (instantaneous) sudden cardiac death as a result of multiple myocardial infarcts. These occurred in the absence of coronary atherosclerosis. The major mechanism by which the infarcts occurred was recurrent coronary artery spasm. The latter can occur spontaneously, asthma patients being particularly prone to it. However, various medications prescribed by different physicians may also have played a role.

Relation of atherosclerosis to arterial wall shear in the left anterior descending coronary artery of man.

Low fluid dynamic shear acting on the vascular endothelium has been suggested as a factor in atherogenesis. This study describes qualitatively differences of wall shear rate in the left anterior descending coronary artery (LAD) of man and relates the distribution of wall shear to that of atheromatous plaques. Selective coronary arteriograms of 21 patients without obstructive LAD diseases were reviewed. Blood velocity, and therefore wall shear in the LAD, was assessed qualitatively based upon the rate of clearance of contrast material. There was a rapid clearing of contrast material along the outer wall of the LAD as it curved around the border of the heart. A much slower clearing occurred along the inner wall, bordering the myocardium, which persisted two to six cardiac cycles after the outer wall had cleared. This suggests that velocity, and therefore shear rate, is lower along the inner wall of the LAD than along the outer wall. In 27 patients who died of noncardiac disease, an uneven distribution of atheromatous plaques in the LAD was observed histologically, with greater involvement of the inner wall. These observations demonstrate an association between the lower shear rate along the inner wall of the LAD and the site of higher concentration of atherosclerosis.

The surgical pathology of rheumatic and floppy mitral valves. Distinctive morphologic features upon gross examination.

A total of 30 surgically resected complete mitral valves were examined, without prior knowledge of the clinical history, to evaluate the reliability of gross inspection only for the correct morphological diagnosis. Twenty valves were rheumatic; 10 were obtained from patients with idiopathic mitral valve prolapse. Two groups were identified: group I correlated with a rheumatic history; group II showed floppy mitral valves, which correlated with mitral valve prolapse. Hence, it is considered that the diagnosis of rheumatic or floppy mitral valve can be established accurately upon gross examination only. The rheumatic valve is fibrotic and firm, leading to thickening and fusion of leaflets and commissures. Narrowing and lowering of the "principal" ostium occurs. This results in a funnel-shaped valve, which is further accentuated by interchordal fusion. Rigidity is its hallmark. Chordal rupture is unlikely. Calcification can be found anywhere in the valve. Hooding is extremely unusual. The floppy valve, by contrast, shows laxity of leaflets, which may lead to the formation of dome-like deformities reaching above the level of the annulus. The chordae are often thin, attenuated, and may have ruptured. The distribution of chordae and mode of anchoring is often chaotic. Fibrosis occurs mainly at the anchoring sites of the chordae underneath or at the margin of the leaflet, or where previously ruptured, intertwined chordae are plastered underneath the dome. Fibrosis is further aggravated at the margins and atrial surface of the leaflets because of regurgitant friction. In spite of fibrosis, the floppy valve remains soft and flexible. Commissural fusion is absent. Interchordal fusion is not a characteristic feature of the floppy mitral valve. Gross inspection will not only correctly discriminate between a rheumatic and floppy mitral valve, but may also contribute to an understanding of the pathogenesis of the valve deformity.

Isolated mitral valve prolapse: chordal architecture as an anatomic basis in older patients.

Ten patients with an average age of 58 years underwent valve replacement because of isolated mitral valve prolapse with severe regurgitation. None had clinical evidence of Marfan's syndrome or another systemic disease that would indicate that a primary connective tissue disorder was the cause of the prolapse. All 10 patients had a dome configuration of the posterior leaflet and one or more ruptured chordae related to it. The gross morphology of the resected specimens revealed marked deviations in chordal branching and the pattern of anchoring in each of the 10 cases, rendering the most severely affected parts of the leaflets less well supported. Similar changes occurred at sites remote from the principal abnormality. Microscopically, the dominant tissue change was myxomatous transformation within the affected leaflets and chordae with secondary changes at both atrial and ventricular surfaces. These findings could indicate that insufficient chordal support may have promoted the development of the floppy valve through a process of chronic undue and unbalanced stress on the valve tension and closure apparatus. The resultant degeneration of the connective tissues, histologically expressed as myxomatous transformation, may underlie stretching and thus redundance of the leaflets and eventually rupture of chordae. It is suggested that this sequence of events be considered as a possible pathogenetic mechanism of isolated mitral valve prolapse, particularly in the subset of aged patients.

Pathological aspects of transcutaneous cardiac pacing.

Although electrical energy has the potential to produce myocardial injury, the risk of tissue damage from transcutaneous cardiac pacing is largely unknown. This study reports the anatomical findings of a canine transcutaneous stimulation study. Ten dogs had 100-mA, 20-msec (pulse duration), transcutaneous impulses delivered across the thorax for 30 minutes at a rate of 80 stimuli per minute. Seventy-two hours later the animals were sacrificed, and the heart, lungs, and tissues of the chest wall were examined for pathological changes. Gross and microscopic lesions consistent with electrically induced myocardial damage were found in all hearts examined. These lesions included myocardial pallor and focal myofibril coagulation necrosis in the right ventricular outflow tract and perivascular microinfarcts in the posterior left ventricular myocardium. These lesions were not extensive; less than 5% of the right ventricular free wall and less than 1% of the left ventricular posterior wall were involved. Lesions of this extent would not be expected to cause clinically detectable changes in cardiovascular status. Short-term use of transcutaneous pacing appears to be safe. Determination of the potential for clinically significant injury with long-term use requires further study.

The comparative effects of the argon, Nd: YAG, and argon-pumped dye lasers on human platelets and erythrocytes in vitro.

The effects of three lasers, Argon, Nd:YAG, and Argon-pumped Dye, on three types of platelet preparations were evaluated. Either EDTA or buffered citrate served as anticoagulants. Platelets separated from plasma and suspended in buffer showed no decrease in counts following lasering, but morphologic damage was evident with transmission electron microscopy (TEM). In platelet-rich plasma, a fall in counts was noted for the Argon and the YAG (at high energy only) but was absent when the Dye laser was employed. Morphologic damage (TEM), however, was noted with all three lasers. When whole blood preparations were used, more marked changes in both RBCs and platelets were seen in samples collected in EDTA compared with citrated samples. Morphologic damage (TEM) to platelets and RBCs occurred with all three lasers. An artifactual increase in "platelet counts," the appearance of spherocytes, and an increase in plasma Hb indicated RBC injury. Both platelets and erythrocytes were sensitive to variations in power (wattage) despite constant total energy delivery.

Right heart catheter lesions: any significance?

In order to determine whether endocardial lesions that developed in relation to an indwelling catheter in the right heart had any significance or characteristics, a study with clinicopathologic correlations was performed in which a total of 57 hearts were found to have right heart endocardial lesions at necropsy. Some of our findings fall within the range of results of various similar studies, e.g., clinical backgrounds and incidence in which these lesions occur. However, others do not; pulmonary embolism was preexisting and coexisting rather than attributable to the heart lesions. Right heart lesions occur significantly more often (P less than 0.01) in patients who received a right heart catheter than those who did not. The morphologic features of these endocardial lesions are sufficiently characteristic to indicate not only that an intracardiac catheter had been present but even what type of catheter it was. Infective endocarditis was found in seven catheterized patients. This process has a tendency to involve valves transmurally, indicating possible need for prosthetic valve replacement if any patients were to survive the underlying disease. Traumatic perforation of the endocardium was uncommon. With the aid of careful indications and strict adherence to guidelines, the risk of fatality from these lesions is extremely unlikely.

Transcutaneous cardiac pacing: determination of myocardial injury in a canine model.

Transcutaneous cardiac pacing holds promise as the initial cardiac pacing technique for emergency patients. Determination of the extent of myocardial injury associated with the use of commercial transcutaneous pacemaker devices has been limited. This study was undertaken to document electrocardiographic, enzymatic, and histologic changes following transcutaneous pacing. Ten mongrel dogs were paced with a transcutaneous cardiac pacemaker for 30 minutes. Electrical pulses of 100 mA lasting 20 ms each were delivered at a rate of 80/min via cutaneous electrodes on the anterior and posterior thorax. Myocardial damage was assessed by serial electrocardiograms (ECGs), serial creatine kinase (CK) determinations with myocardial band (MB) fractionation, and gross and microscopic pathologic examination. Double blind reading of the ECGs showed no significant changes after pacing. CK levels peaked an average of 78 units over baseline levels at 4 hours; however, there was no rise in the CK MB fraction. Pathologic examination revealed micro-infarcts adjacent to intramural vessels in 5 animals, but no clinically significant myocardial injury in the 10 dogs. The absence of enzymatic, cardiographic, and clinically significant pathologic findings was statistically significant (P less than .05). Transcutaneous pacing at low currents and for short periods appears to be a safe technique. This pacing technique deserves further evaluation, and may hold promise as a clinical tool during resuscitation.

Electrocardiographic and hemodynamic changes in experimental right ventricular infarction.

To investigate the electrocardiographic and hemodynamic changes in isolated right ventricular infarction, 0.25 ml or 0.5 ml of metallic mercury was injected into the right coronary artery of 14 closed-chest dogs. At autopsy, at least 60% of the right ventricle was necrotic in every dog. Hemodynamic observations were made in 11 and electrocardiographic mapping was performed in all 14 dogs. Right atrial pressure rose in 10 and left atrial pressure in nine of the 11 dogs; early right atrial pressure did not exceed left atrial pressure, but late right atrial pressure was greater in four dogs. Although cardiac output and blood pressure fell significantly, circulation was maintained. Twelve of 14 dogs had transient ST-segment elevation in the right precordial leads, and 12 developed right bundle branch block. Abnormal Q waves or R waves of 1 mm or less appeared in the right precordial leads in 13 of the 14 dogs. Since right bundle branch block and abnormal Q waves in the right precordial leads have not been recognized as useful signs in human right ventricular infarction, further investigations are warranted to determine their value in clinical applications.

Anomalies of the left atrium and mitral valve: cords, flaps, and duplication of valve.

We studied seven hearts with abnormalities of the atrial septum of the mitral valve. Three had abnormalities of the atrial septum, characterized by a flap or a diaphragm within the left atrium. Another three cases had abnormal cords extending from the atrial septum to the anterior or the posterior mitral leaflets. A seventh case had a duplicated mitral valve. Grossly, the specific conditions among these seven hearts appeared very different: however, we believe that the origin of each anomaly can be explained by one of three developmental aberrations or a combination thereof. Although only one case was associated with severe cardiac disease, such structures may be seen during cardiac imaging or operation.

Recurrent primary coronary artery dissecting aneurysm (hematoma).

A 40-year-old man with recurrent spontaneous (non-iatrogenic) primary coronary artery dissecting aneurysm (hematoma) apparently survived long enough to permit spontaneous healing of the first coronary arterial lesion, as well as the myocardial infarct that accompanied it. Death was due to a recent myocardial infarct, located at a different site than the first one, and caused by a recent coronary artery dissection, involving a different coronary artery. The nature of the coronary artery disease was not identified until the time of necropsy. It was not related to coronary atherosclerosis, or demonstrable systemic vascular disease. Spontaneous primary coronary artery dissecting aneurysm is a rare condition. Survival, with complete healing, without the aid of surgical therapeutic intervention, has not yet been reported. The finding of a healed myocardial infarct, in the presence of grossly normal appearing coronary arteries, indicates a necessity for extremely careful histologic examination, including use of special staining procedures of the arteries supplying the areas of infarction.

Survival in subgroups of patients with left main coronary artery disease. Veterans Administration Cooperative Study of Surgery for Coronary Arterial Occlusive Disease.

This report presents the 42-month survival experience of 91 patients with a significant lesion of the left main coronary artery in the Veterans Administration Cooperative Study of Coronary Bypass Surgery. Survival in surgical patients was significantly better than that in the medical group (p = 0.016), even after adjustments were made for two important differences in baseline characteristics--duration of angina and high risk by angiographic criteria--between the two groups (p = 0.019). Subgroups based on severity of left main stenosis and on left ventricular (LV) function showed significant trends in favor of surgery in patients with more than 75% left main stenosis and in those with abnormal LV function. A similar but nonsignificant trend was seen in the two subgroups with 50-75% stenosis or with normal LV function. The surgical benefits were not significantly different between the categories of the subgroups defined separately by stenosis and LV function. Low-, middle- and high-risk subgroups based on four noninvasive clinical predictors also showed significantly improved survival with surgery in the high-risk group. The low-risk groups showed a slight, nonsignificant disadvantage with surgical treatment. These data support the view that patients with left main disease are not a homogeneous group. High- and low-risk subgroups with different outcomes and responses to treatment can be delineated by angiographic or clinical criteria. For most patients with left main disease, coronary artery bypass grafting offers improved longevity.

Electrocardiographic diagnosis of right ventricular infarction.

The electrocardiographic findings in 11 cases of acute right ventricular infarction associated with acute left ventricular inferior wall myocardial infarction are described. The diagnosis of right ventricular infarction was proved by autopsy findings in five cases and supported by hemodynamic data in the other six. Ten of the 11 patients had typical electrocardiographic changes of acute inferior myocardial infarction and one had that of inferior wall injury. Transient S-T segment elevation was present in one (lead V1) or more of the right precordial leads in eight cases. In the absence of other explanations for the S-T segment elevation, acute right ventricular infarction was most likely the cause. Therefore, when acute inferior myocardial infarction is accompanied by S-T segment elevation in the right precordial leads, the coexistence of right ventricular infarction should be suspected. The sensitivity and specificity of this electrocardiographic sign are yet to be determined.