Chylomicron and very low-density lipoprotein apolipoprotein B metabolism: mechanism of the response to stanozolol in a patient with severe hypertriglyceridemia

Studies of simultaneous autologous 131I-chylomicron (Sf greater than 400) and 125I-very low density lipoprotein (VLDL) (Sf 20 to 400) apolipoprotein B (apo B) were performed both before (triglyceride level c 1500 mg/dL) and during treatment with stanozolol, a 17 alpha-methyl anabolic androgenic steroid (triglyceride level c 750 mg/dL) in a 74-year-old woman with a past history of recurrent chylomicronemic pancreatitis. Both before and during stanozolol treatment chylomicron apo B disappeared rapidly and directly, little appearing in VLDL and virtually none in intermediate (IDL) or low density lipoproteins (LDL). Multicompartmental analysis indicated that the great majority of chylomicron apo B was removed via an extremely rapid compartment (estimated fractional catabolic rate [FCR], 5.0/h), accounting for 66% before and 88% during stanozolol treatment. The remaining 131I-apo B decayed biphasically, with total Sf greater than 400 residence times of 8.6 hours before and 3.7 hours during stanozolol treatment. Hence, despite a moderately depressed adipose tissue lipoprotein lipase activity, the subject's hypertriglyceridemia did not appear to proceed solely from retarded chylomicron removal, nor was the dramatic decrease in triglyceride in response to stanozolol a function only of the acceleration of such removal. VLDL apo B kinetics were analyzed by a multicompartmental model featuring a rapid, stepwise delipidation chain which proceeds either rapidly to IDL and LDL or to a slowly turning over compartment within VLDL. While VLDL. apo B synthesis remained essentially constant, the major effect of stanozolol was a substantial reduction in the fraction of VLDL apo B diverted to this slowly turning over compartment, which decreased from 5.0% before to 1.2% during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thallium imaging in cardiac lymphoma

A clinicopathologic correlation was made of thallium-201 myocardial perfusion imaging in two patients with massive myocardial invasion by malignant lymphoma. Despite extensive tumor involvement, the thallium scintigram was normal in one patient, while the other had only a modest-sized region of reduced tracer uptake. The discrepancy between the results of thallium scans and postmortem observations in these patients is probably related to uptake of thallium by tumor cells. The ability of any cellular and well-perfused tissue to absorb potassium, and potassium analogs such as thallium, suggests that thallium-201 scintigraphy may not be a useful method to screen for cardiac involvement in patients with known malignant neoplasms.     

Interstitial nephritis,proteinuria, and renal failure caused by nonsteroidal anti-inflammatory drugs: Immunologic characterization of the inflammatory infiltrate

Nine patients with the unusual combination of renal failure, nephrotic-range proteinuria, and biopsy-proved interstitial nephritis are described. Six of these patients had received nonsteroidal anti-inflammatory agents (three fenoprofen, one ibuprofen, one zomepirac, and one tolmetin). The remaining three patients had no history of exposure to drugs known to cause interstitial nephritis. Immunologic characterization of the infiltrating cells with monoclonal antibodies showed that the majority of cells in most cases were cytotoxic T cells, although some B cells were present in all cases. Giant collecting duct cells were seen In half the patients with drug exposure but in none of the others. Otherwise, there were no conspicuous morphologic differences between patients with and without drug exposure. Many of the patients had associated glomerular abnormalities. Only the zomepirac and tolmetin recipients showed pure interstitial disease. The three fenoprofen recipients and the zomepirac and tolmetin recipients regained normal renal function after the drug was discontinued. The combination of renal failure, nephrotic range proteinuria, and interstitial nephritis is one form of nephrotoxicity observed in patients treated with nonsteroidal antiinflammatory agents. However, this lesion, which may be mediated by cytotoxic T cells, may also be seen rarely in patients with no apparent drug exposure.     

Late effects of acute infarct dilation on heart size: a two dimensional echocardiographic study

Dilation of the infarct zone (infarct expansion) has been shown to be a cause of regional left ventricular dilation within days of transmural anterior myocardial infarction. Whether this process stabilizes, continues or regresses thereafter, and whether uninfarcted myocardium is affected is unknown. To explore this, two to six (mean four) serial two dimensional echocardiographic studies were obtained over a 3 to 30 month period (mean 13) in 13 patients beginning 10 to 21 days after anterior transmural myocardial infarction. With use of the papillary muscles as internal left ventricular landmarks, anterior and posterior segmental dilation in each patient was assessed from the slope of the regression line of segment length versus time. Study patients were classified into those with (seven patients) and those without (six patients) infarct expansion. Infarct expansion was defined as an anterior segment length 10 to 21 days after infarction that exceeded the upper limit of normal determined from 13 age-and sex-matched normal control subjects. Ten to 21 days after infarction, the average anterior segment length in the seven patients with expansion was 65 percent greater than that in normal control subjects. The seven patients with infarct expansion showed significant and continuing dilation during long-term observation of both the infarcted anterior (p < 0.01) and the uninfarcted posterior (p < 0.05) segments. The average increase in anterior segment length was 1.1 cm (8 percent) and in posterior segment length 0.9 cm (19 percent). This represents an average increase in overall left ventricular circumference of 11 percent during the observation period. The six patients without infarct expansion showed no significant change in anterior or posterior segment length (mean ± standard error of the mean [SEM] ?0.7 ± 0.3 and 0.2 ± 0.3 mm/mo, respectively). Six of the seven patients with infarct expansion were functionally limited by dyspnea or angina, or both; no patient without infarct expansion had functional cardiac limitation.Thus, infarct expansion occurring within 3 weeks of transmural myocardial infarction appears to be the main contributor to left ventricular dilation, and is associated with impaired functional status. Moreover, a significant increase in ventricular size due to infarct expansion appears to predict chronic progressive ventricular enlargement due to lengthening of both the infarcted zone and the uninfarcted segment.     

Richter's syndrome: Diffuse histiocytic lymphoma in patients with chronic lymphocytic leukemia: A report of five cases and review of the literature

The development of diffuse “histiocytic” lymphoma in patients with chronic lymphocytic leukemia (CLL), Richter's syndrome, occurs infrequently, but it is a distinct clinicopathologic phenomenon. In this report we describe five new cases of Richter's syndrome and summarize data on an additional 41 patients. Information from three separate series suggests a 3 to 10 per cent incidence of diffuse histiocytic lymphoma in patients with CLL. There were no features of CLL in these 46 patients in whom diffuse histiocytic lymphoma subsequently developed which would have distinguished them from patients with typical CLL in whom diffuse histiocytic lymphoma never developed. The median interval between the diagnosis of CLL and the recognition of diffuse histiocytic lymphoma in these 46 patients was 24 months (range, less than one month to 156 months). Fever (65 per cent), increasing lymphadenopathy (46 per cent), weight loss (29 per cent) and abdominal pain (26 per cent) were the clinical features which characterized the development of diffuse histiocytic lymphoma. Median durations of survival from the diagnosis of CLL and diffuse histiocytic lymphoma were 28 months and four months, respectively. Thirty-four per cent of the patients had received no treatment for CLL prior to the diagnosis of diffuse histiocytic lymphoma. Cytotoxic therapy for diffuse histiocytic lymphoma was generally unsuccessful in patients with Richter's syndrome (14 per cent complete remission rate). Clinical features of diffuse histiocytic lymphoma, which have been associated with poor response to combination chemotherapy (bulky lymph node masses, gastrointestinal or bone involvement and previous exposure to cytotoxic drugs), were common in these patients and may have contributed to the poor therapeutic response. Morphologic and immunologic studies suggest that the diffuse histiocytic lymphoma seen in patients with CLL arises as a proliferation and “dedifferentiation” of the lymphocytes of the preexisting CLL. Absolute proof that diffuse histiocytic lymphoma arises as a clonal progression of CLL cells is lacking, however, and further study of the genesis of diffuse histiocytic lymphoma in CLL is required.     

The predictive value of a strongly positive stress test in patients with minimal symptoms

The ability of a strongly positive stress test to predict left main coronary artery disease in people with suspected coronary artery disease but with minimal or no angina was investigated in 40 such patients. Nine had a history of myocardial infarction but no angina. Thirty-one had mild angina or a history of mild angina. The stress electrocardiograms were analyzed according to criteria known to be associated with left main coronary artery disease in moderately or severely symptomatic patients; (1) early S-T segment changes (stage I or II of exercise), (2) 2 mm or more S-T segment depression, (3) downsloping S-T segments, (4) associated exercise-induced hypotension, (5) prolonged S-T segment changes after the test (≥8 minutes) and (6) anterior and inferior S-T segment depression. The prevalence of left main coronary artery disease was 35 percent and that of any severe coronary artery disease 75 percent. The criterion of anterior and inferior electrocardiographic changes with exercise was most predictive of left main coronary artery disease (P < 0.01 by χ²). Exercise electrocardiography is useful in the prediction of left main or other severe coronary artery disease even when performed in patients who have minimal angina or in those who are asymptomatic after myocardial infarction.     

Pathogenesis of left ventricular aneurysms: An experimental study in the rat model

Left ventricular aneurysms, convex protrusions at sites of transmural scar, are clinically recognized late after myocardial infarction because of their hemodynamic or arrhythmic complications. Whether aneurysms develop from dilation of freshly infarcted myocardium early after myocardial infarction or from late dilation of scar is not known. To investigate this question, the time course of changes in shape of the left ventricle early and late after myocardial infarction was studied. One hundred forty-one myocardial infarcts were produced in rats by coronary ligation, and the animals were killed at time periods of up to 6 weeks. True aneurysms developed as early as 2 weeks and only in rats with a transmural infarct. The percent of rats that manifested “aneurysmal shape changes” (defined as a protrusion of the full thickness of the left ventricular wall) increased from day 1 to day 5, but did not change significantly thereafter. The extent of left ventricular dilation in hearts with early aneurysmal shape changes did not progress significantly up to day 42. Accordingly, in the rat, regional aneurysmal shape alterations are due not to late dilation of scar tissue, but rather to “expansion” of freshly necrotic myocardium within the first 5 days of infarction. Thus, early changes in shape appear to determine late aneurysm formation.     

The lung in systemic lupus erythematosus: Analysis of the pathologic changes in 120 patients

The nature and frequency of pulmonary involvement in systemic lupus erythematosus (SLE) is controversial. We reviewed the clinical and pathologic features of 120 patients with SLE described in autopsy records at The Johns Hopkins Hospital to determine the pulmonary parenchymal changes that could be attributed directly to SLE. Each case was reviewed to determine the extent of extrapulmonic SLE and possible alternative explanations for the observed lung pathology. Moderate or severe pulmonary parenchymal alterations that were attributed to SLE were found in 22 patients (18 percent). Five patients with interstitial fibrosis, two with pulmonary vasculitis, and one with pulmonary hematoxylin bodies were attributable only to SLE, as were 11 of 15 (73 percent) patients with interstitial pneumonitis. Alternative explanations for findings previously attributed to SLE included congestive heart failure, renal failure, infection, aspiration, oxygen toxicity and increased intracranial pressure. Alveolar hemorrhage, thought to be a feature of acute lupus pneumonitis, was unexplained in only two of 29 (7 percent) patients, alveolar wall necrosis was unexplained in one of seven (14 percent) and edema was unexplained in three of 70 (4 percent). Hyaline membranes, present in four patients, were always explained. Pleuritis and pleural effusions were attributed to SLE in 22 of 36 (61 percent) and three of 28 (11 percent) patients, respectively. The findings suggest that many nonspecific pulmonary lesions previously attributed to SLE, such as alveolar hemorrhage, alveolar wall necrosis, edema and hyaline membranes, are probably secondary to intercurrent infection, congestive heart failure, renal failure or oxygen toxicity.     

Characterization of a peptide alpha-amidation activity in human plasma and tissues

Peptidyl glycine alpha-amidation activity has been detected in human plasma and in several human tissues known to synthesize biologically active alpha-amidated peptides. Activity was monitored by measuring conversion of mono-[125I]-D-Tyr-Val-Gly into mono-[125I]-D-Tyr-Val-NH2. The plasma alpha-amidation activity is dependent on molecular oxygen, copper, and ascorbic acid and appears to recognize a variety of peptide substrates which contain carboxyl terminal glycine residues. Kinetic analyses demonstrated Michaelis-Menten kinetics with a Km of 14 mumol/L for D-Tyr-Val-Gly. Based on gel filtration, the apparent molecular weight of the peptidyl glycine alpha-amidation activity in human serum is 60,000. The level of peptidyl glycine alpha-amidation activity in adult plasma (N = 17) was 106 +/- 3 pmol/mL/h (Mean +/- SEM) with no difference between male and female subjects (range 84 to 126 pmol/mL/h). In subjects under 15 years old (N = 10), mean plasma activity was 128 +/- 10 pmol/mL/h, higher than values for adult control plasma (P less than .05). In serum from hypothyroid adults (N = 13), mean serum activity was 141 +/- 11 pmol/mL/hr, higher than euthyroid controls (P less than .025). The most striking elevations in alpha-amidation activity occurred in plasma from patients with peptide-secreting tumors. Patients with medullary thyroid carcinoma (N = 19) had a mean plasma peptidyl glycine alpha-amidation activity of 142 +/- 52 pmol/mL/h (range 84 to 435 pmol/mL/h). The level of plasma alpha-amidation activity in one patient with metastatic carcinoid tumor was 560 pmol/mL/h.(ABSTRACT TRUNCATED AT 250 WORDS)     

Results of a randomized prospective trial of intraaortic balloon counterpulsation and intravenous nitroglycerin in patients with acute myocardial infarction

A randomized prospective clinical trial compared combined treatment with intraaortic balloon pumping and intravenous nitroglycerin for 4 to 5 days with routine clinical management in 20 patients with extensive myocardium at risk for infarction as evidenced by a thallium defect score of 7.0 units or greater. No significant differences in mortality or clinical outcome were observed between the 10 patients receiving the combined treatment and the 10 receiving routine management. In 14 patients two-dimensional echocardiograms obtained 6 to 24 hours after the onset of symptoms and at follow-up 6 to 16 days later (after completion of combined intraaortic balloon pumping plus nitroglycerin therapy) were analyzed to determine whether infarct segment or noninfarct segment lengths were affected by therapy. Among these 14 patients, 5 (3 receiving the combined therapy and 2 receiving routine management) demonstrated an increase in infarct segment length of greater than 1.0 cm. Mean infarct segment length increased 0.30 +/- 0.44 cm in patients receiving the combined therapy and 0.29 +/- 0.36 cm in patients on routine management (p = NS). In contrast, noninfarct segment length increased greater than 1.0 cm (mean increase 1.20 +/- 0.39) in five of seven patients on routine management but in none of 7 patients receiving intraaortic balloon pumping plus nitroglycerin therapy (mean decrease 0.22 +/- 0.20 cm) (p less than 0.05). No significant differences were noted in left ventricular ejection fraction, as measured by gated blood pool scintigraphy, or thallium perfusion defect score in a comparison of day 1 (pretreatment) with day 4 thallium or day 7 to 14 gated blood pool scintigrams. Thus, in patients with extensive myocardium at risk, it is unlikely that a reduction in mortality or a significant improvement in myocardial perfusion or ventricular function can be obtained by early intervention with intraaortic balloon pumping in combination with nitroglycerin. Although this combined therapy failed to prevent infarct segment lengthening (infarct expansion), the combined afterload-lowering effects of intraaortic balloon pumping and nitroglycerin did appear to prevent dilation or remodeling of noninfarcted segments during the first 2 weeks after acute myocardial infarction.     

The heterogeneity of hypertrophic cardiomyopathy: An autopsy and one dimensional echocardiographic study

Although echocardiography is sensitive in detecting genetically determined idiopathic hypertrophic subaortic stenosis with the two major criteria of systolic anterior motion of the mitral valve and asymmetric septal hypertrophy, the predictive value of these findings in a nonselected population remains uncertain. A study was made of nine consecutive patients with an echocardiographic diagnosis of idiopathic hypertrophic subaortic stenosis who underwent autopsy between 1975 and 1979. The patients ranged in age from 1 month to 74 years (average 53), and six were women. Seven had systolic anterior motion of the mitral valve, and one pseudo systolic anterior motion, eight had asymmetric septal hypertrophy, and three had mid systolic aortic valve closure. All nine had a systolic murmur at the cardiac apex and an abnormal electrocardiogram. At autopsy only two patients had asymmetric septal hypertrophy and myocardial fiber disarray; the other seven had no evidence of hypertrophic Cardiomyopathy on gross examination or light microscopy. Of these seven, two had concentric left ventricular hypertrophy, one coronary atherosclerosis, one cardiac amyloidosis, and three no cardiac disease. These data suggest that systolic anterior motion of the mitral valve and asymmetric septal hypertrophy may be sensitive but are poorly predictive of idiopathic hypertrophic subaortic stenosis in the general hospital population. Because these two findings may be observed even in patients with a normal heart, an echocardiographic diagnosis of idiopathic hypertrophic subaortic stenosis based on these criteria should be made with caution.     

Ischemic ventricular fibrillation: The importance of being spontaneous

Although the energy level required to defibrillate normal myocardium is low and constant, as determined from studies of induced ventricular fibrillation, little is known of the specific energy requirements in regionally ischemic hearts for spontaneous or induced ventricular fibrillation. In this study the lowest energy threshold for defibrillation was determined in 10 open chest dogs with reversible 10 minute coronary occlusions at various sites for each of 44 events of ventricular fibrillation, using apical and superior vena caval electrodes with a generator providing variable output of 1 to 30 watt seconds. The ischemic mass, quantitated from postmortem angiographic and planimetric data, was 52 ± 9 percent (mean ± standard deviation) of the left ventricle in dogs with induced ventricular fibrillation (Group I), 52 ± 12 percent in dogs with spontaneous ventricular fibrillation after occlusion (Group II) and 54 ± 9 percent in dogs with spontaneous ventricular fibrillation after reperfusion (Group III). Defibrillation thresholds in watt seconds were 9 ± 7 in Group I (n = 12), 19 ± 10 in Group II (n = 13) and 18 ± 10 in Group III (n = 19). (Group I versus Groups II and III, probability [p]<0.025). In nonischemic hearts, the defibrillation threshold was 3 ± 2 (n = 32) (p <0.001 compared with values in Group I, II or III). Thus, despite similar masses of ischemia, twice as much energy was required for defibrillation of spontaneous ventricular fibrillation (whether after occlusion or reperfusion) as for induced ventricular fibrillation, suggesting that these conditions are caused by different metabolic or pathologic derangements. Such differences should be considered in assessing interventions such as drug therapy designed to inhibit the repetitive ventricular response and in design of implantable defibrillators.     

Myocardial perfusion imaging and gated cardiac blood pool scanning: clinical application.

Myocardial perfusion imaging with thallium-201 and gated cardiac blood pool scanning are finding increasing use in clinical cardiology. These noninvasive techniques have been found useful in detecting myocardial infarction independent of the electrocardiogram and determining the site and extent of the infarct as well as its effect on left ventricular function. These studies provide important prognostic data and are proving to be of value in evaluating patients with cardiogenic shock. Neither the thallium-201 myocardial perfusion image nor the gated cardiac blood pool scan can distinguish between acute and chronic myocardial damage. In clinical situations where this is important, infarct avid imaging with technetium-99m pyrophosphate allows determination of whether a given perfusion defect or wall motion abnormality is acute. Myocardial perfusion imaging with thallium-201 at rest and after exercise is also proving to be of value in evaluating patients with suspected ischemic heart disease. Initial studies suggest that the technique may be more sensitive than exercise electrocardiography and is of special value in minimizing the occurrence of false positive exercise tests for the diagnosis of ischemic heart disease. The combined tracers technique is also of value in the evaluation of patients undergoing coronary bypass graft surgery and those with cardiomyopathy.     

Simple adjuncts which maintain septal temperature below 20° C during ischemic arrest for coronary artery bypass grafting

One of the key elements of intraoperative myocardial protection is maintaining myocardial temperature below 20° C during ischemic arrest; however, many diverse techniques have been advocated to achieve this goal. One hundred and thirteen patients undergoing myocardial revascularization with one period of ischemic arrest were randomized: group A (n = 52) received continuous (150 to 200 cc/min) profound (4° C) topical hypothermia and group B (n = 61) received identical topical hypothermia plus one initial 500 cc aortic root bolus of cold (4° C) hyperkalemic cardioplegic solution. Perfusion technique was identical for both groups. The two groups were statistically indistinguishable when 30 preoperative and intraoperative characteristics were compared, including the distribution and number of vessels diseased, degree of left ventricle dysfunction, average number of coronary artery bypass grafts, aortic crossclamp times, and cardiopulmonary bypass times. Myocardial septal temperature (° C ± SD) was measured following each distal anastomosis. For group A the values were 29.6 ± 2.7° C for the first anastomosis, 24.4 ± 2.7° C for the second anastomosis, 20.8 ± 2.57° C for the third anastomosis, and 21.5 ± 3.3° C for the fourth anastomosis (p < 0.001). For group B the values were 18.7 ± 4.2° C for the first anastomosis, 17.5 ± 2.9° C for the second anastomosis, 16.7 ± 3.1° C for the third anastomosis, and 16.7 ± 3.1° C for the fourth anastomosis (p < 0.001). These data show that midseptal myocardial temperature can be reliably maintained below 20° C for up to 1 hour of ischemic arrest in patients undergoing coronary artery bypass grafting after one bolus of cold cardioplegia if: (1) perfusion flow and pressure are lowered, (2) venous drainage is maximized, and (3) supplemental topical hypothermia is assiduously carried out. Furthermore, myocardial temperature in group B was reduced more rapidly and remained significantly lower than that in group A. This simplified technique provides effective myocardial cooling without the complexities of multidose cardioplegia or profound systemic hypothermia.     

Effect of intraarterial infusion of the ketoanalogue of leucine on amino acid release by forearm muscle

α-Ketoanalogues of most essential amino acids can be converted to the corresponding amino acids in man and appear to be useful dietary supplements in protein-intolerant patients. Recently, the branchedchain amino acids, especially leucine, have been found to promote protein synthesis in isolated muscle. The present studies were designed to assess the capacity of skeletal muscle to aminate the keto-analogue of leucine and determine if the metabolism of the ketoacid promotes protein synthesis. Six normal postabsorptive males received a 30-min brachial intraarterial infusion of ketoleucine (34.4 μmoles/min). Changes in ipsilateral muscle balance were estimated from whole blood concentrations and flow for 1 hr. Brachial arterial blood ketoleucine concentration increased by an average of 1.02 mM. In a single passage across forearm muscle, 52% of the ketoacid was extracted. Leucine was the only amino acid released in increased amounts, accounting for 31% of ketoleucine extracted. The remainder was apparently oxidized. No one donor capable of supplying all the nitrogen needed for leucine production could be identified, but significant reductions in the release of alanine, glycine, and histidine, and changes from release to uptake of valine and isoleucine, suggest possible contributions from these amino acids. Glutamine-asparagine release did not change. Lysine, tyrosine, and phenylalanine balances were also unchanged, suggesting no anabolic effect of ketoleucine on muscle protein under these conditions. The results demonstrate rapid transamination and utilization of ketoleucine by skeletal muscle in postabsorptive man.     

Predictors of survival after tricuspid valve surgery

The long-term survival rate of 74 consecutive patients who underwent multiple cardiac valve surgery including tricuspid valve surgery was analyzed to identify predictive preoperative clinical variables. Univariate analysis revealed that male sex (p < 0.04), symptoms of New York Heart Association functional class IV heart failure (p < 0.004), ascites or pulmonary edema (p < 0.01), high preoperatlve bilirubin level (p < 0.012), mean pulmonary artery pressure greater than 40 mm Hg (p < 0.038) and pulmonary vascular resistance greater than 6 Wood units (p < 0.02) were each associated with an increased risk of death after surgery. Stepwise multivariate analysis indicated that severity of preoperative edema and mean pulmonary artery pressure were the most predictive combination of independent variables. These 2 variables were used to calculate an estimated probability of 1-year survival after surgery for patients with multivalvular cardiac decompensation. Recognition of these preoperative variables should assist the clinician in determining the risk of surgical intervention.     

Long-term recording of monophasic action potentials from human endocardium

In 36 patients undergoing routine cardiac catheterization, a new “contact electrode” catheter technique was used to record monophasic action potentials (MAPs) from right atrial and right and left ventricular endocardial sites without the application of suction. Although of smaller amplitude, typically ranging from 15 to 40 mV, and of different reversal ratio (33 ± 3%), MAP recordings closely resembled transmembrane action potentials in configuration and duration. Continuous MAP recordings of stable amplitude and, during regular pacing, of constant duration (± 1% at 90% repolarization) could be made from the same endocardial site for test periods of 1 hour (n = 4), permitting direct evaluation of the effect of cycle length alterations on local myocardial repolarization. A linear relation was found between MAP duration and basic cycle length varying from 350 to 700 ms. These rate-dependent changes in MAP duration were caused by a change in the slow phase of repolarization (phase 2), whereas the slope of rapid repolarization (phase 3) was unaltered. Single premature MAPs or MAPs after a pause showed changes in both phases. No MAPs could be recorded in areas of infarcted, aneurysmal myocardium, indicating that local viable myocardium is a prerequisite for the generation of the monophasic signal. Thus, in human subjects this catheter permits safe, long-term recording of MAPs which, although of smaller amplitude than transmembrane action potentials, bear appropriate and predictable phase relations. Such recordings may be useful in evaluating changes in local myocardial electrical activity induced by pacing or resulting from myocardial disease, or both.