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The recently developed echocardiographic technology of color kinesis (CK) displays endocardial motion in color layers on a single end-systolic 2-dimensional echocardiographic frame. Previous work using this method is promising for quantitation of regional function, but there is limited experience in patients with severely reduced left ventricular function. Twenty patients (age 59 +/- 10 years) with dilated cardiomyopathy (left ventricular ejection fraction 22 +/- 8%) underwent CK imaging. Endocardial motion was quantitated by measuring the distance of endocardial motion during the systolic interval and also by calculating the endocardial velocity. CK measurements were compared among 4 wall motion grades (i.e., normal, hypokinetic, akinetic, and dyskinetic) assessed by qualitative wall motion scoring. There was a significant overall difference (p < 0.0001) in the mean systolic endocardial inward motion (i.e., contraction) and outward motion (i.e., expansion) among wall motion grades. The mean endocardial outward distance was significantly greater for the dyskinetic segments than for the other grades (p < 0.001). There were also differences in the mean velocity of endocardial motion among the wall motion grades. In the presence of left bundle branch block, there was no difference in the mean endocardial inward distance of the hypokinetic, akinetic, and dyskinetic septal segments. We conclude that in the absence of left bundle branch block, normal, hypokinetic, akinetic, and dyskinetic ventricular wall segments may be distinguished in patients with dilated cardiomyopathy on the basis of endocardial motion measured with CK.

Achieving defibrillation depends on adequate intracardiac current. The purpose of this study was to determine, in advance of administering shocks which parameters of body habitus can be used to select the electrode size that maximizes intracardiac current in transthoracic defibrillation. We administered direct current shocks to 18 mongrel dogs over a wide range of weight and size (weight 10-30 kg with chest circumferences 44-77 cm) using a damped sine wave defibrillator and self-adhesive electrode pairs of various diameters (4 cm, 5.8 cm, 8 cm and 10 cm), placed on the right and left lateral chest walls. The energy levels used were 50, 100, and 150 J. Intracardiac voltage gradient, a parameter of intracardiac current, was determined in three orthogonal planes using an intramyocardial electrode array placed in the interventricular septum. The relation between intracardiac voltage gradient magnitude magnitude of VG and various parameters (body weight, chest, circumference, chest volume, chest radius, and heart weight divided by chest radius) was determined. The correlation (r) with the smallest P value was between magnitude of VG and the heart weight divided by chest radius (HW/R) (r = 0.71). Intracardiac current was highest at intermediate pad sizes. The electrode pads that maximized magnitude of VG tended to be large for the larger HW/R dogs, and smaller HW/R dogs. In none of the HW/R groups did the largest electrode pads yield the highest intracardiac voltage gradient. We conclude that there is no simple way to determine in advance an electrode pad size that maximizes intracardiac current. The HW/R ratio influences but does not determine intracardiac intracardiac current.

Our purpose was to determine whether prolonged myocardial ischemia attenuates free radical production after early reperfusion. Twenty-two mongrel dogs underwent left anterior descending coronary artery occlusion for 20, 40, or 60 minutes followed by 30 minutes of reperfusion. Electron paramagnetic resonance spectroscopy was used to measure ascorbate free radical in the coronary vein effluent. Ascorbate free radical production during reperfusion was significantly (p < 0.05) reduced in the dogs undergoing 60 minutes of coronary artery occlusion compared with the dogs undergoing 40 and 20 minutes of occlusion. We conclude that prolonged myocardial ischemia results in less free radical production on reperfusion than do shorter periods of ischemia followed by reperfusion.

Currently available transthoracic defibrillators use either a damped sinusoidal or truncated exponential (TE) waveform. Truncated exponential waveforms deliver a long pulse if the transthoracic impedance is high; it has been suggested that such a long pulse may be less effective for defibrillation. Our objective was to compare the ability of damped sinusoidal (DS) waveform shocks versus TE waveform shocks to terminate ventricular fibrillation (VF) and achieve survival from witnessed cardiac arrest. We retrospectively reviewed field-recorded electrocardiograms from 86 patients with witnessed VF, treated by prehospital personnel equipped with DS or TE waveform defibrillators. Forty-four patients received 130 shocks from TE defibrillators; 42 patients received 108 shocks from DS defibrillators. There were no significant differences in time from arrest to first shock (8.0 vs 8.1 minutes), nor were there any differences in the size of the communities involved. The shocks resulted in the following rhythms: organized rhythm: TE: 15 of 130 (12%), DS: 24 of 108 (22%), p = 0.10 (NS); persistent VF: TE: 85 of 130 (65%), DS: 45 of 108 (42%), p <0.01; asystole: TE: 30 of 130 (23%), DS: 39 of 108 (36%), p = NS; and survival to hospital discharge: TE: 5 of 44 (11%), DS: 8 of 42 (19%), p = NS. We conclude that DS waveforms terminated VF more frequently than TE, but there was no significant difference in resumption of an organized rhythm or survival. A prospective comparison of these 2 waveforms is needed.

This study examines in a prospective, multicenter trial the feasibility and advantage of current-based, transthoracic defibrillation. Current-based, damped, sinusoidal waveform shocks of 18, 25, 30, 35, or 40 amperes (A) were administered beginning with 25 A for polymorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) or 18 A for monomorphic VT; success rates were compared with those of energy-based shocks beginning at 200 J for VF/polymorphic VT and 100 J for VT. The current-based shocks were delivered from custom-modified defibrillators that determined impedance in advance of any shock using a "test-pulse" technique; the capacitor then charged to the exact energy necessary to deliver the operator-selected current against the impedance determined by the defibrillator. Three hundred sixty-two patients received > 1 shock for VF, polymorphic VT, or monomorphic VT: 569 current- based shocks and 420 energy-based shocks. Current-based shocks of 35/40 A achieved success rates of up to 74% for VF/polymorphic VT; 30 A shocks terminated 88% of monomorphic VT episodes. Energy-based shocks of 300 J terminated 72% of VF/polymorphic VT; 200-J shocks terminated 89% of monomorphic VT. We could not demonstrate a significant increase in the success rate of current-based shocks over energy-based shocks for patients with high transthoracic impedance; this may be due to inadequate sample size. Thus, current-based defibrillation is clinically feasible and effective. A larger study will be needed to test whether current-based defibrillation is superior to energy-based defibrillation.

Objectives: We sought to demonstrate that direct current (DC) shocks to the heart generate free radicals., Background: Although it is a lifesaving maneuver, defibrillation is known to have myocardial toxicity. The mechanism of this toxicity is unknown. If DC shocks generate free radicals, free radicals could be a mechanism of myocardial injury., Methods: In a canine model, DC shocks of 10 to 100 J were delivered to the epicardium of both beating and fibrillating hearts, and 200-J transthoracic shocks were administered in dogs with beating hearts. Ascorbate free radical (AFR) concentration was measured in arterial blood and blood continuously withdrawn from the coronary sinus. In some dogs, the antioxidant enzymes superoxide dismutase (15,000 U/kg) and catalase (55,000 U/kg) (SOD/Cat) were administered before shocks., Results: Ascorbate free radicals were generated by DC shocks. A peak AFR increase of 14 +/- 2% (mean +/- SEM) was seen 5 to 6 min after 100-J epicardial shocks. A peak AFR increase of 7 +/- 5% occurred after transthoracic shocks. There was a significant linear relation between the shock energy and peak percent AFR increase: %AFR increase = 0.18 (Shock energy) + 2.9 (r = 0.73, p < 0.0001). Shocks delivered to hearts in ventricular fibrillation (30 s) resulted in generation of AFR equal to but not greater than that observed during similar shocks delivered to beating hearts in sinus rhythm. Multiple successive shocks (100 J delivered twice or five times) did not result in a greater AFR increase than single 100-J shocks, indicating that peak, not cumulative, energy is the principal determinant of AFR increase. Animals receiving SOD/Cat before shock administration showed significant attenuation of the AFR increase., Conclusions: Direct current epicardial and transthoracic shocks generate free radicals; antioxidant enzymes reduce the free radical generation by shocks.

Direct current electric shocks have been used to terminate atrial arrhythmias (cardioversion) in humans since the 1960s. The likelihood of successful cardioversion and maintenance of sinus rhythm is increased if the left atrium is not markedly enlarged and fibrotic, if there is no marked left atrial hypertension (e.g., mitral stenosis), and if the arrhythmia is not long-standing. To minimize the risk of thromboembolic phenomena, therapeutic anticoagulation should be established for at least 3 weeks before and for 4 weeks after cardioversion; coumadin is usually used for this purpose. A more recent approach uses transesophageal echocardiography to demonstrate the absence of thrombi in the left atrium and left atrial appendage. If no thrombi are evident, 48 hours of heparin anticoagulation may be adequate prior to cardioversion. Anticoagulation is still required after cardioversion. Quinidine and digitalis, singly or in combination, are frequently used to achieve and maintain sinus rhythm in association with cardioversion. For the procedure itself, traditional hand-held paddle electrodes or self-adhesive electrode pads may be used; the apex-anterior and anterior-posterior positions are equally effective. Gel couplants and firm pressure should always be used with hand-held paddles to reduce transthoracic impedance and maximize current flow. Electrodes should be widely separated to avoid shunting of current along the chest wall between electrodes. Generally, electrodes should be large in size; small "pediatric" electrodes should only be used in infants < 1 year of age (< 10 kg). Shocks should always be synchronized to the R wave to avoid the vulnerable period and the inadvertent induction of ventricular fibrillation. Initial shocks for atrial fibrillation should begin at 100 J; atrial flutter generally requires a smaller shock (initial shocks at 50 J). Effective anesthesia, not merely sedation, is required to achieve amnesia and avoid pain. Exciting new developments in defibrillation and cardioversion have occurred. It is now understood that excessive energy and current may induce cardiac damage, and recent studies suggest such damage may be mediated in part by free radicals. New shock waveforms, such as biphasic and multiphasic waveforms from multiple encircling electrodes, may be superior to the standard damped sinusoidal waveform.

An incident in which a young women became pregnant soon after being treated with 444 MBq 131 I for Graves disease prompted us to search local records for the occurrence of thyroid abnormalities among people exposed in utero to fallout radioiodine. The data base from the Utah Fallout Study (Kerber et al. 1993) indicated that there had been 480 cohort subjects for whom dose to thyroid from fallout radioiodine had been calculated and who could have received any thyroid dose before birth (2473 subjects had been re-examined in 1985-86 of the 4818 examined in 1965-70). Of these 480 subjects in this category, 403 of them could be located in the 1980's and were examined with abnormalities. Although nodules, thyroiditis, hypothyroidism and goiter were seen among the 375 persons with in utero thyroid doses from fallout radioiodine below 0.42 Gy, no thyroid abnormalities of any occurred in the 4 persons with in utero thyroid doses of 0.5 to 2.6 Gy. In addition, no neoplasia was found in any of the 403 subjects examined about 2 decades after in utero fallout exposure. These limited data do not indicate that the fetal thyroid is more sensitive than the postnatal thyroid by more than about a factor of about 4 when thyroid dose is considered and by not much more than unity when the comparison is based on dose equivalent (x ray vs. radioiodine).

Objectives: This study sought to determine the effect on transthoracic impedance of placement of defibrillation electrodes on the female breast versus adjacent to or under the breast., Background: Transthoracic impedance is a major determinant of transthoracic current flow in defibrillation. For a given energy setting, a high transthoracic impedance reduces current flow and may adversely affect the ability of electric shocks to accomplish defibrillation. We hypothesized that the increased interelectrode tissue associated with placement of the apex defibrillation electrode on the female breast would result in increased transthoracic impedance compared with electrode placement lateral to or under the breast., Method: Transthoracic impedance was measured noninvasively by passing a 5-V, 31.25-kHz square wave current through the chest and comparing the low level current flow to known references. We measured transthoracic impedance associated with three different apex defibrillation electrode positions--on the breast, under the breast and lateral to the breast--in 25 women (brassiere size 34A to 48C, 25 to 75 years old, body weight 128 to 328 lb [58 to 148 kg] and 2 men. The measurements were taken with a modified defibrillator that accurately predicts transthoracic impedance without delivering an actual shock. The measurement sequence was random., Results: The average measured transthoracic impedance with placement of the apex defibrillation electrode on the breast was 95 +/- 25 ohms (mean +/- SD), under the breast 84 +/- 17* ohms and lateral to the breast 83 +/- 20* ohms (asterisk indicates p < 0.01 vs. on the breast by analysis of variance). The study cohort was also classified into two groups: large breasted (brassiere size > or = 40) and small breasted (brassiere size < or = 39). The measured transthoracic impedances for the large-breasted group were 112 +/- 20 ohms for on the breast, 94 +/- 13* ohms for under the breast and 98 +/- 19* ohms for lateral to the breast. For the small breasted group, the similar transthoracic impedance measurements were 81 +/- 21, 77 +/- 16 and 71 +/- 13* ohms, respectively., Conclusions: In women, placement of the apex defibrillation electrode on the breast results in higher transthoracic impedance, which will reduce current flow. We recommend placing the apex electrode lateral to or underneath the breast.

Background & Aims: Microsatellite instability is a property of most tumors occurring in the context of hereditary nonpolyposis colon cancer. Instability also occurs in 10%-15% of apparently sporadic colorectal cancers, and it has been hypothesized that this instability may indicate a genetic predisposition to colonic cancer. This study evaluated whether there is a clinically useful association between colon cancer instability and a family history of cancer., Methods: Colon cancer cases (n = 188) from a population-based study were evaluated for microsatellite instability with 10 polymerase chain reaction primer sets. Instability results were compared with family history and other clinical and biological characteristics., Results: Microsatellite instability was found in 16.5% of tumors. It was predominantly a feature of right-sided tumors (P = 0.003) and was associated with the youngest and oldest ages at diagnosis (P = 0.01). Instability was not associated with family history of cancer, sex of the individual, or the glutathione-S-transferase mu 1 null genotype., Conclusions: Although some very small, and as yet undefined, proportion of colon cancer may be caused by inherited mutations leading to microsatellite instability, tumoral instability by itself is not a marker for familiality and should not be considered as evidence for an inherited syndrome.

Purpose: The purpose of this study was to assess risk of developing multiple primaries after a diagnosis of colon cancer and to determine the impact that having a family history of cancer has on cancer risk., Methods: Data from the Utah Cancer Registry and the Utah Population Database were used. A cohort of 2,236 first primary colon cancers were observed for the subsequent development of additional primary cancers., Results: We observed a greater than expected incidence of colon, rectal, and pancreatic cancers among the cohort. The standardized incidence ratios were 2.77 (95 percent confidence interval (CI), 2.07-3.70), 2.26 (95 percent CI, 1.34-3.81), and 2.38 (95 percent CI, 1.32-4.30), respectively. Having a family history of colon or rectal cancer did not greatly influence risk of having a multiple primary. However, there was a trend toward increased risk of pancreatic cancer (hazard rate ratios, 1.99; 95 percent CI, 0.67-5.90) and bladder cancer (hazard rate ratios, 2.35; 95 percent CI, 0.77-7.18) among patients with a family history of rectal cancer. We also observed that risk of uterine cancer in the cohort was positively associated with family history of uterine cancer, risk of breast cancer was positively associated with family history of breast cancer, and risk of prostate cancer was positively associated with family history of prostate cancer., Conclusions: People with colon cancer are at a greater risk of developing colon, rectal, and possibly pancreatic cancer. Although a family history of colon or rectal cancer did not have a large impact on developing other cancers, a family history of other primary cancers did influence risk of other cancers.

Objective: To examine sporadic cases of primary pulmonary hypertension of coancestry., Design: An epidemiologic study of families of patients with primary pulmonary hypertension., Setting: A university-affiliated referral population., Participants: Family members of 13 patients with primary pulmonary hypertension., Measurements: Family pedigrees involving grandparents, parents, siblings, and children were supplemented by genealogic records. Coefficients of kinship (Ck) were calculated for the patients with primary pulmonary hypertension who demonstrated coancestry and compared with 500 sets of controls drawn at random from genealogic records., Results: Two patients with sporadic primary pulmonary hypertension demonstrated coancestry. The great-great grandfather and great-great grandmother of one patient were the great-grandfather and great-grandmother of the other patient. No other cases of primary pulmonary hypertension were identified in these two families. The CK of the affected individuals (CK = 10.02 x 10(-5)) suggests strongly that the observed relationship did not occur by chance alone. Among 500 random sets of matched controls, only two sets yielded CK of 10.02 x 10(-5) or greater (p = 0.004). Coancestry could not be identified for the other five families of patients with sporadic primary pulmonary hypertension for whom genealogic records were available., Conclusions: The finding of coancestry in patients with sporadic primary pulmonary hypertension suggests that a genetic basis exists for some patients with apparently sporadic primary pulmonary hypertension. Familial primary pulmonary hypertension may be more common than previously recognized.

Background: The impact of family history of colon cancer on survival after diagnosis with colon cancer is generally unknown. It is possible that family history is indicative of a genetically inherited form of disease which may alter survival., Methods: The Utah Population Database was used to evaluate survival after diagnosis with colon cancer among 2236 first primary colon cancer cases. This database includes detailed information about family history and is linked to the Utah Cancer Registry to obtain tumour information., Results: Stage at diagnosis was the primary factor associated with death from all causes and from colon cancer. An older age at diagnosis, being female, and having a tumour in the ascending segment of the colon also were associated with poorer survival, although after adjusting for stage at diagnosis these associations disappeared. Having a family history of colon cancer had little impact on survival patterns although there were suggestions that men who were diagnosed at age < or = 55 were more likely to die from all causes as well as colon cancer if they had a sibling with colon cancer (hazard rate ratio [HRR] 2.50, 95% confidence interval [CI]: 1.03-6.10) relative to men > 55 without a sibling with colon cancer., Conclusions: From these data it appears that the major factor which increases survival is being diagnosed at an early stage of disease. These data also suggest that younger men who have a sibling with colon cancer may have a different form of colon cancer which increases their risk of dying.

The measurement of right atrial area was variable between different observers; however, quantitation of tricuspid regurgitation with color Doppler is a reproducible method with an acceptable error of measurement.

The Utah (United States) Population Database was used to evaluate the associations between reproductive factors and colon cancer risk and the impact that family history, age at diagnosis, and tumor site have on these associations. From the cohort of (White) women in the database, all first-primary cases of colon cancer (n = 819) and controls who had complete fertility information (n = 3,202) were examined. The majority of tumors (68.6 percent) among women diagnosed at age 64 years or less were in the distal segment of the colon, while among women 65 or older, the majority of tumors (55.7 percent) were proximal. Women diagnosed before age 65 had a lower risk of colon cancer with increasing numbers of liveborn children (odds ratio [OR] = 0.6, 95 percent confidence interval [CI] = 0.3-0.9 for women with five or more children compared with women with one or two children). A long interval between first and second births (first birth-interval) was associated with increased risk of tumors in the distal segment of the colon (OR = 1.4, CI = 1.0-2.0) and among women diagnosed before age 65 (OR = 1.6, CI = 1.0-2.5); a longer, average birth-interval was associated with increased risk of proximal tumors (OR = 1.5, CI = 1.1-2.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Our purpose was to evaluate the vasodilating responses of atherosclerotic coronary arteries using intraoperative high-frequency (12 MHz) epicardial echocardiography. We obtained continuous high-frequency epicardial echocardiographic recordings during surgery, and determined cross-sectional lumen area from 17 coronary arterial segments (12 patients). Nitroglycerin (100 to 400 micrograms/min) was administered intravenously to reduce mean (+/- SEM) arterial pressure 14 +/- 1.8 mm Hg. The cross-sectional arterial images were classified using 3 different parameters: arterial lumen area, percentage of the arterial wall circumference that was atherosclerotic (wall thickness > 0.7 mm), and presence of an eccentrically shaped arterial lumen (maximal/minimal luminal diameter > 1.5). Nine arterial segments had small (< 5.0 mm2) arterial lumens (1.7 +/- 0.40 mm2 [+/- SEM; range 0.6 to 3.9]). With nitroglycerin, the luminal area increased 0.8 +/- 0.28 mm2 (range 0 to 2.5), and 39 +/- 12.1% (range 0 to 117). The remaining 8 segments had larger (> 5.0 mm2) lumens (8.7 +/- 0.91 mm2 [range 5.0 to 11.9]). With nitroglycerin the luminal area increased 4.3 +/- 1.11 mm2 (range 1.4 to 11.4), and 51 +/- 10.2% (range 16 to 96). Seven arterial segments had eccentric lumens; mean maximal/minimal ratio was 1.8 +/- 0.08 (range 1.6 to 2.0). The area increased 39 +/- 7.3% (range 16 to 71) with nitroglycerin. In the 10 concentrically shaped lumens (maximal/minimal lumen diameters 1.3 +/- 0.04 [range 1.1 to 1.5]), nitroglycerin increased luminal area by 48 +/- 12.6% (range 0 to 117) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To estimate the relative risks and population attributable risks of ovarian cancer associated with family histories of cancer at several sites., Methods: A matched case-control analytic study (662 cases, 2647 controls), employing the Utah Population Database, a genealogy of approximately 1 million individuals linked to cancer incidence data from the Utah Cancer Registry. Family history was assessed using kinship order and a kinship-weighted familial standardized incidence ratio statistic., Results: Family histories of ovarian, uterine, breast, and pancreatic cancer were significantly associated with increased risk of ovarian cancer. The relative risk of ovarian cancer was 4.31 (95% confidence interval [CI], 2.35 to 7.90) for women with a first-degree relative with ovarian cancer, 2.12 (95% CI, 1.19 to 3.78) for women with an affected second-degree relative, and 1.48 (95% CI, 0.98 to 2.24) for women with an affected third-degree relative. The odds ratio (OR) was 2.06 (95% CI, 1.44 to 2.93) for those with the highest familial standardized incidence ratio. No age differences were observed between cases with and without a family history of ovarian cancer. There was substantial heterogeneity of family history effects by cell type. Increased parity was not protective among women with a strong family history of cancer at the sites studied (OR, 1.11; 95% CI, 0.38 to 3.26), although it was protective among women without a family history of these cancers (OR, 0.29; 95% CI, 0.11 to 0.62)., Conclusions: The risk of ovarian cancer was substantially increased among women with family histories of ovarian, uterine, pancreatic, and, to a lesser degree, breast cancer. Among women with family histories of any of these cancers, the risk of ovarian cancer is not diminished by high parity.

This paper discusses the dosimetry methodology used to estimate bone marrow dose and the results of dosimetry calculations for 6,507 subjects in an epidemiologic case-control study of leukemia among Utah residents. The estimated doses were used to determine if a higher incidence of leukemia among residents of Utah could have been attributed to exposure to radioactive fallout from above-ground nuclear weapons tests conducted at the Nevada Test Site. The objective of the dosimetry methodology was to estimate absorbed dose to active marrow specific to each case and each control subject. Data on the residence of each subject were available from records of the Church of Jesus Christ of Latter-day Saints. Deposition of fallout was determined from databases developed using historical measurements and exposure for each subject from each test was estimated using those data. Exposure was converted to dose by applying an age-dependent dose conversion factor and a factor for shielding. The median dose for all case and control subjects was 3.2 mGy. The maximum estimated mean dose for any case or control was 29 +/- 5.6 mGy (a resident of Washington County, UT). Uncertainties were estimated for each estimated dose. The results of the dosimetry calculations were applied in an epidemiological analysis.

Above ground testing of nuclear weapons at the Nevada Test Site (NTS) during the 1950s created radioactive fallout that was dispersed into the atmosphere and deposited over a large geographical area of the U.S. One area believed to have received a considerable amount of exposure to radioiodines (131I and 133I) in the fallout was southwest Utah and southeast Nevada. This paper describes the estimates of doses to the thyroid for a cohort of 3,545 subjects who were children during the atmospheric testing period. This group of children was examined for thyroid disease during 1965-1970 and again in 1985-1986. The cohort was made up of children who lived in three counties in 1965: Washington County, Utah; Lincoln County, Nevada; and Graham County, Arizona (originally thought to be an unexposed group). Pathway analysis was used in the dosimetry, considering exposures through the ingestion of milk and vegetables, inhalation of iodine during the passage of the fallout cloud, and external exposure. Specific data were obtained on diet (including sources and levels of milk and vegetables consumed, residence history, and lifestyle) by interviewing the parents or nearest living relative of subjects. The final dosimetry file for each member of the cohort contained specific doses to the thyroid glands and uncertainties (reported as geometric standard deviations, GSD) related to each dose estimate. The mean absorbed dose to the thyroid for subjects living in Washington County, Utah, was 170 mGy; for Lincoln County, Nevada, 50 mGy; and for those living in Graham County, Arizona, 13 mGy. The maximum dose to any subject was 4,610 mGy. There were 10 subjects who had doses greater than 1 Gy. The majority of uncertainty values calculated in this study were GSD values between 2.0 and 4.0. The results of the dosimetry were combined with the results of clinical examinations of the cohort to determine if a causal relationship exists between dose to thyroid from NTS generated radioactive iodines and the incidence of thyroid disease.

A method is described for estimating excess relative risks of a disease from familial factors. Beginning with population-based series of cases and controls, a cohort of each subject's relatives is formed and checked for disease against a population based registry. The disease experience of the cohort formed from each subject's relatives is summarized as a kinship-weighted familial standardized incidence ratio (FSIR). The FSIR's are used as exposure estimates in conditional linear excess relative risk models, which may be used not only to screen for significant familial disease aggregations, but also to estimate relative risks, population attributable risks, and gene-environment interactions. The method is demonstrated on 4083 breast cancer cases from Utah and a set of matched controls.

Background: Family history of colon cancer has been shown to be related to the risk of developing colon cancer. The impact that a comprehensive family history of colon or other cancers has on the risk of colon cancer has not been thoroughly studied., Purpose: The purpose of this study was to assess the risk of developing colon cancer associated with having a family history of colon, rectal, breast, ovarian, endometrial, or prostate cancer., Methods: A case-control study was conducted using data from the Utah Population Database. Case patients had first primary colon cancers (n = 2543). Three control subjects per case were individually matched to case patients on year of birth, place of birth, marital status, and sex., Results: Those case patients with the highest familial standardized incidence ratio were at an increased risk of developing colon cancer (for men, odds ratio [OR] = 2.51 and 95% confidence interval [CI] = 1.88-3.29; for women, OR = 2.90 and 95% CI = 2.17-3.82). A second- or third-degree relative with colon cancer increased risk from 25% to 52%. Risk associated with family history was greater in those patients diagnosed before age 50 (for men, OR = 3.61 and for women, OR = 7.18) than in those diagnosed at 50 or more years of age (for men, OR = 2.44 and for women, OR = 2.73). The risk associated with a family history of colon cancer was greatest for the distal segment of the colon. Women were at an increased risk of colon cancer if they had a first-degree relative with breast (OR = 1.59; 95% CI = 1.25-2.03), uterine (OR = 1.50; 95% CI = 0.99-2.26), ovarian (OR = 1.63; 95% CI = 1.41-1.89), or prostate (OR = 1.49; 95% CI = 1.21-1.82) cancer; men were at increased risk of colon cancer if they had a first-degree relative with breast (OR = 1.30; 95% CI = 1.02-1.66), uterine (OR = 1.96; 95% CI = 1.34-2.87), or ovarian (OR = 1.59; 95% CI = 0.90-2.81) cancer., Conclusions: These findings support previous observations that people with a family history of colon cancer are at increased risk of colon cancer. Those with a second- or third-degree relative with colon cancer or a first-degree relative with breast, ovarian, uterine, or prostate cancer also have an increased risk of developing colon cancer., Implications: These data support the recommendations that individuals who have a first-degree, and possibly a second- or third-degree, relative with colon cancer should have regular screening for colon cancer.

Objective: To describe methods used to computerize the diet history questionnaire developed for the Coronary Artery Risk Factor Development in Young Adult (CARDIA) study and to describe quality-control procedures used in conjunction with dietary assessment., Design: The computerized diet history is being used in a case-control study. Because of the computerized nature of the questionnaire, we developed quality-control procedures that incorporate listening to an audiotape of the interview while visually reviewing recorded data., Setting: Three centers involved in a population-based epidemiologic study of colon cancer., Subjects: Men and women between the ages of 30 and 79 years., Results: Quality-control results showed that 100% of the computerized forms would be free of errors if the data were subjected to visual review only. Probing errors, which accounted for 47.3% of all errors, were the most commonly encountered errors. In probing errors the interviewer did not probe in a nondirective manner, or the interviewer failed to verify responses that might be considered questionable., Applications: The CARDIA diet history was computerized for use in epidemiologic studies of the association between diet and disease. Review of the audiotapes of the interviews showed that most errors made in obtaining a dietary assessment were not detectable from visual review of the data. Although the quality-control procedures were developed for a computerized diet history questionnaire, they are applicable to other dietary assessment methods.

Objective: Current flow, the major determinant of defibrillation success, depends on delivered energy and transthoracic impedance. Previous experimental data suggest that transthoracic impedance is higher using "pediatric" electrode paddles compared to the larger "adult" electrode paddles. There are few data from actual shocks to support the experimental studies. The purpose of this study was to measure transthoracic impedance during actual shock delivery and to determine the optimal electrode paddle size for pediatric defibrillation and cardioversion., Methods: We prospectively evaluated all shocks of < or = 20 joules given to pediatric patients at the University of Iowa from 1988 to 1992. Data collected included energy selected by the operator, energy delivered by the defibrillator, peak current flow and transthoracic impedance. Data were analyzed by unpaired t test and linear regression., Results: Fifty-five shocks were delivered to 20 patients, age newborn to 8 years. Thirty-seven shocks were given with "pediatric" electrode paddles (surface area 21 cm2) and 18 with "adult" electrode paddles (surface area 83 cm2). Selected energy correlated well with delivered energy (r = .98, P < .0001). Delivered energy using "pediatric" electrodes did not differ from that delivered with "adult" electrodes (8.0 +/- 0.9 joules vs 10.5 +/- 1.2 joules P > .1). However transthoracic impedance was significantly higher with "pediatric" electrodes (78.1 +/- 4.4 ohms vs 54.6 +/- 2.7 ohms P < .0008), resulting in lower peak current flow through "pediatric" electrode paddles (6.2 +/- 0.5 amps vs 8.7 +/- 0.5 amps P < .002). There was no correlation between joules/kg and peak current flow (r = .26, P > .05)., Conclusion: Use of "pediatric" electrode paddles results in higher transthoracic impedance and thus lower peak current flow. In pediatric defibrillation, larger "adult" electrode paddles should be used as soon as chest size permits (approximately 10 kg). Lower transthoracic impedance results in higher current flow that facilitates cardioversion and defibrillation.

Background: A directionally changing shock electrical vector could facilitate defibrillation by depolarizing myocytes with different orientations vis-à-vis the shock field. Such a changing vector can be achieved by a new waveform for transthoracic defibrillation: overlapping sequential pulses. Our purpose was to evaluate this waveform., Methods and Results: Ventricular fibrillation was induced in closed-chest dogs. Single and overlapping truncated exponential waveform pulse shocks were then administered from self-adhesive chest electrodes. Single pulse (control) shocks were 7.5-millisecond duration, while the sequential overlapping pulse shocks, using two different pathways, consisted of two pulses, each 5.0-millisecond duration; the second pulse began 2.5 milliseconds after the start of the first pulse and ended 2.5 milliseconds after the end of the first pulse. Thus, the total duration of the sequential overlapping shock was 7.5 milliseconds. During the overlap phase (2.5 milliseconds), the electrical vector orientation is the summation of the individual vectors. Two different electrode placements and corresponding electrical vector orientations were studied: group 1 (n = 14), left lower chest to right upper chest (pulse 1), overlapped by right lower chest to left upper chest (pulse 2), with the sequence then reversed; and group 2 (n = 11), left chest to right chest (pulse 1) overlapped by dorsal (vertebral column) to ventral (sternum) (pulse 2) with the sequence then reversed. At voltages equivalent to energies of 50, 100, and 150 J, the sequential overlapping pulse shocks achieve higher success rates than the single pulse shocks: At the low energy, 50 J, single pulse shock success rates were 0% (group 2) and 14% (group 1), while the overlapping pulse shocks achieved success rates of 39% (group 2) and 55% (group 1) (P < .05). Similarly, at the highest energy tested, 150 J, single pulse shock success rates were 45% (group 2) and 61% (group 1), while the overlapping pulse shock success was 91% (group 2) and 95% (group 1) (P < .05). In a third group of dogs (n = 3), intracardiac plunge electrodes placed orthogonally in the septum showed that the orthogonal components of intracardiac voltage gradient change varied markedly during the three phases of the sequential overlapping shocks, demonstrating the changing direction of the net electrical vector as the shock proceeded. In a fourth group of dogs (n = 5), short-duration (2.5-millisecond) single pulse shocks were compared with longer 7.5-millisecond single pulse shocks and with the sequential overlapping pulse shocks, all at equivalent energies. Despite substantially higher current flow, the 2.5-millisecond-duration single pulse shocks were not more effective than 7.5-millisecond single pulse shocks, and both 2.5- and 7.5-millisecond duration single pulse shocks had markedly inferior success rates compared with the sequential overlapping pulse shocks., Conclusions: Sequential overlapping pulse shock waveforms facilitate defibrillation compared with single pulse shocks of the same total energy. This is due at least in part to the changing orientation of the electrical vector during the multiple pulse shock.

Transthoracic impedance (TTI) is a major determinant of current flow in defibrillation, and it is therefore important to understand the factors that determine TTI. Our purpose was to evaluate the effect of atrial and ventricular arrhythmias on TTI. In anesthetized, closed-chest dogs we measured TTI by means of a technique previously validated by us, which did not require administration of actual shocks. Measurements were made at baseline (sinus rhythm) and during rapid atrial pacing (atrial fibrillation), rapid ventricular pacing, and electrically induced ventricular fibrillation (VF) with respiration discontinued. TTI was unchanged by rapid atrial or ventricular pacing. When VF was induced and respiration was discontinued, TTI fell immediately from 51.6 +/- 4.3 ohms to 45.6 +/- 4.7 ohms (p < 0.01) and did not change thereafter. The drop in TTI was probably due to respiratory arrest and decreased chest size with full exhalation; when VF was induced but respiration was continued TTI did not change, whereas discontinuing respiration caused TTI to fall even if VF was not induced. We conclude that TTI is not altered by arrhythmias.

The role of free radicals in myocardial reperfusion injury remains controversial. We have developed a new method using ascorbyl free radical (AFR) as a real-time, quantitative marker of free radical generation during myocardial reperfusion. A total of 35 dogs were studied. Twelve open-chest dogs underwent either 5 minutes (n = 5) or 20 minutes (n = 7) of coronary artery occlusion and 30 minutes of reperfusion. Seven additional animals undergoing 20 minutes of coronary occlusion also received the antioxidant enzymes superoxide dismutase and catalase, beginning 10 minutes before occlusion through the end of reperfusion. Exogenous ascorbate was infused intravenously, and the concentration of AFR in the great cardiac vein was continuously measured by electron paramagnetic resonance spectroscopy. Preocclusion AFR concentration was similar in the three groups. Upon reperfusion, AFR rose significantly in each animal group (P < .05). However, the AFR rise in the 20-minute-occlusion group, 38 +/- 17%, was significantly greater than in the 5-minute-occlusion group, 27 +/- 14% (P < .002). In addition, in the animals that received superoxide dismutase and catalase, the rise in the AFR was markedly attenuated, 13 +/- 6% (P < .002). Two dogs that received ascorbate but did not undergo coronary artery occlusion/reperfusion sequences showed no change in coronary venous AFR signal, indicating the stability of the signal over time. Five dogs received ascorbate while undergoing interventions to alter coronary venous flow: intravenous saline, dobutamine, dipyridamole, and nitroglycerin. Coronary venous AFR changes were minimal despite large coronary flow alterations, indicating that the AFR signal is independent of changes in coronary venous flow.(ABSTRACT TRUNCATED AT 250 WORDS)

We present a Monte Carlo method for determining the distribution of founders' genetic contributions to descendant cohorts. The simulation of genes through known pedigrees generates the probability distributions of contributed genes in recent cohorts of descendants, their means, and their variances. Genealogical data from three populations are analyzed: the Hutterite population of North America, the island population of Sottunga from the Aland archipelago, and the large Utah Mormon population. Two applications of the Monte Carlo method are presented. First we investigate the relative opportunity for founder effect in the three populations, which have dissimilar pedigree structures and dissimilar disease gene frequencies. Second, we measure the reproductive success of population founders in terms of the number of genes they contribute to a cohort some number of generations descendant and compare the effects of polygyny versus monogamy on reproductive success. The distribution of Hutterite founder contributions describes the context for a classic founder effect. Hutterite founders have a higher probability of leaving no genes in the population (72%) than Sottunga (48%) and Mormon (48%) founders. However, founder genes that survive among Hutterite descendants do so in larger numbers on average than founder genes in the other two populations. Greater variation among monogamous Hutterite founders compared with Mormon polygynous founders demonstrates that polygyny alone does not maximize the variance in reproductive success; other population characteristics are at least as important for determining variability among individuals in their genetic contributions to a gene pool. Our findings make it difficult to appreciate the reproductive advantage of polygyny in the Mormon population. Although the expected gene contributions and their variances were larger for polygynous founders compared with other Mormons, the main effect of polygyny was to increase the probability that any polygynist left a few genes among descendants. Furthermore, only 12% of the variation in the genetic contributions of Mormon founders is explained by their number of offspring. We conclude that shallow genealogical data (from one or a few generations) provide a poor measure of long-term reproductive success.

We investigated neurohumoral profiles and transmitter and neuroenzyme markers of cardiac autonomic innervation in control (unpaced) dogs and three groups of dogs with pacing-induced heart failure (paced, paced + beta-adrenergic blockade, and paced + cardiac denervation). Left ventricular ejection fraction decreased significantly and to a comparable extent in all paced groups. Pacing increased plasma norepinephrine (NE); increases in NE were not attenuated but instead tended to be exaggerated by treatment with propranolol or cardiac denervation. Atrial hypertrophy occurred in all paced groups compared with the control group. However, atrial and right ventricular hypertrophy were not as pronounced in the paced plus cardiac denervation group as in the paced and paced plus propranolol groups. Pacing also depleted neuropeptide Y and NE from all heart chambers; propranolol treatment did not modify these local tissue changes. Pacing caused selective depletion of neuroenzymes predominantly in the left ventricle; again, propranolol did little to modify these changes. In this study of paced animals with experimentally maintained cardiac dysfunction, failure to modify noradrenergic responses with intrapericardial cardiac denervation suggests that noncardiac sources contribute predominantly to high plasma NE. Failure to modify neurohumoral, neuropeptide, and neuroenzyme responses with beta-antagonist suggests this treatment has little practical direct influence on sympathetic vasomotor activity or neuronal function in heart failure.

We examined the relationship between the survival of women with breast cancer and the gender of their first children using a genealogy-based survival analysis. The study group consisted of 2,155 parous women diagnosed in Utah (United States) with first primary breast cancers (excluding in situ tumors). We calculated hazard rate ratios (HRR) which were adjusted for stage, median survival times, and proportions surviving for three-, five-, and 10-year intervals stratified by age at diagnosis. Median survival among women diagnosed under the age of 45 was 171 months if the first child was female, but only 66 months if the first child was male (HRR = 1.66, 95 percent confidence interval = 1.07-2.57, for male children). For women diagnosed at age 45 or older, all survival times were similar, although women whose first child was male had slightly longer median survival time. These findings suggest that the gender of the first child has a strong influence on survival among women diagnosed under 45 years of age, but not among those diagnosed later in life. Gender of the first offspring may be a useful clinical indicator of prognosis and survival and may provide insights into etiologic and promotional factors for breast cancer.

Objective: To estimate individual radiation doses and current thyroid disease status for a previously identified cohort of 4818 schoolchildren potentially exposed to fallout from detonations of nuclear devices at the Nevada Test Site between 1951 and 1958., Design: Cohort analytic study., Setting: Communities in southwestern Utah, southeastern Nevada, and southeastern Arizona., Participants: Individuals who were still residing in the three-state area (n = 3122) were reexamined in 1985 and 1986, and information on the subjects' and their mothers' milk and vegetable consumption during the fallout period was obtained by telephone interview (n = 3545). After exclusions to eliminate missing data and confounding factors, 2473 subjects were available for analysis., Main Outcome Measures: Individual radiation doses to the thyroid were estimated by combining consumption data with radionuclide deposition rates provided by the US Department of Energy and a survey of milk producers. Relative risk models adjusted for age, sex, and state were fitted using maximum likelihood to period prevalence data for thyroid carcinomas, neoplasms, and nodules., Results: Doses ranged from 0 mGy to 4600 mGy, and averaged 170 mGy in Utah. There was a statistically significant excess of thyroid neoplasms (benign and malignant; n = 19), with an increase in excess relative risk of 0.7% per milligray. A relative risk for thyroid neoplasms of 3.4 was observed among 169 subjects exposed to doses greater than 400 mGy. Positive but nonsignificant dose-response slopes were found for carcinomas and nodules., Conclusions: Exposure to Nevada Test Site-generated radioiodines was associated with an excess of thyroid neoplasms. The conclusions are limited by the small number of exposed individuals and the low incidence of thyroid neoplasms.

In this study, we examine the association between having a family history of breast cancer and survival after diagnosis with breast cancer. Data for this study were from the Utah Population Database, a linked database consisting of genealogy data of Mormon pioneer families, Utah Cancer Registry data, and Vital Statistics data. We observed that women who had a mother with breast cancer were more likely to die of any cause than women without a mother with breast cancer [hazard rate ratio (HRR) = 1.36, 95% confidence limits (CL) = 1.04, 1.79], as were women with over 30 female relatives with breast cancer (HRR = 1.69, 95% CL = 1.16, 2.45). Similar findings were observed for women dying of breast cancer. Other indicators of family history were not associated with survival except within specific age groups. Women diagnosed with breast cancer at age 50 or before had poorer survival if they had a family history of breast cancer. Relative risk estimates were 1.54 (95% CL = 0.98, 2.41) for first degree relative, 1.55 (95% CL = 0.87, 2.78) for mother, and 2.65 (95% CL = 1.23, 5.74) for more than 30 female relatives with breast cancer.

Transesophageal echocardiography (TEE) improves the diagnostic accuracy of transthoracic echocardiography in the identification of potential cardiac sources of embolus. However, there are few studies of the impact of TEE on the medical management of patients with focal cerebral ischemia. The records of 52 consecutive, hospitalized patients undergoing both TEE and transthoracic echocardiography for suspected cardiac source of embolus were reviewed to determine the influence of TEE on the decision to anticoagulate patients. Of 52 patients, 39 had focal cerebral ischemia (transient ischemic attack, n = 9; acute cerebral infarction, n = 30). In 4 of these 39 patients (10%), the TEE results changed the management of anticoagulation. In 19 of 39 patients (49%), the TEE results helped confirm anticoagulation decisions, and in 16 (41%), the results had no effect on anticoagulation decisions, because of overriding clinical information. Ten of the latter 16 patients had TEE evidence for a possible source of an embolus, but were not anticoagulated; 5 of these were poor candidates for long-term anticoagulation, and the others had right-to-left shunting across a patent foramen ovale or an interatrial septal aneurysm. Clinical variables (atrial fibrillation, TEE findings and pre-TEE anticoagulation status) were considered as possible predictors of post-TEE anticoagulation status using logistic regression analysis; the strongest predictor of post-TEE anticoagulation status was pre-TEE anticoagulation status (p < 0.0005). Despite the selection of patients presumed to receive maximal benefit from TEE, this study suggests that TEE findings are not predictive of subsequent anticoagulation management. However, TEE is at least confirmatory of anticoagulation decisions in most cases.

Leukocytes have been implicated as a possible factor in the pathogenesis of postischemic contractile dysfunction, probably through the release of oxygen free radicals. Lidocaine and dextran sulfate are known to inhibit leukocyte adherence to endothelial cells in vitro and in vivo. In an acute open-chest canine model both agents were found to inhibit the augmented accumulation of indium-111-labeled leukocytes in briefly ischemic and subsequently reperfused myocardium. Pharmacologic inhibition of leukocyte accumulation by lidocaine and dextran sulfate, however, was not associated with improvement in postischemic contractile dysfunction.

We evaluated the effects of chronic rapid pacing (240 beats/min) on ventricular geometry and function and on cardiac mass in a canine model. Forty dogs were studied by two-dimensional echocardiography before and after 45 days of pacing. Compared with sham-operated control animals, the paced animals had significant increases in end-diastolic and end-systolic volume and a decrease in ejection fraction. The increase in ventricular volume was primarily the result of dilation of the short axis of the ventricular lumen, without significant changes in the long-axis dimension. Paced animals had biatrial hypertrophy but no change in ventricular or total cardiac mass.

The passage of electrical current across the chest and heart to terminate ventricular fibrillation (defibrillation) or organized supraventricular or ventricular arrhythmias (cardioversion) is effective and safe. This paper reviews the physiology, techniques, and rationale for defibrillation and cardioversion. New developments and future directions are discussed. Rapid defibrillation is the most important factor in survival of out-of-hospital ventricular fibrillation.

In coronary atherosclerosis, the arterial lumen size and shape can be markedly irregular, eccentric and variable. Traditional angiographic interpretation, emphasizing percent diameter stenosis, has been criticized as an inadequate descriptor of such diseased arteries. Computerized quantitative angiographic technologies, yielding a true lumen area measurement, may be superior. High-frequency epicardial echocardiography (HFEE) is a technique that allows on-line evaluation of coronary arterial wall and lumen at the time of cardiac surgery. It has been extensively validated and yields accurate measurements of normal and diseased coronary lumen areas. This study compares quantitative coronary angiography (QCA) estimates of lumen area to those obtained by HFEE to determine if the computerized angiographic method more accurately predicts residual luminal area than traditional angiographic percent diameter stenosis measurements. Although actual luminal morphology was quite variable, there was a good correlation between lumen areas determined by HFEE versus QCA: r = 0.85, n = 67, HFEE = 0.8 QCA - 0.1 (HFEE 4.0 +/- 0.30 mm2, mean +/- SEM range 0.3 to 14.0; QCA 5.1 +/- 0.40 mm2, range 0.7 to 11.8). Percent diameter stenosis determined from the angiograms did not correlate well with HFEE or QCA measurements of residual luminal area. Separation of "normal" arterial segments (defined as < 25% diameter stenosis) from "abnormal" segments (> 50% diameter stenosis) by angiography did not agree with lumen areas as defined by either HFEE or QCA. Better separation occurred when QCA-determined luminal areas were used to separate normal from abnormal arterial segments.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether dual-pathway sequential shocks and single-pathway biphasic shocks improved the efficacy of transthoracic defibrillation, we delivered single or sequential truncated waveform shocks of variable duration, voltage, and direction (polarity) to three groups of closed-chest dogs. Dual-pathway sequential shocks were assessed in group 1 (eight animals), biphasic shocks with a single pathway were compared in 11 dogs (group 2), and the effect of varying the duration of the biphasic shocks was assessed in group 3 (four animals). There was no improvement in success rates of the intervention shocks compared with a standard single "control" shock at any energy level. In this experimental model unidirectional or biphasic sequential shocks given over single or dual pathways were not superior to standard single-pulse transthoracic defibrillation.

Ultrasound contrast techniques are used widely as a screening test for intracardiac shunt. We performed a retrospective analysis of contrast echocardiograms in 29 consecutive patients with atrial septal defect (excluding Eisenmenger's) proved by cardiac catheterization. A positive (right-to-left atrial) ultrasound contrast effect was seen in 25 patients in whom catheterization pulmonary-to-systemic flow rate (Qp/Qs) was 2.2 +/- 0.9 (SD). Four patients had false-negative contrast echocardiography results; their Qp/Qs was 2.9 +/- 0.4 (p = 0.07). The percent left-to-right shunt was higher in the group with false-negative contrast echocardiographic results (65% +/- 4% vs 47% +/- 21%) (p = 0.05). Shunts with Qp/Qs < or = 2.0 had a sensitivity of 100%, whereas those with Qp/Qs > or = 2.1 had a sensitivity of 73%. In the four false-negative contrast echocardiographic results, three had findings of an atrial septal defect by pulsed Doppler, color Doppler, or both. Thus the presence of a large left-to-right shunt may decrease the sensitivity of the ultrasound contrast technique for the detection of an atrial septal defect. Contrast ultrasonography should be used in conjunction with Doppler and two-dimensional echocardiography criteria for diagnosis of atrial septal defect.

Although the mechanisms involved in stunning remain incompletely defined, it appears that intracellular calcium overload, sarcoplasmic reticulum dysfunction, and the generation of OFR are important components of post-ischemic myocyte dysfunction. It is likely that a variety of mechanisms, some possibly remaining to be elucidated, are operative in the pathogenesis of stunning, and that the contribution of a particular process may be influenced by the model and the method of inducing ischemia. Myocardial stunning has been shown to be prevalent in patients with diverse cardiac diseases. Small clinical trials have suggested that electrocardiography, echocardiography, and radionuclide imaging techniques may be useful in identifying patients with stunned myocardium. In patients with depressed cardiac performance due to stunning, therapy with inotropic agents may recruit the viable but injured myocardium to contract and improve cardiac output in the short term. An important issue that will be addressed over the next decade is whether aggressive therapy aimed at reducing myocardial stunning in stable patients should be attempted. Some authorities have suggested that stunning may represent an adaptive response to limit reperfusion injury, and that interfering with this response may not be beneficial in the long term. Further investigation into the cellular and molecular basis of ischemic injury should provide insight into these and other important aspects of myocardial stunning. Methods of attenuating postischemic ventricular dysfunction that appear convincing in the research laboratory may not translate to clinical benefit when applied to humans.