Non-invasive half millimetre 32 detector row computed tomography angiography accurately excludes significant stenoses in patients with advanced coronary artery disease and high calcium scores.

OBJECTIVE: To show an overall diagnostic accuracy > or = 90% for detection of > or = 50% stenoses by coronary half millimetre 32 detector row computed tomography angiography (32 x 0.5-MDCTA) in patients with advanced coronary artery disease (CAD) and a high likelihood of raised calcium scores. METHODS: ECG gated 32 x 0.5-MDCTA (32 x 0.5 mm cross sections, 0.35 x 0.35 x 0.35 mm3 isotropic voxels, 400 ms rotation) was performed after injection of iodixanol (120 ml, 320 mg/ml) in 30 consecutive patients (25 men, mean (SD) age 59 (13) years, body mass index 26.2 (4.9) kg/m2). Native arteries, including > or = 1.5 mm branches, and bypass grafts were screened for > or = 50% stenoses. Stents were excluded. Conventional coronary angiography (performed 18 (12) days before 32 x 0.5-MDCTA) was analysed by quantitative coronary angiography. RESULTS: Median Agatston calcium score was 510 (range 3-5066). Sensitivity, specificity, and positive and negative predictive values for detection of > or = 50% stenoses in native arteries were 76% (29 of 38), 94% (190 of 202), 71% (29 of 41), and 96% (190 of 199), respectively. Overall diagnostic accuracy was 91% (219 of 240). Due to the following artefacts 20% (69 of 352) of the vessels were excluded: motion, noise, and low contrast enhancement isolated or in combination (45 of 69 (65%)); image distortion by implantable cardioverter-defibrillator or pacemaker leads (18 of 69 (26%)); and blooming secondary to severe calcification (6 of 69 (9%)). CONCLUSIONS: Coronary 32 x 0.5-MDCTA accurately excludes > or = 50% stenoses in patients with advanced CAD and high calcium scores with an overall diagnostic accuracy of 91%.

Lesions in the bed nucleus of the stria terminalis disrupt corticosterone and freezing responses elicited by a contextual but not by a specific cue-conditioned fear stimulus.

The bed nucleus of the stria terminalis (BNST) is believed to be a critical relay between the central nucleus of the amygdala (CE) and the paraventricular nucleus of the hypothalamus in the control of hypothalamic-pituitary-adrenal (HPA) responses elicited by conditioned fear stimuli. If correct, lesions of CE or BNST should block expression of HPA responses elicited by either a specific conditioned fear cue or a conditioned context. To test this, rats were subjected to cued (tone) or contextual classical fear conditioning. Two days later, electrolytic or sham lesions were placed in CE or BNST. After 5 days, the rats were tested for both behavioral (freezing) and neuroendocrine (corticosterone) responses to tone or contextual cues. CE lesions attenuated conditioned freezing and corticosterone responses to both tone and context. In contrast, BNST lesions attenuated these responses to contextual but not tone stimuli. These results suggest CE is indeed an essential output of the amygdala for the expression of conditioned fear responses, including HPA responses, regardless of the nature of the conditioned stimulus. However, because lesions of BNST only affected behavioral and endocrine responses to contextual stimuli, the results do not support the notion that BNST is critical for HPA responses elicited by conditioned fear stimuli in general. Instead, the BNST may be essential specifically for contextual conditioned fear responses, including both behavioral and HPA responses, by virtue of its connections with the hippocampus, a structure essential to contextual conditioning. The results are also not consistent with the hypothesis that BNST is only involved in unconditioned aspects of fear and anxiety.

Even minimal symptoms of depression increase mortality risk after acute myocardial infarction.

Mild to moderate levels of depressive symptoms as characterized by Beck Depression Inventory (BDI) scores of > or =10 are associated with decreased survival after acute myocardial infarction (AMI). We investigated whether lower levels of depressive symptoms are also associated with increased mortality risk after AMI. We prospectively studied 285 patients with AMI who survived to discharge for evidence, at the time of hospitalization, of a DSM-IIIR mood disorder (using a structured clinical interview) and for symptoms of depression (using the BDI). The overall mortality rate at 4 months was 6.7%. Multiple logistic regression (chi-square 35.79, p < or =0.001) revealed that the independent predictors of mortality were: age > or =65 years, left ventricular ejection fraction <35%, diabetes mellitus, and any depression (DSM-IIIR mood disorder or BDI > or =10) present at the time of AMI. Among patients > or =65 years old with left ventricular ejection fraction <35%, the 4-month mortality was 12%. However, in this same group, those with any depression at the time of AMI had a 4-month mortality of 50% (relative risk 4.1, p = 0.01). Among patients aged > or =65 years, the mortality according to BDI scale grouping 0 to 3, 4 to 9, and 10+ was 2.6%, 17.1%, and 23.3%, respectively (p <0.002). Highest mortality rates were observed in patients with most severe depressive symptoms. However, compared with those without depression, higher mortality was also observed at very low levels of depressive symptoms (BDI 4 to 9) not generally considered clinically significant and below the level usually considered predictive of increased post-AMI mortality.

Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction.

BACKGROUND: Patients with depression are at greater risk of cardiac death in the first few months after a myocardial infarction (MI). This study was performed to determine whether depression affects adherence to recommendations intended to reduce the risk of cardiac events after an MI. METHODS: All consenting patients admitted to a university-affiliated teaching hospital during an 18-month period were interviewed 3 to 5 days following an acute MI using the Beck Depression Inventory to assess symptoms of depression and using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, to determine the presence of major depression and/or dysthymia. Accessible survivors (n=204; 116 men and 88 women) were interviewed by telephone 4 months later using the Medical Outcomes Study Specific Adherence Scale to measure self-reported adherence to recommendations to modify cardiac risk. RESULTS: Patients who were found in the hospital to have symptoms of at least mild to moderate depression (Beck Depression Inventory score > or =10, n=35 [17.2%]) or to have major depression and/or dysthymia (n=31 [15.2%]) reported lower adherence to a low-fat diet, regular exercise, reducing stress, and increasing social support 4 months later. Those with major depression and/or dysthymia also reported taking medications as prescribed less often than those without major depression and/or dysthymia. Diabetic patients with major depression and/or dysthymia were less likely to follow a diet for patients with diabetes than diabetic patients without depression. CONCLUSIONS: Patients with depression following an acute MI are less likely to adhere to recommended behavior and lifestyle changes intended to reduce the risk of subsequent cardiac events. This finding could explain why depression in the hospital is related to long-term prognosis in patients recovering from an MI.

Self-administration of intravenous amphetamine is predicted by individual differences in sucrose feeding in rats.

RATIONALE: Previous studies have shown that individual differences in oral sucrose consumption are predictive of the psychomotor and dopamine (DA) stimulant properties of amphetamine in rats. OBJECTIVES: The present experiment was designed to examine the relationship between sucrose feeding and the reinforcing properties of amphetamine using the intravenous (i.v.) drug self-administration paradigm. METHODS: Based on a median split of sucrose intake during a final 1-h feeding test session, male Wistar rats were designated as either low (LSF) or high sucrose feeders (HSF). Acquisition of i. v.-amphetamine self-administration across ten daily 30-min sessions was then assessed. Following acquisition, i.v. self-administration of several doses of amphetamine was similarly tested across daily 30-min sessions. RESULTS: Data from this experiment revealed augmented responding in HSF compared with LSF during acquisition of amphetamine self-administration. Correspondingly, when given access to different doses of amphetamine, responding was greater in HSF than in LSF across several doses (3 microg and 10 microg per infusion). CONCLUSIONS: These data support the notion that individual differences in oral sucrose consumption are predictive of the reinforcing properties of psychostimulant drugs.

Self-administration of intravenous amphetamine: effect of nucleus accumbens CCKB receptor activation on fixed-ratio responding.

RATIONALE: The mesolimbic dopamine (DA) system is implicated in psychostimulant drug self-administration. The neuropeptide cholecystokinin (CCK) is co-localised with DA and inhibits nucleus accumbens (NAcc) DAergic neurotransmission via CCKB receptors. OBJECTIVES: The present experiment was designed to examine the effects of intra-NAcc CCKB receptor stimulation on fixed-ratio (FR) amphetamine self-administration. METHODS: Wistar rats with intravenous catheters and NAcc cannulae were trained to self-administer amphetamine under a FR3 schedule of reinforcement. Animals performing stable self-administration were microinjected with pentagastrin and assessed during 3-h sessions. RESULTS: Intra-NAcc pentagastrin dose dependently increased amphetamine intake. CONCLUSIONS: These results are consistent with the notion that NAcc CCKB receptor activation attenuates amphetamine reward.

Estrogen replacement reverses endothelial dysfunction in postmenopausal women.

PURPOSE: To measure the effect of long-term clinical hormone replacement therapy on brachial artery vasomotor responses, and to compare these responses in premenopausal and postmenopausal women. PATIENTS AND METHODS: We studied 23 postmenopausal women, including 18 who were evaluated prior to starting clinically indicated oral hormone replacement therapy. Twelve postmenopausal women received estrogen alone, the other 6 were treated with estrogen/medroxyprogesterone combinations. Eleven premenopausal volunteers served as a comparison group. Change in brachial artery diameter in response to postischemic hyperemic flow and sublingual nitroglycerin was measured by ultrasound. RESULTS: The 18 postmenopausal subjects receiving hormone replacement showed a progressive improvement in their postischemic vasodilation. Mean (+/-SD) postischemic vasodilation was 0.4%+/-7.1% prior to estrogen replacement. There were significant increases in postischemic vasodilation of 4.8%+/-6.6% after 1 month and 8.3%+/-3.4% after 6 months of estrogen replacement. The response to nitroglycerin was similar at all time points studied. Women with the most abnormal responses to hyperemic flow at baseline demonstrated the greatest improvement after 6 months of hormone replacement therapy. Premenopausal and postmenopausal subjects differed in their response to hyperemic flow, with premenopausal women showing 5.8% vasodilatation compared with a 0.6% vasodilation in postmenopausal women (P=0.046). CONCLUSIONS: Endothelial function is abnormal in many postmenopausal women compared with premenopausal women, and in some postmenopausal women it can be enhanced by estrogen replacement therapy. This effect may increase with prolonged use.

Seasonal pattern of acute myocardial infarction in the National Registry of Myocardial Infarction.

OBJECTIVES: The purpose of this study was to determine whether the rate of hospital admission for acute myocardial infarction (AMI) varies seasonally in a large, prospective U.S. registry. BACKGROUND: Identification of specific patterns in the timing of the onset of AMI is of importance because it implies that there are triggers external to the atherosclerotic plaque. Using death certificate data, most investigators have noted a seasonal pattern to the death rate from AMI. However, it is unclear whether this observation is due to variation in the prevalence of AMI or to other factors that may alter the likelihood of a fatal outcome. METHODS: We examined the seasonal mean number of cases of AMI (adjusted for the length of days in each season) that were submitted to the National Registry of Myocardial Infarction (NRMI) by 138 high volume core hospitals over a 3-year period (December 21, 1990 through December 20, 1993) during which the number of hospitals participating in the Registry was stable. Data were analyzed using general linear modeling and analysis of variance. RESULTS: High volume core hospitals reported 83,541 cases of AMI to the Registry during the study period. Approximately 10% more such cases were entered into the Registry in winter or spring than in summer (p < 0.05). The same trends were seen in both northern and southern states, men and women, patients < 70 versus > or = 70 years of age and those with Q wave versus non-Q wave AMI. CONCLUSIONS: We conclude that there is a seasonal pattern to the reporting rate of cases of AMI in the NRMI. This observation further supports the hypothesis that acute cardiovascular events may be triggered by events that are external to the atherosclerotic plaque.

Overnight heart rate and cardiac function in patients with dual chamber pacemakers.

Animal data indicate that chronic, overnight pacing at normal evening heart rates impairs cardiac function. We examined the relationship of pacing rate and cardiac function in nine patients with dual-chamber pacemakers. We investigated two, 3-week pacing regimens (80 and 50 ppm: DDD mode) in a cross-over design. Doppler echocardiograms were performed at 1700 hours (PM) and 0600 hours (AM) at the end of each regimen. Ventricular function and preload decreased overnight (PM vs AM) with both pacing regimens. Compared to the morning values, the ratio of preejection to ejection time (PEP/ET) rose (0.43 vs 0.46), while the mean velocity of circumferential fiber shortening (Vcf) fell (1.16 cm/s vs 1.11 cm/s). Stroke volume (SV) (61 mL vs 53 mL) and ejection fraction (EF) also fell (0.56 vs 0.53) in the morning. End-diastolic volume (EDV) (94 mL vs 88 mL) decreased in the morning, as did the ratio of passive to active filling (E/A) (1.06 vs 0.96). Isovolumic relaxation time (91 ms vs 101 ms) increased overnight at both pacing rates. Systolic function decreased at 80 ppm relative to 50 ppm at both times of day. SV fell (54 mL vs 61 mL), while both EDV (92 mL vs 90 mL) end-systolic volume (ESV) increased (43 mL vs 40 mL). Contractility measured by Vcf (1.09 cm/s vs 1.18 cm/s) and PEP/ET (0.49 vs 0.41) was reduced at 80 ppm. The heart needs to rest at night by slowing its rate of contraction. Pacing at 80 ppm impairs systolic and diastolic ventricular function compared to 50 ppm. Longer term consequences of ostensibly physiological pacing rates merit inquiry, particularly in those with preexisting cardiac dysfunction.

The CCKB antagonist, L-365,260, attenuates fear-potentiated startle.

The neuropeptide cholecystokinin (CCK), via the CCKB receptor, increases behaviors associated with anxiety in laboratory animals and humans. The present experiment assessed the role of endogenous CCKB function in fear-potentiated startle, a test of "anxiety" in rats. The amplitude of the acoustic startle response is potentiated if preceded by a stimulus that has been previously paired with shock. Pretreatment with the CCKB antagonist L-365,260 (0, 0.1, 1.0, and 10.0 mg/kg, IP) did not affect baseline acoustic startle amplitudes, but dose-dependently decreased fear-potentiated startle. These results indicate that the specific attenuation of fear-potentiated startle induced by L-365,260 was not due to a general decrease in motor responsivity. The present findings are consistent with the effects of CCKB antagonists in other tests measuring anxiety in animals.

Permanent cardiac pacemakers in the elderly.

OBJECTIVE: To review (1) Changes in cardiac impulse generation, conduction, and ventricular filling in normal aging and disease; (2) Pacemaker technology and nomenclature; (3) Expert guidelines about pacemaker use; (4) Studies of pacemaker effectiveness and utilization. DESIGN: Articles were identified through a Medline search, review of articles' bibliographies, and contact with pacemaker manufacturer representatives for information on device features and costs. These articles were reviewed, and the relevant data are presented. RESULTS: Abnormalities in impulse generation and conduction are common in the elderly. Pacemaker use is higher in the elderly than in other population groups. Hemodynamic changes associated with aging include an increased contribution of atrial contraction to ventricular filling. Pacemakers, which maintain the synchrony between the atria and ventricles, may be particularly advantageous in the elderly for this reason. Rate-responsive ventricular pacemakers improve the quality of life compared with fixed rate devices in some patients over the age of 75. Dual-chamber, sequential pacemakers are more likely to reduce symptoms of pacemaker syndrome than ventricular pacemakers and probably also prolong survival and reduce risk of atrial fibrillation in certain groups of patients. However, dual chamber devices are more expensive and require more frequent follow-up. Pacemaker utilization can vary widely by region. Decisions about pacemakers require explicit tradeoffs between risk and quality of life on one hand and cost on the other. In many clinical situations, there is controversy as to whether pacemakers should be used. CONCLUSIONS: Pacemakers provide definite benefits to some patients, whereas in others, the likelihood of benefit is uncertain. More sophisticated devices may provide some additional benefit, but they are more costly. Further data is still required to define precisely which groups of patients substantially benefit from complex and expensive pacing modalities compared with simpler ones.

Increased afterload aggravates infarct expansion after acute myocardial infarction.

After acute transmural myocardial infarction, the heart may undergo major remodeling characterized by thinning and dilation of the infarct zone and overall enlargement of the heart. The effect of increased left ventricular pressure on infarct expansion and the extent to which it alters postinfarction remodeling were studied in a rat model. Rats with either aortic banding or a sham operation and a survival period of 3 weeks were further randomized to sham thoracotomy or left coronary ligation. Surviving rats were killed 7 days later and the hearts were fixed in diastole for morphologic analysis. Hearts with aortic banding had a mean peak to peak gradient of 20.7 +/- 4.9 mm Hg across the aortic band at death and a significantly thicker heart than that of the comparison group without an aortic band. Infarct size, as a percent of total left ventricular mass, at the time of death was less in the group with aortic banding, yet infarct expansion was more marked. However, when original infarct size was estimated taking into account the effects of aortic banding, scar formation, infarct expansion and infarct-induced hypertrophy, it was found to be similar in both infarct groups (45.50 +/- 4.2 versus 47.90 +/- 3.1%). Infarct expansion, as measured by cavity dilation and infarct thinning, occurred in both infarct groups but was greater in the group with aortic banding.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury.

Dehydroepiandrosterone (DHEA) is an endogenous steroid that blocks carcinogenesis, retards aging, and exerts antiproliferative properties. In vitro, it is a potent inhibitor of glucose-6-phosphate dehydrogenase, the first committed step of the pentose phosphate pathway. In man, serum levels of DHEA and its sulfate peak in early adulthood and drop markedly with age. Epidemiologic evidence indicates that low levels of DHEA or its sulfate conjugate are linked to an increased risk of developing cancer or of death from cardiovascular disease. Like cancer, atherosclerosis is a proliferative process characterized by both initiation and promotion phases. This similarity provided a framework in which to study the antiatherogenic effects of DHEA. Rabbits were randomly assigned to four groups. Two groups of rabbits received aortic endothelial injury by balloon catheter and were fed a 2% cholesterol diet for 12 wk. DHEA, 0.5%, was incorporated into the diet of one group receiving the 2% cholesterol diet and endothelial injury and also into the diet of one of the control groups. Animals were killed after 12 wk and aortas, hearts, and livers were studied. Plasma samples were analyzed for total cholesterol, VLDL, LDL, HDL, triglycerides, DHEA, and DHEA-sulfate levels. The atherogenic insult resulted in severe atherosclerosis in animals not treated with DHEA. In those receiving DHEA there was an almost 50% reduction in plaque size (P = 0.006), inversely related to the serum level of DHEA attained. Fatty infiltration of the heart and liver were also markedly reduced. These beneficial actions were not attributable to differences in body weight gain, food intake, total plasma cholesterol or distribution of cholesterol among the VLDL, LDL, or HDL fractions. The results show that high levels of plasma DHEA inhibit the development of atherosclerosis and they provide an important experimental link to the epidemiologic studies correlating low DHEA-sulfate plasma levels with an enhanced risk of cardiovascular mortality.

Cellular mechanisms of myocardial infarct expansion.

Infarct expansion is acute regional dilatation and thinning of the infarct zone. There are several possibilities for the mechanism of this alteration in cardiac shape: thinning could be caused by 1) cell rupture, 2) a reduction in the intercellular space, or 3) stretching of myocytes or 4) slippage of groups of myocytes so that less cells are distributed across the wall. To determine the relative contributions of these cellular mechanisms of wall thinning and dilatation, detailed study of transverse histological sections of rat hearts with infarct expansion was performed 1, 2, and 3 days after coronary ligation. The number of cells across the wall was determined in six regions within, adjacent to, and remote from the infarct. Cell counting was performed so that the total number of cells across the wall and the number of cells per unit length (cell density) across the wall were determined. The transmural cell count and the cell density were correlated with the wall thickness in each region. Myocyte cross-sectional areas and sarcomere lengths were also measured. The results from the infarct expansion hearts were compared with those of sham-operated control hearts that had been similarly analyzed. To ensure that mechanisms identified in the rat were applicable to human infarct expansion, five hearts from patients who died within 3 days of infarction and two hearts from patients without coronary disease were studied histologically in a similar fashion. Wall thinning occurred in all regions of the rat infarct expansion hearts compared with controls (p less than 0.0001) but, as expected, was most pronounced in the infarct zone. A decrease in the number of cells across the wall accompanied the wall thinning at each site (p less than 0.0001), and this change in cell number was highly correlated with the changes in wall thickness (r = 0.915, p less than 0.001). Cell density increased from controls only within the infarct zone (p less than 0.001) and accounted for at most 20% of the thinning in that region. The change in cell density was attributable to both cell stretch (measured by increased sarcomere length and decreased myocyte cross-sectional area) and a decrease in the intercellular space. A similar strong correlation between wall thinning and decreased number of cells across the wall was identified in the human hearts (r = 0.94, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty.

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.

Steroid administration after myocardial infarction promotes early infarct expansion. A study in the rat.

Whether steroids lead to thinner scars and larger aneurysms by delaying collagen deposition or worsening infarct expansion before significant collagen deposition begins is unknown. Rats underwent either transmural infarction by left coronary ligation or sham operation. Both infarct and sham rats were randomized to methylprednisolone 50 mg/kg i.p. X 4 or saline treatment within 24 h after operation. Sacrifice occurred before (3 d) or after (7 d) collagen deposition typically begins. Despite similar infarct size, infarct wall thickness was 1.35 +/- 0.08 mm in the saline and 0.99 +/- 0.12 mm in the methylprednisolone group (P less than 0.001) at 3 d. This decrease in wall thickness was explained by a decrease in the number of myocytes across the infarct wall (r = 0.99; P less than 0.001), suggesting that steroids promote myocyte slippage. Furthermore, methylprednisolone caused no further infarct thinning or cavity dilatation beyond 3 d. Thus, high-dose methylprednisolone given within 24 h after transmural infarction worsens infarct expansion before collagen is laid down by promoting the slippage of necrotic myocytes.

Portable intraaortic balloon counterpulsation: clinical experience and guidelines for use.

Intraaortic balloon (IAB) counterpulsation is a proven treatment for patients with refractory ischemia or cardiogenic shock; however its use has been largely limited to tertiary centers due to the difficulties and risks encountered in transporting patients with this device in place. We report our initial experience with 11 patients who underwent IAB counterpulsation at a community hospital utilizing a portable transport IAB system. All 11 patients had successful IAB insertion, resulting in prompt stabilization. Immediate transportation during uninterrupted IAB counterpulsation was successfully accomplished in each case using routine ambulance vehicles, allowing for the prompt initiation of further tertiary care. The role of portable IAB counterpulsation in the community hospital and guidelines for the implementation of this portable IAB system are outlined.