Early angiotensin converting enzyme inhibitor therapy after experimental myocardial infarction prevents left ventricular dilation by reducing infarct expansion: a possible mechanism of clinical benefits

OBJECTIVE: To examine the effects of early angiotensin-converting enzyme (ACE) inhibitor therapy after myocardial infarction on infarct expansion in an experimental rat model. BACKGROUND: ACE inhibitor therapy within 24 h of acute myocardial infarction (AMI) reduces mortality by unknown mechanism(s). METHODS: Rats underwent permanent coronary artery occlusion. A treated group received enalapril (1.9+/-0.2 mg/kg) daily in drinking water beginning 2 h after coronary artery occlusion, a time too late to reduce infarct size. Rats were sacrificed 2 days or 2 weeks after myocardial infarction. Hearts were arrested and fixed at a constant pressure, then sectioned and photographed for morphometric analysis. RESULTS: Infarcts in the control group expanded between 2 days and 2 weeks after myocardial infarction (expansion index 0.7+/-0.1 versus 2.5+/-0.4, P< 0.05). However, infarct expansion remained unchanged in the enalapril group between 2 days and 2 weeks after myocardial infarction (expansion index 0.8+/-0.1 versus 1.3+/-0.1, NS). Two weeks after myocardial infarction, the enalapril group had fewer expanded infarcts than the control group (expansion index 1.3+/-0.1 versus 2.5+/-0.4, P< 0.05). While left ventricular volume increased in the control group between 2 days and 2 weeks after myocardial infarction (0.17+/-0.01 ml versus 0.36+/-0.03 ml, P< 0.05), it remained constant in the enalapril group (0.22+/-0.02 ml versus 0.25+/-0.03 ml, NS). Two weeks after myocardial infarction, the left ventricles were larger in the control group than in the enalapril group (0.36+/-0.03 ml versus 0.25+/-0.03 ml, P< 0.05). CONCLUSIONS: Treatment with enalapril initiated 2 h after AMI prevented left ventricular dilation by limiting infarct expansion. This may explain the mechanism by which ACE inhibitor therapy started within 24 h of an AMI improves survival 5-6 weeks after infarction.     

Effect of angiotensin-converting enzyme inhibitors on the power spectrum of heart rate variability in post-myocardial infarction patients

BACKGROUND: Heart rate variability (HRV) time and frequency domain indices are strong predictors of malignant arrhythmias and sudden cardiac death. The effect of various angiotensin-converting enzyme (ACE) inhibitors on HRV in patients with acute myocardial infarction (AMI) has not been studied. METHODS: Ninety patients with uncomplicated AMI (age range 39-75 years, median 61 years) were assigned randomly to six groups of 15 patients each. They were treated with placebo or one of the following ACE inhibitors for 30 days: captopril, cilazapril, enalapril, lisinopril or quinapril. HRV was assessed 3 days after the onset of AMI (baseline), and 30 days after treatment. Fifteen patients with stable coronary artery disease and 15 healthy volunteers, age- and sex-matched with AMI patients, served as controls. RESULTS: At baseline, time and frequency domain HRV indices in the AMI groups were equally less than those in patients with stable coronary artery disease and normal volunteers. Compared with placebo, quinapril, lisinopril and captopril changed frequency domain HRV indices 30 days after initiation of treatment, indicating an increase in vagal tone, whereas enalapril and cilazapril had no significant effect on these indices. Most of the time domain HRV indices 30 days after initiation of treatment increased significantly in all patients treated with ACE inhibitors, but remained unchanged in the placebo group. Frequency domain and time domain HRV indices 30 days after treatment in the quinapril group did not differ statistically from those in patients with stable coronary artery disease, but were less than those in normal volunteers. CONCLUSIONS: Quinapril, lisinopril and captopril improved frequency domain HRV indices related to vagal tone, whereas cilazapril and enalapril had no effect on these indices. This influence of some ACE inhibitors on HRV may be beneficial in reducing the risk for sudden death in post-myocardial infarction patients.     

Brain alcohol detectability increase with repeated administration in humans: a proton spectroscopy study

BACKGROUND AND PURPOSE: There is evidence that an allelic variation in the angiotensin-converting enzyme (ACE) gene may confer an increased risk of vascular disease. The roles of the ACE insertion/deletion polymorphism and circulating ACE levels are unknown in cerebrovascular disease. METHODS: We studied an insertion/deletion polymorphism within intron 16 of the ACE gene by polymerase chain reaction and plasma ACE activity in 467 cases of stroke, the pathological type of which was established by cranial CT, and 231 control subjects. ACE genotype and activity were related to stroke type and mortality at 4 weeks and 3 months. RESULTS: No difference in genotype frequency was observed between all subjects with stroke and control subjects or between control subjects and subjects with cerebral infarction or cerebral hemorrhage. Plasma ACE activity was significantly lower in stroke patients at presentation (64.1 IU/L) than in control subjects (79.6 IU/L; P<.0001). Twenty-one patients (4.5%) with cerebral infarction died within 4 weeks and 56 patients (12%) within 3 months. These patients had significantly lower plasma ACE activity than patients who survived. There was some evidence that risk of death within 4 weeks increased with the number of D alleles (P=.02). Among survivors, plasma ACE activity showed a mean increase of 6.9 IU/L (95% confidence interval, 3.0 to 10.8) between levels at presentation and at 3 months (73.6 IU/L), the latter being similar to ACE activity in control subjects. CONCLUSIONS: Low ACE activity at sroke presentation and possession of the D allele may be associated with increased risk of early death from acute cerebral infarction.     

Predictors for the massive thrombi occurring in the right coronary artery related to acute myocardial infarction

Acute myocardial infarction (AMI) related to the right coronary artery (RCA) is associated with a lower reperfusion rate and higher reocclusion rate in the acute phase than AMI related to the left coronary artery. The greater susceptibility of the RCA to development of large thrombi makes successful reperfusion more difficult to achieve. This study investigated predictive factors for massive thrombus in the RCA before the selection of the treatment to achieve better rates of reperfusion. We classified 51 patients with AMI related to RCA into the massive (linear intraluminal radiolucency > 3 cm) thrombus group (9 patients) and the non-massive thrombus group (42 patients). 1) History: Patients in the massive thrombus group had a greater incidence of hypertension than the non-massive thrombus group, with more left ventricular hypertrophy (p < 0.05). There were no significant differences in other coronary risk factors. 2) RCA morphology: The maximum RCA diameter was significantly greater in the massive thrombus group than that in the non-massive thrombus group [proximal to the right ventricular branch, 4.2 vs 3.2 mm (median); distal to the right ventricular branch, 4.2 vs 3.4 mm, p < 0.05]. 3) Conditions of onset: The elapsed time was significantly longer in the massive thrombus group (15 hours) than that in the non-massive thrombus group (2.5 hours, p < 0.05). More massive thrombus cases were observed in summer (p < 0.05), but there was no evident correlation between massive thrombus formation and the onset time of day, weather, Hct and coagulation factor at the onset, left ventricular ejection fraction or left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Predischarge two-dimensional echocardiographic evaluation of left ventricular thrombosis after acute myocardial infarction in the GISSI-3 study

Left ventricular (LV) thrombosis can be found in patients with acute myocardial infarction (AMI). No wide multicenter trial on AMI has provided information about LV thrombosis until now. The protocol of the GISSI-3 study included the search for the presence of LV thrombosis in patients from 200 coronary care units that did not specifically focus on LV thrombosis. We examined the GISSI-3 database results related to 8,326 patients at low to medium risk for LV thrombi in which a predischarge echocardiogram (9 +/- 5 days) was available. LV thrombosis was found in 427 patients (5.1%): 292 of 2,544 patients (11.5%) with anterior AMI and in 135 of 5,782 patients (2.3%) with AMI in other sites (p <0.0001). The incidence of LV thrombosis was higher in patients with ejection fraction < or = 40% (151 of 1,432 [10.5%] vs 276 of 6,894 [4%]; p <0.0001) both in the total population and in the subgroup with anterior AMI (106 of 597 [17.8%] vs 186 of 1,947 [9.6%]; p <0.0001). Multivariate analysis showed that only the Killip class > I and early intravenous beta-blocker administration were independently associated with higher LV thrombosis risk in the subgroup of patients with anterior AMI (odds ratio 1.75, 95% confidence interval 1.28 to 2.39; odds ratio 1.32, 95% confidence interval 1.02 to 1.72, respectively). In patients with anterior AMI, oral beta-blocker therapy given or not given after early intravenous beta-blocker administration does not influence the occurrence of LV thrombosis. The rate of LV thrombosis was similar in patients treated or not treated with nitrates and lisinopril both in the total population and in patients with anterior and nonanterior AMI. In conclusion, in the GISSI-3 population at low to medium risk for LV thrombi, the highest rate of occurrence of LV thrombosis was found among patients with anterior AMI and an ejection fraction < 40%. Killip class > I and the early intravenous beta-blocker administration were the only variables independently associated with a higher predischarge incidence of LV thrombosis after anterior AMI.     

Angiotensin-converting enzyme DD genotype and cardiovascular disease in heterozygous familial hypercholesterolemia

BACKGROUND: Controversy exists as to whether the deletion/deletion genotype (DD) of the ACE gene polymorphism increases the risk of myocardial infarction (MI). Studies have suggested that the ACE DD genotype is associated with increased plaque instability. We hypothesized that the ACE DD genotype may increase the risk of myocardial infarction and coronary heart disease (CHD) in patients with heterozygous familial hypercholesterolemia (FH) or familial defective apolipoprotein B-100 (FDB) who, as a group, are at high risk of having lipid-rich plaques in their coronary arteries. METHODS AND RESULTS: We determined the ACE genotypes and incidence of MI or surgical intervention for CHD in 213 adult patients with heterozygous FH or FDB. The incidence of MI in 35 male patients who carried the ACE DD genotype was 2.5 times that observed in male patients with the II or DI genotypes, and the incidence of CHD in male patients with the DD genotype was 2.2 times higher than in those who had ACE DI+II. The potential effects of ACE genotype on CHD could not be directly compared in female patients because of a disparity in the smoking history of the genotypic groups. From logistic regression analysis, the estimated odds ratio associated with the ACE DD genotype was 2.57 for MI and 2.21 for CHD adjusted for age, sex, and smoking history. CONCLUSIONS: The ACE DD genotype is associated with an increased risk of MI and CHD in patients with heterozygous FH or FDB. Determination of the ACE genotype in asymptomatic FH and FDB patients provides an additional means to identify those patients at greatest risk for the premature development of CHD.     

Effect of early enalapril therapy on left ventricular function and structure in acute myocardial infarction

Infarct expansion starts within hours to days after transmural myocardial injury. Previous echocardiographic and left ventriculographic studies demonstrated that angiotensin-converting enzyme (ACE) inhibitor therapy limits left ventricular dilatation, particularly in patients with anterior wall acute myocardial infarction (AMI) or impaired left ventricular function. Forty-three patients with an acute Q-wave AMI were randomized within 24 hours of symptom onset to intravenous enalaprilat (1 mg) or placebo. Patients were then given corresponding oral therapy and followed for 1 month. Predrug and 1-month gated blood pool scans were obtained in 32 patients to evaluate changes in cardiac volumes and ejection fraction. Twenty-three patients underwent magnetic resonance imaging at 1 month to evaluate left ventricular infarct expansion. Blood pressure decreased at 6 hours but returned to baseline in both groups after 1 month of therapy. The change in cardiac volumes from baseline to 1 month differed between the placebo (end-diastolic volume +16 +/- 5 ml, end-systolic volume +8 +/- 6 ml), and enalapril (end-diastolic volume -8 +/- 9 ml and end-systolic volume -14 +/- 7 ml) groups (p < 0.05 vs placebo). Global and infarct zone ejection fractions improved significantly at 1 month in the enalapril group (+6 +/- 3% and 19 +/- 5%, respectively) but did not change over 1 month in the placebo group. Infarct segment length and infarct expansion index by magnetic resonance imaging were significantly less in those treated with enalapril, suggesting less infarct expansion in this group. Thus, early administration of enalaprilat to patients presenting with a first Q-wave AMI prevents cardiac dilatation and infarct expansion.     

Myocardial infarct and diabetes mellitus: incidence, management and prognosis

The authors analyse the data of the Myocardial and Diabetes Register, where 2436 diabetic patients (pts) and 1448 pts with acute myocardial infarction (AMI) were registered between 1st of January, 1992 and 31st of December 1994. In the history of diabetic patients previous AMI was present in 14.4% of the cases. The 21.6% of the AMI pts had diabetes mellitus as well. According to the type of diabetes (IDDM and NIDDM) the prevalence of AMI in the history of the registered persons was significantly different: among pts with NIDDM the previous AMI was found 14.8% of the pts and only 2% of pts with IDDM (p = 0.012). The clinical picture of AMI was also different of AMI pts with and without diabetes: chest pain suggesting AMI was present 10.9% of pts with proved AMI and diabetes mellitus, and 86.2% of pts with AMI without diabetes (p < 0.0001). The Streptokinase treatment was more common among AMI pts without diabetes (18.2% versus 12.5% p = 0.022). The hospital lethality was significantly higher among AMI pts with diabetes (42.8% versus 29.4% (p < 0.0001). The poorer prognosis was independent of age.     

Endothelin and big endothelin in coronary heart disease and acute coronary syndromes

Endothelin (ET), the most potent endogenous vasoconstrictor with mitogenic potency, is generated from its precursor big-endothelin (BET) in a proteolytic process and discussed as a pathogenetic factor in coronary artery disease and in the acute coronary syndromes. Several studies documented elevated plasma endothelin concentrations in acute myocardial infarction, but conflicting results were reported in patients with stable and unstable angina. Only few studies determined big endothelin, although it half-life and plasma concentrations are higher in comparison to endothelin. ET and BET levels (Radioimmunoassay, Biomedica GmbH, Vienna) were determined in patients with stable angina (SAP, n = 20), unstable angina (IAP, n = 12), acute myocardial infarction (AMI, n = 12) and healthy subjects (NP, n = 11). The concentrations of ET and BET (median (minimum-maximum) in fmol/ml) of the patients with stable angina (SAP: ET 0.7 (0.3-1.1); BET 1.7 (0.7-2.9)), unstable angina (IAP: ET 1.0(0.5-1.7); BET 2.5 (1.3-4.1)) and acute myocardial infarction (AMI: ET 1.2 (0.6-2.3); BET 3.6 (3.2-5.3)) showed a significant difference compared to controls (NP: ET 0.5 (0.4-0.7); BET 1.4 (1.1-1.7)) (SAP vs. NP: ET p < 0.01; BET p < 0.05; IAP and AMI vs. NP: ET and BET p < 0.001). Also, the concentrations of the peptides differed significantly dependent on the clinical severity of coronary artery disease (AMI vs. SAP: ET and BET p < 0.001; AMI vs. IAP: BET p < 0.05; IAP vs. SAP: ET p < 0.05; BET p < 0.01). Twelve of 15 patients with big endothelin concentrations over 3 fmol/ml suffered acute myocardial infarction. Seven of 12 patients with AMI showed elevated ET and BET concentrations before the increase of creatinecinase. There was no correlation between number of risk factors per patient, cholesterin and subfractions, severity of CAD classified in one-two-three-vessel disease or coronary score according to modified criteria of the American Heart Association (AHA). We conclude that in patients with coronary artery disease endothelin and big endothelin levels are elevated and related to the clinical and not to the morphological severity of coronary artery disease. Big endothelin is the more sensitive parameter in comparison to endothelin and indicates a severe course of myocardial ischemia in patients with unstable angina. The development of assays with the possibility of a quick determination of the peptides may be valuable for risk stratification of acute coronary events.     

Influence of a history of arterial hypertension and pretreatment blood pressure on the effect of angiotensin converting enzyme inhibition after acute myocardial infarction. Trandolapril Cardiac Evaluation Study

OBJECTIVE: To evaluate the influence of a history of arterial hypertension and the level of pretreatment blood pressure on the efficacy of the angiotensin converting enzyme (ACE) inhibitor trandolapril on mortality and morbidity in patients with acute myocardial infarction (AMI) and left ventricular dysfunction. METHODS: Data from the Trandolapril Cardiac Event study, in which 1749 patients with an enzyme verified AMI and echocardiographic evidence of left ventricular dysfunction were randomized in a double-blind manner to treatment with trandolapril or placebo, were retrospectively analysed. Follow up time was 24-50 months (mean 26 months). RESULTS: Four hundred patients (23%) had a history of arterial hypertension. A total of 173 (43%) patients with a history of hypertension died during follow up versus 500 (37%) patients in the normotensive group. Treatment with trandolapril in the hypertensive individuals was associated with a reduction in the relative risk of death to 0.59 (95% confidence interval 0.44-0.80), versus 0.85 (0.72-1.02) in the normotensive individuals. The significant reduction in mortality in hypertensive individuals persisted after multivariate analysis controlling for a broad spectrum of potential confounders. Also, benefit from ACE inhibition increased with increasing blood pressure at the time of randomization. Significant interactions between benefit from ACE inhibition and hypertension history, and systolic and diastolic blood pressure were found. CONCLUSION: ACE inhibition after AMI complicated by left ventricular dysfunction may be of particular importance in patients with a history of arterial hypertension or a relatively high pretreatment blood pressure. However, further investigations are necessary to establish the clinical impact of these results.     

Angiotensin-converting enzyme and angiotensinogen gene polymorphisms and heart rate variability in twins

Decreased heart rate variability (HRV) is associated with congestive heart failure, post-myocardial infarction, ventricular arrhythmias, sudden cardiac death, and advancing age. A deletion/insertion polymorphism in the angiotensin-converting enzyme (ACE) gene and a substitution (M235T) in the angiotensinogen gene have been associated with risk for heart disease. The aim of this study was to determine the heritability of HRV and related parameters in monozygotic and dizygotic twins and to assess the influence of ACE and angiotensinogen polymorphisms. We studied 95 MZ pairs and 46 DZ pairs. We measured HRV and related parameters, ACE and angiotensinogen levels, plasma norepinephrine, ACE, and angiotensinogen genotypes. We found that HRV and related parameters were significantly influenced by genetic variability, although nonshared genetic effects were also important. Angiotensinogen and plasma norepinephrine were generally correlated with decreased HRV, whereas ACE was correlated with perturbances of normal rhythmic HRV. Nevertheless, the DD ACE genotype was associated with increased HRV (p <0.05), whereas angiotensinogen polymorphisms had no effect. We conclude that HRV and related parameters are in part heritable. Interestingly, the DD ACE genotype is associated with increased HRV.     

Increased levels of erythropoietin in the initial phase of acute myocardial infarction

BACKGROUND: It's know that cardiopulmonary function affects the kidney perfusion and that erythropoietin (EPO) release depends on it. We want to determine the plasma level of EPO in the acute phase of myocardial infarction (AMI). SUBJECTS AND METHODS: A transversal trial was carried out in 37 male patients with AMI aged between 31 and 84. We studied the following variables: cardiovascular risk factors, time lapse from beginning of symptoms until hospital arrival, transcutaneous oxygen saturation (ST02) and EPO plasma levels. 16 healthy males were used as control group. RESULTS: Patients with AMI have different EPO levels than control group (25/37 vs 0/16) (18.90 +/- 8.43 mUI/ml vs 9.70 +/- 3.48 mUI/ml respectively p < 0.001). Hyperintense patients have higher EPO levels than normotense ones (18.53 +/- 8.28 mUI/ml vs 12.88 +/- 7.29 mUI/ml p < 0.05). Hypercholesterolemic patients have higher EPO level than normocholesterolemic ones (19 +/- 8.88 mUI/ml vs 12.40 +/- 6.75 mUI/ml p < 0.01). There were no difference between smokers and no smokers. We didn't find correlation between time lapse and EPO levels. CONCLUSION: The trial remarks EPO levels increase during the initial phase of AMI and it is higher in hypertensive and hypercholesterolemic patients.     

Heparinized saline or normal saline as a flush solution in intermittent intravenous lines in infants and children

Physical exertions are related to sudden cardiac death following acute myocardial infarction (AMI). Abnormalities in the autonomic modulation during exercise were noted in animals with AMI that were susceptible to potentially lethal arrhythmias. This study was done to evaluate the changes in the autonomic activity during exercise and recovery in AMI patients with good exercise capacity, using spectral analysis of R-R intervals of electrocardiogram (ECG). Symptom-limited treadmill exercise test was done on 17 patients of AMI with mild heart failure (in 7-10 days after the attack) and 21 healthy controls. The exercise was divided into 7 stages; rest, early exercise, mid-exercise, peak exercise, early recovery, mid-recovery, and late recovery. Power spectral analysis of R-R intervals of ECG was performed for each stage. Low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) powers, and their ratio were obtained. These parameters were observed throughout the stages in both groups. The trend of their changes during exercise and recovery was essentially the same for both groups; high and low frequency powers progressively decreased during exercise and abruptly increased during early recovery, but did not return to the values at those of rest until 9 minutes into the recovery. When the parameters were compared between the groups, there was a significantly greater decrease of high frequency power during the early exercise (p < 0.05), and a higher ratio of low to high frequency power during the early recovery (p < 0.05) in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hospital mortality in women and men with acute cardiac ischemia: a prospective multicenter study

OBJECTIVES: This study sought to determine gender differences in hospital mortality in patients with acute cardiac ischemia. BACKGROUND: It is unclear why women experience higher mortality from acute myocardial infarction (AMI) than men and whether this applies to all patients with acute ischemia. METHODS: We analyzed data from a prospective multicenter study involving patients presenting to the emergency department (ED) with symptoms suggestive of acute ischemia. RESULTS: Of 10,783 patients, 5,221 (48.4%) were women. Mean age was 60.5 years for women and 56.9 for men (p < 0.001). Women had more hypertension (54.6% vs. 45.9%, p < 0.001) and diabetes (23.3% vs. 17.0%, p < 0.001) than men but fewer previous AMIs (21.1% vs. 28.9%, p < 0.001). Acute ischemia was confirmed in 1,090 women (20.8%) and 1,451 men (26.1%, p < 0.001), including AMI in 322 women (6.2%) and 572 men (10.3%, p < 0.001). Women with an AMI were in a higher Killip class than men: class I in 60.3% versus 72.2%, class II in 19.3% versus 16%, class III in 15.5% versus 8.7% and class IV in 5% versus 3.1%, respectively (p = 0.001). There was no significant difference in mortality from acute ischemia between genders (4.0% vs. 3.5%, p = 0.6), but there was a trend for higher AMI mortality in women (10.3% vs. 7.4%, p = 0.1). After controlling for age, diabetes, heart failure and presenting blood pressure, gender did not predict mortality from acute ischemia (odds ratio 0.9, 95% confidence interval 0.5 to 1.4, p = 0.5). CONCLUSIONS: Among patients presenting to the ED with acute cardiac ischemia, gender does not appear to be an independent predictor of hospital mortality. The trend for higher mortality in women from AMI can be explained by their older age, greater frequency of diabetes and higher Killip class on presentation.     

Two genes in the rat homologous to human NKG2

OBJECTIVES: The purpose of this study was to investigate the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genotype and endothelial cell dysfunction or hypercoagulable state in elderly hypertensive patients. BACKGROUND: Angiotensin-converting enzyme (ACE) insertion/ deletion (I/D) polymorphism was recently reported to be associated with various cardiovascular diseases. However, the precise mechanism of this association remains unknown, and some confounding factors might also affect the association. Endothelial cell dysfunction and coagulation activation play important roles in both the atherosclerotic process and the onset of cardiovascular events. METHODS: We identified the ACE I/D genotype and measured the plasma levels of markers of endothelial cell damage (von Willebrand factor [vWF] and thrombomodulin) and of coagulation activation (prothrombin fragment F1 + 2 [F1 + 2]) in 318 asymptomatic elderly patients with hypertension, aged 59-93 years. RESULTS: The vWF level was significantly higher in those with the DD genotype (n = 54) than in those with the II genotype (n = 131, p < 0.0001) or with the ID genotype (n = 133, p < 0.0001). The TM levels were also higher in patients with the ID genotype (p < 0.005) and the DD genotype (p < 0.01) than in those with the II genotype. There were no differences in F1 + 2 level among the groups. Positive correlations of systolic blood pressure with levels of both vWF and thrombomodulin were found predominantly in patients with the II genotype (both p < 0.001), but no correlation was noted in those with the DD genotype. CONCLUSIONS: Considering the increased plasma levels of both endothelial cell-derived markers in the hypertensive patients with ACE DD genotype, we speculate that the ACE D allele is a risk factor for the development of hypertensive cardiovascular disease associated with endothelial cell damage.     

Bone lesions of multiple myeloma in three dogs

In 41 survivors of acute myocardial infarction (AMI) a prospective study was performed in 2 sequential phases. In phase 1, the role of baroreflex sensitivity and heart rate variability as predictors of inducible and spontaneous sustained ventricular tachyarrhythmias was evaluated. In phase 2, the effects of transdermal scopolamine on baroreflex sensitivity, spectral and nonspectral measures of heart rate variability were investigated. At a mean follow-up of 10 +/- 3 months after AMI, 5 of 41 patients (12%) developed a late arrhythmic event. Of these, all (100%) had inducibility of sustained monomorphic ventricular tachycardia at programmed stimulation compared with 3 of 36 patients (8%) without events (p < 0.0001). At multivariate analysis, baroreflex sensitivity had the strongest relation to both inducibility of sustained monomorphic ventricular tachycardia (p < 0.0001) and occurrence of arrhythmic events (p < 0.0001). Of 41 patients, 28 (68%) consented to undergo phase 2 of the investigation. Baroreflex sensitivity significantly (p < 0.00001) increased after transdermal scopolamine as well as heart rate variability indexes. Of these, the mean of SDs of normal RR intervals for 5-minute segments (p < 0.0001) and the total power (p < 0.0001) had the most significant improvement after scopolamine. The present investigation confirms that assessment of autonomic function is an essential part of arrhythmic risk evaluation after AMI. Transdermal scopolamine, administered to survivors of a recent AMI, reverses the autonomic indexes that independently predict arrhythmic event occurrence. On the basis of these data, transdermal scopolamine could be a potential useful tool in the prophylaxis of life-threatening ventricular arrhythmias after AMI.     

Prognostic value of Doppler transmitral flow velocity patterns in acute myocardial infarction

Doppler transmitral flow patterns are partially dependent on age. We investigated the correlations between the age-adjusted transmitral flow patterns, hemodynamic indexes, and the coronary and clinical outcome in 206 patients with acute myocardial infarction (AMI) and 102 normal control subjects. The peak flow velocity at atrial contraction was significantly lower in 50 of the 206 patients (24%) (low-A group) than in the 102 normal controls. Pulmonary capillary wedge pressure was significantly higher in the low-A group than in the remaining 156 patients with AMI (20 +/- 7 vs 11 +/- 5 mm Hg, p <0.001), and the cardiac index and left ventricular ejection fraction were significantly lower (2.2 +/- 0.6 vs 2.9 +/- 0.7 L/min/m2, p <0.001; 38 +/- 15% vs 52 +/- 13%, p <0.001). The incidence of cardiogenic shock was significantly higher in the low-A group than in the other patients with AMI (42% vs 19%, p <0.001). Regression analysis demonstrated a significant association between decreased atrial filling velocity and increased in-hospital mortality as well as the incidence of heart failure in AMI (p <0.001). The 5-year mortality rate was also significantly higher in the low-A group (p <0.001). The age-adjusted transmitral flow pattern in AMI can identify patients with left ventricular dysfunction, which can lead to a poor prognosis.     

Activity and cleavage site specificity of an anti-HIV-1 hairpin ribozyme in human T cells

The DD genotype is a polymorphism of the angiotensin-converting enzyme (ACE) gene, and is associated with a significantly increased risk of myocardial infarction. As endothelial dysfunction is an important event in both early atherogenesis and late atherosclerosis, we hypothesised that the adverse effect associated with the ACE/DD genotype might be mediated via endothelial damage. Using high resolution ultrasound, we studied the brachial arteries of 184 subjects aged 15-73 (mean 38 +/- 14) years, who were all normotensive, non-diabetic lifelong non-smokers. Arterial diameter was measured at rest, during reactive hyperaemia (with flow increase causing endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN, an endothelium-independent vasodilator). The ACE genotype was determined in each case by DNA amplification; 49/184(27%) had DD, 89 (48%) had ID and 46 (25%) had II genotype. Flow-mediated dilation (FMD) was 8.5% +/- 3.9% in the DD, 7.8% +/- 4.1% in the ID and 7.8% +/- 4.1% in the II subjects (P = NS). GTN-induced dilation was also similar in the 3 groups. On multivariate analysis, endothelium-dependent dilation was inversely related to age (r = -0.33, P < 0.001), vessel size (r = -0.41, P < 0.001) but not ACE genotype (r = 0.002, P = 0.97). The ACE genotype is unrelated to endothelium-dependent dilation in the systemic arteries of clinically well adults. This suggests that the risk associated with this polymorphism may be mediated by other mechanisms.     

Angiotensin I-converting enzyme insertion/deletion polymorphism: clinical implications

Since the identification of an Insertion/Deletion polymorphism in the ACE gene, numerous studies have evaluated the potential risk of the DD genotype in cardiovascular disease and hypertension. The report of many conflicting publications reveals a strong need for reviewing the most important data. There is evidence of the absence of an association between the ACE polymorphism and hypertension in Caucasians. In blacks a positive association between the D allele and high blood pressure was seen, Japanese studies show discrepant results. Several studies showed no association between the ACE polymorphism and the risk of myocardial infarction. However, in certain subpopulations, such as low risk patients or coronary care unit patients, an increased risk of myocardial infarction in DD type is present, and a meta-analysis supports this proposition. Because of conflicting data, the potential association between the ACE polymorphism and coronary artery disease, cerebrovascular disease, left ventricular hypertrophy, hypertrophic and idiopathic dilated cardiomyopathy, carotid artery disease and diabetic and immunoglobin A nephropathy, remains inconclusive.