Lack of relation between venous plasma total catecholamine concentrations and ventricular arrhythmias after acute myocardial infarction.

Electrocardiographic tracings were recorded continuously to monitor ventricular tachycardia and R-on-T and R-on-apex-T ventricular premature beats, and repeated estimations of venous plasma total catecholamine concentrations were carried out in 26 patients admitted to a coronary care unit with acute myocardial infarction. No relation existed between the increased catecholamine concentrations found in these patients and the incidence of ventricular arrhythmias occurring six to 48 hours after the onset of symptoms.     

Reduction of ventricular arrhythmias by early intravenous atenolol in suspected acute myocardial infarction.

The effect of intravenous atenolol on ventricular arrhythmias in acute myocardial infarction was assessed in 182 patients admitted within 12 hours of the onset of chest pain. Ninety-five patients were randomised to receive 5 mg intravenous atenolol followed immediately by 50 mg by mouth and 50 mg 12 hours later, then 100 mg daily for 10 days; 87 patients served as controls. The treated patients had significantly fewer ventricular extrasystoles; 58 control patients (67%) had R-on-T extrasystoles compared with only 25 treated patients (26%) (2p less than 0.0001); repetitive ventricular arrhythmias were detected in 64 control patients (74%) and 55 treated patients (58%) (2p less than 0.05). Heart rate was significantly reduced from 77 +/- 1 beats/min at entry to 65 +/- 1 beats/min (2p less than 0.001) in the first hour after intravenous atenolol, and in addition the rate was significantly different from that in the control group. There was no difference in the incidence of heart failure, but fewer patients in the treated group received other antiarrhythmic agents or digoxin. These results show that early intravenous atenolol prevents ventricular arrhythmias in suspected acute myocardial infarction.     

The effect of bretylium tosylate on ventricular arrhythmias in patients with acute myocardial infarction]

Sixty three patients with the acute myocardial infarction, aged between 34 and 85 years, admitted to the Intensive Cardiological Care Unit during the first 12 hours following the infarction were randomly divided into two groups. Patients of group I (20 subjects) were treated with nitroglycerin and additional intravenous infusions of bretylium tosylate in the dose of 5 mg/kg administered every 6 hours for 48-72 hours. Patients of group II (33 subjects) were mainly treated with intravenous nitroglycerin. A type and incidence of the ventricular arrhythmias, conduction disorders in AV node, and hemodynamic complications were analysed during the first 72 hours. It was found that bretylium tosylate reduces the incidence of ventricular arrhythmias accompanying myocardial infarction but after 2-3 hours following its administration (p < 0.05). Therefore, bretylium tosylate should be administrated to patients with the acute myocardial infarction in combination with other rapidly acting anti-arrhythmic drug. Bretylium tosylate increases also the effectiveness of electric defibrillation in patients with ventricular fibrillation or ventricular tachyarrhythmia. No evidence of the effectiveness of bretylium tosylate on atrio-ventricular conduction and hemodynamic complications of myocardial infarction was found.     

Losartan and acute myocardial infarction in insulin-resistant Zucker fatty rats: reduced ventricular arrhythmias and improved survival

Insulin resistance (IR) and diabetes increase the risk of acute myocardial infarction (MI). Angiotensin receptor blockers (ARBs) have been shown to reduce the risk of cardiovascular events in patients with hypertension and diabetes, and to be beneficial after a large MI. Whether pretreatment with ARBs is beneficial in acute MI is unknown. We evaluated whether pre-, peri-, and post-MI treatment with the ARB losartan improved the outcome in the IR Zucker fatty rat (ZFR). ZFR (n=264) received either losartan (3 mg/kg daily) or vehicle for 7 d prior to MI. Early (24 h) protocol (n=31): ventricular arrhythmias were evaluated post-MI using continuous ambulatory ECG monitoring. Late (38 d) protocol (n=233): losartan was increased to 10 mg/kg daily 10 d post-MI and to 30 mg/kg daily 20 d post-MI. Blood glucose, cardiac hemodynamics and remodeling, GLUT-4, fetal gene expression, and survival were evaluated. In large-MI rats, losartan improved early survival (43% vs. 27% in controls, p=0.01) and late survival (23% vs.15% in controls, p=0.02). Improved early survival was associated with a reduction in ventricular arrhythmias. Losartan reduced pulmonary congestion, cardiac hypertrophy, and fetal gene expression in the absence of statistically significant changes in ventricular dilatation and hemodynamics. Blood glucose and cardiac GLUT-4 expression did not change with losartan. In IR ZFR, losartan improves post-MI survival, likely as a result of an early reduction in ventricular arrhythmias. There was also an associated reduction in pulmonary congestion, hypertrophy, and fetal gene expression.     

Risk of death and recurrent ventricular arrhythmias in survivors of cardiac arrest concurrent with acute myocardial infarction

Aims

Cardiac arrest (CA) is an indication for defibrillator (ICD) implantation unless it occurs in the context of an acute myocardial infarction (AMI). We investigated the ventricular arrhythmia (VA)-free survival of patients resuscitated from CA in the setting of AMI.

Methods

We reviewed a database of 1600 AMI and CA survivors from which 48 patients were identified as having concurrent CA and AMI (CA+AMI group). Those patients were matched by age, gender, race, and left ventricular ejection fraction (LVEF) to 96 patients with AMI but no CA (AMI group) and 48 patients with CA but no AMI (CA group).

Results

Patients and controls were followed for 3.9±3.2 years. Patients in the 3 groups had similar baseline characteristics (age 63±14 yrs, 78% men, 98% white, 53% with CAD, LVEF 33±14%). The 5-year VA-free survival was 67%, 92%, and 80% for the CA+AMI, AMI, and CA groups, respectively, p<0.001.

Conclusion

Patients with concurrent CA and AMI are at high risk of recurrent VA, with VA-free survival rates significantly worse than those of patients with AMI but no CA, and comparable to those of patients with CA outside the context of an AMI. Accordingly, these patients should be considered for ICD implantation.     

Thrombin activity throughout the acute phase of acute ST-elevation myocardial infarction and the relation to outcome

Background: Thrombin and plasmin play a central role in ongoing thrombosis and platelet activation in patients with acute ST-elevation myocardial infarction (STEMI). Data of thrombin and plasmin activity in the early course of STEMI and the relation to outcome are scarce.

Methods: We included 68 consecutive patients (53 male, 59?±?11.4 years) with STEMI who underwent acute catheter-based reperfusion therapy within the first 12?h after onset of symptoms. Blood samples were taken at admission and after 4, 8, 12 and 24?h. Thrombin activity and generation was measured by changes in the thrombin/antithrombin-III complex (TAT) and prothrombin fragment (F1.2); plasmin was measured by changes in the plasmin-α₂/antiplasmin complex (PAP). A follow-up with respect to the combined primary endpoint consisting of death, acute myocardial infarction or urgent need for revascularization up to 6 weeks post-discharge was carried out.

Results: TAT values showed no significant change over time in patients with and without the primary endpoint but there was a borderline difference between these groups at 4?h after admission (event group 9.0 vs no event group 4.7?μg l^?1, p?=?0.057). F1.2 values were different between groups only after 24?h (event group 1.5 vs no event group 0.9?nmol l^?1, p?=?0.028) and did not differ in serial sampling of 24?h. PAP values were higher in patients with events after 4 and 8?h and declined over time in the group without events (p?<0.001). Odds ratios (OR) with respect to the primary endpoint were highest for TAT?>4.8?μg l^?1 at 0?h and TAT?>8.4?μg?l^?1 at 4?h (OR 7.1, 95% confidence interval (CI) 1.5–34, p?=?0.015 and OR 5.5, 95% CI 1.5–20.0, p?=?0.01, respectively). The predictive value of plasmin concentrations were equally high after 4?h (PAP?>962?μg l^?1; OR 6.8, 95% CI 1.8–26.2, p?=?0.005) and 8?h (PAP?>495?μg l^?1, OR 6.7, 95% CI 1.4–32.9, p?=?0.024). Values for F1.2 were only predictive after 24?h (F1.2?>0.85?nmol l^?1, OR 13, 95% CI 1.4–117.8, p?=?0.023).

Conclusions: Markers of thrombin and plasmin activity in acute STEMI are related to outcome. The marker for thrombin generation F1.2 becomes a significant predictor of outcome at 24?h after admission, reflecting the potentially adverse effects of ongoing thrombin generation. This underlines the potential for direct thrombin inhibition and individualization of treatment by thrombin markers in STEMI.     

Molecular ablation of ventricular tachycardia after myocardial infarction

Ventricular tachycardia is a common and lethal complication after myocardial infarction. Here we show that focal transfer of a gene encoding a dominant-negative version of the KCNH2 potassium channel (KCNH2-G628S) to the infarct scar border eliminated all ventricular arrhythmias in a porcine model. No proarrhythmia or other negative effects were discernable. Our results demonstrate the potential viability of gene therapy for ablation of ventricular arrhythmias.     

Relationship between myocardial amiodarone concentration and antiarrhythmic effect in dogs with myocardial infarction and electrically induced ventricular arrhythmias

The relationship between the antiarrhythmic effect of amiodarone and its myocardial concentration was studied in dogs with 1-week-old myocardial infarction and reproducibly inducible sustained ventricular tachycardia or ventricular fibrillation. Three groups of animals (n = 10/group) received amiodarone, 40 mg.kg-1.day-1 (low-dose amiodarone), amiodarone 60 mg.kg-1.day-1 (high-dose amiodarone), or no amiodarone (control group). After 1 week of treatment, programmed electrical stimulation was repeated, and plasma and myocardial amiodarone and desethylamiodarone concentrations were measured. In the control group, sustained ventricular tachycardia or ventricular fibrillation was induced in six dogs (p = NS) when compared with baseline data. In the low-dose amiodarone group, sustained ventricular tachycardia or ventricular fibrillation was induced only in two dogs after 1 week of treatment (p less than 0.01 vs. baseline data). Sustained ventricular tachycardia or ventricular fibrillation was induced in seven dogs after treatment with high-dose amiodarone (p = NS vs. baseline data). Plasma amiodarone concentration in the low-dose amiodarone group (2.54 +/- 1.95 micrograms/mL) was significantly less (p less than 0.01) than that in the high-dose amiodarone group (4.64 +/- 1.66 micrograms/mL). Similarly, the plasma desethylamiodarone in the low-dose amiodarone group (0.32 +/- 0.16 microgram/mL) was significantly less (p less than 0.001) than that in the high-amiodarone dose group (0.56 +/- 0.23 microgram/mL). The myocardial amiodarone concentration in the low-dose amiodarone group (49.7 +/- 23.1 micrograms/g) was significantly lower (p less than 0.001) than that in the high-dose group (98.4 +/- 32.1 micrograms/g).(ABSTRACT TRUNCATED AT 250 WORDS)     

Late ventricular potentials--a new risk factor for cardiac arrhythmias in recent myocardial infarction

The study involved 150 patients with recent myocardial infarction. Ventricular lat potentials were registered in these patients during the first 48 hours and repeated in the third week. Ventricular late potentials were found in 31 patients (21%) in the first 48 hours, and in 27 out of 134 patients (20%) before the release from the hospital. Comparing potentials registration in the acute and late phase of the myocardial infarction it was found that ventricular late potentials occurred in 6 and disappeared in 4 patients. Stable ventricular tachycardia was significantly more frequent (p less than 0.001) within the first 48 hours in patients with ventricular late potentials than those without them (19% vs 3%). Ventricular late tachycardia (over 48 hours) was more frequent (p less than less than 0.001) in patients with ventricular late potentials (21% vs 1%). Premature ventricular excitations of Lown class 2-5 were also more frequent (p less than 0.001) in the group of patients with ventricular late potentials than those without these potential (81% vs 24%) when registered with a 24-hour Holter ECG in the third week following myocardial infarction. Antiarrhythmic drugs did not produce the regression of ventricular late potentials. Non-invasive registration of ventricular late potentials helps to select patients with life-threatening ventricular arrhythmias following the acute myocardial infarction.     

Late gadolinium enhancement MRI quantification to predict left ventricular remodeling after acute myocardial infarction

ObjectivesInfarct size is a major surrogate marker for prognosis in the context of myocardial infarction. There is a growing interest in validating a quantitative assessment approach in order to: (1) standardize these analyses; (2) to precise the individual prognosis of our patients. Several methods are available and were tested across their capacity to predict left ventricular (LV) remodeling at three months.Patients and methodsLate gadolinium enhancement-MRI was performed on day 5 and after a period of three months in 92 patients with STEMI. LV volumes and scar parameters were assessed visually (by using a four scale score) and quantitatively on day 5 and at three months. Dichotomous thresholds were defined first visually (VISUAL), then by 2, 5 and 6 standard deviations above remote myocardium, and by the full-width at half-maximum (FWHM) method.ResultsAll infarct sizing methods showed great relation to LV remodeling at three months (ROC analysis). Univariate predictors of an LV end-systolic volume index (LVESVi) superior to 70 mL/m² were: heart failure, creatin kinase peak and infarct size at day 5. FWHM was shown to be the best of all quantitative methods. An infarct size superior to 44 grams predicted a LVESVi > 70 mL/m² with a sensitivity of 90% and a specificity of 92.5%. FWHM reproducibility was good (r = 0.895, P < 0.0001, Bland Altman bias of 0.8 g).ConclusionIn the context of STEMI, FWHM is a tough and reproducible algorithm to quantitatively assess late gadolinium hyperenhancement, greatly related to functional prognosis at three months follow-up.     

Anaesthetic-related occurrence of early ventricular arrhythmias during acute myocardial ischaemia in rats

The cardiovascular responses of rats anaesthetised with different anaesthetic agents to acute coronary artery ligation were studied. Before thoracotomy, urethane-anaesthetised animals exhibited significantly lower blood pressures. Ligation of the left coronary artery induced a high incidence of ventricular tachycardia or fibrillation in rats anaesthetised with pentobarbitone, urethane, or ether inhalation followed by chloralose. Ketamine-anaesthetised animals had a significantly lower incidence of ventricular arrhythmias. The mortality rate was also lower, though not statistically significant. However, all groups of rats showed essentially similar blood pressure and heart rate changes following coronary artery ligation as well as the time of onset of ventricular tachycardia or fibrillation. The findings demonstrate the influence of anaesthetics on the occurrence of early ventricular arrhythmias following acute coronary artery ligation in rats.     

Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats

We investigated the role of cardiomyocyte apoptosis in the remodeling of the left ventricle from 24 h to 12 wk after myocardial infarction in the rat. Infarct size planimetry, quantification of cardiomyocyte apoptosis, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) methodology, and echocardiography (left ventricular diastolic diameter and ejection fraction) were performed. Sham-operated animals showed low rates of cardiomyocyte apoptosis (0.03%) and no change in diastolic diameter or ejection fraction during the study. Twenty-four hours after infarction, TUNEL positivity was high in the infarct areas (1.4%) and border zones (4.9%). It declined to 0.34% (P < 0.01 vs. sham) at 4 wk and 0.10% at 12 wk in the border zones. In the remote myocardium, cardiomyocyte apoptosis increased to 0.07% (P = 0.03 vs. sham) on day 1 and remained on the same level up to 4 wk. The increase in diastolic diameter 1-4 wk after infarction correlated (r = 0.60, P < 0.01) with cardiomyocyte apoptosis in the noninfarcted myocardium, which quantitatively contributed most (>50%) to the apoptotic cell loss by 4 wk.     

Left ventricular catecholamines during acute myocardial infarction in the dog

To determine whether changes in left ventricular catecholamine content occur during the first 30 to 90 min of acute myocardial infarction, myocardial catecholamine (radioenzymatic assay) over the interval was studied in the dog. In nine pentobarbital-anesthetized opened-chest dogs without coronary ligation, myocardial catecholamine at 2.5 h after pentobarbital (i) consisted mainly of norepinephrine (87% total catecholamine), (ii) showed a base to apex gradient in norepinephrine (1.44 +/- 0.10 vs. 1.03 +/- 0.10 micrograms/g, p less than 0.05) and dopamine (0.20 +/- 0.03 vs. 0.12 +/- 0.02 micrograms/g, p less than 0.05) but not epinephrine (0.017 vs. 0.016 micrograms/g), and (iii) showed no difference in norepinephrine, dopamine, or epinephrine across basal, mid, and apical left ventricular transverse planes spanning the vascular territories of the two coronary arteries. In 18 pentobarbital-anesthetized dogs with coronary ligation, (i) norepinephrine, measured in 14 regions across the mid left ventricle after 90 min ischemia in four dogs, was less in the ischemic center of the occluded bed than normal myocardium (1.01 +/- 0.04 vs. 1.29 +/- 0.04 micrograms/g, p less than 0.05), and (ii) norepinephrine was unchanged in normal myocardium of 14 dogs at 30, 60, 90 min, and 48 h but decreased in ischemic myocardium by 31% at 60 min (0.89 +/- 0.10 vs. 1.29 +/- 0.08 micrograms/g, p less than 0.025) and 79% at 48 h (0.27 +/- 0.04 vs. 1.26 +/- 0.08 micrograms/g, p less than 0.001). Thus, norepinephrine depletion from ischemic but not normal myocardium is detectable by 60 min during acute myocardial infarction.     

Angiotensin AT2 receptor deficiency after myocardial infarction

Hearts of normotensive angiotensin II type 2 receptor (AT₂)-deficient mice do not develop fibrosis after angiotensin II-induced chronic hypertension. Thus, the goal of our study was to clarify whether AT₂ knockouts (KOs) are also characterized by altered left ventricular (LV) function and modified remodeling of the extracellular matrix (ECM) after induction of myocardial infarction (MI). MI was induced in 5-mo-old female AT₂-deficient mice and controls by occlusion of the left coronary artery. Time-matched sham-operated animals served as controls. After 48 h, the first sets of mice were hemodynamically characterized using a pressure-tip catheter (n=8/group). We also obtained pressure volume loops using a microconductance catheter in additional sets of animals 3 wk after induction of MI (n=7/group). Finally, the collagen index was illustrated by Sirius red staining and quantified by digital analysis. Whereas the LV function of sham-operated animals did not differ between both genotypes, the collagen index was 44% lower in KO animals. Forty-eight hours and 3 wk post-MI, systolic and diastolic LV function were impaired in both AT₂-deficient and wild-type (WT) animals to the same extent by approx 45%. No differences were found between the two genotypes with respect to LV hypertrophy and the fibrosis index in the infarcted and noninfarcted areas 3 wk post-MI. While AT₂-KO mice had less cardiac collagen content under basal conditions, the receptor deficiency had no significant influence on LV function at the two investigated time points after induction of MI or on the remodeling of ECM at the latter time point. Thus, hypetension-induced fibrosis is probably triggered by other control mechanisms than fibrosis induced by MI.