DNA damage and arterial hypertension. A systematic review and meta-analysis.

Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P<0.05 and="" 8ohdg="" 13="" 1="" 4="" 12="" vs="" 6="" 97="" 2="" 67="" ng="" mg="" creatinine="" i=""> P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls.

Comet assay in evaluating deoxyribonucleic acid damage after out-of-hospital cardiac arrest.

OBJECTIVE: This study aimed to investigate whether out-of-hospital cardiac arrest (OHCA) may induce severe DNA damage measured using comet assay in successfully resuscitated humans and to evaluate a short-term prognostic role. METHODS: In this prospective, controlled, blinded study (1/2013-1/2014), 41 patients (age, 63±14 years) successfully resuscitated from non traumatic OHCA and 10 healthy controls (age, 53±17 years) were enrolled. DNA damage [double-strand breaks (DSBs) and single-strand breaks (SSBs)] was measured using comet assay in peripheral lymphocytes sampled at admission. Clinical data were recorded (according to Utstein style). A good short-term prognosis was defined as survival for 30 days. RESULTS: Among the patients, there were 71% (29/41) short-term survivors. After OHCA, DNA damage (DSBs and SSBs) was higher (11.0±7.6% and 0.79±2.41% in tail) among patients than among controls (1.96±1.63% and 0.02±0.03% in tail), and it was more apparent for DSBs (p<0.001 and p=0.085). There was no difference in the DNA damage between patients with cardiac and non-cardiac etiology, or between survivors and nonsurvivors. Among Utstein style parameters, ventricular fibrillation, asystole, and early electrical defibrillation influenced DSBs; none of the factors influenced SSBs. Factors influencing survival were SSBs, ventricular fibrillation, length of cardiopulmonary resuscitation by professionals ≤15 min, cardiogenic shock, and postanoxic encephalopathy. In contrast to DSBs [area under the curve (AUC)=0.520], SSBs seem to have a potential in prognostication (AUC=0.639). CONCLUSION: This study for the first time demonstrates revelation of DNA damage using comet assay in patients successfully resuscitated from OHCA. Whether DNA damage measured using comet assay may be a prognostic marker remains unknown, although our data may encourage some suggestions.

Pharmaco-refractory chronic heart failure--the need for drug level tailored management.

Pharmacorefractory chronic heart failure is a serious world-wide problem of systolic dysfunction not improving despite evidence based chronic heart failure pharmacotherapy. With the aim to reverse the poor pharmacorefractory chronic heart failure prognosis, severe sophisticated technical therapeutic approaches (from cardiac resynchronization usually with implantable cardioverter-defibrillator to heart transplantation) have been clinically adopted and detached at least for the most eligible pharmacorefractory chronic heart failure patients. However, both significant limitations of these highly specialised therapeutic techniques (cost, uncertain individual effect, complication, adverse effect, waiting list) and the pharmacorefractory chronic heart failure hopelessness for unfit patients make the effort to stop the pharmacorefractory chronic heart failure genesis never ending longing. Regarding growing knowledge on differences in pharmacokinetics, authors assume that the relative undertreatment despite fixed doses may explain the pharmacorefractory chronic heart failure genesis. If this hypothesis proves to be correct, the evidence based chronic heart failure pharmacotherapy innovatively personalized according to steady state drug serum level may reduce the pharmacorefractory chronic heart failure epidemiology with the lower need for cost-consuming techniques and be the promising strategy for patients left on individually ineffective evidence based chronic heart failure pharmacotherapy.

Electrogastrography in experimental pigs: the influence of gastrointestinal injury induced by dextran sodium sulphate on porcine gastric erythromycin-stimulated myoelectric activity.

OBJECTIVES: Electrogastrography (EGG) is a non-invasive investigation of gastric myoelectrical activity. The aim of study was to evaluate the impact of erythromycin on EGG in gastrointestinal toxic injury induced by dextran sodium sulphate (DSS) in experimental pigs. METHODS: The experiments were carried out on 12 adult pigs (weighing 30-35 kg). EGG was recorded using Digitrapper equipment (Synectics Medical AB, Stockholm). Running spectrum activity was used for EGG evaluation. There were two groups of animals: Group I: 6 controls with erythromycin administration (1,600 mg intragastrically); Group II: 6 animals treated with DSS (for 5 days, 0.25 g/kg per day in a dietary bolus) followed by erythromycin administration. Baseline and subsequent six separate 30-minute EGG-recordings (from time 0 to 360 min) were accomplished in each animal. RESULTS AND CONCLUSION: A total of 84 records were analysed. Baseline dominant frequency of slow waves was fully comparable in both groups. In Group I, there was a significant increase in dominant frequency after erythromycin administration (maximum between 240-360 min). There was a flat non-significant and delayed increase in dominant frequency after erythromycin administration in Group II. The difference between Group I and II at particular time intervals was not significant but a diverse trend was evident. EGG recording enables us to register a gastric myoelectrical effect of prokinetic drugs. Erythromycin induced a significant increase in the dominant frequency of slow waves. DSS caused toxic injury to the porcine gastrointestinal tract responsible for the delayed and weaker myoelectrical effect of erythromycin in experimental animals.

Five-year survival of patients after out-of-hospital cardiac arrest depending on age.

Patient's age belongs to the independent prognostic factors of patients after out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate the influence of age on 5-year survival in professionally cardio-pulmonary resuscitated patients with "primary cardiac" etiology OHCA. In this analysis of prospective multi-centric study, from April 1, 2002 until August 31, 2004, a total of 560 patients were included (aged 16-97 years) from the East Bohemian region, for whom a professional cardio-pulmonary resuscitation for OHCA was attempted. In the age subgroup <70 years there were 307 patients and in the age subgroup ≥ 70 years there were 253 patients. Of the subgroup <70 years, 29 patients (10%) survived to year 5 (58% from the 50 patients surviving to day 30), and in the subgroup ≥ 70 years, we had 4 patients surviving to year 5 (2%) (29% from the 14 patients surviving to day 30), respectively (Fisher's exact test; comparison in the all resuscitated patients: p < 0.001, in the population surviving to day 30: p = 0.071). In conclusion, there was a trend towards a worse outcome in 5-year survival following OHCA in the patients aged ≥ 70 years. Nevertheless, these data support that prognosis OHCA of elders is not associated with universal dismal outcome.

Bland-White-Garland syndrome in adults: sudden cardiac death as a first symptom and long-term follow-up after successful resuscitation and surgery.

Two cases (a 23-year-old man and a 33 year-old-woman) with Bland-White-Garland (BWG) syndrome (an anomalous origin of the left coronary artery from the pulmonary artery) are presented. Their first symptom was survived sudden cardiac death. Both patients underwent surgical repair. One patient received an implantable defibrillator because of serious structural changes in the left ventricle and symptomatic non-sustained ventricular tachycardia; the second patient is free of therapy. During long-term follow-up (10.5 and 4.5 years, respectively), ventricular tachyarrhythmias did not recur. Both cases show good long-term prognosis in resuscitated adult patients after surgical repair for BWG syndrome regardless of the presence of structural changes.

Long-term prognosis after out-of-hospital cardiac arrest with/without ST elevation myocardial infarction.

AIM: To describe the 3-year survival of patients after out-of-hospital cardiac arrest (OHCA) taking into account the presence of ST-segment elevation myocardial infarction (STEMI) and evaluating prognostic factors associated with pre-hospital and hospital care. PATIENT GROUP: Over a period of 29 months and with the aid of a questionnaire supplied to 24 rescue stations, we prospectively included 560 individuals (415 men; aged 16-97 years, median 68) for whom cardio-pulmonary resuscitation (CPR) for OHCA of confirmed cardiac etiology was attempted. RESULTS: Of 149 hospitalized individuals, 28.2% survived 1 year and 25.5% survived 3 years after OHCA. In the subgroup of patients with STEMI (26 individuals; 17.5%), 57.7% survived 1 year and 53.9% survived 3 years. In the subgroup of patients without STEMI (n=123), 22% survived 1 year and 19.5% survived 3 years. The strongest predictors for long-term survival by logistic regression analysis were: age under 70 years, ventricular fibrillation as initial rhythm, CPR without atropine, and STEMI. OHCA occurrence at a public place was an indicator of better survival in the subgroup with STEMI. In the subgroup of patients without STEMI, long-term angiotensin-converting enzyme inhibitor treatment, CPR without atropine, a Glasgow Coma Scale upon hospital admission over 3, no presence of cardiogenic shock, and no manifestations of postanoxic encephalopathy (Fisher's exact test, chi(2) test) were indicators of better survival. CONCLUSION: Among 560 individuals with "primary cardiac" etiology OHCA and initiation of professional CPR, 8% survived 1 year and 7% survived 3 years. A higher survival rate among patients with STEMI was documented.

The highest incidence of out-of-hospital cardiac arrest during a circadian period in survivors.

UNLABELLED: Health care associated with cardiac arrest exhibits a significant economic burden, rather than effectiveness. HYPOTHESIS: The time of the out-of-hospital cardiac arrest (OHCA) onset during a diurnal period alters the survival chance. Professionally resuscitated patients for witnessed OHCA (n = 495) from the study were prospectively followed for 12 months. The distribution of the onset of cardiac arrest during the 24-hour period was tested in the survivors (the total group, the other groups). In the ultrashort-term survivors (n = 136, follow-up = admission to hospital) the highest incidence was seen between 18:01-22:00 h. The same trend was seen in both the short-term (n = 48, follow-up = discharge from hospital) and the long-term survivors (n = 39, follow-up = 1 year). Furthermore, when the ultrashort-, short-, and long-term survivors were analysed according to indicators of prehospital care (early electrical defibrillation < or =5 min, bystander cardiopulmonary resuscitation, ambulance response time < or =10 min; locations of arrest; initial cardiac rhythms) an OHCA peak was observed for early defibrillation and ambulance response time (ultrashort-term survivors, 18:01-22:00 h) and/or in the case of OHCA that occurred in a public place (short-term survivors, 18:01-22:00 h). The lowest incidence of cardiac arrest was between 22:01-06:00 h in all groups. The evening incidence of OHCA reflects a higher chance of survival in our study area (East Bohemian region).

Out-of-hospital cardiac arrests in patients with acute ST elevation myocardial infarctions in the East Bohemian region over the period 2002-2004.

BACKGROUND: Early reperfusion by direct percutaneous coronary intervention (PCI) in patients with ST segment elevation acute myocardial infarctions (STEMI) with an out-of-hospital cardiac arrest (OHCA) reduces hospital and longterm mortality. AIMS: Evaluating the significance of direct PCI for the short-term (discharge from acute hospitalization) and 1-year survival in patients with acute STEMI after OHCA. METHODS: In this prospective study, from April 1, 2002 up to August 31, 2004, a total of 26 hospitalized individuals (22 men, 4 women, aged 35-79 years, median 58.5) from the East Bohemian region with OHCA (primary group of 718 individuals) with acute STEMI were included. Urgent coronary angiography was performed in 20 individuals, and direct PCI was done in 19 of them. The remaining 6 patients did not undergo angiography. RESULTS: Fifteen patients (57.7%) survived acute hospitalization, of whom 11 were without neurological deficits. In the subgroup with urgent coronary angiography 14 patients (70%) survived hospitalization, and in the subgroup without coronarography only 1 patient survived hospitalization (16.7%). In the subgroup with PCIs, 13 out of the 19 patients survived (68.4%). None of the patients died during the 1-year follow-up after being discharged from acute hospitalization. According to the urgent coronarography the artery most commonly responsible for the infarction was the left anterior descending artery (50%). Initial TIMI flow grade 0-I was found in 17 patients and grade II-III in 3 individuals. After PCI, irrespective of stent implantation, an optimal angiographic success (TIMI flow grade II-III) was obtained in 17 cases. CONCLUSION: Short-term survival of patients after OHCA with STEMI treated with direct PCI was found to be 68.4%. Out of 6 patients not receiving reperfusion therapy 1 survived (16.7%). Over the course of the 1-year follow-up none of the patients died.

Characteristics and short-term survival of individuals with out-of-hospital cardiac arrests in the East Bohemian region.

AIM: We describe survival after admission to hospital from out-of-hospital cardiac arrest (OHCA) in the East Bohemian region, according to the Utstein Style guidelines and have identified the main diagnosis including in those who died and had an autopsy. PATIENT GROUP: Over a period of 29 months we used a questionnaire supplied to 24 rescue stations, to identify 718 individuals (511 men and 207 women, aged 16-97 years) with confirmed cardiac arrest who were considered for resuscitation. RESULTS: Out of 560 patients in whom cardiopulmonary resuscitation for OHCA of confirmed cardiac aetiology was attempted, 350 patients (62.5%) died in the field and 61 (10.9%) died during transport. Hospital admission was achieved in 149 cases (26.6%) and, of these, 96 patients died. Fifty-three patients (9.5%) were discharged home alive, 36 (6.4%) with an intact CNS. The first monitored rhythm showed asystole in 264 cases (47.1%) followed by ventricular fibrillation in 227 cases (40.5%). The main diagnosis of coronary heart disease (CHD) was established clinically in 467 cases (83.4%). In 175 autopsy reports this diagnosis was noted in 152 cases (86.9%). CONCLUSION: Of patients resuscitated for OHCA of cardiac aetiology, 9.5% survived to leave the acute hospital. CHD was the principle diagnosis in the entire group and this correlated with the same finding in the group of patients who received an autopsy.

The "edge effect" after implantation of beta-emitting (55Co) stents with high initial activity.

The aim of this study was to evaluate the incidence and the cause of "edge restenosis" after implantation of high activity 41.1 microCi +/- 1.2 microCi = 1520 kBq +/- 44 kBq, beta-emitting (55Co) stents. Proton bombarding in cyclotron has brought the radioactivity. Intravascular ultrasound (IVUS) investigation has been completed in 10 patients. The angiographies performed at 6 month revealed restenosis >50% in 5 cases (50%). The analysis of edges (5 mm distally and proximally to the last stent struts) showed no significant changes in TVV (187.3 +/- 62.60 mm3 and 176.9 +/- 53.5 mm3) but PMV increase significantly (i.e. neointimal proliferation) from 61.9 +/- 31.2 mm3 to 82.2 +/- 43.4 mm3 (p<0.04) and was the major contributor (from 66%) to lumen volume loss (125.4 +/- 40.7 mm3 and 94.7 +/- 22.2 mm3, p<0.02). In conclusion, neither statistically significant positive nor negative remodelling at the "stent edges", were present. Statistically significant increase in plaque +/- media volume (i.e. neointimal hyperplasia) and reduction in lumen volume were found. The cause of "edge restenosis" was especially (from 66%) due to increase in plaque +/- media volume (i.e. neointimal hyperplasia). Probably, main reason for "edge effect"/neointimal hyperplasia was in this trial sharp fall-off in radiation at the edges of the stents.

Intravascular ultrasound study of the effect of beta-emitting ((55)Co) stents on vascular remodeling and intimal proliferation.

The aim of this study was to evaluate vessel remodeling after implantation of high-activity (mean, 41.1 +/- 1.2 microCi) beta-emitting ((55)Co) stents. Proton bombarding in cyclotron has brought the radioactivity. Intravascular ultrasound (IVUS) investigation has been completed in 10 patients. The angiographies performed at 6 months revealed restenosis > 50% in five cases (50%). IVUS analysis demonstrated an absence of remodeling behind the stent, with no changes in total vessel volume (TVV; 353.6 +/- 126.3 and 343.9 +/- 90.6 mm(3)) or plaque + media volume (PMV; 171.7 +/- 57.4 and 166.8 +/- 42.6 mm(3)). On the other hand, lumen volume (LV) within the stent decreased significantly from 181.9 +/- 80.2 to 154.6 +/- 45.2 mm(3) (P < 0.02). This was due to presence of neointimal hyperplasia (NIH) at both extremities of implanted stents. No chronic recoil of the implanted stents was found. The analysis of edges (5 mm distally and proximally to the last stent struts) showed no significant changes in TVV (187.3 +/- 62.60 and 176.9 +/- 53.5 mm(3)), but PMV increase significantly from 61.9 +/- 31.2 to 82.2 +/- 43.4 mm(3) (P < 0.04) and LV decreased from 125.2 +/- 40.7 to 94.7 +/- 22.0 mm(3) (P < 0.02). In conclusion, single (55)Co radioactive beta-emitting stents with high initial activity are effective in reducing neointimal hyperplasia only within the stent body, as measured by IVUS, and they do not solve the problem of restenosis at the stent extremities as well as at the stent edges. Edge restenosis in this high radioactive stents was mainly (from 66%) due to neointimal proliferation.

Treatment of coronary bifurcation lesions by stent implantation only in parent vessel and angioplasty in sidebranch: immediate and long-term outcome.

The aim of this study was to evaluate the immediate and long-term outcome of intracoronary stent implantation for the treatment of bifurcation lesions. We treated 30 patients with bifurcation stenosis with the Bx Velocity stent implanted only in the parent vessel and with balloon angioplasty of the sidebranch. Angiographic success was 86.7% (n = 26 patients) in both branches and 100% in the main branch. Clinical success was achieved in 29 patients (96.7%). One patient (3.3%) suffered from a small non-Q wave myocardial infarction. All 30 patients underwent control coronary angiography at 6 months unless performed earlier due to symptoms. After the 6-month follow-up, a total of 27 patients (90%) were asymptomatic; angiographic restenosis (> 50%) was found in four cases (13.3%). There was no sidebranch restenosis. During the follow-up, one patient (3.3%) had unstable angina and angiography revealed severe diffuse restenosis within the whole stent; this patient was referred for coronary artery bypass surgery. Two patients had mild angina (Canadian Cardiovascular Society Class II) and 1 patient had silent ischemia during exercise stress test. These patients underwent repeat coronary angioplasty. The rate of major adverse cardiac events was 16.6% and target vessel revascularization rate was 13.3%. We concluded that stent implantation only in the parent vessel with angioplasty of the sidebranch in bifurcation lesions is safe and has a high clinical success rate and low rate of target lesion revascularization.