Low dose Iloprost effect on platelet aggregation in comatose out-of-hospital cardiac arrest patients: A predefined sub-study of the ENDO-RCA randomized -phase 2- trial.

PURPOSE: This is a predefined sub-study of the Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA) trial. We aim to investigate Iloprost, a prostacyclin analogue, safety by evaluating change in whole blood platelet aggregometry (Multiplate) in out of hospital cardiac arrest (OHCA) patients from baseline to 96-h post randomization. METHODS: A randomized, placebo controlled double-blinded trial in 46 OHCA patients. Patients were allocated 1:2 to 48 h Iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Platelet aggregation was determined by platelet aggregation tests ASPI-test (arachidonic acid); TRAP-test (thrombin-receptor activating peptide (TRAP)-6; RISTO test (Ristocetin); ADP test (adenosin diphosphat). RESULTS: There was no significant difference between the iloprost and placebo groups according to ASPI, TRAP, RISTO and ADP platelet aggregation assays. Further, no significant differences regarding risk of bleeding were found between groups (Risk of bleeding: ASPI <40 U; TRAP <92 U; RISTO <35 U; ADP <50 U). CONCLUSIONS: In conclusion, the iloprost infusion did not influence platelet aggregation as evaluated by the ASPI, TRAP, RISTO and ADP assays. There was no increased risk of bleeding or transfusion therapy. A decline in platelet aggregation was observed for the ASPI and ADP assays during the initial 96 h after OHCA. TRIAL REGISTRATION: Trial registration at clinicaltrials.gov (identifier NCT02685618) on 18-02-2016.

Hemodynamic Response to Rapid Saline Infusion Compared with Exercise in Healthy Participants Aged 20-80 Years.

BACKGROUND AND OBJECTIVE: Rapid saline infusion and exercise has been proposed as methods to unmask cardiovascular disease. However, the normal hemodynamic response to rapid saline infusion has not been compared to exercise nor is it known whether the responses are age-dependent.We assessed the hemodynamic response to rapid saline infusion in healthy participants over a wide age-range and compared it to exercise in the same participants. METHODS AND RESULTS: Fifty healthy participants (young <40 years, n = 16, middle-aged 40-59 years, n = 15, elderly 60-80 years, n = 19) underwent right heart catheterization at rest, during semisupine ergometer exercise at three exercise levels (25%, 50%, and 75% of peak VO2) and after rapid saline infusion (10 ml/kg at a rate of 150 ml/min). Rapid saline infusion significantly increased pulmonary capillary wedge pressure (PCWP) similarly across all age groups (∆PCWP 6 ±â€¯2; 7 ±â€¯2; 6 ±â€¯4 mmHg for the young, middle-aged and elderly respectively) with no correlation between age and ∆PCWP (r = 0.05; p = 0.74). However, there was a negative correlation between age and ∆stroke volume (SV) as elderly participants had a lower increase in SV following rapid saline infusion (r = 0.44; p = 0.002). On the contrary, exercise-induced significantly larger and age-dependent increases in PCWP (r = 0.58; p < 0.0001). Exercise also caused a larger increase in SV compared with rapid fluid loading (p = 0.0003) CONCLUSION: Unlike exercise, rapid saline infusion caused an age-independent increase in PCWP in healthy adults. Suggesting that age-related impairments beyond passive stiffness have a greater impact on exercise-induced increase in PCWP. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01974557.

Phenylephrine increases near-infrared spectroscopy determined muscle oxygenation in men.

Phenylephrine increases mean arterial pressure (MAP) by enhanced total peripheral resistance (TPR) but near-infrared spectroscopy (NIRS) determined muscle oxygenation (SmO2) increases. We addressed that apparent paradox during supine rest and head-up tilt (HUT). Variables were determined ± phenylephrine in males during supine rest (n = 17) and 40° HUT (n = 7). MAP, stroke volume (SV), heart rate (HR), and TPR were derived by Modelflow® and NIRS determined biceps SmO2 and (tibial) bone oxygenation (StibialO2). For ten subjects, cardiac filling and the diameter of the inferior caval vein (ICV collapsibility index: ((ICVexpiration - ICVinspiration)/ICVexpiration) × 100) were assessed by ultrasound. Pancreatic polypeptide (PP) and atrial natriuretic peptide (proANP) in plasma were determined by immunoassay. Brachial artery blood flow was assessed by ultrasound and skin oxygenation (SskinO2) monitored by white light spectroscopy. Phenylephrine increased MAP by 34% and TPR (62%; P < 0.001) during supine rest. The ICV collapsibility index decreased (24%; P < 0.001) indicating augmented cardiac preload although volume of the left atrium and ventricle did not change. SV increased (18%; P < 0.001) as HR decreased (24%; P < 0.001). ProANP increased by 9% (P = 0.002) with unaffected PP. Brachial artery blood flow tended to decrease while SskinO2 together with StibialO2 decreased by 11% (P = 0.026) and 20% (P < 0.001), respectively. Conversely, phenylephrine increased SmO2 (9%) and restored the HUT elicited decrease in SmO2 (by 19%) along with SV (P = 0.02). Phenylephrine reduces skin and bone oxygenation and tends to reduce arm blood flow, suggesting that the increase in SmO2 reflects veno-constriction with consequent centralization of the blood volume.

Catheter drainage of the pericardium. Practical method to maintain long-term patency.

Pericardiocentesis with catheter insertion and drainage is widely used in management of large pericardial effusions and cardiac tamponade. Two potential problems with an indwelling pericardial catheter system are catheter blockage and infection. We have utilized slow infusion of heparinized saline solution (3 ml/hr) via a continuous flush device to maintain catheter patency for up to seven days (mean 3.6) in 16 patients. Pericardial effusions were secondary to malignancy, uremia, and cardiac surgery. This article describes practical aspects of the technique. Most pericardial effusions can be successfully treated with pericardiocentesis and catheter drainage, provided the drainage is continued reliably and safely for several days. Surgical treatment such as subxiphoid pericardiostomy or partial pericardiectomy should be reserved for loculated effusions, clotted blood, subacute effusive-constrictive pericarditis, or significant recurrences after initial drainage.

Multiple calcified thrombi (rocks) in the right ventricle.

Large, organized right ventricular thrombi are rare. This report describes a 51 year old man with a history of recurrent pulmonary emboli treated with inferior vena cava ligation who subsequently developed multiple mobile calcified thrombi in the right ventricle. He was treated successfully by surgical resection. Unusual clinical presentation on admission consisted of a two component friction rub secondary to calcified masses rubbing against each other in systole and diastole. Cardiac catheterization showed a constrictive-restrictive pattern that persisted after surgery. The role of noninvasive studies in the diagnosis and long-term follow-up of the patient is emphasized.

Estimation of absolute left ventricular volume from gated radionuclide ventriculograms. A method using phase image assisted automated edge detection and two-dimensional echocardiography.

Twenty-four patients underwent gated cardiac blood pool (GBP) imaging, two-dimensional echocardiography (2-D echo), and single-plane contrast ventriculography (within 24 hours). Variable left ventricular (LV) regions of interest on GBP images were identified by an automated threshold radial search. To avoid excluding LV counts we indexed the search threshold to the threshold identified by a phase image generated by Fourier analysis. LV depth calculated by 2-D echo was used for attenuation correction of LV counts. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by dividing attenuation, background and deadtime corrected LV count rates by the background corrected count rate/ml of venous blood drawn during the study. Correlations between radionuclide and contrast volumes were good (EDV + ESV r = 0.97, EDV r = 0.94, ESV r = 0.95). Regression lines were close to the lines of identity. This method, in which GBP imaging and automated LV edge finding are complemented by 2-D echo for count attenuation correction, demonstrated reliable and reproducible noninvasive estimates of absolute LV volume.

Detection and estimation of rheumatic mitral regurgitation in the presence of mitral stenosis by pulsed Doppler echocardiography.

The sensitivity and specificity of pulsed Doppler echocardiography (PDE) in diagnosis and estimation of the severity of mitral regurgitation in the presence of rheumatic mitral stenosis was studied in 34 patients (18 women and 16 men) ranging in age from 33 to 70 years (mean 55). Definitive diagnosis of mitral regurgitation was confirmed in all patients by angiography and in 20 patients also by indicator dilution technique. Mitral regurgitation was detected by PDE in all patients with angiographically proven severe mitral regurgitation and in 7 of 8 patients with moderate mitral regurgitation. In patients with trace to mild mitral regurgitation, PDE was positive in only 7 of 13 patients. When subdivided for mild, moderate and severe mitral regurgitation, PDE sensitivity for diagnosis was 54, 88, and 100%, respectively; overall accuracy was 79% and specificity was 100%. Average systolic dispersion on time-interval histogram was 59% for mild, 89% for moderate, and 100% for severe mitral regurgitation. Groups of patients with mild mitral regurgitation could be differentiated from those with moderate (p less than 0.05) and severe (p less than 0.01) mitral regurgitation. A significant overlap of individual values, however, occurred. In 7 of 11 patients with moderate to severe mitral regurgitation, systolic turbulence also was detected in the left atrium. PDE was sensitive and specific in diagnosing moderate to severe mitral regurgitation in the presence of mitral stenosis. Assessment of precise severity of mitral regurgitation is still a problem in individual patients.

Cardiac arrhythmias due to oral aminophylline in patients with chronic obstructive pulmonary disease.

The effect of orally-administered aminophylline on cardiac arrhythmias was studied in 15 patients with stable chronic obstructive pulmonary disease by continuous 24-hour ambulatory electrocardiographic recordings. During the control period, the mean frequency of ventricular ectopic beats (VEBs) per hour was 43 +/- 26 (range 0.3 to 401), and heart rate was 80 +/- 3 beats per minute. All grades of ventricular arrhythmias were seen with occasional VEBs in five patients, frequent in three, multifocal in four, coupled beats in two, and short runs of ventricular tachycardia in one patient. Seven patients had occasional atrial premature contractions, six paroxysmal atrial tachycardia, and one patient had stable atrial fibrillation. Mean frequency of VEBs per hour and heart rate were statistically similar in patients undergoing two 24-hour control recordings. Mean grade of atrial and ventricular arrhythmias also remained similar on two control recordings. After oral aminophylline, the mean frequency of VEBs per hour increased to 72 +/- 41 (P = 0.006). Heart rate increased to 88 +/- 4 beats per minutes (P = less than 0.01). The mean grade of ventricular or atrial arrhythmias remained unchanged. We conclude that orally-administered aminophylline has both arrhythmogenic and chronotropic effects, but does not change the grade of arrhythmia.

Carotid sinus syncope induced by malignant tumors in the neck. Emergence of vasodepressor manifestations following pacemaker therapy.

Three patients had carotid sinus syncope secondary to malignant neoplasms in the neck. Pacemaker therapy controlled the cardioinhibitory reflex with bradycardia, but the patients manifested varying episodes of hypotension due to a vasodepressor reflex that most likely resulted from persistent irritation of the carotid sinus by the tumor. These episodes seemed to be self-limiting. Surgical treatment in resistant cases is a possibility.

Improved pacing tolerance of the ischemic human myocardium after administration of carnitine.

The possibility that DL-carnitine has a protective effect during myocardial ischemia was evaluated by performing two rapid coronary sinus pacing studies 15 minutes apart in 21 patients with coronary artery disease. Eleven patients received DL-carnitine (20 or 40 mg/kg) before the second pacing study. The treated group had a significant increase in mean heart rate (12.5 beats/min, P less than 0.001), pressure-rate product (1,912 units, P less than 0.01) and pacing duration (3.2 minutes, P less than 0.001) after the administration of carnitine. The treated group also had improvements in percent myocardial lactate extraction (8.8 percent increase, P less than 0.001) and left ventricular end-diastolic pressure (a decrease of 5.3 mm Hg, P less than 0.05). There was significantly less S-T segment depression during the second pacing period in both the untreated and treated groups. The results of this study suggest that in ischemic human hearts with reasonably well preserved left ventricular function, DL-carnitine may improve the tolerance for stress associated with an increase in heart rate and pressure-rate product.

Pharmacokinetics of l-carnitine in man following intravenous infusion of dl-carnitine.

The pharmacokinetics of l-carnitine were studied in adult male patients following intravenous infusion of dl-carnitine hydrochloride-L-Carnitine appears to distribute into a rapidly perfused and then a more slowly perfused body space following administration. The overall apparent distribution volume Vd (ss) is consistent with extracellular body water. Serum levels of l-carnitine, from two different dose levels were adequately described by a two-compartment model. 80% of the administered dose was recovered in 24 hour post dose urine.