Effect of dipyridamole on myocardial reperfusion injury: A double-blind randomized controlled trial in patients undergoing elective coronary artery bypass surgery.

Dipyridamole reduces reperfusion-injury in preclinical trials and may be beneficial in patients undergoing coronary angioplasty, but its effect on patients undergoing coronary artery bypass grafting (CABG) is unknown. We hypothesized that dipyridamole limits myocardial reperfusion-injury in patients undergoing CABG. The trial design was a double-blind trial randomizing between pretreatment with dipyridamole or placebo. In all, 94 patients undergoing elective on-pump CABG were recruited between February 2010 and June 2012. The primary endpoint was plasma high-sensitive (hs-) troponin-I at 6, 12, and 24 hours after reperfusion. Secondary endpoints were the occurrence of bleeding, arrhythmias, need for inotropic support, and intensive care unit length of stay. Finally, 79 patients (33 dipyridamole) were included in the per-protocol analysis. Dipyridamole did not significantly affect postoperative hs-troponin-I (change in plasma hs-troponin I -3% [95% confidence interval -23% to 36%]; P > 0.1). Secondary endpoints did not differ between groups. Dipyridamole prior to CABG does not significantly reduce postoperative hs-troponin release.

[Physical risks whilst walking the Nijmegen Four Days Marches in 2007: electrolyte imbalance in 1 in 5 walkers]. / Fysieke risico's tijdens het lopen van de Nijmeegse Vierdaagse in 2007: elektrolytendisbalans bij 1 op de 5 wandelaars.

OBJECTIVE: To determine the physiological impact and health risks for walkers during the Nijmegen (the Netherlands) Four Days Marches in 2007, the largest walking event in the world with more than 45,000 participants. DESIGN: Observational study. METHODS: 66 volunteers were randomly selected and counterbalanced for distance walked and gender in this observational study. Subjects walked 30 km (n = 20; 10 men), 40 km (n = 25; 14 men) or 50 km (n = 21; 10 men) per day, for 4 consecutive days. Core body temperature, fluid intake, changes in body weight, plasma sodium concentrations and energy usage were measured before and after the marches. RESULTS: During this event, ambient temperatures ranged from 11.0 degrees C to a maximum 25.4 degrees C expressed as 'wet bulb globe temperature' (WBGT). Heart rate (+38 beats per minute) and core body temperature (+0.8 degree C) significantly increased in all subjects during each day (about 9 hours walking per day at an average of 4.6 km/h), but hyperthermia was not diagnosed (definition: > 39.0 degrees C). Average fluid intake varied between 2.6 and 3.3 l/d with a range of 0.3-12 l/d. The relative change in body weight associated with this was -3.1 to +4.3%. Mean plasma sodium concentration decreased from 142.4 to 140.6 mmol/l over each walking day. The plasma sodium correlated negatively with fluid intake (r = -0.32; p < o.001), change in body weight (r = -0.13; p < 0.05), and walking time (r = -0.37; p < 0.001). A high prevalence of hyponatraemia (5%) and hypernatraemia (16%) was observed; extrapolating these findings to the entire field a large group (about 10,000) would have been at risk with this electrolyte imbalance. CONCLUSION: This study showed that walking the Four Days Marches in Nijmegen with mild ambient conditions led to one in five participants incurring disturbances in fluid and electrolyte balance. Nonetheless, the participants were well able to keep their increasing core temperature within safe limits. Apart from the frequent electrolyte imbalance, the fluid intake varied strongly between individuals.

Dipyridamole enhances ischaemia-induced reactive hyperaemia by increased adenosine receptor stimulation.

BACKGROUND AND PURPOSE: Dipyridamole enhances post-occlusive reactive hyperaemia (PORH) in the human forearm vascular bed. We hypothesize that this effect is completely mediated by increased adenosine receptor stimulation. To test this hypothesis, the effect of caffeine (an adenosine receptor antagonist) on dipyridamole-induced augmentation of PORH was explored. EXPERIMENTAL APPROACH: The forearm vasodilator responses to three increasing periods of forearm ischaemia (2, 5 and 13 min) were determined during placebo infusion. Forty minutes after the last reperfusion period, this procedure was repeated during intra-arterial infusion of dipyridamole (7.4 nmol min(-1) per 100 ml forearm). At least 2 weeks later, this whole procedure was repeated, but now in the presence of caffeine (90 microg min(-1) per 100 ml volume). KEY RESULTS: After 2, 5 and 13 min of ischaemia, the average forearm blood flow increased to 5.6+/-0.7, 9.7+/-1.3 and 34.5+/-2.1 ml min(-1) per 100 ml. After infusion of dipyridamole into the brachial artery, these numbers were significantly increased to 7.7+/-0.8, 12.5+/-1.5 and 41.6+/-3.1 ml min(-1) per 100 ml. This response was abolished by the concomitant infusion of caffeine (6.6+/-0.5, 10.2+/-0.6, 35.1+/-2.2 (caffeine) versus 7.4+/-0.4, 10.5+/-0.6, 33.7+/-2.2 ml min(-1)per 100 ml (caffeine/dipyridamole)). CONCLUSIONS AND IMPLICATIONS: Caffeine prevented the augmenting effect of dipyridamole on PORH. This indicates that dipyridamole-induced augmentation of PORH is mediated via increased adenosine receptor stimulation as a result of elevated extracellular formation of adenosine during ischaemia.

The EuroSCORE as predictor for prolonged hospital and intensive care stay after cardiac surgery?

OBJECTIVE: Validation of the EuroSCORE as predictor for a prolonged hospital and intensive care stay after CABG vs. institution-specific scoring systems. METHODS: For the evaluation of a prolonged hospital stay, 3359 patients were included in the analysis of EuroSCORE vs. the CORRAD morbidity score. For a prolonged intensive care stay, 1638 patients were included in the analysis of the EuroSCORE vs. the PICUS score. RESULTS: There was no significant difference in hospital stay between the three different EuroSCORE risk groups. The difference in hospital stay between the high-risk and low-risk groups, identified by the CORRAD morbidity score, was significant (6.9 vs.11.2 days). For a prolonged intensive care stay, the patients identified as high risk by the EuroSCORE and by the PICUS score also had a significantly longer intensive care stay; however, the discriminatory power was low. CONCLUSION: The EuroSCORE is not of value as a predictive system for a prolonged hospital stay. There is a relation between the high-risk patients identified by the EuroSCORE and a prolonged intensive care stay.